bluuebunny/crossref_metadata_2025 huggingface dataset:
External Urethral Orifice Metastasis of Cervical Cancer Treated With Intraluminal Urethral Brachytherapy Using a Lumencath Applicator: the First Case Report
Authors: Takagawa Yoshiaki , Izumi Sachiko , Okano Tomoyuki , Takahashi Eiichi , Wakamatsu Yuki , Takahara Megumi , Okada Haruka , Kita Midori
Published: June 2021

Background: This is the first case report of external urethral orifice metastasis in primary cervical cancer.Case presentation: The patient was histologically diagnosed with cervical squamous cell carcinoma, which involved not only the lower third of the vagina but also isolated metastasis of the external urethral orifice. We performed definitive chemoradiotherapy with weekly cisplatin and external beam radiation therapy followed by brachytherapy (BT). Considering tumor involvement, we used the Tandem, Cylinder, and Lumencath applicators to treat not only the cervix and vagina but also the entire urethra in BT sessions. The prescribed BT dose was 24 Gy in four fractions. The average clinical target volume (CTV) D90 of the cervix, vagina, and urethra in BT sessions were 7.3, 6.0, and 5.6 Gy, respectively. The average CTVs of the urethra in D0.1 cc and D1 cc were 18.1 Gy and 9.0 Gy, respectively. No grade ≥3 acute and late toxicities were observed during the 9-month follow-up. We achieved excellent local control for both primary tumor and external urethral orifice metastasis of cervical cancer.Conclusion: This rare case report suggested that gynecologists and radiation oncologists should keep in mind to examine not only the cervix and vagina but also the external urethral orifice for patients with primary cervical cancer. Intraluminal urethral BT using the Lumencath applicator is a good treatment option for cervical cancer with urethral involvement.
AMPK-SIRT1 Pathway Modulates The Apoptosis, Proliferation and Migration of AR42J Cells By Regulating p53 and NF-κB
Authors: Yu Wei-Li , Wang Xiao-Die , Wang Fu-Gui , Lu Zhong-Hua , Sun Yun
Published: June 2021

Background: Acute pancreatitis (AP) is an acute abdomen caused by abnormal activation of trypsin. AMPK-SIRT1 pathway has been reported to be related to various diseases, but the function in AP remains unclear. This study is designed to investigate the mechanism and effect of AMPK-SIRT1 pathway in AP.Methods: An experimental AP model of AR42J cells was stimulated with caerulein after pretreated with compound C or metformin. The mRNA and protein expressions of genes were analyzed by qRT-PCR and western blot. Cell apoptosis, proliferation and migration were measured using flow cytometry, MTT and transwell assay. Results: After pretreated with metformin, expressions of p-AMPKα, SIRT1 were elevated, ace-p53, ace-NF-κB were attenuated, cell apoptosis, proliferation, and migration were decreased. After pretreated with compound C, the reverse effects occurred. p-AMPKα and SIRT1 expressions were decreased, ace-p53 and ace-NF-κB were rasied, and cell apoptosis, proliferation, and migration were enhanced after caerulein induced in each group. Conclusion: When AP happened, expressions of p-AMPKα and SIRT1 were reduced, resulting in up-regulation of acetylation levels of p53 and NF-κB, acceleration of cell apoptosis, proliferation and migration. It hinted that AMPK-SIRT1 pathway could modulate the apoptosis, proliferation, migration and inflammation reaction of AR42J cells by regulating p53 and NF-κB.
Complete Genome Sequence of a Putative Novel Ilarvirus Isolated From Eleocharis Dulcis
Authors: Lv Lanqing , Wu Xinyang , Weng Jiajia , Lai Yuchao , Han Kelei , Lu Yuwen , Peng Jiejun , Lin Lin , Rao Shaofei , Wu Guanwei , Chen Jianping , Zheng Hongying , Jiang Wen , Yan Fei
Published: June 2021

The complete genomic sequence of a novel ilarvirus from Eleocharis dulcis, tentatively named water chestnut virus A (WCVA), was determined using next generation sequencing (NGS) combined with reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) PCR. The three genomic RNA components of WCVA were 3578 (RNA1), 2873 (RNA2) and 2073 (RNA3) nucleotides long, with four predicted open reading frames containing conserved domains and motifs typical of ilarviruses. Phylogenetic analyses of each predicted protein consistently placed WCVA in subgroup 4 of the genus Ilarvirus, together with prune dwarf virus, viola white distortion associated virus, fragaria chiloensis latent virus and potato yellowing virus. The genetic distances and lack of serological reaction to antisera of other ilarviruses suggest that WCVA is a novel member of the genus.
Comparison of Autorefraction, Cyclorefraction, and Subjective Manifest Refraction in Keratoconic Eyes
Authors: Zareei Athar , Alamolhoda Marziyeh , Abdolahian Milad , Khatami Kiana , Bamdad Shahram
Published: June 2021

Purpose: This study aimed to estimate the agreement of astigmatism between an autorefractor (Topcon), cycloplegic refraction, subjective manifest refraction, front and back corneal astigmatism. Moreover, this study aimed to investigate which factors influence the difference between cycloplegic refraction and subjective manifest refraction in these keratonic eyes.Methods: subjective manifest refraction, Autorefractmeter were measured in 64 keratonic eyes of 43 patients (21-45 years old) before and after using cycloplegic drop. We measured Corneal values by using Scheimpflug tomography. Astigmatic power was converted to vectors. The agreement of astigmatism between an autorefractor (Topcon), cycloplegic refraction, subjective manifest refraction, front and back corneal astigmatism was measured overall and in each vector. The difference between Cycloplegic refraction and subjective manifest refraction was calculated in each vector axis. Factors were anticipated associated with discrepancy by using Multivariable Regression Analysis.Results: The maximum estimations of agreement were found berween autorefratometer and subjective manifest refraction in cylindrical power(Icc:0.703,P<0.026), cylindrical axis(Icc:0.943,P<0.0001) and astigmatic vestors of J0 (Icc:0.972,P<0.0001) and J45( Icc:827,P=0.006). The significant factors Associated With discrepancy between cyclorefraction and subjective manifest refraction in both vectors(J0 and J45) were Q-value(B Coefficient= -4.91, P<0.0001) (B Coefficient=1.01, P<0.0001), corneal astigmatism(B Coefficient= 0.66, P=0.001) (B Coefficient=0.11, P=0.001), Kmax(B Coefficient= -0.52, P<0.0001) (B Coefficient=0.07, P=0.02), IHA(B Coefficient=0.04, P=0.005) (B Coefficient= -0.03, P<0.0001). The significant associated factors for axis changes between cycloplegic refraction and subjective manifest refraction were cone location (B Coefficient= -33.34, P=0.001) and corneal astigmatism(B Coefficient= -0.1, P=0.04).Conclusion: Maximum agreement of subjective manifest refraction astigmatism is with auto refractometer in keratoconus patients, so it could be said that the result of the auto refractometer is the most appropriate starting point during subjective refraction in these patients. It can be predicted that the closer the keratoconus cone location relative to the center of the cornea and the lower the keratoconus patient's corneal astigmatism, the more the probability of axis changes by cycloplegic drop.
Involvement of IGF-1R-PI3K-AKT-mTOR Pathway in Increased Number of GnRH3 Neurons During Androgen-induced Sex Reversal of the Brain in Female Tilapia
Authors: Oda Akari , Inoue Sakura , Kaneko Ryo , Narita Yasuto , Shiono Suzuka , Kaneko Toyoji , Tseng Yung-Che , Ohtani-Kaneko Ritsuko
Published: June 2021

The neuroplastic mechanism of sex reversal in the fish brain remains unclear due to the difficulty in identifying the key neurons involved. Mozambique tilapia show different reproductive behaviours between sexes; males build circular breeding nests while females hold and brood fertilized eggs in their mouth. In tilapia, gonadotropin-releasing hormone 3 (GnRH3) neurons, located in the terminal nerve, regulate male reproductive behaviour. Mature males have more GnRH3 neurons than mature females, and these neurons have been indicated to play a key role in the androgen-induced female-to-male sex reversal of the brain. We aimed to elucidate the signalling pathway involved in the androgen-induced increase in GnRH3 neurons in mature female tilapia. Applying inhibitors to organotypic cultures of brain slices, we showed that the insulin-like growth factor (IGF)-1 receptor (IGF-1R)/PI3K/AKT/mTOR pathway contributed to the androgen-induced increase in GnRH3 neurons. The involvement of IGF-1 and IGF-1R in 11-ketotestosterone (11-KT)-induced development of GnRH3 neurons was supported by an increase in Igf-1 mRNA shortly after 11-KT treatment, the increase of GnRH3 neurons after IGF-1 treatment and the expression of IGF-1 in GnRH3 neurons. Our findings highlight the involvement of IGF-1 and its downstream signalling pathway in the sex reversal of the tilapia brain.
Barriers to Accessing Internet-based Home Care for Older Patients: A Qualitative Study
Authors: Zhao Baosheng , Zhang Xiaoman , Huang Rendong , Yi Mo , Dong Xiaofei , Li Zhenxiang
Published: June 2021

Background Due to the increasingly ageing society and the shortage of nursing human resources in China, the imbalance between the home care needs of elderly patients and the inadequate supply of nursing services is increasing. Based on this medical situation, China is implementing internet-based home care (with the nurses who provide this care called online nurses or sharing nurses) based on the concept of the sharing economy, internet technology and knowledge from the home care experience in other countries. Internet-based home care follows an online application/offline service model. Patients place orders through an app, nurses grab orders instantly, and managers dispatch orders through a web platform based on various factors such as nurses' qualifications, professionalism and distance from the patient. In this way, home care is provided for people with limited mobility, such as elderly or disabled people, patients in rehabilitation and terminal patients. Only by fully understanding the barriers to accessing internet-based home care can we provide quality nursing services to elderly patients and achieve the sustainable development of internet-based home care.Objective The goal of this study was to use qualitative methods to explore barriers to accessing internet-based home care for older patients.Methods Based on Levesque’s access to health care framework, semi-structured personal interviews were conducted with 19 elderly patients in a descriptive qualitative study using directed content analysis.Results We identified four barriers to accessing internet-based home care for older patients: barriers to perceiving, seeking, paying for, and engaging in internet-based home care. Specific barriers included traditional perceptions, barriers to internet use, high payment costs, uneven quality of services, and concerns about privacy and patient safety.Conclusions Internet-based home care has maximized nursing human resources and effectively met the demand for home care, but it has also introduced new risks and challenges. To make internet-based home care universally available to elderly patients, it is necessary to strengthen publicity, optimize the network application process, improve the health insurance system, formulate unified nursing service standards, and address safety risks.
Routinely Collected Antenatal Data for Longitudinal Prediction of Preeclampsia in Nulliparous Women: A Population-based Study
Authors: Sandström Anna , Snowden Jonathan M , Bottai Matteo , Stephansson Olof , Wikström Anna-Karin
Published: June 2021

The objective was to evaluate the sequentially updated predictive capacity for preeclampsia during pregnancy, using multivariable longitudinal models including data from antenatal care. This population-based cohort study in the Stockholm-Gotland Counties, Sweden, included 58899 pregnancies of nulliparous women 2008–2013. Prospectively collected data from each antenatal care visit was used, including maternal characteristics, reproductive and medical history, and repeated measurements of blood pressure, weight, symphysis-fundal height, proteinuria, hemoglobin and blood glucose levels. We used a shared-effects joint longitudinal model including all available information up until a given gestational length (week 24, 28, 32, 34 and 36), to update preeclampsia prediction sequentially. Outcome measures were prediction of preeclampsia, preeclampsia with delivery < 37, and preeclampsia with delivery ≥ 37 weeks’ gestation. The area under the curve (AUC) increased with gestational length. AUC for preeclampsia with delivery < 37 weeks’ gestation was 0.73 (95% CI 0.68–0.79) at week 24, and increased to 0.87 (95% CI 0.84–0.90) in week 34. For preeclampsia with delivery ≥ 37 weeks’ gestation, the AUC in week 24 was 0.65 (95% CI 0.63–0.68), but increased to 0.79 (95% CI 0.78–0.80) in week 36. The addition of routinely collected clinical measurements throughout pregnancy improve preeclampsia prediction and may be useful to individualize antenatal care.
A Cross-sectional Study of Undergraduate Teaching of Trauma and Orthopaedics in the UK and the Relationship between Medical Schools and Interest in Trauma and Orthopaedics as a Career.
Authors: Choi Sarah , Ooi Setthasorn , Carpenter Eleanor
Published: June 2021

Aims: Adequate exposure and teaching of Trauma and Orthopaedics (T&O) to medical students is fundamental in order to obtain sufficient knowledge and sustain their interest in T&O as a career. The primary aim is to assess the exposure and delivery of T&O at all medical schools in the UK. The secondary aim is to determine whether there are any associations between attending a particular medical school and having a strong interest in pursuing a career in T&O. Methods: To explore the primary aim, all 33 UK medical schools were investigated in the study, by means of a questionnaire distributed to medical students. This did not include ‘new’ medical schools, defined as those established from 2014 onwards. To investigate the secondary aim of exploring associations between students’ and alumni’s medical schools and their interest in T&O as a career, British Orthopaedic Training Association (BOTA) members were reviewed, using the General Medical Council register to identify the universities from which members had graduated. The authors have made the assumption that membership of BOTA signified an interest in T&O as a career. Results: Results were obtained for all 33 medical schools. The mean total teaching time specifically for T&O throughout medical school was 18 days, ranging from 3 to 60 days in total. 118 BOTA members were reviewed. No member of BOTA in the study had attended medical school in Keele, Liverpool, Plymouth or Lancashire. These universities taught below the national average number of days in T&O. Conclusions: There is a large national variance in the number of compulsory teaching days provided for T&O. The authors advocate medical schools to aim for at least the national average in duration of T&O of 18 days.
Job Crafting Interventions: What Works, for Whom, Why, and in Which Contexts? Research Protocol for a Realist Synthesis With Coincidence Analysis
Authors: Roczniewska Marta , Rogala Anna , Marszałek Magdalena , Hasson Henna , Bakker Arnold B. , Schwarz Ulrica von Thiele
Published: June 2021

Background:Job crafting (JC) refers to self-initiated changes that employees introduce to their jobs to optimize their job design and increase the fit between the job and their needs and preferences. These behaviors can be stimulated by job crafting training interventions, which aim to change how individual employees design, organize, or manage their work. However, knowledge on JC interventions and their effects is still scarce. Additionally, the findings are spread across distinct theoretical approaches and the interventions are implemented in various ways. We have yet to determine which context and intervention factors are necessary or sufficient to achieve desired outcomes. The overall aim of this project will be to investigate how to implement effective JC interventions. Specifically, we will detect what factors are minimally sufficient and/or necessary to produce a successful JC intervention, as well as the multiple alternative paths to their success.Methods: We will perform a realist synthesis of the JC interventions literature combined with coincidence analysis (CNA). We will search electronic databases of journals and utilize Rayyan software to make decisions regarding inclusion. Data regarding context (e.g., fit), intervention (e.g., types of activities), mechanisms (e.g., intention implementation), and outcomes (e.g., employee well-being, job performance) will be extracted using a pre-piloted form and coded into a crisp-set (factor present vs. absent). Analyses will be carried out using CNA package in R.Discussion:This realist synthesis will address gaps in knowledge about the context, intervention and mechanism-related factors that may impact the effects of JC interventions. Consequently, this review will help develop a program theory for JC interventions that explains what works, how and under which circumstances. Applying CNA to synthesize these complex solutions across multiple studies provides an innovative method that may be used in future realist syntheses evaluating the implementation of interventions. Finally, our synthesis will provide knowledge relevant to organizational practitioners and scholars who want to implement JC interventions.Systematic review registration:https://osf.io/2q7cn (registration pending)
Vectorial Competence Potential of Culex Quinquefasciatus (Say, 1923) from the Amazon Region to Transmit West Nile Virus Isolated in Brazil
Authors: Reis Lúcia Aline Moura , Silva Eliana Vieira Pinto da , Freitas Maria Nazaré Oliveira , Caldeira Rossela Damasceno , Araújo Pedro Arthur da Silva , Silva Fábio Silva da , Junior José Wilson Rosa , Brandão Roberto Carlos Feitosa , Medeiros Daniele Barbosa de Almeida , Martins Lívia Caricio , Dias Daniel Damous , Neto Joaquim Pinto Nunes
Published: June 2021

The West Nile virus is characterized as a neurotropic pathogen that causes the West Nile fever. It is transmitted by mosquitoes, mainly of the Culex genus. In 2018, the Evandro Chagas Institute carried out the first isolation of WNV strain from a horse brain sample and in 2021 the same institute also isolated the WNV in a pool of mosquitoes of the Culex spp. from the Carajás region (Pará). Thus, this study aimed to determine the vectorial competence of Culex quinquefasciatus from the Amazon region of Brazil for transmission the WNV Brazilian strain. Oral infection of Cx. quinquefasciatus females belonging to F1 generation was performed with infected blood with WNV. Subsequently, analysis of infection, dissemination and transmission rates was performed, as well as verification of viral titers in the samples. The study demonstrated that Cx. quinquefasciatus can act as a potential vector of WNV in Brazil, since it was found that the Brazilian strain was able to overcome the host's anatomical barriers and spread to various regions, among them in saliva, in which, despite the low viral titers identified, it had a transmission rate of 100% on the 21st day after infection.
A Natural History Comparison of SOD1-mutant Patients with Amyotrophic Lateral Sclerosis between Chinese and German Populations
Authors: Tang Lu , Dorst Johannes , Chen Lu , Liu Xiaolu , Ma Yan , Günther Kornelia , Michels Sebastian , Müller Kathrin , Freischmidt Axel , Weishaupt Jochen H. , Fan Dongsheng , Ludolph Albert C.
Published: June 2021

Background: The gene coding the Cu/Zn superoxide dismutase (SOD1) was the first-identified causative gene of amyotrophic lateral sclerosis (ALS), and the second most common genetic cause for ALS worldwide. The promising therapeutic approaches targeting SOD1 mutations are on the road. The purpose of the present study was to compare the mutational and clinical features of Chinese and German patients with ALS carrying mutations in SOD1 gene, which will facilitate the strategy and design of SOD1-targeted trials. Methods: Demographic and clinical characteristics were collected from two longitudinal cohorts in China and Germany. Chinese and German patients carrying SOD1 mutations were compared with regard to mutational distribution, age of onset, site of onset, body mass index (BMI) at diagnosis, diagnostic delay, progression rate, and survival. Results: A total of 66 Chinese and 84 German patients with 69 distinct SOD1 mutations were identified. The most common mutation in both populations was p.His47Arg. It was found in 8 Chinese and 2 German patients and consistently showed a slow progression of disease in both countries. Across all mutations, Chinese patients showed a younger age of onset (43.9 vs 49.9 years, p=0.002), a higher proportion of young-onset cases (62.5% vs 30.7%, p<0.001) and a lower BMI at diagnosis (22.8 vs 26.0, p<0.001) compared to German patients. Although riluzole intake was less frequent in Chinese patients (28.3% vs 81.3%, p<0.001), no difference in survival between populations was observed (p=0.90). Across both cohorts, female patients had a longer diagnostic delay (15.0 vs 11.0 months, p=0.01) and a prolonged survival (248.0 vs 60.0 months, p=0.005) compared to male patients. Conclusions: Our data demonstrate the distinct mutational and clinical spectrums of SOD1-mutant patients in Asian and European populations. Clinical phenotypes seem to be primarily influenced by mutation-specific, albeit not excluding ethnicity-specific factors. Further large-scale transethnical studies are needed to clarify determinants and modifiers of SOD1 phenotypes.
Carbon-ion Evokes Metabolic Reprogramming and Individualized Response in Prostate Cancer
Authors: Pei Yulei , Ning Renli , Li Ping , Hu Wei , Deng Yong , Hong Zhengshan , Sun Yun , Guo Xiaomao , Zhang Qing
Published: June 2021

Background: Carbon ion radiotherapy (CIRT) is a novel and powerful tool for prostate cancer (PCa). However, the underlying mechanism for individualized treatment response after CIRT was not clear, and there was still no effective indicator to timely demonstrate the treatment response. Metabolic reprogramming is one of the main hallmarks of malignancy. Metabolic status might have a high relationship with the radiosensitivity and the individualized radiation response. The significant changes of metabolites profiles were detected after radiotherapy in the serum sample of different malignancies. But there was limited data regarding CIRT induced metabolic changes in prostate cancer. Our aim was to preliminary investigate the carbon-ion induced metabolic reprogramming in PCa patients and the individualized response of PCa patients to carbon ion. Methods: Urine samples collected from 15 pathology confirmed PCa patients before and after CIRT were enrolled into this analysis. High-throughput UPLC-MS/MS system was used for metabolites detection. XCMS online, MetDNA and MSDIAL were used for peak detection and identification of metabolites. Statistical analysis and metabolic pathway analysis were performed on Metaboanalyst.Results: A total of 1701 metabolites were monitored by high-throughput UPLC-MS/MS and 217 metabolites were identified. The PCA scores plot revealed clear discrimination of the patient’s urine metabolites profiles before (pre-CIRT) and after (pre-CIRT) CIRT treatment. 35 metabolites significantly altered after CIRT, and these metabolites mainly were amino acid. Pathway enrichment analysis further identified these metabolites could be enriched in 8 pathways (FDR<0.05, impact>2), while arginine biosynthesis and histidine metabolism pathways were the most significant. In addition, the HCA shows that after CIRT, the patients can be clustered into two groups according to the metabolites profiles. The discriminatory metabolites after CIRT in patients urine mainly enriched in the pathway of arginine biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis. Conclusion: Metabolic reprogramming and metabolic inhibition seems one of the most important mechanisms of CIRT to cure PCa. Urine metabolites also showed their potentials to timely identify the individualized response of PCa patients to CIRT.
Bacterial Communities of Sediments in a Seawater-Freshwater Transition Zone During the Wet and Dry Seasons in Pearl River Estuary
Authors: Li Yongbin , Huang Duanyi , Sun Weimin , Sun Xiaoxu , Yan Gen , Gao Wenlong , Lin Hanzhi
Published: June 2021

Seawater intrusion has a detrimental effect on agriculture, industry and human health. One question of particular interest is how the microbial community responds to and reflects seawater intrusion with seasonal variation. The current study explored the seasonal changes in bacterial community composition and interaction in the vicinity of Pearl River Estuary in January (dry season) and September (wet seasons). Results indicated that the salinity (expressed as electrical conductivity value) of sediment samples obtained in dry season was higher than that in wet season. The salt stress induced a declined alpha diversity but resulted in a loosely connected and unstable biotic interaction network in the bacterial communities. Random forest prediction and redundancy analysis of bacterial community indicated that salinity substantially affected the bacterial communities. Multiple lines of evidence, including the enrichment of bacterial taxa in the high-salinity location, microbe-microbe interactions, environment-microbe interactions, and machine learning approach, demonstrated that the families Moraxellaceae and Planococcaceae were the keystone taxa and were resistant to salt stress, which suggested that both of them can be used as potential biological indicators of monitoring and controlling seawater intrusion in coastal zone areas.
Elaiophylin Targets EIF4B to Regulate the Proliferation, Invasion, and Apoptosis of Esophageal Squamous Cell Carcinoma via the PI3K/AKT Signaling Pathway
Authors: Lijuan Gao , Yongshun Chen , Bin Li
Published: June 2021

BackgroundEsophageal cancer remains a dominating cause of cancer-associated death and has shown a sharp increase of more than 6-fold increase rates all over the world. It is divided into two main pathological types: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Most of the patients are diagnosed at the advanced stage with distant metastasis and poor prognosis. Thus, it is urgent for us to identify new more effective drugs to improve the prognosis of patients with esophageal cancer. Elaiophylin is a novel autophagy inhibitor at the late stage, which is a C2 symmetric macrolides separated from Streptomyces Niger. It was proved to have anti-tumor ability of various of cancers, yet little is known whether it could inhibit the progression of esophageal squamous cancer. The study is aimed to explore the effect of Elaiophylin on ESCC. MethodsThe protein expression level was detected by western blot assay. The viability of ESCC cells was detected by CCK8 assay. The proliferation rate was measured by ki67 immunofluorescent staining. The migratory ability of ESCC cells was identified by transwell assay. The apoptosis rate of ESCC cells was explored by Annexin V/PI analysis. And the genes might be regulated by Elaiophylin was analyzed by RNA-seq assay and verified by RT-qPCR assay. The experiments in vivo were conducted by subcutaneous into tumor in BALB/C-Nu mice. ResultsIn the study, we firstly found that the Elaiophylin was a novel autophagy inhibitor in ESCC cells which is consistent with the previous studies. In addition, Elaiophylin can inhibit the proliferation and migration of ESCCs, and accelerate its apoptosis. And the activity of PI3K/AKT pathway was inhibited by Elaiophylin, the mRNA and protein expression level of EIF4B was both downregulated by Elaiophylin. Mechanistically, silencing of EIF4B could inhibit the proliferation and migration of ESCC cells and promoted apoptosis, which could be rescued by EIF4B-OE. Moreover, EIF4B overexpression suppressed the apoptosis, while increased the proliferation and migration of ESCC cells which resulted from Elaiophylin. Finally, Elaiophylin could inhibit the proliferation of esophageal cancer in vivo compared to the control group. ConclusionsTogether, our results indicated that Elaiophylin is a novel autophagy inhibitor governing growth and migratory ability of ESCC cells through PI3K/AKT signaling pathway and inhibit the proliferation of esophageal tumor in vivo. simultaneously, and identified EIF4B as a target of Elaiophylin, which might provide a new therapeutic strategy for esophageal squamous cell carcinoma.
Effects of Long-Term Warming on Microbial Nutrient Limitation of Soil Aggregates on the Qinghai-Tibet Plateau
Authors: Chen Wenjing , Zhou Huakun , Qiao Leilei , Li Yuanze , Wu Yang , Zhai Jiaying , Liu Guobin , Xue Sha
Published: June 2021

Background and aims Global warming has increasingly serious impacts on the structure and function of the Tibetan Plateau ecosystem. However, the mechanism by which warming affects the biogeochemical processes and consequently the microbial nutrient limitation in soil aggregates is not clear. Methods In the present study, we used open-top chamber experiments to simulate warming in an alpine meadow and an alpine shrubland on the Qinghai-Tibet Plateau to understand how warming affects nutrient utilization and microorganism-limiting mechanisms in soil aggregates. Results The results showed that long-term warming treatment had contrasting effects on soil organic carbon (SOC) content of the alpine meadow and that of the shrubland. This difference was more pronounced with the increase in soil aggregate size, and the SOC content in microaggregates (MIGA) was significantly higher than that in large macroaggregates (LMGA). Soil enzyme activity increased with the decrease in aggregate size and was not significantly affected by warming treatment. Enzyme stoichiometry demonstrated that microbial P limitation is widespread on the Tibetan Plateau, and the long-term warming treatment exacerbated it, which has significant differences in shrubland. At the same time, the long-term warming treatment had no significant effect on C limitation in the alpine shrubland and the alpine meadow, but soil aggregate size affected the C limitation patterns of microorganisms and showed strong limitations in MIGA. Conclusions The microbial P limitation in shrubland is more sensitive to warming than that of grassland. Soil aggregates mediate the acquisition of carbon by microorganisms, and the carbon limitation in MIGA is the greatest. By providing a new perspective on this topic, our study increased our understanding of the effects of warming on microbial nutrient utilization and restriction patterns in soil aggregates.
Effects of drought stress and rehydration on physiological and biochemical of four oak species in China
Authors: Xiong Shifa , Wang Yangdong , Chen Yicun , Gao Ming , Zhao Yunxiao , Wu Liwen
Published: June 2021

Background: Quercus fabri Hance, Quercus serrata Thunb, Quercus acutissima Carruth, and Quercus variabilis BL are four Chinese oak species commonly used for forestation. In recent years, with the global warming caused by the greenhouse effect, seedlings in mountainous areas after afforestation often suffer seasonal drought stress, which seriously affects their survival and growth. In order to ensure the survival of seedlings, we need to select oak species with strong drought resistance. Therefore, we first need to understand the differences in drought resistance of the four oak tree species at the seedling stage, and comprehensively evaluate their drought resistance capabilities by studying the changes in the physiological and biochemical characteristics of the seedlings under continuous drought and rehydration conditions.Methods: The four oak seedlings were divided into drought-rewatering treatment group and normal watering control group. For the seedlings of the drought-rewatering treatment group, drought stress lasting 31 days was used, and then re-watering and recovering for 5 days. The water parameters, osmotic adjustment substance content, antioxidant enzyme activity and photosynthesis parameters of the seedlings in the two groups were measured every 5 days. Principal component analysis, correlation analysis and membership function were used to analyze the physiological and biochemical characteristics of the seedlings of the four oak in two groups.Results and conclusions: Compared with the control group, the relative water content, water potential, net photosynthetic rate, transpiration rate, and stomatal conductance levels of the four oaks all showed a downward trend under continuous drought stress, and showed an upward trend after rehydration. The soluble protein, soluble sugar, proline, peroxidase, superoxide dismutase and catalase content of the four oaks increased first and then decreased under drought stress, and then increased after rehydration. The content of glycine betaine and malondialdehyde continued to increase, and gradually decreased after rehydration. The weight of each index was calculated by PCA, and then the comprehensive evaluation of each index was carried out through the membership function method. The drought resistance levels of the four oak species were as follows: Q. serrata > Q. fabri > Q. variabilis > Q. acutissima.
Expression Levels of MCP-1, HGF, and IGF-1 in Endometriotic Patients Compared with Non-endometriotic Controls
Authors: Heidari Sahel , Khodaverdi Sepideh , Kolahdouz-Mohammadi Roya , Tajik Nader , Delbandi Ali-Akbar
Published: June 2021

To study the concentrations of monocyte chemoattractant protein-1 (MCP-1), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1) in peritoneal fluid (PF) and serum, and to evaluate their expressions by PF and peripheral blood mononuclear cells (PFMCs and PBMCs, respectively), and ectopic and eutopic endometrial stromal cells of patients with endometriosis (EESCs and EuESCs, respectively) compared with controls. The concentrations of mentioned cytokines in serum and PF, as well as their expression in PBMCs, PFMCs, EuESCs and EESCs from endometriosis patients and controls were assessed. The levels of MCP-1, HGF, and IGF-1 in serum and PF in women with endometriosis were significantly higher than the controls (P < 0.05-P < 0.001). Gene expression of MCP-1 and IGF-1 in the PFMCs, PBMCs and EESCs also showed an increased level compared to controls (P < 0.05-P < 0.0001). The protein expressions of MCP-1 and IGF-1 by PFMCs were statistically higher in endometriotic women (P < 0.05 and P < 0.01, respectively). The gene and protein expression of HGF in PFMCs and its gene expression by EESCs were significantly higher in endometriotic women compared to controls (P < 0.05-P < 0.01). The higher concentrations of mentioned cytokines in serum and PF and their higher expressions by PFMCs and EESCs in endometriosis patients may contribute to the development of endometriosis.
Placental Trophoblast Derived Exosomes Regulate Endometrial Epithelial Receptivity in Dairy Cows During Pregnancy
Authors: Su Yue , Li Qianru , Zhang Qiaochu , Li Zhiming , Yao Xinxin , Guo Yong , Xiao Longfei , Wang Xiangguo , Ni Hemin
Published: June 2021

Background

Inadequate feto-maternal interaction will directly lead to the failures of pregnancy and bring serious damage to dairy cows. Exosomes are widely involved in endometrial matrix remodeling, immune function changes, placental development, and other processes of embryo implantation and pregnancy of dairy cows. However, the role of placental trophoblast cells derived exosomes is still unclear in regulating the receptivity of endometrial cells and facilitating the interaction between mother and fetus.
Methods

In this study, bovine trophoblast cells (BTCs) were obtained from bovine placenta and immortalized through the transfection of telomerase reverse transcriptase (TERT) gene. After that, the effect of trophoblast derived exosomes (TDEs) on endometrial receptivity in endometrial epithelial cells (EECs) was detected and the mechanism explored that TDEs and their proteins participated in feto-maternal interaction during bovine pregnancy. EECs were co-cultured with the exosomes derived from progesterone (P4) and treated with BTCs.
Results

Immortalized BTCs still possessed the basic and key properties of primary BTCs without showing a neoplastic transformation sign. Exosomes derived from P4 and treated with BTCs enhanced the expression of endometrial receptivity factors in EECs by changing the extracellular environment, metabolism and redox balance in EECs with proteome alignment, compared with those untreated according to the DIA quantitation analysis.
Conclusions

Our study found that trophoblast derived exosomal proteins are one of the most critical elements in feto-maternal interaction and their changes act as a key signal in altering endometrial receptivity and provided a potential target for improving fertility.
Multinomial Classification of Patterns in Lung Cancer Biopsy Slides Using Customized Convolutional Neural Network
Authors: Yang Jung Wook , Song Dae Hyun , An Hyo Jung , Seo Sat Byul
Published: June 2021

Identifying the lung carcinoma subtype in small biopsy specimens is an important part of determining a suitable treatment plan but is often challenging without the help of special and/or immunohistochemical stains. Pathology image analysis that tackles this issue would be helpful for diagnoses and subtyping of lung carcinoma. In this study, we developed AI models to classify multinomial patterns of lung carcinoma (adenocarcinoma, squamous cell carcinoma, small cell carcinoma, large cell neuroendocrine carcinoma) and non-neoplastic lung tissue based on convolutional neural networks (CNN or ConvNet). Four CNNs that were pre-trained using transfer learning and one CNN built from scratch were used to classify patch images from pathology whole-slide images (WSIs). We evaluated the diagnostic performance of each model in the test sets. The Xception model achieved the highest performance among pre-trained CNNs with an accuracy of 0.86 and an area under the curve (AUC) of 0.97. The built from scratch CNN model obtained an accuracy of 0.92 and an AUC ranging from 0.99 to 1.00 for subtyping lung carcinoma tasks. These results demonstrate how promising CNN models are for developing improved diagnostic workflow systems for diagnosis and subtyping of lung carcinoma. Of particular note is the fact that the built from scratch CNN described in this paper achieves prompt and consistent results so has the potential to be applied in working hospitals for pathological diagnoses.
All-Purpose Nanostrategy Based on Dose Deposition Enhancement, Cell Cycle Arrest, DNA Damage and ROS Production as Prostate Cancer Radiosensitizer for Potential Clinical Translation
Authors: Guo Xiao-xiao , Guo Zhen-hu , Wu Meng , Lu Jing-song , Xie Wen-sheng , Zhong Qiu-zi , Chi Yong-jie , Sun Xiao-dan , Wang Xiu-mei , Wang Jian-ye , Liu Ming , Zhao Lingyun
Published: June 2021

Background

Radiotherapy (RT) is one of the main treatments for men with prostate cancer (PCa). Yet, to date, with numerous sophisticated nano-formulations as radiosensitizers have been synthesized with inspiring therapeutic effect both in vitro and in vivo, there still lacks the successful clinical translation of such nanosystems. Meanwhile, almost all the attention has been paid on the enhanced dose deposition effect by secondary electrons of nanomaterials with high atomic numbers (Z), despite that cell-cycle arrest, DNA damage and also reactive oxygen species (ROS) production are critical working mechanisms accounting for radiosensitization.
Methods

Herein, an ‘all-purpose’ nanostrategy based on dose deposition enhancement, cell cycle arrest and ROS production as prostate cancer radiosensitizer for potential clinical translation was proposed. The rather simple structure of docetaxel loaded Au nanoparticles (NPs) with prostate specific membrane antigen (PSMA) ligand conjugation have been successfully synthesized by a rather facile protocol.
Results

Enhanced cellular uptake achieved via selective internalization of the NPs by PCa cells with positive PSMA expression could guarantee the enhanced dose deposition. Moreover, the as-synthesized nanosystem could arrest cell cycle at G2/M phases, which would reduce the ability of DNA damage repair for more irradiation sensitive of the PCa cells. Meanwhile, G2/M phases arrest would further promote cascade retention and enrichment of the NPs within the cells. Furthermore, ROS generation and double strand breaks greatly promoted by the NPs under irradiation (IR) could also provide an underlying basis for effective radiosensitizers.
Conclusions

Investigations from in vitro and in vivo confirmed the as-synthesized NPs as an effective nano-radiosensitizer with ideal safety. More importantly, all the moieties within the present nanosystem have been approved by FDA for the purpose of PCa treatment, thus making the it highly attractive for clinical translation.
METTL3-Mediated m6A Modification is Involved in Neural Tube Defects via Modulating Wnt/β-Catenin Signaling Pathway
Authors: Zhang Li , Cao Rui , Li Dandan , Sun Yuqing , Zhang Juan , Wang Xiuwei , Khan Ajab , Liu Zhizhen , Niu Bo , Xu Jun , Xie Jun
Published: June 2021

Neural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with a NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Therefore, identifiable of novel pathogenic strategies for NTDs patients is urgently required. Increasing evidence indicates that METTL3-mediated m6A modification is present in many physiopathological processes of cell apoptosis and survival. Our results demonstrate that SAM play not only a compensatory role, SAM can also lead to m6A modification changes in neural tube development and regulation. This research provides a good theoretical basis for further research on folic acid deficiency leading to NTDs, reveals the important role of SAM in the development of NTDs, and provides new clue for clinical researchers and clinical work.
Current prevalence and determinants of anaemia in under-five children in rural Bangladesh: a cross sectional study
Authors: Mollah Md. Moniruzzaman , Mosaddi Ashik , Hossain Asgor , Roy Andrew A. , Naznin Sultana , Hassan Parvez
Published: June 2021

Background
Anaemia and its association with low physical and cognitive development in under-five children remain as a common public health burden in developing countries including Bangladesh. Childhood anemia is significantly associated with age, rural residence, infant and young child feeding (IYCF) practices, infectious disease, maternal illiteracy etc. We have studied to identify current prevalence, and to explore associated socio-demographic, health, and nutritional factors of anaemia in under-five children of rural Bangladesh.
Methods and materials
A cross-sectional study was conducted at five remote northern districts of Bangladesh involving rural children aged 6 - <60 months. We used an interviewer-administered questionnaire for data collection. Potential study subjects were approached conveniently at selected rural health centres. Chi-squared test was the main statistical model to identify association between explanatory variables and anaemia. A p-value <0.05 was considered as significant.
Results
Overall prevalence of anaemia (N = 258) was 61.23% with mild, moderate and severe anaemia of 28.29%, 28.68% and 4.26% respectively. The prevalence of anaemia was the highest (72%) in age group 6-24 months, which were followed by 63% in >24-36 months and 44.3% in >36-<60 months categories. The following explanatory variables showed statistically significant association with high anaemia: younger-age (p = <0.001), low family income, and maternal education (p = <0.001), exclusive versus non-exclusive breast feeding (p = 0.02), and timely versus delayed or early weaning (p = <0.001). Non consumption of animal proteins, fruits and green leafy vegetables were also significantly linked to high anaemia prevalence (p = 0.001). Further, underweight, stunting, and wasting were significantly related to anaemia (p = 0.02, 0.006, and 0.001 respectively).
Conclusion
Prevalence of anaemia in under-five children of rural Bangladesh remains noticeably high. Age, maternal education, family income, consumption of animal protein, green leafy vegetables, and fruits along with underweight, stunting and wasting are inversely related to anaemia prevalence. Exclusive breast feeding and timely weaning may reduce risk of anaemia.
Integration and Gene Co-Expression Network Analysis of scRNA-seq Transcriptomes Reveal Heterogeneity and Key Functional Genes in Human Spermatogenesis
Authors: Salehi Najmeh , Karimi-Jafari Mohammad Hossein , Totonchi Mehdi , Amiri-Yekta Amir
Published: June 2021

Spermatogenesis is a complex process of cellular division and differentiation that begins with spermatogonia stem cells and leads to functional spermatozoa production. However, many of the molecular mechanisms underlying this process remain unclear. Single-cell RNA sequencing (scRNA-seq) is used to sequence the entire transcriptome at the single-cell level to assess cell-to-cell variability. Here, more than 33,000 testicular cells from five scRNA-seq datasets with normal spermatogenesis were integrated to identify single-cell heterogeneity on a more comprehensive scale. Clustering, cell type assignments, differential expressed genes and pseudotime analysis characterized 5 spermatogonia, 4 spermatocyte, and 4 spermatid cell types during the spermatogenesis process. The UTF1 and ID4 genes were introduced as most specific markers that can differentiate two undifferentiated spermatogonia stem cell sub-cellules, and C7orf61 and TNP, two round spermatid sub-cellules. The topological analysis of the weighted gene co-expression network along with the integrated scRNA-seq data revealed some bridge genes between spermatogenesis’s main stages such as DNAJC5B, C1orf194, HSP90AB1, BST2, EEF1A1, CRISP2, PTMS, NFKBIA, CDKN3, and HLA-DRA. The importance of these key genes is confirmed by their role in male infertility in the available studies. It can be stated that, this integrated scRNA-seq of spermatogenic cells offers novel insights into cell-to-cell heterogeneity and suggests a list of key players with a pivotal role in male infertility from the fertile spermatogenesis datasets. These key functional genes can be introduced as candidates for filtering and prioritizing of genotype-to-phenotype association in male infertility.
Gut Microbiome Alteration of Cold-adapated Antarctic copepod Tigriopus kingsejongensis with Temperature Changes and Developmental Stages
Authors: Oh Han Na , Ri Myeong Nu , Kim Taeyune , Min Gi-Sik , Kim Sanghee , Sul Woo Jun
Published: June 2021

Tigriopus kingsejongensis, a copepod species, reported from the King Sejong Station, Antarctica, serves as a valuable food resource in ecosystems. Some copepods were temperature-sensitive in growth and post-embryonic development. We cultured T. kingsejongensis at three different temperatures (2°C, 8°C, and 15°C) in a laboratory to observe the alterations in the stool microbiome of copepods depending on the cultivation temperature and developmental stages. We observed copepod gut microbiome changes by increasing temperatures: a lower microbial diversity, a higher abundance of aquatic microbes, Vibrio, and a lower abundance of the psychrophilic microbes, Colwellia. Also, the copepod gut microbiome, according to the developmental stage, was changed: a lower microbial diversity in egg-attached copepods than nauplius at 8°C. We further analyzed three shotgun metagenomes from T. kingsejongensis stool samples at different temperatures and obtained 44 metagenome-assembled genomes (MAGs). We noted that MAGs of V. splendidus D contained glycosyl hydrolase (GHs) encoding chitinases and virulence factors with higher relative abundance at 15°C than at lower temperatures. These results that temperature and developmental stages affect the gut microbiome of copepods are helpful to understand the changes in the low-temperature adapted copepod with climate change.