bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Propofol on Hypoxia- and TNF-α-Mediated Brain-Derived Neurotrophic Factor/Tyrosine Kinase Receptor B Pathway Dysregulation in Primary Rat Hippocampal Neurons and Astrocytes
Authors: Tao Weiping , Zhang Xuesong , Ding Juan , Yu Shijian , Ge Peiqing , Han Jingfeng , Luo Xing , Cui Wei , Chen Jiawei 
Published: June 2021

Abstract
Background: BDNF/TrkB pathway dysregulation may be induced by hypoxia and inflammation, and play pivotal roles during the development of neurological disorders. Propofol is an anesthetic agent with neuro-protective properties. We aimed to verify whether propofol affected BDNF/TrkB pathway in neurons exposed to hypoxia or TNF-α.Methods: Primary rat hippocampal neurons and astrocytes were cultured and exposed to propofol followed by hypoxia or TNF-α treatment. The production of BDNF and the expression/truncation/phosphorylation of TrkB were measured. The underlying mechanisms such as ERK, CREB, p35 and Cdk5 were investigated.Results: In hippocampal neurons and astrocytes, hypoxia and TNF-α reduced the production of BDNF. Pretreatment of hippocampal neurons with 25μM propofol reversed the inhibitory effect of hypoxia or TNF-α on BDNF production. However, even 100μM propofol had no such effect in astrocytes. Further, we found that in hippocampal neurons hypoxia and TNF-α increased the phosphorylaion of ERK (p-ERK) and CREB at Ser142 (p-CREBSer142), while reduced the phosphorylation of CREB at Ser133 (p-CREBSer133), which were all reversed by 25μM propofol and 10μM ERK inhibitor. In addition, neither hypoxia nor TNF-α affected TrkB expression, truncation or phosphorylation in hippocampal neurons and astrocytes. However 50μM propofol induced TrkB phosphorylation without affecting its expression and truncation only in hippocampal neurons. Furthermore, we detected that in hippocampal neurons, 50μM propofol induced p35 expression and Cdk5 activation, and blockade of p35 or Cdk5 mitigated propofol-induced TrkB phosphorylation.Conclusions: Propofol, via ERK/CREB and p35/Cdk5, may modulate BDNF/TrkB pathway in hippocampal neurons that were exposed to hypoxia or TNF-α.
Changes In The Gut Microbiota After Hepatitis C Virus Eradication
Authors: Honda Takashi , Ishigami Masatoshi , Yamamoto Kenta , Takeyama Tomoaki , Ito Takanori , Ishizu Yoji , Kuzuya Teiji , Nakamura Masanao , Kawashima Hiroki , Miyahara Ryoji , Ishikawa Tetsuya , Hirooka Yoshiki , Fujishiro Mitsuhiro 
Published: June 2021

Abstract
The gut microbiota interacts with infectious diseases and affects host immunity. It has also been reported that liver disease is associated with changes in the gut microbiota. To investigate changes in the gut microbiota before and after eradication of hepatitis C virus (HCV) by direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C (CHC), we investigated 42 samples from 14 CHC patients who received DAA therapy for HCV. Faecal samples were obtained before treatment (Pre), when treatment ended (EOT), and 24 weeks after treatment ended (Post24). The target V3–4 region of the 16S rRNA gene from faecal samples was amplified using the Illumina Miseq sequencing platform. The diversity of the gut microbiota did not differ significantly between Pre, EOT, and Post24. PCoA analysis showed that for each patient, the values at Pre, EOT, and Post 24 were concentrated within a small area. LEfSe analysis showed that the relative abundances of Faecalibacterium and Bacillus were increased at EOT and further increased at Post24, and these genera were significantly increased at Post24 compared to Pre. These results suggest that changes in the gut microbiota need to be considered as among the various effects on living organisms observed after HCV elimination.
Tolerance of Dosed Physical Loads in the Rehabilitation of Patients With a Recent Experience of Myocardial Infarction or Unstable Angina
Authors: Chenguang Mu , Ivanovna Kushakova Nadezhda , Evgenievich Bobyrev Vladimir 
Published: June 2021

Abstract
Objective: The study of reaction to dosed physical load of patient with recent experience of myocardial infarction or unstable angina to assess objectively physical condition and performance, to appoint an adequate individual program of physical rehabilitation and to optimize the effectiveness of the sanatorium stage of rehabilitation of this category of patients.Design: Study and observational analysis.Parameter: The subsidiary «Sanatorium-resort rehabilitation center «Slaviansk resort», the sanatorium «Yubileiny», Ukraine.Participants: Patients with recent experience of myocardial infarction or unstable angina who arrived at the sanatorium stage of rehabilitation from cardiological hospitals of Donetsk and Lugansk regions (Ukraine).Intervention: Non-invasive treatment (i.e. therapeutic exercise)Results: 3530 patients who arrived at the sanatorium stage of rehabilitation from cardiological hospitals of Donetsk and Lugansk regions (Ukraine) on 29,4 ±2,4 day of illness were examined. Men accounted for 64%, women - 36%. The average age of the patients was 54,4 ±1,8 years old. 1127 people (31,93 %) had a Q-positive myocardial infarction (MI), 388 people (10,99 %) – a Q-negative, 2015 people (57,08 %) – an unstable angina.When studying the tolerance to dosed physical activity, threshold or inadequate reactions were observed in 144 patients (12.78%) who had Q-positive myocardial infarction, 13 patients (3.35%) who had Q-negative myocardial infarction and 89 patients (4.42%) who had unstable angina. Threshold or inadequate responses in patients with recent experience of Q-positive myocardial infarction were recorded 3-4 times more often. The electrocardiographic examination revealed most often changes in the terminal part of the ventricular complex in the form of inversion or reversal of T waves, to a greater extent in patients who had Q-positive myocardial infarction.Conclusions: It was found in the course of study that patients with recent experience of Q-positive myocardial infarction master less physical activity at the sanatorium stage of rehabilitation than patients of other groups. Our study has shown that an insufficient level of physical activity does not give an optimal effect in increasing the functional reserves of the cardiovascular system and the body as a whole, and insufficient control of an increase in the level of physical activity is fraught with negative consequences.Careful selection of optimal physical activity for this category of patients allowed to prescribe adequate physical activity to patients and avoid possible complications.
A Low-Power and Low Cost Smart Streetlight System Based on Internet of Things Technology
Authors: Zhang Jingjing , Zeng Weihua , Hou Shengli , Chen Yuqi , Guo Linyan , Li Yanxing 
Published: June 2021

Abstract
Street lighting, as the most essential and universal component of the urban lighting system, accounts for a large portion of public electricity usage. Therefore, improving street lamps working efficiency is vital for energy savings. This paper demonstrates the design of a smart street lighting system supported by the combination of NB-IoT and LoRa communication technology. By adopting an optimized street lamp control algorithm, the system can realize the automatic control of street lights according to the real-time traffic flow information. This system has been installed on Luyang Avenue, Lucheng City, Shanxi Province, China in May 2019. It managed to reduce the electricity consumption in this region significantly in June 2019, which was 18% lower than that in April 2019 and 19.7% lower than that in June 2018. By illustrating the unique advantages of this system in energy savings and cost reduction, this paper displays its potential for further application in the construction of smart cities on a large scale.
Efferent and Afferent Connections of the Supratrigeminal Neurons Conveying Orofacial Muscle Proprioception in Rats
Authors: Yoshida Atsushi , Inoue Misaki , Sato Fumihiko , Morita Yayoi , Tsutsumi Yumi , Furuta Takahiro , Uchino Katsuro , Akhter Fatema , Bae Yong Chul , Tachibana Yoshihisa , Inoue Tomio 
Published: June 2021

Abstract
The supratrigeminal nucleus (Su5) is a key structure for controlling jaw-movements since it receives proprioceptive sensation from jaw-closing muscle spindles (JCMSs) and sends projection to the trigeminal motor nucleus (Mo5). However, the central projection and regulation of JCMS proprioceptive sensation have not been fully understood. Therefore, we aimed to reveal the efferents and afferents of the Su5 by means of neuronal tract tracings. Anterograde tracer injections into the Su5 revealed that the Su5 sent contralateral projections (or bilateral projections with a contralateral predominance) to the Su5, basilar pontine nuclei, pontine reticular nucleus, deep mesencephalic nucleus, superior colliculus, caudo-ventromedial edge of ventral posteromedial thalamic nucleus, parafascicular thalamic nucleus, zona incerta, and lateral hypothalamus, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) to the intertrigeminal region, trigeminal oral subnucleus, dorsal medullary reticular formation, and hypoglossal nucleus as well as the Mo5. Retrograde tracer injections into the Su5 demonstrated that the Su5 received bilateral projections with a contralateral predominance (or contralateral projections) from the primary and secondary somatosensory cortices, granular insular cortex and Su5, and ipsilateral projections (or bilateral projections with an ipsilateral predominance) from the dorsal peduncular cortex, bed nuclei of stria terminalis, central amygdaloid nucleus, lateral hypothalamus, parasubthalamic nucleus, trigeminal mesencephalic nucleus, parabrachial nucleus, juxtatrigeminal region, trigeminal oral and caudal subnuclei, and dorsal medullary reticular formation. These findings suggest that the Su5 receiving JCMS proprioceptive sensation has efferent and afferent connections with multiple brain regions, which are involved in emotional and autonomic functions as well as orofacial motor functions.
Dihydroartemisinin Exhibits Antitumor Activity Toward Human Gastric Cancer Cells Through the Endoplasmic Reticulum Stress Pathway
Authors: Chen Si , Wang Hanlin , Chen Tie , Deng Furong , Li Hongbin , Xia Lixin , Zhang Jian 
Published: June 2021

Abstract
Background: Gastric cancer is the most fatal digestive tract tumor. The current treatment of gastric cancer often causes adverse effects. Dihydroartemisinin (DHA), a first-line antimalarial drug, is a derivative of a compound from a well-known Chinese medicinal plant Artemisia annua. DHA demonstrates antitumor activities toward many different types of cancer while exerts no apparent adverse effects on normal cells, making it a promising lead compound for cancer treatment. DHA induces apoptosis in Gastric cancer cell line 7901 (SGC-7901). However, the exact mechanism of this antitumor activity remains not fully explored. Methods: A CCK-8 assay to detect cell viability with DHA treatment in gastric cancer SGC-7901. The colony formation was visualized by crystal violet staining. The DHA-treatment cells were stained by Annexin-V FITC/PI dye and then subject to cell flow cytometry. The apoptosis was further observed in the Hoechst staining assay. Real-time qPCR was conducted to detect apoptosis-related markers. Western blotting was conducted to detect the protein levels of the endoplasmic reticulum (ER) stress pathway-related proteins. KIRA6, an ER stress pathway inhibitor was applied to find out whether it could reverse the cell death. Results: DHA induced dose-dependent apoptosis in Gastric SGC-7901 cell with an IC50 of about 4 mg/ mL. It significantly increased the proportion of apoptotic cells in a dose-dependent pattern in the Annexin V/PI flow cytometry. Significantly higher percentages of cells with a more prominently stained nucleus were observed in the Hoechst staining assay. In qPCR assay, the mRNA level of Bcl-2 was significantly decreased while that of Bax was significantly increased in a dose-dependent manner after DHA treatment. In the western blot assay, increased Bax and Bim and decreased Caspase 9, Bcl-2 were observed. Consistently, the levels of pro-apoptotic proteins were increased while those of anti-apoptotic ones were decreased as shown in the Human Apoptosis Array assay after DHA treatment. DHA stimulated the expression of GRP78, ATF4, IRE1, CHOP, and phosphorylated c-Jun (p-c-Jun) as revealed in western blotting. The cell death caused by DHA treatment was reversed by KIRA6. Conclusions: DHA exerts its antitumor activity on SGC-7901 cells through the IRE1/c-Jun ER stress pathway.
Ctnna3 Deficiency Promotes Heart Regeneration by Enhancing Cardiomyocyte Proliferation in Neonatal Mice
Authors: zou sha , Dai Wuhou , Li Jifen , Wang Hongyan , Tao Wufan 
Published: June 2021

Abstract
Heart regeneration requires renewal of lost cardiomyocytes. However, the mammalian heart loses its proliferative capacity soon after birth, and the molecular signaling underlying the loss of cardiac proliferation postnatally is not fully understood. Here we report that ablation of Ctnna3, coding for an αT-catenin protein and highly expressed in hearts, accelerated heart regeneration following heart apex resection in neonatal mice. Our results show that Ctnna3 deficiency enhances cardiomyocyte proliferation in hearts from P7 mice by upregulating Yap expression. Our study demonstrates that Ctnna3 deficiency is sufficient to promote heart regeneration and cardiomyocyte proliferation in neonatal mice and indicates that functional interference of α-catenins might help to stimulate myocardial regeneration after injury.
Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model
Authors: Xu Yinlan , Wan Shuangxiu , Sun Panpan , Khan Ajab , Guo Jianhua , Zheng Xiaozhong , Sun Yaogui , Fan Kuohai , Yin Wei , Li Hongquan , Sun Na 
Published: June 2021

Abstract

Background

PCV2 (Porcine circovirus type 2) is one of the major pathogens commonly in pigs, which can cause immunosuppression and apoptosis. Vaccinations and single drugs are not totally prevent and treat PCV2 diseases. We have previously reported that the synergistic anti-PCV2 effects of Matrine and Osthole were better than Matrine or Osthole alone in vitro, Matrine and Osthole were purchased with a clear content, chemical structure and plant origin. This study aimes to evaluate theirs synergistic anti-PCV2 effect and mechanism in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups, namly: normal control group, PCV2 infected group, Matrine combined with Osthole high dose treatment group (40 mg/kg + 12 mg/kg), medium dose treatment group (20 mg/kg + 6 mg/kg), low dose treatment group (10 mg/kg + 3 mg/kg), Matrine treatment group (40 mg/kg), Osthole treatment group (12 mg/kg) and Ribavirin positive control group (40 mg/kg). PCV2 was intraperitoneally (i.p.) injected in all mice except the normal control group. At 5 days post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for 5 consecutive days.
Results

The synergistic inhibition effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly stronger than that of Matrine and Osthole alone. The protein expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax were significantly reduced, but the protein expression of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological change caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils.
Conclusions

The synergistic effect of anti-apoptosis was better than that of Matrine and Osthole alone, although both of Matrine and Osthole could also directly inhibited the expression of PCV2 Cap and then inhibited the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provide a new insight into controlling PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.
To Explore the Effect of NLR and PLR on Prognosis of Rectal Cancer on the basis of T3 substage, and to draw the related nomogram
Authors: Li Donglin , Wang Shuang , Yang Yongping , Zhao Zeyun , Shang An , Guo Yu , Wang Min 
Published: June 2021

Abstract
Background: Approximately 50% of patients with rectal cancer are classified into T3 stage, and they are positioned as substage by various criteria. These patients with different neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) develop disparate outcomes. We sought to develop and validate nomograms to predict survival in patients with rectal cancer on the basis of T3 substage.Methods: We conducted a retrospective cohort study by collecting 170 cases from China. Individuals with rectal cancer after 2 or more years of follow up after surgery were eligible for inclusion. Candidate predictors consisted of NLR, PLR, T3 substage and clinical characteristics available at the time of rectal cancer diagnosis. The optimal cut-off values for NLR and PLR were determined using X-Tile (Version 3.6.1) software and were determined before statistical analyses. Variables with P values below 0.1 in the univariable analyses were further evaluated using Cox multivariate analysis. Model discrimination was assessed using receiver operating characteristic (ROC) curve and concordance index (C-index) analysis. Results were internally validated using related software.Results: We analyzed data from 170 patients with T3 rectal cancer. The optimal cut-off value of NLR in relation to overall and disease-free survival were 3.1 and 2.9, and that of PLR were 181.9 and 202.7. Among them, postoperative adjuvant chemotherapy, T3 substage, N stage, CA199 and NLR were independent risk factors affecting overall survival（OS）and disease-free survival (DFS). There was no significant difference in survival rate between T3a and T3b, or between T3c and T3d. The final nomograms of 2-year OS (area under the curve,0.886; The c-index,0.870) and 2-year DFS (area under the curve,0.895; The c-index,0.867) were developed according to independent risk factors analyzed by SPSS 26 (SPSS Inc., Chicago, IL, USA) software. The calibration curves showed negligible optimism.Conclusion: We developed nomograms based on postoperative adjuvant chemotherapy, T3 substage, N stage, CA199 and NLR to help identify patients with poor prognosis and to guide individualized therapy.
Repurposing the Combination Drug of Favipiravir, Hydroxychloroquine and Oseltamivir as a Potential Inhibitor Against SARS-CoV-2: A Computational Study
Authors: Yadav Pooja , CHOWDHURY PAPIA 
Published: June 2021

Abstract
The virus SARS-CoV-2 has created a situation of global emergency all over the world from the last few months. We are witnessing a helpless situation due to COVID-19 as no vaccine or drug is effective against the disease. In the present study, we have tested the repurposing efficacy of some currently used combination drugs against COVID-19. We have tried to understand the mechanism of action of some repurposed drugs:Favipiravir (F), Hydroxychloroquine (H) and Oseltamivir (O). The ADME analysis have suggested strong inhibitory possibility of F, H, O combination towards receptor protein of 3CLpro of SARS-CoV-2 virus. The strong binding affinity, number of hydrogen bond interaction between inhibitor, receptor and lower inhibition constant computed from molecular docking validated the better complexation possibility of F + H + O:3CLprocombination. Various thermodynamical output from Molecular dynamics (MD) simulations like potential energy (Eg), temperature (T), density, pressure, SASA energy, interaction energies, Gibbs free energy (ΔGbind) etc., also favored the complexation between F + H + O and CoV-2 protease. Our in-silico results have recommended the strong candidature of combination drugs Favipiravir, Hydroxychloroquine and Oseltamivir as a potential lead inhibitor for targeting SARS-CoV-2 infections.
Prevalence and Time-Course of Diaphragmatic Dysfunction Following Lung Resection: A Repeated Ultrasonic Assessment
Authors: Daniel Matthieu , Lang Elodie , Huynh Thi Mum , Martin Julien , Brebion Myriam , Guessous Karim , Zlotnik Diane , Gouzien Laura , Chaouch Oussama , Delval Paul , Ferraris Arnaud , Pimpec-Barthes Françoise Le , Cholley Bernard 
Published: June 2021

Abstract
BACKGROUND: There is little information regarding diaphragmatic dysfunction (DD) following thoracic surgery. Ultrasound allows for non-invasive repeated assessments of diaphragmatic excursion (DE) and thickening fraction (DTF) at the bedside, reflecting DD. We aimed at determining the prevalence of DD and the time-course of DE and DTF following elective thoracic surgery. Secondary endpoints included the association between DD and postoperative complications. METHODS: We led a prospective, single center, observational study in consecutive patients undergoing thoracic surgery. DE and DTF were measured by two observers blinded to each other at 3 different time-points: prior to surgery (D-1), immediately after extubation (D0) and on postoperative day 3 (D3). The changes in excursion and thickening fraction of both hemi-diaphragms over time were compared according to the side (operated or non-operated) using a two-way ANOVA. The association with postoperative complications was assessed using logistic regression.RESULTS: Fifty patients, 60% males, aged 60±15 years were included. Surgical procedures included lobectomy (n=30), wedge-resection (n=17) or pneumonectomy (n=3). DD was highly prevalent after thoracic surgery and was observed on the operated side (or both sides) in, at least, 68% of patients immediately after surgery (D0). Among those patients, 46% still had this DD on the operated side on D3. On the operated side, we observed a decrease in DE and DTF at D0 (-0.71±0.12mm, P<0.05; -44±30%, P<0.05) and D3 (-0.82±0.19mm, P<0.05; -39±19%, P<0.05) with respect to values at D-1. On the non-operated side, mean values for DE and DTF did not change significantly over the study period. Persistent DD on the operated side, defined by a DD present at the two postoperative time-points, was associated with an increased risk of lung infection (P=0.001), ICU-admission (P=0.04) according to univariate analysis and a prolonged length in hospital (OR:1.3, 95% CI [1.1-1.7], P=0.016) according to multivariate analysis.CONCLUSIONS: Diaphragmatic Dysfunction (DD) was very common after thoracic surgery, mainly concerned the operated side and was associated with an increase in the diaphragmatic excursion on the non-operated side. When this dysfunction failed to regress within 72 hours, it was associated with a significant increase in the length of hospital stay.