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This study analyzed which imaging characteristics may contribute to misdiagnosis of benign and malignant thyroid nodules (TNs) through strain imaging (SI). We analyzed SI parameters and conventional ultrasound (CUS) characteristics of 264 nodules with histopathology results and we applied binary logistic regression analysis to select independent variables for incorrect SI results. The elastography imaging (EI) score and the virtual touch tissue imaging (VTI) score of malignant TNs were remarkably higher than that in benign TNs. VTI, of which the false-positive rate (FPR), the false-negative rate (FNR), and the cutoff value were 47.6% (39/82), 17.6% (32/182) and 3.5, presented higher diagnostic performance than EI. Aspect ratio (odd ratio [OR]: 14.208) and intra-nodular calcification (OR: 20.384) were significantly associated with false-positive VTI findings, while posterior acoustic feature (OR: 30.424) was significantly associated with false-negative VTI findings. Sex (OR: 0.221) and aspect ratio (OR: 0.268) were negatively associated with false-negative EI findings. In conclusion, sex and aspect ratio significantly affect the accuracy of EI results, while aspect ratio, intra-nodular calcification and posterior acoustic features notably affect the accuracy of VTI results. These CUS features of TNs should not be ignored before explaining SI examination results., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Background: Brain metastasis (BM) is thought to be related to the mortality and poor prognosis of non-small cell lung cancer (NSCLC). Despite promising development of NSCLC treatment, the treatment of NSCLC BM is still not optimistic due to the existence of the blood-brain barrier (BBB) that prevent drug penetration, as well as the short median survival time of the patients left for treatment. In this context, further development of quick and effective pre-clinical models is needed in NSCLC BM treatment. Here, we report a model system using zebrafish to promote the development of drugs for patients with NSCLC BM., Methods: Three different NSCLC cell lines (H1975, A549 and H1299) were used to establish zebrafish BM models. The embryo age and cell number for injection were first optimized. Metastatic cells were observed in the brain blood vessels of zebrafish and were verified by hematoxylin-eosin (HE) staining. Then, the metastasis potentials of H1975 and A549 with manipulated microRNA-330-3p (miR-330-3p) expression were also investigated. Finally, sensitivities of H1975 and A549 to osimertinib and gefitinib were tested., Results: This zebrafish BM model could distinguish NSCLC cell lines with different BM potential. Over-expressed miR-330-p significantly improved the BM potential of the A549 cells while knockdown miR-330-p reduced the BM ability of the H1975 cells. Both osimertinib and gefitinib showed inhibition effect in zebrafish BM model with the inhibition rate higher than 50 %. H1975 cell showed much higher sensitivity to osimertinib rather than gefitinib both in vivo and in vitro., Conclusions: We established zebrafish brain metastasis model for studying mechanism and treatment of NSCLC BM. This study provided a useful model for NSCLC brain metastasis that could be used to study the mechanism that drive NSCLC cells to the brain as well as identify potential therapeutic options., (© 2021. The Author(s).)

Background: Knee osteoarthritis (KOA) refers to a chronic deteriorating disease distinguished by degeneration of joint cartilage. Many clinical studies have demonstrated that isokinetic muscle strength training can improve muscle function in patients with KOA. However, although such studies deduce an excellent effect, the results remain controversial. Therefore, the present systematic review seeks to explore the curative effects of isokinetic muscle strength training to establish if it can improve muscle function in patients experiencing KOA., Methods: This review will entail a systematic review and a comprehensive examination to establish all randomized controlled studies covering curative effects of isokinetic muscle strength training to improve muscle function in patients with KOA. We will obtain data from PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure, and WanFang databases from inception to September 2021. In addition, the study will employ the criterion postulated by Cochrane to ascertain a quality evaluation and risk assessment of the studies included for analysis. Also, we will employ relative risk, mean differences, and standardized mean differences with 95% confidence intervals to estimate the effective measures. Also, we will employ Cochran Q test and I2 statics to assess heterogeneity among the 2 studies., Results: Overall, this study anticipates providing accurate results and balanced inferences on curative effects of isokinetic muscle strength training for improving muscle function in patients with KOA., Conclusion: The study's inferences will offer evidence to decide whether isokinetic muscle strength training is an effective measure for improving muscle function in patients with KOA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

A series of indole-based [1,2,4]triazolo [4,3-a]pyridine derivatives was designed and synthesized as novel microtubulin polymerization inhibitors by using a conformational restriction strategy. These compounds exhibited moderate to potent anti-proliferative activities against a panel of cancer cell lines (HeLa, A549, MCF-7 and HCT116). Among them, compound 12d featuring a N-methyl-5-indolyl substituent at the C-6 position of the [1,2,4]triazolo [4,3-a]pyridine core exhibited the highest antiproliferative activity with the IC 50 values ranging from 15 to 69 nM, and remarkable inhibitory effect on tubulin polymerization with an IC 50 value of 1.64 μM. Mechanistic studies revealed that compound 12d induced cellular apoptosis and cell cycle arrest at the G 2 /M phase in a dose-dependent fashion. Moreover, compound 12d significantly suppressed wound closure and disturbed microtubule networks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aβ 1-42 aggregation effectively ranged from 45.9-94.5 % at 20 μM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self-induced Aβ 1-42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu 2+ , and could effectively inhibit and disaggregate Cu 2+ -induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ 1-42 -induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)

Cornus Officinalis (Cornus), the dried pulp of mature Cornus, is used to treat liver diseases. However, the pharmacological mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC) has not been systematically studied. The chemical compounds and the bioactive chemical compounds of Cornus were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database was used to explore the targets in liver cancer pathogenesis. The disease-drug Venn diagram was constructed using the VENN 2.1 and the STRING database was used to analyze protein-protein Interaction Network (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R package. Molecular docking was performed using Discovery Studio were assessed using Pymol and Discovery Studio 2016. Cell survival of BEL-7404 cells treated by Hydroxygenkwanin (HGK) were valued through CCK-8 assay. Expressions of caspase-3 and cleaved PARP was detected through Western blot. Pharmacological network diagrams of the Cornus compound-target network and HCC-related target network were successfully constructed. A total of 20 active compounds, 1841 predicted biological targets of Cornus, and 7100 HCC-related targets were identified. 37 target genes between Cornus and HCC were screened trough the network pharmacology. Molecular docking studies suggested that HGK has the highest affinity with caspase-3. HGK could induce apoptosis of HCC cells and significantly activate the caspase-3 protease activity in BEL-7404. This study systematically elaborated the mechanism of Cornus in the treatment of HCC and provided a new perspective to exploit Antineoplastic from Cornus., (Copyright © 2021. Published by Elsevier B.V.)

Objective To investigate the differences of gut microbiota between patients with abdominal aortic aneurysm and atherosclerosis.Methods From December 2018 to June 2019,20 fresh stool samples were collected respectively from the patients with abdominal aortic aneurysm and atherosclerosis treated at the Department of Vascular Surgery,Peking Union Medical College Hospital.The 16S rDNA high-throughput sequencing was employed to compare the composition,abundance,and α and β diversities of gut microbiota between the two disease groups,and further determine the significantly differential genera.Results The two groups had great similarities in the composition of gut microbiota.There was no statistical difference in α diversity.Although β diversity did not have statistically significant difference,certain microbial taxa showed differences between the two groups.The LEfSe demonstrated that the abdominal aortic aneurysm group had higher relative abundance of Leuconostocaceae , Ruminococcaceae , Weissella ,and Faecalibacterium while lower relative abundance of Firmicuteria , Selenomonadales ,and Veillonellaceae .Conclusion The structure of gut microbiota has differences between patients with abdominal aortic aneurysm and atherosclerosis,and sample size should be enlarged to validate the results.

Objective: To analyze the clinical characteristics, diagnosis and prognostic factors of bone marrow necrosis (BMN) patients, aim to avoid misdiagnosis, missed diagnosis or delayed treatment., Methods: The clinical data of 51 BMN patients treated in the Affiliated Hospital of Xuzhou Medical University from January 2010 to December 2017 were retrospectively analyzed. The types of primary disease, etiology, clinical manifestations, laboratory tests, radiological findings, treatment outcomes and prognostic factors were summrized, and the reasons for misdiagnosis were analyzed., Results: Among 51 BMN patients, the hematologic tumor was detected out in 32 patients; solid tumors caused- BMN was detected out in 14 patients, benign lesions for 5 patients. The time of interval from the appearance of symptoms to the confirmation of BMN was 7 days to 6 months, with a median of 35 days. Misdiagnosis and missed diagnosis occurred in 25.5% of the BMN patients. Anemia was found in all of the 51 BMN patients, fever accounted for 58.8%, systemic bone pain for 52.9%, bleeding for 29.4%, lymphadenectasis for 37.3%, and hepatosplenomegaly for 19.6%. Leukoerythroblastic anemia accounted for 84.3%, bicytopenia for 51.0%, pancytopenia for 25.5%, and monocytopenia for 23.5%. The serologic test revealed no specific results. The first bone marrow aspiration were 38 patients and multi-site puncture were 7 patients. The diagnostic coincidence rate of bone marrow smear was 88.2%. Among 51 BMN patients, 41 patients received bone marrow biopsy, and the diagnostic coincidence rate of bone marrow biopsy was 75.6%. The abnormal signals were found in multiple vertebral bodies by spinal/pelvic MRI scan in 13 BMN patients; PET-CT scan revealed a diffuse pattern of low FDG uptake in the bone marrow in 16 patients, with a local increase in FDG uptake accompanied by bone marrow involvement. For 46 patients with BMN combined with malignancies, among which 35 patients died (76.1%) and the median survival time was 25 days. Among the 32 patients with hematologic tumors, early death occurred in 12 patients, BMN disappeared in 11 out of 20 patients received active chemotherapy for the primary disease, 9 patients died within 1 week to 3 months. Fourteen patients combined with bone marrow metastatic carcinoma died within 2 weeks to 3 months. Focal necrosis disappeared in 4 out of 5 BMN patients secondary to non-malignant diseases after symptomatic supportive treatment and still alived. Multiple logistic regression was performed to analyze factors affecting the prognosis of BMN patients, the result showed that the prognosis of BMN was closely related to the factors of primary disease (benign and malignant). The reasons for misdiagnosis and missed diagnosis were as follows: hidden onset of the primary disease, nonspecific symptoms, insufficient understanding and alertness of the physicians regarding the primary clinical characteristics and hematological abnormalities, and failure to receive multiple sites bone marrow punctures or bone marrow biopsies., Conclusion: BMN usually occurs concomitantly to hematologic tumors and bone marrow metastases from solid tumors. Its prognosis is closely related to the nature and severity of the primary disease and its own severity. In the clinic, BMN should be suspected in patients with severe bone pain, fever, hepatosplenomegaly, hemocytopenia, lymphadenectasis and leukoerythroblastic anemia. Bone marrow puncture at multiple positions and bone marrow biopsy can compensate for each other in the diagnosis of BMN. The combined use of the two methods can improve the diagnostic coincidence rate of BMN, and the positive rate of the etiological diagnosis of BMN.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common cause of dementia in an aging population. The majority of research effort has focused on the role of neurons in neurodegeneration and current therapies have limited ability to slow disease progression. Recently more attention has been given to the role of astrocytes in the process of neurodegeneration. Specifically, reactive astrocytes have both advantageous and adverse effects during neurodegeneration. The ability to isolate and depict astrocyte phenotype has been challenging. However, with the recent development of single-cell sequencing technologies researchers are provided with the resource to delineate specific biomarkers associated with reactive astrocytes in AD. In this review, we will focus on the role of astrocytes in normal conditions and the pathological development of AD. We will further review recent developments in the understanding of astrocyte heterogeneity and associated biomarkers. A better understanding of astrocyte contributions and phenotypic changes in AD can ultimately lead to more effective therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Monterey, Wei, Wu and Wu.)

Large quantities of bacteria, including Firmicutes , Actinobacteria , and Bacteroidetes , colonize the surface of the respiratory mucosa of healthy people. They interact and coexist with the local mucosal immune system of the human airway, maintaining the immune stability and balance of the respiratory system. While suffering from chronic respiratory diseases, the microbial population in the airway changes and the proportion of Proteobacteria is increased in patients with asthma. The abundance of the microbial population in patients with chronic obstructive pulmonary disease (COPD) is decreased, and conversely, the proportion of Firmicutes and Proteobacteria increased. The diversity of airway microorganisms in cystic fibrosis (CF) patients is decreased, while pathogenic bacteria and conditional pathogenic bacteria are proliferated in large numbers. The proportion of Firmicutes and Proteobacteria is increased in patients with upper airway cough syndrome (UACS), which replaces the dominance of Streptococcus and Neisseria in the pharynx of a normal population. Therefore, a clear understanding of the immune process of the airway flora and the immune dysfunction of the flora on the pathogenesis of chronic respiratory diseases can provide new ideas for the prevention and treatment of human respiratory diseases., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Mei-Ying Guo et al.)

Metal-organic frameworks (MOFs) with carboxylate ligands as co-catalysts are very efficient for the oxygen evolution reaction (OER). However, the role of local adsorbed carboxylate ligands around the in-situ-transformed metal (oxy)hydroxides during OER is often overlooked. We reveal the extraordinary role and mechanism of surface-adsorbed carboxylate ligands on bi/trimetallic layered double hydroxides (LDHs)/MOFs for OER electrocatalytic activity enhancement. The results of X-ray photoelectron spectroscopy (XPS), synchrotron X-ray absorption spectroscopy, and density functional theory (DFT) calculations show that the carboxylic groups around metal (oxy)hydroxides can efficiently induce interfacial electron redistribution, facilitate an abundant high-valence state of nickel species with a partially distorted octahedral structure, and optimize the d-band center together with the beneficial Gibbs free energy of the intermediate. Furthermore, the results of in situ Raman and FTIR spectra reveal that the surface-adsorbed carboxylate ligands as Lewis base can promote sluggish OER kinetics by accelerating proton transfer and facilitating adsorption, activation, and dissociation of hydroxyl ions (OH - )., (© 2021 Wiley-VCH GmbH.)

Long-term missing teeth can lead to alveolar bone loss in the edentulous area. Guided bone regeneration (GBR) is a bone augmentation method. It is widely used in clinical practice and broadens the indications of orthodontic treatment to a certain extent. This article reports a case of an adult patient with edentulous space in the maxillary central incisor, which was successfully closed through orthodontic treatment combined with GBR. This study will provide a re-ference for future clinical work.

Despite the global economic importance of the wheat leaf rust pathogen Puccinia triticina ( Pt ), genomic resources for Pt are limited and chromosome-level assemblies of Pt are lacking. Here, we present a complete haplotype-resolved genome assembly at a chromosome-scale for Pt using the Australian pathotype 64-(6),(7),(10),11 (Pt64; North American race LBBQB) built upon the newly developed technologies of PacBio and Hi-C sequencing. PacBio reads with ∼200-fold coverage (29.8 Gb data) were assembled by Falcon and Falcon-unzip and subsequently scaffolded with Hi-C data using Falcon-phase and Proximo. This approach allowed us to construct 18 chromosome pseudomolecules ranging from 3.5 to 12.3 Mb in size for each haplotype of the dikaryotic genome of Pt64. Each haplotype had a total length of ∼147 Mb, scaffold N 50 of ∼9.4 Mb, and was ∼93% complete for BUSCOs. Each haplotype had ∼29,800 predicted genes, of which ∼2,000 were predicted as secreted proteins (SPs). The investigation of structural variants (SVs) between haplotypes A and B revealed that 10% of the total genome was spanned by SVs, highlighting variations previously undetected by short-read based assemblies. For the first time, the mating type (MAT) genes on each haplotype of Pt64 were identified, which showed that MAT loci a and b are located on two chromosomes (chromosomes 7 and 14), representing a tetrapolar type. Furthermore, the Pt64 assembly enabled haplotype-based evolutionary analyses for 21 Australian Pt isolates, which highlighted the importance of a haplotype resolved reference when inferring genetic relationships using whole genome SNPs. This Pt64 assembly at chromosome-scale with full phase information provides an invaluable resource for genomic and evolutionary research, which will accelerate the understanding of molecular mechanisms underlying Pt -wheat interactions and facilitate the development of durable resistance to leaf rust in wheat and sustainable control of rust disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Song, Ding, Dong, Hasan and Park.)

Spinal cord injury disrupts ascending and descending neural signals causing sensory and motor dysfunction. Neuromodulation with electrical stimulation is used in both clinical and research settings to induce neural plasticity and improve functional recovery following spinal trauma. However, the mechanisms by which electrical stimulation affects recovery remain unclear. In this study we examined the effects of cortical electrical stimulation following injury on transcription at several levels of the central nervous system. We performed a unilateral, incomplete cervical spinal contusion injury in rats and delivered stimulation for one week to the contralesional motor cortex to activate the corticospinal tract and other pathways. RNA was purified from bilateral subcortical white matter and 3 levels of the spinal cord. Here we provide the complete data set in the hope that it will be useful for researchers studying electrical stimulation as a therapy to improve recovery from the deficits associated with spinal cord injury., (© 2021. The Author(s).)

Objective: To investigate the efficacy and tolerability of Polatuzumab vedotin+rituximab±bendamustine (Pola-(B)R) in relapse/refractory diffuse large B cell lymphoma (R/R DLBCL) patients. Methods: The clinical data of 21 patients enrolled in Chinese Pola compassionate use program (CUP) in 4 centers from November 2019 to August 2020 were collected. There were 15 males and 6 females, and the median age was 56 years (ranged 25-76 years). Of the patients, 10 cases received Pola-BR regimen and the other 11 received Pola-R. Their clinical features, regimens, efficacy, and adverse events (AEs) were retrospectively analyzed. Results: Twenty-one patients with at least one efficacy evaluation were included. At data analysis cut-off point (12 Aug. 2020), the best overall response (BOR) rate was 81.0% (17/21) and the complete response (CR) rate was 19.0% (4/21). Kaplan-Meier survival estimation was performed, at a median follow-up of 54 days, three patients (14.3%) had disease progressed, and 18 patients (85.7%) were censored; the median progression-free survival (mPFS) was estimated to be 148 days. The incidence of adverse effects (AEs) of any grade was higher in Pola-BR group than Pola-R group (80.0% vs 63.6%). However, the incidence of grade 3-4 AEs were close in the two groups (30.0% vs 29.3%). The most common hematological toxicities were thrombocytopenia (28.6%, 6/21), neutropenia (28.6%, 6/21) and anemia (14.3%, 3/21), respectively. One patient with pneumonia and 1 patient with hemophagocytic syndrome recovered after symptomatic treatment. No peripheral neuropathy of grade≥2 was observed. Conclusions: The preliminary data suggested that, for heavily treated Chinese R/R DLBCL, the Pola-(B)R regimen still achieves promising efficacy and tolerable safety.

Due to tumor heterogeneity, the consistency of programmed cell death-ligand 1 (PD-L1) expression between circulating tumor cells (CTCs) and tissue is controversial. This study aimed to establish a method for detecting CTC PD-L1 expression and exploring the impact of the same on the prognosis of lung cancer. In 32 patients with non-small cell lung cancer, lung cancer cells in the blood were enriched using CD326 immunomagnetic beads. Goat anti-mouse polyclonal CD326 antibody stained the epithelial lung cancer cells and anti-PD-L1 antibody was used to detect the expression of CTC PD-L1. The DAKO Link 48 automatic staining device detected the expression in lung cancer tissue. The consistency of PD-L1 expression was analyzed in lung cancer tissue and CTCs. The effect of plasma interferon gamma, tumor necrosis factor alpha, and interleukin-2 on PD-L1 expression and prognosis was analyzed. The number of CTCs detected in patients was 1-36, with a median of 2. There was no significant difference in PD-L1 expression fractions between CTCs and paired tumor tissue (p>0.05). The correlation coefficient was 0.20. Regardless of lung cancer tissue or CTCs, there was no statistically significant difference in the blood cytokine levels between the two groups with positive or negative PD-L1 expression (p>0.05). There was no correlation between CTCs and PD-L1 in 23 untreated patients. The expression of PD-L1 in CTCs and lung cancer tissue is heterogeneous and unaffected by the peripheral cytokines' levels. PD-L1 expression has no correlation between CTCs and tissues and is not related to prognosis.

Background: Oligodendrocytes, responsible for axon ensheathment, are critical for central nervous system (CNS) development, function, and diseases. OLIG2 is an important transcription factor (TF) that acts during oligodendrocyte development and performs distinct functions at different stages. Previous studies have shown that lncRNAs (long non-coding RNAs; > 200 bp) have important functions during oligodendrocyte development, but their roles have not been systematically characterized and their regulation is not yet clear., Results: We performed an integrated study of genome-wide OLIG2 binding and the epigenetic modification status of both coding and non-coding genes during three stages of oligodendrocyte differentiation in vivo: neural stem cells (NSCs), oligodendrocyte progenitor cells (OPCs), and newly formed oligodendrocytes (NFOs). We found that 613 lncRNAs have OLIG2 binding sites and are expressed in at least one cell type, which can potentially be activated or repressed by OLIG2. Forty-eight of them have increased expression in oligodendrocyte lineage cells. Predicting lncRNA functions by using a "guilt-by-association" approach revealed that the functions of these 48 lncRNAs were enriched in "oligodendrocyte development and differentiation." Additionally, bivalent genes are known to play essential roles during embryonic stem cell differentiation. We identified bivalent genes in NSCs, OPCs, and NFOs and found that some bivalent genes bound by OLIG2 are dynamically regulated during oligodendrocyte development. Importantly, we unveiled a previously unknown mechanism that, in addition to transcriptional regulation via DNA binding, OLIG2 could self-regulate through the 3' UTR of its own mRNA., Conclusions: Our studies have revealed the missing links in the mechanisms regulating oligodendrocyte development at the transcriptional level and after transcription. The results of our research have improved the understanding of fundamental cell fate decisions during oligodendrocyte lineage formation, which can enable insights into demyelination diseases and regenerative medicine.

A pair of stereoisomers of new 4,5-dihydroxypiperine was isolated from P. retrofractum and showed profound activity on AlCl 3 -induced dementia. In order to determine their absolute configurations and biological activities, all four possible stereoisomers of 4,5-dihydroxypiperine were synthesized from piperidine by Sharpless asymmetric dihydroxylation and Mitsunobu reaction. Their absolute configurations were established as (4R,5R) (1), (4S,5S) (2), (4S,5R) (3) and (4R,5S) (4) by NMR, optical rotation and CD spectra. It is note that only compound 4 improved behavioral disorder in AlCl 3 -induced dementia. Accordingly, the pair of stereoisomers isolated from P. retrofractum was determined to be (4S,5S) and (4R,5S)-isomers (2 and 4). The ratio of the epimers was present as 1:0.7 (4:2)., (Copyright © 2021. Published by Elsevier Ltd.)

Pseudorabies virus (PRV) is related to alphaherpesvirus and varicellovirus. pUL16 is a conserved protein in all herpesviruses, and studies have shown that UL16 can interact with the viral proteins pUL11, pUL49, pUL21, gD, and gE. In this study, we found that pUL16 interacted with the viral capsid protein VP26, which could not translocate into the nucleus itself but did appear in the nucleus. We further determined whether pUL16 assists the translocation of VP26 into the nucleus. We found that pUL16 interacted with VP26 with or without viral proteins, and since VP26 itself did not contain a nuclear location signal, we concluded that pUL16 assisted the translocation of VP26 into the nucleus. Deletion of UL16 and UL35 significantly reduced the 50 % tissue culture infective dose, virulence, attachment, and internalization of PRV in cells. These results show that the interaction between pUL16 and VP26 influences the growth and virulence of pseudorabies virus. Our research is the first study to show that pUL16 interacts with VP26, which may explain the targeting site of UL16 and viral capsids. It is also the first to show that UL16 assists the transport of other viral proteins to organelles. Previous researches on pUL16 usually emphasized its interaction with pUL11, pUL21, and gE, and sometimes commented on pUL49 and gD. Our research focuses on the novel interaction between pUL16 and VP26, thereby enriching the studies on herpesviruses and possibly providing different directions for researchers., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment., Methods: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR., Results: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities., Conclusion: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients., Clinical Trial Registration: ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: The purpose of present study was to identify the differentially expressed genes (DEGs) associated with BMP-9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by using bioinformatics methods., Methods: Gene expression profiles of BMP-9-induced MSCs were compared between with GFP-induced MSCs and BMP-9-induced MSCs. GSE48882 containing two groups of gene expression profiles, 3 GFP-induced MSC samples and 3 from BMP-9-induced MSCs, was downloaded from the Gene Expression Omnibus (GEO) database. Then, DEGs were clustered based on functions and signaling pathways with significant enrichment analysis. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in cytoplasm, nucleus, and extracellular exosome signaling pathway., Results: A total of 1967 DEGs (1029 upregulated and 938 downregulated) were identified from GSE48882 datasets. R/Bioconductor package limma was used to identify the DEGs. Further analysis revealed that there were 35 common DEGs observed between the samples. GO function and KEGG pathway enrichment analysis, among which endoplasmic reticulum, protein export, RNA transport, and apoptosis was the most significant dysregulated pathway. The result of protein-protein interaction (PPI) network modules demonstrated that the Hspa5, P4hb, Sec61a1, Smarca2, Pdia3, Dnajc3, Hyou1, Smad7, Derl1, and Surf4 were the high-degree hub nodes., Conclusion: Taken above, using integrated bioinformatical analysis, we have identified DEGs candidate genes and pathways in BMP-9 induced MSCs, which could improve our understanding of the key genes and pathways for BMP-9-induced osteogenic of MSCs.

Background: Lima bean (Phaseolus lunatus L.) is a member of subfamily Phaseolinae belonging to the family Leguminosae and an important source of plant proteins for the human diet. As we all know, lima beans have important economic value and great diversity. However, our knowledge of the chloroplast genome level of lima beans is limited., Results: The chloroplast genome of lima bean was obtained by Illumina sequencing technology for the first time. The Cp genome with a length of 150,902 bp, including a pair of inverted repeats (IRA and IRB 26543 bp each), a large single-copy (LSC 80218 bp) and a small single-copy region (SSC 17598 bp). In total, 124 unique genes including 82 protein-coding genes, 34 tRNA genes, and 8 rRNA genes were identified in the P. lunatus Cp genome. A total of 61 long repeats and 290 SSRs were detected in the lima bean Cp genome. It has a typical 50 kb inversion of the Leguminosae family and an 70 kb inversion to subtribe Phaseolinae. rpl16, accD, petB, rsp16, clpP, ndhA, ndhF and ycf1 genes in coding regions was found significant variation, the intergenic regions of trnk-rbcL, rbcL-atpB, ndhJ-rps4, psbD-rpoB, atpI-atpA, atpA-accD, accD-psbJ, psbE-psbB, rsp11-rsp19, ndhF-ccsA was found in a high degree of divergence. A phylogenetic analysis showed that P. lunatus appears to be more closely related to P. vulgaris, V.unguiculata and V. radiata., Conclusions: The characteristics of the lima bean Cp genome was identified for the first time, these results will provide useful insights for species identification, evolutionary studies and molecular biology research.

Background: Poor sleep quality is increasingly recognized as an important and potentially modifiable risk factor for cardiovascular disease (CVD). Impaired endothelial function may be 1 mechanism underlying the association between poor sleep and CVD risk. The present study examined the relationship between objective measures of sleep quality and endothelial function in a sample of untreated hypertensive adults., Methods: Participants were 127 men (N = 74) and women (N = 53), including 55 African Americans and 72 White Americans, aged 40-60 years (mean age, 45.3 ± 8.5 years), with untreated hypertension (systolic blood pressure 130-159 mm Hg and/or diastolic blood pressure 85-99 mm Hg). Noninvasive brachial artery flow-mediated dilation (FMD) was assessed by ultrasound. Sleep parameters, including sleep efficiency (SE), total sleep time (TST), and subjective sleep quality, were assessed over 7 consecutive days by wrist actigraphy., Results: Participants averaged 7.76 ± 1 hours in bed, with an average SE of 78 ± 9%, and TST of 6 ± 1 hours. Brachial FMD averaged 3.5 ± 3.1%. In multivariate analyses controlling for sex, race, body mass index, clinic blood pressure, income, smoking, alcohol use, and baseline arterial diameter, SE was positively associated with FMD (β = 0.28, P = 0.012). Subjective sleep quality (β = -0.04, P = 0.63) and TST (β = -0.11, P = 0.25) were unrelated to FMD., Conclusions: Poor sleep as indicated by low SE was associated with impaired FMD. These findings for SE are consistent with previous observations of other measures implicating poor sleep as a CVD risk factor. Interventions that improve sleep may also help lower CVD risk., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Borylated aza-arenes are of great importance in the area of organic synthesis. A radical borylative cyclization of isocyanoarenes with N-heterocyclic carbene borane (NHC-BH 3 ) under metal-free conditions was developed. The reaction allows the efficient assembly of several types of borylated aza-arenes (phenanthridines, benzothiazoles, etc.), which are difficult to access using alternative methods. Mild reaction conditions, a good functional-group tolerance, and generally good efficiencies were observed. The utility of these products is demonstrated, and the mechanism is discussed.

α-Haloboronates are useful organic synthons that can be converted to a diverse array of α-substituted alkyl borons. Methods to α-haloboronates are limiting and often suffer from harsh reaction conditions. Reported herein is a photochemical radical C-H halogenation of benzyl N-methyliminodiacetyl (MIDA) boronates. Fluorination, chlorination, and bromination reactions were effective by using this protocol. Upon reaction with different nucleophiles, the C-Br bond in the brominated product could be readily transformed to a series of C-C, C-O, C-N, C-S, C-P, and C-I bonds, some of which are difficult to forge with α-halo sp 2 -B boronate esters. An activation effect of B(MIDA) moiety was found., (© 2020 Wiley-VCH GmbH.)

The multi metal organic frameworks (BTC-CoNiFeZn) were used as the precursors of in situ structure reconstruction in alkaline solution, and we synthesized hierarchical porous Ni,Fe-codoped Co-hydroxide nanowire array (Ni0.8Fe0.2/Co-H NAs/NF) catalyst for the oxygen evolution reaction (OER). Benefiting from the rational micro-structure, rich ion-accessible nanopores, and abundant defect sites, the target catalysts possess enhanced intrinsic activity. The obtained Ni0.8Fe0.2/Co-H NAs/NF catalysts show superior OER catalytic activity with a low overpotential of 231 mV at 10 mA cm-2, a small Tafel slope of 32.9 mV dec-1, and high cycle stability for 135 h with performance degradation of only about 4.4%.

Spinal cord injury (SCI) is one of the most devastating neural injuries without effective therapeutic solutions. Astrocytes are the predominant component of the scar. Understanding the complex contributions of reactive astrocytes to SCI pathophysiologies is fundamentally important for developing therapeutic strategies. We have studied the molecular changes in the injury environment and the astrocyte-specific responses by astrocyte purification from injured spinal cords from acute to chronic stages. In addition to protein-coding genes, we have systematically analyzed the expression profiles of long non-coding RNAs (lncRNAs) (>200 bp), which are regulatory RNAs that play important roles in the CNS. We have identified a highly conserved lncRNA, Zeb2os, and demonstrated using functional assays that it plays an important role in reactive astrogliosis through the Zeb2os/Zeb2/Stat3 axis. These studies provide valuable insights into the molecular basis of reactive astrogliosis and fill the knowledge gap regarding the function(s) of lncRNAs in astrogliosis and SCI., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Guchang Zhixie Wan (GZW) is a commonly used Chinese medicine for the treatment of ulcerative colitis (UC). This research explored the potential pharmacological mechanism of GZW in UC. The active ingredients, potential targets, and UC-related genes of GZW were retrieved from public databases. The pharmacological mechanisms including key components, potential targets and signal pathways were determined through bioinformatics analysis. The results of this study were verified through virtual molecular docking and cell experiments. Network analysis revealed that 26 active GZW compounds and 148 potential GZW target proteins were associated with UC. Quercetin, kaempferol and β-sitosterol were identified as the core active ingredients of GZW. IFNG, IL-1A, IL-1B, JUN, RELA, and STAT1 were indicated as key targets of GZW. These key targets have a strong affinity for quercetin, kaempferol, and β-sitosterol. GO and KEGG enrichment analysis showed that GZW target proteins are highly enriched in inflammatory, immune, and oxidative stress-related pathways. This study confirmed the therapeutic effect and revealed potential molecular mechanism of GZW on UC. And the protective effects of GZW on inflammatory bowel disease pathway were also revealed through STAT3/NF-κB/IL-6 pathway. The findings of this study enhanced our understanding of GZW in the treatment of UC and provided a feasible method for discovering potential drugs from traditional Chinese medicine formulations., (© 2020 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Total knee arthroplasty is a common surgery for end-stage of knee osteoarthritis. Proprioceptive training has become an important part in athletes training programmes in different sports. However, the effects of proprioceptive training on the recovery of total knee arthroplasty were unknown. This meta-analysis, with its comprehensive and rigorous methodology, will provide better insight into this problem., Methods and Analysis: Electronic databases including PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI) database, Wanfang Database and Chinese Biomedical Literature Database (CBM) were searched from its inception to October 21, 2020. We only included proprioceptive training vs placebo in patients after total knee arthroplasty and pooled results were summarized by STATA 12.0 software. Two researchers independently selected the study and assessed the quality of the included studies. The heterogeneity was measured by I2 tests (I2 < 50 indicates little heterogeneity, I2 ≥ 50 indicates high heterogeneity). Publication bias was ruled out by funnel plot and statistically assessed by Beggs test (P > .05 as no publication bias)., Results: Results will be published in relevant peer-reviewed journals., Conclusion: Our study aims to systematically present the clinical effects of proprioceptive training after total knee arthroplasty patients, which will be provide clinical guidance for total knee arthroplasty patients., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: In previous analyses of the MURANO study, fixed-duration venetoclax plus rituximab (VenR) resulted in improved progression-free survival (PFS) compared with bendamustine plus rituximab (BR) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). At the 4-year follow-up, we report long-term outcomes, response to subsequent therapies, and the predictive value of molecular and genetic characteristics., Patients and Methods: Patients with CLL were randomly assigned to 2 years of venetoclax (VenR for the first six cycles) or six cycles of BR. PFS, overall survival (OS), peripheral-blood minimal residual disease (MRD) status, genomic complexity (GC), and gene mutations were assessed., Results: Of 389 patients, 194 were assigned to VenR and 195 to BR. Four-year PFS and OS rates were higher with VenR than BR, at 57.3% and 4.6% (hazard ratio [HR], 0.19; 95% CI, 0.14 to 0.25), and 85.3% and 66.8% (HR, 0.41; 95% CI, 0.26 to 0.65), respectively. Undetectable MRD (uMRD) at end of combination therapy (EOCT) was associated with superior PFS compared with low MRD positivity (HR, 0.50) and high MRD positivity (HR, 0.15). Patients in the VenR arm who received ibrutinib as their first therapy after progression (n = 12) had a reported response rate of 100% (10 of 10 evaluable patients); patients subsequently treated with a venetoclax-based regimen (n = 14) had a reported response rate of 55% (six of 11 evaluable patients). With VenR, the uMRD rate at end of treatment (EOT) was lower in patients with GC than in those without GC ( P = .042); higher GC was associated with shorter PFS. Higher MRD positivity rates were seen with BIRC3 and BRAF mutations at EOCT and with TP53 , NOTCH1 , XPO1 , and BRAF mutations at EOT., Conclusion: Efficacy benefits with fixed-duration VenR are sustained and particularly durable in patients who achieve uMRD. Salvage therapy with ibrutinib after VenR achieved high response rates. Genetic mutations and GC affected MRD rates and PFS.

Novel nano-composites were prepared by coating epoxy resin-based cationic polymer in nano-thickness via in-situ curing on the nano-wall of macroporous SiO 2 with pore size of 0.5∼1 μm. By changing the thickness of polymer coating the specific surface area and porosity varied in range of 115∼74 m 2 /g and 90.4∼83.9 %, respectively. Through ion exchange phospholipase D (PLD, from Streptomyces sp) was efficiently immobilized on the nano-composites as support and the immobilized PLD was applied for the highly efficient synthesis of phosphatidylserine (PS). The loading amount of PLD on the nano-composited support reached to a maximum of 90.2 mg/g support , 4 times as high as that on the pure macroporous silica. The specific activity of the immobilized PLD reached as high as 16,230 U/g protein , while that of free PLD was 18,780 U/g protein . Under a wide range of temperature and pH the stability and activity of the immobilized PLD were greatly improved as compared with the free ones. Under optimized conditions at 45 °C and pH 7.0, the PS yield reached as high as 96.2 % within 40 min. After 28 days storage the immobilized PLD retained 82.2 % of original activity, and after 12 cycling reuses it retained 79.3 % of PS yield, which indicated that the immobilized PLD exhibited good stability., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purposes: To investigate the efficiency of Thyroid Imaging Reporting and Data System (TI-RADS) proposed by KWAK, the American College of Radiology, and the 2015 American Thyroid Association (ATA) guidelines for thyroid nodules with Hashimoto's thyroiditis (HT) and to determine whether HT influence the diagnostic performance of these risk-stratification systems., Methods: A total of 101 nodules with HT and 101 nodules with non-HT were retrospectively analyzed by ultrasound-based diagnostic classifications and compared with histopathological results. The areas under the receiver operating characteristic curve (AUCs) were calculated for comparative analysis., Results: In the HT group, KWAK TI-RADS has the best sensitivity (91.67%), while ACR TI-RADS has the highest specificity (82.93%) and accuracy (81.19%). The AUCs of ACR TI-RADS, ATA guidelines, and KWAK TI-RADS were 0.844, 0.782, and 0.830, respectively. In the non-HT group, the sensitivity and specificity of three risk-stratification systems had no significant difference. The AUCs of ACR TI-RADS, ATA guidelines, and KWAK TI-RADS were 0.872, 0.839, and 0.874, respectively. No significant difference was found in diagnostic effectiveness of the same systems with both contexts., Conclusions: ACR TI-RADS performed the most effective for thyroid nodules in HT, whereas KWAK TI-RADS was the best for those in non-HT. Both of TI-RADS (ACR and KWAK) provided higher diagnostic effectiveness than ATA guidelines in HT or in non-HT. Moreover, HT could not affect the diagnostic performance of these risk-stratification systems., (Copyright © 2020. Published by Elsevier B.V.)

Musculoskeletal disorders are the leading causes of disability and result in reduced quality of life. The neuro-osteogenic network is one of the most promising fields in orthopaedic research. Neuropeptide Y (NPY) system has been reported to be involved in the regulations of bone metabolism and homeostasis, which also provide feedback to the central NPY system via NPY receptors. Currently, potential roles of peripheral NPY in bone metabolism remain unclear. Growing evidence suggests that NPY can regulate biological actions of bone marrow mesenchymal stem cells, hematopoietic stem cells, endothelial cells, and chondrocytes via a local autocrine or paracrine manner by different NPY receptors. The regulative activities of NPY may be achieved through the plasticity of NPY receptors, and interactions among the targeted cells as well. In general, NPY can influence proliferation, apoptosis, differentiation, migration, mobilization, and cytokine secretion of different types of cells, and play crucial roles in the development of bone delayed/non-union, osteoporosis, and osteoarthritis. Further basic research should clarify detailed mechanisms of action of NPY on stem cells, and clinical investigations are also necessary to comprehensively evaluate potential applications of NPY and its receptor-targeted drugs in management of musculoskeletal disorders., Competing Interests: Conflict-of-interest statement: The authors certify that they, or any members of their immediate families, have no funding or commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The leaf rust pathogen, Puccinia triticina ( Pt ), threatens global wheat production. The deployment of leaf rust ( Lr ) resistance (R) genes in wheat varieties is often followed by the development of matching virulence in Pt due to presumed changes in avirulence (Avr) genes in Pt . Identifying such Avr genes is a crucial step to understand the mechanisms of wheat-rust interactions. This study is the first to develop and apply an integrated framework of gene expression, single nucleotide polymorphism (SNP), insertion/deletion (InDel), and copy number variation (CNV) analysis in a rust fungus and identify candidate avirulence genes. Using a long-read based de novo genome assembly of an isolate of Pt ('Pt104') as the reference, whole-genome resequencing data of 12 Pt pathotypes derived from three lineages Pt104, Pt53, and Pt76 were analyzed. Candidate avirulence genes were identified by correlating virulence profiles with small variants (SNP and InDel) and CNV, and RNA-seq data of an additional three Pt isolates to validate expression of genes encoding secreted proteins (SPs). Out of the annotated 29,043 genes, 2392 genes were selected as SP genes with detectable expression levels. Small variant comparisons between the isolates identified 27-40 candidates and CNV analysis identified 14-31 candidates for each Avr gene, which when combined, yielded the final 40, 64, and 69 candidates for AvrLr1 , AvrLr15, and AvrLr24 , respectively. Taken together, our results will facilitate future work on experimental validation and cloning of Avr genes. In addition, the integrated framework of data analysis that we have developed and reported provides a more comprehensive approach for Avr gene mining than is currently available.

To investigate the effect of typical manure application on soil microbes in paddy fields, a field experiment on manure application in Chongming Island was carried out. The composition and variety of soil microorganisms in rice paddy fields were analyzed using high-throughput theory (CK), chicken manure (CM), pig manure (PM), and organic fertilizer (OF). The results showed that compared with CK, the application of organic manure increased soil organic matter (SOM), and the application of chicken manure significantly increased the soil ammonia nitrogen (NH 4 + -N) and total nitrogen (TN) contents ( P <0.05). Soil microbial diversity in the PM group was significantly higher than that in the CK group ( P <0.05), and the soil microbial community richness in the OF group was significantly higher than that in the CM group ( P <0.05). pH, total phosphorus (TP), total nitrogen, and Pb were the important factors affecting the composition of soil microbial communities in paddy fields. The microbial community structure in the CM group was significantly different from those in the other three groups. Compared with CK, the OF group increased the relative abundance of Nitrospira , and the CM group significantly reduced the relative abundance of the denitrifying bacteria Ignavibacteriae ( P <0.01) to 40.56%, but significantly increased the relative abundance of nitrifying bacteria Thauera ( P <0.05) to 203.00%. The PM group significantly increased the relative abundance of ammoniated bacteria Armatimonadetes ( P <0.05) to 57.51% and the anaerobic strain Anaerolinea to 102.00%. The application of chicken manure and pig manure significantly increased the relative abundance of pathogens Pseudomonas and Flavisolibacter ( P <0.05), respectively, while the application of organic manure reduced the relative abundance of Flavisolibacter . Overall, the application of manure increased the abundance of bacteria involved in the nitrogen cycle of paddy soils and played a positive role in regulating the nitrogen balance in paddy soils. However, direct application of chicken manure and fresh pig manure increased the abundance of pathogenic bacteria, which had a certain degree of stress on the soil health in the paddy field.

Objectives: Large-scale genetic analysis of common variation in schizophrenia has been a powerful approach to understanding this complex but highly heritable psychotic disorder. To further investigate loci, genes and pathways associated more specifically in the well-characterized Australian Schizophrenia Research Bank cohort, we applied genome-wide single-nucleotide polymorphism analysis in these three annotation categories., Methods: We performed a case-control genome-wide association study in 429 schizophrenia samples and 255 controls. Post-genome-wide association study analyses were then integrated with genomic annotations to explore the enrichment of variation at the gene and pathway level. We also examine candidate single-nucleotide polymorphisms with potential function within expression quantitative trait loci and investigate overall enrichment of variation within tissue-specific functional regulatory domains of the genome., Results: The strongest finding ( p  = 2.01 × 10 -6 , odds ratio = 1.82, 95% confidence interval = [1.42, 2.33]) in genome-wide association study was with rs10252923 at 7q21.13, downstream of FZD1 (frizzled class receptor 1). While this did not stand alone after correction, the involvement of FZD1 was supported by gene-based analysis, which exceeded the threshold for genome-wide significance ( p  = 2.78 × 10 -6 )., Conclusion: The identification of FZD1 , as an independent association signal at the gene level, supports the hypothesis that the Wnt signalling pathway is altered in the pathogenesis of schizophrenia and may be an important target for therapeutic development.

Background: During the COVID-19 epidemic period, Traditional Chinese Medicine (TCM) course for international students of Medical Bachelor, Bachelor of Surgery (MBBS) program in Zhejiang University has shifted from traditional classroom to online environment. This study aimed to investigate MBBS international students' perception on online TCM course, and to assess the online learning efficacy., Methods: A total of 84 MBBS international students attending course of "Basic Traditional Chinese Medicine" during 2020 academic years at Zhejiang University were enrolled in this study. A quantitative questionnaire was respectively completed before and after the TCM course using a pretest-post-test design. By means of two online learning platforms, Learning in ZJU and DingTalk, TCM course was broadcast in both live and archived format to students., Results: A total of 48 participants completed both baseline and follow-up questionnaires. The majority of participants preferred face-to-face classroom learning (26, 54.17% of total) when compared with online learning. Students felt that the course had brought in much benefits (mean 3.88, SD 0.87), and they were satisfied with the course content (mean 3.83, SD 0.95). Students' TCM related knowledge and their behaviors of discussion and consulting were significantly improved by online TCM course (all P  < 0.001). Students' awareness of the necessity of TCM education and their feeling of difficulty in learning TCM were significantly strengthened ( P  = 0.042, 0.025, respectively)., Conclusion: Online learning is a good alternative for TCM course of MBBS international students when classroom learning is suspended, whereas it cannot replace the need for onsite and face-to-face learning., (© 2020 Korea Institute of Oriental Medicine. Publishing services by Elsevier B.V.)

This study aims to examine the effects among college students of mindfulness on smartphone addiction before going to bed at night. We examined the mediating roles of self-control and rumination on the mindfulness-smartphone addiction path. Participants ( n = 270, 59.3% females, 18-24 years old) completed self-reporting questionnaires measuring mindfulness, self-control, smartphone addiction, and rumination. In addition to the correlation analysis, we adopted a stepwise regression analysis with bootstrapping to test the mediating effects. It was found that mindfulness was inversely related to smartphone addiction before going to sleep. Most importantly, self-control and rumination significantly mediated the effects of mindfulness on smartphone addiction among college students. The findings of this study indicated that mindfulness training is beneficial to improve the ability of self-control and reduce rumination levels, thereby inhibiting the negative impact of smartphone addiction on college students before they go to sleep, and further promoting their sleep health and mental health., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2020 by the authors.)

Pseudorabies virus (PRV) is the etiological agent of Aujeszky's disease, which has caused severe economic loss in China since its re-emergence in 2011. UL46, a late gene of herpesvirus, codes for the abundant but non-essential viral phosphoproteins 11 and 12 (VP11/12). In this study, VP11/12 was found to localize inside both the nucleus and cytoplasm. The nuclear localization signal (NLS) of VP11/12 was identified as 3 RRARGTRRASWKDASR 18 . Further research identified α5 and α7 to be the receptors for NLS and the chromosome region maintenance 1 (CRM1) to be the receptor for the nuclear export signal. Moreover, we found that PRV VP11/12 interacts with EP0 and the stimulator of interferon genes protein (STING), whereas the NLS of VP11/12 is the important part for VP11/12 to interact with UL48. To our knowledge, this is the first study to provide reliable evidence verifying the nuclear localization of VP11/12 and its role as an additional shuttling tegument protein for PRV. In addition, this is also the first study to elucidate the interactions between PRV VP11/12 and EP0 as well as between PRV VP11/12 and STING, while identifying the precise interaction sites of PRV VP11/12 and VP16., (Copyright © 2020 Xu, Gao, Wu, Zheng, Tong, Cheng, Liu, Zhu, Fu, Jiang, Li, Kong, Li and Tong.)

With the wide application of nanomaterials in consumer products in the market, it is necessary to understand the existence and release of nanomaterials in consumer products, as well as the current situation of exposure assessment of consumers. China has been a large industrial producer with a huge consumer market, but the supervision of consumer goods with nanomaterials is almost blank. This article summarized and classified the existing consumer products of nanomaterials in the international market, and discussed the release of key nanomaterials in consumer products and the exposure assessment methods of consumers, in order to provide a scientific basis for the establishment of a regulatory system for consumer products of nanomaterials in China in the future.

Coronavirus disease 2019 (COVID-19) can cause great damage to the elderly patients and lead to high mortality. The clinical presentations and auxiliary examinations of the elderly patients with COVID-19 are atypical, due to the physiological ageing deterioration and basal pathological state. The treatment strategy for the elderly patients has its own characteristics and treatment protocol should be considered accordingly. To improve the diagnosis, treatment, and prevention of COVID-19 in the elderly, the Expert Committee of Geriatric Respiratory and Critical Care Medicine, China Society of Geriatrics established the "Expert consensus for the diagnosis, treatment, and prevention of coronavirus disease 2019 in the elderly" . We focused on the clinical characteristics and key points for better treatment and prevention of COVID-19 in the elderly. (1) For diagnosis, atypical clinical presentation of COVID-19 in the elderly should be emphasized, which may be complicated by underlying disease. (2) For treatment, strategy of multiple disciplinary team (mainly the respiratory and critical care medicine) should be adopted and multiple systemic functions should be considered. (3) For prevention, health care model about integrated management of acute and chronic diseases, in and out of hospital should be applied.

Background: Robust imaging biomarkers are needed for risk stratification in stage I lung adenocarcinoma patients in order to select optimal treatment regimen. We aimed to construct and validate a radiomics nomogram for predicting the disease-free survival (DFS) of patients with resected stage I lung adenocarcinoma, and further identifying candidates benefit from adjuvant chemotherapy (ACT)., Methods: Using radiomics approach, we analyzed 554 patients' computed tomography (CT) images from three multicenter cohorts. Prognostic radiomics features were extracted from computed tomography (CT) images and selected using least absolute shrinkage and selection operator (LASSO) Cox regression model to build a radiomics signature for DFS stratification. The biological basis of radiomics was explored in the Radiogenomics dataset (n=79) by gene set enrichment analysis (GSEA). Then a nomogram that integrated the signature with these significant clinicopathologic factors in the multivariate analysis were constructed in the training cohort (n=238), and its prognostic accuracy was evaluated in the validation cohort (n=237). Finally, the predictive value of nomogram for ACT benefits was assessed., Results: The radiomics signature with higher score was significantly associated with worse DFS in both the training and validation cohorts (P<0.001). The GSEA presented that the signature was highly correlated to characteristic metabolic process and immune system during cancer progression. Multivariable analysis revealed that age (P=0.031), pathologic TNM stage (P=0.043), histologic subtype (P=0.010) and the signature (P<0.001) were independently associated with patients' DFS. The integrated radiomics nomogram showed good discrimination performance, as well as good calibration and clinical utility, for DFS prediction in the validation cohort. We further found that the patients with high points (point ≥8.788) defined by the radiomics nomogram obtained a significant favorable response to ACT (P=0.04) while patients with low points (point <8.788) showed no survival difference (P=0.7)., Conclusions: The radiomics nomogram could be used for prognostic prediction and ACT benefits identification for patient with resected stage I lung adenocarcinoma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-19-577). The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Membrane trafficking during cytokinesis is essential for the delivery of membrane lipids and cargoes to the division site. However, the molecular mechanisms are still incompletely understood. In this study, we demonstrate the importance of uncharacterized fission yeast proteins Mso1 and Sec1 in membrane trafficking during cytokinesis. Fission yeast Mso1 shares homology with budding yeast Mso1 and human Mint1, proteins that interact with Sec1/Munc18 family proteins during vesicle fusion. Sec1/Munc18 proteins and their interactors are important regulators of SNARE complex formation during vesicle fusion. The roles of these proteins in vesicle trafficking during cytokinesis have been barely studied. Here, we show that fission yeast Mso1 is also a Sec1-binding protein and Mso1 and Sec1 localize to the division site interdependently during cytokinesis. The loss of Sec1 localization in mso1Δ cells results in a decrease in vesicle fusion and cytokinesis defects such as slow ring constriction, defective ring disassembly, and delayed plasma membrane closure. We also find that Mso1 and Sec1 may have functions independent of the exocyst tethering complex on the plasma membrane at the division site. Together, Mso1 and Sec1 play essential roles in regulating vesicle fusion and cargo delivery at the division site during cytokinesis.

A stable pillared-layer metal-organic framework (MOF) was obtained through post-synthesis modification from an unstable fence-like MOF for the first time. By virtue of high exposure of active sites on the layers, the evolved MOF with Fe doping exhibits an ultralow overpotential of 238 mV at 10 mA cm-2 during the oxygen evolution reaction (OER). Moreover, it shows a superior electrocatalytic stability with almost no attenuation for more than 168 h.

The migration of nitrogen (N) and phosphorous (P) from farmland to river not only results in fertilizer inefficiency, but also aggravates water pollution and eutrophication. It is of great significance to construct a reasonable vegetation buffer zone between the river and farmland to protect water quality. By using constructed buffer strips and runoff hydrometric devices, quantitative research was conducted on removal loads of N and P in a field experiment of different vegetated and slope strips. Results showed that removal rates of TN, NH 4 + -N, and TP by different vegetated strips were 2-3 times higher than the control group. The removal ratios of seepage accounted for 73.6%, 66.9%, 73.9% of total seepage and runoff in three vegetated strips, respectively. On the 2% gradient strips with Cynodon dactylon, the removal ratios of TN, NH 4 + -N, and TP were 36%, 34%, 37%, which were higher than that with 5% gradient, respectively. And removal ratios from the seepage of 2%, 3%, 4%, and 5% gradient strips were 71.66%, 68.14%, 64.39%, and 61.93% of the total, respectively. The conclusion can provide the basis of vegetation and slope optimization for the design and construction of a riparian buffer zone, so as to control non-point source pollution effectively.

The objective of this study was to evaluate the effect of periodontally accelerated osteogenic orthodontics (PAOO) on gingivae and alveolar bone by analysis of clinical and cone beam computed tomography (CBCT) parameters in the treatment of 20 skeletal Class III patients. The patients included in this study were divided into test and control groups. Periodontal parameters such as probing depth (PD), gingival recession (GR), keratinized gingival width, and alveolar bone thickness of CBCT scans were measured and recorded preoperation (T0) and at 6 months postoperative (T1). The difference in PD from T0 to T1 between the two groups was not statistically significant (0.01 ± 0.46 mm vs 0.22 ± 0.65 mm, respectively; P > .05). No significant difference in GR was observed from T0 to T1 between the two groups (0.03 ± 0.26 mm vs -0.03 ± 0.27 mm, respectively; P > .05). Alveolar bone thickness (4 mm apical to the cementoenamel junction [CEJ]) change from T0 to T1 was -0.31 ± 0.35 mm for the control group and 0.06 ± 0.69 mm for the test group ( P < .05). Meanwhile, alveolar bone thickness (6 mm apical to CEJ) changes from T0 to T1 were -0.38 ± 0.54 mm and 0.10 ± 0.80 mm for the control and test groups, respectively ( P < .05). It was determined that PAOO in the treatment of skeletal Class III patients is effective and safe to periodontium on the basis of clinical and CBCT parameters.

Objectives/background: Disruptions to mood, cognition, and other daytime functioning are common and debilitating symptoms of Parkinson's disease (PD), and there is evidence that sleep problems contribute to these symptoms. However, previous studies are limited by reliance on self-reported sleep and cross-sectional designs. With the aim of assessing sleep as a possible treatment target for improving daytime functioning in PD, we used smartphone-based ecological momentary assessment (EMA) and actigraphy to investigate temporal associations between sleep (objective and subjective) and daytime functioning., Participants/methods: Twenty participants with mild-moderate PD wore actigraphs and completed sleep diaries for 14-15 days. They reported daytime functioning (anxiety, positive affect, cognitive function, fatigue, and social function) twice daily via smartphone-administered questionnaires. Multilevel modeling examined whether sleep quantity/quality predicted next-day functioning, and whether current mood (anxiety, positive affect) predicted later sleep., Results: Average completion rates for sleep diaries and daytime questionnaires were 94% and 91%, respectively. Subjective sleep quality predicted next-day anxiety (B = -.75, SE = .25, p = .003), but objective sleep did not predict any daytime functioning variables ( p 's>.112). Positive affect predicted later subjective sleep quality (B = 0.03, SE = .01, p = .003) but not objective sleep quantity/quality ( p 's>.107)., Conclusions: We demonstrated the feasibility of using EMA in PD. On a daily timescale, subjective sleep quality was bidirectionally associated with mood, whereas objective sleep was not associated with any daytime functioning. This discrepancy suggests that perception of sleep is important for mood in PD, which could provide targets for non-pharmacological interventions.

Leaf rust, caused by Puccinia triticina ( Pt ), is one of the most devastating diseases of wheat, affecting production in nearly all wheat-growing regions worldwide. Despite its economic importance, genomic resources for Pt are very limited. In the present study, we have used long-read sequencing (LRS) and the pipeline of FALCON and FALCON-Unzip (v4.1.0) to carry out the first LRS-based de novo genome assembly for Pt . Using 22.4-Gb data with an average read length of 11.6 kb and average coverage of 150-fold, we generated a genome assembly for Pt104 [strain 104-2,3,(6),(7),11; isolate S423], considered to be the founding isolate of a clonal lineage of Pt in Australia. The Pt104 genome contains 162 contigs with a total length of 140.5 Mb and N 50 of 2 Mb, with the associated haplotigs providing haplotype information for 91% of the genome. This represents the best quality of Pt genome assembly to date, which reduces the contig number by 91-fold and improves the N 50 by 4-fold as compared to the previous Pt race1 assembly. An annotation pipeline that combined multiple lines of evidence including the transcriptome assemblies derived from RNA-Seq, previously identified expressed sequence tags and Pt race 1 protein sequences predicted 29,043 genes for Pt104 genome. Based on the presence of a signal peptide, no transmembrane segment, and no target location to mitochondria, 2,178 genes were identified as secreted proteins (SPs). Whole-genome sequencing (Illumina paired-end) was performed for Pt104 and six additional strains with differential virulence profile on the wheat leaf rust resistance genes Lr26 , Lr2a , and Lr3ka . To identify candidates for the corresponding avirulence genes AvrLr26 , AvrLr2a , and AvrLr3ka , genetic variation within each strain was first identified by mapping to the Pt104 genome. Variants within predicted SP genes between the strains were then correlated to the virulence profiles, identifying 38, 31, and 37 candidates for AvrLr26 , AvrLr2a , and AvrLr3ka , respectively. The identification of these candidate genes lays a good foundation for future studies on isolating these avirulence genes, investigating the molecular mechanisms underlying host-pathogen interactions, and the development of new diagnostic tools for pathogen monitoring., (Copyright © 2020 Wu, Dong, Song and Park.)

Objective: To study the effect of the injected bone marrow mesenchymal stem cells (BMSC) on rats with pulmonary fibrosis induced by paraquat (PQ) during different poisoning periods and explore the potential mechanism. Methods: From October to December 2018, BMSCs of SPF SD rats were isolated and purified by whole-bone marrow adherent culture method and cultured to the Third Generation (P3) . The surface antigens CD29, CD90, CD45 and CD34 of P3 BMSC were detected by Flow cytometry, the formation of alkaline phosphatase (ALP) , calcium nodules and fat droplets were observed by ALP, Alizarin Red staining and oil red O staining. At the same time, 36 SPF male rats were randomly divided into 6 groups: NC Group (Blank Control Group, injected with the same amount of saline) and PQ group (PQ model group, injected with 20% PQ solution 18 mg/kg intraperitoneally) , bMSC-A group, BMSC-B group, BMSC-C group and BMSC-D group were injected with BMSC suspension 1×10(6) cells/mice at 3 h、3 d、7 d and 14 d after PQ poisoning. After 28 days, the rats were killed, the lung organ coefficients were calculated, the hydroxyproline (HYP) content in lung tissue was calculated by alkaline hydrolysis, and the lung injury and fibrosis were observed by HE and Masson staining, serum TGF-1、TNF-α、MMP-9 and TIMP-1 were detected by Elisa. Results: High Purity BMSCs were successfully isolated and obtained. The P3 BMSC generation was positive expression of CD29、CD90、and negative expression of CD34、CD45, and had the potential of osteogenic and adipogenic differentiation. The results of HE staining and Masson staining showed that the alveolar structure in NC group was intact and homogeneous, in PQ group, the alveolar structure was severely damaged and a lot of collagen fibers and fibroblasts were deposited, and the degrees of lung injury in each BMSC intervention group were obviously less than in PQ group, in BMSC-A group and BMSC-B group, the degrees of reduction were obvious. Compared with NC group, the Lung organ coefficient, HYP content in lung tissue and TGF-β1, TIMP-1 levels in serum were significantly higher in PQ group ( P <0.05) , while TNF-α and MMP-9 had no significant difference ( P >0.05) . Compared with PQ group, the lung organ Coefficients, HYP, TGF-1 and TIMP-β1 in BMSC-A and BMSC-B groups were lower than those in PQ group ( P <0.05) . The Lung organ coefficients, TGF-β1 and TIMP-1 in BMSC-C and BMSC-D groups were lower than those in PQ group, there was no significant difference ( P >0.05) . Conclusion: Early BMSC injecting can alleviate pulmonary fibrosis induced by PQ. The mechanism may be that BMSC can reduce pulmonary fibrosis through reducing the level of TGF-β1 and regulating the balance of TIMP-1/MMP-9, threrby reducing inflammatory damage and increasing the degradation of extracellular matrix (ECM) .