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In plants, macroautophagy/autophagy has mainly been associated with stress-related processes but how it impacts normal physiological and developmental processes remains largely unexplored. Pollen germination is the critical first step toward fertilization in flowering plants. It is metabolically demanding and relies on high levels of cytoplasmic reorganization activities to support a dramatic morphological transformation that underlies the development of a pollen tube as the conduit to deliver sperm for fertilization. The role of autophagy in this process remains unclear. Here we provide evidence that pollen germination is accompanied by elevated autophagic activity and successful pollen tube emergence depends on autophagy-mediated cytoplasmic deletion. Genetic and cytological experiments demonstrate that inhibition of autophagy prevents pollen germination while induces the persistence of a layer of undegraded cytoplasm at the germination aperture. Together, these results unveil a novel compartmentalized autophagy. Furthermore, high-throughput comparative lipidomic analyses show that suppressed autophagy-induced inhibition of pollen germination is accompanied by altered profiles of stored and signaling lipids. Proteomic analyses reveal that autophagy likely exert its role in pollen germination via downstream mitochondria-related pathways. These findings reveal a critical role for autophagy in initiating pollen germination and provide evidences for compartmental cytoplasmic deletion being crucial for male fertility. Abbreviations : 3-MA: 3-methyladenine; ATG: autophagy-related gene; Cer: ceramide; CL: cardiolipin; Con A: concanamycin A; DAG: diradylglycerol; GO: gene ontology; HAG: hour after germination; LC-MS: liquid chromatography-mass spectrometry; MAG: min after germination; MDC: monodansylcadaverine; PE: phosphatidylethanolamine; PI: phosphatidylinositol; PLD: phospholipase D; PtdIns3K: phosphatidylinositol 3-kinase; RT-qPCR: quantitative real-time reverse transcription PCR; TAG: triradylglycerol; TEM: transmission electron microscopy; TMT: tandem mass tagging.

Background: Visual Analog Scale (VAS) as determined by the patient is recommended by the European Position Paper on Rhinosinusitis and Nasal Polyps 2012 in evaluation of the total severity of the chronic rhinosinusitis (CRS) patients' symptoms., Objective: To evaluate the correlation between evaluations performed by otorhinolaryngologists and CRS patients with commonly used systems., Methods: Scores of VAS and Sino-Nasal Outcome Test-20 (SNOT-20) Chinese version were obtained from 110 CRS patients with nasal polyps (CRSwNPs, n = 61) and without nasal polyps (CRSsNPs, n = 49) before surgery, which were compared with scores of Lund-Kennedy endoscopic staging system, the Lund-Mackay computed tomography (CT) staging system, and VAS from 3 attending otorhinolaryngologists., Results: The median VAS scores given by CRS patients (6.0; 4.25-7.5) do not correlate significantly with the VAS scores by the 3 otorhinolaryngologists (5.5; 4.83-6.5) with a correlation coefficient of .218 (-0.146 to 0.466). For CRS patients, there was only a moderate correlation between scores of VAS and the SNOT-20 ( r  = .37), and no significant difference of VAS scores between CRSwNP and CRSsNP, and between unilateral and bilateral nasal polys. For otorhinolaryngologists, a higher median VAS score was found in CRSwNP (6.0; 5.17-7.0), especially in bilateral (6.0; 5.0-7.08) and revision surgery (6.08; 5.33-7.63). The VAS scores of otorhinolaryngologists correlated significantly with the Lund-Mackay CT score ( r  = .7536) and Lund-Kennedy endoscopic staging ( r  = .5947)., Conclusions: VAS scores between patients and physicians are not correlated significantly in this study, but they fall within the same therapeutic range and do not change the clinical management of the patients.

Aim: The aim of this study was to investigate whether variability in warfarin stable dose (WSD) could be influenced by vitamin K-related polymorphisms in patients with heart valve replacement. Patients & methods: Twenty-nine vitamin K-related SNPs in 208 patients who initially took warfarin and achieved WSD were genotyped. Results: After conducting conditional analysis for both VKORC1 -1639G>A and CYP2C9 *3, LRP1 rs1800139 and LRP1 rs1800154 were significantly associated with WSD (p = 0.007 and p = 0.015, respectively). Multivariate analysis showed that LRP1 rs1800139 accounted for 5.9% WSD variability. Conclusion: Our results suggest that a novel vitamin K-related gene, LRP1 , exerts a relevant influence on WSD, independent of VKORC1 -1639G>A and CYP2C9 *3.

Massive neuron loss is the key reason for poor prognoses in patients with traumatic brain injury (TBI), and astrocytes function as nutrition-providing neurons. Therefore, researchers must determine the potential role of astrocytes in neural regeneration after TBI. Our previous studies established that upregulating CD24 in the hippocampus might improve cognitive functions after TBI. However, whether CD24 in hippocampal astrocytes is involved in neural regeneration after TBI remains unknown. Therefore, we detected the CD24 expression in the ipsilateral hippocampus via western blot and quantitative real-time PCR. We further investigated the CD24 expression patterns in hippocampal astrocytes via immunofluorescence staining. We then injected adeno-associated virus-Gfa2-siRNA-CD24 (AAV-CD24) into the astrocytes to downregulate CD24 and analyzed the related cellular signals. Golgi-Cox staining and the growth associated protein-43 (GAP43) level were used to observe neuronal morphology and neural regeneration around the astrocytes in the ipsilateral hippocampus, and the Morris water maze test was used to assess neural functional recovery. The CD24 protein and mRNA levels in the cornu ammonis and dentate gyrus regions of the ipsilateral hippocampus were elevated after TBI, and high CD24 expression was widespread in the hippocampal astrocytes after TBI. Specific inhibition of CD24 in the hippocampal astrocytes interfered with the activation of Src homology region 2 containing protein tyrosine phosphatase 2 (SHP2) and extracellular signal regulated kinase (ERK), shortened the neuronal dendritic spines, decreased the GAP43 level and impaired the cognitive functions of the TBI-model mice. These results revealed that elevated hippocampal CD24 in astrocytes participated in neural regeneration in mice after TBI, possibly by activating the SHP2/ERK pathway., Competing Interests: None., (AJTR Copyright © 2020.)

Background & Aims: The pathological hallmark of nonalcoholic fatty liver disease (NAFLD) is an imbalance in hepatic lipid homeostasis, in which lipophagy has been found to play a vital role. However, the underlying molecular mechanisms remain unclear. We investigated the role of chaperone-mediated autophagy (CMA) in the pathogenesis of NAFLD., Methods: CMA activity was evaluated in liver tissues from NAFLD patients and high-fat diet (HFD)-fed mice. Liver-specific LAMP2A-knockout mice and HepG2 cells lacking LAMP2A [L2A(-) cells] were used to investigate the influence of CMA on lipolysis in hepatocytes. The expression of Plin5, a lipid droplet (LD)-related protein, was also evaluated in human and mouse liver tissues and in [L2A(-)] cells., Results: Here, we found disrupted CMA function in the livers of NAFLD patients and animal models, displaying obvious reduction of LAMP2A and concurrent with decreased levels of CMA-positive regulators. More LDs and higher serum triglycerides accumulated in liver-specific LAMP2A-knockout mice and L2A(-) cells under high-fat challenge. Meanwhile, deleting LAMP2A hindered LD breakdown but not increased LD formation. In addition, the LD-associated protein Plin5 is a CMA substrate, and its degradation through CMA is required for LD breakdown., Conclusions: We propose that the disruption of CMA-induced Plin5 degradation obstacles LD breakdown, explaining the lipid homeostasis imbalance in NAFLD., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tight junctions (TJs) are intercellular structures which are essential for epithelial barrier function and play an important role in antimicrobial defense. Epithelium dysfunction and type-2-skewed inflammation are two main pathological phenomena of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the effect of pro-inflammatory type-2 cytokine IL-13 on TJs in CRSwNP is poorly understood. Nasal biopsies of CRSwNP patients and in vitro IL-13-matured human nasal epithelial cells (hNECs) were used to analyze epithelial markers and TJ proteins. Epithelium permeability, transepithelial electrical resistance (TEER), expression of TJs were quantified for IL-13-matured hNECs and that with RV infection. The expression of occludin, claudin-3, and ZO-1 were significantly decreased in CRSwNP biopsies and in hNECs after IL-13 treatment. IL-13 treatment increased epithelium permeability, decreased TEER and altered hNECs composition resulting in lesser ciliated cells and mucus over-secretion. Interestingly, claudin-3 is selectively expressed on ciliated cells. While RV infection induced minimal changes to TJs, the IL-13-matured hNECs has reduced capacity for upregulation of IFN- λ 1 and CXCL10 but further increased the expression of TSLP upon RV infection. These findings suggested that IL-13-mediated dysfunction of TJs and compromised epithelial barrier. IL-13-induced cilia loss conferred lowered viral replication and impaired antiviral responses of nasal epithelium against RV infection., (Copyright © 2020 Huang, Liu, Ong, Yuan, Zhou, Wang, Tan, Chow, Yang, Shi, Ye and Wang.)

The large-conductance calcium-activated potassium channel (BK Ca ) plays an important role in the regulation of insect neural circuits and locomotion, and thus is a potential target of insecticides. In this study, iberiotoxin, an inhibitor of BK Ca , was found to prolong the anesthetic time of ethyl acetate on Plutella xylostella larvae. Therefore, the coding sequence of slowpoke gene coding the alpha subunit of BK Ca was cloned to investigate the function of this channel in P. xylostella, and the gene expression profile in the developmental stages and tissues was also characterized. The total length of pxslo DNA was more than 19.9 kb, which harbored four alternative splicing sites (ASP-A, ASP-C, ASP-E, and ASP-G), and the coding sequence of pxslo with the highest frequency of splicing (GenBank ID: MN938456) was 3,405 base pair. The characterized PxSlo protein contained conserved domains previously identified in other insects. Quantitative reverse transcription-polymerase chain reaction analysis showed that pxslo was expressed in all the developmental stages of P. xylostella, with the highest level in adults. In the larval stage, pxslo was mainly expressed in the head and epidermis, while a limited protein was expressed in the midgut. In the adult stage, pxslo was highly expressed in the head, followed by in the ovarian tubule, and was not expressed in the testis or wings. These results suggest that BK Ca plays an important physiological role in P. xylostella and provides useful information for the functional study and screening of BK Ca inhibitors., (© 2020 Wiley Periodicals LLC.)

Phosphoribosyl-pyrophosphate synthetase 2 (PRPS2) is a rate-limiting enzyme and plays an important role in purine and pyrimidine nucleotide synthesis. Recent studies report that PRPS2 is involved in male infertility. However, the role of PRPS2 in hypospermatogenesis is unknown. In this study, the relationship of PRPS2 with hypospermatogenesis and spermatogenic cell apoptosis was investigated. The results showed that PRPS2 depletion increased the number of apoptotic spermatogenic cells in vitro. PRPS2 was downregulated in a mouse model of hypospermatogenesis. When PRPS2 expression was knocked down in mouse testes, hypospermatogenesis and accelerated apoptosis of spermatogenic cells were noted. E2F transcription factor 1 (E2F1) was confirmed as the target gene of PRPS2 and played a key role in cell apoptosis by regulating the P53/Bcl-xl/Bcl-2/Caspase 6/Caspase 9 apoptosis pathway. Therefore, these data indicate that PRPS2 depletion contributes to the apoptosis of spermatogenic cells and is associated with hypospermatogenesis, which may be helpful for the diagnosis of male infertility., Competing Interests: None

BACKGROUND This study assessed the additional benefits of bupivacaine when combined with ketorolac for transversus abdominis plane (TAP) block after gynecological laparoscopic surgery. MATERIAL AND METHODS This randomized, observer-blind trial recruited 153 patients who underwent gynecological laparoscopic surgery. Patients were randomly assigned to receive bupivacaine combined with ketorolac 15 mg/side for TAP block (TK group), bupivacaine for TAP block and 30 mg postoperative intravenous ketorolac (T group), or 30 mg postoperative intravenous ketorolac alone (C group). The primary endpoints included consumption of sufentanil for 24 h postoperatively, actual press times of the patient-controlled analgesia (PCA) pump, and effective press times of the PCA pump, whereas the secondary endpoints included numerical rating scale (NRS) pain scores at rest and during activity, satisfaction with analgesia, episodes of nausea and vomiting and length of hospital stay. RESULTS Sufentanil consumption, actual press times of the PCA pump, and effective press times of the PCA pump were lower in the TK and T groups than in the C group. NRS scores at rest and during activity at 1, 2, 4, 6, and 24 hours were significantly lower in the TK and T groups than in the C group. The TK and T groups showed greater satisfaction with analgesia than the C group, while the TK group showed greater overall satisfaction than the C group. Lengths of stay, rates of nausea and vomiting, and venting times did not differ significantly among the three groups. CONCLUSIONS Combined ketorolac and bupivacaine as TAP block improved the effectiveness of analgesia without increasing adverse events. Trial registration number: ChiCTR1900022577.

Though therapy that promotes anti-tumor response about CD8 + tumor-infiltrating lymphocytes (TILs) has shown great potential, clinical responses to CD8 + TILs immunotherapy vary considerably, largely because of different subpopulation of CD8 + TILs exhibiting different biological characters. To define the relationship between subpopulation of CD8 + TILs and the outcome of antitumor reaction, the phenotype and function of CD103 + CD8 + TILs in esophageal squamous cell carcinoma (ESCC) were investigated. CD103 + CD8 + TILs were presented in ESCC, which displayed phenotype of tissue-resident memory T cells and exhibited high expression of immune checkpoints (PD-1, TIM-3). CD103 + CD8 + TILs were positively associated with the overall survivals of ESCC patients. This population of cells elicited potent proliferation and cytotoxic cytokine secretion potential. In addition, CD103 + CD8 + TILs were elicited potent anti-tumor immunity after anti-PD-1 blockade and were not affected by chemotherapy. This study emphasized the feature of CD103 + CD8 + TILs in immune response and identified potentially new targets in ESCC patients.

A syndrome (Zheng in Chinese) plays a critical role in disease identification, diagnosis, and treatment in traditional Chinese medicine (TCM). Clinically, the liver Qi stagnation and spleen deficiency syndrome (LQSSDS) is one of the most common syndrome patterns. Over the past few decades, several animal models have been developed to understand the potential mechanisms of LQSSDS, but until now, simulation of the syndrome is still unclear. Recently, several studies have confirmed that an animal model combining a disease and a syndrome is appropriate for simulating TCM syndromes. Overlapping previous studies have reported that depression is highly associated with LQSSDS; hence, we attempted to develop a rat model combining depression and LQSSDS. We exposed the rats to different durations of chronic unpredictable mild stress (CUMS). Subsequently, the evaluation indicators at macrolevel consisted of behavioral tests including open field test, sucrose preference test, and forced swim test, food intake, body weight, white adipose tissue, fecal water content, visceral hypersensitivity, and small bowel transit, and the evaluation indicators at microlevel included changes of hypothalamic-pituitary-adrenal axis. Serum D-xylose absorption was used to comprehensively confirm and assess whether the model was successful during the CUMS-induced process. The results showed that rats exposed to 6-week CUMS procedure exhibited significantly similar traits to the phenotypes of LQSSDS and depression. This study provided a new rat model for the LQSSDS and could potentially lead to a better understanding of the pathophysiology of LQSSDS and the development of new drugs for this syndrome., (© 2020 American Association for Anatomy.)

This study is aimed at identifying the effects of dietary fiber on gut health, as well as the association between that understanding and fiber consumption in fish. A total of 300 juvenile largemouth bass (micropterus salmoides, initial average weight: 15.38 ± 0.16g) were randomly divided into three treatment groups (4 replicates per group). Fish were fed with isoproteic and isolipidic diets containing 0% (low fiber, LF), 4% (moderate fiber, MF) and 8% (high fiber, HF) soybean fiber, respectively. The intestine and intestinal content of test fish per treatment group after 56 days of treatment were sampled. The results showed that the anterior intestinal sections had normal histological architecture, and no considerable damage or inflammation was observed in any histological section from all subjects examined. Curiously, fish fed the MF diet had better histological alterations than the other treatments. Meanwhile, the intestinal antioxidant capacity in the MF group was significantly promoted when compared to the other groups, as well as up-regulated expression of antioxidant-related genes including sod, cat and gp x with increasing dietary fiber concentrations. Importantly, the administrations of MF diet remarkably elevated largemouth bass innate immune parameters include intestinal inducible nitric oxide synthase (iNOS) activity, nitric oxide (NO) and total protein content. Similarly, dietary administrations of fiber down-regulated notablely the expression of pro-inflammatory cytokines including IL-8, IL-1β and TNFα, whereas up-regulated tolerogenic cytokine IL-10 and TGF-β1 mRNA levels. In addition, dietary fibers also modulated the community structure of the intestinal microbiota by significantly altering bacterial diversity. Dietary supplemental fibers regulated intestinal microbiota in largemouth bass, characterized by a reduced abundance of Fusobacteria along with increased abundances of Proteobacteria and Firmicutes. Taken together, the present results suggested that moderate fiber supplementation was beneficial to promoting intestinal health status of fish through antioxidant and anti-inflammatory effects, which could be at least partially responsible by the modulation of gut microbial composition., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

As an ancient lineage of ferns, Ophioglossaceae are evolutionarily among the most fascinating because they have the highest chromosome count of any known organism as well as the presence of sporophores, subterranean gametophytes, eusporangiate sporangia without annuli, and endophytic fungi. Previous studies have produced conflicting results, identifyingsome lineages with unresolved relationships, and have paid much attention to the subfamily Botrychioideae. But the other species-rich subfamily, Ophioglossoideae, has remained largely understudied and only up to 12 accessions of Ophioglossoideae have been sampled. In this study, DNA sequences of seven plastid markers of 149 accessions (75 in Ophioglossoideae) representing approximately 82 species (approximately 74% of estimated species diversity sensu J. Syst. Evol., 2016, 54, 563) in the family, and two Marattiaceae and two Psilotaceae, are used to infer a phylogeny. Our major results include: (1) Ophioglossaceae are resolved as monophyletic with strong support, and so are all four subfamilies and genera sensu PPG I except Botrypus and Ophioglossum; (2) a new genus Sahashia is segregated from Botrypus so that the monophyly of Botrypus can be retained; (3) the monophyly of Ophioglossum in its current circumscription is uncertain in spite of our large character sampling; (4) there is substantial cryptic speciation in Ophioderma detected by our molecular and morphological study; (5) the recognition of Holubiella is advocated based on its morphology and its sister relationship with Sceptridium; and (6) a novel sister relationship between Botrychium and the JHS clade (Japanobotrychium + (Holubiella + Sceptridium)) is discovered., (© The Willi Hennig Society 2020.)

To systemically evaluate the efficacy and safety of Banmao Capsules in the adjuvant treatment for non-small cell lung cancer(NSCLC). All of randomized controlled trials(RCT) about Banmao Capsules in adjuvant treatment for non-small cell lung cancer were retrieved in PubMed, EMbase, Cochrane Library, CNKI, VIP, CBM, WanFang database from database inception to August 2019. Two researchers extracted data and assessed literature quality separately, and made a Meta-analysis by RevMan 5.3 software. Thirteen trials involving 1 148 patients, including 595 in treatment group and 553 in control group, were enrolled in the review. The Meta-analysis showed that compared with conventional treatment, adjuvant treatment of NSCLC with Banmao Capsules can enhance the objective tumor response rate(RR=1.43,95%CI[1.30,1.58],P<0.01), and the disease control rate(RR=1.16,95%CI[1.11,1.22],P<0.01); improve the quality of life(RR=1.56,95%CI[1.27,1.92],P<0.01); reduce the incidence of myelosuppression(RR=0.41,95%CI[0.26,0.66],P<0.01), gastrointestinal reactions(RR=0.46,95%CI[0.33,0.65],P<0.01), liver and kidney dysfunction(RR=0.44,95%CI[0.29,0.66],P<0.01). The results showed that in the treatment of NSCLC, Banmao Capsules can increase the short-term efficacy, improve the quality of life of patients, and reduce the side effects of platinum-based chemotherapy drugs. More high-quality and large-scale randomized controlled trials are required in the future.

Background: The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood., Methods: COVID-19 survivors were recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated., Findings: Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities ( P  = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect ( P  = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase., Interpretation: Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae., Funding: Key Scientific Research Projects of Henan Higher Education Institutions., Competing Interests: The authors have no interests to declare., (© 2020 The Authors.)

A new triterpenoid glucoside, leuctriterpencoside ( 1 ), along with two known compounds ( 2-3 ) were isolated from Leucas zeylanica. The structure of the new compound was elucidated using comprehensive spectroscopic methods. Compound 1 showed significant inhibitory activity against α-glucosidase (IC 50 value of 0.85 ± 0.12  μ M).

Warfarin international normalized ratio (INR)-related phenotypes such as the percentage of INR time in the therapeutic range (PTTR) and INR variability are associated with warfarin adverse reactions. However, INR-related phenotypes greatly vary among patients, and the underlying mechanism remains unclear. As a key cofactor for coagulation proteins, vitamin K can affect warfarin INR values. The aim of this study was to address the influence of vitamin K-related single-nucleotide polymorphisms (SNPs) on warfarin INR-related phenotypes. A total of 262 patients who were new recipients of warfarin therapy and followed up for 3 months were enrolled. Twenty-nine SNPs were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass array. Sixteen warfarin INR-related phenotypes were observed. After association analysis, 11 SNPs were significantly associated with at least one INR-related phenotype, and 6 SNPs were associated with at least 2 INR-related phenotypes (P < 0.05). In these SNPs, rs1800139, rs1800154, rs1800141, and rs486020 were the most representative. rs1800139, rs1800154, and rs1800141 locate in LRP1 and were found to be correlated with 1-month and 2-month INR variability (P < 0.05). Besides, the APOA1 rs486020 was significantly associated with the first month PTTR (P = 0.009), and patients with C-allele had higher PTTR than those with G-alleles almost during the entire monitoring period. In conclusion, the study revealed that the polymorphisms of LRP1 and APOA1 gene may play important roles in the variation of warfarin INR-related phenotypes. Our results provide new information for improving warfarin anticoagulation management.

Lepisoroid ferns (tribe Lepisoreae, Polypodiaceae) are arguably one of the most confusing fern groups in Polypodiaceae in terms of delimitation of genera largely because of their simple morphology. Previous molecular studies either had very small taxon sampling of the non-Lepisorus genera and did not well resolve the relationships among these genera, or had a relatively large sampling at species level but the critical species were missing or their relationships were not well resolved. A recent study resolved the newly sampled Lepisorus jakonensis as sister to the remaining genera in Lepisoreae excluding Paragramma, and the authors lumped all the six well recognized genera into Lepisorus. In the present study, to infer a phylogeny we used DNA sequences of five plastid markers (matK, rbcL, rbcL-atpB, rps4 &rps4-trnS, trnL &trnL-F) of 172 accessions representing ca. 44 species of non-Lepisorus genera and 54 accessions representing ca. 50 species of Lepisorus as ingroup, and 10 non-Lepisoreae accessions from the most closely related four genera (Leptochilus, Microsorum, Phymatosorus, and Goniophlebium) in Microsoroideae and one genus (Pyrrosia) in Platycerioideae. Our major results include: (1) All seven currently defined genera except Lepisorus in Lepisoreae are confirmed to be monophyletic; (2) The Lepisorus jakonensis clade is confirmed to be the second earliest diverged lineage in Lepisoreae; (3) Neolepisorus is resolved as sister to the rest in a clade containing all non-Lepisorus genera except Paragramma; (4) Lemmaphyllum is sister to a clade containing Lepidomicrosorium, Neocheiropteris, and Tricholepidium; and (5) Ellipinema gen. nov. is segregated from Lepisorus based on the phylogeny and morphology in order to stabilize the current usage of the existing six non-Lepisorus genera and species names in these genera. A key to all eight genera of Lepisoreae is provided., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To explore the feasibility of using faster regional convolutional neural network (Faster R-CNN) to evaluate the status of circumferential resection margin (CRM) of rectal cancer in the magnetic resonance imaging (MRI). Methods: This study was registered in the Chinese Clinical Trial Registry (ChiCTR-1800017410). Case inclusion criteria: (1) the positive area of CRM was located between the plane of the levator ani, anal canal and peritoneal reflection; (2) rectal malignancy was confirmed by electronic colonoscopy and histopathological examination; (3) positive CRM was confirmed by postoperative pathology or preoperative high-resolution MRI. Exclusion criteria: patients after neoadjuvant therapy, recurrent cancer after surgery, poor quality images, giant tumor with extensive necrosis and tissue degeneration, and rectal tissue construction changes in previous pelvic surgery. According to the above criteria, MRI plain scan images of 350 patients with rectal cancer and positive CRM in The Affiliated Hospital of Qingdao University from July 2016 to June 2019 were collected. The patients were classified by gender and tumor position, and randomly assigned to the training group (300 cases) and the validation group (50 cases) at a ratio of 6:1 by computer random number method. The CRM positive region was identified on the T2WI image using the LabelImg software. The identified training group images were used to iteratively train and optimize parameters of the Faster R-CNN model until the network converged to obtain the best deep learning model. The test set data were used to evaluate the recognition performance of the artificial intelligence platform. The selected indicators included accuracy, sensitivity, positive predictive value, receiver operating characteristic (ROC) curves, areas under the ROC curves (AUC), and the time taken to identify a single image. Results: The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the CRM status determined by the trained Faster R-CNN artificial intelligence approach were 0.884, 0.857, 0.898, 0.807, and 0.926, respectively; the AUC was 0.934 (95% CI: 91.3% to 95.4%). The Faster R-CNN model's automatic recognition time for a single image was 0.2 s. Conclusion: The artificial intelligence model based on Faster R-CNN for the identification and segmentation of CRM-positive MRI images of rectal cancer is established, which can complete the risk assessment of CRM-positive areas caused by in-situ tumor invasion and has the application value of preliminary screening.

Background: Aucubin (Au), an iridoid glycoside from natural plants, has antioxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in an H 2 O 2 -induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model., Methods: In vitro experiments, the various concentrations of Au (50 μg/ml, 100 μg/ml, or 200 μg/ml) were added in culture medium at 0 h and 6 h after neurons stimulated by H 2 O 2 (100 μM). After exposed for 12 h, neurons were collected for western blot (WB), immunofluorescence, and M29,79-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In vivo experiments, Au (20 mg/kg or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling. Brain water content, neurological deficits, and cognitive functions were measured at specific time, respectively. Cortical tissue around focal trauma was collected for WB, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry, and enzyme linked immunosorbent assay (ELISA) at 72 h after TBI. RNA interference experiments were performed to determine the effects of nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with Au (40 mg/kg) treatment. Mice were intracerebroventricularly administrated with lentivirus at 72 h before TBI establishment. The cortex was obtained at 72 h after TBI and used for WB and q-PCR., Results: Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS), and reduced cell apoptosis both in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages, and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1 (HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au., Conclusions: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.

The complete mitochondrial genome of Chinapotamon maolanense was obtained for the first time. The complete mitochondrial genome of C. maolanense is 17,130 bp in length, including 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 control region. In addition, the mitogenome has 18 noncoding regions ranging from 1 to 1553 bp in length., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Outcomes of endovascular treatment of anterior cerebral artery (ACA) aneurysms are still not well-characterized., Objective: The study aimed to review the clinical effect, procedure-related complications and follow-up outcomes and to evaluate the safety and efficacy of endovascular treatment of ACA aneurysms in our center experience., Methods: From August 2014 to August 2018, a total of 75 consecutive patients with 77 ACA aneurysms were treated via the endovascular approach after providing informed consent. A retrospective review of the clinical, radiological, and endovascular details of these patients was conducted., Results: The mortality and the morbidity in this study were 4% and 9.3%, respectively. Compared with A1 and A2 aneurysms, intraoperative rupture was more common in A3 aneurysms (P = 0.029). Difference between the ruptured and unruptured aneurysms in the distribution of therapeutic strategy (P = 0.003) and immediate embolization degree (P = 0.004) was also significant. Statistical analysis demonstrated that the larger aneurysm (P = 0.031) was, the greater the ratio of aneurysm size to parent artery diameter (P = 0.029) was, the more likely the unruptured aneurysms were to occur ischemic events. Higher Hunt-Hess grade (P = 0.0066) was an independent risk factor for poor clinical outcome., Conclusion: Endovascular treatment is feasible and effective for ACA aneurysms., Competing Interests: Declaration of Competing Interest The authors declare that we have no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown., Methods: Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed., Results: Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9)., Conclusions: Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

The aim of this study was to build a formula to predict short-term prognosis using main pulmonary artery (MPA) parameters reconstructed from computed tomographic pulmonary angiography in non-high-risk acute pulmonary embolism (PE) patients. After reconstructing the MPA and its centerline, the MPA, the right and left pulmonary artery inlet, and the MPA outlet plane were differentiated to measure the cross-sectional area (CSA), the maximal diameter and the hydraulic diameter. The MPA bifurcation area, volume and angle were measured. MPA dilation was defined as >29 mm at the transverse section plane. The patients were randomly divided into a training set and a validation set. A least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was used to build a predictive formula. The performances of the predictive formula from LASSO were tested by the area under the receiver operating characteristic curve (AUC) and precision-recall (PR) curve with 10-fold cross-validation. The clinical utility was assessed by decision curve analysis (DCA). In total, 296 patients were enrolled and randomly divided (50:50) into a training set and a validation set. The LASSO predictive formula (lambda.1SE) was as follows: 0.92 × MPA bifurcation area + 0.50 × MPA outlet hydraulic diameter + 0.10 × MPA outlet CSA. The AUCs of the predictive formula were 0.860 (95% CI: 0.795-0.912) and 0.943 (95% CI: 0.892-0.975) in the training set and validation set, respectively. The LASSO predictive formula had a higher average area under the PR curve than MPA dilation (0.71 vs. 0.23 in the training set and 0.55 vs. 0.23 in the validation set) and added a net benefit in clinical utility by DCA. Integration of MPA outlet CSA, hydraulic diameter, and bifurcation area with the LASSO predictive formula as a novel weighting method facilitated the prediction of poor short-term prognosis within 30 days after hospital admission in non-high-risk acute PE patients., (Copyright © 2020 Jia, Li, Hou and Zhou.)

This study aims to observe the efficacy of supplemented Er-xian decoction combined with acupoint application in treating poor ovarian response (POR). This study was a randomized controlled trial. A total of 80 patients, who were treated in the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from January 2016 to December 2017, were divided into two groups by tables of random numbers: experimental group (n = 40), and control group (n = 40). In the experimental group, patients orally received supplemented Er-xian decoction with acupoint application. In the control group, a Kuntai capsule was administered according to the course of treatment. The therapeutic effects in the two groups were observed and compared. In the experimental group, the total effective rate was 90%, the cure rate was 15% (six patients), the markedly effective rate was 35% (14 patients), the effective rate was 40% (16 patients), and the ineffective rate was 10% (four patients). In the control group, the total effective rate was 50%, the cure rate was 5% (two patients), the markedly effective rate was 15% (six patients), the effective rate was 30% (12 patients), and the ineffective rate was 50% (20 patients). The differences were statistically significant (P > 0.05). Definite efficacy was observed when a poor ovarian response was treated by supplemented Er-xian decoction combined with acupoint application. Improvements in perimenopausal symptoms, menstruation conditions, hormone levels, inhibin B (INHB), and antral follicle count (AFC) were markedly better in the experimental group than in the control group. In addition, the treatment was safe and had few side effects.

Ovarian cancer (OC) is one of the most common tumors in females. Growing evidence shows that microRNA-506-3p (miR-506-3p) is downregulated in OC tissues. The purpose of this study was to investigate the mechanism of miR-506-3p in modulating OC. Quantitative reverse transcriptase PCR (qRT-PCR) was employed to investigate the expression of miR-506-3p and its target in OC tissues or cell lines. CCK-8 or colony formation assay was used to examine cell viability or proliferation, respectively. Flow cytometry was demonstrated to detect cell apoptosis. Western blot was then applied to analyze underlying mechanisms. The potential target of miR-506-3p was examined via luciferase reporter assay. MiR-506-3p was significantly downregulated in both human OC tissues and cell lines. Overexpression of miR-506-3p not only decreased cell viability of OC cell lines but also promoted cell apoptosis, thus inhibiting OC progression. Moreover, SIRT1 (Sirtuin 1) was found to be a direct target of miR-506-3p, and SIRT1 expression was negatively regulated by miR-506-3p in OC cell lines. Further investigation revealed that overexpression of SIRT1 could promote cell viability as well as inhibit cell apoptosis, showing the reversed effect on OC progression compared to miR-506-3p. Lastly, AKT (Protein kinase B) /FOXO3a (Forkhead box O3) signaling pathway was inactivated by miR-506-3p while activated by SIRT1, relating to regulation of miR-506-3p on OC progression. Our results revealed a novel mechanism by which miR-506-3p inhibited proliferation while promoted apoptosis of OC via inactivation of SIRT1/AKT/FOXO3a signaling pathway, suggesting that miR-506-3p might be a potential target for OC.

Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammation-related signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its role in vascular inflammation and AAA progression remains to be elucidated. In the present study, the effect and potential mechanisms of BP-1-102 on angiotensin II (AngII) induced AAA in ApoE -/- mice were investigated. AAA was induced in ApoE -/- mice with infusion of AngII for 28 days. BP-1-102 was administrated orally to mice every other day. Mice were sacrificed on day 7, day 14, and day 28 to evaluate the treatment effects. BP-1-102 markedly decreased AAA incidence and aortic diameter, maintained elastin structure and volume, reduced the expression of pro-inflammatory cytokines and MMPs, and inhibited inflammatory cells infiltration. Moreover, BP-1-102 dramatically reduced the expression of JAK2, p-STAT3, p-NF-κB, and Bcl-xL but maintained the expression of LC3B and Beclin in AAA tissues. In vitro, vascular smooth muscle cells (VSMCs) were treated with AngII and/or BP-1-102 at indicated time and concentration. BP-1-102 inhibited AngII-induced JAK2/STAT3 and NF-κB signaling activation and maintained autophagy-related proteins expression in VSMCs. Taken together, our findings suggest that BP-1-102 inhibits vascular inflammation and AAA progression through decreasing JAK2/STAT3 and NF-κB activation and maintaining autophagy.

Background: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented., Methods: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded., Results: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy., Conclusions: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC., (© 2019 American Cancer Society.)

Timosaponin AIII (Timo AIII) is a natural steroidal saponin isolated from the traditional Chinese herb Anemarrhena asphodeloides Bge with proved effectiveness in the treatment of numerous cancers. However, whether Timo AIII suppresses tumor angiogenesis remains unclear. In the present study, we investigated the antiangiogenesis effects of Timo AIII and the underlying mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish embryos in vivo. We showed that treatment with Timo AIII (0.5-2 µM) partially disrupted the intersegmental vessels (ISVs) and subintestinal vessels (SIVs) growth in transgenic zebrafish Tg(fli-1a: EGFP) y1 . Timo AIII (0.5-4 µM) dose-dependently inhibited VEGF-induced proliferation, migration, invasion, and tube formation of HUVECs, but these inhibitory effects were not due to its cytotoxicity. We further demonstrated that Timo AIII treatment significantly suppressed the expression of VEGF receptor (VEGFR) and the phosphorylation of Akt, MEK1/2, and ERK1/2 in HUVECs. Timo AIII treatment also significantly inhibited VEGF-triggered phosphorylation of VEGFR2, Akt, and ERK1/2 in HUVECs. Moreover, we conducted RNA-Seq and analyzed the transcriptome changes in both HUVECs and zebrafish embryos following Timo AIII treatment. The coexpression network analysis results showed that various biological processes and signaling pathways were enriched including angiogenesis, cell motility, cell adhesion, protein serine/threonine kinase activity, transmembrane signaling receptor activity, growth factor activity, etc., which was consistent with the antiangiogenesis effects of Timo AIII in HUVECs and zebrafish embryos. We conclude that the antiangiogenesis effect of Timo AIII is mediated through VEGF/PI3K/Akt/MAPK signaling cascade; Timo AIII potentially exerts antiangiogenesis effect in cancer treatment.

The infrageneric relationships and taxonomy of the largest fern genus, Asplenium (Aspleniaceae), have remained poorly understood. Previous studies have focused mainly on specific species complexes involving a few or dozens of species only, or have achieved a large taxon sampling but only one plastid marker was used. In the present study, DNA sequences from six plastid markers (atpB, rbcL, rps4, rps4-trnS, trnL and trnL-F) of 1030 accessions (616 of them newly sequenced here) representing c. 420 species of Asplenium (60% of estimated species diversity), 16 species of Hymenasplenium, three Diplaziopsidaceae, and four Rhachidosoraceae were used to produce the largest genus-level phylogeny yet for ferns. Our major results include: (i) Asplenium as broadly circumscribed is monophyletic based on our inclusion of representatives of 32 of 38 named segregate genera; (ii) 11 major clades in Asplenium are identified, and their relationships are mostly well-resolved and strongly supported; (iii) numerous species, unsampled in previous studies, suggest new relationships and numerous cryptic species and species complexes in Asplenium; and (iv) the accrued molecular evidence provides an essential foundation for further investigations of complex patterns of geographical diversification, speciation and reticulate evolution in this family., (© The Willi Hennig Society 2019.)

Only a few types of inflammasomes have been described in central nervous system cells. Among these, the absent in melanoma 2 (AIM2) inflammasome is primarily found in neurons, is highly specific and can be activated only by double-stranded DNA. Although it has been demonstrated that the AIM2 inflammasome is activated by poly(deoxyadenylic-deoxythymidylic) acid sodium salt and leads to pyroptotic neuronal cell death, the role of AIM2 inflammasome-mediated pyroptosis in early brain injury (EBI) after subarachnoid haemorrhage (SAH) has rarely been studied. Thus, we designed this study to explore the mechanism of gasdermin D(GSDMD)-induced pyroptosis mediated by the AIM2 inflammasome in EBI after SAH. The level of AIM2 from the cerebrospinal fluid (CSF) of patients with SAH was detected. The pathway of AIM2 inflammasome-mediated pyroptosis, the AIM2/Caspase-1/GSDMD pathway, was explored after experimental SAH in vivo and in primary cortical neurons stimulated by oxyhaemoglobin (oxyHb) in vitro. Then, we evaluated GSDMD-induced pyroptosis mediated by the AIM2 inflammasome in AIM2 and caspase-1- deficient mice and primary cortical neurons generated through lentivirus (LV) knockdown. Compared with that of the control samples, the AIM2 level in the CSF of the patients with SAH was significantly increased. Pyroptosis-associated proteins mediated by the AIM2 inflammasome were significantly increased in vivo and in vitro following experimentally induced SAH. After AIM2 and caspase-1 were knocked down by an LV, GSDMD-induced pyroptosis mediated by the AIM2 inflammasome was alleviated in EBI after SAH. Intriguingly, when caspase-1 was knocked down, apoptosis was significantly suppressed via impeding the activation of caspase-3. GSDMD-induced pyroptosis mediated by the AIM2 inflammasome may be involved in EBI following SAH. The inhibition of AIM2 inflammasome activation caused by knocking down AIM2 and caspase-1 alleviates GSDMD-induced pyroptosis in EBI after SAH.

Background: Idiopathic pulmonary fibrosis (IPF) is a serious lung problem with advancing and diffusive pulmonary fibrosis as the pathologic basis, and with oxidative stress and inflammation as the key pathogenesis. Glycyl-L-histidyl-l-lysine (GHK) is a tripeptide participating into wound healing and regeneration. GHK-Cu complexes improve GHK bioavailability. Thus, the current study aimed to explore the therapeutic role of GHK-Cu on bleomycin (BLM)-induced pulmonary fibrosis in a mouse model., Methods: BLM (3 mg/kg) was administered via tracheal instillation (TI) to induce a pulmonary fibrosis model in C57BL/6j mice 21 days after the challenge of BLM. GHK-Cu was injected intraperitoneally (i.p.) at different dosage of 0.2, 2 and 20 μg/g/day in 0.5 ml PBS on alternate day. The histological changes, inflammation response, the collagen deposition and epithelial-mesenchymal transition (EMT) was evaluated in the lung tissue. EMT was evaluated by ɑ-SMA and fibronectin expression in the lung tissue. NF-κB p65, Nrf2 and TGFβ1/Smad2/3 signalling pathways were detected by immunoblotting analysis., Results: GHK-Cu complex inhibited BLM-induced inflammatory and fibrotic pathological changes, alleviated the inflammatory response in the BALF by reducing the levels of the inflammatory cytokines, TNF-ɑ and IL-6 and the activity of MPO as well as reduced collagen deposition. In addition, the GHK-Cu treatment significantly reversed the MMP-9/TIMP-1 imbalance and partially prevented EMT via Nrf2, NF-κB and TGFβ1 pathways, as well as Smad2/3 phosphorylation., Conclusions: GHK-Cu presented a protective effect in BLM-induced inflammation and oxidative stress by inhibiting EMT progression and suppressing TGFβ1/Smad2/3 signalling in pulmonary fibrosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study assesses the chemical characteristics of As in aerosol PM 2.5 samples that were collected from July 2011 to May 2012 in Beijing, China. Total As, As(Ⅲ), and As(Ⅴ) were analyzed by inductively coupled plasma mass spectrometry (ICP-MS), high performance liquid chromatography (HPLC), and hydride generation atomic fluorescence (HG-AFS), respectively. The average concentrations of total As, As(Ⅲ) and As(Ⅴ) over the entire sampling period were (21.82±17.01), (3.15±1.94), and (10.78±5.39) ng·m -3 , respectively. The average concentrations of total As, As(Ⅲ) and As(Ⅴ) were (16.62±5.80), (18.34±9.00), (21.49±10.22), and (29.52±27.97) ng·m -3 during the spring, (5.42±2.5), (1.61±0.51), (2.88±1.12), and (3.27±1.23) ng·m -3 during the summer, and (7.55±1.47), (13.57±13.34), (12.75±6.54), and (8.68±3.57) ng·m -3 during the winter, respectively. The average concentrations of As(Ⅲ) in different seasons were higher than As(Ⅴ) concentrations. Seasonal characteristics may be caused by seasonal differences in diffusion conditions, emission sources, and atmospheric oxidation. The ratios of average concentrations of As(Ⅲ)/As(Ⅴ) were 0.67 in spring, 0.13 in summer, 0.27 in autumn, and 0.44 in winter. Ratios of As(Ⅲ)/As(Ⅴ) were negatively correlated with relative humidity, which indicates that high humidity conditions may not have been favorable for the transformation of As(Ⅲ) into As(Ⅴ). As(Ⅲ)/As(Ⅴ) and As(Ⅲ) both showed positive correlations with Ca 2+ , thereby indicating that soil dust may have been an important source of As(Ⅲ).

In the adult rodents' brain, CD24 expression is restricted to immature neurons located in the neurogenesis areas. Our previous studies have confirmed that CD24 expression could be markedly elevated in the cerebral cortex after traumatic brain injury (TBI) both in humans and in mice. Although there is a close relationship between CD24 and neurogenesis, it remains unknown about the specific role of CD24 in neurogenesis areas after TBI. Here, the expression of CD24 was detected in the ipsilateral hippocampus by the Western blotting and real-time quantitative polymerase chain reaction. RNA interference was applied to investigate the effects of CD24 on post-traumatic neurogenesis. Brain sections were labeled with CD24 and doublecortin (DCX) via immunofluorescence. The Morris water maze test was used to assess cognitive functions. The results indicated that both mRNA and protein levels of CD24 were markedly elevated in the hippocampus after TBI. Meanwhile, TBI could cause a decrease of DCX-positive cells in the dentate gyrus of the hippocampus. Downregulation of CD24 significantly inhibited the phosphorylation of Src homology region 2-containing protein tyrosine phosphatase 2 in the ipsilateral hippocampus. Meanwhile, inhibition of CD24 could reduce the number of DCX-positive cells in the dentate gyrus area and impair cognitive functions of the TBI mice. These data suggested that hippocampal expression of CD24 might positively regulate neurogenesis and improve cognitive functions after TBI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Three new methylated Δ 8 -pregnene steroids, stemphylisteroids A-C (1-3) were isolated from the medicinal plant Polyalthia laui-derived fungus Stemphylium sp. AZGP4-2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. The absolute configuration of 1 was determined by X-ray crystallographic analysis. Compound 1 show antibacterial activity against Escherichia coli with the MIC value of 6.25 μg/mL, and 2 exhibited a broad spectrum of antibacterial activities against six pathogenic bacteria with the MIC values ranging from 12.5 to 50 μg/mL. The discovery of three methylated Δ 8 -pregnene steroids 1-3 are a further addition to diverse and complex array of methylated steroids., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A novel cyclopentenone derivative, talarocyclopenta A (1), a new phenolicethers derivative, talarocyclopenta B (2) and a new itaconic acid derivative, talarocyclopenta C (3) together with four known itaconic acid derivatives (4-7) were isolated from the Talaromyces assiutensis JTY2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. Among them, talarocyclopent (1) is the first represent an unusual type of cyclopentenone derivative, possessing a cyclopentenone unit, a 2-butanone unit and a 3-hydroxybutyric acid unit. All isolated compounds were evaluated for their anti-inflammatory and antibacterial activities. Compounds 1-4 showed inhibitory activities against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro. Compound 2 showed broad spectrum antibacterial against six terrestrial pathogenic bacteria., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Two new polyketides, 8- O -methylnodulisporin F ( 1 ) and nodulisporin H ( 2 ), two new naphthoquinones, 5-hydroxy-2-methoxy-6,7-dimethyl-1,4-naphthoquinone ( 3 ) and 5-hydroxy-2-methoxynaphtho[9- c ]furan-1,4-dione ( 4 ), and a new naphthofuran 1,3,8-trimethoxynaphtho[9- c ]furan ( 5 ), along with five known compounds 4- O -methyl eleutherol ( 6 ), 2-acetyl-7-methoxybenzofuran ( 7 ), (-)-orthosporin ( 8 ), diaporthin ( 9 ), and 6-hydroxymellein ( 10 ), were obtained from the EtOAc extract of the mangrove-derived fungus Daldinia eschscholtzii HJ004. The structures of the isolated compounds were elucidated by extensive NMR and MS analyses, while the absolute configurations of the stereogenic carbons were established based on experimental and calculated electronic circular dichroism spectra. Compounds 4 and 7 displayed a potent inhibitory activity against α -glucosidase with the IC 50 values of 5.7 and 1.1 μg/mL, respectively. Compounds 1 and 2 showed a moderate antibacterial activity against Staphylococcus aureus , methicillin-resistant S. aureus (MRSA) and Bacillus cereus , with minimum inhibitory concentration (MIC) values ranging from 6.25 to 12.5 μg/mL. Compound 3 exhibited antibacterial activity against B. cereus with the MIC value of 12.5 μg/mL.

Mesenchymal stem cells (MSCs) exhibit therapeutic benefits on aortic aneurysm (AA); however, the molecular mechanisms are not fully understood. The current study aimed to investigate the therapeutic effects and potential mechanisms of murine bone marrow MSC (BM-MSCs)-derived conditioned medium (MSCs-CM) on angiotensin II (AngII)-induced AA in apolipoprotein E-deficient (apoE -/- ) mice. Murine BM-MSCs, MSCs-CM or control medium were intravenously administrated into AngII-induced AA in apoE -/- mice. Mice were sacrificed at 2 weeks after injection. BM-MSCs and MSCs-CM significantly attenuated matrix metalloproteinase (MMP)-2 and MMP-9 expression, aortic elastin degradation and AA growth at the site of AA. These treatments with BM-MSCs and MSCs-CM also decreased Ly6c high monocytes in peripheral blood on day 7 and M1 macrophage infiltration in AA tissues on day 14, whereas they increased M2 macrophages. In addition, BM-MSCs and MSCs-CM reduced MCP-1, IL-1Ra and IL-6 expression and increased IL-10 expression in AA tissues. In vitro, peritoneal macrophages were co-cultured with BM-MSCs or fibroblasts as control in a transwell system. The mRNA and protein expression of M2 macrophage markers were evaluated. IL-6 and IL-1β were reduced, while IL-10 was increased in the BM-MSC systems. The mRNA and protein expression of M2 markers were up-regulated in the BM-MSC systems. Furthermore, high concentration of IGF1, VEGF and TGF-β1 was detected in MSCs-CM. Our results suggest that MSCs-CM could prevent AA growth potentially through regulating macrophage polarization. These results may provide a new insight into the mechanisms of BM-MSCs in the therapy of AA., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Four new xanthene derivatives, penicixanthenes A-D ( 1 - 4 ), and one known compound 5 were isolated from a marine mangrove endophytic fungus Penicillium sp. JY246 that was obtained from the stem of Ceriops tagal . Their structures were determined by detailed NMR, MS spectroscopic data, modified Mosher's method, and calculated electronic circular dichroism data. All of the isolated compounds were examined for insecticidal activity. Compounds 2 and 3 showed growth inhibition activity against newly hatched larvae of Helicoverpa armigera Hubner with the IC 50 values 100 and 200 μg/mL, respectively, and compounds 1 , 3 , and 4 showed insecticidal activity against newly hatched larvae of Culex quinquefasciatus with LC 50 values of 38.5 (±1.16), 11.6 (±0.58), and 20.5 (±1) μg/mL, respectively. The four xanthene derivatives have the potential to be developed as new biopesticides.

Two novel epimer pairs of acetaminophen derivatives penicilquei A-D (1-4) were isolated from Penicillium herquei JX4. Their structures were elucidated using comprehensive spectroscopic methods. The absolute configurations of penicilquei A-D (1-4) were determined by modifified Mosher's method, and comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Penicilquei A-D (1-4) are the first example of acetaminophen derivatives featuring an unprecedented carbon skeleton. The inhibitory activities of all compounds against nine phytopathogenic fungi and α-glucosidase were evaluated. Penicilquei A-D (1-4) showed strong inhibitory activities against at least eight phytopathogenic fungus., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To systemically evaluate the efficacy and safety of Cinobufacini Injection in combination with platinum-contained first-line chemotherapy for treatment of non-small cell lung cancer(NSCLC). The randomized controlled trials(RCT) about the Cinobufacini in combination with platinum-contained first-line chemotherapy(versus chemotherapy alone) were collected through PubMed,Cochrane library,CNKI,VIP,CBM,and Wan Fang Database from database inception to December 2018. Two researchers extracted data and assessed the literature quality separately,and made a Meta-analysis by using Rev Man 5. 3 software. Twenty-seven RCTs were included in the present review,involving 2 125 patients,1 082 in treatment group and 1 043 in control group. The Meta-analysis results showed that as compared with chemotherapy alone,the combination of Cinobufacini and platinum-contained first-line chemotherapy could enhance one year survival rate(RR = 1. 34,95%CI[1. 17,1. 55],P< 0. 01),two year survival rate(RR = 1. 84,95% CI[1. 31,2. 59],P<0. 01),objective tumor response rate(RR = 1. 47,95%CI[1. 33,1. 63],P<0. 01); improve the quality of life for patients(RR =1. 54,95%CI[1. 37,1. 72],P < 0. 01); and reduce the incidences of WBC toxicity(RR = 0. 63,95% CI[0. 49,0. 80],P < 0. 01),platelet toxicity(RR = 0. 54,95%CI[0. 35,0. 84],P<0. 01),gastrointestinal reactions(RR = 0. 60,95%CI[0. 45,0. 80],P<0. 05),pain(RR = 1. 68,95% CI[1. 38,2. 03],P< 0. 01),and hair loss reaction(RR = 0. 76,95% CI[0. 59,0. 98],P < 0. 05). The results showed that for the treatment of NSCLC,the addition of cinofacini to conventional platinum-contained chemotherapy can increase the long-term and short-term efficacy of chemotherapy,improve the quality of life for patients,and reduce the side effects of platinumbased chemotherapy drugs. However,more high quality and large-scale randomized controlled trials are required to verify this conclusion in the future.

Objective: Lactulose is effective in the treatment and prevention of overt hepatic encephalopathy (OHE), but there are limited data on its use on microbiota in relations to minimal hepatic encephalopathy (MHE) recovery. The present study aimed to assess the efficacy of lactulose in recovery of MHE in aspects of cognitive function, quality of life, and impact on intestinal microbiota., Methods: This multicenter, open-label randomized controlled trial was conducted in 11 teaching hospitals in China. Participants were randomly allocated on a 2:1 basis to receive lactulose (Gp-L) or no therapy as control (Gp-NL) for 60 days. The primary endpoint was the MHE reversal rate. Gut microbiota were compared between MHE patients and healthy volunteers, as well as lactulose-responders and non-responders., Results: A total of 98 cirrhotic patients were included in the study, with 31 patients in the Gp-NL group and 67 patients in the Gp-L group. At day 60, the MHE reversal rate in Gp-L (64.18%) was significantly higher than that in Gp-NL (22.58%) (P = .0002) with a relative risk of 0.46 (95% confidence interval 0.32-0.67). Number needed to treat was 2.4. Further, there was significantly more improvement in physical functioning in Gp-L (4.62 ± 6.16) than in Gp-NL (1.50 ± 5.34) (P = .0212). Proteobacteria was significantly higher in MHE patients compared with healthy volunteers (12.27% vs 4.65%, P < .05). Significant differences were found between lactulose responders and non-responders in Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria., Conclusions: Treatment with lactulose significantly improves MHE recovery rate, and gut microbiota change in MHE patients can modulate the effectiveness of this therapy. Chinese Clinical Trial Register (ChiCTR) (ID: ChiCTR-TRC-12002342)., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate the effectiveness and safety of Chinese medicine (CM) for Idiopathic pulmonary fibrosis (IPF) patients., Methods: To screened relevant articles, PubMed, Cochrane Library, Excerpta Medica Datase (EMBASE), China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang Database and Chinese Biomedical Database (CBM) were searched in English or Chinese until December 2015 for randomized controlled trials, which compared CM treatment (CM group) with Western medicine or placebo (control group) on IPF. The outcome measures included acute exacerbation, pulmonary function, the St George's respiratory questionnaire (SGRQ) scores, 6-minute walk test (6MWT) distance, adverse events and mortality., Results: This meta-analysis included 25 randomized controlled trials involving 1,471 patients. Compared with the control group, CM group was superiori in reducing the risk of exacerbation [relative risk (RR)=0.40, 95% CI 0.22 to 0.72, P<0.05], improving in forced expiratory volume in one second (FEV1) [standard mean difference (SMD)=0.62, 95% CI 0.40 to 0.84, P<0.01] and diffusion capacity for carbon monoxide (DLCO, SMD=0.40, 95% CI 0.22 to 0.58, P<0.01), but there was no significant difference in vital capacity (VC, SMD=0.10, 95% CI-0.12 to 0.31, P>0.05). This meta-analysis also revealed that CM therapy significantly decreased the SGRQ score (SMD=-0.60, 95% CI-1.14 to-0.05, P<0.05) and improved 6MWT distance (SMD=0.59, 95% CI 0.34 to 0.84, P<0.01), compared with the control group. Meanwhile, CM therapy was associated with a low incidence of adverse effects (RR=0.19, 95% CI 0.08 to 0.43, P<0.01). However, there was no significant difference in mortality (RR=0.24, 95% CI 0.05 to 1.10, P>0.05) between CM and control groups., Conclusions: The pooled outcomes suggest that CM treatment appears benefit in reducing the risk of exacerbation, improving lung function and decreasing the incidence of adverse effects and enhancing the quality of life. However, the outcomes were limited because of the low quality of the included studies. More rigorous clinic trials need to be carried out to provide sufficient and accurate evidence in the future.

Astaxanthin (ATX) is a carotenoid that exerts strong anti-oxidant and anti-inflammatory property deriving from its highly unsaturated molecular structures. However, the low stability and solubility of ATX results in poor bioavailability, which markedly hampers its application as therapeutic agent in clinic advancement. This study investigated a promising way of transferrin conjugated to poly (ethylene glycol) (PEG)-encapsulated ATX nanoparticles (ATX-NPs) on targeted delivery and evaluated the possible mechanism underlying neuroprotection capability. As a result, the ATX integrated into nanocarrier presented both well water-dispersible and biocompatible, primely conquering its limitations. More than that, the transferrin-containing ATX-NPs exhibited enhanced cellular uptake efficiency than that of ATX-NPs without transferrin conjugated in primary cortical neurons. Additionally, compared to free ATX, transferrin-containing ATX-NPs with lower ATX concentration showed powerful neuroprotective effects on OxyHb-induced neuronal damage. Taken together, the improved bioavailability and enhanced neuroprotective effects enabled ATX-NPs as favorable candidates for targeted delivery and absorption of ATX. We believe that these in vitro findings will provide insights for advancement of subarachnoid hemorrhage therapy., (Copyright © 2019 You, Wu, Zhou, Zhang, Yuan, Wen, Xu, Cui, Tang and Zhang.)

Seed germination and formation are the beginning and ending, respectively, of a plant life cycle. These two processes are under fine regulation by the internal genetic information. Previously, we demonstrated that Arabidopsis MIDASIN 1 (MDN1) is required for ribosome biogenesis, and its dysfunction leads to pleiotropic developmental phenotypes, including impaired embryogenesis and slow seed germination. In this study, we further found that the weak mutant of MDN1 , mdn1-1 , exhibits an increased seed size phenotype. Seed proteomic analysis reveals that a number of proteins involved in seed development and response to external environments are mis-regulated by the MDN1 dysfunction. Many 2S seed storage proteins (SSPs) and late embryogenesis abundant (LEA) proteins are over-accumulated in the dry seeds of mdn1-1 . Further, some genes encoding seed storage reserves are also upregulated in mdn1-1 seedlings. More interestingly, abscisic acid-insensitive 5 (ABI5) is over-accumulated in mdn1-1 seeds, and the loss of its function partially rescues the low seed germination rate of mdn1-1 . Together, this study further demonstrates that MDN1 is essential for establishing a normal seed proteome, and its mutation triggers ABI5-mediated repression of seed germination.

Samples of particulate matter from coal-fired boilers of different tons were collected in Lanzhou city, and the water-soluble inorganic ions, carbonaceous species, water-soluble organic compounds (WSOC) and polycyclic aromatic hydrocarbons (PAHs) were analyzed. The results showed that SO 4 2- , Cl - , and Ca 2+ were the most important water-soluble ions in the coal-fired boiler samples, accounting for 35.13%, 23.16%, and 22.20% of the total mass of water-soluble ions, respectively. The pyrolysis composition spectra of the carbonaceous species were similar among the coal-fired boilers, and organic carbon fraction (OC1, OC2, OC3, and OC4),and elemental carbon fraction (EC1, EC2, and EC3) accounted for 1.04%, 8.26%, 20.09%, 6.78%, 51.08%, 7.09%, and 5.66% of the total carbon (TC), respectively. EC1 had the highest content and was the most important carbonaceous species. The average ratios of WSOC/TC and WSOC/OC were 0.09±0.07 and 0.23±0.12, respectively, and the difference among the boilers of different tons was large. Phenanthrene (Phe), pyrene (Pyr), and benzene(k)anthracene (BkF) were the three main components of the PAHs, accounting for 16.69%, 11.93%, and 10.66% of the total PAHs, respectively. The particulate water-soluble ions, organic/elemental carbon aerosol (OCEC) and WSOC emitted from different tons coal-fired boilers were not significantly linearly related to the tonnage of the steam boiler, and low molecular weight PAHs decreased with the increase of tonnage of the steam boiler.