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Objective To study the relationship between DNA double-strand break (DSB) repair gene mutations and the risk of papillary thyroid microcarcinoma (PTMC). Methods One hundred patients with PTMC or benign thyroid nodules (BTNs) at Henan Cancer Hospital were retrospectively analyzed. The DSB repair capacity of peripheral blood T lymphocytes in the two groups was assessed by flow cytometry. Data were compared using Student’s t-test to evaluate the relationship between DSB repair capacity and the risk of PTMC. Factors influencing DSB repair capacity were analyzed by multivariate logistic regression analysis. The relationship between PTMC and DSB repair capacity was analyzed by univariate analysis. Targeted next-generation DNA sequencing was applied to screen and analyze DSB repair genes related to PTMC. Results The DSB repair capacity was 31.30% in the PTMC group and 44.40% in the BTN group, with that of the former being significantly lower (P OR = 3.642; 95% CI 1.484–8.935, P = 0.020). Moreover, univariate analysis showed that a reduction in DSB repair capacity was a risk factor for PTMC(OR = 2.333; 95% CI 1.027–5.300, P = 0.043).Targeted next-generation DNA sequencing was performed on the DSB repair genes discovered, and those that were mutated in association with PTMC were Rad50 and FANCA; Rad51 mutations were related to BTN. Conclusion Radiation exposure is positively associated with induced DSB repair gene mutations, which may cause a reduced capacity for DSB repair and eventually lead to PTMC.

Background "Diffuse midline glioma, H3 K27M-mutant" (DMG) mainly arises within the pontine, thalamic, and spinal cord regions. Because of the rarity of spinal cord gliomas, the general knowledge surrounding DMGs is mainly based on pontine and thalamic gliomas, whereas tumor location tends to influence the clinicopathological features and prognosis. Objective To determine the clinicopathological characteristics and molecular profiles of DMGs located in the spinal cord. Methods The clinical and molecular pathologic features and prognosis were comprehensively analyzed in a series of 44 patients with spinal cord DMGs. Results The median age was 36 yr, and 88.7% of patients (39/44) were adults (≥18 yr). Histopathologically, malignant grades included grade II (16 cases), grade III (20 cases), and grade IV (8 cases). Compared with patients with histological grade IV, patients with lower histological grade (grade II/III) were older (37 vs 24 yr, P = .020) and were associated with longer overall survival (24.1 vs 8.6 mo, P = .007). All 30 tested tumors were isocitrate dehydrogenase (IDH) wild type, and 96% of cases (22/23) presented with unmethylated O6-methylguanine-DNA methyltransferase. Univariate and multivariate analyses showed that histological grade and presurgery McCormick Scale scores were independent prognostic factors for overall survival, whereas extensive surgical resection and chemoradiotherapy were not significantly associated with improved survival. The most frequent anatomic locations were the cervical enlargement (C4-T1, n = 16) and conus medullaris (T12-L1, n = 13), which exhibited distinctive clinical characteristics and molecular features. Conclusion The findings provide guidelines for the evidence-based practice of the specialized management of spinal cord DMGs.

Non‐small‐cell lung cancer (NSCLC), with its aggressive biological behavior, is one of the most diagnosed cancers. Tumor‐associated inflammatory cells play important roles in the interaction between chronic inflammation and lung cancer, however the mechanisms involved are far from defined. In the present study, by developing an orthotopic NSCLC mouse model based on chronic inflammation, we proved that an inflammatory microenvironment accelerated the growth of orthotopic xenografts in vivo. Tumor‐associated macrophages, the most abundant population of inflammatory cells, were identified. Treatment with macrophage‐conditioned medium (MCM) promoted the growth and migration of NSCLC cells. Using bioinformatics analysis, we identified downregulated PP2Ac expression in NSCLC cells upon treatment with MCM. We further confirmed that this downregulation was executed in an NF‐κB pathway‐dependent manner. As IκB kinase (IKK) has been proved to be a substrate of PP2Ac, inhibition on PP2Ac could result in amplification of NF‐κB pathway signaling. Overexpression of PP2Ac, or the dominant‐negative forms of IKK or IκB, attenuated the acceleration of growth and metastasis by MCM. Using bioinformatics analysis, we further identified that CXCL1 and COL6A1 could be downstream of NF‐κB/PP2Ac pathway. Luciferase assay and ChIP assay further confirmed the location of response elements on the promoter regions of CXCL1 and COL6A1. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted proliferation and migration., Tumor‐associated macrophages, the prominent type of inflammatory cells in non‐small‐cell lung cancer, can promote the growth and metastasis of cancer cells. Overexpression of PP2Ac, or the dominant‐negative forms of IKK or IκB, attenuated the acceleration on cancer cell growth and metastasis by TAMs. CXCL1 and COL6A1 could be downstream of NF‐κB/PP2Ac pathway. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted cancer cell proliferation and migration.

Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.

Traditional Chinese medicine (TCM) is gaining increasing popularity worldwide for the function of health promotion and adjuvant therapy. However, the world's understanding of TCM is far from enough, which seriously limits the modernization and internationalization of TCM. Therefore, modern and efficient analytical methods are urgently needed to understand the mechanism of TCM. Optogenetics is one of the most prevalent technologies in the 21st century and has been used to explore life science, especially neuroscience. It already has had great influences in the study of neural circuits and animal models of mental diseases and was named “Method of the Year” by the Nature Methods journal in 2010. Increased interests occurred in the applications of optogenetics to explore a myriad of medical and mental health disorders. However, it has not so far been noticed by TCM researchers. We elaborated on an idea that introducing this technique into the field of TCM research to improve diagnosis, treatments, and evaluating the therapeutic effects. In this review, we made a systematic prospect in the theory, feasibility, and application of TCM optogenetics. We mainly focused on applying optogenetic methodologies to make a more comprehensive understanding of TCM.

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion: M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.

Aims To develop an artificial intelligence-based approach with multi-labelling capability to identify both ST-elevation myocardial infarction (STEMI) and 12 heart rhythms based on 12-lead electrocardiograms (ECGs). Methods and results We trained, validated, and tested a long short-term memory (LSTM) model for the multi-label diagnosis of 13 ECG patterns (STEMI + 12 rhythm classes) using 60 537 clinical ECGs from 35 981 patients recorded between 15 January 2009 and 31 December 2018. In addition to the internal test above, we conducted a real-world external test, comparing the LSTM model with board-certified physicians of different specialties using a separate dataset of 308 ECGs covering all 13 ECG diagnoses. In the internal test, the area under the curves (AUCs) of the LSTM model in classifying the 13 ECG patterns ranged between 0.939 and 0.999. For the external test, the LSTM model for multi-labelling of the 13 ECG patterns evaluated by AUC was 0.987 ± 0.021, which was superior to those of cardiologists (0.898 ± 0.113, P Conclusions We demonstrated the usefulness of an LSTM model in the multi-labelling detection of both rhythm classes and STEMI in competitive testing against board-certified physicians. This AI tool exceeding the cardiologist-level performance in detecting STEMI and rhythm classes on 12-lead ECG may be useful in prioritizing chest pain triage and expediting clinical decision-making in healthcare.

Background:. Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network. Methods:. A total of 183 rectal cancer patients’ data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve. Results:. An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00. Conclusion:. Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging. Trial registration:. chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665.

IgA nephropathy (IgAN), an immune complex-mediated process and the most common primary glomerulonephritis, can progress to end-stage renal disease in up to 40% of patients. Accordingly, a therapeutic strategy targeting a specific molecular pathway is urgently warranted. Aided by structure characterisation and target identification, we predicted that a novel ring-fused 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (LCC18) targets the NLRP3 inflammasome, which participates in IgAN pathogenesis. We further developed biomarkers for the disease. We used two complementary IgAN models in C57BL/6 mice, involving TEPC-15 hybridoma-derived IgA, and in gddY mice. Moreover, we created specific cell models to validate therapeutic effects of LCC18 on IgAN and to explain its underlying mechanisms. IgAN mice benefited significantly from treatment with LCC18, showing dramatically improved renal function, including greatly reduced proteinuria and renal pathology. Mechanistic studies showed that the mode of action specifically involved: (1) blocking of the MAPKs/COX-2 axis-mediated priming of the NLRP3 inflammasome; (2) inhibition of ASC oligomerisation and NLRP3 inflammasome assembly by inhibiting NLRP3 binding to PKR, NEK7 and ASC; and (3) activation of autophagy. LCC18 exerts therapeutic effects on murine IgAN by differentially regulating NLRP3 inflammasome activation and autophagy induction, suggesting this new compound as a promising drug candidate to treat IgAN. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Purpose Due to the rarity of diffuse spinal cord astrocytoma, an effective model is still lacking to stratify their prognosis. Here, we aimed to establish a prognostic model through comprehensively evaluating clinicopathological features and preoperative peripheral blood inflammatory markers in 89 cases. Methods We performed univariate and multivariate Cox regression to identify prognosis factors. The Kaplan–Meier curves and ROC curves were employed to compare the prognostic value of selected factors. Results In addition to clinicopathological factors, we revealed the preoperative peripheral blood leukocyte count, neutrophils-to-lymphocytes ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were also significantly correlated with overall survival of spinal cord astrocytoma in univariate Cox regression, and NLR was still significant in multivariate Cox analysis. Further, we demonstrated that NLR ≤ 3.65 and preoperative McCormick score (MMS) ≤ 3 were independently correlated with better survival of WHO grade IV tumors. Meanwhile, Ki-67 3.65 or MMS = 4. Conclusion We successfully constructed a comprehensive prognostic model including preoperative peripheral blood inflammatory markers, which can stratify diffuse spinal cord astrocytoma into 4 subgroups.

Fusion of petals to form a corolla tube is considered a key innovation contributing to the diversification of many flowering plant lineages. Corolla tube length often varies dramatically among species and is a major determinant of pollinator preference. However, our understanding of the developmental dynamics underlying corolla tube length variation is very limited. Here we examined corolla tube growth in the Mimulus lewisii species complex, an emerging model system for studying the developmental genetics and evo-devo of pollinator-associated floral traits. We compared developmental and cellular processes associated with corolla tube length variation among the bee-pollinated M. lewisii, the hummingbird-pollinated Mimulus verbenaceus, and the self-pollinated Mimulus parishii. We found that in all three species, cell size is non-uniformly distributed along the mature tube, with the longest cells just distal to the stamen insertion site. Differences in corolla tube length among the three species are not associated with processes of organogenesis or early development but are associated with variation in multiple processes occurring later in development, including the location and duration of cell division and cell elongation. The tube growth curves of the small-flowered M. parishii and large-flowered M. lewisii are essentially indistinguishable, except that M. parishii tubes stop growing earlier at a smaller size, suggesting a critical role of heterochrony in the shift from outcrossing to selfing. These results not only highlight the developmental process associated with corolla tube variation among species but also provide a baseline reference for future developmental genetic analyses of mutants or transgenic plants with altered corolla tube morphology in this emerging model system.

The Atlantic sea nettle ( Chrysaora quinquecirrha) has an important evolutionary position due to its high ecological value. However, due to limited sequencing technologies and complex jellyfish genomic sequences, the current C. quinquecirrha genome assembly is highly fragmented. Here, we used the most advanced high-throughput chromosome conformation capture (Hi-C) technology to obtain high-coverage sequencing data of the C. quinquecirrha genome. We then anchored these data to the previously published contig-level assembly to improve the genome. Finally, a high-continuity genome sequence of C. quinquecirrha was successfully assembled, which contained 1 882 scaffolds with a N50 length of 3.83 Mb. The N50 length of the genome assembly was 5.23 times longer than the previously released one, and additional analysis revealed that it had a high degree of genomic continuity and accuracy. Acquisition of the high-continuity genome sequence of C. quinquecirrha not only provides a basis for the study of jellyfish evolution through comparative genomics but also provides an important resource for studies on jellyfish growth and development.

Background Deep-learning algorithms to annotate electrocardiograms (ECGs) and classify different types of cardiac arrhythmias with the use of a single-lead ECG input data set have been developed. It remains to be determined whether these algorithms can be generalized to 12-lead ECG-based rhythm classification. Methods We used a long short-term memory (LSTM) model to detect 12 heart rhythm classes with the use of 65,932 digital 12-lead ECG signals from 38,899 patients, using annotations obtained by consensus of 3 board-certified electrophysiologists as the criterion standard. Results The accuracy of the LSTM model for the classification of each of the 12 heart rhythms was ≥ 0.982 (range 0.982-1.0), with an area under the receiver operating characteristic curve of ≥ 0.987 (range 0.987-1.0). The precision and recall ranged from 0.692 to 1 and from 0.625 to 1, respectively, with an F1 score of ≥ 0.777 (range 0.777-1.0). The accuracy of the model (0.90) was superior to the mean accuracies of internists (0.55), emergency physicians (0.73), and cardiologists (0.83). Conclusions We demonstrated the feasibility and effectiveness of the deep-learning LSTM model for interpreting 12 common heart rhythms according to 12-lead ECG signals. The findings may have clinical relevance for the early diagnosis of cardiac rhythm disorders.

Abnormal protein glycosylation is associated with many diseases including cardiovascular disease, diabetes, and cancer. Therefore, selective capturing of glycoproteins under physiological or weak acid conditions (tumor microenvironment) is vital for disease diagnosis and further comprehensive analysis. Here, we propose a strategy of intermolecular B-N bond-based phenylboronic acid affinity to capture glycoproteins under neutral and slightly acidic conditions. Surprisingly, the captured glycoproteins were released in alkaline solution. This is contrary to the traditional phenylboric acid affinity, and we studied this from the perspective of materials, proteins, and incubation conditions. We identified the synergistic effect of intermolecular B-N bond-based phenylboronic acid affinity, electrostatic interaction, and polymer brush structure-based glycoprotein adsorption under slightly acidic conditions. The electrostatic repulsion between Fe3O4@SiO2@poly (2-aminoethyl methacrylate hydrochloride)-4-carboxyphenylboronic acid (Fe3O4@SiO2@PAMA-CPBA) nanoparticles and transferrin (TRF) was far greater than the specific binding between phenylboric acid of CPBA and glycosylation residues of TRF resulting in the release of the captured glycoproteins in alkaline solution. Fe3O4@SiO2@PAMA-CPBA nanoparticles exhibited different selectivity capabilities toward different glycoproteins in multiprotein solutions due to protein interactions. These results may pave a new way for the design of phenylboric acid-based materials towards glycoprotein adsorption in a physiological environment.

Choledocholithiasis is a chronic common disease. The incidence of cholelithiasis is 5%-15%, of which 5%-30% are combined with Choledocholithiasis. Although endoscopic cholangiopancreatography (ERCP) + endoscopic sphincterotomy (EST) is the most common treatment procedure, which clearance rate is up to 95%, the incidence of recurrent choledocholithiasis was 4%-25%. The risk factors of recurrence after choledocholithiasis clearance are the focuses of current researches, which are caused by multiple factors. We first systematically summarize the risk factors of common bile duct stones (CBDS) recurrence into five aspects: first-episode stone related factors, congenital factors, biological factors, behavioral intervention factors, and the numbers of stone recurrence.

The endometrium undergoes a pregnancy-delivery-repair cycle multiple times during the reproductive lifespan in females. Decidualization is one of the critical events for the success of this essential process. We have previously reported that Notch1 is essential for artificial decidualization in mice. However, in a natural pregnancy, the deletion of Notch1 (PgrCre/+Notch1f/f, or Notch1d/d) only affects female fertility in the first 30 days of a 6-month fertility test, but not the later stages. In the present study, we undertook a closer evaluation at the first pregnancy of these mice to attempt to understand this puzzling phenomenon. We observed a large number of pregnancy losses in Notch1d/d mice in their first pregnancy, which led to the subfertility observed in the first 30 days of the fertility test. We then demonstrated that the initial pregnancy loss is a consequence of impaired decidualization. Furthermore, we identified a group of genes that contribute to Notch1 regulated decidualization in a natural pregnancy. Gene ontogeny analysis showed that these differentially expressed genes in the natural pregnancy are involved in cell–cell and cell–matrix interactions, different from genes that have been previously identified from the artificial decidualization model, which contribute to cell proliferation and apoptosis. In summary, we determined that Notch1 is essential for normal decidualization in the mouse uterus only in the first pregnancy but not in subsequent ones.Summary sentenceNotch1 is essential for normal decidualization in the mouse uterus only in the first pregnancy but not in subsequent ones; the initial pregnancy loss is a consequence of impaired decidualization.

Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small‐molecule palladium complex, can inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukaemia and multiple myeloma. Given that this compound is particularly active against B‐cell malignancies, we have been suggested that it can alleviate immune complexes (ICs)–mediated conditions, especially IgA nephropathy (IgAN). The therapeutic effects of Tris DBA on glomerular cell proliferation and renal inflammation and mechanism of action were examined in a mouse model of IgAN. Treatment of IgAN mice with Tris DBA resulted in markedly improved renal function, albuminuria and renal pathology, including glomerular cell proliferation, neutrophil infiltration, sclerosis and periglomerular inflammation in the renal interstitium, together with (Clin J Am Soc Nephrol. 2011, 6, 1301‐1307) reduced mitochondrial ROS generation; (Am J Physiol‐Renal Physiol. 2011. 301, F1218‐F1230) differentially regulated autophagy and NLRP3 inflammasome; (Clin J Am Soc Nephrol. 2012, 7, 427‐436) inhibited phosphorylation of JNK, ERK and p38 MAPK signalling pathways, and priming signal of the NLRP3 inflammasome; and (Free Radic Biol Med. 2013, 61, 285‐297) blunted NLRP3 inflammasome activation through SIRT1‐ and SIRT3‐mediated autophagy induction, in renal tissues or cultured macrophages. In conclusion, Tris DBA effectively ameliorated the mouse IgAN model and targeted signalling pathways downstream of ICs‐mediated interaction, which is a novel immunomodulatory strategy. Further development of Tris DBA as a therapeutic candidate for IgAN is warranted.

Background The feasibility of submandibular gland (SMG) preservation in oral squamous cell carcinoma (SCC) has occasionally been analyzed, but the differences in survival associated with the presence or absence of SMG preservation remain unknown. We aimed to prospectively evaluate the oncologic results of SMG preservation in cT1-2 N0 buccal SCC. Methods This was a prospective, non-randomized cohort study. Patients with surgically treated cT1-2 N0 buccal SCC were prospectively enrolled and divided into two groups based on the management of the SMG. Level 1b lymph nodes were categorized into six groups based on the positional relationship between the lymph node and the SMG. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS). Results A total of 31 of the 137 included patients underwent SMG-sparing neck dissection. Patients with SMG preservation were likely to be young persons. Superior metastasis occurred in 11 patients with a prevalence of 8.0%, followed by an anterior metastasis rate of 5.1%, and no metastases developed deeply or within the SMG. The 5-year LRC rates in the SMG-sparing and SMG-excision groups were 74 and 75%, respectively, and the difference was not significant (p = 0.970). The 5-year DSS rates in the SMG-sparing and SMG-excision groups were 74 and 69%, respectively, and the difference was not significant (p = 0.709). Conclusions SMG involvement was rare, and the superior group carried the highest risk for lymph node metastasis. SMG-sparing neck dissection is selectively suggested in cT1-2 N0 buccal SCC patients, and could avoid postoperative asymmetric appearance and dry mouth.

With about 153 species, the genus Androsace (Primulaceae) is known for its horticultural and economic importance. In this study, we report the complete chloroplast genome of Androsace erecta Maximowicz, a morphologically distinct species of Sect. Orthocaulon native to the Western China. The plastome of A. erecta is highly conserved in genome size, structure, and content when compared to all previously published plastomes of the genus. The phylogenomic analysis strongly supported A. erecta as sister to a clade comprising species of Sections Aizoideia and Chamaejasme. Lastly, we selected the four most variable regions across the Androsace species plastomes (trnKUUU-rps16, trnSGCU-trnGUCC , psbE-petL, and infA-rps8), which were considered to be suitable candidate DNA barcodes for Androsace.

Doxorubicin cardiotoxicity is frequently reported in patients undergoing chemotherapy. The present study investigates whether cardiomyopathy induced by doxorubicin can be improved by the natural flavone acacetin in a mouse model and uncovers the potential molecular mechanism using cultured rat cardiomyoblasts. It was found that the cardiac dysfunction and myocardial fibrosis induced by doxorubicin were significantly improved by acacetin in mice with impaired Nrf2/HO‐1 and Sirt1/pAMPK molecules, which is reversed by acacetin treatment. Doxorubicin decreased cell viability and increased ROS production in rat cardiomyoblasts; these effects are significantly countered by acacetin (0.3‐3 μM) in a concentration‐dependent manner via activating Sirt1/pAMPK signals and enhancing antioxidation (Nrf2/HO‐1 and SOD1/SOD2) and anti‐apoptosis. These protective effects were abolished in cells with silencing Sirt1. The results demonstrate for the first time that doxorubicin cardiotoxicity is antagonized by acacetin via Sirt1‐mediated activation of AMPK/Nrf2 signal molecules, indicating that acacetin may be a drug candidate used clinically for protecting against doxorubicin cardiomyopathy.

More than 80,000 angiosperm species produce flowers with petals fused into a corolla tube. As an important element of the tremendous diversity of flower morphology, the corolla tube plays a critical role in many specialized interactions between plants and animal pollinators (e.g., beeflies, hawkmoths, hummingbirds, nectar bats), which in turn drives rapid plant speciation. Despite its clear significance in plant reproduction and evolution, the corolla tube remains one of the least understood plant structures from a developmental genetics perspective. Through mutant analyses and transgenic experiments, here we show that the tasiRNA-ARF pathway is required for corolla tube formation in the monkeyflower speciesMimulus lewisii. Loss-of-function mutations in theM. lewisiiorthologs ofARGONAUTE7andSUPPRESSOR OF GENE SILENCING 3cause a dramatic decrease in abundance ofTAS3-derived small RNAs and a moderate up-regulation ofAUXIN RESPONSE FACTOR 3(ARF3) andARF4, which lead to inhibition of lateral expansion of the bases of petal primordia and complete arrest of the upward growth of the inter-primordial regions, resulting in unfused corollas. By using an auxin reporter construct, we discovered that auxin distribution is continuous along the petal primordium base and the inter-primordial region during the critical stage of corolla tube formation in the wild-type, and that this auxin distribution is much weaker and more restricted in the mutant. Together, these results suggest a new conceptual model highlighting the central role of auxin directed synchronized growth of the petal primordium base and the inter-primordial region in corolla tube formation.

Background Although miR-758-3p has been reported to be associated with multiple cancers, including hepatocellular carcinoma, bladder cancer, gastric cancer and papillary thyroid cancer, its role in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods The expression levels of miR-758-3p in ccRCC tissues and cell lines were examined using qRT-PCR. Survival analysis was performed using Kaplan-Meier, while the prognostic significance of miR-758-3p was evaluated by Cox regression analysis. The effects of miR-758-3p on cell proliferation, migration and invasion were analyzed with CCK-8, crystal violet and transwell assays. Luciferase reporter assays were performed to determine the effect of miR-758-3p on MDM2. Western blot was applied to measure the expression of MDM2. Results The expression levels of miR-758-3p were down-regulated in human ccRCC tissues and cell lines. Moreover, the expression of miR-758-3p was closely associated with histological grade, TNM stage and vascular invasion. High expression of miR-758-3p was found to be capable of predicting favorable clinical prognosis in ccRCC patients. Additionally, whilst the proliferation, migration and invasion of ccRCC cells were inhibited upon overexpression of miR-758-3p, the effects were reversed upon miR-758-3p knockdown. Moreover, miR-758-3p was a modulator of MDM2 in ccRCC. Conclusion This study demonstrated that miR-758-3p is a potential prognostic biomarker for ccRCC patients. Data from this study showed that miR-758-3p exhibits different biological functions that inhibit the progression of ccRCC cells, hence it can be a potential therapeutic target candidate for treating ccRCC.

Carassotrema schistorchis is a digenea parasite whose juvenile and adult stages parasitize the intestinal tract of definitive host fish. There is no available ecological information about this parasitic infection in wild host fish. The present work aimed to investigate the infection rate and distribution of C. schistorchis in wild silver carp, Hypophthalmichthys molitrix, and to assess the influence of environmental factors on infection by the parasite. From October 2016 to May 2019, a total of 554 wild silver carp were collected from two reservoirs. These collected fish were weighed, measured, and dissected to observe the presence of C. schistorchis following standard methodology. Ecological analysis results showed that the frequency distribution of C. schistorchis in the host population was aggregated distribution. The abundance of C. schistorchis exhibited a positive correlation with the host age and condition factor of silver carp, but it showed no relationship with water temperature, pH or DO. The condition factor value of infected fish was significantly higher than that of uninfected fish. These results indicated that food intake, not environmental factors, directly determined infection by the parasite in the host, indicating that an increased food intake would increase the risk of infection. Thus, the number of parasites could be used as an indirect biological marker for assessing the effectiveness of silver carp in filter-feeding on plankton. The following analysis indicated that silver carp with a body length of 50–55 cm showed the highest efficiency in controlling phytoplankton biomass. This study provides important information for understanding the ecology of C. schistorchis in wild silver carp., Graphical abstract Image 1, Highlights • First report on the ecological information of Carassotrema schistorchis in wild silver carp. • Food intake, not environmental factors, determined the abundance of C. schistorchis in the host. • Silver carp with a body length of 50–55 cm showed the highest efficiency in controlling plankton.

Background Due to their rarity, the clinicopathological characteristics and prognostic factors of spinal cord gliomas are still unclear. Here, we aimed to clarify these issues in a cohort of 108 spinal cord astrocytomas. Methods We characterized the clinicopathological characteristics, including 2016 World Health Organization (WHO) grade, age, sex, location, segment length, resection, pre‐ and postsurgery, Modified McCormick Scale (MMS), radio‐ and chemotherapy, and Ki‐67 and H3 K27M mutations, in 108 spinal cord astrocytomas through heatmaps. The Cox regression analysis and Kaplan‐Meier curves were used to study the prognostic value of these clinicopathological features. Results There are a total 38 H3 K27M‐mutant tumors, including 31 cases with histological grade II/III tumors. The age of low‐grade astrocytoma patients (WHO grade I/II, n = 54) was significantly younger (27.0 vs 35.5 years, P = .001) than those with high‐grade tumors (WHO grade III/IV, n = 54). All patients underwent surgical resection with neurophysiological monitoring, and the surgery did not result in significant changes in MMS. The presurgery MMS was associated with overall survival in the high‐grade subgroup (P = .008) but not in the low‐grade subgroup (P = .312). While, the high content of resection improved the survival of only patients with low‐grade astrocytomas (P = .016) but not those with high‐grade astrocytomas (P = .475). Both the low‐grade and high‐grade astrocytomas had no obvious benefit from neither adjuvant chemotherapy nor radiotherapy (all P > .05). Conclusions We characterized the clinicopathological characteristics and their prognostic values in 108 spinal cord astrocytomas, which could help with evidence‐based management of spinal cord astrocytomas., We characterized the clinicopathological characteristics and their prognostic values in 108 spinal cord astrocytomas, which could help with evidence‐based management of spinal cord astrocytomas.

Sepiapterin reductase, a homodimer composed of two subunits, plays an important role in the biosynthesis of tetrahydrobiopterin. Furthermore, sepiapterin reductase exhibits a wide distribution in different tissues and is associated with many diseases, including brain dysfunction, chronic pain, cardiovascular disease and cancer. With regard to drugs targeting sepiapterin reductase, many compounds have been identified and provide potential methods to treat various diseases. However, the underlying mechanism of sepiapterin reductase in many biological processes is unclear. Therefore, this article summarized the structure, distribution and function of sepiapterin reductase, as well as the relationship between sepiapterin reductase and different diseases, with the aim of finding evidence to guide further studies on the molecular mechanisms and the potential clinical value of sepiapterin reductase. In particular, the different effects induced by the depletion of sepiapterin reductase or the inhibition of the enzyme suggest that the non‐enzymatic activity of sepiapterin reductase could function in certain biological processes, which also provides a possible direction for sepiapterin reductase research.

IgA nephropathy (IgAN), the most common primary glomerular disorder, has a relatively poor prognosis yet lacks a pathogenesis-based treatment. Compound K (CK) is a major absorbable intestinal bacterial metabolite of ginsenosides, which are bioactive components of ginseng. The present study revealed promising therapeutic effects of CK in two complementary IgAN models: a passively induced one developed by repeated injections of IgA immune complexes and a spontaneously occurring model of spontaneous grouped ddY mice. The potential mechanism for CK includes 1) inhibiting the activation of NLRP3 inflammasome in renal tissues, macrophages and bone marrow–derived dendritic cells, 2) enhancing the induction of autophagy through increased SIRT1 expression, and 3) eliciting autophagy-mediated NLRP3 inflammasome inhibition. The results support CK as a drug candidate for IgAN.

Gallbladder carcinoma (GBC) is a vicious and invasive disease. The major challenge in the clinical treatment of GBC is the lack of a suitable prognosis method. Chemokine receptors such as CXCR3, CXCR4 and CXCR7 play vital roles in the process of tumour progression and metastasis. Their expression levels and distribution are proven to be indicative of the progression of GBC, but are hard to be decoded by conventional pathological methods, and therefore, not commonly used in the prognosis of GBC. In this study, we developed a computer‐aided image analysis method, which we used to quantitatively measure the expression levels of CXCR3, CXCR4 and CXCR7 in the nuclei and cytoplasm of glandular and interstitial cells from a cohort of 55 GBC patients. We found that CXCR3, CXCR4 and CXCR7 expressions are associated with the clinicopathological variables of GBC. Cytoplasmic CXCR3, nuclear CXCR7 and cytoplasmic CXCR7 were significant predictive factors of histology invasion, whereas cytoplasmic CXCR4 and nuclear CXCR4 were significantly correlated with T and N stage and were associated with the overall survival and disease‐free survival. These results suggest that the quantification and localisation of CXCR3, CXCR4 and CXCR7 expressions in different cell types should be considered using computer‐aided assessment to improve the accuracy of prognosis in GBC.

Background Non-virus genetic treatment for Parkinson’s disease (PD) via plasmid glial cell-line derived neurotrophic factor (pGDNF) has shown potential for repairing damaged dopaminergic neurons. However, development of this gene therapy is largely hampered by the insufficient transfection efficiency as a result of the cell membrane, lysosome, and cytoskeleton meshwork. Methods In this study, we propose the use of polyethylenimine (PEI)-superparamagnetic iron oxide-plasmid DNA (pDNA)-loaded microbubbles (PSp-MBs) in conjunction with focused ultrasound (FUS) and two-step magnetic navigation to provide cavitation, proton sponge effect and magnetic effects to increase the efficiency of gene delivery. Results The gene transfection rate in the proposed system was 2.2-fold higher than that of the commercial agent (TransIT®-LT1). The transfection rate could be boosted ∼11%, ∼10%, and 6% by cavitation-magnetic hybrid enhanced cell membrane permeabilization, proton sponge effect, and magnetic-assisted cytoskeleton-reorganization, respectively. In vivo data suggested that effective gene delivery with this system results in a 3.2-fold increase in recovery of dopaminergic neurons and a 3.9-fold improvement in the motor behavior when compared to untreated genetic PD mice. Conclusions We proposed that this novel FUS-magnetic hybrid gene delivery platform could be integrated with a variety of therapeutic genes for treating neurodegenerative diseases in the future.

Objective This study set out to probe into the effects of long non-coding RNA (LncRNA) differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis and autophagy of breast cancer (BC) cells. Methods The expression levels of DANCR, miR-758-3p and paired box 6 (PAX6) in BC tissues and cell lines were detected. The transcription and protein levels of PAX6, apoptosis-related factors (caspase-3, caspase-9, Bax/Bcl-2), and autophagy-related factors (LC3B, Atg5, Beclin-1) in BC cells were detected. The cell proliferation, apoptosis, autophagy and the regulatory relationship between genes and target genes were analyzed. Results DANCR and PAX6 were up-regulated in BC tissues and cell lines, while miR-758-3p was opposite. Down-regulating DANCR inhibited the malignant proliferation of BC cells and also promoted apoptosis and autophagy, which showed that caspase-3, caspase-9, Bax/Bcl-2, LC3B, Atg5 transcription and protein levels increased, while Beclin-1 transcription and protein levels decreased. DANCR regulated miR-758-3p in a targeted manner, and its over-expression could weaken the anti-cancer effect of miR-758-3p on BC cells. In addition, miR-758-3p also directly targeted PAX6, and knocking down its expression could weaken the inhibitory effect of down-regulating PAK6 on BC cell apoptosis and autophagy. We also found that DANCR acted as a competitive endogenous RNA sponge miR-758-3p, thus regulating the PAX6 expression. Conclusion DANCR-miR-758-3p-PAX6 molecular network plays a key regulatory role in BC cell apoptosis and autophagy, which may provide reference for treating patients.

Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small-molecule palladium complex, has been shown to inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukemia, and multiple myeloma. In the current study, we examined the therapeutic effects of Tris DBA on glomerular cell proliferation, renal inflammation, and immune cells. Treatment of accelerated and severe lupus nephritis (ASLN) mice with Tris DBA resulted in improved renal function, albuminuria, and pathology, including measurements of glomerular cell proliferation, cellular crescents, neutrophils, fibrinoid necrosis, and tubulointerstitial inflammation in the kidneys as well as scoring for glomerulonephritis activity. The treated ASLN mice also showed significantly decreased glomerular IgG, IgM, and C3 deposits. Furthermore, the compound was able to 1) inhibit bone marrow–derived dendritic cell–mediated T cell functions and reduce serum anti-dsDNA autoantibody levels; 2) differentially regulate autophagy and both the priming and activation signals of the NLRP3 inflammasome; and 3) suppress the phosphorylation of JNK, ERK, and p38 MAPK signaling pathways. Tris DBA improved ASLN in mice through immunoregulation by blunting the MAPK (ERK, JNK)-mediated priming signal of the NLRP3 inflammasome and by regulating the autophagy/NLRP3 inflammasome axis. These results suggest that the pure compound may be a drug candidate for treating the accelerated and deteriorated type of lupus nephritis.

The incredible diversity of floral color and pattern in nature is largely determined by the transcriptional regulation of anthocyanin and carotenoid biosynthetic genes. While the transcriptional control of anthocyanin biosynthesis is well understood, little is known about the factors regulating the carotenoid biosynthetic pathway in flowers. Here, we characterize the Reduced Carotenoid Pigmentation 2 (RCP2) locus from two monkeyflower (Mimulus) species, the bumblebee-pollinated M. lewisii and hummingbird-pollinated M. verbenaceus. We show that loss-of-function mutations of RCP2 cause drastic down-regulation of the entire carotenoid biosynthetic pathway in these species. Through bulk segregant analysis and transgenic experiments, we have identified the causal gene underlying RCP2, encoding a tetratricopeptide repeat (TPR) protein that is closely related to the Arabidopsis Reduced Chloroplast Coverage (REC) proteins. RCP2 appears to regulate carotenoid biosynthesis independently of RCP1, a previously identified R2R3-MYB master regulator of carotenoid biosynthesis. We show that RCP2 is required for chromoplast development and suggest that it most likely regulates the expression of carotenoid biosynthetic genes through chromoplast-to-nucleus retrograde signaling. Furthermore, we demonstrate that M. verbenaceus is just as amenable to chemical mutagenesis and in planta transformation as the more extensively studied M. lewisii, making these two species an excellent platform for comparative developmental genetics studies of two closely related species with dramatic phenotypic divergence.

Sestrin2 (SESN2) is a highly evolutionary conserved protein and involved in different cellular responses to various stresses. However, the potential function of SESN2 in immune system remains unclear. The present study was designed to test whether dendritic cells (DCs) could express SESN2, and investigate the underlying molecular mechanism as well as its potential significance. Herein, we firstly reported that SESN2 was expressed in DCs after high mobility group box-1 protein (HMGB1) stimulation and the apoptosis of DCs was obviously increased when SESN2 gene silenced by siRNA. Cells undergone SESN2-knockdown promoted endoplasmic reticulum (ER) stress (ERS)-related cell death, markedly exacerbated ER disruption as well as the formation of dilated and aggregated structures, and they significantly aggravated the extent of ERS response. Conversely, overexpressing SESN2 DCs markedly decreased apoptotic rates and attenuated HMGB1-induced ER morphology fragment together with inhibition of ERS-related protein translation. Furthermore, sesn2−/−-deficient mice manifested increased DC apoptosis and aggravated ERS extent in septic model. These results indicate that SESN2 appears to be a potential regulator to inhibit apoptotic ERS signaling that exerts a protective effect on apoptosis of DCs in the setting of septic challenge.

Background: Artificial intelligence-assisted image recognition technology is currently able to detect the target area of an image and fetch information to make classifications according to target features. This study aimed to use deep neural networks for computed tomography (CT) diagnosis of perigastric metastatic lymph nodes (PGMLNs) to simulate the recognition of lymph nodes by radiologists, and to acquire more accurate identification results. Methods: A total of 1371 images of suspected lymph node metastasis from enhanced abdominal CT scans were identified and labeled by radiologists and were used with 18,780 original images for faster region-based convolutional neural networks (FR-CNN) deep learning. The identification results of 6000 random CT images from 100 gastric cancer patients by the FR-CNN were compared with results obtained from radiologists in terms of their identification accuracy. Similarly, 1004 CT images with metastatic lymph nodes that had been post-operatively confirmed by pathological examination and 11,340 original images were used in the identification and learning processes described above. The same 6000 gastric cancer CT images were used for the verification, according to which the diagnosis results were analyzed. Results: In the initial group, precision-recall curves were generated based on the precision rates, the recall rates of nodule classes of the training set and the validation set; the mean average precision (mAP) value was 0.5019. To verify the results of the initial learning group, the receiver operating characteristic curves was generated, and the corresponding area under the curve (AUC) value was calculated as 0.8995. After the second phase of precise learning, all the indicators were improved, and the mAP and AUC values were 0.7801 and 0.9541, respectively. Conclusion: Through deep learning, FR-CNN achieved high judgment effectiveness and recognition accuracy for CT diagnosis of PGMLNs. Trial Registration: Chinese Clinical Trial Registry, No. ChiCTR1800016787; http://www.chictr.org.cn/showproj.aspx?proj= 28515. Key words: Faster region-based convolutional neural networks; Perigastric metastatic lymph nodes; Deep learning; Gastric cancer

Limited evidence was seen as the association between fine particulate matter (PM2.5) and physician visits for allergic rhinitis (AR), especially in countries with extreme air pollution exposure. This paper addressed the issues about the association between PM2.5 and daily outpatient visits for AR among individuals residing in Beijing, China. Data on daily outpatient visits for AR obtained from Beijing Medical Claim Data for Employees and daily PM2.5 concentrations available from US embassy reports were linked by date from January 1, 2010, to June 30, 2012. A time-series analysis was conducted with a generalized additive Poisson model to assess the association between PM2.5 and AR, adjusting for daily average temperature, relative humidity, day of the week, calendar time, and public holiday. Totally, 229,685 outpatient visits for AR were included in the analysis. The daily mean (SD) concentration of PM2.5 was 99.5 (75.3) μg/m3 during the study period. We found that a 10-μg/m3 increase in PM2.5 content was associated with a 0.47% (95% CI: 0.39% to 0.55%) increase in the number of outpatient visits on the same day. Furthermore, results from subgroup analyses suggested that the association was consistently significant among the groups of different ages (

BackgroundIn recent years, acupuncture has been increasingly integrated into pediatric care worldwide. However, recent epidemiological studies about pediatric users of acupuncture are lacking. The current study aimed to fill the gap and carry out the large-scale investigation on the basis of the pediatric population in Taiwan.MethodsWe conducted a nationwide population-based study to investigate the utilization of acupuncture in Taiwan. We analyzed data from the Longitudinal Health Insurance Database 2000 (LHID 2000). The datasets contained all original claims data for 1 million beneficiaries who were randomly sampled from the registry of all beneficiaries enrolled in the Taiwan’s National Health Insurance Program from January 1, 2000 to December 31, 2011. Children younger than 18 years old were enrolled into our study for analysis. The demographic data, treatment modalities and distributions by disease categories of the pediatric acupuncture users were analyzed by descriptive statistics. Logistic regression analysis was used to investigate the trends in acupuncture use over time.ResultsThe one-year prevalence of pediatric acupuncture users increased from 1.78% in 2002 to 5.34% in 2011. Acupuncture use significantly increased each year (p-value 9 years old) children tended to receive acupuncture treatment due to injury and musculoskeletal system disorders more than younger (≤9 years old) children.ConclusionsOur study revealed that the utilization of acupuncture in pediatrics became increasingly popular year by year in Taiwan from 2002 to 2011. The results of this study may provide some valuable information for further clinical practice and acupuncture research, as well as to the government and societies concerning pediatric health care.

Background: Carotid intima-media thickness (cIMT) has been associated with an elevated risk of ischemic stroke (IS) in several studies, but the results are inconsistent. We investigated whether the association between cIMT and IS varied across different IS subtypes, and further assessed gene&ndash, cIMT interactions&rsquo, association with IS risk. Methods: A total of 1048 IS cases (795 large-artery atherosclerosis (LAA) cases, 103 small-vessel occlusion (SVO) cases, and 150 other subtypes) and 2696 IS-free controls across 2179 families were included in the analysis. Self-reported IS cases were confirmed through medical records&rsquo, review and head imaging by computed tomography and/or magnetic resonance imaging. The mean values of the common cIMT obtained in bilateral distal and proximal carotid artery segments were used. The genotype information of rs2910164 polymorphism in microRNA-146a (miR-146a) was also collected. Results: We found that cIMT was significantly associated with a higher risk of IS and LAA subtype but not SVO subtype in the multivariate-adjusted models. The odds ratio (OR) and 95% confidence interval (CI) in the highest quartile versus the lowest quartile of cIMT was 2.48 (1.92&ndash, 3.20) for IS and 2.75 (2.08&ndash, 3.64) for LAA (both p trend &lt, 0.001). The results also showed that there was a significant interaction between cIMT and rs2910164 genotype with the risk of IS (p interaction = 0.03) and LAA (p interaction = 0.02). The associations of cIMT with IS and LAA were strengthened among participants carried rs2910164_GG genotype compared with those with rs2910164_CC genotype. Conclusions: Our results indicate that higher cIMT levels were significantly associated with IS and LAA subtype but not SVO subtype, and the relations were modified by rs2910164 polymorphism in miR-146a.

Anthocyanins play a variety of adaptive roles in both vegetative tissues and reproductive organs of plants. The broad functionality of these compounds requires sophisticated regulation of the anthocyanin biosynthesis pathway to allow proper localization, timing, and optimal intensity of pigment deposition. While it is well-established that the committed steps of anthocyanin biosynthesis are activated by a highly conserved MYB-bHLH-WDR (MBW) protein complex in virtually all flowering plants, anthocyanin repression seems to be achieved by a wide variety of protein and small RNA families that function in different tissue types and in response to different developmental, environmental, and hormonal cues. In this review, we survey recent progress in the identification of anthocyanin repressors and the characterization of their molecular mechanisms. We find that these seemingly very different repression modules act through a remarkably similar logic, the so-called 'double-negative logic'. Much of the double-negative regulation of anthocyanin production involves signal-induced degradation or sequestration of the repressors from the MBW protein complex. We discuss the functional and evolutionary advantages of this logic design compared with simple or sequential positive regulation. These advantages provide a plausible explanation as to why plants have evolved so many anthocyanin repressors.

One‐lung ventilation (OLV), a common ventilation technique, is associated with perioperative lung injury, tightly connected with inflammatory responses. Dexmedetomidine has shown positive anti‐inflammatory effects in lung tissues in pre‐clinical models. This study investigated the efficacy of dexmedetomidine for suppressing inflammatory responses in patients requiring OLV. We searched PubMed, MEDLINE, Embase, Scopus, Ovid, and Cochrane Library for randomized controlled trials focusing on dexmedetomidine’s anti‐inflammatory effects on patients requiring OLV without any limitation on the year of publication or languages. 20 clinical trials were assessed with 870 patients in the dexmedetomidine group and 844 in the control group. Our meta‐analysis investigated the anti‐inflammatory property of dexmedetomidine perioperatively [T1 (30‐min OLV), T2 (90‐min OLV), T3 (end of surgery) and T4 (postoperative day 1)], demonstrating that dexmedetomidine’s intraoperative administration resulted in a significant reduction in serum concentration of interleukin‐6, tumor necrosis factor‐α and other inflammatory cytokines perioperatively. By calculating specific I 2 index, significant heterogeneity was observed on all occasions, with I 2 index ranging from 95% to 99%. For IL‐6 changes, sensitivity analysis showed that the exclusion of a single study led to a significant decrease of heterogeneity (96%–0%; p

Eukaryotic cells contain numerous membraneless organelles that are made from liquid droplets of proteins and nucleic acids and that provide spatiotemporal control of various cellular processes. However, the molecular mechanisms underlying the formation and rapid stress-induced alterations of these organelles are relatively uncharacterized. Here, we investigated the roles of DEAD-box helicases in the formation and alteration of membraneless nuclear dicing bodies (D-bodies) in Arabidopsis thaliana. We uncovered that RNA helicase 6 (RH6), RH8, and RH12 are previously unidentified D-body components. These helicases interact with and promote the phase separation of SERRATE, a key component of D-bodies, and drive the formation of D-bodies through liquid-liquid phase separations (LLPSs). The accumulation of these helicases in the nuclei decreases upon Turnip mosaic virus infections, which couples with the decrease of D-bodies. Our results thus reveal the key roles of RH6, RH8, and RH12 in modulating D-body formation via LLPSs.

The orange-spotted grouper (Epinephelus coioides) is an important marine farmed fish in China. It is affected by the bacterial pathogen Vibrio alginolyticus, which causes high mortality and substantial economic losses. We studied the transcriptional changes of the IgZ gene in E. coioides following V. alginolyticus stimulation and investigated the distribution of IgZ in different tissues. The highest expression level of IgZ occurred in the head kidney. When fish were stimulated with live and inactivated V. alginolyticus, the expression levels of IgZ in the head kidney, spleen, intestine, gills and blood cells were significantly upregulated. In an in situ hybridization study, IgZ mRNA-positive cells were detected in the head kidney, spleen and gill, but positive signals were not detected in the liver and intestine. IgZ-labelled cells increased in the head kidney, spleen and gills post-infection with V. alginolyticus for 21 days. The present study provides additional evidence that IgZ is involved in mucosal immune responses and helps explain the role of IgZ in E. coioides defence against V. alginolyticus infection.

Renal cell carcinoma (RCC) is a type of urinary tumor with a high incidence and is often associated with tumor metastasis. Long non-coding RNA (lncRNA) regulates tumorigenesis, progression, and metastasis. However, the role and the predictive value of lncRNA in RCC progression and metastasis have not been elucidated. The purpose of this study was to evaluate the effect of a newly discovered lncRNA LOC648987 on RCC proliferation and metastasis. LOC648987 was identified by RT-PCR for high expression in human RCC tissues as well as in metastatic RCC tissues. In the cell experiments, we infected the RCC cell lines ACHN and 786-O cells with LOC648987-shRNA and its negative control (shNC). The results showed that the knockdown of LOC648987 inhibited the proliferation of ACHN and 786-O cells and colony formation. The cell cycle and the apoptosis progression of ACHN and 786-O cells were assessed using flow cytometry. The knockdown of LOC648987 significantly inhibited the progression of ACHN and 786-O cells from G0/G1 to S phase and promoted cell apoptosis. The metastasis promoting effects of LOC648987 on ACHN and 786-O cells were verified by transwell migration assays, which depended on vimentin and MMP-9 to regulate the epithelial–mesenchymal transition. Finally, the promotion of LOC648987 on RCC tumorigenesis was evaluated in BALb/c nude mice. These data confirmed that lncRNA LOC648987 promoted RCC cell proliferation and tumor metastasis and regulated the expression of EMT-related proteins in RCC cells.

Background Sepsis is a condition of organ dysfunction caused by infection, and is unavoidably related to costs and mortality; however, no biomarker has yet been identified to clearly predict the prognosis of septic patients. In this study, we aimed to explore the role of guanine-rich sequence factor 1 (GRSF1) in evaluating the severity and prognosis of sepsis. Methods The expression of GRSF1 in peripheral blood was measured and analyzed in 42 septic participants and 32 healthy controls respectively by using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Clinical data were assessed by correlation analysis. In addition, GRSF1 expression was investigated in cecal ligation and puncture (CLP) induced mice septic models by RT-qPCR and western blot (WB). Results The expression of GRSF1 expression in septic patients in the first day of electronic intensive care unit (eICU) administration was significantly lower in comparison with HC. Further analysis showed GRSF1 expression was strongly related to the Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score. Low expression of GRSF1 predicted high mortality within 24 hours in septic patients and in CLP-induced mice. Conclusions Decreased expression of GRSF1 was significantly correlated with high mortality in septic patients, and also in experimental septic mice. The GRSF1 protein may be a potential prognostic biomarker in sepsis.

This study aimed to determine the metabolites associated with ventricular septal defect (VSD) and the underlying mechanisms. Blood samples and thymus tissues were collected from VSD patients to perform LC-MS-based metabolomics assay and generate iPS cell-derived cardiomyocytes, respectively. VSD rat model was used

Despite the role of polyploidy in multiple evolutionary processes, its impact on plant diversification remains controversial. An increased polyploid frequency may facilitate speciation through shifts in ecology, morphology or both. Here we used Allium to evaluate: (1) the relationship between intraspecific polyploid frequency and species diversification rate; and (2) whether this process is associated with habitat and/or trait shifts. Using eight plastid and nuclear ribosomal markers, we built a phylogeny of 448 Allium species, representing 46% of the total. We quantified intraspecific ploidy diversity, heterogeneity in diversification rates and their relationship along the phylogeny using trait-dependent diversification models. Finally, we evaluated the association between polyploidisation and habitat or trait shifts. We detected high ploidy diversity in Allium and a polyploidy-related diversification rate shift with a probability of 95% in East Asia. Allium lineages with high polyploid frequencies had higher species diversification rates than those of diploids or lineages with lower polyploid frequencies. Shifts in speciation rates were strongly correlated with habitat shifts linked to particular soil conditions; 81.7% of edaphic variation could be explained by polyploidisation. Our study emphasises the role of intraspecific polyploid frequency combined with ecological drivers on Allium diversification, which may explain plant radiations more generally.

Background Despite progress achieved in bladder cancer (BC) treatment, the prognosis of patients with advanced BC (ie, metastasized from the bladder to other organs) is poor. Although mortality in cases of low-grade BC is rare, the treatment, such as a radical cystectomy, often has a serious impact on the quality of life. Thus, research is needed to identify more effective treatment strategies and this work is aiming to examine the potential application of combination of radiofrequency ablation (RFA) and SB435142, a inhibitor of transforming growth factor β (TGFβ)/Smad pathway. Methods BC cells were transplanted into nude mice (thymusdeficiency Bal B/c) to form subcutaneous tumors. The mice with subcutaneous tumors were then treated with RFA and oral administration of SB431542, an inhibitor of TGFβ/Smad signaling pathway. The antitumor effect of RFA was measured by tumor proliferation curves and micro-positron emission computed tomography (micro-PET). The effect of SB431542 on epithelial-mesenchymal transition (EMT) related regulators in subcutaneous tumor tissues formed by BC cells were examined by quantitative real-time polymerase chain reaction (qPCR) experiments. Results The SB431542 treatment enhanced the antitumor effect of RFA on subcutaneous growth of BCs. SB431542 also decreased EMT-related regulators in subcutaneous tumor tissues formed by BC cells in nude mice. Conclusion SB431542 enhances the effect of RFA on BC.

RNA kissing complexes are essential for genomic RNA dimerization and regulation of gene expression, and their structures and stability are critical to their biological functions. In this work, we used our previously developed coarse-grained model with an implicit structure-based electrostatic potential to predict three-dimensional (3D) structures and stability of RNA kissing complexes in salt solutions. For extensive RNA kissing complexes, our model shows great reliability in predicting 3D structures from their sequences, and our additional predictions indicate that the model can capture the dependence of 3D structures of RNA kissing complexes on monovalent/divalent ion concentrations. Moreover, the comparisons with extensive experimental data show that the model can make reliable predictions on the stability for various RNA kissing complexes over wide ranges of monovalent/divalent ion concentrations. Notably, for RNA kissing complexes, our further analyses show the important contribution of coaxial stacking to the 3D structures and stronger stability than the corresponding kissing-interface duplexes at high salts. Furthermore, our comprehensive analyses for RNA kissing complexes reveal that the thermally folding pathway for a complex sequence is mainly determined by the relative stability of two possible folded states of kissing complex and extended duplex, which can be significantly modulated by its sequence.

Residual cancer after incomplete ablation remains a major problem for radiofrequency ablation (RFA). We aimed to investigate the synergetic treatment efficacy of RFA combined with ultrasonic cavitation for liver tumor. Sixty rabbits with VX2 liver tumor were randomly divided into three groups. Group A was control group without any treatment. Combined ultrasonic cavitation with RFA was performed for group B1. Group B2 underwent RFA alone. The histopathological results were compared at the 5th, 11th, and 18th day of experiment, and the survival time and metastasis were assessed. The tumor volume growth rate, percentage of necrosis area, microvessel density, and apoptosis index showed significant differences among these groups at the 5th day, 11th day, and 18th day of experiment (P < .05). In contrast, the difference of metastatic score was not significant at the 5th and 11th day (P > .05). At the 18th day, the metastatic score of group A was significant higher than that of group B1 (P < .05), whereas the differences between group A and group B2, or group B1 and group B2 were not significant (P > .05). The median/range interquartile of survival time in groups A, B1, and B2 were 25/8 days, 50/19 days, and 48/20 days, respectively, and there was significant difference between groups A and B1 or B2 (P < .05). The difference between groups B1 and B2 was not significant (P > .05). Ultrasonic cavitation after incomplete RFA for liver tumor improved the antitumor effect, which could be considered as a potentially useful combined therapeutic strategy for liver malignancy. Keywords: Radiofrequency ablation, Ultrasound, Liver neoplasms, Residual cancer, Microbubbles

Objective Diabetes-associated cognitive decline (DACD) is increasingly being concerned, and oxidative stress plays a vital role in the pathological process. AB-38b is a novel synthetic compound with two specific active groups of biphenyl dicarboxylate and α, β unsaturated ketone, showing good antioxidant activity. The aim of this study was to investigate the ameliorative effects of AB-38b on DACD in mice, and to explore the possible mechanisms from glyoxylase 1 (Glo-1) enhancement and NF-E2-related factor-2 (Nrf2) activation. Methods Experimental type 2 mouse model of diabetes with C57BL/6 mice was made through high-fat diet combining with intraperitoneal streptozotocin. Diabetic mice were treated by gavage with AB-38b (0, 10, 20 and 40 mg/kg) or resveratrol (40 mg/kg), a typical inducer of Nrf2, for 8 weeks. Cognitive performances were evaluated by the novel object recognition task. Then brain tissues were collected to assess hippocampal damages, protein glycation, Glo-1 functions and protein expression, and the classic Nrf2/ARE pathway. Result AB-38b markedly increased the preference index to novel object and the number of neurons in hippocampal CA1 area of diabetic mice. AB-38b significantly elevated the activity and protein of Glo-1, while reduced the levels of advanced glycation end products (AGEs) and protein expression of its receptor RAGE. Moreover, AB-38b raised Nrf2 expression and phosphorylation, as well as the protein expression and enzymatic activity of γ-glutamylcysteine synthetase, a well-known gene of Nrf2/ARE pathway, in hippocampus of the diabetic mice. Conclusion AB-38b improved the cognitive performances of diabetic mice, which was achieved via up-regulation of Glo-1 and activation of Nrf2/ARE pathway.

Cynatratoside-C, isolated from Cynanchum atratum, is a promising alternative agent for the control of the ecoparasite Ichthyophthirius multifiliis. However, the pharmacokinetics and residue elimination of cynatratoside-C in fish have yet to be reported. Here, we aimed to investigate the pharmacokinetics and residue elimination of cynatratoside-C in grass carp following a single intraperitoneal (i.p.) dose of 2 mg/kg body weight at a water temperature of 23.0 ± 0.3 °C. The concentrations of cynatratoside-C in the serum, liver, kidney, and muscle were determined using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). We found that the pharmacokinetics of cynatratoside-C in the grass carp was described by a two-compartment model. The absorption half-life (t1/2Kα), distribution half-life (t1/2α), and elimination half-life (t1/2β) of cynatratoside-C in the serum were 0.28 h, 1.45 h, and 69.32 h, respectively. The maximum cynatratoside-C concentration (Cmax) in the serum was 123.81 μg/L, with a time to peak concentration (Tmax) of 0.5 h. The post-injection residue concentration of cynatratoside-C (during the elimination period) was highest in the liver and lowest in the muscle. The concentration of cynatratoside-C in the muscle fell below the limit of quantification (1.24 ng/g) 15 days post-administration. Thus, for grass carp, we recommend a withdrawal period of 15 days following a single i.p. dose of 2 mg cynatratoside-C/kg body weight at a water temperature of 23.0 ± 0.3 °C.

Largemouth bronze gudgeon (Coreius guichenoti) is a fish endemic to the middle and upstream reaches of the Yangtze River in China. Indoor culture and domestication of C. guichenoti have yet to see success in part because of Ichthyophthirius multifiliis infection, which causes 100% mortality in these fish. Here, we investigated whether the complement components C3 and C9 in C. guichenoti play a role in immune reactions against I. multifiliis. Full-length C3 and C9 cDNA sequences were determined and analyzed. The C3 cDNA sequence comprised 5142 bp encoding 1643 amino acids. The C9 cDNA sequence comprised 2206 bp with an open reading frame of 2085 bp. The mRNA expression of C3 and C9 genes was detected in the liver, spleen, and trunk kidney, and as well as that of C3 gene in head kidney. I. multifiliis infection significantly upregulated mRNA expression of C3 and C9 in liver and spleen. However, no transcript was detected in the skin of C. guichenoti post-infection with I. multifiliis, and might be responsible for C. guichenoti to be vulnerable to the parasite. The results suggest that C3 and C9 are involved in defense against the ectoparasite I. multifiliis, and promote understanding function of the complement components C3 and C9 in C. guichenoti.