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Convolutional Neural Network (CNN) plays a vital role in the development of computer vision applications. The depth neural network composed of U-shaped structures and jump connections is widely used in various medical image tasks. Recently, based on the self-attention mechanism, the Transformer structure has made great progress and tends to replace CNN, and it has great advantages in understanding global information. In this paper, the ConvWin Transformer structure is proposed, which refers to the W-MSA structure in Swin and combines with the convolution. It can not only accelerate the convergence speed, but also enrich the information exchange between patches and improve the understanding of local information. Then, it is integrated with UNet, a U-shaped architecture commonly used in medical image segmentation, to form a structure called ConvWin-UNet. Meanwhile, this paper improves the patch expanding layer to perform the upsampling operation. The experimental results on the Hubmap datasets and synapse multi-organ segmentation dataset indicate that the proposed ConvWin-UNet structure achieves excellent results. Partial code and models of this work are available at https://github.com/xmFeng-hdu/ConvWin-UNet.

Bacterial infection and the subsequent lack of osseointegration are two of the main problems encountered during the early stage of implantation. To resolve these issues, in this study, the micro/nanostructure on titanium surface was fabricated by dual-acid treatment and anodic oxidation, and then GelMA hydrogel loaded with GL13K was coated onto the micro/nanostructured titanium. The surface properties of different titanium substrates were characterized by scanning electron microscopy, atomic force microscope, water contact angle measurement, and

Long-term time series prediction is a challenging and essential task both in theory and practice. Recently, information granulation is shown to be an appropriate tool for the long-term forecast. Though some models for the long-term prediction problem have been proposed using information granulation recently, there is still a growing need to develop new prediction approaches for time series data based on information granule, which can capture the dynamic trend change with high accuracy. In this article, a long-term prediction approach, based on back-propagation neural network and information granule, is proposed. First, the individual numerical intervals for the time series are obtained by using the principle of justifiable granularity in information granule. Then, an automatic linear trend extraction method is developed to extract the trend change, which is inherited in granules. Finally, a hierarchy of neural network is constructed to carry out prediction by using information granule as input. Experiments using publicly available time series datasets demonstrate that the proposed approach can achieve better performance than the existing models for long-term prediction.

Background The clinicopathological value and exploration of the potential molecular mechanism of microRNA-183-5p (miR-183-5p) have been investigated in various cancers. This study further explored the transcriptome profile regulated by miR-183-5p. Methods Messenger RNA (mRNA) expression data, miRNA expression, and clinical information of stomach adenocarcinoma (STAD) were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) that related to mir-189-5p expression and cancer proliferation were acquired using bioinformatics analysis. The biological functions of these genes were analyzed in terms of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes relating to gastric cancer (GC) signal pathway were explored. The results were validated by further experiments. Results A total of 308 genes were found to be regulated by miR-183-5p, and they were related to cancer and GC patients' survival outcome. The biological function of these genes was found to act mainly on biological processes and the involved signal pathways included neuroactive ligand-receptor interaction, cell adhesion molecules, and axon guidance. In addition, miR-183-5p was also shown to regulate the mTOR, Wnt, MAPK, and PI3K-Akt signaling pathways through the genes WNT2B, NGFR, and NTRK2. Conclusions The miRNA miR-183-5p participates in the tumorigenesis and development of GC via certain signaling pathways, in particular the nerve- and immunity-related genes.

The totally implantable venous access port (TIVAP) is an intravenous-infusion device, with a lower complication rate than other such devices. If patients fail to maintain the catheter, however, complications can still occur. Patients' needs may vary by the period of the port's use.The study intended to explore the differences in the needs of breast-cancer (BC) patients with TIVAPs for health education and nursing care at different periods of the port's use and to determine the kinds of targeted health education that can improve patients' quality of life.The research team designed a questionnaire that the participants completed.The study took place at the Breast Center at the Fourth Hospital of Hebei Medical University in Shijiazhuang, China.Participants were 442 BC patients at the hospital between March and June 2020, who had TIVAPs at different stages.The study included three groups: (1) the preoperative group-participants in the preoperative period prior to the TIVAP implantation after they had signed a consent; (2) the chemotherapy group-participants in the chemotherapy period during the TIVAP's use for chemotherapy-agent transfusion, and (3) the maintenance group-participants in the maintenance period during which the TIVAD was in place but wasn't being used.The research team analyzed the results from the questionnaires, categorizing them as: (1) methods of knowledge acquisition, (2) methods of distribution of knowledge, (3) needs of participants in the different groups, and (4) distribution of symptoms among the groups.Compared to other methods, the nursing staff was the main source that participants used to access the TIVAP-related information at different periods: preoperative group (79.6%), chemotherapy group (90.7%), and maintenance group (90.2%).The differences between the periods were statistically significant (P = .00). A traditional mode of education-the medical staff's explanations-was the most common in all groups: preoperative group (79.6%), chemotherapy group (83.3%), and (3) maintenance group (80.7%). Patients wanted new modes of receiving information: talks, a poster, and a medical system. TIVAP patients paid different amounts of attention to educational contents at the different stages (χ2 = 29.816, P = .00).BC patients' needs for health education and nursing vary at different stages when using TIVAPs. Nurses are the main source of knowledge about TIVAP in different periods for BC patients, and the nurses should obtain multidisciplinary health knowledge to enhance the benefits of the education for patients. The current education for patient is traditional, and hospitals need to implement new modes of education such as medical systems and network platforms, lectures, and posters for health education.

Micro RNAs (MiRNAs) act as a key regulator participating in various biological process, and the roles of that play in chronic obstructive pulmonary disease (COPD) are discovered. However, recent pharmacological treatment for COPD focus on alleviating symptoms and reducing the risk events. The heterogeneous COPD causes variable responses to pharmacological interventions. COPD treatment has gradually developed into precision medicine, integrating clinical and biomarker information to optimize personalized therapy. Thus, targeting miRNAs represents a promising strategy for COPD individual therapy. Twelve COPD patients, 7 community-acquired pneumonia and 4 normal people were recruited. Total RNAs were collected from the bronch alveolar lavage cells and peripheral blood plasma of each participant. miRNAs were profiled by microarray and systematically compared between patients with different groups. Bioinformatic analysis identified pathways relevant to the pathogenesis of COPD. Next, the target pathway networks were mapped. Compared different groups, we obtain differential expression of miRNAs (Q value (Adjusted P value) .05 and |log2FC|2). Gene ontology enrichment analyses showed that differentially expressed miRNAs function as regulators in different modules of cellular component, molecular function and biological process. Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that signals, such as MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway and oxidative stress may participate in the pathogenesis of COPD. In the miRNAs target pathway networks, novel-hsa-miR26-3p or hsa-miR-3529-3p/CDC42/MAPK signaling pathway may play a role in regulating COPD. Our findings demonstrate critical roles of the miRNAs in COPD molecular pathology. The data support a plausible mechanism that miRNAs may be involved in the development of COPD by affecting the inflammatory and oxidative stress. Moreover, hsa-miR-4748/CDC42/MAPK signaling pathway may contribute to the pathogenesis of COPD, providing a potential novel therapeutic strategy in COPD.

Deep venous thrombosis (DVT) therapy during pregnancy warrants special consideration for the woman and the fetus. This study aimed to evaluate the impact of umbilical cord-derived mesenchymal stem cells (UC-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) in terms of pro-angiogenic capacity and amelioration of pregnancy outcomes. The pregnant DVT rat model was successfully established by the "stenosis" method. Three consecutive injections of both UC-MSCs and BM-MSCs improved angiogenesis and ameliorated the embryo absorption rate in pregnant SD rats with DVT, in which UC-MSCs promoted angiogenesis more significantly. Furthermore, the levels of serum vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor (EGF) were significantly higher in the UC-MSC group compared to those of the BM-MSC group. Thereafter, differentially expressed genes (DEGs) in thrombosed inferior vena cava tissues in the UC-MSC and BM-MSC groups were identified using transcriptome sequencing and further assessed by RT-qPCR and western blotting. The bioinformatics analysis indicated that the enriched DEG terms occurred in the cytokine activity, and the DEG pathways were significantly enriched in the cytokine-cytokine receptor interaction. In addition, both the mRNA and protein levels of angiogenic genes and their receptors, including VEGF-A, VEGF receptor-1, EGF, and EGF receptor, were significantly higher in the UC-MSC group. In conclusion, the BM-MSCs and UC-MSCs both significantly stimulate angiogenesis and ameliorate the embryo absorption rate in pregnant SD rats with DVT, but the difference in cytokine secretion causes UC-MSCs to have more potent angiogenic effects than BM-MSCs.

Stable electrode-electrolyte interphases on both electrodes are indispensable to warrant cycling stability of high-voltage Li-metal batteries. Here, we reveal a unique cooperative reaction mechanism to form protective interphase layers on both Li-metal anode and high-voltage cathodes, which is exemplified by a multifunctional additive ethoxy(pentafluoro)cyclotriphosphazene (PFPN). The F-rich PFPN first reacts with Li-metal anode to form LiF-rich solid electrolyte interphase (SEI), which stabilizes the Li deposition/dissolution processes. Meanwhile, the in-situ generated PFPN derivatives with a de-fluorated structure are prone to be oxidized on cathode, forming a robust cathode-electrolyte interphase (CEI) to prevent electrolyte oxidation and electrode degradation at high voltage. With PFPN to harness the aggressive battery electrodes, Li-metal batteries with high-voltage LiCoO2 (4.5 V) and LiNi0.5Mn1.5O2 (4.9 V) cathodes exhibit improved cycling stability and rate capability. In particular, the LiNi0.5Mn1.5O2|Li full cell with limited Li supply (N/P =7.6) demonstrates outperformed capacity retention of 90.7 % after 100 cycles, which is almost twice that of the cell using PFPN-free conventional electrolyte (47.5 %).

Background: Conflicting data exist regarding the influence of thiopurines exposure on adverse pregnancy outcomes in female patients with inflammatory bowel disease (IBD). Objective: The aim of this study was to provide an up-to-date and comprehensive assessment of the safety of thiopurines in pregnant IBD women. Methods: All relevant articles reporting pregnancy outcomes in women with IBD received thiopurines during pregnancy were identified from the databases (PubMed, Embase, Cochrane Library, and ClinicalTrials.gov) with the publication data up to April 2020. Data of included studies were extracted to calculate the relative risk (RR) of multiple pregnancy outcomes: congenital malformations, low birth weight (LBW), preterm birth, small for gestational age (SGA), and spontaneous abortion. The meta-analysis was performed using the random-effects model. Results: Eight studies matched with the inclusion criteria and a total of 1201 pregnant IBD women who used thiopurines and 4189 controls comprised of women with IBD received drugs other than thiopurines during pregnancy were included. Statistical analysis results demonstrated that the risk of preterm birth was significantly increased in the thiopurine-exposed group when compared to IBD controls (RR, 1.34; 95% CI, 1.00-1.79; p=0.049; I2 =41%), while no statistically significant difference was observed in the incidence of other adverse pregnancy outcomes. Conclusion: Thiopurines used in women with IBD during pregnancy is not associated with congenital malformations, LBW, SGA, or spontaneous abortion, but appears to have an association with an increased risk of preterm birth.

To figure out the spectra features of malformations of cortical development (MCDs) and the differences between MCDs subcategories. Twenty patients and 18 controls were studied. The patients included two subcategories: disorders of migration (DOM) and postmigration (DOPM). Spectra of patients were acquired from both the lesion and the normal-appearing contralateral side (NACS), and they were compared to those of the controls obtained from the frontal lobe. Compared to the controls, a decreased NAA (P = 0.002) was identified in MCDs. After dividing the MCDs into the DOM and DOPM, we found that NAA reduction was only notable in the DOM (P = 0.007). Moreover, Ins and Cr of the DOPM were higher than those of the controls (P = 0.017 and 0.013) and the DOM (P = 0.027 and 0.001). Compared to the NACS, a decreased NAA (P = 0.042) and an increased Ins (P = 0.039) were identified in the lesion of MCDs. After dividing the MCDs into the DOM and DOPM, we found no significant differences in the DOM, but Ins, Cr, and Glx of the lesion were higher than those of the NACS (P = 0.007, 0.005 and 0.047) in the DOPM. In addition, we found that Cr and Glx correlated positively to the seizure frequency (P = 0.003 and 0.016). Decreased NAA was the prominent abnormality confirmed in MCDs. Spectra of different MCDs subcategories were different: the DOM was characterized by decreased NAA, while the DOPM was characterized by increased Ins.

Combining isocitrate dehydrogenase mutation (IDHmut) with O6 -methylguanine-DNA methyltransferase promoter methylation (MGMTmet) has been identified as a critical prognostic molecular marker for gliomas. The aim of this study was to determine the ability of glioma radiomics features from magnetic resonance imaging (MRI) to predict the co-occurrence of IDHmut and MGMTmet by applying the tree-based pipeline optimization tool (TPOT), an automated machine learning (autoML) approach. This was a retrospective study, in which 162 patients with gliomas were evaluated, including 58 patients with co-occurrence of IDHmut and MGMTmet and 104 patients with other status comprising: IDH wildtype and MGMT unmethylated (n = 67), IDH wildtype and MGMTmet (n = 36), and IDHmut and MGMT unmethylated (n = 1). Three-dimensional (3D) T1-weighted images, gadolinium-enhanced 3D T1-weighted images (Gd-3DT1WI), T2-weighted images, and fluid-attenuated inversion recovery (FLAIR) images acquired at 3.0 T were used. Radiomics features were extracted from FLAIR and Gd-3DT1WI images. The TPOT was employed to generate the best machine learning pipeline, which contains both feature selector and classifier, based on input feature sets. A 4-fold cross-validation was used to evaluate the performance of automatically generated models. For each iteration, the training set included 121 subjects, while the test set included 41 subjects. Student's t-test or a chi-square test was applied on different clinical characteristics between two groups. Sensitivity, specificity, accuracy, kappa score, and AUC were used to evaluate the performance of TPOT-generated models. Finally, we compared the above metrics of TPOT-generated models to identify the best-performing model. Patients' ages and grades between two groups were significantly different (p = 0.002 and p = 0.000, respectively). The 4-fold cross-validation showed that gradient boosting classifier trained on shape and textual features from the Laplacian-of-Gaussian-filtered Gd-3DT1 achieved the best performance (average sensitivity = 81.1%, average specificity = 94%, average accuracy = 89.4%, average kappa score = 0.76, average AUC = 0.951). Using autoML based on radiomics features from MRI, a high discriminatory accuracy was achieved for predicting co-occurrence of IDHmut and MGMTmet in gliomas. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Transcription factor Broad Complex (BR-C) is an ecdysone primary response gene in insects and participates in the regulation of insect growth and development. In this study, we performed a genome-wide identification of BR-C target genes in silkworm (Bombyx mori) using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). As a result, a total of 1006 BR-C ChIP peaks were identified, and 15% of peaks were located in the promoter regions of 133 protein-coding genes. Functional annotation revealed that these ChIP peak-associated genes, as potential BR-C targets, were enriched in pathways related to biosynthetic process, metabolic process, and development. Transcriptome analysis and quantitative real-time polymerase chain reaction (PCR) examination revealed that developmental changes in expression patterns of a portion of potential BR-C targets, including HR96 and GC-α1, were similar to those of BR-C. ChIP-PCR examination confirmed that BR-C could directly bind to the promoters of potential targets. Further, dual luciferase assays demonstrated that HR96 promoter activity was significantly upregulated following BR-C overexpression, and this upregulation was abolished when the binding motif in the promoter was truncated. This study will be helpful for deciphering the regulatory roles of BR-C during insect growth and development.

Speckle reduction is a fundamental problem in coherent imaging systems. In this paper, to suppress the speckle in SAR images, we propose a novel truncated nonconvex nonsmooth model. It incorporates...

Andrographis paniculata (AP) is a traditional medicinal plant with many pharmacological activities, including anti-inflammatory, antimicrobial, immunity stimulation and so on. Several studies have reported that AP plays a strong role in promoting the immune system of aquatic animals to resist several pathogens. In the present study, we investigate the effects of a diet containing AP on the immune responses, growth, and the resistance to Vibrio alginolyticus (V. alginolyticus) in Litopenaeus vannamei (L. vannamei). Four diets were formulated by adding AP at the dosage of 0% (Control), 0.25%, 0.5%, and 1% in the basal diet, respectively. Each diet was randomly fed to one group with three replicates of shrimps in a 28-day feeding trial. The results showed that dietary AP improved the growth performance and non-specific immune function of shrimps. To investigate the effect of AP on disease resistance of L. vannamei, shrimps fed with diet containing AP were challenged with V. alginolyticus. Compared with the control group, the shrimps fed diet containing AP showed significantly higher survival. Furthermore, the hepatopancreas injury in the shrimp fed with AP was less than control group at 6 h after V. alginolyticus infection. However, no difference was observed in the degree of hepatopancreas injury between AP groups and control group at 12 h and 24 h after V. alginolyticus infection. Based on this result, the samples at 6 h after V. alginolyticus infection was selected for subsequent detection. Reactive oxygen species (ROS) accumulation in hemocytes and O

MYC proto-oncogene (MYC), a first oncogenic nuclear transcription factor isolated from the human genome, belongs to the helix loop helix/leucine zipper protein family (bHLHzip). MYC plays an important part in the process of various physiological and biochemical of vertebrate, such as cell growth, proliferation, cycle, and autophagy. However, its molecular regulation mechanism and function in invertebrates are still unclear. In this study, a novel transcription factor MYC gene was screened, cloned, and characterized from Penaeus vannamei. The open reading frame of PvMYC was 1593bp, encode a polypeptide of 530 amino acids with molecular weight of 58.5 kDa, and a theoretical PI of 5.75. The results of tissue distribution showed that PvMYC was constitutively expressed in all detected tissues, and highest expression in hepatopancreas. The expression level of PvMYC up-regulated significantly and responded to low temperature stress by nuclear ectopic after low temperature stress. Overexpression of PvMYC in shrimp hemocytes negatively regulated the expression of Beclin-1 and reduced the conversion from LC3I to LC3II, yet p62 was decreased significantly. Meanwhile, RAPA eliminated the inhibition of autophagy caused by overexpression of PvMYC. ROS levels and autophagy flux showed the similar trend under low temperature stress after silencing PvMYC. The expression levels of Beclin-1, key ATG gene and LC3II increased significantly, while p62 decreased significantly under the same conditions. In addition, the Total hemocyte count (THC) decreased sharply, and accelerated the injury of hepatopancreas under low temperature stress after silencing PvMYC. Collectively, these results suggest that PvMYC has vital role in the cold adaptation mechanism of P. vannamei by negatively regulating autophagy.

Zero queueing delay is highly desirable in large-scale computing systems. Existing work has shown that it can be asymptotically achieved by using the celebrated Power-of-$d$-choices (pod) policy with a probe overhead $d = \omega\left(\frac{\log N}{1-\lambda}\right)$, and it is impossible when $d = O\left(\frac{1}{1-\lambda}\right)$, where $N$ is the number of servers and $\lambda$ is the load of the system. However, these results are based on the model where each job is an indivisible unit, which does not capture the parallel structure of jobs in today's predominant parallel computing paradigm. This paper thus considers a model where each job consists of a batch of parallel tasks. Under this model, we propose a new notion of zero (asymptotic) queueing delay that requires the job delay under a policy to approach the job delay given by the max of its tasks' service times, i.e., the job delay assuming its tasks entered service right upon arrival. This notion quantifies the effect of queueing on a job level for jobs consisting of multiple tasks, and thus deviates from the conventional zero queueing delay for single-task jobs in the literature. We show that zero queueing delay for parallel jobs can be achieved using the batch-filling policy (a variant of the celebrated pod policy) with a probe overhead $d = \omega\left(\frac{1}{(1-\lambda)\log k}\right)$ in the sub-Halfin-Whitt heavy-traffic regime, where $k$ is the number of tasks in each job { and $k$ properly scales with $N$ (the number of servers)}. This result demonstrates that for parallel jobs, zero queueing delay can be achieved with a smaller probe overhead. We also establish an impossibility result: we show that zero queueing delay cannot be achieved if $d = \exp\left({o\left(\frac{\log N}{\log k}\right)}\right)$., Comment: 36 pages, 5 figures

Hepatocellular carcinoma (HCC) is an aggressive malignancy with high rates of metastasis and relapse. Isoquercitrin (ISO), a natural flavonoid present in the Chinese bayberry and other plant species, reportedly exerts notable inhibitory effects on tumor cell proliferation, though the mechanism is unknown. In the present study, we exposed HepG2 and Huh7 human liver cancer cells to ISO and examined the roles of autophagy and apoptosis in ISO-mediated cell death. We found that ISO exposure inhibited cell viability and colony growth, activated apoptotic pathway, and triggered dysregulated autophagy by activating the AMPK/mTOR/p70S6K pathway. Autophagy inhibition using 3-methyladenine (3-MA) or Atg5-targeted siRNA decreased the Bax/Bcl-2 ratio, caspase-3 activation, and PARP cleavage and protected cells against ISO-induced apoptosis. Moreover, autophagy inhibition reversed the upregulation of AMPK phosphorylation and downregulation of mTOR and p70S6K phosphorylation elicited by ISO. By contrast, application of a broad-spectrum caspase inhibitor failed to inhibit autophagy in ISO-treated cells. These data indicate that ISO simultaneously induced apoptosis and autophagy, and abnormal induction of autophagic flux contributed to ISO-triggered caspase-3-dependent apoptosis.

A new species of the ampharetid genus Amphicteis, A. hwanghaiensissp. nov., is described based on material from the Yellow Sea. The new species is characterized by the possession of long, stout, golden paleae with blunt tips, digitiform rudimentary notopodia on the abdominal uncinigers, uncini with a subrostral process, and a narrow rectangular hump separating branchial groups. Amphicteis dalmatica was redescribed from type materials at the Australian Museum, Sydney, and the differences between A. dalmatica and A. hwanghaiensissp. nov. are discussed. A key to distinguish Amphicteis species described or reported in Western Pacific waters is provided.

Objective The study aimed to investigate the effect of α2A-adrenergic receptor (ADRA2A) on cervical cancer and the potential mechanisms of ADRA2A on phosphatidylinositol 3'-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in cervical cancer cells. Methods In our study, ADRA2A expression was evaluated by analyzing cervical cancer RNA sequencing dataset from the GEPIA. The prognostic values of ADRA2A were evaluated by Kaplan-Meier method using the Cancer Genome Atlas (TCGA) database data. In addition, the expression of ADRA2A in cervical cancer cell lines was detected by qRT-PCR and Western blot. Subsequently, the roles of ADRA2A on cell proliferation, apoptosis, migration, invasion and senescence in HeLa and SiHa cells were evaluated. Moreover, tumorigenesis in nude mice was used to investigate the role of ADRA2A in vivo. We also detected the expression changes of key factors in PI3K/Akt/mTOR pathway after overexpression and silencing of ADRA2A in HeLa and SiHa cells. Results ADRA2A expression was significantly downregulated in cervical cancer tissues and cell lines. The high expression of ADRA2A was significantly associated with a better prognosis in cervical cancer patients. ADRA2A overexpression significantly suppressed cell proliferation, migration and invasion, and promoted cell senescence and apoptosis in cervical cancer cells. On the contrary, silencing ADRA2A dramatically facilitated cell proliferation, migration and invasion, and inhibited cell senescence and apoptosis in cervical cancer cells. The expressions of p-PI3K, p-AKT and p-mTOR in cervical cancer cells were notably decreased by ADRA2A overexpression and increased by silencing ADRA2A. In addition, we also confirmed that ADRA2A overexpression could suppress the xenograft tumor growth in vivo. Conclusion Our study demonstrated that ADRA2A could suppress cell proliferation, migration and invasion, as well as promote cell senescence and apoptosis through inhibiting PI3K/Akt/mTOR pathway in cervical cancer.

Uveitis is considered the most frequent extra-articular manifestation of Ankylosing Spondylitis (AS). Genetic factors play an important role in the pathogenesis of AS with uveitis. In this study, we investigated susceptibility genes of AS concomitant with uveitis.First, 9p21-24 was selected as the region of susceptibility genes. Second, several candidate genes were selected from this region by bioinformatics analysis. Thirdly, a two-stage case control study was used to verify these candidate genes. The first stage included 50 AS with uveitis, 50 AS without uveitis, and 145 healthy controls. The qPCR+direct sequencing and cloning sequencing were used to identify SNPs in this stage. The second stage included 245 AS with uveitis, 360 AS without uveitis, and 530 healthy controls.IFNA1, IFNB1, IFNA8, and IFNA13 were selected as candidate genes. In the first stage, it was found that the frequency of IFNA1 rs28383797 (G allele) and IFNA13 rs653778 (T allele) in AS with uveitis was higher than that in AS without uveitis and healthy controls. In the second stage, more samples were used to verify the two SNPs. After comprehensive data analysis in the two stages, the frequency of rs28383797 G allele and rs653778 T allele in AS with uveitis was significantly higher than that in AS without uveitis (Rs653778 (T allele) of IFNA13 and rs28383797 (G allele) of IFNA1 were associated with AS concomitant uveitis, and may act as the susceptibility genes of AS with uveitis in the Chinese population.

Mycobacterium kansasii is an opportunistic pathogen that causes both intrapulmonary and extrapulmonary infections. The symptoms of the pulmonary diseases caused by M. kansasii closely resemble Mycobacterium tuberculosis. Rapid and accurate differentiation of M. kansasii from M. tuberculosis, as well as other mycobacteria, is crucial for developing effective therapeutics and disease treatment. In this study, we combined loop-mediated isothermal amplification (LAMP) with lateral flow biosensors (LFB) to detect M. kansasii, by targeting the species-specific sequence of rpoB, a gene which encodes the β subunit of bacterial RNA polymerase. The assay was validated to ensure that it was highly selective by testing M. kansasii, M. tuberculosis, other species of respiratory bacteria, and other nontuberculous mycobacteria. The detection limit of the assay was 1 fg/μL of DNA and 50 CFU of bacilli in sputum. The M. kansasii-LAMP-LFB assay is a fast, cheap, and accurate method for detecting M. kansasii by constant temperature amplification and simple interpretation.

Adverse events (AEs) assessment by clinicians is a standard practice in a clinical setting. However, studies have found clinicians tend to report fewer AEs, especially subjective AEs. We aimed to explore the difference of subjective AEs assessment between clinicians and patients based on PRO-CTCAE, and to discuss the necessity of incorporating patient into the evaluation of AEs.Between April and July 2019, two different questionnaires with the same subjective AEs were given to patients and clinicians in the Day Chemotherapy ward of Breast Center in the Fourth Hospital of HeBei Medical University. Patients completed a Simplified Chinese version of PRO-CTCAE, including six common subjective AEs of chemotherapy: nausea, vomiting, diarrhea, fatigue, pain, and constipation. Clinicians completed the common terminology criteria for adverse events (CTCAE) with the same AEs. General information of enrolled patients and results from the questionnaires were collected and analyzed.384 paired questionnaires were collected. Clinicians reported less subjective AEs than patients, and the general agreement between patients and clinicians was poor. When considering the grade difference, we utilize weighted kappa coefficient to analysis, and agreement between patients and clinicians was poor (k 0.4) regardless of the frequency, the severity and interfering with daily life of AEs, and the most discrepancies were within one point. Patients tended to grade severer than the clinician.The results of this study showed that there were differences between clinicians and patients in subjective adverse events evaluation. Patient reporting of symptoms can be used as a supplementary method to incorporate the current approach to monitor subjective AEs, to improve the timeliness and accuracy of clinical evaluation of subjective AEs.

Vinyl alcohol (VA), for a long time, is thought to be a missing source of formic acid (FA) in the atmospheric models. However, a recent study has shown that FA is just a byproduct in the OH-initiated oxidation of VA, which stimulates investigation on the other sinks of VA in the atmosphere. In this study, the detailed ozonolysis mechanism of VA was investigated theoretically for the first time. The results show that two primary ozonides (

Endoreplication, known as endocycle, is a variant of the cell cycle that differs from mitosis and occurs in specific tissues of different organisms. Endoreplicating cells generally undergo multiple rounds of genome replication without chromosome segregation. Previous studies demonstrated that Drosophila fizzy-related protein (Fzr) and its mammalian homolog Cdh1 function as key regulators of endoreplication entrance by activating the anaphase-promoting complex/cyclosome to initiate the ubiquitination and subsequent degradation of cell cycle factors such as Cyclin B (CycB). However, the molecular mechanism underlying Fzr-mediated endoreplication is not completely understood. In this study, we demonstrated that the transcription factor Myc acts downstream of Fzr during endoreplication in Drosophila salivary gland. Mechanistically, Fzr interacts with chromatin-associated histone H2B to enhance H2B ubiquitination in the Myc promoter and promotes Myc transcription. In addition to negatively regulating CycB transcription, the Fzr-ubiquitinated H2B (H2Bub)-Myc signaling cascade also positively regulates the transcription of the MCM6 gene that is involved in DNA replication by directly binding to specific motifs within their promoters. We further found that the Fzr-H2Bub-Myc signaling cascade regulating endoreplication progression is conserved between insects and mammalian cells. Altogether, our work uncovers a novel transcriptional cascade that is involved in Fzr-mediated endoreplication.

Colorimetric chemosensors have attracted tremendous interest for sensing hazardous substances in an uncomplicated and economical manner. Herein, a series of push-pull dicyanovinyl-substituted oligothiophene derivatives were designed, and the impacts of different end-cappers on their photophysical properties were comprehensively investigated. Interestingly, combined with a zinc porphyrin derivative (Zn-TPP), one dicyanovinyl-substituted oligothiophene derivative (NA-3T-CN) can be further developed into colorimetric and fluorescent sensor array for dual-mode detection of aliphatic amines and hydrazine. The obtained sensors showed satisfactory results between optical response and analyte's concentration both in selective single-sensor type and in enhanced multisensory mode. Based on the fluorescence change of the NA-3T-CN system, the detection limit for N2H4 was calculated to be around 1.22 × 10-5 mol/L in THF. The stained TLC-supported sensor array offers obvious optical changes for down to 0.5 wt % hydrazine solution for naked-eye sensing. An aromatic amine like aniline has no obvious effect on the dicyanovinyl-substituted oligothiophene derivatives. We also found that a zinc porphyrin derivative has an obvious colorimetric response to the presence of hydrazine, ethanolamine, and aniline. Furthermore, smartphone-enabled readout system and data treatment based on RGB changes of the sensor array were performed, and the discrimination capability among hydrazine, aliphatic amines, and aromatic amine was satisfactory. In this regard, related push-pull oligothiophene derivatives not only can be regarded as models for a fundamental understanding of the relationship between molecular structure and photophysical properties but also present potential applications in the field of real-time and visual detection of hazardous chemicals.

X-ray computed tomography has been a useful technology in cancer detection and radiation therapy. However, high radiation dose during CT scans may increase the underlying risk of healthy organs. Usually, sparse-view X-ray projection is an effective method to reduce radiation. In this paper, we propose a constrained nonconvex truncated regularization model for this low-dose CT reconstruction. It preserves sharp edges very well. Although this model is quite complicated to analyze, we establish two useful theoretical results for its minimizers. Motivated by them, an iterative support shrinking algorithm is introduced. To handle more nondifferentiable points of the regularization function except zero point, we use a general proximally linearization technique at them, which is helpful to implement our algorithm. For this algorithm, we prove the convergence of the objective function, and give a lower bound theory of the iterative sequence. Numerical experiments and comparisons demonstrate that our model with the proposed algorithm performs good for low-dose CT reconstruction.

Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) has displayed vital regulatory function in various tumors. However, the biological function of ZEB1-AS1 in cholangiocarcinoma (CCA) remains unclear. In this study, we confirmed that ZEB1-AS1 expression was increased in CCA tissues and cells, respectively. Upregulated ZEB1-AS1 was related to lymph node invasion, advanced TNM stage and poor survival of CCA patients. ZEB1-AS1 exhibited high sensitivity and specificity to be an independent poor prognostic factor of patients with CCA. Functionally, knocking down ZEB1-AS1 attenuated tumor cell stemness, restrained cellular viability in vitro and in vivo, and inhibited CCA cell migration and invasion by reversing epithelial-mesenchymal transition. For the mechanism, androgen receptor (AR) directly promoted ZEB1-AS1 expression, and further ZEB1-AS1 increased oncogene homeobox B8 (HOXB8) by sponging miR-133b. In addition, malignant phenotypes of CCA promoted by ZEB1-AS1 dysregulation were rescued separately through interfering miR-133b and HOXB8, suggesting AR/ZEB1-AS1/miR-133b/HOXB8 exerted crucial functions in tumorigenesis and progression of CCA.

Ginkgo biloba leaf extract (GBE) has been extensively used in the treatment of diseases due to its anti-inflammatory, antioxidant, and immunomodulatory effects. In aquaculture, GBE is widely used as a feed additive, which is important to enhance the immunity of aquatic animals. The current study evaluated the effects of adding GBE to the diet of Penaeus vannamei (P. vannamei) under intensive aquaculture. The GBE0 (control group), GBE1, GBE2, and GBE4 groups were fed a commercial feed supplemented with 0.0, 1.0, 2.0, and 4.0 g/kg GBE for 21 days, respectively. The results showed that dietary GBE could alleviate hepatopancreas tissue damage and improve the survival rate of shrimp, and dietary 2 g/kg GBE could significantly increase the total hemocyte count (THC), the hemocyanin content, the antioxidant gene's expression, and the activity of their encoded enzymes in P. vannamei. Furthermore, transcriptome data revealed that immunity-related genes were upregulated in the GBE2 group compared with the GBE0 group after 21 days of culture. Drug metabolism-cytochrome P450, sphingolipid metabolism, linoleic acid metabolism, glycerolipid metabolism, fat digestion and protein digestion and absorption pathways were significantly enriched, according to KEGG results. Surprisingly, all of the above KEGG-enriched pathways were significantly upregulated. These findings demonstrated that supplementing P. vannamei with 2 g/kg GBE improved its environmental adaptability by improving immunity, lipid metabolism, and detoxification. In this study, a comprehensive evaluation of the effects of dietary GBE on the intensive aquaculture of P. vannamei was conducted to provide a reference for the healthy culture of P. vannamei.

Thymosin alpha1 (Ta1) is widely used to treat patients with coronavirus disease 2019 (COVID-19), however, its effect remains unclear. This systematic review and meta-analysis aimed to evaluate the effect of Ta1 as a COVID-19 therapy.PubMed, EMBASE, the Cochrane library, Web of Science, and the reference lists of relevant articles were searched to identify eligible studies. Assessment of heterogeneity was done using the I-squared (IA total of 9 studies were included, on a total of 5352 (Ta1 = 1152, control = 4200) patient outcomes. Meta-analysis results indicated that Ta1 therapy had no statistically significant effect on mortality [RR 1.03 (0.60, 1.75), p = 0.92, IThe results of this meta-analysis do not support the use of Ta1 in hospitalized adult COVID-19 patients.

Polypropylene fiber-reinforced concrete (PFRC) is a cement-based composite material with short-cut fibers which has been utilized to provide multidimensional reinforcement and enhance toughness of concrete. However, this improvement is closely related to the microstructural morphology of the concrete. A nondestructive technique using X-ray computed tomography (CT) was therefore used to grasp the microscopic texture of PFRC samples. The results showed that the orientation of microcracks, which appear in the interfacial transition zone, are along the surface of the coarse aggregate. The range of distribution of fibers is proportional to fiber volume fraction. The coarse aggregate influence distribution and orientation of polypropylene fibers whose shape are mainly fold line and curve. The dispersion of pores with small volume is uniform, and the distance between the pores with larger volume is short. The proportion of pores with the diameter in the range 0∼199 μm exceeds 70%, of which the sum of volume exceeds a half of total volume with the amount being about 1% of total amount.

Trafficking protein particle (TRAPP) complexes subunit gene AtTrs33 plays an important role in keeping apical meristematic activity and dominance in Arabidopsis. TRAPP complexes, composed of multimeric subunits, are guanine-nucleotide exchange factors for certain Rab GTPases and are believed to be involved in the regulation of membrane trafficking, but the cases in Arabidopsis are largely unknown. Trs33, recently proposed to be a component of TRAPP IV, is non-essential in yeast cells. A single copy of Trs33 gene, AtTrs33, was identified in Arabidopsis. GUS activity assay indicated that AtTrs33 was ubiquitously expressed. Based on a T-DNA insertion line, we found that loss-of-function of AtTrs33 is lethal for apical growth. Knock-down or knock-in of AtTrs33 affects apical meristematic growth and fertility, which indicates that AtTrs33 plays an important role in keeping apical meristematic activity and dominance in Arabidopsis. Analysis of auxin responses and PIN1/2 localization indicate that impaired apical meristematic activity and dominance were caused by altered auxin responses through non-polarized PIN1 localization. The present study reported that AtTrs33 plays an essential role in Arabidopsis cell growth and organization, which is different with its homologue in yeast. These findings provide new insights into the functional divergence of TRAPP subunits.

In this paper, we propose a fast and provably convergent smoothing gradient descent type algorithm with extrapolation for solving a general class of nonsmooth and nonconvex inverse problems arising from image processing. Our algorithm has a localizer selective policy to switch between gradient descent scheme with or without extrapolation to possibly speed up the decreasing of the smoothed objective function and ensure the convergence. Moreover, the algorithm adaptively reduces the smoothing factor to guarantee that any accumulation point of the generated sequence is an (affine-scaled) Clarke stationary point of the original nonsmooth and nonconvex problem. Extensive numerical experiments and comparisons indicate the effectiveness of the proposed algorithm in natural image deblurring, CT and MRI reconstruction.

ROOT HAIR DEFECTIVE3 (RHD3) is a plant member of atlastin GTPases, which belong to an evolutionally conserved family of proteins that mediate the homotypic fusion of the endoplasmic reticulum (ER). An atlastin in mammalian cells has recently been shown to act as an ER-phagy receptor for selective autophagy of the ER (ER-phagy) during nutrient starvation. Although RHD3 has been indicated to play a role in ER stress response, it is not very clear how RHD3 is involved in the process. In this study, we showed that the

BACKGROUND: Periodontitis is a highly prevalent dental disease which is associated with diabetes and is challenging to cure in diabetic patients. However, the mechanism of comorbid diabetes and periodontitis is still unclear. This study aimed to uncover the role of endoplasmic reticulum (ER) stress in high glucose-associated periodontitis. METHODS: Periodontal tissues were obtained from diabetic patients with periodontitis, periodontitis patients without systemic disease, and healthy teeth. The expressions of ER stress-related factors GRP78, ATF6, PERK and XBP1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immumohistochemical staining. Periodontal ligament stem cells (PDLSCs) from three states of periodontal tissues were isolated and cultured as diabetic PDLSCs (dPDLSCs), inflamed PDLSCs (iPDLSCs) and healthy PDLSCs (hPDLSCs), and the cell stemness was assayed. Different concentrations (8, 11, and 25 mmol/L) of D-glucose were used on hPDLSCs to simulate high glucose microenvironment. The changes of osteogenic ability of PDLSCs were observed, and the expressions of ER stress-related factors in different time point (6, 12, 24, and 72 h) were detected. Finally, GRP78 shRNA lentivirus was used to block ER stress on PDLSCs in the 25 mmol/L D-glucose microenvironment, and the osteogenic ability of PDLSCs was observed. RESULTS: The results showed that the expressions of GRP78, ATF6, PERK, and XBP1 were highest in the diabetic periodontitis group and lowest in the healthy periodontal tissue group (P

Neuronal primary cilia are crucial for body weight maintenance. Type III adenylyl cyclase (AC3) is abundantly enriched in neuronal cilia, and mice with global AC3 ablation are obese. However, whether AC3 regulates body weight through its ciliary expression and the mechanism underlying this potential regulation are not clear. In this study, humanized AC3 knock‐in mice that are resistant to high‐fat diet (HFD)‐induced obesity are generated, and increases in the number and length of cilia in the ventromedial hypothalamus (VMH) are shown. It is demonstrated that mice with specifically knocked down ciliary AC3 expression in the VMH show pronounced HFD‐induced obesity. In addition, in vitro and in vivo analyses of the VMH show that ciliary AC3 regulates autophagy by binding an autophagy‐related gene, gamma‐aminobutyric acid A receptor‐associated protein (GABARAP). Mice with GABARAP knockdown in the VMH exhibit exacerbated HFD‐induced obesity. Overall, the findings may reveal a potential mechanism by which ciliary AC3 expression regulates body weight in the mouse VMH., Type III adenylyl cyclase (AC3) is abundantly enriched in neuronal cilia. This paper reports that ciliary AC3 in the ventromedial hypothalamus (VMH) is essential to high‐fat diet (HFD)‐induced obesity. Cell lines and mouse models show that in the VMH, ciliary AC3 regulates autophagy by binding an autophagy‐related gene, gamma‐aminobutyric acid A receptor‐associated protein (GABARAP). Mice with GABARAP knockdown in the VMH exhibit exacerbated HFD‐induced obesity.

Vibrio alginolyticus is a devastating bacterial pathogen of Pacific white shrimp (Litopenaeus vannamei), which often causes acute hepatopancreatic necrosis syndrome (AHPNS) and early mortality syndrome (EMS). Elucidation of molecular mechanisms of L. vannamei in responding to infection is essential for controlling the epidemic. In the present study, transcriptomic profiles of L. vannamei hepatopancreas were explored by injecting with PBS or V. alginolyticus. Hepatopancreas morphology of L. vannamei was also assessed. The result reveals that compared with the hepatopancreas of PBS group, the storage cells (R-cell), secretory cells (B-cell) and star-shaped polygonal structures of the lumen were disappeared and necrotic after challenged by V. alginolyticus at 24 h. Transcriptome data showed that a total of 314 differential expression genes were induced by V. alginolyticus, with 133 and 181 genes up- and down-regulated, respectively. These genes were mainly associated with lysosome pathway, glycerophospholipid metabolism, drug metabolism-other enzymes, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis and PPAR signal pathway. Among these pathways, the lysosome pathway, glycerophospholipid metabolism and PPAR signal pathway were both related with lipid metabolism. Therefore, we detected the lipid accumulation in hepatopancreas by Oil Red O staining, TG and CHOL detection and the relative mRNA expression of several lipid metabolism related genes in the hepatopancreas of shrimp after challenge to V. alginolyticus. The present data reveals that lipids from the L. vannamei are nutrient sources for the V. alginolyticus and define the fate of the infection by modulating lipid homeostasis. These findings may have important implication for understanding the L. vannamei and V. alginolyticus interactions, and provide a substantial dataset for further research and may deliver the basis for preventing the bacterial diseases.

Motivated by various data science applications including de-anonymizing user identities in social networks, we consider the graph alignment problem, where the goal is to identify the vertex/user correspondence between two correlated graphs. Existing work mostly recovers the correspondence by exploiting the user-user connections. However, in many real-world applications, additional information about the users, such as user profiles, might be publicly available. In this paper, we introduce the attributed graph alignment problem, where additional user information, referred to as attributes, is incorporated to assist graph alignment. We establish sufficient and necessary conditions for recovering vertex correspondence exactly, where the conditions match for a wide range of practical regimes. Our results recover existing tight information-theoretic limits for models where only the user-user connections are available, and further span the full spectrum between these models and models where only attribute information is available.

Recent studies have shown that the Total Generalized Variation (TGV) is highly effective in preserving sharp features as well as smooth transition variations for image processing tasks. However, currently there is no existing work that is suitable for applying TGV to 3D data, in particular, triangular meshes. In this article, we develop a novel framework for discretizing second-order TGV on triangular meshes. Further, we propose a TGV-based variational method for the denoising of face normal fields on triangular meshes. The TGV regularizer in our method is composed of a first-order term and a second-order term, which are automatically balanced. The first-order term allows our TGV regularizer to locate and preserve sharp features, while the second-order term allows our regularizer to recognize and recover smoothly curved regions. To solve the optimization problem, we introduce an efficient iterative algorithm based on variable-splitting and augmented Lagrangian method. Extensive results and comparisons on synthetic and real scanning data validate that the proposed method outperforms the state-of-the-art visually and numerically.

Background The Artemisia species are widely distributed around the world, and have found important usage in traditional medicinal practice. This study was designed to investigate the metabolites of Tibetan Artemisia species and understand the metabolic pathways. Methods The metabolites from three Artemisia species in Tibet, were analyzed using LC–MS/MS. The differential metabolites were classified and analyzed by principal component analysis (PCA), partial least squares analysis and hierarchical clustering. KEGG Pathway enrichment analysis was used to identify the key metabolic pathways involved in the differential metabolites of three Artemisia species. Result The metabolites of three Artemisia species were analyzed. Under the positive ion mode in LC–MS/MS, 262 distinct metabolites were differentially detected from Artemisia sieversiana and Artemisia annua, 312 differential metabolites were detected from Artemisia wellbyi and Artemisia sieversiana, 306 differential metabolites were screened from Artemisia wellbyi and Artemisia annua. With the negative ion mode, 106 differential metabolites were identified from Artemisia sieversiana and Artemisia annua, 131 differential metabolites were identified from Artemisia wellbyi and Artemisia sieversiana,133 differential metabolites were differentially detected from Artemisia wellbyi and Artemisia annua. The selected differential metabolites were mainly organic acids and their derivatives, ketones, phenols, alcohols and coumarins. Among these natural compounds, artemisinin, has the highest relative content in Artemisia annua. Conclusions This is the first reported attempt to comparatively determine the types of the metabolites of the three widely distributed Artemisia species in Tibet. The information should help medicinal research and facilitate comprehensive development and utilization of Artemisia species in Tibet.