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Liver-intestine cadherin (CDH17) is a novel member of the cadherin superfamily implicated in gastric cancer progression. To determine the role of CDH17 in the process of gastric cancer invasive growth, in the present study, RNA interference mediated by recombinant lentivirus vectors expressing artificial CDH17 miRNA was applied to induce a long-lasting down-regulation of CDH17 gene expression in BGC823 cells. The expression levels of CDH17, tumor cell motility, migration potential, and pro-liferation were measured by flow cytometry, real-time RT-PCR, Western blot analysis, immunofluorescence staining, wound healing assay, and MTT assay, respectively. Results show that four recombinant plasmid expression vectors encoding pre-miRNA against CDH17, pcDNA-CDH17-miR-SR1, -SR2, -SR3, and -SR4 were constructed correctly and down-regulated the CDH17 mRNA levels by 5.5, 57, 91, and 98%, respectively, in BGC823 cells which had an overexpression of CDH17. We packaged the recombinant lentiviral vector for CDH17 RNA interference with pcDNA-CDH17-miR-SR4 which had the highest interfering efficiency and succeeded in construction of the stable transfectants. Of note, more than 90% knockdown of CDH17 expression in BGC823 cells was obtained by miRNA technique. The CDH17-miRNA-transfected cells showed significant decrease in cell proliferation, cell motility, and migration in comparison with the control cells. Thus, we proposed that CDH17 may be an oncogene up-regulating invasive features of gastric cancer cells and could be a hopeful target for the control of gastric cancer progression. [ABSTRACT FROM AUTHOR]

The ectoparasites of rodents and other small mammals usually involve five categories of arthropods-fleas, sucking lice, gamasid mites, chigger mites, and occasionally, ticks. These ectoparasites are medically important, serving as vectors for diseases such as plague, murine typhus, scrub typhus, forest encephalitis, Lyme disease, and other zoonoses. Field surveys, collection, and specimen preparation of ectoparasites are crucial for studying taxonomy, faunistics, ecology, and epidemiology. They are also essential for vector surveillance. The present protocol summarizes the on-site monitoring and specimen-making of ectoparasites of rodents and other sympatric small mammals. Besides the collection and specimen preparation of small mammal hosts, the protocol describes in detail the collection, fixation, specimen-making, and taxonomic identification of ectoparasites and provides some monitoring indices. The on-site monitoring indices include the host density index and the infestation indices of ectoparasites (prevalence, mean abundance, mean intensity). The methodologies outlined in this protocol provide technical guidance and references for vector monitoring (surveillance) and control. Key features • Collection and specimen preparation of small mammal hosts, including rodents (rats, mice, and voles) and other sympatric small mammals (shrews, tree shrews, and pikas). • Collection, fixation, specimen-making, and taxonomic identification of ectoparasites, including fleas, sucking lice, gamasid mites, chigger mites, and ticks. • On-site monitoring indices-host density index and infestation indices of ectoparasites: prevalence, mean abundance, and mean intensity. Graphical overview Flowchart for collection and specimen-making of ectoparasites and their hosts. A. Process for the collection and specimen preparation of small mammal hosts. B. Collection and fixation of ectoparasites. C. Process for specimen-making for different categories of ectoparasites., Competing Interests: Competing interestsThe authors declare they have no conflict of interest., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Objectives: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are prevalent functional gastrointestinal disorders (FGIDs). In this study we aimed to explore the causal association between physical activity or sedentary behavior and the risk of FD and IBS., Methods: Mendelian randomization (MR) analysis was employed. Candidate genetic instruments for physical activity and sedentary behavior were retrieved from the latest published Genome-Wide Association Study (GWAS), which included up to 703 901 participants. Summary-level GWAS data for FD (8 875 cases and 320 387 controls) and IBS (9 323 cases and 301 931 controls) were obtained from the FinnGen study. The causal effects were mainly estimated by inverse variance weighted (IVW) method. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, leave-one-out analysis, and the funnel plot., Results: No significant association of moderate-to-vigorous intensity physical activity (MVPA), leisure screen time (LST), sedentary behavior at work (SDW), and sedentary commuting (SDC) with the risk of FD was found. However, there was a suggestive correlation between MVPA and the decreased risk of FD (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.39-0.99, P = 0.047). Genetically predicted MVPA decreased the risk of IBS (OR 0.58, 95% CI 0.40-0.84, P = 0.004), while increased LST was positively associated with IBS risk (OR 1.33, 95% CI 1.15-1.53, P < 0.001). No causal effects of SDW or SDC on IBS risk were observed., Conclusion: MVPA and LST are causally linked to the development of IBS, which will facilitate primary prevention of IBS., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Actinomycetes are remarkable natural sources of active natural molecules and enzymes of considerable industrial value. Streptomyces mobaraensis is the first microorganism found to produce transglutaminase with broad industrial applications. Although transglutaminase in S. mobaraensis has been well studied over the past three decades, the genome of S. mobaraensis and its secondary metabolic potential were poorly reported. Here, we presented the complete genome of S. mobaraensis DSM40587 obtained from the German Collection of Microorganisms and Cell Cultures GmbH. It contains a linear chromosome of 7,633,041 bp and a circular plasmid of 23,857 bp. The chromosome with an average GC content of 73.49% was predicted to harbour 6683 protein-coding genes, seven rRNA and 69 tRNA genes. Comparative genomic analysis reveals its meaningful genomic characterisation. A comprehensive bioinformatics investigation identifies 35 putative BGCs (biosynthesis gene clusters) involved in synthesising various secondary metabolites. Of these, 13 clusters showed high similarity (> 55%) to known BGCs coding for polyketides, nonribosomal peptides, hopene, RiPP (Ribosomally synthesized and post-translationally modified peptides), and others. Furthermore, these BGCs with over 65% similarity to the known BGCs were analysed in detail. The complete genome of S. mobaraensis DSM40587 reveals its capacity to yield diverse bioactive natural products and provides additional insights into discovering novel secondary metabolites., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD)., Methods: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022., Results: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05)., Conclusion: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD). Methods: A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P <0.05 was considered statistically significant. Results: A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z =-3.49, P <0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z =-4.11, P <0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z =-5.41, P <0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z =-2.37, P =0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z =-3.58, P <0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z =-2.52, P =0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z =-3.50, P <0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z =-2.55, P =0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z =-2.32, P =0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z =-2.16, P =0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion: The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

Chigger mites are the vector of scrub typhus. This study estimates the infestation status and ecological characteristics of chiggers on the chestnut white-bellied rat Niviventer fulvescens in Southwest China between 2001 and 2019. Chiggers were identified under the microscope, and infestation indices were calculated. The Preston's log-normal model was used to fit the curve of species abundance distribution. A total of 6,557 chiggers were collected in 136 of 342 N. fulvescens rats, showing high overall infestation indices (prevalence=39.8%, mean abundance=19.2, mean intensity=48.2) and high species diversity (S=100, H'=3.0). Leptotrombidium cangjiangense, Neotrombicula japonica, and Ascoschoengastia sifanga were the three dominant chigger species (constituent ratio=42.9%; 2,736/6,384) and exhibited an aggregated distribution among different rat individuals. We identified 100 chigger species, with 3 of them (Leptotrombidium scutellare, Leptotrombidium wenense, and Leptotrombidium deliense) as the main vectors of scrub typhus in China and nine species as potential vectors of this disease. Disease vector occurrence on N. fulvescens may increase the risk of spreading scrub typhus from rats to humans. Chigger infestation on N. fulvescens varied significantly in different environments. The species abundance distribution showed a log-normal distribution pattern. The estimated number of chigger species on N. fulvescens was 126 species.

Objective: This study aimed to establish a nomogram model to predict the mortality risk of patients with dangerous upper gastrointestinal bleeding (DUGIB), and identify high-risk patients who require emergent therapy., Methods: From January 2020 to April 2022, the clinical data of 256 DUGIB patients who received treatments in the intensive care unit (ICU) were retrospectively collected from Renmin Hospital of Wuhan University (n=179) and the Eastern Campus of Renmin Hospital of Wuhan University (n=77). The 179 patients were treated as the training cohort, and 77 patients as the validation cohort. Logistic regression analysis was used to calculate the independent risk factors, and R packages were used to construct the nomogram model. The prediction accuracy and identification ability were evaluated by the receiver operating characteristic (ROC) curve, C index and calibration curve. The nomogram model was also simultaneously externally validated. Decision curve analysis (DCA) was then used to demonstrate the clinical value of the model., Results: Logistic regression analysis showed that hematemesis, urea nitrogen level, emergency endoscopy, AIMS65, Glasgow Blatchford score and Rockall score were all independent risk factors for DUGIB. The ROC curve analysis indicated the area under curve (AUC) of the training cohort was 0.980 (95%CI: 0.962-0.997), while the AUC of the validation cohort was 0.790 (95%CI:0.685-0.895). The calibration curves were tested for Hosmer-Lemeshow goodness of fit for both training and validation cohorts (P=0.778, P=0.516)., Conclusion: The developed nomogram is an effective tool for risk stratification, early identification and intervention for DUGIB patients., (© 2023. Huazhong University of Science and Technology.)

In this study, the mitochondrial genome of Eulaelaps silvestris , which parasitizes Apodemus chevrieri , was sequenced and assembled to fill the gap in understanding the molecular evolution of the genus Eulaelaps . The E. silvestris mitochondrial genome is a double-stranded DNA molecule with a length of 14 882 bp, with a distinct AT preference for base composition and a notably higher AT content than GC content. The arrangement between genes is relatively compact, with a total of 10 gene intergenic regions and 12 gene overlap regions. All protein-coding genes had a typical ATN initiation codon, and only 2 protein-coding genes had an incomplete termination codon T. Out of the 13 protein-coding genes, the 5 most frequently used codons ended in A/U, with only 1 codon ending in G/C had an relative synonymous codon usage value >1. Except for trnS 1 and trnS 2 , which lacked the D arm, all other tRNAs were able to form a typical cloverleaf structure; and there were a total of 38 mismatches in the folding process of tRNA genes. Unlike the gene arrangement order of the arthropod hypothetical ancestor, the E. silvestris mitochondrial genome underwent fewer rearrangements, mainly near tRNA genes and control regions. Both the maximum likelihood tree and the Bayesian tree showed that the family Haemogamasidae is most closely related to the family Dermanyssidae. The results not only provide a theoretical basis for studying the phylogenetic relationships of the genus Eulaelaps , but also provide molecular evidence that the family Haemogamasidae does not belong to the subfamily Laelapidae.

Some mites of the family Haemogamasidae can transmit a variety of zoonotic diseases and have important public health and safety implications. Currently, however, little attention has been paid to molecular data of Haemogamasidae species, limiting our understanding of their evolutionary and phylogenetic relationships. In this study, the complete mitochondrial genome of Eulaelaps huzhuensis was determined for the first time, and its genomic information was analyzed in detail. The mitochondrial genome of E. huzhuensis is 14,872 bp in length with 37 genes and two control regions. The base composition showed a distinct AT preference. Twelve protein-coding genes have a typical ATN as the start codon, and three protein-coding genes have incomplete stop codons. During the folding of tRNA genes, a total of 30 mismatches occurred, and three tRNA genes had an atypical cloverleaf secondary structure. The order of the E. huzhuensis mitochondrial genome arrangement is a new type of rearrangement in Mesostigmata. The phylogenetic analysis confirmed that the family Haemogamasidae is a monophyletic branch and does not belong to a subfamily of the Laelapidae. Our results lay the foundation for subsequent studies on the phylogeny and evolutionary history of the family Haemogamasidae., (© 2023. The Author(s).)

The prevalence of superbugs, represented by methicillin-resistant Staphylococcus aureus (MRSA), has become a serious clinical and public safety concern with rising incidence in hospitals. Polyketides with diverse chemical structures harbor many antimicrobial activities, including those of rifampin and rapamycin against MRSA. Streptomyces sp. QHH-9511 was isolated from a niche habitat in the Qinghai-Tibet Plateau and used to produce antibacterial metabolites. Herein, an integrated approach combining genome mining and metabolic analysis were employed to decipher the chemical origin of the antibacterial components with pigmented properties in strain QHH-9511, a novel Streptomyces species from a lichen symbiont on the Qinghai-Tibet Plateau. Genomic phylogeny assembled at the chromosome level revealed its unique evolutionary state. Further genome mining uncovered 36 candidate gene clusters, most of which were uncharacterized. Meanwhile, based on liquid chromatography coupled to diode array detection mass spectrometry, a series of granaticins, BSMs, chromones, phaeochromycins, and related molecules were discovered by using the Global Natural Product Social molecular networking platform. Subsequently, several pigment compounds were isolated and identified by high-resolution mass spectrometry and/or nuclear magnetic resonance, among which the structure-activity relationships of seven aromatic polyketides showed that the fused lactone ring of the C-2 carboxyl group could increase antibacterial activity. Genetic experiments indicated that all seven aromatic polyketides are a series of metabolic shunts produced by a single type II polyketide synthase (PKS) cluster. Comparative genomic analysis of granaticin producers showed that the granaticin gene cluster is widely distributed. This study provides an efficient method to combine genome mining and metabolic profiling techniques to uncover bioactive metabolites derived from specific habitats, while deepening our understanding of aromatic polyketide biosynthesis. IMPORTANCE Undescribed microorganisms from special habitats are being screened for anti-superbug drug molecules. In a project to screen actinomycetes for anti-MRSA activity, we isolated a Streptomyces strain from Qinghai Lake lichens. The phylogeny based on the genome assembled at the chromosome level revealed this strain's unique evolutionary state. The chemical origins of the antibacterial components with pigment properties in strain QHH-9511 were determined using an integrated approach combining genome mining and metabolic analysis. Further genome mining uncovered 36 secondary metabolite gene clusters, the majority of which were previously unknown. A series of aromatic compounds were discovered using molecular network analysis, separation, and extraction. Genetic experiments revealed that all seven aromatic polyketides are a series of metabolic shunts produced by a single cluster of type II PKSs. This study describes a method for identifying novel Streptomyces from specific habitats by combining genome mining with metabolic profiling techniques.

Laetiporus sulphureus mushroom is a complementary and alternative medicine that has anticancer, antioxidation, and analgesic effects and immunomodulatory activity; it is used as a treatment for cough and rheumatism and is a functional food that can improve physical fitness. Even though L. sulphureus has garnered considerable biotechnological and pharmacological interest due to its excellent cellulose-degrading ability and diverse biological activities, its biosynthetic potential regarding polysaccharides and secondary metabolites has not been thoroughly examined. In this study, we sequenced and assembled the whole genome of a wild L. sulphureus isolate, NWAFU-1, from the Qinling Mountains in China. Comparative genomes analysis revealed genomic differences between subspecies, and phylogenomic analysis revealed evolutionary divergence as well as genome expansion and contraction of individual Polyporaceae family species. Bioinformatics investigation identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary-metabolite biosynthesis, which included multiple terpenoids, nonribosomal peptides, and polyketides. The locations of biosynthetic core genes were mapped and displayed on chromosomes and contigs. Totals of 143 proteins from 126 coding genes were identified and divided into 14 cytochrome P450 families. Furthermore, the biosynthetic network of tetracyclic triterpenoid active components was postulated by genome mining of related genes combined with the molecular network of metabolites. The genome analysis of L. sulphureus in this study improves the understanding of the biosynthesis of active compounds, which will lay a theoretical foundation for subsequent research on active-compound biosynthesis and promote the application of Laetiporus in the field of drug research and functional-food creation. IMPORTANCE L. sulphureus is a parasitic basidiomycete fungus that causes brown rot. The fruiting bodies of L. sulphureus are used as ancient medicines in China and Europe to cure cancer, analgesia, cough, and rheumatism and are considered a functional food that regulates the body and improves health. L. sulphureus was inferred to be a tetrapolar system based on a high-quality genome, which will aid molecular breeding and artificial farming. Screening polysaccharide synthesis candidate genes and comparing carbohydrate-associated genes in brown-rot basidiomycetes help understand their growth. Identifying core genes for secondary-metabolite biosynthesis, gene cluster family analysis, and comparative cluster analysis will guide heterologous-biosynthesis investigations of these genes and help elucidate the biosynthetic pathways for L. sulphureus bioactive natural components. The biosynthesis network of tetracyclic triterpenes was mapped using metabolite profiling and genome scanning. This work explores the biosynthetic capacity of L. sulphureus -derived natural products and lays the foundation for biosynthetic studies of them.

Chigger mites are arthropods and are the sole vectors of scrub typhus, and rodents as well as other small mammals are the most common hosts of chigger mite larvae. Therefore, it is of great medical significance to study the ecology of chigger mites. In this study, a detailed analysis of chigger mites was conducted based on field survey data. A total of 4,941 chigger mites were collected from 86 hosts at 34 survey sites in Ruili, Yunnan Province, China. Among the 4,941 chiggers, five genera in one subfamily were identified; Schoengastiella ligula was the dominant chigger species with the highest infestation index, prevalence (Pm, 42.86%) and mean intensity (MI, 59.09%) (P<0.001). The association coefficient (V) between S. ligula and Gahrliepia radiopunctata was positively correlated (P<0.05), indicating the tendency of chiggers to select and coexist on the same host at the same time. The dominant species Leptotrombidium kunmingense, Ascoschoengastia indica, S. ligula and G. radiopunctata showed aggregation distribution patterns, indicating that the distribution of chiggers among different hosts was not uniform. Low altitudes and low latitudes appeared to be more favorable for the growth and reproduction of chigger mites (P<0.05). It is suggested to collect as many host samples as possible in future field investigations to better understand the dynamics of chigger mite populations and their primary hosts.

Objective: To observe the effect of electroacupuncture (EA) on the expression of Iba-1, complement C1q and CD68 in hippocampus of SAMP8 mice, so as to explore its mechanisms underlying improvement of Alzheimer's disease (AD)., Methods: Twenty-four male SAMP8 mice were randomly and equally divided into model and EA groups, and 12 SAMR1 mice were used as the control group. EA (2 Hz, 1.5-2.0 mA) was applied to "Baihui" (GV20), "Dazhui"(GV14) and "Shen-shu"(BL23) for 20 min once daily in the EA group, each course of treatment was 8 days, with an interval of 2 days between two courses, and the mice were treated for 3 courses. Morris water maze test was performed to assess the learning-memory ability of mice. The positive expression levels of Iba-1 and CD68 proteins in the hippocampus CA1 region were detected by immunohistochemistry. The mRNA and protein expression levels of Iba-1,C1q and CD68 in the hippocampus were detected by real-time PCR and Western blot, separately., Results: Compared with the control group, the average escape latency of Morris water maze test was prolonged in the model group ( P <0.01), duration of swimming in the original platform quadrant and the number of original platform crossing were significantly shorter and decreased respectively ( P <0.01). Compared with the model group, the average escape latency in the EA group was shortened ( P <0.05, P <0.01), the duration of swimming in the original platform quadrant and the number of original platform crossing were significantly prolonged and increased ( P <0.01). The immunoactivity of Iba-1 and CD68 in hippocampal CA1 region, and mRNA and protein expression levels of hippocampal Iba-1,C1q and CD68 were significantly up-regulated in the model group in contrast to the control group ( P <0.01, P <0.05), and obviously down-regulated except the mRNA expression level of hippocampal Iba-1 in the EA group relevant to the model group ( P <0.01, P <0.05)., Conclusion: EA can improve the learning and memory ability of SAMP8 mice, which may be associated with its effect in inhibiting of complement C1q-dependent microglial phagocytosis in the hippocampus.

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with a poor prognosis, and its treatment remains a great challenge. Dihydrotanshinone I (DHTS) has been reported to exert antitumor effect in many cancers. However, the role of DHTS in ESCC remains unclear., Aim: To investigate the antitumor effect of DHTS in ESCC and the underlying mechanisms., Methods: CCK-8 assay and cell cycle analysis were used to detect proliferation and cell cycle in ESCC cells. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining were used to detect apoptosis in ESCC cells. Western blot was used to detect the expression of proteins associated with the mitochondrial pathway. Immunofluorescence was used to detect the expression of phosphorylated STAT3 (pSTAT3) in DHTS-treated ESCC cells. ESCC cells with STAT3 knockdown and overexpression were constructed to verify the role of STAT3 in DHTS induced apoptosis. A xenograft tumor model in nude mice was used to evaluate the antitumor effect of DHTS in vivo ., Results: After treatment with DHTS, the proliferation of ESCC cells was inhibited in a dose- and time-dependent manner. Moreover, DHTS induced cell cycle arrest in the G0/1 phase. Annexin V-PE/7-AAD double staining assay and Hoechst 33258 staining revealed that DHTS induced obvious apoptosis in KYSE30 and Eca109 cells. At the molecular level, DHTS treatment reduced the expression of pSTAT3 and anti-apoptotic proteins, while increasing the expression of pro-apoptotic proteins in ESCC cells. STAT3 knockdown in ESCC cells markedly promoted the activation of the mitochondrial pathway while STAT3 overexpression blocked the activation of the mitochondrial pathway. Additionally, DHTS inhibited tumor cell proliferation and induced apoptosis in a xenograft tumor mouse model., Conclusion: DHTS exerts antitumor effect in ESCC via STAT3-mediated activation of the mitochondrial pathway. DHTS may be a novel therapeutic agent for ESCC., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The typical single-chromosome mitochondrial (mt) genome of animals has fragmented into multiple minichromosomes in the lineage Mitodivisia, which contains most of the parasitic lice of eutherian mammals. These parasitic lice differ from each other even among congeneric species in mt karyotype, i.e. the number of minichromosomes, and the gene content and gene order in each minichromosome, which is in stark contrast to the extremely conserved single-chromosome mt genomes across most animal lineages. How fragmented mt genomes evolved is still poorly understood. We use Polyplax sucking lice as a model to investigate how tRNA gene translocation shapes the dynamic mt karyotypes., Results: We sequenced the full mt genome of the Asian grey shrew louse, Polyplax reclinata. We then inferred the ancestral mt karyotype for Polyplax lice and compared it with the mt karyotypes of the three Polyplax species sequenced to date. We found that tRNA genes were entirely responsible for mt karyotype variation among these three species of Polyplax lice. Furthermore, tRNA gene translocation observed in Polyplax lice was only between different types of minichromosomes and towards the boundaries with the control region. A similar pattern of tRNA gene translocation can also been seen in other sucking lice with fragmented mt genomes., Conclusions: We conclude that inter-minichromosomal tRNA gene translocation orientated towards the boundaries with the control region is a major contributing factor to the highly dynamic mitochondrial genome organization in the parasitic lice of mammals., (© 2021. The Author(s).)

Keratin 18 (KRT18), one of the most abundant keratins in epithelial and endothelial cells, has been reported to be aberrantly expressed in many malignancies and extensively regarded as a biomarker and important regulator in multiple cancers, including gastric cancer (GC). But the molecular regulatory mechanisms of KRT18 in GC patients and cells are largely unknown. In the present study, we analyzed the expression level of KRT18 in 450 stomach adenocarcinoma tissue samples from TCGA database and found a significantly higher expression level in tumor tissues. We then explored the potential functions of KRT18 in AGS cells (human gastric adenocarcinoma cell line) by KRT18 knockdown using siRNA and whole transcriptome RNA-seq analysis. Notably, KRT18 selectively regulates expression of cell proliferation and apoptotic genes. Beyond this, KRT18 affects the alternative splicing of genes enriched in apoptosis, cell cycle, and other cancer-related pathways, which were then validated by reverse transcription-quantitative polymerase chain reaction approach. We validated KRT18-KD promoted apoptosis and inhibited proliferation in AGS cells. We then used RNA-seq data of GC samples to further demonstrate the modulation of KRT18 on alternative splicing regulation. These results together support the conclusion that KRT18 extensively modulates diverse alternative splicing events of genes enriched in proliferation and apoptosis processes. And the dysregulated splicing factors at transcriptional or posttranscriptional level by KRT18 may contribute to the alternative splicing change of many genes, which expands the functional importance of keratins in apoptotic and cell cycle pathways at the posttranscriptional level in GC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Xu, Lin, Chen, Xu, Liu and Dong.)

Effective acquirement of highly pure circulating tumor cells (CTCs) is very important for CTC-related research. However, it is a great challenge since abundant white blood cells (WBCs) are always co-collected with CTCs because of nonspecific bonding or low depletion rate of WBCs in various CTC isolation platforms. Herein, we designed a three-dimensional (3D) conductive scaffold microchip for highly effective capture and electrochemical release of CTCs with high purity. The conductive 3D scaffold was prepared by dense immobilization of gold nanotubes (Au NTs) on porous polydimethylsiloxane and was functionalized with a CTC-specific biomolecule facilitated by a Au-S bond before embedding into a microfluidic device. The spatially distributed 3D macroporous structure compelled cells to change migration from linear to chaotic and the densely covered Au NTs enhanced the topographic interaction between cells and the substrate, thus synergistically improving the CTC capture efficiency. The Au NT-coated 3D scaffold had good electrical conductivity and the Au-S bond was breakable by voltage exposure so that captured CTCs could be specifically released by electrochemical stimulation while nonspecifically bonded WBCs were not responsive to this process, facilitating recovery of CTCs with high purity. The 3D conductive scaffold microchip was successfully applied to obtain highly pure CTCs from cancer patients' blood, benefiting the downstream analysis of CTCs.

The differential diagnosis of benign ascites and malignant ascites is incredibly challenging for clinicians. This research aimed to develop a user-friendly predictive model to discriminate malignant ascites from non-malignant ascites through easy-to-obtain clinical parameters. All patients with new-onset ascites fluid were recruited from January 2014 to December 2018. The medical records of 317 patients with ascites for various reasons in Renmin Hospital of Wuhan University were collected and reviewed retrospectively. Thirty-six parameters were included and selected using univariate logistic regression, multivariate logistic regression, and receiver operating characteristic (ROC) curve analyses to establish a mathematical model for differential diagnosis, and its diagnostic performance was validated in the other groups. Age, cholesterol, hypersensitivity C-reactive protein (hs-CRP) in serum, ascitic fluid adenosine deaminase (AF ADA), ascitic fluid lactate dehydrogenase (AF LDH) involvement in a 5-marker model. With a cut-off level of 0.83, the sensitivity, specificity, accuracy, and area under the ROC of the model for identifying malignant ascites in the development dataset were 84.7%, 88.8%, 87.6%, and 0.874 (95% confidence interval [CI], 0.822-0.926), respectively, and 80.9%, 82.6%, 81.5%, and 0.863 (95% CI,0.817-0.913) in the validation dataset, respectively. The diagnostic model has a similar high diagnostic performance in both the development and validation datasets. The mathematical diagnostic model based on the five markers is a user-friendly method to differentiate malignant ascites from benign ascites with high efficiency., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Chigger mites is a group of arthropods and some of them are vectors of scrub typhus. As a common synanthropic rodent species, the Brown rat (Rattus norvegicus) often harbors lots of ectoparasites including chigger mites. According to some "data mining" strategies, the present study took the advantage of the abundant original data from a long-term field ecological investigation between 2001 and 2015 to make a detailed analysis of chigger mites on R. norvegicus in Yunnan Province, Southwest of China. From 18 of 33 investigated counties, only 1414 chigger mites were collected from 1113 Brown rats with relatively low infestations. The 1414 individual chigger mites were identified as comprising 61 species, 11 genera and 2 subfamilies of the family Trombiculidae with a high species diversity (S=61, H'=3.13). Of 61 mite species, there were four main species, Walchia ewingi, Ascoschoengastia indica, W. koi and A. rattinorvegici, which accounted for 44.41% of the total mites. All the chigger mites were of aggregated distribution among different individuals of R. norvegicus. The Brown rats in the outdoor habitats harbored much more individuals and species of chigger mites with a higher mean abundance (MA=1.46) and mean intensity (MI=12.53) than in the indoor habitats (P<0.05). The overall infestation of the rats was significantly higher in the mountainous landscapes than in the flatland landscapes (P<0.001). The species similarity (C ss ) of the mites on the male and female rats reached 64.44% with sex biased infestations. The male rats harbored more species and individuals of the mites than the female rats. The adult rats harbored more species and individuals of the mites than the juvenile rats. The species abundance distribution of the mites was successfully fitted by Preston's lognormal model with ŝ(R)=15e -[0.31(R-1)]2 (α=0.31, R 2 =0.95). On the basis of fitting the theoretical curve by Preston's model, the total mite species on R. norvegicus was estimated to be 86 species, and 25 rare mite species were missed in the sampling field investigation. The curve tendency of the species-plot relationship indicates that R. norvegicus have a great potential to harbor many species of chigger mites, and more species of the mites would be collected if more rats are sampled.

Abatement of odour emissions in poultry production is important to ensure the quality and safety in the poultry industry as well as for the benefit of the environment. This study was conducted to compare the effects of supplementation with different amounts of dietary soybean oligosaccharides (SBO) and chlortetracycline (CHL) on the major odour-causing compounds in the excreta and on the caecal microbiota in broiler chickens. One-day-old broiler chickens were subjected to a 42-day experiment involving 6 treatments with 6 replicates per treatment (10 birds/cage). The treatments were as follows: negative control (NC; basal diet), positive control (PC; basal diet supplemented with CHL) and basal diet supplemented with 0.5, 2.0, 3.5 and 5.0 g/kg SBO (0.5SBO, 2.0SBO, 3.5SBO and 5.0SBO, respectively). Fresh excreta were sampled for the analysis of odour compounds by HPLC. Caecum content was collected for the caecal microbiota analysis through 16S rRNA sequencing. Results showed that on day 42, the excreta indole concentration in the broilers fed with 2.0SBO, 3.5SBO and 5.0SBO and PC was significantly decreased (P < 0.01) compared with that in the NC-fed broilers. The excreta skatole concentration (P < 0.001) and pH (P < 0.05) were also decreased by SBO and CHL, and they were lowest in birds fed with 3.5SBO. The formate concentrations in birds fed with 3.5SBO and 5.0SBO were higher than those in birds fed with the other diets (P < 0.001). Similarly, acetate concentration (P = 0.003) was increased in birds fed with 3.5SBO. Deep sequencing of 16S rRNA revealed that the composition of the caecal microbial digesta was slightly or significantly changed by the SBO or by the CHL supplementation, respectively. The SBO supplementation decreased the abundance of Bacteroides, Bilophilaand Escherichia, which were associated with the skatole and indole concentrations in the excreta. By contrast, the CHL supplementation demonstrated a strong tendency to enrich Ruminococcus and to reduce the abundance of Rikenella. These results indicated that supplementation with dietary SBO is beneficial in attenuating the concentration of odour-causing compounds and that it modulates the composition of caecal microbiota in broiler chickens., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: This study is designed to investigate the efficacy and safety of direct-acting oral anticoagulants (DOACs) for the treatment of chronic portal vein thrombosis (PVT) in liver cirrhosis patients., Materials and Methods: In a prospective cohort study, patients were divided into DOACs group (oral rivaroxaban tablets or dabigatran etexilate capsules) and control group (no anticoagulant treatment). Based on propensity score matching method, 40 patients with cirrhosis and chronic PVT in each of the groups were recruited for this study. CT portal venography was used to monitor the portal vein area. Color Doppler ultrasound was used to monitor the portal vein flow rate. Biochemical testing and thromboelastography (TEG) were also used for monitoring the status of PVT., Results: After 3 months of DOACs treatment, the complete/partial recanalization rate of DOACs was 12.8% (5/39). After 6 months of DOACs treatment, the PVT complete/partial recanalization rate of DOACs was 28.2% (11/39). The recanalization rate and portal vein flow velocity improvement were higher than those in the control group (P < 0.05). Patients' total bilirubin level and Child-Pugh scores were improved in the DOACs group. The TEG coagulation index was lower in the DOACs group than in the control group (P < 0.05). There was no statistically significant difference between the DOACs group and control group in the cases of bleeding (P > 0.05)., Conclusion: DOACs are effective and safe for chronic PVT in patients with liver cirrhosis. The TEG can predict the risk of bleeding in patients with chronic PVT in cirrhosis, which is more sensitive than conventional coagulation function test.

To examine how host plant genotype, endophytic fungal species, and their interaction may affect growth and key chemical content and composition in an important orchid species, we assessed four Dendrobium catenatum cultivars co-cultured with three fungi previously isolated from D. catenatum. Fungal endophytes (Tulasnella sp., Leptosphaeria microscopica, and Guignardia sp.) specifically affected the growth and chemical composition of the four cultivars. Fungal infection significantly increased certain growth traits, especially mid-stem thickness, stem biomass, stem polysaccharide and ethanol-soluble extractive content, and leaf flavonoid and phenol content. Presence or abundance of some key chemical components was also altered by fungal treatment. These increases and alterations were highly dependent on the host genotype. The findings of this study contribute to our understanding of Dendrobium and endophytic fungi interactions, and provide vital information for improving the development and use of endophytic fungi in D. catenatum breeding., (Copyright © 2020 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD), a neurodegenerative disorder characterized by amyloid deposits and neurofibrillary degeneration, is the most common type of dementia and has no incurable therapies at the moment. Electroacupuncture (EA) therapy has been widely used in clinical treatment of AD, and has attained approving effects. This article reviews the development of researches on the mechanisms of EA underlying improving AD by diminishing β amyloid protein （Aβ） neurotoxicity, from 1) up-regulating hippocampal cellular autophagy, 2) improving cerebral energy metabolism by activating oxidation stress-related factors peroxisome proliferator-activated receptor γ coactivator 1 alpha and sirtuin 1 in the hippocampus and frontal cerebral cortex, 3) relieving inflammatory reaction by lowering expression of tumor necrosis factor-alpha and high-mobility group box 1 and increasing expression of Interleukin 10, and 4) promoting degradation of Aβ 1-42 by down-regulating expression of insulin degeneration enzyme, lipoprotein, transthyretin, apolipoprotein and α2 mcroglobulin. Meanwhile, a comprehensive clinical therapy of AD is proposed.

High efficient detection of effusion tumor cells (ETCs) has great clinical significance to identify malignant from benign effusions, but few strategies are designed to enrich and identify tumor cells from effusions. Herein, we developed a three-dimensional scaffold microchip (3D scaffold chip) which could efficiently isolate individual ETC and ETC cluster (ETC/cluster) from pleural effusions and ascites by molecular recognition and physical obstruction. The 3D scaffold chip could enrich ETCs with 94.7% capture efficiency from 2 mL effusions in 20 min and was successfully applied to analysis of pleural effusions or ascites from 152 patients. The results showed that patients with malignant effusions possessed a much higher number of ETC/cluster than that of patients with benign effusions and receiver operating characteristic (ROC) analysis revealed that ETC/cluster count can be used as a complementary biomarker for diagnosis of malignant effusions. Finally, univariate and multivariate logistic regression analyses were adopted to find effusion variables with statistical difference in diagnosis of malignant effusions, and three variables (ETC/cluster count and effusion carcinoembryonic antigen) were selected to establish a three-marker predictive model for differentiating malignant and benign effusions in the training set. ROC analysis revealed that the AUC (area under the curve), sensitivity, and specificity of the predictive model were 0.939, 90.4%, and 91.8%, respectively. The three-marker predictive model was successfully applied to the validation set and proved that this model was promising for clinical diagnosis of effusions from patients.

Current strategies for in vitro isolation of circulating tumor cells (CTCs) fail to detect extremely rare CTCs heterogeneously distributed in blood. It is possible to devise methods for in vivo capture of CTCs based on processing almost all of the blood in the human body to improve detection sensitivity, but the complicated manipulation, biosafety concerns, and limited capture efficiency of conventional detection strategies prohibit their implementation in the clinic. Herein, we present a flexible three-dimensional (3-D) CTC-Net probe for intravascular collection of CTCs. The CTC-Net, consisting of a 3-D elastic scaffold with an interconnected, spatially distributed network accommodates a large quantity of immobilized antibodies and provides an enhanced substrate-cell contact frequency, which results in an enhanced capture efficiency and effective detection of heterogeneous CTCs. The as-prepared CTC-Net can be readily compressed and injected into blood vessels and fully unfolded to form a 3-D "fishing-net" structure for capture of the CTCs, and then retracted for imaging and downstream gene analysis of the captured CTCs. Significant advantages for the CTC-Net over currently available in vitro and in vivo procedures are demonstrated for detection of extremely rare CTCs from wild-type rats and successful capture of CTCs and CTC clusters before metastasis in the case of tumor-bearing rats. Our research demonstrates for the first time the use of a 3-D scaffold CTC-Net probe for in vivo capture of CTCs. The method shows exceptional performance for cell capture, which is readily implemented and holds great potential in the clinic for early diagnosis of cancer.

Choroidal neovascularization (CNV) is an acknowledged pathogenic mechanism of various ocular diseases, and in situ cells and mobilized bone marrow-derived cells (BMCs) are thought to participate in this process. We aimed to evaluate the roles of integrin α5 in BMCs and vascular endothelial cells (VECs) in the CNV process mediated by SDF-1/CXCR4 signaling. Adult wild-type mice were engrafted with whole BMCs obtained from GFP transgenic mice and then laser injured to induce CNV. BMCs and RF/6A cells were cultured to discover the mechanism of CNV in vitro. BMCs were mobilized to CNV areas, which expressed elevated SDF-1 and CXCR4. When SDF-1 was intravitreally injected, the number of BMCs was profoundly increased. In the SDF-1-treated group, the levels of integrin α5 expressed on BMCs and VECs were significantly higher than those on the cells in the control group. SDF-1 significantly increased the expression and positive ratio of integrin α5, which was involved in the recruitment and differentiation of BMCs into BMC-derived VECs, and these effects were suppressed by the CXCR4 inhibitor AMD3100. The PI3K/AKT pathway rather than the ERK pathway mediated SDF-1/CXCR4 induction of integrin α5. Integrin α5 suppression efficiently prevented the production of TGF-β and bFGF but not VEGF. Inhibiting the SDF-1/CXCR4-PI3K/AKT-integrin α5 axis reduced CNV severity. Integrin α5 participates in BMC recruitment and differentiation in SDF-1/CXCR4-induced CNV and inhibition of this pathway may be a new approach to inhibit CNV., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Identifying the early-stage colon adenocarcinoma (ECA) patients who have lower risk cancer vs. the higher risk cancer could improve disease prognosis. Our study aimed to explore whether the glandular morphological features determined by computational pathology could identify high risk cancer in ECA via H&E images digitally., Methods: 532 ECA patients retrospectively from 2 independent data centers, as well as 113 from The Cancer Genome Atlas (TCGA), were enrolled in this study. Four tissue microarrays (TMAs) were constructed across ECA hematoxylin and eosin (H&E) stained slides. 797 quantitative glandular morphometric features were extracted and 5 most prognostic features were identified using minimum redundancy maximum relevance to construct an image classifier. The image classifier was evaluated on D2/D3 = 223, D4 = 46, D5 = 113. The expression of Ki67 and serum CEA levels were scored on D3, aiming to explore the correlations between image classifier and immunohistochemistry data and serum CEA levels. The roles of clinicopathological data and ECAHBC were evaluated by univariate and multivariate analyses for prognostic value., Results: The image classifier could predict ECA recurrence (accuracy of 88.1%). ECA histomorphometric-based image classifier (ECAHBC) was an independent prognostic factor for poorer disease-specific survival [DSS, (HR = 9.65, 95% CI 2.15-43.12, P = 0.003)]. Significant correlations were observed between ECAHBC-positive patients and positivity of Ki67 labeling index (Ki67Li) and serum CEA., Conclusion: Glandular orientation and shape could predict the high risk cancer in ECA and contribute to precision oncology. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients.

The role of endogenous serotonin (5-HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real-time recording of biomolecules, the dynamic monitoring of 5-HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich-like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real-time monitoring of distension-evoked 5-HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5-HT overflow, and 5-HT level is closely associated with the physiological or pathological states of the intestine., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To explore the effect of early intervention electroacupuncture (EA) at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) on the learning-memory ability and the expression of phosphorylated Tau protein in the hippocampus of SAMP8 mice, so as to provide reference for the intervening period of EA for Alzheimer's disease (AD)., Methods: A total of 36 3-month old SAMP8 mice were randomly divided into a model group, a 3-month-old EA group and a 9-month-old EA group, 12 mice in each group. Twelve normal SAMR1 mice with the same age were taken as the control group. The mice in the 3-month-old EA group and 9-month-old EA group were treated with EA at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) separately 3 months old and 9 months old (continuous wave, 2 Hz, 1.5-2 mA), 20 min each time, once a day, 8 days as a course of treatment, with an interval of 2 days between courses, totally 3 courses of treatment were given. The mice sample in each group was collected at the age of 10 months after the learning-memory ability tested by Morris water maze. The expression of phosphorylated Tau protein in the hippocampus was detected by immunohistochemistry and Western blot, and the expression of Tau mRNA was detected by real-time PCR., Results: Compared with the control group, in the model group, the escape latency was significantly increased ( P <0.01), the time of stay in the original platform quadrant and the number of crossing the platform quadrant were reduced ( P <0.01), and the expressions of phosphorylated Tau protein and Tau mRNA in hippocampus were increased ( P <0.01). Compared with the model group, in the 3-month-old EA group and 9-month-old EA group, the escape latency was significantly reduced ( P <0.05), the time of stay in the original platform quadrant and the number of crossing the platform quadrant were increased ( P <0.05), and the expressions of phosphorylated Tau protein and Tau mRNA in hippocampus were reduced ( P <0.05). Compared with the 9-month-old EA group, in the 3-month-old EA group, the escape latency was significantly reduced ( P <0.05), the time of stay in the original platform quadrant and the number of crossing the platform quadrant were increased ( P <0.05), and the expressions of phosphorylated Tau protein and Tau mRNA were reduced ( P <0.01)., Conclusion: The early EA intervention could more effectively improve the learning-memory ability and inhibit phosphorylation of Tau protein in the hippocampus of SAMP8 mice.

Objective: To investigate the correlation between serum interleukin-38 (IL-38) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with pulmonary embolism (PE). Methods: The 94 patients with AECOPD admitted to Tianjin Chest Hospital from August 2015 to April 2018 were suspected of PE. They were divided into two groups based on CT pulmonary angiography (CTPA) and color Doppler ultrasound of lower extremity veins: 39 cases in PE group and 55 cases in Non-PE group. The general data and laboratory examination results of these subjects were recorded. Serum IL-38 was measured by double antibody enzyme-linked immunosorbent assays (ELISA). The between-group differences of above parameters were analyzed. Pearson correlation or Spearman rank correlation was used to analyze the association of IL-38 with each variable in AECOPD patients. Binary Logistic regressions were conducted to determine the risk factors of AECOPD with PE. ROC curve was used to assess the value of serum IL-38 in predicting AECOPD with PE. Results: The serum level of IL-38 was lower in PE group than in Non-PE group [46.3 (33.1, 58.1) vs 61.5 (46.6, 72.5) ng/L, P< 0.05]. Correlation analysis showed that serum IL-38 levels were negatively correlated with C reactive protein and fibrinogen in patients with AECOPD ( r= -0.38,-0.29, all P< 0.05). Binary Logistic regressions showed that lower serum IL-38 level was a risk factor of AECOPD with PE ( OR= 0.78, 95 %CI : 0.61-0.94, P< 0.05). The area under the ROC curve was 0.74 (95% CI: 0.63-0.84, P< 0.05). When cutoff value of serum IL-38 was 52.1ng/L, the sensitivity was 70.9% and the specificity was 69.2% respectively. Conclusion: IL-38 could relieve the hypercoagulability by inhibiting inflammation in patients with AECOPD and could act as a predictor of AECOPD with PE.

Background: Identifying intestinal node-negative gastric adenocarcinoma (INGA) patients with high risk of recurrence could help perceive benefit of adjuvant therapy for INGA patients following surgical resection. This study evaluated whether the computer-extracted image features of nuclear shapes, texture, orientation, and tumor architecture on digital images of hematoxylin and eosin stained tissue, could help to predict recurrence in INGA patients., Methods: A tissue microarrays cohort of 160 retrospectively INGA cases were digitally scanned, and randomly selected as training cohort (D1 = 60), validation cohort (D2 = 100 and D3 = 100, D2 and D3 are different tumor TMA spots from the same patient), accompanied with immunohistochemistry data cohort (D3' = 100, a duplicate cohort of D3) and negative controls data cohort (D5 = 100, normal adjacent tissues). After nuclear segmentation by watershed-based method, 189 local nuclear features were captured on each TMA core and the top 5 features were selected by Wilcoxon rank sum test within D1. A morphometric-based image classifier (NGAHIC) was composed across the discriminative features and predicted the recurrence in INGA on D2. The intra-tumor heterogeneity was assessed on D3. Manual nuclear atypia grading was conducted on D1 and D2 by two pathologists. The expression of HER2 and Ki67 were detected by immunohistochemistry on D3 and D3', respectively. The association between manual grading and INGA outcome was analysis., Results: Independent validation results showed the NGAHIC achieved an AUC of 0.76 for recurrence prediction. NGAHIC-positive patients had poorer overall survival (P = 0.017) by univariate survival analysis. Multivariate survival analysis, controlling for T-stage, histology stage, invasion depth, demonstrated NGAHIC-positive was a reproducible prognostic factor for poorer disease-specific survival (HR = 17.24, 95% CI 3.93-75.60, P < 0.001). In contrast, human grading was only prognostic for one reader on D2. Moreover, significant correlations were observed between NGAHIC-positive patients and positivity of HER2 and Ki67 labeling index., Conclusions: The NGAHIC could provide precision oncology, personalized cancer management.

Tumor cells with p53 inactivation frequently exhibit chemotherapy resistance, which poses a long-standing challenge to cancer treatment. Here we unveiled a previously unrecognized role of TET2 in mediating p53-loss induced chemotherapy resistance in colon cancer. Deletion of TET2 in p53-null colon cancer cells enhanced DNA damage and restored chemotherapy sensitivity. By taking a two-pronged approach that combined pharmacological inhibition with genetic depletion, we discovered that p53 destabilized TET2 at the protein level by promoting its autophagic degradation. At the molecular level, we further revealed a physical association between TET2 and p53 that facilitated the nucleoplasmic shuttling of TET2, as well as its recruitment to the autophagosome for degradation. Our study has unveiled a functional interplay between TET2 and p53 during anti-cancer therapy. Our findings establish the rationale for targeting TET2 to overcome chemotherapy resistance associated with mutant p53 tumors.

The experiment was conducted to investigate the in vitro effects of inulin and soya bean oligosaccharide (SBO) on the metabolism of L-tryptophan (L-try) to skatole production, and the intestinal microbiota in broilers. Treatments were as follows: caecal microbiota control (Cc), Cc + inulin, Cc + SBO, rectal microbiota control (Rc), Rc + inulin and Rc + SBO. Microbial suspensions were anaerobically incubated at 38°C for 24 hr. The results showed that concentrations of skatole and acetic acid were significantly lower in caecal microbiota fermentation broth (MFB) than those in rectal MFB (p < .05). Addition of inulin or SBO significantly decreased the concentrations of indole and skatole and rate of L-try degradation (p < .05). Inulin groups had lower indole than SBO groups (p < .05). PCR-DGGE analysis revealed that addition of inulin or SBO decreased the microbiota richness (p < .05), but no significant differences in Shannon index (p > .05). Four distinct bands were detected in inulin and SBO groups, which were related to two of Bacteroides, one of Firmicutes and Bifidobacteria. Six bands were detected only in control groups, which represented uncultured Rikenellaceae, Roseburia, Escherichia/Shigella dysenteriae, Bacteroides uniformis (T), Parabacteroides distasonis and Enterobacter aerogenes. Populations of Lactobacilli, Bifidobacteria and total bacteria in inulin groups were higher than those in control groups (p < .05). For SBO groups, only population of total bacteria increased (p < .05). However, there were no significant differences in Escherichia coli population among treatments (p > .05). These results suggest that reduced concentrations of skatole and indole in the presence of inulin and SBO may be caused by decrease in L-try degradation rate, which were caused by change in microbial ecosystem and pH value. Uncultured B. uniformis (T) and E. aerogenes may be responsible for degradation of L-try to skatole., (© 2017 Blackwell Verlag GmbH.)

Aim: To investigate the antitumor activity of α-hederin in hepatocellular carcinoma (HCC) cells and its underlying mechanisms in vitro and in vivo ., Methods: SMMC-7721, HepG-2 and Huh-7 HCC cells were cultured in vitro and treated with α-hederin (0, 5 μmol/L, 10 μmol/L, 15 μmol/L, 20 μmol/L, 25 μmol/L, 30 μmol/L, 35 μmol/L, 40 μmol/L, 45 μmol/L, 50 μmol/L, 55 μmol/L, or 60 μmol/L) for 12 h, 24 h, or 36 h, and cell viability was then detected by the Cell Counting Kit-8. SMMC-7721 cells were treated with 0, 5 μmol/L, 10 μmol/L, or 20 μmol/L α-hederin for 24 h with or without DL-buthionine- S , R -sulfoximine (2 mmol/L) or N -acetylcysteine (5 mmol/L) pretreatment for 2 h, and additional assays were subsequently performed. Apoptosis was observed after Hoechst staining. Glutathione (GSH) and adenosine triphosphate (ATP) levels were measured using GSH and ATP Assay Kits. Intracellular reactive oxygen species (ROS) levels were determined by measuring the oxidative conversion of 2',7'-dichlorofluorescin diacetate. Disruption of the mitochondrial membrane potential was evaluated using JC-1 staining. The protein levels of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, apoptosis-inducing factor and cytochrome C were detected by western blotting. The antitumor efficacy of α-hederin in vivo was evaluated in a xenograft tumor model., Results: The α-hederin treatment induced apoptosis of HCC cells. The apoptosis rates in the control, low-dose α-hederin (5 μmol/L), mid-dose α-hederin (10 μmol/L) and high-dose α-hederin (20 μmol/L) groups were 0.90% ± 0.26%, 12% ± 2.0%, 21% ± 2.1% and 37% ± 3.8%, respectively ( P < 0.05). The α-hederin treatment reduced intracellular GSH and ATP levels, induced ROS, disrupted the mitochondrial membrane potential, increased the protein levels of Bax, cleaved caspase-3, cleaved caspase-9, apoptosis-inducing factor and cytochrome C, and decreased Bcl-2 expression. The α-hederin treatment also inhibited xenograft tumor growth in vivo ., Conclusion: The α-hederin saponin induces apoptosis of HCC cells via the mitochondrial pathway mediated by increased intracellular ROS and may be an effective treatment for human HCC., Competing Interests: Conflict-of-interest statement: The authors declare that there are no conflicts-of-interest regarding the publication of this paper.

Current prognostic signatures need to be improved in identifying high-risk patients of gastric cancer (GC). Thus, we aimed to develop a reliable prognostic signature that could assess the prognosis risk in GC patients. Two microarray datasets of GSE662254 (n = 300, training set) and GSE15459 (n = 192, test set) were included into analysis. Prognostic genes were screened to construct prognosis-related gene pairs (PRGPs). Then, a penalized Cox proportional hazards regression model identified seven PRGPs, which constructed a prognostic signature and divided patients into high- and low-risk groups according to the signature score. High-risk patients showed a poorer prognosis than low-risk patients in both the training set (hazard ratios [HR]: 6.086, 95% confidence interval [CI]: 4.341-8.533) and test set (1.773 [1.107-2.840]). The PRGPs signature also achieved a higher predictive accuracy (concordance index [C-index]: 0.872, 95% CI: 0.846-0.897) than two existing molecular signatures (0.706 [0.667-0.744] for a 11-gene signature and 0.684 [0.642-0.726] for a 24-lncRNA signature) and TNM stage (0.764 [0.715-0.814]). In conclusion, our study identified a novel gene pairs signature in the prognosis of GC., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

From a previous field investigation in Yunnan, southwest China between 2001 and 2015, we selected two types of landscapes to make a retrospectively comparative study on the distribution of small mammals and their ectoparasitic chigger mites. One landscape is "mountainous uncultivated land (MUL)" with higher biodiversity, which is located in a famous "World Nature Heritage Site", the Three-Parallel-Rivers Region in the northwest of Yunnan. The other is "cultivated flatland landscape (CFL)" with lower biodiversity, which is located in the south of Yunnan. The landscapes with different biodiversity apparently influenced the distribution of small mammals and their ectoparasitic chigger mites. Much more species of small mammals and mites were found in MUL than in CFL. A total of 3,177 small mammals captured from MUL were identified as 55 species, 30 genera and 10 families in five orders. From these small mammal hosts, 5,882 chigger mites were collected and identified as 127 species, 15 genera and 3 subfamilies in two families. A total of 1,112 small mammals captured from CFL were identified as 19 species, 12 genera and 5 families in three orders. From these hosts, 17,742 chiggers were collected and identified as 86 species, 12 genera and 3 subfamilies in two families. Both the species diversity (S = 55) and community diversity (H = 2.673) of small mammals in MUL were much higher than those in CFL (S = 19; H = 0.926). There were also higher values of β diversity in MUL than in CFL. Different main reservoir rodent hosts of zoonoses (including tsutsugamushi disease) were found in two types of landscapes. Rattus tanezumi (one main reservoir host) was most abundant in CFL, which accounted for 80.22% of all the small mammals. Another two main reservoir hosts, Eothenomys miletus and Apodemus chevrieri were the dominant species in MUL, but they were not as abundant as R. tanezumi in CFL. Different vector species of chigger mites also existed in MUL and CFL. Leptotrombidium deliense (a main and powerful vector of tsutsugamushi disease in China) and Ascoschoengastia indica (a potential vector of tsutsugamushi disease) were the dominant species of chigger mites in CFL (Cr = 25.81% for A. indica; Cr = 23.47% for L. deliense). Leptotrombidium scutellare (also a main vector of tsutsugamushi disease in China) was the dominant chigger species in MUL (Cr = 26.09%). Higher infestation of vector mites on small mammals was found in the simple landscape with lower biodiversity (CFL) than in the complex landscape with higher biodiversity (MUL). The overall prevalence (P), mean abundance (MA) and mean intensity (MI) of chigger mites on small mammals were much higher in CFL than in MUL. The main vector mite species on their main rodent hosts also showed a higher P, MA and MI in CFL than in MUL.

There are several main vectors of scrub typhus in China, and Leptotrombidium rubellum Wang et Liao, 1984 is one of them, which was previously considered to be restricted to the coastal regions of Changle to Xiamen, Fujian province of east China. Ecological investigation of chigger mites in recent years demonstrated the presence of L. rubellum also in Yunnan province. Chigger mites were collected from 34 counties, in which 127,460 larval mites were collected from 14,381 small mammal hosts. A total of 277 species belonging to 26 genera and three subfamilies were identified. A total of 705/127,460 (0.55%) L. rubellum were collected from eight counties. Leptotrombidium rubellum was collected mainly at low elevations in southern Yunnan. A total of 663/705 (94.04%) of L. rubellum were collected from Rattus flavipectus (Milne-Edwards, 1871) found in outdoor habitats with relatively high infestation prevalence and mean intensity. Although it was collected from several hosts, the primary host was Rattus tanezumi. This represents a new distribution record of L. rubellum for Yunnan province., (Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.)

The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn's colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Aim: To elucidate the impact of Schistosoma ( S .) japonicum infection on inflammatory bowel disease by studying the effects of exposure to S. japonicum cercariae on dextran sodium sulfate (DSS)-induced colitis., Methods: Infection was percutaneously established with 20 ± 2 cercariae of S. japonicum , and colitis was induced by administration of 3% DSS at 4 wk post infection. Weight change, colon length, histological score (HS) and disease activity index (DAI) were evaluated. Inflammatory cytokines, such as IL-2, IL-10 and IFN-γ, were tested by a cytometric bead array and real-time quantitative polymerase chain reaction (RT-PCR). Protein and mRNA levels of IRE1α, IRE1β, GRP78, CHOP, P65, P-P65, P-IκBα and IκBα in colon tissues were examined by Western blot and RT-PCR, respectively. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling positive cells, cleaved-caspase 3 expression and Bcl2/Bax were investigated to assess the apoptosis in colon tissues., Results: Mice infected with S. japonicum cercariae were less susceptible to DSS. Mice infected with S. japonicum cercariae and treated with DSS showed decreased weight loss, longer colon, and lower HS and DAI compared with mice treated with DSS alone. A substantial decrease in Th1/Th2/Th17 response was observed after infection with S. japonicum . Endoplasmic reticulum (ER) stress and the nuclear factor-kappa B (NF-κB) pathway were reduced in mice infected with S. japonicum cercariae and treated with DSS, along with ameliorated celluar apoptosis, in contrast to mice treated with DSS alone., Conclusion: Exposure to S. japonicum attenuated inflammatory response in a DSS-induced colitis model. In addition to the Th1/Th2/Th17 pathway and NF-κB pathway, ER stress was shown to be involved in mitigating inflammation and decreasing apoptosis. Thus, ER stress is a new aspect in elucidating the relationship between helminth infection and inflammatory bowel disease (IBD), which may offer new therapeutic methods for IBD., Competing Interests: Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.

Tumor metastasis is attributed to circulating tumor cells (CTC) or CTC clusters. Many strategies have hitherto been designed to isolate CTCs, but there are few methods that can capture and gently release CTC clusters as efficient as single CTCs. Herein, we developed a three-dimensional (3D) scaffold chip with thermosensitive coating for high-efficiency capture and release of individual and cluster CTCs. The 3D scaffold chip successfully combines the specific recognition and physically obstructed effect of 3D scaffold structure to significantly improve cell clusters capture efficiency. Thermosensitive gelatin hydrogel uniformly coated on the scaffold dissolves at 37 °C quickly, and the captured cells are gently released from chip with high viability. Notably, this platform was applied to isolate CTCs from cancer patients' blood samples. This allows global DNA and RNA methylation analysis of collected single CTC and CTC clusters, indicating the great potential of this platform in cancer diagnosis and downstream analysis at the molecular level.

Objective: Recent studies have reported conflicting results on the correlation between metformin use and outcomes in patients with colorectal cancer (CRC). A meta-analysis was performed to evaluate the efficacy of metformin therapy on the prognosis of CRC patients with type 2 diabetes mellitus (T2DM)., Methods: We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and the Web of Science for related articles up to August 2016. Two investigators independently identified and extracted information. Pooled risk estimates [hazard ratios ( HR s)] and 95% confidence intervals ( CI s) were calculated using fixed-effects models. The risk of publication bias was assessed by examining funnel plot asymmetry as well as Egger's test and Begg's test., Results: Of 81 articles identified, 8 retrospective cohort studies, representing 6098 cases of CRC patients with T2DM who used metformin and 4954 cases of CRC patients with T2DM who did not use metformin, were included in this meta-analysis. There was no significant heterogeneity and quality difference between studies. Metformin users had significantly improved overall survival (OS) ( HR  = 0.82, 95% CI : 0.77-0.87, P  = 0.000). However, Metformin use cannot affect CRC-specific survival ( HR  = 0.84, 95% CI : 0.69-1.02, P  = 0.079) compared to non-users., Conclusion: This meta-analysis suggests that metformin use may improve survival among CRC patients with T2DM. However, prospective controlled studies are still needed to rigorously evaluate the efficacy of metformin as an anti-tumor agent.

Chigger mites are a large group of arthropods and the larvae of mites are ectoparasites. Some species of ectoparasitic mites (larvae) can be the transmitting vectors of tsutsugamushi disease (scrub typhus). Yunnan Province is located in the southwest of China with complicated topographic landform and high biodiversity, where there are five zoogeographical subregions. Rodents and some other small mammals were trapped and examined for ectoparasitic chigger mites in 29 investigation sites in Yunnan during 2001-2013. From 13,760 individuals and 76 species of small mammal hosts, we collected 274 species of mites, which were identified as comprising 26 genera in two families. The species diversity of chigger mites (274 species) in the present study were not only much higher than that from other provinces of China but also largely exceeded that recorded from other regions and countries in the world. Of the five zoogeographical subregions, both the species diversity and Shannon-Weiner's diversity of mites were the highest in subregion II (southern subregion of Hengduan Mountains) with middle altitudes and middle latitude. Both the species diversity of mites and Shannon-Wiener diversity index showed a parabolic tendency from the low altitude (<500 m) to the high altitude (>3500 m) along the vertical gradients with the peak occurring in the middle-altitude regions (2000-2500 m). Of four dominant hosts, the species richness of mites was highest on Eothenomys miletus (S = 165) and Shannon-Wiener diversity index was highest on Rattus norvegicus (H = 3.13). Along latitude gradients, species richness of chigger mites increased first and then decreased, peaking at 25° to 26° N with 193 mite species. The geographical location, complex topography, and landscape with diverse small mammal hosts in Yunnan Province have contributed to the extremely high species diversity of mites in the province. The large sampling size of small mammal hosts in a wide geographical scope within a long time span also made it possible to have collected so many species of chigger mites.

Sclerosing angiomatoid nodular transformation (SANT) is a rare benign splenic vascular lesion. Since it was first defined in 2004, a total of 132 cases of SANT have been reported in ~50 studies in the English literature. However, it remains difficult to form a definitive pre-operative differential diagnosis of SANT compared with other splenic tumors or malignant lesions. The present study reports a pathologically proven case of SANT in a 29-year-old man who initially presented with left upper quadrant and back discomfort. The study also provides a review of the current knowledge on the condition, including the clinical profile, imaging features, cytological features, differential diagnosis and treatment of SANT. The most important distinguishing features of SANT are its typical vascular character and lack of other features that are typical of a granuloma. A splenectomy is required and the diagnosis is based on pathological analysis.

Effective isolation of circulating tumor cells (CTCs) has great significance for cancer research but is highly challenged. Here, we developed a microchip embedded with a three-dimensional (3D) PDMS scaffold by a quadratic-sacrificing template method for high-efficiency capture of CTCs. The microchip was gifted with a 3D interconnected macroporous structure, strong toughness, and excellent flexibility and transparency, enabling fast isolation and convenient observation of CTCs. Especially, 3D scaffold chip perfectly integrates the two main strategies currently used for enhancement of cell capture efficiency. Spatially distributed 3D scaffold compels cells undergoing chaotic or vortex migration in the channel, and the spatially distributed nanorough skeleton offers ample binding sites, which synergistically and significantly improve CTCs capture efficiency. Our results showed that 1-118 CTCs/mL were identified from 14 cancer patients' blood and 5 out of these cancer patients showed 1-14 CTC clusters/mL. This work demonstrates for the first time the development of microchip with transparent interconnected 3D scaffold for isolation of CTCs and CTC clusters, which may promote in-depth analysis of CTCs.