Ezrin's role in gastric cancer progression: Implications for immune microenvironment modulation and therapeutic potential.

At present, surgical resection is the most effective method for the treatment of gastric cancer. However, death caused by inoperable metastasis is still very common, despite research in this area. The mechanisms underlying the occurrence, development, and metastasis of gastric cancer are not fully understood. Ezrin, a plasma membrane-microfilament junction participates in a variety of cellular activities and is closely related to tumorigenesis and development. Few studies have explored the relationship between the tumor immune microenvironment and ezrin expression in gastric cancer. In this study, we used proteomic techniques to analyze the differentially expressed proteins between the gastric cancer cell lines MKN-45 and HGC-27 and screened ezrin as the target protein. We collected patient information from The TCGA and GEO databases, and the results showed that ezrin was positively correlated with adverse clinical features. We further explored the relationship between ezrin expression levels, immune microenvironment, and genomic changes. We found that ezrin was involved in immune regulation and genomic instability in gastric cancer. When the expression of ezrin is high, immune cell infiltration also increases. We also predicted that ezrin is closely related to immunotherapy and chemosensitivity. Single-cell transcriptome data showed that the ezrin gene was mainly expressed in B cells and epithelial cells, and the expression of EZR in these epithelial cells was positively correlated with the epithelial-mesenchymal transformation pathway and Pi3k-AKT pathway score. Through functional verification of the stably transfected cell line constructed by lentivirus, the results of the liver metastasis model in nude mice suggested that high expression of ezrin leads to the formation of more metastatic foci. In summary, our results clarify the prognostic, immunological, and therapeutic value of ezrin in gastric cancer and provide a theoretical basis for more accurate treatment.

AMP-activated protein kinase is necessary for Treg cell functional adaptation to microenvironmental stress.

CD4+FOXP3+ regulatory T (Treg) cells maintain self-tolerance, suppress the immune response to cancer, and protect against tissue injury in the lung and other organs. Treg cells require mitochondrial metabolism to exert their function, but how Treg cells adapt their metabolic programs to sustain and optimize their function during an immune response occurring in a metabolically stressed microenvironment remains unclear. Here, we tested whether Treg cells require the energy homeostasis-maintaining enzyme AMP-activated protein kinase (AMPK) to adapt to metabolically aberrant microenvironments caused by malignancy or lung injury, finding that AMPK is dispensable for Treg cell immune-homeostatic function but is necessary for full Treg cell function in B16 melanoma tumors and during acute lung injury caused by influenza virus pneumonia. AMPK-deficient Treg cells had lower mitochondrial mass and exhibited an impaired ability to maximize aerobic respiration. Mechanistically, we found that AMPK regulates DNA methyltransferase 1 to promote transcriptional programs associated with mitochondrial function in the tumor microenvironment. In the lung during viral pneumonia, we found that AMPK sustains metabolic homeostasis and mitochondrial activity. Induction of DNA hypomethylation was sufficient to rescue mitochondrial mass in AMPK-deficient Treg cells, linking DNA methylation with AMPK function and mitochondrial metabolism. These results define AMPK as a determinant of Treg cell adaptation to metabolic stress and offer potential therapeutic targets in cancer and tissue injury.

ELOA3: A primate-specific RNA polymerase II elongation factor encoded by a tandem repeat gene cluster.

The biological role of the repetitive DNA sequences in the human genome remains an outstanding question. Recent long-read human genome assemblies have allowed us to identify a function for one of these repetitive regions. We have uncovered a tandem array of conserved primate-specific retrogenes encoding the protein Elongin A3 (ELOA3), a homolog of the RNA polymerase II (RNAPII) elongation factor Elongin A (ELOA). Our genomic analysis shows that the ELOA3 gene cluster is conserved among primates and the number of ELOA3 gene repeats is variable in the human population and across primate species. Moreover, the gene cluster has undergone concerted evolution and homogenization within primates. Our biochemical studies show that ELOA3 functions as a promoter-associated RNAPII pause-release elongation factor with distinct biochemical and functional features from its ancestral homolog, ELOA. We propose that the ELOA3 gene cluster has evolved to fulfil a transcriptional regulatory function unique to the primate lineage that can be targeted to regulate cellular hyperproliferation.

Occurrence of metabolic syndrome in untreated bipolar disorders: a cross-sectional study.

OBJECTIVE: This cross-sectional study aimed to observe the occurrence of metabolic syndrome in untreated individuals with bipolar disorders. METHODS: A total of 125 untreated individuals with bipolar disorders were collected as the study group, and 201 cases from the health examination centre of our hospital were selected as the control group. The participants enrolled were assessed for general demographic data, case characteristics, and metabolic indexes including body mass index (BMI), blood pressure, triglyceride, high-density lipoprotein-cholesterol, cholesterol, low-density lipoprotein-cholesterol, and fasting plasma glucose. RESULTS: The incidence of metabolic syndrome in the bipolar disorders group was higher compared to the control group (9.6% VS. 8.5%). After calibrating sex and age data, a significant difference between the two groups was observed (P < 0.05). Diastolic and systolic blood pressure were higher in the bipolar disorders group compared to the control group (P < 0.01). Men with bipolar disorders had a higher risk of developing metabolic syndrome than women (14.5% vs. 5.8%). Bipolar disorders, sex, age, and BMI were identified as independent risk factors for metabolic syndrome. No significant difference was found in terms of metabolic index and incidence of metabolic syndrome between individuals with depressive episodes (n = 37) and manic episodes (n = 75). CONCLUSION: Patients with bipolar disorders were found to have a higher risk of developing metabolic syndrome than healthy individuals. Bipolar disorders, male sex, age, and BMI may contribute to an increased risk of developing metabolic syndrome.

IL15 modification enables CAR T cells to act as a dual targeting agent against tumor cells and myeloid-derived suppressor cells in GBM.

INTRODUCTION: The immunosuppressive tumor microenvironment (TME) is a major barrier to the efficacy of chimeric antigen receptor T cells (CAR-T cells) in glioblastoma (GBM). Transgenic expression of IL15 is one attractive strategy to modulate the TME. However, at present, it is unclear if IL15 could be used to directly target myeloid-derived suppressor cells (MDSCs), a major cellular component of the GBM TME. Here, we explored if MDSC express IL15Rα and the feasibility of exploiting its expression as an immunotherapeutic target. METHODS: RNA-seq, RT-qPCR, and flow cytometry were used to determine IL15Rα expression in paired peripheral and tumor-infiltrating immune cells of GBM patients and two syngeneic murine GBM models. We generated murine T cells expressing IL13Rα2-CARs and secretory IL15 (CAR.IL15s) or IL13Rα2-CARs in which IL15 was fused to the CAR to serve as an IL15Rα-targeting moiety (CAR.IL15f), and characterized their effector function in vitro and in syngeneic IL13Rα2+glioma models. RESULTS: IL15Rα was preferentially expressed in myeloid, B, and dendritic cells in patients' and syngeneic GBMs. In vitro, CAR.IL15s and CAR.IL15f T cells depleted MDSC and decreased their secretion of immunosuppressive molecules with CAR.IL15f T cells being more efficacious. Similarly, CAR.IL15f T cells significantly improved the survival of mice in two GBM models. TME analysis showed that treatment with CAR.IL15f T cells resulted in higher frequencies of CD8+T cells, NK, and B cells, but a decrease in CD11b+cells in tumors compared with therapy with CAR T cells. CONCLUSIONS: We demonstrate that MDSC of the glioma TME express IL15Ra and that these cells can be targeted with secretory IL15 or an IL15Rα-targeting moiety incorporated into the CAR. Thus, IL15-modified CAR T cells act as a dual targeting agent against tumor cells and MDSC in GBM, warranting their future evaluation in early-phase clinical studies.

Diversity and Distribution of Calonectria Species from Plantation and Forest Soils in Fujian Province, China.

To meet the growing demand for wood and pulp products, Eucalyptus plantations have expanded rapidly during the past two decades, becoming an integral part of the southern China landscape. Leaf blight caused by various Calonectria spp., is a serious threat to these plantations. In order to explore the diversity and distribution of Calonectria spp. in Fujian Province soils, samples were collected in Eucalyptus plantations and adjacent plantings of Cunninghamia lanceolata, Phyllostachys heterocycle and Pinus massoniana as well as in natural forests. Three hundred and fifty-three Calonectria isolates were recovered from soil samples and they were identified based on a comparison of multilocus DNA sequence data for the act (actin), cmdA (calmodulin), his3 (histone H3), rpb2 (the second largest subunit of RNA polymerase), tef1 (translation elongation factor 1-alpha) and tub2 (ß-tubulin) gene regions, as well as morphological characteristics. Six known taxa including Calonectria aconidialis, Ca. hongkongensis, Ca. ilicicola, Ca. kyotensis, Ca. pacifica, Ca. pseudoreteaudii and one novel species described here as Ca. minensis sp. nov. were identified. Of these, Ca. aconidialis and Ca. kyotensis were the most prevalent species, and found in eight and seven sites, and four and five forest types, respectively. Calonectria spp. were most abundant in soils from Eucalyptus stands, followed by P. heterocycle and natural forests. Relatively few species were found in the soils associated with Cunninghamia lanceolata and Pinus massoniana. The abundance of known Calonectria spp. suggests that these fungi have been relatively well sampled in Fujian. The results are also consistent with the fact that most Calonectria diseases are found on Angiosperm as opposed to Gymnosperm plants.

Effect of minimally invasive repair of pectus excavatum on postoperative chest flatness, cardiopulmonary function, and bone metabolism indexes in children at different ages.

OBJECTIVE: To observe the effects of minimally invasive surgical repair of pectus excavatum (NUSS) on the degree of chest flatness, cardiopulmonary function, and bone metabolism indexes in children of various age groups. METHODS: In this retrospective study, 62 children with pectus excavatum admitted to our hospital were divided into two groups: group A (3-12 years old) and group B (>12 years old), with 31 cases in each group. All of them were treated with NUSS. The treatment effectiveness, perioperative indexes (operation time, blood loss, ground time, and hospitalization time), degree of chest flatness, cardiopulmonary function, bone metabolism indicators, and complications were compared between the two groups. RESULTS: There was no significant difference between patients in the two groups in terms of operation time, blood loss, ground time, and hospitalization time (all P>0.05). The overall response rate to treatment in group A (93.55%) was higher than that of group B (70.97%; P<0.05). Three months after the operation, the chest flatness as well as serum alkaline phosphatase and its bone isoform levels in both groups were decreased, while left ventricular ejection fraction, cardiac index, stroke volume, FEV1, and peak expiratory flow levels were increased compared to before the operation, and the improvement in the above indicators of group A was better than Group B (all P<0.05). There was no significant difference in the incidence of complications between the two groups (16.13% vs. 9.68%; P>0.05). CONCLUSION: NUSS surgery can achieve satisfactory results in treating children with pectus excavatum at different ages. However, in a certain age range, a younger age indicates a better effect. NUSS procedure effectively improves postoperative flat chest, cardiopulmonary function, and bone metabolism indexes.

Comparison of Hyphal Fragments and Spores to Evaluate the Pathogenicity of the Eucalyptus Leaf and Shoot Pathogen Calonectria pseudoreteaudii.

The genus Calonectria includes many aggressive plant-pathogenic species with a worldwide distribution. Calonectria leaf blight is one of the most prominent diseases of Eucalyptus trees in Southeast Asian and South American plantations. Inoculation trials to evaluate pathogenicity of Calonectria spp. typically use conidial suspensions but this is not possible for species that do not sporulate sufficiently in culture. Calonectria pseudoreteaudii is one of the species that is most aggressive to Eucalyptus in China but most isolates fail to produce conidia in culture, requiring an alternative procedure for artificial inoculation. This study compared inoculations utilizing conidial and hyphal fragment suspensions. Two Eucalyptus genotypes were used, and these were inoculated with different concentrations of hyphal fragments or conidia of three C. pseudoreteaudii isolates. Three days after inoculation, the treated Eucalyptus plants displayed similar disease symptoms, regardless of whether they had been inoculated with conidia or hyphal fragments. This was consistent for all C. pseudoreteaudii isolates and also the different Eucalyptus genotypes. The results demonstrate that hyphal fragment suspensions can be used to provide a reliable indication of C. pseudoreteaudii isolate pathogenicity when conidia are not available for inoculation studies.

Scene-Specialized Multitarget Detector with an SMC-PHD Filter and a YOLO Network.

You only look once (YOLO) is one of the most efficient target detection networks. However, the performance of the YOLO network decreases significantly when the variation between the training data and the real data is large. To automatically customize the YOLO network, we suggest a novel transfer learning algorithm with the sequential Monte Carlo probability hypothesis density (SMC-PHD) filter and Gaussian mixture probability hypothesis density (GM-PHD) filter. The proposed framework can automatically customize the YOLO framework with unlabelled target sequences. The frames of the unlabelled target sequences are automatically labelled. The detection probability and clutter density of the SMC-PHD filter and GM-PHD are applied to retrain the YOLO network for occluded targets and clutter. A novel likelihood density with the confidence probability of the YOLO detector and visual context indications is implemented to choose target samples. A simple resampling strategy is proposed for SMC-PHD YOLO to address the weight degeneracy problem. Experiments with different datasets indicate that the proposed framework achieves positive outcomes relative to state-of-the-art frameworks.

Novel species of Calonectria isolated from soil near Eucalyptus plantations in southern China.

Calonectria species are soil-borne and widely distributed in tropical and subtropical regions around the world. The species in this genus include many important plant pathogens that cause serious diseases to economically important crops and forest trees. Previous research results indicated that the leaf blight and cutting rot caused by Calonectria species caused big losses to the Eucalyptus industry in southern China, and large number of Calonectria species identified in China have been collected from soil in Eucalyptus plantations. In this study, Calonectria samples were isolated from soils close to Eucalyptus plantations in Guangdong Province, southern China. These isolates were identified by DNA sequence analyses based on the calmodulin (cmdA), histone H3 (his3), translation elongation factor 1-alpha (tef1), and ß-tubulin (tub2) gene regions, and combined with morphological characteristics. One novel species of Calonectria was identified and described, named Calonectria xianrensis, which resides in the Prolate Group. Results in this study suggest that more species of Calonectria may be distributed in soils in China.

Phylogeny and Pathogenicity of Celoporthe Species from Plantation Eucalyptus in Southern China.

The family of Cryphonectriaceae (Diaporthales) includes many important tree pathogens, such as those that cause severe cankers on Eucalyptus trees. Recently, stem canker and cracked bark were observed on 8-year-old Eucalyptus grandis × E. urophylla trees in a plantation in southern China. Fruiting structures typical of Cryphonectriaceae fungi were observed on the surface of the diseased tissues. In this study, the isolated fungi were identified based on DNA sequence analyses and morphological characteristics, and their pathogenicity was tested on three Eucalyptus clones. DNA sequence comparisons of the internal transcribed spacer (ITS) regions (including the intervening 5.8S nrRNA gene), two regions of ß-tubulin (BT2/BT1), and partial translation elongation factor1-α (TEF-1α), indicated that these isolates represent Celoporthe syzygii and one previously undescribed species. The undescribed species was also morphologically distinct from the other species of Celoporthe. The new species was described and named C. cerciana sp. nov. The results of this study based on the ITS, BT2/BT1, and TEF-1α sequences indicated that more than one haplotype was isolated from the same Eucalyptus tree. The findings of a previous study, whereby C. eucalypti was isolated from the same plantation as that of this study, revealed the high species diversity of Celoporthe within a single plantation, which is associated with a single Eucalyptus sp. in southern China. The results further suggested that hybridization may occur between C. syzygii and C. eucalypti. In addition to the Eucalyptus trees, C. syzygii was also isolated from native Melastoma candidum in the same Eucalyptus plantation. The inoculation results showed that these fungi isolated from E. grandis × E. urophylla and M. candidum are pathogenic to all three tested E. grandis hybrid clones. Significant differences in tolerance were observed between the tested Eucalyptus clones, suggesting that disease-tolerant Eucalyptus genotypes can be selected for disease management.

Calonectria species isolated from Eucalyptus plantations and nurseries in South China.

Diseases caused by species of Calonectria (Ca.) represent a serious threat to the growth and sustainability of Eucalyptus plantations in China. Symptoms caused by these fungi mainly include leaf blight on trees in plantations and rotting of stems and leaves in nurseries. Extensive surveys have recently been conducted where Calonectria species were collected in Eucalyptus plantations and nurseries in the FuJian, GuangDong, GuangXi, and YunNan Provinces of South China. Additional isolates were baited from soil samples in the Hong Kong Region. The aim of this study was to identify the 115 Calonectria isolates obtained using comparisons of DNA sequence data for the ß-tubulin (tub2), calmodulin (cmdA), histone H3 (his3) and partial translation elongation factor-1α (tef1) gene regions as well as their morphological features. Seven known species were identified, including Calonectria arbusta, Ca. asiatica, Ca. chinensis, Ca. eucalypti, Ca. hongkongensis, Ca. mossambicensis and Ca. pentaseptata. In addition, six novel taxa were collected and are described here as Ca. aciculata, Ca. honghensis, Ca. lantauensis, Ca. pseudoturangicola, Ca. pseudoyunnanensis, and Ca. yunnanensis spp. nov. Overall, the results reflect a high diversity of Calonectria species in China.

Risk analysis and outcomes of bronchopulmonary sequestrations.

BACKGROUND: Researched and discussed the risks and outcomes of bronchopulmonary sequestrations, especially the intralobar type. METHODS: A retrospective review of our experiences with bronchopulmonary sequestrations from January 2012 to April 2015 is reported. The present study researched and discusses the risks and outcomes of bronchopulmonary sequestrations, especially the intralobar type, compared with other types of bronchopulmonary sequestrations in symptoms, surgery, pathology, and excretion. RESULTS: A total of 126 bronchopulmonary sequestrations were diagnosed. All fetal chest cases (18-30 weeks) of solid or high-echo masses were diagnosed antenatally and then confirmed by ultrasound. Enhanced computed tomography was used to confirm the diagnosis. Eighty-three boys and 43 girls were included. The mean age at surgery was 4.2 ± 0.5 months. There were 103 cases of left, 22 cases of right, and 1 case of bilateral sequestration. There were 62 extralobar cases, 51 intralobar cases, 13 cases within the diaphragm, and a rare bilateral case. A preoperative history of recurrent respiratory tract infection was present in 39 cases, including 10 extralobar and 29 intralobar cases. Operations were completed successfully, and diagnoses were confirmed pathologically. Thirty-seven cases were associated with congenital bronchopulmonary malformation changes, of which 4 were extralobar, 31 were intralobar, and 2 were within the diaphragm. CONCLUSIONS: The intralobar type was relatively uncommon among bronchopulmonary sequestrations. However, due to communication with normal lung tissue, infection is common in the intralobar type. Computed tomography examinations are very important immediately after birth. It is necessary to resect the mass in early childhood.

[Dynamics of carbon and nitrogen storage of Cupressus chengiana plantations in the arid valley of Minjiang River, Southwest China].

The carbon and nitrogen storage and distribution patterns of Cupressus chengiana plantation ecosystems with different stand ages in the arid valley of Minjiang River were studied. The results showed that carbon contents in different organs of C. chengiana were relatively stable, while nitrogen contents were closely related to different organs, and soil organic carbon and nitrogen contents increased with the stand age. Carbon and nitrogen storage in vegetation layer, soil layer, and the whole ecosystem of the plantation increased with the stand age. The values of total carbon storage in the 13-, 11-, 8-, 6- and 4-year-old C. chengiana plantation ecosystems were 190.90, 165.91, 144.57, 119.44, and 113.49 t x hm(-2), and the values of total nitrogen storage were 19.09, 17.97, 13.82, 13.42, and 12.26 t x hm(-2), respectively. Most of carbon and nitrogen were stored in the 0-60 cm soil layer in the plantation ecosystems and occupied 92.8% and 98.8%, respectively, and the amounts of carbon and nitrogen stored in the top 0-20 cm soil layer, accounted for 54.4% and 48.9% of those in the 0-60 cm soil layer, respectively. Difference in distribution of carbon and nitrogen storage was observed in the vegetation layer. The percentage of carbon storage in tree layer (3.7%) were higher than that in understory vegetation (3.5%), while the percentage of nitrogen storage in tree layer (0.5%) was lower than that in understory (0.7%). The carbon and nitrogen storage and distribution patterns in the plantations varied obviously with the stand age, and the plantation ecosystems at these age stages could accumulate organic carbon and nitrogen continuously.

Highly aligned dense carbon nanotube sheets induced by multiple stretching and pressing.

The CNT sheet fabricated by the floating catalyst chemical vapor deposition (CVD) method has attracted great attention due to its easy fabrication process and promising mass production at low cost. However, the randomly oriented CNT sheet with a loose stacking density shows relatively poor mechanical properties. In this work, a highly aligned dense CNT sheet was successfully fabricated by a simple process of two-time stretching and pressing of a multilayered CVD-grown CNT sheet. Drastic nanotube rearrangements occurred during stretching and pressing processes. A polymer-like tensile necking behavior was observed during the stretching process, accompanied by inter-tube junction breakage due to long-distance slippage. Simultaneously the CNT sheet was thickened after the stretching process due to the increase of the inter-layer space, which could be effectively eliminated by the following pressing treatment. After two-time stretching and pressing, a highly aligned dense CNT sheet was fabricated with the volume density increasing to 0.98 g cm(-3) (by 109%) and the tensile strength increasing to 598 MPa (by 221%) compared to the as-prepared CNT sheet.