Potential role of POFUT1 as a prognostic predictor in low-grade gliomas: Immune microenvironment insights from a pan-cancer analysis.

The POFUT1 gene, known to be up-regulated in various tumor tissues and associated with tumor biology, has yet to be explored for its potential role in immune response regulation and tumor immune microenvironment. The normalized pan-cancer dataset (TCGA Pan-Cancer) was downloaded from the UCSC database, followed by analysis of POFUT1 expression in various tumors and functional enrichment analysis. The correlation between POFUT1 expression levels and patient prognosis was assessed. GSEA of POFUT1 based on low-grade glioma (LGG) samples and immune infiltration analyses of LGG and glioblastoma (GBM) were conducted. The correlation between POFUT1 expression levels and infiltration levels of 22 immune cells in LGG and GBM was examined, as well as the correlation between immune cell infiltration levels and LGG patient prognosis. Additionally, the relationship between POFUT1 expression levels and characteristic gene expression of identified immune cells was evaluated. Lastly, external dataset validation was performed using the integrated CGGA dataset. Significant differences were observed in POFUT1 expression levels across 20 tumor types. High POFUT1 expression correlated with poor prognosis in GBMLGG, and LGG patients. Enrichment analysis and GSEA of POFUT1 in LGG demonstrated involvement in tumor-related and immune-related pathways. A positive correlation was identified between POFUT1 expression levels and infiltration levels of resting memory CD4+ T cells, as well as M2 macrophages or M2-like TAMs in the LGG immune microenvironment, potentially contributing to poor prognosis. External dataset validation revealed a positive correlation between M2 macrophages or M2-like TAMs and POFUT1 expression levels in LGG, and a negative correlation with LGG patient prognosis. POFUT1's negative impact on LGG prognosis may result from its influence on M2 macrophage and M2-like TAM infiltration levels within the immune microenvironment. This suggests its potential as a prognostic predictor and therapeutic target for LGG.

B cell receptor repertoire analysis in primary Sjogren's syndrome salivary glands identifies repertoire features associated with clinical activity.

BACKGROUND: Primary Sjogren's syndrome (pSS) is a complex autoimmune disease featuring damage to salivary and lacrimal glands, with the possibility of manifestations across multiple organs. Antibody-producing B cells have long been appreciated to play a significant role in pSS pathogenesis, with a number of autoreactive antibody species having been identified to be elevated in pSS patients. While several studies have attempted to characterize the BCR repertoires of peripheral blood B cells in pSS patients, much remains unknown about the repertoire characteristics of gland-infiltrating B cells. METHODS: Through paired scRNAseq and scBCRseq, we profiled the BCR repertoires of both infiltrating and circulating B cells in a small cohort of patients. We further utilize receptor reconstruction analyses to further investigate repertoire characteristics in a wider cohort of pSS patients previously profiled through RNAseq. RESULTS: Via integrated BCR and transcriptome analysis of B cell clones, we generate a trajectory progression pattern for infiltrated memory B cells in pSS. We observe significant differences in BCR repertoires between the peripheral blood and labial gland B cells of pSS patients in terms of relative expansion, isotype usage, and BCR clustering. We further observe significant decreases in IgA2 isotype usage among pSS patient labial and parotid gland B cells these analyses relative to controls as well as a positive correlation between kappa/lambda light chain usage and clinical disease activity. CONCLUSIONS: Through BCR repertoire analysis of pSS patient salivary glands, we identify a number of novel repertoire characteristics that may serve as useful indicators of clinical disease and disease activity. By collecting these BCR repertoires into an accessible database, we hope to also enable comparative analysis of patient repertoires in pSS and potentially other autoimmune disorders.

Influence of elevated temperature on the species and mobility of chromium in ferrous sulfate-amended contaminated soil.

Ferrous sulfate (FeSO4) combined with acid pretreatment is usually employed to remediate contaminated soils containing Cr(VI). However, the long-term efficiency of this stabilization method is important for its sustainability. In this study, a gradient temperature-elevating exposure test was employed to investigate the stability of Cr in FeSO4-remediated soil when exposed to elevated temperatures (40 °C, 120 °C, and 500 °C), possibly caused by hot weather and/or wildfires. The results of chemical extraction and X-ray absorption near edge structure spectroscopy (XANES) showed that the Cr(VI) in contaminated soil was successfully transformed to Cr(III) after stabilization, resulting in the dramatic decrease of water-leachable Cr(VI). The stabilization efficiency was further improved under 40 °C treatment after 30 days. Subsequently, the 120 °C treatment (7 days) had relatively little effect on the Cr speciation and mobility in soils. However, even one day of 500 °C calcination resulted in the deterioration of stabilization efficiency, and the water-leachable Cr(VI) re-increased and became higher than the Chinese environmental standards (total Cr 15 mg/L, Cr(VI) 5 mg/L) for the classification of hazardous solid wastes. XANES results reflected that heating at 500 °C facilitate the formation of Cr2O3, which was mainly caused by thermal decomposition and dehydration of Cr(OH)3 in the soil. Besides, the transformation of Cr species resulted in the enhanced association of Cr with the most stable residual fraction (88.3%-91.6%) in soil. Based on chemical extraction results, it was suggested that the oxidation of Cr(III) to Cr(VI) contributed to the re-increased mobility of Cr(VI) in soil. However, the XANES results showed that almost no significant re-oxidization of Cr(III) to Cr(VI) happened after heating at 500 °C, which was probably caused by XANES linear combination fits (LCF) uncertainties. Moreover, the changes in soil properties, including a rise in pH to a slightly alkaline range and/or the decomposition of organic matter, possibly contributed to the enhanced mobility of Cr(VI) in soil. This study contributes to clarifying the mobility and transformation of Cr in contaminated soils and provides a support for the sustainable management of remediated soils.

Intestinal epithelial Krüppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability.

Maintenance of intestinal barrier function contributes to gastrointestinal homeostasis and therefore cardiovascular diseases. A number of studies show that intestinal permeability is affected by excessive inflammatory responses. Krüppel-like factor (KLF) 4 is one of the critical transcriptional factors, which controls multiple immune responses. In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found that overexpression of epithelial Klf4 in atherosclerotic mice significantly increased intestinal tight junction expression and ameliorated endotoxemia, whereas replenishment of LPS abolished these benefits. Overexpression of Klf4 reversed LPS-induced permeability and downregulation of ZO-1 and Occludin in Caco-2 cells in vitro. HFHC diet stimulated the expression of epithelial microRNA-34a, whereas silence of epithelial Klf4 abolished the benefits of microRNA-34a sponge, a specific miR-34a inhibitor, on intestinal permeability and atherosclerotic development. A clinical cohort of 24 atherosclerotic patients supported colon KLF4/NF-κB/tight junction protein axis mediated intestine/cardiovascular interaction in patients with atherosclerosis. Taken together, intestinal epithelial KLF4 protects against intestinal inflammation and barrier dysfunction, ameliorating atherosclerotic plaque formation.

Beam-shaped femtosecond laser printing of quasi-capsule-shaped holographic terahertz metasurfaces.

Terahertz (THz) metasurfaces have opened up a new avenue for the THz wavefront modulation. However, high-efficient and low-cost fabrication of THz metasurfaces remains a great challenge today. Here, quasi-capsule-shaped polarization-multiplexed holographic THz metasurfaces were printed by a beam-shaped femtosecond laser. The laser beam was spatially modulated by holograms of optimized cylindrical lens loaded on a spatial light modulator (SLM). The size of quasi-capsule apertures can be exquisitely and flexibly controlled by adjusting the focal length in holograms, pulse energy, and pulse number. Based on near-field diffraction and Burch encoding, an array of 100 × 100 basic unit apertures were initially designed, and a polarization-multiplexed THz metasurface was finally printed with a dimension of 8 mm × 8 mm. The function of polarization multiplexing was demonstrated, by which two kinds of images were reconstructed in response to X and Y-polarization THz waves, respectively. The present work highlights a great leap in fabrication method for THz metasurfaces and hopefully stimulates the development of miniaturized and integrated THz systems.

The MQRG score: a novel prognostic tool for adrenocortical carcinoma patients based on mitochondrial quality.

Objectives: Adrenal tumors are common, but adrenocortical carcinomas (ACCs) are a rare and challenging form of cancer to diagnose and manage.This study aimed to explore the critical role of mitochondrial quality in maintaining cellular function and the implications of the abnormal expression of mitochondrial metabolism-related proteins observed in ACC patients. We focused on identifying the connection between mitochondrial quality and the development of ACC at molecular and genomic levels. Methods: We compared mitochondrial quality-related genes (MQRGs) across ACC subtypes using overall survival (OS) and disease-free survival (DFS) as evaluation indicators. Furthermore, a novel MQRG score was developed to predict clinical prognosis and guide immunotherapy responses accurately. Results: The majority of MQRGs were upregulated in the ACC samples, correlating to poor prognosis. The MQRG score was confirmed as an independent prognostic factor for ACC, with the high-risk MQRG score group showing a significantly shorter overall survival period. Conclusions: Multilayer alterations in MQRGs are associated with patient prognosis and immune cell infiltration characteristics. This comprehensive analysis of MQRGs can contribute to a deeper understanding of potential differences in ACC patients' tumor microenvironment. This can influence clinical decision-making and advanced prognosis prediction, thereby offering new insights into personalized treatments in ACC.

Three-dimensional analysis of hard and soft tissue changes in skeletal class II patients with high mandibular plane angle undergoing surgery.

This study aimed to study 3-dimensional (3D) changes of hard and soft tissues of skeletal class II patients after 2-jaw surgery and genioplasty. 32 adult patients diagnosed with mandibular hypoplasia who underwent 2-jaw surgery of maxillary impaction, mandibular advancement and genioplasty were enrolled. Cone-beam computed tomography and 3D stereophotogrammetry was conducted 1 week before and 6 months after surgery. Dolphin imaging software was used to establish a 3D digitizing model and 3D measurement system. Paired t-test was performed to compare the values before and after surgery. Pearson's correlation test assessed the degree of correlations between hard and soft tissue change. The mean impaction of the maxilla was 2.600 ± 3.088 mm at A. The mean advancement of the mandible was 7.806 ± 2.647 mm at B. There was a significant upward and forward movement for most landmarks of the nose and lip, while a significant decrease in nasal tip height (lateral view), upper lip height, and upper and lower vermilion height. The nose's width was significantly increased. For maxillary, Sn, Ac-r, Ac-l, and Ls demonstrated a significant correlation with A and U1 in the anteroposterior axis. However, there were no significant correlations among them in the vertical axis. For mandibular, Li demonstrated a significant correlation with L1 in the anteroposterior axis specifically for the mandible. Notably, correlations between the landmarks of the chin's hard and soft tissues were observed across all axes. The utilization of 3-D analysis facilitated a quantitative comprehension of both hard and soft tissues, thereby furnishing valuable insights for the strategic formulation of orthognathic treatment plans targeting patients with skeletal class II conditions.

PND-Net: Physics-inspired Non-local Dual-domain Network for Metal Artifact Reduction.

Metal artifacts caused by the presence of metallic implants tremendously degrade the quality of reconstructed computed tomography (CT) images and therefore affect the clinical diagnosis or reduce the accuracy of organ delineation and dose calculation in radiotherapy. Although various deep learning methods have been proposed for metal artifact reduction (MAR), most of them aim to restore the corrupted sinogram within the metal trace, which removes beam hardening artifacts but ignores other components of metal artifacts. In this paper, based on the physical property of metal artifacts which is verified via Monte Carlo (MC) simulation, we propose a novel physics-inspired non-local dual-domain network (PND-Net) for MAR in CT imaging. Specifically, we design a novel non-local sinogram decomposition network (NSD-Net) to acquire the weighted artifact component and develop an image restoration network (IR-Net) to reduce the residual and secondary artifacts in the image domain. To facilitate the generalization and robustness of our method on clinical CT images, we employ a trainable fusion network (F-Net) in the artifact synthesis path to achieve unpaired learning. Furthermore, we design an internal consistency loss to ensure the data fidelity of anatomical structures in the image domain and introduce the linear interpolation sinogram as prior knowledge to guide sinogram decomposition. NSD-Net, IR-Net, and F-Net are jointly trained so that they can benefit from one another. Extensive experiments on simulation and clinical data demonstrate that our method outperforms state-of-the-art MAR methods.

Hepatitis B virus-mediated sodium influx contributes to hepatic inflammation via synergism with intrahepatic danger signals.

The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome has been involved in the pathogenesis of various chronic liver diseases. However, its role in hepatitis B virus (HBV)-associated hepatitis remains unknown. Here we demonstrate the synergistic effect of HBV with potential intrahepatic danger signals on NLRP3 inflammasome activation. HBV exposure at the appropriate temporal points enhances potassium efflux-dependent NLRP3 inflammasome activation in macrophages and also increases NLRP3 inflammasome-mediated inflammation in HBV-transgenic mouse model. HBV-mediated synergism with intrahepatic signals represented by ATP molecules on NLRP3 activation was observed via relevance analysis, confocal microscopy, and co-immunoprecipitation, and its effector cytokines exhibit positive associations with hepatic inflammation in patients with severe hepatitis B. Furthermore, the synergism of HBV on NLRP3 inflammasome activation owes to increased sodium influx into macrophages. Our data demonstrate that HBV contributes to hepatic inflammation via sodium influx-dependent synergistic activation of NLRP3 inflammasome, which provides a deeper understanding of immune pathogenesis in HBV-associated hepatitis.

Coordination effect enhanced visualization of latent fingerprint with Eu (TTA)3phen-SiO2 microspheres.

Latent fingerprint (LFP) powders are crucial in the detection of LFPs in forensic science. However, it is often plagued by poor image resolution and low contrast. Herein, enhanced LFP fluorescence (FL) visualizations are achieved by doping Eu(III) coordination compound Eu(TTA)3phen directly into SiO2 microspheres instead of Eu(III) ions. Using the synthesized Eu(TTA)3phen-SiO2 microspheres, the fine characteristic structure of LFP can be seen and recognized under 365 nm irradiation, up to Level 3. However, the Eu3+-SiO2 microspheres were difficult to recognize the Level 2,3 fingerprint structure. The difference between the ridge and furrow gray values of Eu(TTA)3phen-SiO2 microspheres is 2.1 times that of Eu3+-SiO2 microspheres. The coordination effect increased the asymmetry around Eu(III) ions, resulting in the ultrasensitive 5D0→7F2 transition, thus increasing the FL intensity, and the uniform doping of the Eu(III) coordination compound into SiO2 also reduced the surface FL quenching due to shielding from oxygen. Under this dual effect, the LFP performance of Eu(TTA)3phen-SiO2 microspheres has been significantly improved. We believe that this novel and easy LFP visualization method is a promising routine in specific target detection including criminal investigation, customhouse check-in, and drug control.

Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data.

Inflammatory cytokine storms (CS) in COVID-19 patients are associated with elevated levels of 13 specific cytokines, potentially impacting male fertility by causing testicular cell damage and disrupting the immune microenvironment. Some patients present with scrotal discomfort and orchitis. However, few studies have explored cytokine expression in testicular cells and their role in cell-to-cell communication. In this study, we integrated single-cell sequencing data sets of testicular cells, annotating 20 cell clusters using marker genes and the Human Cell Landscape database. We constructed cell pseudo-chronological trajectories, hub genes, and analyzed the cytokine interaction network between sperm cells using CellChat. Our findings identified 12 types of testicular cells, with four cytokines (IL8, CCL2, CCL3, and TNF) potentially involved in immune processes. Pseudo-chronological trajectory analysis indicated IL8 and CCL3's essential roles in testicular macrophages and endothelial cell development, affecting the immune microenvironment. We determined eight key cytokines (IL1, IL2, IL4, IL6, CCL, CSF3, TNF, and IFN-II) functions in cell interaction networks. Network analysis of exogenous cytokines directly acting on testicular cells showed IL2 potentially affecting all testicular cells, suggesting a vital role in cell communication. This research offers valuable insights into CSs effects on testicular cells and their potential impact on male fertility during COVID-19 infection.

Single-cell Clonal Tracing of Glandular and Circulating T cells identifies a population of CD9+CD8+T cells in primary Sjogren's Syndrome.

Primary Sjogren's syndrome (pSS) is a complex chronic autoimmune disease in which local tissue damage in exocrine glands are combined with broader systemic involvement across the body in tissues including the skin. These combined manifestations negatively impact patient health and quality of life. While studies have previously reported differences in immune cell composition in the peripheral blood of pSS patients relative to healthy controls, a detailed immune cell landscape of the damaged exocrine glands of these patients remains lacking. Through single-cell transcriptomics and repertoire sequencing of immune cells in paired peripheral blood samples and salivary gland biopsies, we present here a preliminary picture of adaptive immune response in pSS. We characterize a number of points of divergence between circulating and glandular immune responses that have been hitherto underappreciated, and identify a novel population of CD8+CD9+ cells with tissue-residential properties that are highly enriched in the salivary glands of pSS patients. Through comparative analyses with other sequencing data, we also observe a potential connection between these cells and the tissue-resident memory cells found in cutaneous vasculitis lesions. Together, these results indicate a potential role for CD8+CD9+ cells in mediating glandular and systemic effects associated with pSS and other autoimmune disorders.

Nursing Management of Abdominal Wound Dehiscence of an Infant With Severe Undernutrition and Peristomal Moisture-Associated Dermatitis After Ileostomy Closure: A Case Study.

BACKGROUND: Abdominal wound dehiscence (AWD) is a costly postoperative complication; its management is particularly challenging for WOC nurses when it occurs secondary to an ostomy closure. CASE: We present a case of AWD secondary to ileostomy closure in Baby Q, a 9-month 19-day-old female infant. A silver wound contact dressing was used on her dehisced wound followed by negative pressure wound therapy and adhesive tape to pull the wound edge together and promote granulation. We used a combination of enteral nutrition, parenteral nutrition, total parenteral nutrition, and total enteral nutrition adjusting the feeding plan stepwise according to her nutritional status. CONCLUSIONS: Malnutrition and severe peristomal skin complications may contribute to the risk of AWD in infants undergoing reversal of a temporary ostomy. Assessing and treating nutritional status and peristomal skin is imperative before performing ostomy closure.

Overexpression of fibroblast growth factor receptor 2 in bone marrow mesenchymal stem cells enhances osteogenesis and promotes critical cranial bone defect regeneration.

Background: Reconstruction of cranial bone defects is one of the most challenging problems in reconstructive surgery, and several biological tissue engineering methods have been used to promote bone repair, such as genetic engineering of bone marrow mesenchymal stem cells (BMSCs). Fibroblast growth factor receptor 2 (Fgfr2) is an important regulator of bone construction and can be used as a potential gene editing site. However, its role in the osteogenesis process of BMSCs remains unclear. This article clarifies the function of Fgfr2 in BMSCs and explores the role of Fgfr2-overexpressed BMSCs carried by light-induced porous hydrogel (GelMA) in the repair of cranial bone defects. Methods: Lenti-virus was used to overexpress Fgfr2 in BMSCs, and cell counting kit-8, transwell, and flow cytometry assays were conducted to investigate the proliferation, migration, and characteristics. After 0, 3, 7, and 10 days of osteogenic or chondrogenic induction, the changes in osteogenic and chondrogenic ability were detected by real-time PCR, western blot, alkaline phosphatase staining, alizarin Red staining, and alcian blue staining. To investigate the viability of BMSCs carried by GelMA, calcein and propyl iodide staining were carried out as well. Finally, a critical cranial bone defect model was established in 6-week-old male mice and micro-computerized tomography, masson staining, and immunohistochemistry of OCN were conducted to test the bone regeneration properties of implanting Fgfr2-overexpressed BMSCs with GelMA in cranial bone defects over 6 weeks. Results: Overexpression of Fgfr2 in BMSCs significantly promoted cell proliferation and migration and increased the percentage of CD200+CD105+ cells. After osteogenic and chondrogenic induction, Fgfr2 overexpression enhanced both osteogenic and chondrogenic ability. Furthermore, in cranial bone defect regeneration, BMSCs carried by light-induced GelMA showed favorable biocompatibility, and Fgfr2-overexpressed BMSCs induced superior cranial bone regeneration compared to a normal BMSCs group and an untreated blank group. Conclusion: In vitro, Fgfr2 enhanced the proliferation, migration, and stemness of BMSCs and promoted osteogenesis and chondrogenesis after parallel induction. In vivo, BMSCs with Fgfr2 overexpression carried by GelMA showed favorable performance in treating critical cranial bone defects. This study clarifies the multiple functions of Fgfr2 in BMSCs and provides a new method for future tissue engineering.

Roles, biological functions, and clinical significances of RHPN1-AS1 in cancer.

For the complex and multifaceted challenge of cancer eradication, a comprehensive approach is required. Molecular strategies are critical in the fight against cancer as they allow us to understand the underlying fundamental mechanisms and develop specialized treatments. The role of long non-coding RNAs (lncRNAs), a class of ncRNA molecules longer than 200 nucleotides, in cancer biology has attracted growing attention in recent years. These roles include but are not limited to regulating gene expression, protein localization, and chromatin remodeling. LncRNAs can influence a range of cellular functions and pathways, including those involved in cancer development. The first study on RHPN1 antisense RNA 1 (RHPN1-AS1), a 2030-bp transcript originating from human chromosome 8q24, in uveal melanoma (UM) demonstrated that this lncRNA was significantly upregulated in several UM cell lines. Further studies in various cancer cell lines showed that this lncRNA is significantly overexpressed and exerts oncogenic functions. This review will provide an overview of current knowledge regarding the roles played by RHPN1-AS1 in the emergence of various cancers, focusing on its biological and clinical functions.

Evaluation of a computer-aided diagnostic model for corneal diseases by analyzing in vivo confocal microscopy images.

Objective: In order to automatically and rapidly recognize the layers of corneal images using in vivo confocal microscopy (IVCM) and classify them into normal and abnormal images, a computer-aided diagnostic model was developed and tested based on deep learning to reduce physicians' workload. Methods: A total of 19,612 corneal images were retrospectively collected from 423 patients who underwent IVCM between January 2021 and August 2022 from Renmin Hospital of Wuhan University (Wuhan, China) and Zhongnan Hospital of Wuhan University (Wuhan, China). Images were then reviewed and categorized by three corneal specialists before training and testing the models, including the layer recognition model (epithelium, bowman's membrane, stroma, and endothelium) and diagnostic model, to identify the layers of corneal images and distinguish normal images from abnormal images. Totally, 580 database-independent IVCM images were used in a human-machine competition to assess the speed and accuracy of image recognition by 4 ophthalmologists and artificial intelligence (AI). To evaluate the efficacy of the model, 8 trainees were employed to recognize these 580 images both with and without model assistance, and the results of the two evaluations were analyzed to explore the effects of model assistance. Results: The accuracy of the model reached 0.914, 0.957, 0.967, and 0.950 for the recognition of 4 layers of epithelium, bowman's membrane, stroma, and endothelium in the internal test dataset, respectively, and it was 0.961, 0.932, 0.945, and 0.959 for the recognition of normal/abnormal images at each layer, respectively. In the external test dataset, the accuracy of the recognition of corneal layers was 0.960, 0.965, 0.966, and 0.964, respectively, and the accuracy of normal/abnormal image recognition was 0.983, 0.972, 0.940, and 0.982, respectively. In the human-machine competition, the model achieved an accuracy of 0.929, which was similar to that of specialists and higher than that of senior physicians, and the recognition speed was 237 times faster than that of specialists. With model assistance, the accuracy of trainees increased from 0.712 to 0.886. Conclusion: A computer-aided diagnostic model was developed for IVCM images based on deep learning, which rapidly recognized the layers of corneal images and classified them as normal and abnormal. This model can increase the efficacy of clinical diagnosis and assist physicians in training and learning for clinical purposes.

Quantitative discrimination of algae multi-impacts on N2O emissions in eutrophic lakes: Implications for N2O budgets and mitigation.

It is generally accepted that eutrophic lakes significantly contribute to nitrous oxide (N2O) emissions. However, how these emissions are affected by the formation, disappearance, and mechanisms of algal blooms in these lakes has not been systematically investigated. This study examined and determined the relative contribution of spatiotemporal N2O production pathways in hypereutrophic Lake Taihu. Synchronously, the multi-impacts of algae on N2O production and release potential were measured in the field and in microcosms using isotope ratios of oxygen (δ18O) and bulk nitrogen (δ15N) to N2O and to intramolecular 15N site preference (SP). Results showed that N2O production in Lake Taihu was derived from microbial effects (nitrification and incomplete denitrification) and water air exchanges. N2O production was also affected by the N2O reduction process. The mean dissolved N2O concentrations in the water column during the pre-outbreak, outbreak, and decay stages of algae accumulation were almost the same (0.05 µmol·L-1), which was 2-10 times higher than in lake areas algae was not accumulating. However, except for the central lake area, all surveyed areas (with and without accumulated algae) displayed strong release potential and acted as the emission source because of dissolved N2O supersaturation in the water column. The mean N2O release fluxes during the pre-outbreak, outbreak, and decay stages of algae accumulation areas were 17.95, 26.36, and 79.32 µmol·m-2·d-1, respectively, which were 2.0-7.5 times higher than the values in the non-algae accumulation areas. In addition, the decay and decomposition of algae released large amounts of nutrients and changed the physiochemical properties of the water column. Additionally, the increased algae biomass promoted N2O release and improved the proportion of N2O produced via denitrification process to being 9.8-20.4% microbial-derived N2O. This proportion became higher when the N2O consumption during denitrification was considered as evidenced by isotopic data. However, when the algae biomass was excessive in hypereutrophic state, the algae decomposition also consumed a large amount of oxygen, thus limiting the N2O production due to complete denitrification as well as due to the limited substrate supply of nitrate by nitrification in hypoxic or anoxic conditions. Further, the excessive algae accumulation on the water surface reduced N2O release fluxes via hindering the migration of the dissolved N2O into the atmosphere. These findings provide a new perspective and understanding for accurately evaluating N2O release fluxes driven by algae processes in eutrophic lakes.

Serotonin-induced stereospecific formation and bioactivity of the eicosanoid 17,18-epoxyeicosatetraenoic acid in the regulation of pharyngeal pumping of C. elegans.

17,18-Epoxyeicosatetraenoic acid (17,18-EEQ), the most abundant eicosanoid generated by cytochrome P450 (CYP) enzymes in C. elegans, is a potential signaling molecule in the regulation of pharyngeal pumping activity of this nematode. As a chiral molecule, 17,18-EEQ can exist in two stereoisomers, the 17(R),18(S)- and 17(S),18(R)-EEQ enantiomers. Here we tested the hypothesis that 17,18-EEQ may function as a second messenger of the feeding-promoting neurotransmitter serotonin and stimulates pharyngeal pumping and food uptake in a stereospecific manner. Serotonin treatment of wildtype worms induced a more than twofold increase of free 17,18-EEQ levels. As revealed by chiral lipidomics analysis, this increase was almost exclusively due to an enhanced release of the (R,S)-enantiomer of 17,18-EEQ. In contrast to the wildtype strain, serotonin failed to induce 17,18-EEQ formation as well as to accelerate pharyngeal pumping in mutant strains defective in the serotonin SER-7 receptor. However, the pharyngeal activity of the ser-7 mutant remained fully responsive to exogenous 17,18-EEQ administration. Short term incubations of well-fed and starved wildtype nematodes showed that both racemic 17,18-EEQ and 17(R),18(S)-EEQ were able to increase pharyngeal pumping frequency and the uptake of fluorescence-labeled microspheres, while 17(S),18(R)-EEQ and also 17,18-dihydroxyeicosatetraenoic acid (17,18-DHEQ, the hydrolysis product of 17,18-EEQ) were ineffective. Taken together, these results show that serotonin induces 17,18-EEQ formation in C. elegans via the SER-7 receptor and that both the formation of this epoxyeicosanoid and its subsequent stimulatory effect on pharyngeal activity proceed with high stereospecificity confined to the (R,S)-enantiomer.

Orthodontic-surgical treatment for severe skeletal class II malocclusion with vertical maxillary excess and four premolars extraction: A case report.

BACKGROUND: Patient satisfaction with facial appearance at the end of orthodontic camouflage treatment is very important, especially for skeletal malocclusion. This case report highlights the importance of the treatment plan for a patient initially treated with four-premolar-extraction camouflage, despite indications for orthognathic surgery. CASE SUMMARY: A 23-year-old male sought treatment complaining about his unsatisfactory facial appearance. His maxillary first premolars and mandibular second premolars had been extracted, and a fixed appliance had been used to retract his anterior teeth for two years without improvement. He had a convex profile, a gummy smile, lip incompetence, inadequate maxillary incisor inclination, and almost a class I molar relationship. Cephalometric analysis showed severe skeletal class II malocclusion (A point-nasion-B point = 11.5°) with a retrognathic mandible (sella-nasion-B point = 75.9°), a protruded maxilla (sella-nasion-A point = 87.4°), and vertical maxillary excess (upper incisor to palatal plane = 33.2 mm). The excessive lingual inclination of the maxillary incisors (upper incisor to nasion-A point line = -5.5°) was due to previous treatment attempts to compensate for the skeletal class II malocclusion. The patient was successfully retreated with decompensating orthodontic treatment combined with orthognathic surgery. The maxillary incisors were repositioned and proclined in the alveolar bone, the overjet was increased, and a space was created for orthognathic surgery, including maxillary impaction, anterior maxillary back-setting, and bilateral sagittal split ramus osteotomy to correct his skeletal anteroposterior discrepancy. Gingival display was reduced, and lip competence was restored. In addition, the results remained stable after 2 years. The patient was satisfied with his new profile as well as with the functional malocclusion at the end of treatment. CONCLUSION: This case report provides orthodontists a good example of how to treat an adult with severe skeletal class II malocclusion with vertical maxillary excess after an unsatisfactory orthodontic camouflage treatment. Orthodontic and orthognathic treatment can significantly correct a patient's facial appearance.

The prognostic value of tumor mutation burden (TMB) and its relationship with immune infiltration in breast cancer patients.

OBJECTIVE: Although the tumor mutation burden (TMB) was reported as a biomarker for immunotherapy of various cancers, whether it can effectively predict the survival prognosis in breast cancer patients remains unclear. In this study, the prognostic value of TMB and its correlation with immune infiltration were explored by using multigroup studies. METHODS: The somatic mutation data of 986 breast cancer patients were obtained from TCGA database. Breast cancer patients were divided into a low-TMB group and a high-TMB group according to the quartile of TMB scores. The differentially expressed genes (DEGs) were identified by the "limma" R program. The CIBERSORT algorithm was utilized to estimate the immune cell fraction of each sample. The TIMER database was utilized to evaluate the association between CNVs of immune genes and tumor immune cell infiltration and the prognostic value of the immune cells in breast cancer. RESULTS: In breast cancer, TP53, PIK3CA, TTN, CDH1 and other genes were the most important mutated genes. Higher survival rate of patients was found in the low-TMB group. Among the top 10 DEGs, three of them belong to the KRT gene family. GSEA enrichment analysis showed that MAPK, Hedgehog, mTOR, TGF-bate and GnRH signaling pathways were enriched in the low-TMB group. The infiltration levels of the most of immune cells were higher in the low-TMB group (P < 0.01). Higher expression of CCL18 and TRGC1 was correlated with poor prognosis. Breast cancer patients with CCL18 copy number variations, especially arm-level gains, showed significantly decreased immune cell infiltration. In the low B cell infiltration group, the survival prognosis of breast cancer patients was poor. CONCLUSIONS: TMB is a potential prognosis marker in breast cancer. Immune-related gene CCL18 and TRGC1 are biomarkers of poor prognosis while immune (B cell) infiltration is a biomarker of good prognosis.