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Background Intra-abdominal infections are the second most common cause of sepsis in the intensive care unit. Intestinal epithelial injury due to abdominal sepsis results in a variety of pathological changes, such as intestinal bacteria and toxins entering the blood, leading to persistent systemic inflammation and multiple organ dysfunction. The increased apoptosis of intestinal epithelial cells induced by sepsis further exacerbates the progression of sepsis. Although several studies have revealed that circRNAs are involved in intestinal epithelial injury in sepsis, few studies have identified the roles of circRNAs in intestinal epithelial apoptosis. Methods We used laser capture microdissection to obtain purified epithelial cells located in intestinal crypts from four patients with abdominal sepsis induced by intestinal perforation and four samples from age and sex-matched non-septic patients. Microarray analysis of circRNAs was conducted to assess differentially expressed circRNAs between patients with and without sepsis. Lastly, in vitro and in vivo assays were performed to study the mechanism of circFLNA in intestinal epithelial apoptosis during sepsis. Results circFLNA was upregulated in the intestinal epithelium after abdominal sepsis induced by intestinal perforation. Inhibition of miR-766-3p impaired si-circFLNA-mediated inhibition of apoptosis and inflammation factor levels in lipopolysaccharide (LPS)-treated HIEC-6 cells. circFLNA aggravated apoptosis and inflammation through the Fas-mediated apoptosis pathway in both LPS-treated HIEC-6 cells and a mouse cecal ligation and puncture model. Conclusion Our findings showed that circFLNA promotes intestinal injury in abdominal sepsis through the Fas-mediated apoptosis pathway by sponging miR-766-3p. The circFLNA/miR-766-3p/Fas axis has potential as a novel therapeutic target for treating intestinal injury in sepsis.

Hydrogen technology is widely considered a novel clean energy source, and electrolysis is an effective method for hydrogen evolution. Therefore, efficient hydrogen evolution reaction (HER) catalysts are urgently needed to replace precious metal catalysts and meet ecological and environmental protection standards. Herein, Ni–Mn–P electrocatalysts are synthesized using facile electrodeposition technology. The influence of the Mn addition on the catalytic behavior is studied by the comprehensive analysis of catalytic performance and morphology of the catalysts. Among them, the Ni–Mn–P0.01 catalyst exhibits small coral-like structures, greatly improving the adsorption and desorption of hydrogen ions and reducing the overpotential hydrogen evolution. Consequently, overpotential at 10 mA cm−2 electric current density is 113 mV, and the value of the Tafel slope achieves 74 mV/dec. Furthermore, the Ni–Mn–P catalyst shows long-time (20 h) stability at current densities of 10 and 60 mA/cm2. The results confirm that the synergistic effect of Ni, Mn, and P accelerates the electrochemical reaction. Meanwhile, the addition of manganese element can change the micromorphology of the catalyst, thereby exposing more active sites to participate in the reaction, enhancing water ionization, improving the catalytic performance. This study opens a new way toward improving the activity of the catalyst by adjusting Mn concentration during the electrodeposition process.

Implementing quantum algorithms on realistic devices requires translating high-level global operations into sequences of hardware-native logic gates, a process known as quantum compiling. Physical limitations, such as constraints in connectivity and gate alphabets, often result in unacceptable implementation costs. To enable successful near-term applications, it is crucial to optimize compilation by exploiting the capabilities of existing hardware. Here we implement a resource-efficient construction for a quantum version of AND logic that can reduce the compilation overhead, enabling the execution of key quantum circuits. On a high-scalability superconducting quantum processor, we demonstrate low-depth synthesis of high-fidelity generalized Toffoli gates with up to 8 qubits and Grover’s search algorithm in a search space of up to 64 entries. Our experimental demonstration illustrates a scalable and widely applicable approach to implementing quantum algorithms, bringing more meaningful quantum applications on noisy devices within reach.

Esophageal Carcinoma (ESCA) is a common and lethal malignant tumor worldwide. A role for mitochondria in tumorigenesis and progression has been proposed. The mitochondrial biomarkers were useful in finding significant prognostic gene modules associated with ESCA. In the present work, we obtained the transcriptome expression profiles and corresponding clinical information of ESCA from The Cancer Genome Atlas (TCGA). Differential expressed genes (DEGs) were overlapped with mitochondria related genes to obtain mitochondria related DEGs. The univariate cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate cox regression was sequentially used to define the risk scoring model for mitochondria-related DEGs, and its prognostic value was verified in the external datasets GSE53624. Based on risk score, ESCA patients were divided into high and low risk groups. GO, KEGG and Gene Set Enrichment Analysis (GSEA) were performed to further investigate the difference between low and high risk groups in the gene pathway level. CIBERSORT was used to evaluate immune cell infiltration. The mutation difference between high and low risk groups was compared by the R package “Maftools”. Cellminer was used to assess the interactions of the risk scoring model and drug sensitivity. As the most important outcome of the study, we obtained 306 mitochondria related DEGs, and constructed a 6-gene risk scoring model (APOOL, HIGD1A, MAOB, BCAP31, SLC44A2 and CHPT1). Between high and low risk group, pathways including “hippo signaling pathway” and “cell-cell junction” was enriched. According to CIBERSORT, samples with high risk demonstrated higher abundance of CD4+ T cells, NK cells, M0 and M2 Macrophages, and lower abundance of M1 Macrophages. The immune cell marker genes were correlated with risk score. In mutation analysis, the mutation rate of TP53 was significantly different between the high and low risk groups. Drugs with strong correlation with model genes and risk score were selected. In conclusion, we focused on the role of mitochondria-related genes in cancer development, and proposed a prognostic signature for individualized integrative assessment.

A Gram-negative, non-motile, aerobic bacterium, named 02-257T, was isolated from Antarctic soil. The cells are surrounded by relatively thin capsules and were catalase-positive and oxidase-negative cocci. Growth of strain 02-257T was observed at 4–35 °C (optimum, 28–30 °C), pH 6.0–8.0 (optimum, pH 6.0) and with 0–1.5% NaCl (optimum, 0 %). Strain 02–257 showed the highest 16S rRNA gene sequence similarity to Paraconexibacter algicola Seoho-28T (95.06 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 02-257T is a member of a novel species belonging to the clade formed by members of the genus Paraconexibacter in the family Paraconexibacteraceae . The DNA G+C content was 72.9 mol%. Strain 02-257T contained C16 : 0-iso (23.0 %), C18 : 1 ω9c (13.8 %), C16 : 0 (12.5 %) and C17 : 1 ω9c-iso (10.8 %) as major cellular fatty acids and menaquinone MK-7(H4) was detected as the only isoprenoid quinone. Diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositole mannoside, phosphatidylinositole dimannoside, unidentified phosphoglycolipid, unidentified aminophospholipid, two unidentified phospholipids, three unidentified aminolipids and six unidentified lipids were the major polar lipids. meso-Diaminopimelic acids were the diagnostic diamino acids in the cell-wall peptidoglycan. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain 02-257T is considered to represent a novel species of the genus Paraconexibacter , for which the name Paraconexibacter antarcticus sp. nov. is proposed. The type strain is 02-257T (=CCTCC AB 2021030T=KCTC 49619T).

Carbonates are considered to be important hosts of oxidized carbon during subduction processes. Here we investigate the redox interactions between dolomite and metallic iron in laser-heated diamond anvil cells up to ∼20 GPa. The identification of recovered samples via in-situ synchrotron X-ray diffraction and ex-situ Raman spectroscopy shows that the reaction occurs with the formation of ferropericlase, graphite and hexagonal diamond, while CaCO3 remains stable. The experimental results indicate dolomite and metallic iron phases cannot coexist and demonstrate a possible formation mechanism of ultradeep diamonds via redox reaction between dolomite and iron under the mantle transition zone conditions. The results are significant for understanding carbon transportation during subduction processes and have further implications to the processes in the more complex systems regarding to carbonate-silicate-metal phase relations.

The TiO2/Mn0.2Cd0.8S hollow heterojunction with Mn/Cd bimetallic synergy is prepared via a continuous chemical-hydrothermal-etching method. There, the TiO2 shell and Mn0.2Cd0.8S nanoparticles were deposited by continuous chemical-hydrothermal method on the surface of SiO2 template, and subsequently the SiO2 template was etched via a chemical method. Evaluated by HER, the as-prepared TiO2/Mn0.2Cd0.8S hollow heterojunction exhibits an obvious photocatalytic enhancement to about ~5822.94 μmol/g∙h(~40 folds of TiO2, ~7 folds of Mn0.2Cd0.8S), which can be mainly ascribed to that, the narrow band gap of Mn0.2Cd0.8S can increase the visible light energy utilization, the TiO2/Mn0.2Cd0.8S heterojunction and Mn/Cd bimetallic synergy can separate/transfer the photo-generated charge carriers efficiently, and the sufficient specific surface areas and actives from 3D hollow structure can promote the charge carrier diffusing into water quickly for achieving H2 generation. Additionally, the hollow 3D structure can provide a decent physical-chemical stability to improve the photocatalytic stability.

Multi-modal dense video captioning is a task using multiple information to detect all meaningful events and generate a textual description for each event. The existing works mainly rely on single visual or dual audio-visual modals in dense video captioning, while completely ignoring the text modal (subtitle). The text modal has a similar data structure as the video captions, which provides immediate semantic information to the content description for a video. In this paper, we propose a novel framework, called Two-Stage Cross-Modal Encoding Transformer Network (TS-CMETN), to realize the multi-modal dense video captioning task by fusing multiple features, including audio, visual, and text. First, we design a two-stage feature fusion encoder that hierarchically achieves the intra- and inter-modal information interaction. Second, we propose an anchor-free temporal event proposal module, which efficiently generates event proposals at each time step without the complex anchor calculation. Extensive experiments on the ActivityNet Captions dataset show that our proposed framework achieves high performance. Moreover, our approach can adaptively handle cases of the missing text modal. Our code and data are available at https://github.com/xieyulai/TM-CMETN .

A rod-shaped, Gram-stain-negative, non-motile and aerobic bacterium, designated Q8-18T, was isolated from soil of glacier foreland in Austre Lovénbreen, Arctic, and subjected to a polyphasic taxonomic study. Strain Q8-18T grew optimally at 20 °C, pH 5.0–8.0 and in the presence of 0–1.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Q8-18T belonged to the family Sphingobacteriaceae . Strain Q8-18T showed the highest sequence similarity to Pedobacter mendelii CCM 8685T (96.8%), Pedobacter lithocola CCM 8691T (96.8%), Pedobacter roseus CL-GP80T (96.7%), Pedobacter changchengzhani E01020T (96.7%), Pedobacter alluvionis DSM 19624T (96.6%), Pedobacter jejuensis THG-DR3T (96.3%), Pedobacter ginsengiterrae DCY49T (95.9%) and Pedobacter jamesrossensis CCM 8689T (95.9%). A whole genome-level comparison of strain Q8-18T with P. roseus CL-GP80T, P. changchengzhani E01020T, P. alluvionis DSM 19624T and Pedobacter heparinus LMG 10339T revealed average nucleotide identity values of 77.0, 76.0, 77.0 and 70.4%, respectively. The only respiratory isoprenoid quinone was menaquinone-7. The polar lipid profile of strain Q8-18T was found to contain one phosphatidylethanolamine, eight unidentified aminolipids, one aminophospholipids and five unidentified lipids. The G+C content of the genomic DNA was determined to be 35.4 mol%. The main fatty acids were summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c), iso-C15 : 0 and anteiso-C15 : 0. On the basis of the evidence presented in this study, a novel species of the genus Pedobacter , Pedobacter mucosus sp. nov., is proposed, with the type strain Q8-18T (=CCTCC AB 2020009T=KCTC 82636T).

A CoxP QDs-MoS2 nanosheets@Ni3S2 nanoarrays/NF with electrocatalytic overall water splitting is fabricated via a simple hydrothermal-electrodeposition method. There, the MoS2@Ni3S2/NF is prepared by a hydrothermal method on the surface of NF, and subsequently the CoxP QDs are deposited by an electrodeposition method on the surface of MoS2 nanosheets. As demonstrated, the as-prepared CoxP QDs-MoS2@Ni3S2/NF presents low overpotentials of 54 mV(HER) at 10 mA cm−2 and 207 mV(OER) at 100 mA cm−2 in 1.0 M KOH, and exhibits a decent overall water splitting performance, including the overpotential of 1.39 V(vs RHE) at 10 mA cm−2, which can be mainly ascribed to the hierarchical nanostructure can increase MoS2 nanosheets and CoxP QDs efficiently for increasing the HER/OER active sites. Additionally, the extra HER active sites of edge S atoms from MoS2 nanosheets, the extra OER active sites induce by the presence of Ni3+/Ni2+ and Co3+/Co2+ mixed state, and low overpotential of Ni3S2, MoS2 and CoxP QDs are also important reasons.

The diffusion of defects (e.g., vacancies and interstitials) and elements used for dating (e.g., He and Pb) in a mineral structure is a thermal process: This is the primary assumption used to determine the age and thermal history of minerals. For instance, thermal history reconstruction, through the number and length distribution of tracks produced by spontaneous fission of 238U, is obtained by assuming a thermal event to be the only energy source for shortening of fission tracks. Here, we report a new, non-thermal energy source that induces additional shortening of fission tracks by the irradiation of alpha-recoils from the alpha-decay of 238U and 232Th. We simulate alpha-decay induced track-shortening by combining ion accelerator irradiations with transmission electron microscopy. This allows for the first observation of track-shrinkage during in situ ion irradiation. We show that rather than alpha-particles, alpha-recoils induce a significant shortening of fission tracks by nuclear-collisions. The shortening of track-length can be quantified as a function of alpha-decay event dose. However, apatite is less sensitive than zircon to this non-thermal process. The findings exemplify the interactions among different types of self-irradiation from alpha-particles, alpha-recoils and fission-fragment nuclei in single mineral grains and have important implications for the use of zircon and apatite for radiometric dating and thermochronology.

Objective: To explore the value of multi-voxel-based monomer 1H-MRS (magnetic resonance imaging) in the classification of gliomas. Methods: 26 gliomas confirmed by surgery and pathology were examined by conventional MRI, multi-voxel 2D, and monomer 1H-MRS before surgery. Three types of regions of interest (ROI) were used to measure Cho/NAA (Choline hydroxide solution/N-acetyl aspartic acid) values in the tumor. Methods: In the multi-voxel 2D hydrogen proton spectrum, the solid part of the tumor or the most intensive region of the tumor was selected to determine the Cho/NAA value. At the same time, in the multi-voxel 2D hydrogen proton spectrum, the Fun/tool spectra's copy-2DBmin analysis software was used to obtain the Cho/NAA value distribution. Anatomically superimposed the pseudo-color image, and measure the Cho/NAA value in its largest Cho/NAA value region. In addition, based on the level set algorithm, it uses the Otsu algorithm to initially locate the edema area and provide the initial contour. Results: The Cho/NAA values measured by the ROI selection method were statistically significant, and the sensitivity and specificity of judging the benign and malignant gliomas indicated that Method 3 had the highest diagnostic value. Conclusion: Multi-voxel-based monomeric 1H-MRS magnetic resonance imaging has the highest value in guiding glioma classification and can improve the accuracy of glioma classification.

Peri-islet glial cells (PIGCs) are positioned to control neuronal-endocrine-vascular cell communication within the islet, but their role in islet cell function is not known. Hypothalamic glial cells become reactive in response to high fat diet (HFD) feeding and are implicated in the pathogenesis of obesity and type 2 diabetes. We hypothesize that metabolic stress such as diet-induced obesity and hyperglycemia promote the expansion of PIGCs, similar to what has been observed in the central nervous system. To test this hypothesis, we used the glial cell marker, glial fibrillary acidic protein (GFAP) , to identify PIGCs and compared GFAP immunoreactivity in pancreas from the following groups. First, pancreas was harvested from HFD- or chow fed control C57BL/6J male mice after 2 days, 2 weeks or 8 weeks on diet (n=6-8/group) . Second, pancreas was taken from 12-wk old db/db male mice and their control littermates with or without empagliflozin (EMPA) treatment (20mg/kg/d for 6 weeks; n=4-7/group) . Islet PIGC area was quantified as GFAP-positive area/total islet area x100%. Mann-Whitney test and one-way ANOVA were used for data analysis. We found that HFD feeding increased mouse pancreatic peri-islet GFAP expression relative to chow controls at 2 days (HFD 1.4±0.2%, chow 0.8±0.1%; p=0.02) , 2 weeks (HFD 3.5±0.4%, chow 1.2±0.1%; p In conclusion, these findings indicate that islet gliosis is observed in two obese and hyperglycemic mouse models and raise the possibility that pancreatic ‘gliosis’ may have a relevant role in islet-cell function regulation under metabolic challenge. Disclosure J.Niu: None. J.B.Moss: None. W.Rosario: Employee; Merck & Co., Inc. R.Arumugam: None. D.J.Hackney: None. R.L.Hull-meichle: Research Support; Casma Therapeutics. J.Tong: None. Funding National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (R01DK097550) ;Department of Veterans Affairs (IBX004063)

Two-dimensional transition-metal dichalcogenides hold great potential in rechargeable lithium-ion batteries. Their electrochemical properties are closely related to the structural evolutions during lithium-ion migration. Understanding these migration/reaction mechanisms is important to help improve battery performance. Herein, we report the real-time and atomic-scale observation of phase transitions during the lithiation and delithiation for V5S8 via in situ electron diffraction and high-resolution transmission electron microscopy techniques. We find that the phase transformation proceeds via a sequence of order to antisite disorder intercalation and topotactic-based conversion reaction. During the intercalation reaction, the lithium ion destroys the orderings of the interstitial V with the formation of Li/V antisite. Such a reaction is found to be reversible, i.e., the extraction of lithium from LixV5S8 leads to the recovery of V orderings. The conversion reaction involves heterogeneous nucleation of Li2S with 3-20 nm nanodomains, which maintain the crystallographic integrity with LixV5S8. These findings elucidate the complex interactions between the lithium ion and host V5S8 during ionic migration in solids, which should be helpful in understanding the relationship between phase transformation kinetics and battery performance.

Aim: Mycobacterium tuberculosis in vitro biofilm is associated with the virulence and persistence capability. Our aim is to delineate factors involved in biofilms development. Materials & methods: We performed transposon mutants screen and found that mutation of MSMEG_3641, a homolog of M. tuberculosis Rv1836c, can change M. smegmatis colony morphology and biofilm. Results: MSMEG_3641 contains a vWA domain that is highly conserved among Mycobacteria. The phenotypes of MSMEG_3641 mutants include disrupted biofilm, weakened migration ability and changed colony morphology. All phenotypes might be contributed to the enhanced cell wall permeability and declined cell aggregation ability. Conclusion: To our knowledge, this is the first report concerning the mycobacteria Von Willebrand factor domain function, especially in colony morphology and biofilm development.

The existing optical performance monitoring (OPM) scheme based on deep neural network has no selection capability of the input data. They always accept and process all, which may result in serious monitoring errors and reduce the credibility of the monitoring system. Because the transmitted data in the future heterogeneous fiber-optic networks are diverse, and it's likely to exceed the scope of the monitoring system. We propose an unsupervised generative adversarial network (GAN) as the judgement module in the new OPM framework to select the legal data within the scope of the monitoring system. The generator consists of encoder-decoder-encoder (EDE) sub-network, jointly learns the image and latent feature distribution of the legal data. And the training data for the network in the new added judgement module is the same as the OPM analyzer network's, therefore, no extra data are collected, which is low-cost. In the simulation, four modulation formats under two bit-rates are taken into account to verify the model performance in the judgement module. When 60 Gbps 64QAM signal is selected as illegal data, the max value of the area under the curve (AUC) is 0.942. The judgement time for single image is about 12 ms. Moreover, the influence of the task weights and the latent feature shape on the judgement performance are investigated. The new added judgement module largely increases the credibility and safety of the existing OPM scheme.

Black rockfish is an economically important fish in East Asia. Little mention has been paid to the sperm cryopreservation in black rockfish. In this study, the optimal cryodiluent was selected from 48 combinations by detecting various sperm parameters. Transcriptome and methylome analysis were further performed to explore the molecular mechanism of inevitable cryoinjuries. The results showed that cryopreservation had negative effects on the viability, DNA integrity, mitochondrial activity, total ATPase and LDH of sperm even with optimal cryodiluent (FBS + 15% Gly). Transcriptome and methylome analysis revealed that the expression of 179 genes and methylation of 1266 genes were affected by cryopreservation. These genes were enriched in GO terms of death, G-protein coupled receptor signaling pathway, response to external stimulus and KEGG pathways of phospholipase D signaling pathway and xenobiotic and carbohydrate metabolism pathways. The role of PIK3CA and CCNA2 were highlighted in the protein-protein interaction network, and the sperm quality-related imprinted gene

Black rockfish (Sebastes schlegelii) is a viviparous teleost fish whose spermatozoa were transferred into the female ovary cavity and stored for up to five months and then fertilized with the matured eggs. There is no clarity about the molecular characteristics of ovarian follicles during female sperm storage in Sebastes schlegelii. In this study, histological observation, transcriptomic analysis and hormone level detection were performed in ovaries at stages of pre-mating (PRM), post-mating (POM) and pre-fertilization (PRF). Histological observation displayed that oocytes developed from the primary growth (PG) stage to the mature stage during the three stages. Furthermore, somatic cells around the oocyte were proliferated and spermatozoa were found near the layer of epithelial cells. Transcriptomic analysis showed that there were 437 and 747 differentially expressed genes (DEGs) in ovarian comparison of PRM-vs-POM and POM-vs-PRF, respectively. GO enrichment and KEGG analysis revealed that lots of DEGs from PRM-vs-POM were linked to immune-related pathways, such as antigen processing and presentation, immune response, and complement and coagulation cascade. Meanwhile, seven DEGs associated with immune response were differentially expressed after spermatozoa treatment in ovarian tissue in vitro. While the DEGs from POM-vs-PRF were mostly enriched in the pathways related to homeostasis maintenance and cellular junction and metabolism. In addition, we found increased estrogen (E2) and 11-ketotestosterone (11-KT) level and decreased testosterone level in ovarian follicles during the sperm storage period by ELISA, suggesting that sex hormones are involved in the dynamic change of ovarian follicles. In total, this study could provide new hints for understanding the immune adaption and developmental signatures of ovarian follicles post copulation in black rockfish and other viviparous fish.

Strain Q3-56T, isolated from Arctic tundra soil, was found to be a Gram-stain-negative, yellow-pigmented, oxidase- and catalase-positive, non-motile, non-spore-forming, rod-shaped and aerobic bacterium. Strain Q3-56T grew optimally at pH 7.0 and 28 °C. The strain could tolerate up to 1 % (w/v) NaCl with optimum growth in the absence of NaCl. The strain was not sensitive to oxacillin and ceftazidime. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Q3-56T belonged to the genus Dyadobacter . Strain Q3-56T showed the highest sequence similarities to Dyadobacter luticola T17T (96.58 %), Dyadobacter ginsengisoli Gsoil 043T (96.50 %), Dyadobacter flavalbus NS28T (96.43 %) and Dyadobacter bucti QTA69T (96.43 %). The predominant respiratory isoprenoid quinone was identified as MK-7, The polar lipid profile of strain Q3-56T was found to contain one phosphatidylethanolamine, three unidentified aminolipids, three unidentified lipids and one unidentified phospholipid. The G+C content of the genomic DNA was determined to be 49.1 mol%. The main fatty acids were summed feature 3 (comprising C16 : 1 ω7c/C16 : 1 ω6c), iso-C15 : 0, C16 : 1 ω5c and iso-C16 : 1 3-OH. On the basis of the evidence presented in this study, a novel species of the genus Dyadobacter , Dyadobacter sandarakinus sp. nov., is proposed, with the type strain Q3-56T (=CCTCC AB 2019271T=KCTC 72739T). Emended descriptions of Dyadobacter alkalitolerans , Dyadobacter koreensis and Dyadobacter psychrophilus are also provided.

Objective: Septic shock is the severe complication of sepsis, with a high mortality. The inflammatory response regulates the immune status and mediates the progression of septic shock. In this study, we aim to identify the key immune-related genes (IRGs) of septic shock and explore their potential mechanism.Methods: Gene expression profiles of septic shock blood samples and normal whole blood samples were retrieved from the Gene Expression Omnibus (GEO) and Genotype-Tissue Expression Portal (GTEx). The differential expression genes (DEGs) and septic shock-specific immune-related genes (SSSIRGs) were evaluated and identified, along with the immune components by “cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT, version x)” algorithm. Additionally, in order to explore the key regulatory network, the relationship among SSSIRGs, upstream transcription factors (TFs), and downstream signaling pathways were also identified by Gene Set Variation Analysis (GSVA) and co-expression analysis. Moreover, the Connectivity Map (CMap) analysis was applied to find bioactive small molecules against the members of regulation network while Chromatin Immunoprecipitation sequencing (ChIP-seq) and Assay for Targeting Accessible-Chromatin with high-throughput sequencing (ATAC-seq) data were used to validate the regulation mechanism of the network.Results: A total of 14,843 DEGs were found between 63 septic shock blood samples and 337 normal whole blood samples. Then, we identified septic shock-specific 839 IRGs as the intersection of DEGs and IRGs. Moreover, we uncovered the regulatory networks based on co-expression analysis and found 28 co-expression interaction pairs. In the regulation network, protein phosphatase 3, catalytic subunit, alpha isozyme (PPP3CA) may regulate late estrogen response, glycolysis and TNFα signaling via NFκB and HLA; Kirsten rat sarcoma viral oncogene homolog (KRAS) may be related to late estrogen response and HLA; and Toll-like receptor 8 (TLR8) may be associated with TNFα signaling via NFκB. And the regulation mechanisms between TFs and IRGs (TLR8, PPP3CA, and KRAS) were validated by ChIP-seq and ATAC-seq.Conclusion: Our data identify three SSSIRGs (TLR8, PPP3CA, and KRAS) as candidate therapeutic targets for septic shock and provide constructed regulatory networks in septic shock to explore its potential mechanism.

Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.

Sub-seafloor sediment is the largest microbial habitat on Earth. The study of microbes in sub-seafloor sediment is largely limited by the technical challenge of acquiring ambient microbial DNA because of sediment heterogeneity. Changes in the extraction method, even just by one step, can affect the extraction yields for complicated sediment samples. In this work, sub-seafloor sediment samples from the Baltic Sea with high organic carbon content were used to evaluate the influence of different grinding beads on DNA extraction. We found that the grinding beads can affect the DNA extraction from the organic-matter- and biosiliceous-clay-rich samples. A mixture of 0.5-mm and 0.1-mm grinding beads exhibited higher DNA yields and recovered more unique taxa than other bead combinations, such as Stenotrophomonas from Gammaproteobacteria and Leptotrichia from Fusobacteria; therefore, these beads are more suitable than the others for DNA extraction from the samples used in this study. This advantage might be magnified in samples with high biomass. On the contrary, the use of only small beads might lead to underestimation for certain Gram-positive strains. Overall, the discovery of abundant widespread deep biosphere clades in our samples indicated that our optimized DNA extraction method successfully recovered the in situ microbial community.

Fe-bearing phase E coexisting with ringwoodite and wadsleyite has been synthesized at near-geotherm temperatures in hydrous KLB-1 peridotite compositions held at 18 and 19 GPa, and 1400 °C for 27 h. The long heating duration time of syntheses implies that phase E can be a stable component of the mantle under hydrous conditions. Single-crystal X-ray diffraction analyses show that the M1 octahedral site is 72.1–75.2 at% occupied, whereas the M2 and tetrahedral Si sites are 2.4–2.9 at% and 18.9–19.8 at% occupied, respectively. The M1 site occupancies show a positive correlation with Fe/Mg molar ratios, indicating that Fe mainly occupies the M1 site in the phase E structure. High-pressure Raman spectroscopy shows that the framework Raman frequencies of Fe-bearing phase E increase continuously with increasing pressures up to 19 GPa at room temperature, and there is no indication for a major change in the crystal structure. If transition-zone regions adjacent to subducting slabs are hydrated by fluids generated at the top of the lower mantle, Fe-bearing phase E is expected to occur at wadsleyite-ringwoodite phase transition boundary (about 520 km) as an important phase for incorporating water.

Objective Bariatric surgery acutely improves glucose control, an effect that is generally sustained for years in most patients. The acute postoperative glycemic reduction is at least partially mediated by enhanced incretin secretion and islet function, and occurs independent of caloric restriction, whereas the sustained improvement in glucose control is associated with increased insulin sensitivity. However, studies in humans with bariatric surgery suggest that these elevations are not static but undergo coordinated regulation throughout the postoperative time course. The studies described here test the hypothesis that incretin secretion, islet function, and peripheral insulin sensitivity undergo temporal regulation following bariatric surgery as a means to regulate glucose homeostasis. Methods Incretin secretion, islet function, and insulin sensitivity in mice with vertical sleeve gastrectomy (VSG) were compared to sham-operated controls that were pair-fed for 90d, matching food consumption and body-weight between groups. Results Glucose clearance and insulin secretion were enhanced in VSG mice compared to controls during mixed-meal tolerance tests (MMTT) at 12 and 80 days postoperatively, as were prandial GLP-1, GIP, and glucagon levels. Insulin sensitivity was comparable between groups 14d after surgery, but significantly greater in the VSG group at day 75, despite similar body-weight gain between groups. Glucose stimulated insulin secretion was greater in VSG mice compared to controls in vivo (I.P. glucose injection) and ex vivo (islet perifusion) indicating a rapid and sustained enhancement of β-cell function after surgery. Notably, glycemia following a MMTT was progressively higher over time in the control animals but improved in the VSG mice at 80d despite weight regain. However, meal-stimulated incretin secretion decreased in VSG mice from 10 to 80 days postoperative, as did meal-stimulated and I.P. glucose-stimulated insulin secretion. This occurred over the same time period that insulin sensitivity was enhanced in VSG mice, suggesting postoperative islet output is tightly regulated by insulin demand. Conclusions These data demonstrate a dynamic, multifactorial physiology for improved glucose control after VSG, whereby rapidly elevated insulin secretion is complimented by later enhancements in insulin sensitivity. Critically, the glucose lowering effect of VSG is demonstrably larger than that of caloric-restriction, suggesting these adaptations are mediated by surgical modification of gastrointestinal anatomy and not weight-loss per se., Highlights • β-cell glucose sensitivity is enhanced 90d after VSG compared to controls, coincident with improved glucose tolerance. • Prandial GLP-1 and GIP are elevated 12d following VSG but return to preoperative levels 80d after VSG. • Insulin sensitivity is enhanced 75d after surgery, but not 14d after surgery, in mice with VSG compared to controls. • Mixed-meal glucose control is improved from 12d to 80d in VSG mice, but worsens in controls despite similar body-weight.

Black rockfish (Sebastes schlegelii) is a teleost species where eggs are fertilized internally and retained in the maternal reproductive system, where they undergo development until live birth (termed viviparity). In the present study, we report a chromosome-level black rockfish genome assembly. High-throughput transcriptome analysis (RNA-seq and ATAC-seq), coupled with in situ hybridization (ISH) and immunofluorescence, identify several candidate genes for maternal preparation, sperm storage and release, and hatching. We propose that zona pellucida (ZP) genes retain sperm at the oocyte envelope, while genes in two distinct astacin metalloproteinase subfamilies serve to release sperm from the ZP and free the embryo from chorion at pre-hatching stage. Finally, we present a model of black rockfish reproduction, and propose that the rockfish ovarian wall has a similar function to uterus of mammals. Taken together, these genomic data reveal unprecedented insights into the evolution of an unusual teleost life history strategy, and provide a sound foundation for studying viviparity in non-mammalian vertebrates and an invaluable resource for rockfish ecology and evolution research.

Exogenous ghrelin reduces glucose-stimulated insulin secretion and endogenous ghrelin protects against hypoglycemia during starvation. Islet ε-cells produce ghrelin and δ-cells express growth hormone secretagogue receptor (GHSR), suggesting the possibility of a paracrine mechanism for islet ghrelin to reach high local concentrations and affect insulin secretion. GHSR has high constitutive activity and may act independently of ghrelin. The objective in this study was to determine whether an intraislet ghrelin-GHSR axis modulates insulin secretion and glucose metabolism using mouse models lacking ghrelin (Ghrl−/−) or GHSR (Ghsr−/−). Ghsr−/− and Ghsr+/+ mice had comparable islet ghrelin concentrations. Exogenous ghrelin decreased insulin secretion in perifused isolated islets in a GHSR-dependent manner. Islets isolated from Ghrl−/− or Ghsr−/− mice did not differ from controls in glucose-, alanine-, or GLP-1–stimulated insulin secretion during perifusion. Consistent with this finding, Ghrl−/− and Ghsr−/− male mice studied after either 6 or 16 h of fasting had blood glucose concentrations comparable with those of controls following intraperitoneal glucose, or insulin tolerance tests, or after mixed nutrient meals. Collectively, our data provide strong evidence against a paracrine ghrelin-GHSR axis mediating insulin secretion or glucose tolerance in lean, chow-fed adult mice.

P450c17, a key enzyme in the steroid generation pathway, plays an important role in the production of sex steroid and cortisol. In this study, two cyp17 gene isoforms, Pocyp17-I and Pocyp17-II were isolated from Paralichthys olivaceus gonads. Domain architecture analysis of Pocyp17-I and Pocyp17-II revealed that they had three regions important to enzymatic function. Structural analysis showed that Pocyp17-I and Pocyp17-II had 8 and 9 exons respectively, and the difference was caused by the insertion of an extra intron (intron1) in the latter. Quantitative real-time polymerase chain reaction results indicated that the expression of these two genes showed sexually dimorphism that Pocyp17-I and Pocyp17-II were highest expressed in testis and ovary, respectively. The in situ hybridization analysis of gonads indicated that Pocyp17-I and Pocyp17-II mRNA were both detected in oocytes, spermatocytes and Sertoli cells. After injection of androgen and estrogen (17α-methyltestosterone, 17β-estradiol) of different concentrations, the expression level of Pocyp17-I decreased significantly (P 0.01), whereas estrogen had no influence on Pocyp17-II, but androgen upregulated the expression of Pocyp17-II (P 0.05). Moreover, Pocyp17-I expression level was down-regulated significantly by NR0b1 but up-regulated by NR5a2 (P 0.05), whereas Pocyp17-II expression level was down-regulated significantly by NR0b1 and NR5a2 (P 0.05). All these results demonstrated that there were differences in expression patterns, feedback actions of sex hormones and transcriptional regulations between cyp17-I and cyp17-II, which revealed that cyp17-I and cyp17-II might perform different functions in sex hormones biosynthesis and gonadal differentiation in Japanese flounder.