Abstract
Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of ...the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.
Background: Several studies have reported that mindfulness meditation has a potential effect in controlling headaches, such as migraine and tension-type headache; however, its role remains ...controversial. This review assessed the evidence regarding the effects of mindfulness meditation for primary headache pain.
Methods: Only English databases (PubMed, Cochrane Central Register of Controlled Trials the Cochrane Library, PsycINFO, Psychology and behavioral science collection, PsyArticles, Web of Science, and Scopus) were searched from their inception to November 2016 with the keywords ("meditation" or "mindfulness" or "vipassana" or "dzogchen" or "zen" or "integrative body-mind training" or "IBMT" or "mindfulness-based stress reduction" or "MBSR" or "mindfulness-based cognitive therapy" or "MBCT" and "Headache" or "Head pain" or "Cephalodynia" or "Cephalalgia" or "Hemicrania" or "Migraine"). Titles, abstracts, and full-text articles were screened against study inclusion criteria: controlled trials of structured meditation programs for adult patients with primary headache pain. The quality of studies included in the meta-analysis was assessed with the Yates Quality Rating Scale. The meta-analysis was conducted with Revman 5.3.
Results: Ten randomized controlled trials and one controlled clinical trial with a combined study population of 315 patients were included in the study. When compared to control group data, mindfulness meditation induced significant improvement in pain intensity (standardized mean difference, −0.89; 95% confidence interval, −1.63 to −0.15; P = 0.02) and headache frequency (−0.67; −1.24 to −0.10; P = 0.02). In a subgroup analysis of different meditation forms, mindfulness-based stress reduction displayed a significant positive influence on pain intensity (P < 0.000). Moreover, 8-week intervention had a significant positive effect (P < 0.000).
Conclusions: Mindfulness meditation may reduce pain intensity and is a promising treatment option for patients. Clinicians may consider mindfulness meditation as a viable complementary and alternative medical option for primary headache.
Background
Pulmonary arterial hypertension (PAH) is characterized by the apoptosis resistance and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Its pathogenesis has not been ...revealed. Here, we carried out experiments to investigate the functions of miR‐140‐5p and tumor necrosis factor‐α (TNF‐α).
Methods
We selected GSE703 from Gene Expression Omnibus (GEO) Database to conduct microarray analysis using R software and Gene Set Enrichment Analysis (GSEA). Combing bioinformatics results, the upregulation of miR‐140‐5p inhibited PAH progression through targeting TNF‐α. RNA expression was measured by quantitative real‐time polymerase chain reaction (RT‐qPCR) and protein level was measured by western blot analysis and enzyme‐linked immunosorbent assays (ELISA). We conducted monocrotaline (MCT) injection to rats to form PAH animal models. The lung tissues were observed by hematoxylin–eosin (HE) staining and Sirius red‐picric acid staining. Right ventricular systolic pressure (RVSP) and the ratio of right ventricle (RV)‐to‐left ventricle (LV) plus septum (S) weight (RV/LV + S) were measured in MCT‐induced animal models. Overexpression of miR‐140‐5p and TNF‐α were utilized to research the proliferation, migration, and phenotypic variation of hypoxia‐mediated PASMCs. The binding between miR‐140‐5p and TNF‐α 3′‐untranslated region (3′‐UTR) was confirmed via luciferase reporter assay.
Results
Downregulation of miR‐140‐5p and upregulation of TNF‐α were observed in PAH rat model and hypoxia‐mediated PASMCs. And we proved that overexpression of miR‐140‐5p could suppress the proliferation, migration, and phenotypic variation of PASMCs, therefore inhibiting PAH pathogenesis. Luciferase assay verified that miR‐140‐5p targeted TNF‐α directly. A converse correlation was also shown between miR‐140‐5p and TNF‐α in PASMCs.
Conclusions
miR‐140‐5p and TNF‐α are important regulators in PAH pathology and may serve as a therapeutic target for PAH.
miR‐140‐5p might inhibit the occurrence and development of pulmonary arterial hypertension (PAH) by repressing tumor necrosis factor‐α (TNF‐α) expression via the TNF signaling pathway. These findings may help in the search of promising strategies for achieving better treatment outcome in patients diagnosed with PAH.
B cells consistently represent abundant cellular components in tumors; however, direct evidence supporting a role for B cells in the immunopathogenesis of human cancers is lacking, as is specific ...knowledge of their trafficking mechanisms. Here, we demonstrate that chemokine (C‐X‐C motif) receptor 3–positive (CXCR3+) B cells constitute approximately 45% of B‐cell infiltrate in human hepatocellular carcinoma (HCC) and that their levels are positively correlated with early recurrence of HCC. These cells selectively accumulate at the invading edge of HCC and undergo further somatic hypermutation and immunoglobulin G–secreting plasma cell differentiation. Proinflammatory interleukin‐17+ cells are important for the induction of epithelial cell–derived CXCR3 ligands CXCL9, CXCL10, and CXCL11, which subsequently promote the sequential recruitment and further maturation of CXCR3+ B cells. More importantly, we provide evidence that CXCR3+ B cells, but not their CXCR3– counterparts, may operate in immunoglobulin G–dependent pathways to induce M2b macrophage polarization in human HCC. Depletion of B cells significantly suppresses M2b polarization and the protumorigenic activity of tumor‐associated macrophages and restores the production of antitumorigenic interleukin‐12 by those cells in vivo. Conclusion: Selective recruitment of CXCR3+ B cells bridges proinflammatory interleukin‐17 response and protumorigenic macrophage polarization in the tumor milieu, and blocking CXCR3+ B‐cell migration or function may help defeat HCC.(Hepatology 2015;62:1779–1790)
Objectives:
Autism spectrum disorder (ASD) is a juvenile onset neurodevelopmental disorder with social impairment and stereotyped behavior as the main symptoms. Unaffected relatives may also exhibit ...similar ASD features due to genetic factors. Although previous studies have demonstrated atypical brain morphological features as well as task-state brain function abnormalities in unaffected parents with ASD children, it remains unclear the pattern of brain function in the resting state.
Methods:
A total of 42 unaffected parents of ASD children (pASD) and 39 age-, sex-, and handedness-matched controls were enrolled. Multiple resting-state fMRI (rsfMRI) analyzing methods were applied, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC), to reveal the functional abnormalities of unaffected parents in ASD-related brain regions. Spearman Rho correlation analysis between imaging metric values and the severity of ASD traits were evaluated as well.
Results:
ALFF, ReHo, and DC methods all revealed abnormal brain regions in the pASD group, such as the left medial orbitofrontal cortex (mOFC) and rectal gyrus (ROI-1), bilateral supplementary motor area (ROI-2), right caudate nucleus head and right amygdala/para-hippocampal gyrus (ROI-3). FC decreasing was observed between ROI-1 and right anterior cingulate cortex (ACC), ROI-2, and bilateral precuneus. FC enhancing was observed between ROI-3 and right anterior cerebellar lobe, left medial temporal gyrus, left superior temporal gyrus, left medial frontal gyrus, left precentral gyrus, right postcentral gyrus in pASD. In addition, ALFF values in ROI-1, DC values in ROI-3 were positively correlated with AQ scores in pASD (
ρ
1
= 0.298,
P
1
= 0.007;
ρ
2
= 0.220,
P
2
= 0.040), while FC values between ROI-1 and right ACC were negatively correlated with AQ scores (ρ
3
= −0.334,
P
3
= 0.002).
Conclusion:
rsfMRI metrics could be used as biomarkers to reveal the underlying neurobiological feature of ASD for unaffected parents.
B cells are prominent components of human solid tumours, but activation status and functions of these cells in human cancers remain elusive. Here we establish that over 50% B cells in hepatocellular ...carcinoma (HCC) exhibit an FcγRII
activated phenotype, and high infiltration of these cells positively correlates with cancer progression. Environmental semimature dendritic cells, but not macrophages, can operate in a CD95L-dependent pathway to generate FcγRII
activated B cells. Early activation of monocytes in cancer environments is critical for the generation of semimature dendritic cells and subsequent FcγRII
activated B cells. More importantly, the activated FcγRII
B cells from HCC tumours, but not the resting FcγRII
B cells, without external stimulation suppress autologous tumour-specific cytotoxic T-cell immunity via IL-10 signals. Collectively, generation of FcγRII
activated B cells may represent a mechanism by which the immune activation is linked to immune tolerance in the tumour milieu.
Characterization of the dynamic change in the immunological landscape during malignant transformation from precancerous lesions to cancerous lesions in squamous cell carcinoma (SCC) is critical for ...the application of immunotherapy. Here, we performed single-cell RNA-Seq (scRNA-Seq) of 131,702 cells from 13 cancerous tissues of oral squamous cell carcinoma (OSCC), 3 samples of precancerous oral leukoplakia, and 8 adjacent normal samples. We found that tumor-infiltrating CD4· and CD8· T cells were functionally inhibited by immunosuppressive ligands expressed on various types of myeloid cells or neutrophils in the process of oral carcinogenesis. Notably, we identified a subset of myofibroblasts that exclusively expressed tryptophan 2,3-dioxygenase (TDO2). These TDO2· myofibroblasts were located distally from tumor nests, and both CD4· and CD8· T cells were enriched around them. Functional experiments revealed that TDO2· myofibroblasts were more likely to possess the ability for chemotaxis toward T cells but induced the transformation of CD4· T cells into Tregs and caused CD8· T cell dysfunction. We further showed that use of the TDO2 inhibitor LM10 attenuated the inhibitory states of T cells, restored the T cell antitumor response, and prevented the progression of OSCC malignant transformation in murine models. Our study reveals a multistep transcriptomic landscape of OSCC and demonstrates that TDO2· myofibroblasts are potential targets for immunotherapy.
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•The cyclic deformation mechanisms are revealed at different temperatures.•Interfacial microstructure evolutions are obtained during cyclic loading.•Dislocation density tends to ...remain stable in the cyclic saturation stage.•Stress amplitude and hardening rate increase with increasing strain rate.
The fatigue performance and deformation mechanism of Ni-based single crystal superalloys under cyclic tension–compression loading are studied by molecular dynamics simulations. The effects of temperature and strain rate on the cyclic deformation of superalloys are discussed. The results show that there are three different cyclic deformation mechanisms at different temperature ranges. In the low temperature range, dislocations and stacking faults shearing γ' phase is the main deformation mechanism. In the high temperature range, Orowan bypassing and climbing mechanism dominates the deformation. While in the medium temperature range, the deformation mechanism gradually transforms from the dislocation and stacking faults shearing the γ' phase to the Orowan bypassing and climbing. The simulation results also reveal that the superalloys exhibit a cyclic saturation stage after the initial cyclic hardening. The cyclic saturation stage is a dynamic equilibrium of dislocation proliferation and annihilation, indicating that the superalloys have excellent fatigue mechanical properties. Moreover, the dislocation density and the proportion of stacking faults increase with increasing strain rate, resulting in faster cyclic stability and higher stress amplitude for the superalloys. These results provide important information for understanding the fatigue mechanisms of superalloys from an atomistic perspective.
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•Effects of plant C inputs on composition and properties of soil DOM were estimated.•Plant C was from either rhizodeposits or decomposition of different tissue ...litters.•Rhizodeposition and litter decomposition had significant effects on soil DOM.•Effects of rhizodeposition on soil DOM were significantly altered by salinity.•Effects of litter on soil DOM varied greatly among plant tissue types.
The dynamics of composition and properties of dissolved organic matter in soil depend on plant carbon inputs and microbial degradation. However, uncertainties remain regarding the relative contributions of different plant carbon inputs sources, i.e., from litter decomposition versus rhizodeposits, to soil dissolved organic matter, which may limit the understanding of soil carbon dynamics. In this study, effects of plant carbon inputs from either rhizodeposition or litter (leaf, stem, rhizome, and root litter) decomposition on composition and optical properties of soil dissolved organic matter were estimated. Rhizodeposition and litter decomposition of P. australis had significant effects on soil dissolved organic matter, and its variation was mainly associated with the third fluorescent component (C3). Effects of rhizodeposition on soil dissolved organic matter were significantly altered by soil salinity, exhibiting increased chromophoric dissolved organic matter and fulvic acid C3 under saline conditions. Effects of litter decomposition on soil chemistry and dissolved organic matter varied greatly among plant tissues. Compared with rhizome and root, leaf and stem decomposed more thoroughly and significantly increased the contents of fulvic acid C3. This was supported by increased aromaticity associated with leaf inputs and increased plant-derived dissolved organic matter associated with stem and leaf inputs. These findings highlight the significant influence of rhizodeposition and litter decomposition on soil dissolved organic matter, and suggest that the roles of salinization and plant tissue type merit consideration in further studies on plant–soil carbon cycling.
The hybrid water electrolysis affords a green route for the generation of fine chemicals accompanied with hydrogen production relying on the rapid development of anodic electrocatalysts. Herein, a ...nickel‐cobalt layered double hydroxide (NiCo LDH) modified nickel foam, prepared at room temperature via simple soaking processes, could effectively catalyze the dehydrogenation oxidation of primary amines to generate aromatic and aliphatic nitriles with good yields. Further expanding the application of the easily available electrode, the NiCo LDH electrode could function as the electron reservoir to realize the decoupled water electrolysis with 100% coulombic efficiency in the membrane-free electrolytic cell.
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•CoNi LDH grown on nickel foam was facilely synthesized via simple soaking processes.•CoNi LDH boosted primary amine electrooxidation coupled with hydrogen production.•Aromatic and aliphatic nitriles were generated over NiCo LDH anode with good yields.•Decoupled water electrolysis was achieved relying on NiCo LDH as electron reservoir.•Hydrogen production in the membrane-free cell reduced electrolytic equipment costs.
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