Objective
Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in‐depth understanding of the contribution of gut ...microbiota to the immunopathogenesis of SLE.
Methods
Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole‐genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single‐nucleotide polymorphism–based strain‐level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides.
Results
Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA‐442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE‐enriched species.
Conclusion
This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen‐mimicking peptides. Our data demonstrate that microbiome‐altering approaches may offer valuable adjuvant therapies in SLE.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Despite the improved survival rate among systemic lupus erythematosus (SLE) patients, there are many factors associated with the mortality of SLE. In the current study, death-related factors of ...patients associated with course of disease were surveyed. Retrospective study was used. Mortalities among these three groups (group A, B and C, the course of disease was ≤5 years, 5–10 years and >10 years, respectively) were calculated and compared. Various factors related to mortality were analyzed. Male SLE patients died relatively more than female patients. The total mortality was 8.5 %. The mortalities were significant difference in group A, B and C which were 9.4, 4.8 and 8.9 %, respectively. The mortalities of group A and group C were significantly higher than that of group B, but there was no significant difference between mortalities of group A and group C. The most common death-related factor was infection, followed by involved disorders in renal, brain, multisystem, heart, etc. The mortalities resulted from neuropsychiatric systemic lupus erythematosus (NPSLE), pulmonary infection, involved digestive system and hematological system were significantly different between three groups. There was no difference between mortalities of group A and group C associated with pulmonary infection and NPSLE. Patients in group C died more than in group A from involved renal, heart, multisystem, etc, while group A had more patients than group C who died of pulmonary infection, involved hematological system. In conclusion, Male SLE patients have worse outcome than female patients. Infection and active SLE are not only contributors to the death of early stage patients, but also to that of later stage patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Multiprotein bridge factor 2 （MBF2） gene was first identified as a coactivator involved in BmFTZ-F 1-mediated activation of the Fushi tarazu gene. Herein, nine homologous genes of MBF2 gene are ...identified. Evolutionary analysis showed that this gene family is insect-specific and that the family members are closely related to response to pathogens （REPAT） genes. Tissue distribution analysis revealed that these genes could be expressed in a tissue-specific manner. Developmental profiles analysis showed that the MBF2 gene family members were highly expressed in the different stages. Analysis of the expression patterns of nine MBF2 family genes showed that Bacillus bombysepticus treatment induced the up-regulation of several MBF2 family genes, including MBF2-4, -7, -9, -8. Furthermore, we found the MBF2 family genes were modulated by starvation and the expression of these genes recovered upon re-feeding, except for MBF2-5, -9. These findings suggested roles for these proteins in insect defense against pathogens and nutrient metabolism, which has an important guiding significance for designing pest control strategies.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background: This study reports a 10-year retrospective analysis of multiple trauma complicated by pulmonary contusion. The purpose of this study is to ascertain the risk factors for mortality due to ...trauma in patients with pulmonary contusion, the impact of various treatment options for prognosis, and the risk factors for concurrent Acute Respiratory Distress Syndrome(ARDS). Methods: We retrospectively analyzed 252 trauma patients with lung contusion admitted to the General Hospital of Guangzhou Military Command from January 2000 to June 2011 by using the statistical processing system SPSS 17.0 for Windows. Results: We included 252 patients in our study, including 214 males and 38 females. The average age was 37.1±14.9 years. There were 110 cases admitted to the ICU, of which 26 cases with ARDS. Nine of the 252 patients died. We compared those who survived with those who died by gender and age, the difference was not statistically significant(P=0.199, P=0.200). Separate univariate analysis of those who died and those who survived found that shock on admission(P=0.000), coagulation disorders(P=0.000), gastrointestinal bleeding(P=0.02), the need for emergency surgery on admission(P=0.000), pre-hospital intubation(P=0.000), blood transfusion within 24 hours(P=0.006), the use of mechanical ventilation(P=0.000), and concurrent ARDS(P=0.000) are poor prognosis risk factors. Further logistic analysis, including the admission GCS score(OR=0.708, 95%CI 0.516-0.971, P=0.032), ISS score(OR 1.135, 95%CI 1.006-1.280, P=0.039), and concurrent ARDS(OR=15.814, 95%CI 1.819-137.480, P=0.012), identified the GCS score, ISS score and concurrent ARDS as independent risk factors of poor prognosis. Shock(OR=9.121, 95%CI 0.857-97.060, P=0.067) was also related to poor prognosis. Patients with injury factors such as road accident, falling injury, blunt injury and crush injury, et al.(P=0.039), infection(P=0.005), shock(P=0.004), coagulation disorders(P=0.006), emergency surgery(P=0.01), pre-hospital intubation(P=0.000), chest tube insertion(P=0.004), blood transfusion(P=0.000), usage of hormones(P=0.002), phlegm(P=0.000), ventilation(P=0.000) were at a significantly increased risk for ARDS complications. Conclusions: Those patients with multiple trauma and pulmonary contusion admitted to the hospital with shock, coagulopathy, a need for emergency surgery, pre-hospital intubation, and a need for mechanical ventilation could have a significantly increased risk of mortality and ARDS incidence. A risk for poor prognosis was associated with gastrointestinal bleeding. A high ISS score, high APACHE Ⅱ, and low GCS score were independent risk factors for poor prognosis. If patients developed an infection or were given drainage, hormones, and phlegm treatment, they were at higher risk of ARDS. Pre-hospital intubation and drainage were independent risk factors for ARDS. In patients with ARDS, the ICU stay, total length of stay, and hospital costs might increase significantly. A GCS score<5.5, APACHE Ⅱ score>16.5, and ISS score>20.5 could be considered indicators of poor prognosis for patients with multiple trauma and lung contusion.
The mountainous hydrological process usually shows high variation to climate change and human action. In the Longitudinal Range-Gorge Region（LRGR）, Southwestern China and Southeast Asian, the ...transboundary runoff variations are much more sensitive and complex under the interaction of climate change, ＂corridor-barrier＂ functions in LRGR,and dams building. In this paper, based on the long hydrological records（1956-2013） from three mainstream hydrological stations in Nu River,Lancang River, and Red River, the region runoff variations were analyzed. The results show out： i） the regional runoff changes were strongly influenced by the ＂Corridor-Barrier＂ functions in LRGR from west to east, the variability extent of annual runoff increased, but tended to decrease after 2009 and the reduced extents also increased; ii） the annual runoff change in the three rivers had high concentration degrees; iii） there were periodicities of 33 years of runoff change in Nu River and Lancang River, and 30 years in Red River, and the lower flow period would continue for 8-9 years in Nu River and Lancang River but only for 4 years in Red River; iv） since 2010, as the two mega dams of Xiaowan and Nuozhadu built in Lancang River mainstream, their variations of annual runoff were quite different. The research results could offer a scientific base for sustainable utilization,conservation, and management of the regional water resources
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced ...by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC→BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.
Abstract
Orientation estimation is an important task in three-dimensional cryo-EM image reconstruction. By applying the common line method, the orientation estimation task can be formulated as a ...least squares (LS) problem or a least un-squared deviation (LUD) problem with orthogonality constraint. However, the non-convexity of the orthogonality constraint introduces numerical difficulties to the orientation estimation. The conventional approach is to reformulate the orthogonality constrained minimization problem into a semi-definite programming problem using convex relaxation strategies. In this paper, we consider a direct way to solve the constrained minimization problem without relaxation. We focus on the weighted LS problem because the LUD problem can be reformulated into a sequence of weighted LS problems using the iteratively re-weighted LS approach. As a classical approach, the projected gradient descent (PGD) method has been successfully applied to solve the convex constrained minimization problem. We apply the PGD method to the minimization problem with orthogonality constraint and show that the constraint set is a generalized prox-regular set, and it satisfies the norm compatibility condition. We also demonstrate that the objective function of the minimization problem satisfies the restricted strong convexity and the restricted strong smoothness over a constraint set. Therefore, the sequence generated by the PGD method converges when the initial conditions are satisfied. Experimental results show that the PGD method significantly outperforms the semi-definite relaxation methods from a computation standpoint, and the mean square error is almost the same or smaller.
In this paper, we consider decomposing an image into its cartoon and texture components. Traditional methods, which mainly rely on the gradient amplitude of images to distinguish between these ...components, often show limitations in decomposing small-scale, high-contrast texture patterns and large-scale, low-contrast structural components. Specifically, these methods tend to decompose the former to the cartoon image and the latter to the texture image, neglecting the scale features inherent in both components. To overcome these challenges, we introduce a new variational model which incorporates an Formula Omitted-based total variation norm for the cartoon component and an Formula Omitted norm for the scale space representation of the texture component. We show that the texture component has a small Formula Omitted norm in the scale space representation. We apply a quadratic penalty function to handle the non-separable Formula Omitted norm minimization problem. Numerical experiments are given to illustrate the efficiency and effectiveness of our approach.
Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABAA receptors (GABAARs). GABAARs ...consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, d-subunit-containing GABAARs GABAA(d)Rs, had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABAAR family. First, the fear extinction in individual mice was positively correlated with the level of GABAA(d)R expression and function in their mPFC. Second, knockdown of GABAA(d)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABAA(d)R-deficient mice also showed fear extinction deficits, and re-expressing GABAA(d)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABAA(d)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABAA(d)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABAA receptors in fear extinction through a route relying on nonsynaptic plasticity.
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