Metabolic abnormalities constitute a significant characteristic of systemic lupus erythematosus (SLE). We utilised a two-sample Mendelian randomisation (MR) study to evaluate the potential causal ...association between 486 blood metabolites and SLE. Exposure data at the metabolite level were extracted from 7824 European Genome-wide association studies (GWAS). Preliminary analysis utilised SLE GWAS data from FinnGen. The primary method for causal analysis relied on random inverse variance weighting (IVW). To ensure robustness, sensitivity analyses included the Cochran Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. Steiger testing and linkage disequilibrium score regression were employed to validate the identified metabolites. This study identified 12 metabolites, comprising six known chemical structures: 1,5-anhydroglucitol(1,5-AG) odds ratio (OR) = 0.100, 95% confidence interval (CI): 0.015-0.773, P = 0.027), gamma-glutamylthreonine (OR = 0.077, 95% CI: 0.010-0.574, P = 0.012), 5-dodecenoate(12:1n7) (OR = 0.205, 95% CI: 0.061-0.685, P = 0.010), linoleoylglycerophosphoethanolamine * (OR = 0.159, 95% CI: 0.027-0.933, P = 0.044), erythrose (OR = 88.331,95% CI:1.098-63.214, P = 0.040) and 1-, adrenate (22:4n6) (OR = 9.876, 95% CI: 1.753-55.639, P = 0.001). Additionally, we found associations between SLE and six unknown chemical structures: X-06351 (OR = 0.071, 95% CI: 0.006-0.817, P = 0.034), X-10810 (OR = 4.268 95% CI: 1.260-14.459, P = 0.020), X-11412 (OR = 5.418 95% CI: 1.068-27.487, P = 0.041), X-11905 (OR = 0.551, 95%CI: 0.304-0.997, P = 0.049), X-12038 (OR = 0.178 95%CI: 0.032-0.988, P = 0.045), X-12217 (OR = 0.174 95%CI: 0.044-0.680, P = 0.014). This study offers evidence supporting a causal relationship between SLE and 12 circulating metabolites, six of which have known chemical structures and six that remain unidentified. These findings introduce a new perspective for further exploration of SLE mechanisms.
T cells, as a major lymphocyte population involved in the adaptive immune response, play an important immunomodulatory role in the early stages of autoimmune diseases. Autophagy is a cellular ...catabolism mediated by lysosomes. Autophagy maintains cell homeostasis by recycling degraded cytoplasmic components and damaged organelles. Autophagy has a protective effect on cells and plays an important role in regulating T cell development, activation, proliferation and differentiation. Autophagy mediates the participation of T cells in the acquired immune response and plays a key role in antigen processing as well as in the maintenance of T cell homeostasis. In autoimmune diseases, dysregulated autophagy of T cells largely influences the pathological changes. Therefore, it is of great significance to study how T cells play a role in the immune mechanism of autoimmune diseases through autophagy pathway to guide the clinical treatment of diseases.
A controlled decoherence environment is studied experimentally by free electron interaction with semiconducting and metallic plates. The results are compared with physical models based on decoherence ...theory to investigate the quantum-classical transition. The experiment is consistent with decoherence theory and rules out established Coulomb interaction models in favor of plasmonic excitation models. In contrast to previous decoherence experiments, the present experiment is sensitive to the onset of decoherence.
The timing of uplift of the Tibetan Plateau remains controversial, with estimates varying from Eocene to more recent than Pliocene. In particular, the paleoaltimetry of the Qiangtang terrane, on the ...central Tibetan Plateau, is completely unknown. Here, we present new stable isotope results of fluvial/lacustrine carbonate cement, pedogenic carbonate and marl from the Kangtuo and Suonahu formations deposited between ∼51 and ∼28Ma in the Heihuling–Bamaoqiongzong area of the northern Qiangtang terrane. The lithofacies associations indicate that the Kangtuo formation was deposited in alluvial fan and fluvial floodplain environments, and the Suonahu formation was deposited in near shore lacustrine, playa-lake and channelized fluvial environments. Carbon and oxygen isotope values, coupled with the sedimentary facies interpretations, point to evaporation and low respiration rates in the Eocene–Oligocene paleosols, suggesting an arid climate in the high Qiangtang area at the time. The δ18Opsw values of paleo-surface water reconstructed from the lowest (i.e. the least evaporated) δ18Oc (PDB) values of the unaltered authigenic carbonates are used to make the minimum estimates of the average paleoelevation of the drainage basin. The paleoelevation of the northern Qiangtang terrane is reconstructed as above 5000m by at least the middle Oligocene (28Ma), similar to the present elevation in this area. The aridity and the positive shift in oxygen isotope values of surface waters in our study area may suggest that the high Lhasa terrane established by the middle Oligocene blocked the northward transport of tropical moisture. Maintenance of high elevation (>5000m) from at least the Oligocene to the present suggests that the Qiangtang crust was already thickened by that time, and that underthrusting of India beneath Asia since then has continued to provide additional material while at the same time driving Asian lower crust eastward by crustal flow.
► Paleoelevation attained above 5000m of Qiangtang by at least before 28Ma. ► Paleoenvironment was dry in Qiangtang during Paleogene. ► Elevation maintained is balanced by northward underthrusting of Indian lithosphere.
Whether the circulating levels of pentraxin 3 (PTX3), an acute phase reactant (APR), are higher in active Takayasu arteritis (TAK), and if so, whether PTX3 is more accurate than C-reactive protein ...(CRP) in TAK activity assessment has been investigated in this study.
Research works such as PubMed, Embase, ScienceDirect, Cochrane Library, and two Chinese literature databases (CNKI and WanFang) were searched for studies conducted till August 30th, 2019. Two investigators searched the studies independently, who evaluated the quality of the study using the Newcastle-Ottawa scale (NOS) and extracted data. Pooled standard mean difference (SMD) and diagnostic indexes, with a 95% confidence interval (CI), were calculated using a random-effect model.
Totally, 8 studies involving 473 TAK (208 active and 265 inactive TAK) patients and 252 healthy controls were eventually included in the meta-analysis. PTX3 level in the blood in active TAK patients were found to be higher than that in dormant TAK with pooled SMD of 0.761 (95% CI = 0.38-1.14, p<0.0001; I2 = 68%, p of Q test = 0.003). And there was no publication bias. Among the 8 studies, 5 studies identified active TAK with both PTX3 and CRP. The pooled sensitivity, specificity, and AUC values of PTX3 in active TAK diagnosis were higher than those of CRP (0.78 95% CI = 0.65-0.87 vs. 0.66 95% CI = 0.53-0.77, p = 0.012; 0.85 95% CI = 0.77-0.90 vs. 0.77 95% CI = 0.56-0.90, p = 0.033; 0.88 95% CI = 0.85-0.90 vs. 0.75 95% CI = 0.71-0.79, p < 0.0001). It showed potential publication bias using Egger's test (p of PTX3 = 0.031 and p of CRP = 0.047).
PTX3 might be better than CRP in the assessment of TAK activity. Yet, it should be cautious before clinical use for moderate heterogeneity and potential publication bias of the meta-analysis.
With great interest, we have read the recent article "The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis" by Yu et al. While we have a great ...appreciation for the work conducted by the authors there are some methodological issues need to be considered. First, the period of articles included in the study, almost before 2013, implied that most follow-up days in these articles were earlier than the established date of a unified definition of IgG4-RD, 2011. Thus, it may lead to misclassification bias in the study. Second, IgG4-RD is a fibrous-inflammatory process that often involves multiple organs; however, malignant tumors related to IgG4-RD proposed in the study were only confined to four diseases. Therefore, we suggest adding subgroup analysis for more malignancies depending on the prevalence of IgG4-RD involved organs to ensure better clinical practice. Third, the causation between IgG4-RD and malignancy remains obscure currently. The time course for development in different malignancies varies significantly so that we cannot infer that malignancies discovered after IgG4-RD are directly relevant. With problems mentioned above, we recommend solutions to make this article more convincing.
Despite being the second most common tumor in men worldwide, the tumor metabolism-associated mechanisms of prostate cancer (PCa) remain unclear. Herein, this study aimed to investigate the ...metabolism-associated characteristics of PCa and to develop a metabolism-associated prognostic risk model for patients with PCa.
The activity levels of PCa metabolic pathways were determined using mRNA expression profiling of The Cancer Genome Atlas Prostate Adenocarcinoma cohort
single-sample gene set enrichment analysis (ssGSEA). The analyzed samples were divided into three subtypes based on the partitioning around medication algorithm. Tumor characteristics of the subsets were then investigated using t-distributed stochastic neighbor embedding (t-SNE) analysis, differential analysis, Kaplan-Meier survival analysis, and GSEA. Finally, we developed and validated a metabolism-associated prognostic risk model using weighted gene co-expression network analysis, univariate Cox analysis, least absolute shrinkage and selection operator, and multivariate Cox analysis. Other cohorts (GSE54460, GSE70768, genotype-tissue expression, and International Cancer Genome Consortium) were utilized for external validation. Drug sensibility analysis was performed on Genomics of Drug Sensitivity in Cancer and GSE78220 datasets. In total, 1,039 samples and six cell lines were concluded in our work.
Three metabolism-associated clusters with significantly different characteristics in disease-free survival (DFS), clinical stage, stemness index, tumor microenvironment including stromal and immune cells, DNA mutation (
and
), copy number variation, and microsatellite instability were identified in PCa. Eighty-four of the metabolism-associated module genes were narrowed to a six-gene signature associated with DFS,
,
,
,
,
, and
(p <0.05). A risk model was developed, and external validation revealed the strong robustness our risk model possessed in diagnosis and prognosis as well as the association with the cancer feature of drug sensitivity.
The identified metabolism-associated subtypes reflected the pathogenesis, essential features, and heterogeneity of PCa tumors. Our metabolism-associated risk model may provide clinicians with predictive values for diagnosis, prognosis, and treatment guidance in patients with PCa.
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•Microbial C-, N-requirement coexists, P-requirement occurs with sufficient organic matter.•As N-, P-requirements enhanced, microbial community diversity declined but robustness ...increased.•Bacteria are more sensitive to nutrient restriction than fungi.•The antagonism between microbial dominant and sub-dominant taxa improves nutrient acquisition.
Various nutrient requirements of soil microorganisms often occur in restoration ecosystems, but the responses of microbial communities in different vegetation types remain unclear. In this study, we selected four types of vegetation (grassland desert (GD), desert steppe (DS), typical steppe (TS), and artificial forest (AF)) on the Mu Us Desert, and examined the soil physicochemical properties, extracellular enzyme activities (carbon (C)-, nitrogen (N)-, and phosphorus (P)-acquisition enzymes), and community characteristics. Our results revealed that the N-requirement of microorganisms in the area was higher than that of other elements, particularly when organic C was scarce, whereas severe P requirement was detected in the presence of abundant organic matter. Compared with TS, we detected a higher diversity of microorganisms in GD, DS, and AF, and the microbial communities were dominated by a few taxa with loose internal connections and higher C and N requirements. Stronger N and P requirements reduced the diversity of microorganisms and the relative abundance of dominant taxa in TS, but increased the stability of bacterial communities. Our results further indicate that bacteria play a more active role in coping with the transformation of nutrient requirements. When C- and N-requirements of microorganisms were transformed to N and P, the abundance of dominant and sub-dominant taxa decreased and increased, respectively. Collectively, the results of this study indicate that efficient vegetation restoration in desert areas may lead to stronger nutrient requirements for microorganisms, thus reducing the diversity of microorganisms and causing unpredictable consequences for ecological sustainable development.
In Western Himalayan Syntaxis, the India‐Asia continental collision occurred at ca. 50 Ma, while its uplift history and exhumation mechanism are still in dispute despite decades of studies. A new ...type of eclogite was found in Naran, located ca. 30 km southwest of the Upper Kaghan Valley. Phase equilibrium calculations and thermobarometer performed on the Naran eclogite documented the peak‐P metamorphic condition of 720–780°C at 2.4–2.8 GPa. Two further exhumation stages were identified with the first one at high‐P granulite‐facies conditions of 750–800°C at 1.6–1.9 GPa, and the second at amphibolite‐facies conditions of 550–630°C at 0.5–0.8 GPa. SIMS U‐Pb dating of metamorphic zircons yielded an age of 46 ± 2 Ma, which is interpreted to constrain the high‐P metamorphism age along the northwestern margin of the Indian plate. SIMS U‐Pb dating of rutile yielded a cooling age of 26 ± 3 Ma, which is interpreted as cooling age in the amphibolite facies. The average speculated exhumation rate of the Naran massif (∼3 mm a−1) was much lower than that recovered from the Upper Kaghan Valley massif (86–143 mm a−1). The tectonic and metamorphic evolution of the whole Western Himalayan Syntaxis shows the difference in temporal and spatial change within the Paleogene era, indicating the inconsistent exhumation histories of the continental slices. Such a multi‐slice exhumation process was probably related to the closure of the Neo‐Tethys ocean and the break‐off of the Indian lithospheric slab.
Key Points
Naran eclogite underwent peak metamorphism at ca. 46 Ma with PT conditions of 710–770°C, 2.2–2.8 GPa
U‐Pb dating of rutile indicated cooling age of ca. 26 Ma with PT conditions of 580–630°C and 0.6–0.8 GPa
Naran eclogite represents a new type of HP rock sequence with a much lower exhumation rate (3 mm a−1) than Kaghan eclogite (30–143 mm mm a−1)
Lithium (Li) has grown to be a strategic key metal due to the enormous demand for the development of new energy industries over the world. As one of the most significant sources of Li resources, ...pegmatite-type Li deposits hold a large share of the mining market. In recent years, several large and super-large spodumene (Spd)-rich pegmatite deposits have been discovered successively in the Hoh-Xil–Songpan-Garzê (HXSG) orogenic belt of the northern Tibetan Plateau, indicative of the great Li prospecting potential of this belt. Hyperspectral remote sensing (HRS), as a rapidly developing exploration technology, is especially sensitive to the identification of alteration minerals, and has made important breakthroughs in porphyry copper deposit exploration. However, due to the small width of the pegmatite dykes and the lack of typical alteration zones, the ability of HRS in the exploration of Li-rich pegmatite deposits remains to be explored. In this study, Li-rich pegmatite anomalies were directly extracted from ZY1-02D hyperspectral imagery in the Zhawulong (ZWL) area of western Sichuan, China, using target detection techniques including Adaptive Cosine Estimator (ACE), Constrained Energy Minimization (CEM), Spectral Angle Mapper (SAM), and SAM with BandMax (SAMBM). Further, the Li-rich anomalies were superimposed with the distribution of pegmatite dykes delineated based on GF-2 high-resolution imagery. Our final results accurately identified the known range of Spd pegmatite dykes and further predicted two new exploration target areas. The approaches used in this study could be easily extended to other potential mineralization areas to discover new rare metal pegmatite deposits on the Tibetan Plateau.
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