A Discussion on the Detachment Structural Deformation and Its Influence on Pore Structure Evolution in Shale on the Western of the Xuefeng Mountain, South China

Detachment structures occur widely in the crust, and it is the commonest and most important deformation type developed in the region between orogenic belts and basins. Organic-rich shale, as the weak layers, usually acts as slippery layers in detachment structural deformation systems. The “comb-like” and “tough-like” fold belts on the western side of the Xuefeng Mountain result from the multilayer detachment, and their formation is different from the typical Jura type structures. The reason is that there are several detachment layers and detachment systems in the stratigraphic column from the Neoproterozoic upwards to the Mesozoic in the study area. As the stress decoupling role, the shale slippery layers tend to undergo strong deformation in the detachment systems and impacted on pore structure evolution in the shale. In order to obtain the detachment structural deformation and its influence on pore structure evolution in shale on the Middle and Upper Yangtze, the structural and textural, geochemical and mineralogical properties analysis, porosity and pore structure feature investigations are performed using shale samples collected from the same shale bed of the Longmaxi Formations (Lower Silurian) of Western of the Xuefeng Mountain, South China

PKCε Activator Protects Hippocampal Microvascular Disruption and Memory Defect in 3×Tg-Alzheimer\u27s Disease Mice with Cerebral Microinfarcts

BACKGROUND: Current evidence suggests that microvessel disease is involved in Alzheimer\u27s disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs. METHODS: To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 months old were examined for confocal immunohistochemistry at a single cell or microvessel level in the hippocampal CA1 area, important for spatial memory storage, and in the dorsal hippocampus by western blots. RESULTS: In 3×Tg mice without cerebral microinfarcts, an accelerating age-related increase in (mild) oxidative stress and hypoxia inducible factor (HIF)-1α, but a reduction in VEGF, mitochondrial transcription factor A (TFAM), and MnSOD were associated with capillary loss. The change was less pronounced in arterioles. However, in 3×Tg mice with cerebral microinfarcts, increasing arteriolar diameter and their wall cells were related with the strong oxidative DNA damage 8-hydroxy-2\u27-deoxyguanosine (8-OHdG), apoptosis (cleaved caspase 3), and sustained hypoxia (increased HIF-1α and VEGF/PKCε/extracellular signal regulated kinase or ERK pathway). Microocclusion enhanced the loss of the synaptic marker spinophilin, astrocytic number, and astrocyte-vascular coupling areas and demyelination of axons. DCPLA-ME prevented spatial memory defect; strong oxidative stress-related apoptosis; sustained hypoxia (by reducing HIF-1α and VEGF); and exaggerated cell repair in arteriolar walls, pericapillary space dilation, neuro-glial-vascular disruption, and demyelination. CONCLUSION: In conclusion, in 3×Tg mice with cerebral microinfarcts, sustained hypoxia (increased HIF-1α and VEGF signals) is dominant with arteriolar wall thickening, and DCPLA has a protective effect on sustained hypoxia

Numerical analysis of an implicit fully discrete local discontinuous Galerkin method for the fractional Zakharov–Kuznetsov equation

In this paper we develop and analyze an implicit fully discrete local discontinuous Galerkin (LDG) finite element method for a time-fractional Zakharov–Kuznetsov equation. The method is based on a finite difference scheme in time and local discontinuous Galerkin methods in space. We show that our scheme is unconditional stable and L 2 error estimate for the linear case with the convergence rate  through analysis

Constraints for post-orogenic extension of the northern margin of the Qaidam Basin from the Late Silurian–Late Devonian igneous rocks in the Gahai–Nanshan area

Objective  The northern margin tectonic zone of the Qaidam Basin underwent a transition from oceanic subduction to continental subduction during the Early Paleozoic, resulting in the formation of the ultrahigh-pressure metamorphic zone known as the northern Qaidam tectonic zone (NQTZ). There has been a longstanding debate regarding the collapse time of the NQTZ. The Maoniushan Formation has long been regarded as a sign of the end of orogeny; however, recent studies show that the Maoniushan Formation has spanned a long time, and it is controversial when the orogenic belt began to collapse. This study aims to determine the age and genetic background of the Maoniushan Formation and to understand the tectonic transition process of the northern Qinghai–Tibet Plateau from the Proto-Tethys to the Paleo-Tethys.   Methods  Deep-earth samples, including volcanic and intrusive rocks, offer valuable insights into the activity of the crust during this period. In order to investigate the volcaniclastic rocks and granites in the Gahai–Nanshan area, located in the eastern section of the NQTZ, zircon LA–ICP–MS U–Pb chronology and Lu–Hf isotope methods were employed to explore the formation age of igneous rocks and the characteristics of source rocks.   Results  The zircon U–Pb chronology reveals that the volcaniclastic rocks of the Maoniushan Formation originated approximately 423 Ma. Furthermore, the intrusive granite was formed at 370 Ma, indicating that the volcanic eruption occurred during the Late Silurian, while the subsequent intrusion and crystallization of the granites occurred during the Late Devonian. The zircon Lu–Hf isotope data reveals that the εHf(t) values of the Late Silurian tuffs are concentrated within the range of –11.5 to –8.3, and the corresponding two-stage Hf model ages are primarily between 1945–2133 Ma. These results indicate that the volcanic rocks predominantly originated from partially melting ancient crustal materials. In contrast, the εHf(t) values of the Late Devonian intrusive granites exhibit a distribution within the range of 3.9–9.1, accompanied by two-stage Hf model ages primarily falling within the 792–1118 Ma range. The results suggest that the granites mainly resulted from partially melting Meso-Neoproterozoic crustal materials. Based on a comprehensive analysis of regional geological and petrological data, it is postulated that the Late Silurian–Early Devonian witnessed pronounced orogenesis resulting from continental deep subduction. This event led to substantial crustal thickening in the NQTZ, where the thickened crustal basement of the Oulongbruk experienced partial melting, ultimately giving rise to the volcanic rocks observed during this period. During the Late Devonian, delamination of the thickened crust facilitated the upwelling of the asthenosphere mantle, triggering regional crustal extension. The interaction between mantle material and crust results in the formation of granitic–volcanic rocks.   Conclusion  The Maoniushan Formation in the region encapsulates a significant period, making it unsuitable to represent the end of orogeny. Late Devonian igneous rocks indicate that the NQTZ entered a period of substantial crustal extension during this time. [ Significance ] The late Devonian igneous rocks of Maoniushan Formation regionally mark the end of orogeny and the beginning of the Paleo-Tethys tectonic domain

PKCε Activation Restores Loss of PKCε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, and Microvessels in Aged and Alzheimer\u27s Disease Hippocampus

Vascular endothelial dysfunction and capillary loss are currently considered to be a primary phenotype of normal human aging and Alzheimer\u27s disease (AD). Activation of protein kinase C (PKCε) improves several molecular, cellular, physiological, and behavioral endpoints, yet it is not known whether a loss of PKCε activity occurs in the microvascular endothelium in aged and AD hippocampi, whether this loss contributes to microvascular change, or whether activation of PKCε protects against microvascular damage, an early change that induces age-associated memory defect and AD. We investigated the effect of the PKCε activation on microvascular loss in the hippocampus, important for memory storage. In cultured human brain microvascular endothelial cells, tert-butyl hydroperoxide induced oxidative stress and a decrease in manganese superoxide dismutase (MnSOD) mRNA and protein expression that were blocked by the antioxidant drugs. The PKCε activators bryostatin and DCPLA methyl ester increased PKCε, associated with an increase in MnSOD mRNA and its protein as well as vascular endothelial growth factor (VEGF), which was inhibited by the mRNA-stabilizing HuR inhibitors. In rats (\u3e24 months old) and AD transgenic mice Tg2576 (5 months old), bryostatin or DCP-LA prevented a decrease in vascular PKCε, MnSOD, and VEGF and prevented microvascular loss and age-related memory impairment. An autopsy-confirmed AD hippocampus showed a decrease in PKCε and MnSOD mRNAs and their proteins and VEGF as well as in microvascular density compared to non-AD controls. In conclusion, the PKCε activation can rescue a decrease in PKCε, MnSOD, and VEGF via posttranscription regulation and alleviate oxidative stress, and in doing so, prevent microvascular loss during aging and AD

Geographically associated endophytic fungi contribute to the tropane alkaloids accumulation of Anisodus tanguticus

Anisodus tanguticus is a valuable plant for extracting tropane alkaloids. However, the mechanisms by which plant microbiome mediate the accumulation of tropane alkaloids in Anisodus tanguticus are still not well understood. In this study, we collected 55 wild Anisodus tanguticus populations on the Tibetan Plateau and the tropane alkaloids content, and root-related bacteria and fungi diversity were analyzed using HPLC and 16 s rDNA and ITS sequencing. The results showed that tropane alkaloids content has obvious geographical distribution characteristics. Anisodine content had a significant positive correlation with latitude, while anisodamine and atropine content had a significant negative correlation with latitude. Variation partition analysis (VPA) showed that root endophytes play a significant role in promoting tropane alkaloid production in Anisodus tanguticus roots. The root endophytes alone explained 14% of the variation, which was the largest contributor. Soil properties variables could independently explain 5% of the variation, and climate variables could explain 1% of the variation. Of these, endophytic fungi alone accounted for 11%, while bacteria explained only 5%. Random forests and Mantel test showed that different regionally enriched endophytic fungi have a greater impact on the accumulation of tropane alkaloids than the whole endophytic fungi. Richness and relative abundance of enriched endophytic fungi in Hengduan-Qilian Mountains (HQ) group has a significant positive correlation with anisodine content, while richness and relative abundance of enriched endophytic fungi in Himalayas-Hengduan Mountains (HH) group has a significant positive correlation with anisodamine and atropine content. And, these enriched endophytic fungi have high network connectivity and distributed in separate network modules. This study further confirmed that endophytes were closely related to tropane alkaloids accumulation in Anisodus tanguticus and contribute to promote sustainable development, cultivation, and precision medicine of Anisodus tanguticus

Comprehensive analyses for the coagulation and macrophage-related genes to reveal their joint roles in the prognosis and immunotherapy of lung adenocarcinoma patients

PurposeThis study aims to explore novel biomarkers related to the coagulation process and tumor-associated macrophage (TAM) infiltration in lung adenocarcinoma (LUAD).MethodsThe macrophage M2-related genes were obtained by Weighted Gene Co-expression Network Analysis (WGCNA) in bulk RNA-seq data, while the TAM marker genes were identified by analyzing the scRNA-seq data, and the coagulation-associated genes were obtained from MSigDB and KEGG databases. Survival analysis was performed for the intersectional genes. A risk score model was subsequently constructed based on the survival-related genes for prognosis prediction and validated in external datasets.ResultsIn total, 33 coagulation and macrophage-related (COMAR) genes were obtained, 19 of which were selected for the risk score model construction. Finally, 10 survival-associated genes (APOE, ARRB2, C1QB, F13A1, FCGR2A, FYN, ITGB2, MMP9, OLR1, and VSIG4) were involved in the COMAR risk score model. According to the risk score, patients were equally divided into low- and high-risk groups, and the prognosis of patients in the high-risk group was significantly worse than that in the low-risk group. The ROC curve indicated that the risk score model had high sensitivity and specificity, which was validated in multiple external datasets. Moreover, the model also had high efficacy in predicting the clinical outcomes of LUAD patients who received anti-PD-1/PD-L1 immunotherapy.ConclusionThe COMAR risk score model constructed in this study has excellent predictive value for the prognosis and immunotherapeutic clinical outcomes of patients with LUAD, which provides potential biomarkers for the treatment and prognostic prediction

Triassic magmatism in the eastern part of the South China Block: Geochronological and petrogenetic constraints from Indosinian granites

The granitic dykes in the Badu Group, Zhejiang Province, South China provide important insights on tectonic setting and crustal evolution of the South China Block (SCB) and the Indochina Block during Triassic. Here we report LA-ICP-MS U–Pb data of granitic rocks from the Hucun and Kengkou which show early Triassic ages of 242 ± 2 and 232 ± 3 Ma, respectively, representing their timing of emplacement. The dyke rocks are enriched in K, Al, LREE, Rb, Th, U, and Pb, and are depleted in Nb, Ta, Sr, and Ti. The rocks are characterized by highly fractionated REE patterns with (La/Yb)N ratios of 28.46–38.07 with strong negative Eu anomalies (Eu/Eu* = 0.65–0.73). In situ Hf isotopic analyses of zircons from the Hucun granite yielded ɛHf(t) values of −13.9 to −6.4 and two-stage depleted mantle Hf model ages of 1.68–2.15 Ga, which indicate that the magma was formed by partial melting of the Paleoproterozoic metasedimentary protoliths in the Cathaysia Block. The zircons from the Kengkou granite have ɛHf(t) values ranging from −40.7 to 31.5 and yield two-stage depleted mantle Hf model ages of 0.99–2.49 Ga, indicating magma origin from a mixed source. The Hucun and Kengkou dykes, together with the Triassic A-type granites in SE China were probably generated during magmatism associated with crust–mantle decoupling along the convergent plate boundary between SCB and the Indochina Block