Autophagy Inhibitor LRPPRC Suppresses Mitophagy through Interaction with Mitophagy Initiator Parkin

Autophagy plays an important role in tumorigenesis. Mitochondrion-associated protein LRPPRC interacts with MAP1S that interacts with LC3 and bridges autophagy components with microtubules and mitochondria to affect autophagy flux. Dysfunction of LRPPRC and MAP1S is associated with poor survival of ovarian cancer patients. Furthermore, elevated levels of LRPPRC predict shorter overall survival in patients with prostate adenocarcinomas or gastric cancer. To understand the role of LRPPRC in tumor development, previously we reported that LRPPRC forms a ternary complex with Beclin 1 and Bcl-2 to inhibit autophagy. Here we further show that LRPPRC maintains the stability of Parkin that mono-ubiquitinates Bcl-2 to increase Bcl-2 stability to inhibit autophagy. Under mitophagy stress, Parkin translocates to mitochondria to cause rupture of outer mitochondrial membrane and bind with exposed LRPPRC. Consequently, LRPPRC and Parkin help mitochondria being engulfed in autophagosomes to be degraded. In cells under long-term mitophagy stress, both LRPPRC and Parkin become depleted coincident with disappearance of mitochondria and final autophagy inactivation due to depletion of ATG5-ATG12 conjugates. LRPPRC functions as a checkpoint protein that prevents mitochondria from autophagy degradation and impact tumorigenesis

Final Amalgamation Processes of the Southern Altaids: Insights from the Triassic Houhongquan Ophiolitic Mélange in the Beishan Orogen (NW China)

AbstractThe Permian–Triassic tectonic setting is still controversial in the southern Altaids. The Beishan orogen is an ideal region to address the final tectonic of the Altaids. These systematic mapping, geochemistry, and geochronology studies on the Houhongquan ophiolitic mélange in the south Beishan are conducted to address this issue. New mapping reveals that the Houhongquan ophiolitic mélange consists of blocks of gabbro, basalt, chert, granite, and strongly deformed and cleaved sandstone in the southern Beishan. The studies reveal that the mafic fragments are relics of normal-mid-ocean ridge (N-MOR) and suprasubduction zone (SSZ) types of oceanic lithosphere. The four sandstone matrix samples yield the maximum depositional ages of 222±5 Ma, 233.8±2.3 Ma, 263.4±2.5 Ma, and 263.5±2.8 Ma, respectively, indicating that the youngest sandstones were tectonic emplaced in the Houhongquan ophiolitic mélange after ca. 222 Ma. The sandstone matrices display two types of age spectra. Early Permian sandstones have a single Devonian to Early Permian peak age patterns, indicating the existence of an independent Permian intraoceanic arc. In contrast, Late Triassic sandstones have multiple peaks with some Precambrian zircons, suggesting that they were sourced from a continental arc. Accordingly, we consider that the Houhongquan ophiolitic mélange tectonic was emplaced in the intraoceanic island arc during the Middle Permian and docked to a continental margin arc during the Late Triassic. Thus, we argue that the terminal amalgamation timing of the southern Altaids was probably during ca. 222-217 Ma

Development and evaluation of an eHealth self-management intervention for patients with chronic kidney disease in China: protocol for a mixed-method hybrid type 2 trial

Background: Chronic kidney disease (CKD) is a significant public health concern. In patients with CKD, interventions that support disease self-management have shown to improve health status and quality of life. At the moment, the use of electronic health (eHealth) technology in self-management interventions is becoming more and more popular. Evidence suggests that eHealth-based self-management interventions can improve health-related outcomes of patients with CKD. However, knowledge of the implementation and effectiveness of such interventions in general, and in China in specific, is still limited. This study protocol aims to develop and tailor the evidence-based Dutch ‘Medical Dashboard’ eHealth self-management intervention for patients suffering from CKD in China and evaluate its implementation process and effectiveness. Methods: To develop and tailor a Medical Dashboard intervention for the Chinese context, we will use an Intervention Mapping (IM) approach. A literature review and mixed-method study will first be conducted to examine the needs, beliefs, perceptions of patients with CKD and care providers towards disease (self-management) and eHealth (self-management) interventions (IM step 1). Based on the results of step 1, we will specify outcomes, performance objectives, and determinants, select theory-based methods and practical strategies. Knowledge obtained from prior results and insights from stakeholders will be combined to tailor the core interventions components of the ‘Medical Dashboard’ self-management intervention to the Chinese context (IM step 2–5). Then, an intervention and implementation plan will be developed. Finally, a 9-month hybrid type 2 trial design will be employed to investigate the effectiveness of the intervention using a cluster randomized controlled trial with two parallel arms, and the implementation integrity (fidelity) and determinants of implementation (IM step 6). Discussion: Our study will result in the delivery of a culturally tailored, standardized eHealth self-management intervention for patients with CKD in China, which has the potential to optimize patients’ self-management skills and improve health status and quality of life. Moreover, it will inform futur

A rare cause of abdominal pain managed unconventionally: acute renal infarction caused by atrial fibrillation: a case report

BackgroundAtrial fibrillation is one of the most common arrhythmias. The main thrombotic complication of arterial fibrillation is ischemic stroke, but it can also cause acute renal infarction from embolization. The low incidence and nonspecific clinical manifestations of acute renal infarction make it difficult to diagnose, often leading to either delayed diagnosis or misdiagnosis. Due to its rarity, more efficient treatment guidelines are helpful for the management of acute renal infarction related to the thromboembolic complication of arterial fibrillation.Case reportsWe report a case of acute renal infarction due to underlying arterial fibrillation, where a novel interventional therapeutic method was used. A 66-year-old Chinese man with arterial fibrillation, not on anticoagulation due to the patient's preference, and coronary artery disease post-percutaneous coronary intervention to left anterior descending artery about 1 year ago, was currently on dual antiplatelet therapy. He suddenly developed intermittent and sharp left-sided abdominal pain and was found to have an acute left renal infarction on computed tomography scan. Angiogram showed acute occlusion of the left renal artery due to thromboembolism. For this patient, a combination method of local thrombus aspiration, angioplasty, and infusion of nitroglycerin and diltiazem were used, restoring blood flow to the left kidney. After recovery, the patient was discharged on aspirin, clopidogrel, and warfarin. At 6 months follow-up, there was no residual kidney dysfunction.ConclusionsAcute renal infarction from thromboembolism is a rare but serious complication of arterial fibrillation. More efficient and different options for intervention methods will benefit the treatment of this disease. Here, we report a combination therapeutic method that has not been used in acute renal infarction associated with arterial fibrillation, and which restored renal perfusion and prevented long-term kidney injury

Andean-type orogenic plateau as a trigger for aridification in the arcs of northeast Pangaea

Abstract The interplay between continental motions during the assembly of Pangaea and late Palaeozoic climate change, including severe glaciation and global aridification, remains enigmatic. Here we identify the provenance of Permian–Early Triassic sediments that recorded climate change of North China and estimate palaeoelevation to constrain tectonic-climate interaction during the assembly of northeast Pangaea. Detrital zircon U-Pb-Hf analysis indicates the sediments were locally sourced from the ancient basement and associated with a late Palaeozoic (410–260 million years ago) continental arc, devoid of input from juvenile arcs of the Altaids. These sediments were interpreted as deposited in a retroarc foreland basin ascribed to subduction of the Palaeo-Asian Ocean. Crustal thickness estimated from whole-rock La/Yb yields an average value of 58 ± 11 km, which corresponds to a palaeoelevation of 3.8 ± 0.7 km. The results reveal the existence in North China of an orogenic plateau comparable to the Altiplano of the Andes that blocked moisture transport from the ocean and served as an important orographic barrier to trigger Permian aridification

Architecture of ophiolitic mélanges in the Junggar region, NW China

Ophiolitic mélanges, units that contain components of an ophiolite suite, provide crucial information on earth history and orogenic evolution. In this paper, four ophiolitic mélanges are characterized, including the Baijiantan-Yeyagou, Hebukesair, Zhaheba and Hongguleleng mélanges in the Junggar region (NW China), southern Altaids. Detailed geological mapping, structural, geochronological, and geochemical analyses constrain ages, geochemical affinities and relationships of magmatic with clastic rocks. MORB-/OIB-type (meta)gabbros and plagiogranite are the oldest mélange components, slightly older or coeval with associated chert and MORB-/OIB-type basalt; these rocks collectively constitute an ophiolite suite. Ophiolitic rocks predate associated clastic sedimentary rocks (conglomerate and turbidite) by ∼90-25 My, and associated SSZ-type hornblende gabbro, basaltic andesite, diabase, diorite and rhyolite by ∼78-37 My, except in the Hongguleleng mélange, where ophiolitic rocks predate latter units by ∼9-25 My. The ophiolitics are repeated by imbricate thrusts and duplexes, and folded. Ophiolitic blocks in mélanges locally preserve similar structures. Such blocks commonly have MORB and/or OIB geochemical affinities. Significantly older ages of MORB/OIB igneous rocks compared to ages of associated clastic sedimentary/SSZ-type igneous rocks shows that the former rocks formed as part of the crust of a large ocean, far from a convergent margin. The far-traveled oceanic crustal slices were imbricated and disrupted into block-in-matrix structures during accretion and incorporation into a subduction complex. SSZ-type magmatic rocks locally intrude into and extrude onto clastic rocks, demonstrating that a mélange contains multi-stage magmatic rocks. Folds, tilted structures and shear band cleavages are locally cross-cut by dikes, and these rocks are themselves have been dismembered into blocks. An intruded conglomerate in the Hongguleleng mélange contains pebbles of gabbro and basaltic andesite, the latter of which overlies sandstone. Superimposed folds in clastic rocks and chert record the polydeformation of the mélanges. Determination of the complex relationships of multi-stage magmatism and deformation illuminates the tectonic history of ophiolitic mélanges in the Junggar region. This history includes formation and subduction-accretion of the crust of a large ocean and post-subduction intracontinental deformation