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Purpose:Glioblastoma (GBM) is one of the most aggressive and lethal cancer types in humans. The standard treatment approach is surgery followed by chemoradiation. However, the molecular mechanisms of innate tumor radioresistance remain poorly understood.Experimental Design:We tested the expression of Smoothened (Smo) in primary and recurrent GBM tissues and cells. Then, we determined radiation effectiveness against primary and recurrent GBM cells. Lastly, the functional role of Smo in GBM radioresistance was further confirmed by in vitro and in vivo experiments.Results:We reported that Smo was significantly upregulated in recurrent GBM cell lines and tumor tissues following radiation treatment. Higher Smo expression indicated poor prognosis of GBM patients after radiation treatment. Smo had radioresistance effects in both GBM cells and human tumor xenografts. The mechanisms underlying these effects involved the attenuation of DNA damage repair caused by IR. Importantly, we found that the effect of Smo on radioresistance was mediated by Claspin polyubiquitination and proteasomal degradation, leading to the regulation of ATR–Chk1 signaling. Moreover, we found that Smo reduced Claspin polyubiquitination and proteasomal degradation by promoting USP3 transcription. Furthermore, we demonstrated that the Smo inhibitor GDC-0449 induced radiosensitivity to GBM.Conclusions:These data suggest that Smo confers radiation resistance in GBM by promoting USP3 transcription, leading to the activation of Claspin-dependent ATR–Chk1 signaling. These findings identify a potential mechanism of GBM resistance to radiation and suggest a potential therapeutic target for radiation resistance in GBM.

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As quantum programming evolves, more and more quantum programming languages are being developed. As a result, debugging and testing quantum programs have become increasingly important. While bug fixing in classical programs has come a long way, there is a lack of research in quantum programs. To this end, this paper presents a comprehensive study on bug fixing in quantum programs. We collect and investigate 96 real-world bugs and their fixes from four popular quantum programming languages Qiskit, Cirq, Q#, and ProjectQ). Our study shows that a high proportion of bugs in quantum programs are quantum-specific bugs (over 80%), which requires further research in the bug fixing domain. We also summarize and extend the bug patterns in quantum programs and subdivide the most critical part, math-related bugs, to make it more applicable to the study of quantum programs. Our findings summarize the characteristics of bugs in quantum programs and provide a basis for studying testing and debugging quantum programs.

Microglial cells are key component of central nervous system (CNS) and mediate the immune response of the brain under physiological or pathological conditions. It tends to activate into a pro‐inflammatory M1 phenotype after traumatic brain injury (TBI) and promote secondary brain damage. Recently, necroptosis was found to promote microglial activation and neuroinflammation after TBI. However, the mechanism and specific interventions of microglial necroptosis after TBI remain poorly investigated. Here, we reported that overexpress the charged multivesicular body protein 4b (CHMP4B) which is a core member of the endosomal sorting required for transport complex III (ESCRT‐III) significantly decreased the level of necroptosis in microglia, improved neurological function recovery and protected against cell death after TBI. Further investigation showed that forkhead transcription factor O1 (FOXO1) was a crucial transcription factor that increased CHMP4B transcription by binding to the promoter region, thereby inhibiting necroptosis in microglia. Collectively, our findings demonstrated that CHMP4B relieved microglial necroptosis and neuroinflammation after TBI, and promote the recovery of nerve function. FOXO1 is an important factor in promoting CHMP4B expression. This study provides the novel viewpoint for TBI prevention and treatment.

Purpose: Glioblastoma (GBM) is one of the most aggressive and lethal cancer types in humans. The standard treatment approach is surgery followed by chemoradiation. However, the molecular mechanisms of innate tumor radioresistance remain poorly understood. Experimental Design: We tested the expression of Smoothened (Smo) in primary and recurrent GBM tissues and cells. Then, we determined radiation effectiveness against primary and recurrent GBM cells. Lastly, the functional role of Smo in GBM radioresistance was further confirmed by in vitro and in vivo experiments. Results: We reported that Smo was significantly upregulated in recurrent GBM cell lines and tumor tissues following radiation treatment. Higher Smo expression indicated poor prognosis of GBM patients after radiation treatment. Smo had radioresistance effects in both GBM cells and human tumor xenografts. The mechanisms underlying these effects involved the attenuation of DNA damage repair caused by IR. Importantly, we found that the effect of Smo on radioresistance was mediated by Claspin polyubiquitination and proteasomal degradation, leading to the regulation of ATR–Chk1 signaling. Moreover, we found that Smo reduced Claspin polyubiquitination and proteasomal degradation by promoting USP3 transcription. Furthermore, we demonstrated that the Smo inhibitor GDC-0449 induced radiosensitivity to GBM. Conclusions: These data suggest that Smo confers radiation resistance in GBM by promoting USP3 transcription, leading to the activation of Claspin-dependent ATR–Chk1 signaling. These findings identify a potential mechanism of GBM resistance to radiation and suggest a potential therapeutic target for radiation resistance in GBM.

Background: The microglia-mediated inflammatory response is a vital mechanism of secondary damage following traumatic brain injury (TBI), but its underlying mechanism of microglial activation is unclear. Methods: Controlled cortical impact (CCI) was induced in adult male C57BL/6J mice, and we also used glutamate to construct a classical in vitro injury model in BV2 cell line. The activation of microglia was determined by western blot assessments and immunostaining. The inflammatory factors were determined by ELLSA. The oxidative stress marker and mitochondrial ROS were determined by immunoblotting and MitoSox Red staining. Transmission electron microscopy (TEM) was used to observe a typical morphology of necroptotic cells. Results: Our quantitative proteomics identified 2499 proteins, 157 were significantly differentially expressed between brain tissues at 6 hours after CCI (CCI6h) and sham groups, and 109 were significantly differentially expressed between CCI24h and sham brain tissues. Moreover, compared with sham groups, the terms “acute-phase response”, “inflammation”, and “protein binding” were significantly enriched in CCI groups. Interestingly, fetuin-A, a liver-secreted acute-phase glycoprotein, was involved in these biological processes. Using experimental TBI models, we found that the fetuin-A level peaked at 6 h and then decreased gradually. Importantly, we showed that fetuin-A reduced the cortical lesion volume and edema area and inhibited the inflammatory response, which was associated with suppressing microglial necroptosis, thus decreasing microglial polarization to the M1 phenotype. Furthermore, administration of fetuin-A attenuated mitochondrial oxidative stress in glutamate-treated BV2 cells, which is a critical mechanism of necroptosis suppression. In addition, we demonstrated that fetuin-A treatment promoted translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus in vivo; however, the Nrf-2 inhibitor ML385 and si-heme oxygenase-1 (HO-1) disrupted the regulation of oxidative stress by fetuin-A and induced increased ROS levels and necroptosis in glutamate-treated BV2 cells. Interestingly, the mechanism of fetuin-A in BV2 cells also protects neurons from adverse factors in co-culture assays.Conclusions: Our results demonstrate that fetuin-A activates Nrf-2/HO-1, suppresses oxidative stress and necroptosis levels, and thereby attenuates the abnormal inflammatory response following TBI, providing a potential therapeutic strategy for TBI treatment.

Prokineticin-2 (Prok2) is an important secreted protein likely involved in the pathogenesis of several acute and chronic neurological diseases through currently unidentified regulatory mechanisms. The initial mechanical injury of neurons by traumatic brain injury triggers multiple secondary responses including various cell death programs. One of these is ferroptosis, which is associated with dysregulation of iron and thiols and culminates in fatal lipid peroxidation. Here, we explore the regulatory role of Prok2 in neuronal ferroptosis in vitro and in vivo. We show that Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. Mice injected with adeno-associated virus-Prok2 before controlled cortical impact injury show reduced neuronal degeneration and improved motor and cognitive functions, which could be inhibited by Fbxo10 knockdown. Our study shows that Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis., Prokineticin-2 (Prok2) is a secreted protein involved in many physiological processes. Here, the authors show that Prok2 prevents neuronal cell ferroptosis after traumatic brain injury and its administration before cortical injury reduces neuronal degeneration, and motor and cognitive impairments.

Ischemic stroke poses a significant health risk due to its high rate of disability and mortality. To address this problem, several therapeutic approaches have been proposed, including interruption targeting programmed cell death (PCD). Ferroptosis is a newly defined PCD characterized by iron-dependent accumulation of lipid peroxidation, and is becoming a promising target for treating numerous diseases. To explore the underlying mechanisms of the initiation and execution of ferroptosis in ischemic stroke, we established stroke models in vivo and in vitro simulating ischemia/reperfusion (I/R) neuronal injury. Different from previous reports on stroke, we tested ferroptosis by measuring the levels of core proteins, such as ACSL4, 15-LOX2, Ferritin and GPX4. In addition, I/R injury induces excessive degradation of ferritin via the autophagy pathway and subsequent increase of free iron in neurons. This phenomenon has recently been termed ferritinophagy and reported to be regulated by nuclear receptor coactivator 4 (NCOA4) in some cell lines. Increased NCOA4 in cytoplasm was detected in our study and then silenced by shRNA to investigate its function. Both in vivo and in vitro, NCOA4 deletion notably abrogated ferritinophagy caused by I/R injury and thus inhibited ferroptosis. Furthermore, we found that NCOA4 was upregulated by ubiquitin specific peptidase 14 (USP14) via a deubiquitination process in damaged neurons, and we found evidence of pharmacological inhibition of USP14 effectively reducing NCOA4 levels to protect neurons from ferritinophagy-mediated ferroptosis. These findings suggest a novel and effective target for treating ischemic stroke.

Many recent machine learning models show dynamic shape characteristics. However, existing AI compiler optimization systems suffer a lot from problems brought by dynamic shape models, including compilation overhead, memory usage, optimization pipeline and deployment complexity. This paper provides a compiler system to natively support optimization for dynamic shape workloads, named DISC. DISC enriches a set of IR to form a fully dynamic shape representation. It generates the runtime flow at compile time to support processing dynamic shape based logic, which avoids the interpretation overhead at runtime and enlarges the opportunity of host-device co-optimization. It addresses the kernel fusion problem of dynamic shapes with shape propagation and constraints collecting methods. This is the first work to demonstrate how to build an end-to-end dynamic shape compiler based on MLIR infrastructure. Experiments show that DISC achieves up to 3.3× speedup than TensorFlow/PyTorch, and 1.8× than Nimble.

Glioblastoma (GBM) is the most universal type of primary brain malignant tumour, and the prognosis of patients with GBM is poor. S100A11 plays an essential role in tumour. However, the role and molecular mechanism of S100A11 in GBM are not clear. Here, we found that S100A11 was up‐regulated in GBM tissues and higher S100A11 expression indicated poor prognosis of GBM patients. Overexpression of S100A11 promoted GBM cell growth, epithelial‐mesenchymal transition (EMT), migration, invasion and generation of glioma stem cells (GSCs), whereas its knockdown inhibited these activities. More importantly, S100A11 interacted with ANXA2 and regulated NF‐κB signalling pathway through decreasing ubiquitination and degradation of ANXA2. Additionally, NF‐κB regulated S100A11 at transcriptional level as a positive feedback. We also demonstrated the S100A11 on tumour growth in GBM using an orthotopic tumour xenografting. These data demonstrate that S100A11/ANXA2/NF‐κB positive feedback loop in GBM cells that promote the progression of GBM.

To cope with the high resource (network and compute) demands of real-time video analytics pipelines, recent systems have relied on frame filtering. However, filtering has typically been done with neural networks running on edge/backend servers that are expensive to operate. This paper investigates on-camera filtering, which moves filtering to the beginning of the pipeline. Unfortunately, we find that commodity cameras have limited compute resources that only permit filtering via frame differencing based on low-level video features. Used incorrectly, such techniques can lead to unacceptable drops in query accuracy. To overcome this, we built Reducto, a system that dynamically adapts filtering decisions according to the time-varying correlation between feature type, filtering threshold, query accuracy, and video content. Experiments with a variety of videos and queries show that Reducto achieves significant (51-97% of frames) filtering benefits, while consistently meeting the desired accuracy.

Myxoma is the most common tumor in the heart. A typical myxoma is relatively straightforward to diagnose. However, certain cardiac myxomas have rare features. We report three extremely rare cases of cardiac myxoma. One case involved a myxoma that originated from the annulus of the tricuspid after valvuloplasty, one case involved myxomas associated with left atrial thrombus and severe mitral stenosis, and the third case involved myxoma combined with severe calcification. All three cases were diagnosed by echocardiography and pathology. We also review clinical presentations and diagnostic characteristics of cardiac myxomas.

Tumour invasion is closely related to the prognosis and recurrence of glioblastoma multiforme and partially attributes to epithelial‐mesenchymal transition. Long intergenic non‐coding RNA 00511 (LINC00511) plays a pivotal role in tumour; however, the role of LINC00511 in GBM, especially in the epigenetic molecular regulation mechanism of EMT, is still unclear. Here, we found that LINC00511 was up‐regulated in GBM tissues and relatively high LINC00511 expression predicted poorer prognosis. Moreover, ectopic LINC00511 enhanced GBM cells proliferation, EMT, migration and invasion, whereas LINC00511 knockdown had the opposite effects. Mechanistically, we confirmed that ZEB1 acted as a transcription factor for LINC00511 in GBM cells. Subsequently, we found that LINC00511 served as a competing endogenous RNA that sponged miR‐524‐5p to indirectly regulate YB1, whereas, up‐regulated YB1 promoted ZEB1 expression, which inversely facilitated LINC00511 expression. Finally, orthotopic xenograft models were performed to further demonstrate the LINC00511 on GBM tumorigenesis. This study demonstrates that a LINC00511/miR‐524‐5p/YB1/ZEB1 positive feedback loop provides potential therapeutic targets for GBM progression.

Visual tracking can be formulated as a Markov decision process over a parameterized family of policies. In this case, the problem of visual tracking is to make decisions about whether and how to adjust the agent. This paper introduce an end-to-end methodology which contains a framework from motion prediction to online update for single object tracking. For the prediction phase, we incorporate heatmap with appearance feature to learn a deep metric, and we introduce Region Proposal Network to regress a reliable location. For the online update phase, we take tracking as agent decision making process via learning a policy to pick a proper action about whether and how to update the state transition using Actor-Critic Network. The proposed tracking framework can be trained as an end-to-end fashion, and we demonstrate that our tracking performance is rather competitive with other state-of-the-art visual tracking algorithms. Other than this, from the experimental results we can see that, our prediction network using heatmap learning can acheive rather robust results under usual circumstance, and using reinforcement learning to make online decisions can be helpful when dealing with more complicated cases.

Myxoma is the most common tumor in the heart. A typical myxoma is relatively straightforward to diagnose. However, certain cardiac myxomas have rare features. We report three extremely rare cases of cardiac myxoma. One case involved a myxoma that originated from the annulus of the tricuspid after valvuloplasty, one case involved myxomas associated with left atrial thrombus and severe mitral stenosis, and the third case involved myxoma combined with severe calcification. All three cases were diagnosed by echocardiography and pathology. We also review clinical presentations and diagnostic characteristics of cardiac myxomas.

Firstly, hydrotalcite (HT) was synthesized by the urea method. Then, sodium methyl allyl sulfonate (SMAS) was used as intercalation agent to prepare intercalated HT (SMAS–HT). Finally, a novel poly(acrylic-co-acrylamide)/HT nanocomposite superabsorbent was prepared by inverse suspension polymerization, using N,N′-methylenebisacrylamide (NMBA) as a cross-linking agent and potassium persulfate (KPS) as an initiator. The morphology of the superabsorbents was characterized by FT-IR, XRD, SEM and TEM. The influences of the amount of SMAS–HT on the water (salt) absorbency were investigated. Results showed that the intercalation was successful and the intercalated SMAS–HT incorporated into the superabsorbent was completely exfoliated. The superabsorbent particles approach a spherical shape and the average size is 200–300 nm. The particle sizes of the superabsorbents decrease with increasing the content of SMAS–HT. In addition, the superabsorbent acquired its highest water (salt) absorbency when the content of SM...