GCformer: An Efficient Framework for Accurate and Scalable Long-Term Multivariate Time Series Forecasting

Transformer-based models have emerged as promising tools for time series forecasting. However, these model cannot make accurate prediction for long input time series. On the one hand, they failed to capture global dependencies within time series data. On the other hand, the long input sequence usually leads to large model size and high time complexity. To address these limitations, we present GCformer, which combines a structured global convolutional branch for processing long input sequences with a local Transformer-based branch for capturing short, recent signals. A cohesive framework for a global convolution kernel has been introduced, utilizing three distinct parameterization methods. The selected structured convolutional kernel in the global branch has been specifically crafted with sublinear complexity, thereby allowing for the efficient and effective processing of lengthy and noisy input signals. Empirical studies on six benchmark datasets demonstrate that GCformer outperforms state-of-the-art methods, reducing MSE error in multivariate time series benchmarks by 4.38% and model parameters by 61.92%. In particular, the global convolutional branch can serve as a plug-in block to enhance the performance of other models, with an average improvement of 31.93\%, including various recently published Transformer-based models. Our code is publicly available at https://github.com/zyj-111/GCformer

Potential Disease-Modifying Effects of Lithium Carbonate in Niemann-Pick Disease, Type C1

Background: Niemann-Pick disease type C1 (NP-C1) is a rare, autosomal-recessive neurodegenerative disorder with no United States Food and Drug Administration (FDA)-approved drug. Lithium has been shown to have considerable neuroprotective effects for neurological disorders such as bipolar disorder, Alzheimer’s disease and stroke and has been tested in many clinical trials. However, the pharmacological effect of lithium on NP-C1 neurodegenerative processes has not been investigated. The aim of this study was to provide an initial evaluation of the safety and feasibility of lithium carbonate in patients with NP-C1.Methods: A total of 13 patients diagnosed with NP-C1 who met the inclusion criteria received lithium orally at doses of 300, 600, 900, or 1,200 mg daily. The dose was reduced based on tolerance or safety observations. Plasma 7-ketocholesterol (7-KC), an emerging biomarker of NP-C1, was the primary endpoint. Secondary endpoints included NPC Neurological Severity Scores (NNSS) and safety.Results: Of the 13 patients with NP-C1 (12–33 years) enrolled, three withdrew (discontinuation of follow-up outpatient visits). The last observed post-treatment values of 7-KC concentrations (128 ng/ml, SEM 20) were significantly lower than pretreatment baselines values (185 ng/ml, SEM 29; p = 0.001). The mean NNSS was improved after lithium treatment at 12 months (p = 0.005). Improvement in swallowing capacity was observed in treated patients (p = 0.014). No serious adverse events were recorded in the patients receiving lithium.Conclusion: Lithium is a potential therapeutic option for NP-C1 patients. Larger randomized and double-blind clinical trials are needed to further support this finding.Clinical Trial Registration:ClinicalTrials.gov, NCT03201627

reductiveleachingoflowgrademanganeseorewithpreprocessedcornstalk

Cornstalk is usually directly used as a reductant in reductive leaching manganese. However, low utilization of cornstalk makes low manganese dissolution ratio. In the research, pretreatment for cornstalk was proposed to improve manganese dissolution ratio. Cornstalk was preprocessed by a heated sulfuric acid solution (1.2 M of sulfuric acid concentration) for 10 min at 80℃. Thereafter, both the pretreated solution and the residue were used as a reductant for manganese leaching. This method not only exhibited superior activity for hydrolyzing cornstalk but also enhanced manganese dissolution. These effects were attributed to an increase in the amount of reductive sugars resulting from lignin hydrolysis. Through acid pretreatment for cornstalk, the manganese dissolution ratio was improved from 50.14% to 83.46%. The present work demonstrates for the first time the effective acid pretreatment of cornstalk to provide a cost-effective reductant for manganese leaching

KCa3.1 Inhibition Switches the Astrocyte Phenotype during Astrogliosis Associated with Ischemic Stroke Via Endoplasmic Reticulum Stress and MAPK Signaling Pathways

Ischemic stroke is a devastating neurological disease that can initiate a phenotype switch in astrocytes. Reactive astrogliosis is a significant pathological feature of ischemic stroke and is accompanied by changes in gene expression, hypertrophied processes and proliferation. The intermediate-conductance Ca2+-activated potassium channel KCa3.1 has been shown to contribute to astrogliosis-induced neuroinflammation in Alzheimer’s disease (AD). We here present evidence, from both astrocytes subjected to oxygen–glucose deprivation (OGD) and from the brains of mice subjected to permanent middle cerebral artery occlusion (pMCAO), that KCa3.1 represents a valid pharmacological target for modulation of astrocyte phenotype during astrogliosis caused by ischemic stroke. In the primary cultured astrocytes, OGD led to increased expression of KCa3.1, which was associated with upregulation of the astrogliosis marker, glial fibrillary acidic protein (GFAP). Pharmacological blockade or genetic deletion of KCa3.1 suppressed OGD-induced up-regulation of GFAP, endoplasmic reticulum (ER) stress marker 78 kDa glucose-regulated protein (GRP78) and phosphorylated eIF-2α through the c-Jun/JNK and ERK1/2 signaling pathways. We next investigated the effect of genetic deletion of KCa3.1 in the pMCAO mouse model. KCa3.1 deficiency also attenuated ER stress and astrogliosis through c-Jun/JNK and ERK1/2 signaling pathways following pMCAO in KCa3.1−/− mice. Our data suggest that blockade of KCa3.1 might represent a promising strategy for the treatment of ischemic stroke

The potassium channel KCa3.1 constitutes a pharmacological target for astrogliosis associated with ischemia stroke

Abstract Background Reactive astrogliosis is one of the significantly pathological features in ischemic stroke accompanied with changes in gene expression, morphology, and proliferation. KCa3.1 was involved in TGF-β-induced astrogliosis in vitro and also contributed to astrogliosis-mediated neuroinflammation in neurodegeneration disease. Methods Wild type mice and KCa3.1−/− mice were subjected to permanent middle cerebral artery occlusion (pMCAO) to evaluate the infarct areas by 2,3,5-triphenyltetrazolium hydrochloride staining and neurological deficit. KCa3.1 channels expression and cell localization in the brain of pMCAO mice model were measured by immunoblotting and immunostaining. Glia activation and neuron loss was measured by immunostaining. DiBAC4 (3) and Fluo-4AM were used to measure membrane potential and cytosolic Ca2+ level in oxygen-glucose deprivation induced reactive astrocytes in vitro. Results Immunohistochemistry on pMCAO mice infarcts showed strong upregulation of KCa3.1 immunoreactivity in reactive astrogliosis. KCa3.1−/− mice exhibited significantly smaller infarct areas on pMCAO and improved neurological deficit. Both activated gliosis and neuronal loss were attenuated in KCa3.1−/− pMCAO mice. In the primary cultured astrocytes, the expressions of KCa3.1 and TRPV4 were increased associated with upregulation of astrogliosis marker GFAP induced by oxygen-glucose deprivation. The activation of KCa3.1 hyperpolarized membrane potential and, by promoting the driving force for calcium, induced calcium entry through TRPV4, a cation channel of the transient receptor potential family. Double-labeled staining showed that KCa3.1 and TRPV4 channels co-localized in astrocytes. Blockade of KCa3.1 or TRPV4 inhibited the phenotype switch of reactive astrogliosis. Conclusions Our data suggested that KCa3.1 inhibition might represent a promising therapeutic strategy for ischemia stroke

A high-performance self-powered broadband photodetector based on a CH3NH3PbI3 perovskite/ZnO nanorod array heterostructure

Here we report a self-powered photodetector based on a ZnO/CH3NH3PbI3 heterojunction and a MoO3 hole-transport layer. The organolead iodide perovskite photodetector is sensitive to broadband wavelengths from the ultraviolet light to the entire visible light region (250-800 nm), showing a high photo-responsivity of 24.3 A W-1 and a high detectivity value of 3.56 × 1014 cm Hz1/2 W-1 at 500 nm without external bias voltage. Meanwhile, we found that the photodetective performances are closely related to the thickness of the MoO3 layer, which acts as a hole-transport layer and an electron-blocking layer and can effectively decrease the recombination of holes and electrons. Additionally, the as-fabricated photodetector exhibits good stability and only 9.3% photoelectric response current decay after a 3-month illumination test. The high detectivity and responsivity of such a ZnO nanorod/perovskite heterojunction are clearly demonstrated and should be widely applicable to other photoelectric detection devices.Peer reviewe

Additional file 1: of The potassium channel KCa3.1 constitutes a pharmacological target for astrogliosis associated with ischemia stroke

Figure S1. Cerebral blood flow (CBF) of ischemic brain hemisphere before and during permanent middle cerebral artery occlusion (pMCAO) was monitored by transcranial laser Doppler. The arrow depicted the start of pMCAO. (TIFF 58 kb