BOK Is a Non-canonical BCL-2 Family Effector of Apoptosis Regulated by ER-Associated Degradation.

The mitochondrial pathway of apoptosis is initiated by mitochondrial outer membrane permeabilization (MOMP). The BCL-2 family effectors BAX and BAK are thought to be absolutely required for this process. Here, we report that BCL-2 ovarian killer (BOK) is a bona fide yet unconventional effector of MOMP that can trigger apoptosis in the absence of both BAX and BAK. However, unlike the canonical effectors, BOK appears to be constitutively active and unresponsive to antagonistic effects of the antiapoptotic BCL-2 proteins. Rather, BOK is controlled at the level of protein stability by components of the endoplasmic reticulum (ER)-associated degradation pathway. BOK is ubiquitylated by the AMFR/gp78 E3 ubiquitin ligase complex and targeted for proteasomal degradation in a VCP/p97-dependent manner, which allows survival of the cell. When proteasome function, VCP, or gp78 activity is compromised, BOK is stabilized to induce MOMP and apoptosis independently of other BCL-2 proteins.

Melatonin ameliorates 10-hydroxycamptothecin-induced oxidative stress and apoptosis via autophagy-regulated p62/Keap1/Nrf2 pathway in mouse testicular cells.

10-Hydroxycamptothecin (HCPT) is a widely used clinical anticancer drug but has a significant side effect profile. Melatonin has a beneficial impact on the chemotherapy of different cancer cells and reproductive processes, but the effect and underlying molecular mechanism of melatonin's involvement in the HCPT-induced side effects in cells, especially in the testicular cells, are poorly understood. In this study, we found that melatonin therapy significantly restored HCPT-induced testicular cell damage and did not affect the antitumor effect of HCPT. Further analysis found that melatonin therapy suppressed HCPT-induced DNA damage associated with ataxia-telangiectasia mutated- and Rad3-related and CHK1 phosphorylation levels in the testis. Changes in apoptosis-associated protein levels (Bax, Bcl-2, p53, and Cleaved caspase-3) and in reactive oxygen species-associated proteins (Nrf2 and Keap1) and index (malondialdehyde and glutathione) suggested that melatonin treatment relieved HCPT-induced cell apoptosis and oxidative damage, respectively. Mechanistically, melatonin-activated autophagy proteins (ATG7, Beclin1, and LC3bII/I) may induce p62-dependent autophagy to degrade Keap1, eliciting Nrf2 from Keap1-Nrf2 interaction to promote antioxidant enzyme expression such as HO-1, which would salvage HCPT-induced ROS production and mitochondrial dysfunction. Collectively, this study reveals that melatonin therapy may protect testicular cells from HCPT-induced damage via the activation of autophagy, which alleviates oxidative stress, mitochondrial dysfunction, and cell apoptosis.

Evaluating combustion kinetics and quantifying fuel-N conversion tendency of shoe manufacturing waste.

Combustion is an effective and cost-efficient thermochemical conversion method for solid waste, showing promise for the resource utilization of shoe manufacturing waste (SMW). However, SMW is generally composed of different components, which can lead to unstable combustion and excessive pollutant emissions, especially NOx. To date, combustion characteristics, reaction mechanism and fuel nitrogen (fuel-N) conversion of different SMW components remain unclear. In this work, the combustion behavior of typical SMW components combustion was investigated using Thermogravimetric coupled with Fourier transform infrared spectrum (TG-FTIR). A simplified single-step reaction mechanism was proposed according to the temperature interval to estimate reaction mechanism of SMW. Additionally, the relationship between fuel-N conversion tendency and fuel properties was established. The results indicate that the values for the comprehensive combustion performance index (S) and flammability index (C) range from 1.65 to 0.44 and 3.98 to 1.37, respectively. This demonstrates the significant variability in combustion behavior among different SMW components. Cardboard, leather and sponge have higher values of S and C, suggesting a better ignition characteristic and a stable combustion process. During the combustion of SMW, nitrogen oxides (NO and N2O) are the main nitrogen-containing compounds in the flue gases, with NO being the major contributor, accounting for over 82.97 % of the nitrogen oxides. NO has a negative correlation with nitrogen content, but it is opposite for N2O, HCN and NH3. Furthermore, the conversion of NO, N2O and NH3 is proportional to logarithmic values of O/N, while its conversion to HCN is proportional to logarithmic values of VM/N. These findings facilitate the prediction of the fuel-N conversion of solid waste combustion. This work might shed light on combustion optimization and in-situ pollutant emission control in solid waste combustion.

Computed tomography-based radiomics improves non-invasive diagnosis of Pneumocystis jirovecii pneumonia in non-HIV patients: a retrospective study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) could be fatal to patients without human immunodeficiency virus (HIV) infection. Current diagnostic methods are either invasive or inaccurate. We aimed to establish an accurate and non-invasive radiomics-based way to identify the risk of PCP infection in non-HIV patients with computed tomography (CT) manifestation of pneumonia. METHODS: This is a retrospective study including non-HIV patients hospitalized for suspected PCP from January 2010 to December 2022 in one hospital. The patients were randomized in a 7:3 ratio into training and validation cohorts. Computed tomography (CT)-based radiomics features were extracted automatically and used to construct a radiomics model. A diagnostic model with traditional clinical and CT features was also built. The area under the curve (AUC) were calculated and used to evaluate the diagnostic performance of the models. The combination of the radiomics features and serum ß-D-glucan levels was also evaluated for PCP diagnosis. RESULTS: A total of 140 patients (PCP: N = 61, non-PCP: N = 79) were randomized into training (N = 97) and validation (N = 43) cohorts. The radiomics model consisting of nine radiomic features performed significantly better (AUC = 0.954; 95% CI: 0.898-1.000) than the traditional model consisting of serum ß-D-glucan levels (AUC = 0.752; 95% CI: 0.597-0.908) in identifying PCP (P = 0.002). The combination of radiomics features and serum ß-D-glucan levels showed an accuracy of 95.8% for identifying PCP infection (positive predictive value: 95.7%, negative predictive value: 95.8%). CONCLUSIONS: Radiomics showed good diagnostic performance in differentiating PCP from other types of pneumonia in non-HIV patients. A combined diagnostic method including radiomics and serum ß-D-glucan has the potential to provide an accurate and non-invasive way to identify the risk of PCP infection in non-HIV patients with CT manifestation of pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05701631).

CircPTEN suppresses human clear cell renal carcinoma progression and resistance to mTOR inhibitors by targeting epigenetic modification.

Renal cell carcinoma (RCC) is known to be the most commonly diagnosed kidney cancer. Clear cell RCC (ccRCC) represents approximately 85 % of diagnosed RCC cases. Targeted therapeutics, such as multi-targeted tyrosine kinase inhibitors (TKI) and mTOR inhibitors, are widely used in ccRCC therapy. However, patients treated with mTOR and TKI inhibitors easily acquire drug resistance, making the therapy less effective. Here, we demonstrated that circPTEN inhibits the expression of its parental gene PTEN by reducing methylation of the PTEN promotor and inhibits GLUT1 expression by reducing m6A methylation of GLUT1, which suppresses ccRCC progression and resistance to mTOR inhibitors.

TRIM44 Promotes Rabies Virus Replication by Autophagy-Dependent Mechanism.

Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host-virus interactions through specific pathways, but their involvement in response to rabies virus (RABV) infection remains poorly understood. Here, we identified that several TRIM proteins are upregulated in mouse neuroblastoma cells (NA) after infection with the rabies virus using RNA-seq sequencing. Among them, TRIM44 was found to regulate RABV replication. This is supported by the observations that downregulation of TRIM44 inhibits RABV replication, while overexpression of TRIM44 promotes RABV replication. Mechanistically, TRIM44-induced RABV replication is brought about by activating autophagy, as inhibition of autophagy with 3-MA attenuates TRIM44-induced RABV replication. Additionally, we found that inhibition of autophagy with rapamycin reverses the TRIM44-knockdown-induced decrease in LC3B expression and autophagosome formation as well as RABV replication. The results suggest that TRIM44 promotes RABV replication by an autophagy-dependent mechanism. Our work identifies TRIM44 as a key host factor for RABV replication, and targeting TRIM44 expression may represent an effective therapeutic strategy.

Design and application of a multimodality-compatible 1Tx/6Rx RF coil for monkey brain MRI at 7T.

OBJECTIVE: Blood-oxygen-level-dependent functional MRI allows to investigte neural activities and connectivity. While the non-human primate plays an essential role in neuroscience research, multimodal methods combining functional MRI with other neuroimaging and neuromodulation enable us to understand the brain network at multiple scales. APPROACH: In this study, a tight-fitting helmet-shape receive array with a single transmit loop for anesthetized macaque brain MRI at 7T was fabricated with four openings constructed in the coil housing to accommodate multimodal devices, and the coil performance was quantitatively evaluated and compared to a commercial knee coil. In addition, experiments over three macaques with infrared neural stimulation (INS), focused ultrasound stimulation (FUS), and transcranial direct current stimulation (tDCS) were conducted. MAIN RESULTS: The RF coil showed higher transmit efficiency, comparable homogeneity, improved SNR and enlarged signal coverage over the macaque brain. Infrared neural stimulation was applied to the amygdala in deep brain region, and activations in stimulation sites and connected sites were detected, with the connectivity consistent with anatomical information. Focused ultrasound stimulation was applied to the left visual cortex, and activations were acquired along the ultrasound traveling path, with all time course curves consistent with pre-designed paradigms. The existence of transcranial direct current stimulation electrodes brought no interference to the RF system, as evidenced through high-resolution MPRAGE structure images. SIGNIFICANCE: This pilot study reveals the feasibility for brain investigation at multiple spatiotemporal scales, which may advance our understanding in dynamic brain networks.

Special issue "The advance of solid tumor research in China": Presurgical therapy in the management of local retroperitoneal recurrence of renal cell carcinoma after radical nephrectomy.

Local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) is rare in patients with renal cell carcinoma (RCC); however, it is associated with poor prognosis and lacks standard treatment. Our study aimed to assess oncological outcomes and prognostic factors of patients that underwent targeted therapy for RPR after RN, and to evaluate the role of presurgical targeted therapy in this context. This was a retrospective multicenter study of 85 patients with RPR treated with targeted therapy for RPR after RN (July 2008-October 2020). Clinical and pathological characteristics were reported using descriptive statistics. Cancer-specific survival (CSS) was examined using the Cox proportional hazards model. The median follow-up time was 50 months (95% confidence interval [CI]: 33.3-66.7) after the RPR diagnosis. The median CSS was 96 months in the presurgical targeted therapy followed by surgical resection group and 42 months (95% CI: 28.8-55.2) in the targeted therapy alone group (P = .0011). In multivariate analysis, International Metastatic RCC Database Consortium classification intermediate/poor risk, number of recurrence lesions and surgical resection were independent predictors of CSS. Presurgical targeted therapy may increase the feasibility of tumor resection for RPR after RN. Patients who underwent surgical resection following presurgical targeted therapy had better CSS than those treated with targeted therapy alone.

SLG2 specifically regulates grain width through WOX11-mediated cell expansion control in rice.

Grain size is specified by three dimensions of length, width and thickness, and slender grain is a desirable quality trait in rice. Up to now, many grain size regulators have been identified. However, most of these molecules show influence on multi-dimensions of grain development, and only a few of them function specifically in grain width, a key factor determining grain yield and appearance quality. In this study, we identify the SLG2 (SLENDER GUY2) gene that specifically regulates grain width by affecting cell expansion in the spikelet hulls. SLG2 encodes a WD40 domain containing protein, and our biochemical analyses show that SLG2 acts as a transcription activator of its interacting WOX family protein WOX11. We demonstrate that the SLG2-associated WOX11 binds directly to the promoter of OsEXPB7, one of the downstream cell expansion genes. We show that knockout of WOX11 results in plants with a slender grain phenotype similar to the slg2 mutant. We also present that finer grains with different widths could be produced by combining SLG2 with the grain width regulator GW8. Collectively, we uncover the crucial role of SLG2 in grain width control, and provide a promising route to design rice plants with better grain shape and quality.

Relationship between machining accuracy and optical properties of convex blazed grating in ultra-precision cutting.

For ultra-precision machining of convex blazed grating elements there are inevitable machining errors, surface defects, and surface roughness, all of which can have an impact on their diffraction efficiency. In this paper, we use PCGrate software based on the integration method to establish the machining error model, surface defect model, and surface roughness model of convex spherical blazed grating with a curvature radius of 41.104 mm, a substrate diameter of 14 mm, a grating density of 53.97 line/mm and a blazed angle of 3.86° as the basic specification. To investigate the effect of base curvature radius error, grating period error, blazed angle error, grating ridge and valley passivation radius, Poisson burr height, and blaze surface roughness on their -1 order diffraction efficiency in the 0.95-2.5 µm spectral range. The results show that when the curvature radius error of the spherical base is less than ±80µm, the influence on diffraction efficiency can be ignored. Among the three groups of grating microstructure parameters, the influence of blazed angle on grating diffraction efficiency is the largest, followed by a grating period, and the influence of grating apex angle is the smallest, among which when the error of blazed angle is less than ±0.1° and the error of grating period is less than ±0.1µm, the influence on diffraction efficiency can be ignored. The effect of the passivation radius of the grating valley on the diffraction efficiency is smaller than that of the passivation radius of the grating ridge, and the maximum reduction of diffraction efficiency is 0.096 and 0.144 when the grating ridge and valley passivation radius are 50nm∼650 nm, respectively. The diffraction efficiency decreases significantly in the wavelength range of 1.9-2.5 µm with the increase of Poisson burr height and blaze surface roughness, and its effect on the diffraction efficiency can be neglected when the Poisson burr height is less than 0.5 µm and the blaze surface roughness value is less than RMS 1 nm. The machining error, surface defect, and surface roughness models of the convex blazed grating are optimized to provide a comprehensive machining accuracy basis for ultra-precision cutting of convex grating components.

Stabilization of high internal-phase Pickering emulsion using nobiletin crystals: assembly of supramolecular metal-polyphenolic coordination complexes for surface coating.

BACKGROUND: High internal-phase Pickering emulsions have attracted interest due to their unique properties and they have the potential for broad application in the food field, for example as fat replacers, for packaging, for delivery of nutrients or probiotics, and in the 3D printing of food. However, efficient and edible high internal-phase Pickering stabilizers are still a persistent challenge for food scientists. RESULTS: Nobiletin (NOB) was selected as a model substance. The particles' physicochemical properties (droplet size, rheological behavior, and transmission profile) showed that supramolecular metal-polyphenolic coordination networks could suppress the ripening and growth of crystals on the oil-water interface. When the ratio of tannic acid (TA) to Fe3+ was 3:1, the growth of NOB crystals could be inhibited effectively. Due to the reduction of energy steric hindrance in the adsorption process, the resulting NOB-TA3 -Fe3+ 1 (NT3 Fe1 ) nanoparticles had the greatest potential to extend emulsion storage time. CONCLUSION: The NOB-TA3 -Fe3+ 1 (NT3 Fe1 ) nanoparticles were able to stabilize a high internal-phase emulsion, of which the oil phase was 80%, for at least 30 days, eventually leading to high system viscosity. The findings in this work provide a novel selection of healthy emulsifiers and an effective emulsion delivery system for hydrophobic and crystalline nutrients. © 2023 Society of Chemical Industry.

Modulation of SF3B1 in the pre-mRNA spliceosome induces a RIG-I-dependent type I IFN response.

Nucleic acid-sensing pathways play critical roles in innate immune activation through the production of type I interferon (IFN-I) and proinflammatory cytokines. These factors are required for effective antitumor immune responses. Pharmacological modulators of the pre-mRNA spliceosome splicing factor 3b subunit 1 (SF3B1) are under clinical investigation as cancer cytotoxic agents. However, potential roles of these agents in aberrant RNA generation and subsequent RNA-sensing pathway activation have not been studied. In this study, we observed that SF3B1 pharmacological modulation using pladienolide B (Plad B) induces production of aberrant RNA species and robust IFN-I responses via engagement of the dsRNA sensor retinoic acid-inducible gene I (RIG-I) and downstream interferon regulatory factor 3. We found that Plad B synergized with canonical RIG-I agonism to induce the IFN-I response. In addition, Plad B induced NF-κB responses and secretion of proinflammatory cytokines and chemokines. Finally, we showed that cancer cells bearing the hotspot SF3B1K700E mutation, which leads to global aberrant splicing, had enhanced IFN-I response to canonical RIG-I agonism. Together, these results demonstrate that pharmacological modulation of SF3B1 in cancer cells can induce an enhanced IFN-I response dependent on RIG-I expression. The study suggests that spliceosome modulation may not only induce direct cancer cell cytotoxicity but also initiate an innate immune response via activation of RNA-sensing pathways.

Second-line treatment with axitinib plus toripalimab in metastatic renal cell carcinoma: a retrospective multicenter study.

Aim: To evaluate the efficacy and safety of second-line treatment with axitinib plus toripalimab in patients with metastatic renal cell carcinoma and failure of VEGFR tyrosine kinase inhibitors. Methods: Data were collected restropectively. Kaplan-Meier analysis and Cox proportional hazards model determined the efficacy outcomes. Results: In 57 patients, objective response rate was 31.6% and median progression-free survival (PFS) was 11.7 months, while median overall survival was not reached. Median PFS was not reached in favorable-risk patients, whereas PFS of 11.0 and 7.8 months were observed in intermediate- and poor-risk patients, respectively (p = 0.011). The treatment-related toxicities were mild in nature. Conclusion: Second-line therapy with axitinib plus toripalimab provided durable response rate, longer PFS and a tolerable safety profile.

Renal cell carcinoma is the most common type of kidney cancer. In cases of metastatic RCC, the combination of axitinib (a VEGFR tyrosine kinase inhibitor) and toripalimab (a recombinant humanized anti-PD-L1 monoclonal antibody) may be beneficial. We investigated the efficacy and safety of second-line treatment with axitinib plus toripalimab in patients with metastatic renal cell carcinoma and anti-VEGFR tyrosine kinase inhibitor therapy failure. Data on patients treated with axitinib plus toripalimab were collected retrospectively and we evaluated the response rate, survival status and toxicities. In total, 31.6% of patients responded to the treatment, with a median progression-free survival of 11.7 months. The combination therapy was safe, with hypertension being the most common grade ≥3 adverse event.

Panaxydol Derived from Panax notoginseng Promotes Nerve Regeneration after Sciatic Nerve Transection in Rats.

BACKGROUND: Peripheral nerve regeneration is a coordinated process of Schwann cell (SC) reprogramming and intrinsic neuronal growth program activation. Panaxydol (PND) is a strong biologically active traditional Chinese medicine monomer extracted from Panax notoginseng rhizomes. In vitro, PND protects neurons and SCs from injury and stimulates the expression and secretion of neurotrophic factors (NTFs) by SCs. We hypothesized that PND may also promote peripheral nerve regeneration in adult animals. METHODS: PND (10 mg/kg body weight) was injected intraperitoneally into the Sprague-Dawley (SD) rats for two consecutive weeks after sciatic nerve transection. The morphology of the repaired sciatic nerve was evaluated after 16 weeks, and sensory and motor function recovery was evaluated using functional and behavioral techniques. RESULTS: PND was biologically safe at an injection dose of 10 mg/kg/day. After 14 days, it significantly increased the myelination of regenerated nerve fibers, and promoted sensory and motor function recovery. In the early stage of injury, PND significantly upregulated the mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptors in distal injured nerves, which may represent a possible mechanism by which PND promotes nerve regeneration in vivo. CONCLUSIONS: Our study demonstrated that PND leads to sensory and motor recovery in a sciatic nerve transection model rat. Furthermore, we showed that BDNF mRNA level was significantly increased in the injured distal nerve, potentially contributing to the functional recovery. Further research is warrantied to examine whether direct injection is a more efficient method to increase BDNF expression compared to an exogenous BDNF administration.

Linear Spatial Misregistration Detection and Correction Based on Spectral Unmixing for FAHI Hyperspectral Imagery.

In push-broom hyperspectral imaging systems, the sensor rotation to the optical plane leads to linear spatial misregistration (LSM) in hyperspectral images (HSIs). To compensate for hardware defects through software, this paper develops four methods to detect LSM in HSIs. Different from traditional methods for grayscale images, the method of fitting the sum of abundance (FSAM) and the method of searching for equal abundance (SEAM) are achieved by hyperspectral unmixing for a selected rectangular transition areas containing an edge, which makes good use of spatial and spectral information. The method based on line detection for band-interleaved-by-line (BIL) images (LDBM) and the method based on the Fourier transform of BIL images (FTBM) aim to characterize the slope of line structure in BIL images and get rid of the dependence on scene and wavelength. A full strategy is detailed from aspects of data selection, LSM detection, and image correction. The full spectrum airborne hyperspectral imager (FAHI) is China's new generation push-broom scanner. The HSIs obtained by FAHI are tested and analyzed. Experiments on simulation data compare the four proposed methods with traditional methods and prove that FSAM outperforms other methods in terms of accuracy and stability. In experiments on real data, the application of the full strategy on FAHI verifies its effectiveness. This work not only provides reference for other push-broom imagers with similar problems, but also helps to reduce the requirement for hardware calibration.

Separable regulation of POW1 in grain size and leaf angle development in rice.

Leaf angle is one of the key factors that determines rice plant architecture. However, the improvement of leaf angle erectness is often accompanied by unfavourable changes in other traits, especially grain size reduction. In this study, we identified the pow1 (put on weight 1) mutant that leads to increased grain size and leaf angle, typical brassinosteroid (BR)-related phenotypes caused by excessive cell proliferation and cell expansion. We show that modulation of the BR biosynthesis genes OsDWARF4 (D4) and D11 and the BR signalling gene D61 could rescue the phenotype of leaf angle but not grain size in the pow1 mutant. We further demonstrated that POW1 functions in grain size regulation by repressing the transactivation activity of the interacting protein TAF2, a highly conserved member of the TFIID transcription initiation complex. Down-regulation of TAF2 rescued the enlarged grain size of pow1 but had little effect on the increased leaf angle phenotype of the mutant. The separable functions of the POW1-TAF2 and POW1-BR modules in grain size and leaf angle control provide a promising strategy for designing varieties with compact plant architecture and increased grain size, thus promoting high-yield breeding in rice.

Dynamic Spatiotemporal Pattern Recognition With Recurrent Spiking Neural Network.

Our real-time actions in everyday life reflect a range of spatiotemporal dynamic brain activity patterns, the consequence of neuronal computation with spikes in the brain. Most existing models with spiking neurons aim at solving static pattern recognition tasks such as image classification. Compared with static features, spatiotemporal patterns are more complex due to their dynamics in both space and time domains. Spatiotemporal pattern recognition based on learning algorithms with spiking neurons therefore remains challenging. We propose an end-to-end recurrent spiking neural network model trained with an algorithm based on spike latency and temporal difference backpropagation. Our model is a cascaded network with three layers of spiking neurons where the input and output layers are the encoder and decoder, respectively. In the hidden layer, the recurrently connected neurons with transmission delays carry out high-dimensional computation to incorporate the spatiotemporal dynamics of the inputs. The test results based on the data sets of spiking activities of the retinal neurons show that the proposed framework can recognize dynamic spatiotemporal patterns much better than using spike counts. Moreover, for 3D trajectories of a human action data set, the proposed framework achieves a test accuracy of 83.6% on average. Rapid recognition is achieved through the learning methodology-based on spike latency and the decoding process using the first spike of the output neurons. Taken together, these results highlight a new model to extract information from activity patterns of neural computation in the brain and provide a novel approach for spike-based neuromorphic computing.

Hierarchical Dynamical Model for Multiple Cortical Neural Decoding.

Motor brain machine interfaces (BMIs) interpret neural activities from motor-related cortical areas in the brain into movement commands to control a prosthesis. As the subject adapts to control the neural prosthesis, the medial prefrontal cortex (mPFC), upstream of the primary motor cortex (M1), is heavily involved in reward-guided motor learning. Thus, considering mPFC and M1 functionality within a hierarchical structure could potentially improve the effectiveness of BMI decoding while subjects are learning. The commonly used Kalman decoding method with only one simple state model may not be able to represent the multiple brain states that evolve over time as well as along the neural pathway. In addition, the performance of Kalman decoders degenerates in heavy-tailed nongaussian noise, which is usually generated due to the nonlinear neural system or influences of movement-related noise in online neural recording. In this letter, we propose a hierarchical model to represent the brain states from multiple cortical areas that evolve along the neural pathway. We then introduce correntropy theory into the hierarchical structure to address the heavy-tailed noise existing in neural recordings. We test the proposed algorithm on in vivo recordings collected from the mPFC and M1 of two rats when the subjects were learning to perform a lever-pressing task. Compared with the classic Kalman filter, our results demonstrate better movement decoding performance due to the hierarchical structure that integrates the past failed trial information over multisite recording and the combination with correntropy criterion to deal with noisy heavy-tailed neural recordings.

Diagnostic Performance of American College of Radiology TI-RADS: A Systematic Review and Meta-Analysis.

OBJECTIVE. The objective of our study was to investigate the diagnostic performance of the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) in the risk stratification of thyroid nodules. MATERIALS AND METHODS. A literature search of MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar was performed for articles published before July 31, 2019. We included studies using ACR TI-RADS for stratification of thyroid nodules and cytology results from ultrasound-guided fine-needle aspiration biopsy (FNAB), pathology results from surgical resection of the thyroid, or both FNAB cytology and surgical pathology results as the reference standard. Summary estimates of sensitivity and specificity were calculated with the bivariate random-effects modeling and are visually presented in forest plots. We performed multiple subgroup analyses and meta-regression to explore the effects of various clinical settings. We compared ACR TI-RADS with the American Thyroid Association (ATA) guidelines and Korean Thyroid Imaging Reporting and Data System (TIRADS) in studies providing head-to-head comparison. RESULTS. Sixteen studies with 18,614 patients involving a total of 21,882 nodules, were included. The pooled sensitivity and specificity of ACR TI-RADS were 0.89 (95% CI, 0.81-0.93) and 0.70 (95% CI, 0.60-0.78), respectively. The calculated area under summary ROC curve was 0.86 (95% CI, 0.83-0.89), with a diagnostic odds ratio of 18.46 (95% CI, 9.77-34.88). Meta-regression revealed that patient number was a significant factor for heterogeneity (p = 0.02). Ten studies compared the performance of ACR TI-RADS and ATA guidelines: The pooled sensitivity was 0.83 versus 0.87 (p = 0.5), respectively, and the pooled specificity was 0.69 versus 0.50 (p = 0.1). In six studies providing direct comparison of ACR TI-RADS and Korean TIRADS, the pooled sensitivity was 0.85 versus 0.91 (p = 0.13), and the pooled specificity was 0.57 versus 0.24 (p < 0.001). CONCLUSION. ACR TI-RADS showed favorable sensitivity and moderate specificity in risk stratification of thyroid nodules. The use of ACR TI-RADS could avoid a large number of unnecessary biopsies, although at the cost of a slight decline in sensitivity.

MiR-133a-3p attenuates resistance of non-small cell lung cancer cells to gefitinib by targeting SPAG5.

BACKGROUND: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), clinically used to treat patients with non-small cell lung cancer driven by EGFR mutations. Unfortunately, EGFR-TKI resistance has become a clinical problem for the effective treatment of NSCLC patients. The purpose of this study was to explore the effect and mechanism of miR-133a-3p on the gefitinib sensitivity of NSCLC cells. METHODS: The gefitinib-resistant PC9 (PC9/GR) cells were established through repeated long-term exposure to gefitinib for half a year. Then, PC9/GR cells were transfected with miR-133a-3p mimics and PC9 cells were transfected with miR-133a-3p inhibitors to increase or decrease the expression of miR-133a-3p. CCK-8 assay, colony formation assay, and caspase-3 activity assay were employed to detect cell resistance to gefitinib. Quantitative real-time PCR and Western blotting were used to evaluate the levels of miR-133a-3p, SPAG5, and other related genes. Starbase database was used to predict the target gene of miR-133a-3p and the prognosis of NSCLC patients. Target gene of miR-133a-3p was verified through dual-luciferase reporter gene assay. RESULTS: MiR-133a-3p was significantly downregulated in gefitinib-resistant cell line PC9/GR vs. gefitinib-sensitive cell line PC9. Overexpression of miR-133a-3p increased the sensitivity of NSCLC cells to gefitinib and vice versa. Furthermore, SPAG5 is an important target gene of miR-133a-3p, and SPAG5 can reverse miR-133a-3p-mediated gefitinib sensitivity of NSCLC cells. CONCLUSIONS: These findings indicated that miR-133a-3p/SPAG5 axis played a vital role in acquired resistance to gefitinib in NSCLC cells, and miR-133a-3p may represent a potential therapeutic strategy for the treatment of human NSCLC.