Detection of pTDP-43 via routine muscle biopsy: A promising diagnostic biomarker for amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, pathologically characterized by TDP-43 aggregates. Recent evidence has been indicated that phosphorylated TDP-43 (pTDP-43) is present not only in motor neurons but also in muscle tissues. However, it is unclear whether testing pTDP-43 aggregation in muscle tissue would assist in the diagnosis of ALS. We propose three key questions: (i) Is aggregation of pTDP-43 detectable in routine biopsied muscles? (ii) Can detection of pTDP-43 aggregation discriminate between ALS and non-ALS patients? (iii) Can pTDP-43 aggregation be observed in the early stages of ALS? We conducted a diagnostic study comprising 2 groups: an ALS group in which 18 cases underwent muscle biopsy screened from a registered ALS cohort consisting of 802 patients and a non-ALS control group, in which we randomly selected 54 muscle samples from a biospecimen bank of 684 patients. Among the 18 ALS patients, 3 patients carried pathological GGGGCC repeats in the C9ORF72 gene, 2 patients carried SOD1 mutations, and 7 patients were at an early stage with only one body region clinically affected. The pTDP-43 accumulation could be detected in routine biopsied muscles, including biceps brachii, deltoid, tibialis anterior, and quadriceps. Abnormal aggregation of pTDP-43 was present in 94.4% of ALS patients (17/18) compared to 29.6% of non-ALS controls (16/54; p < 0.001). The pTDP-43 aggregates were mainly close to the sarcolemma. Using a semi-quantified pTDP-43 aggregates score, we applied a cut-off value of 3 as a diagnostic biomarker, resulting in a sensitivity of 94.4% and a specificity of 83.3%. Moreover, we observed that accumulation of pTDP-43 occurred in muscle tissues prior to clinical symptoms and electromyographic lesions. Our study provides proof-of-concept for the detection of pTDP-43 accumulation via routine muscle biopsy which may serve as a novel biomarker for diagnosis of ALS.

Accurate preoperative prediction of nodal metastasis in papillary thyroid microcarcinoma: Towards optimal management of patients.

OBJECTIVE: To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the "low-risk" classification for tailored treatment strategies. METHODS: This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis. RESULTS: Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule-capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility. CONCLUSION: This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of "low-risk" categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.

Optimizing robotic thyroid surgery: lessons learned from an retrospective analysis of 104 cases.

Background: Robotic assistance in thyroidectomy is a developing field that promises enhanced surgical precision and improved patient outcomes. This study investigates the impact of the da Vinci Surgical System on operative efficiency, learning curve, and postoperative outcomes in thyroid surgery. Methods: We conducted a retrospective cohort study of 104 patients who underwent robotic thyroidectomy between March 2018 and January 2022. We evaluated the learning curve using the Cumulative Sum (CUSUM) analysis and analyzed operative times, complication rates, and postoperative recovery metrics. Results: The cohort had a mean age of 36 years, predominantly female (68.3%). The average body mass index (BMI) was within the normal range. A significant reduction in operative times was observed as the series progressed, with no permanent hypoparathyroidism or recurrent laryngeal nerve injuries reported. The learning curve plateaued after the 37th case. Postoperative recovery was consistent, with no significant difference in hospital stay duration. Complications were minimal, with a noted decrease in transient vocal cord palsy as experience with the robotic system increased. Conclusion: Robotic thyroidectomy using the da Vinci system has demonstrated a significant improvement in operative efficiency without compromising safety. The learning curve is steep but manageable, and once overcome, it leads to improved surgical outcomes and high patient satisfaction. Further research with larger datasets and longer follow-up is necessary to establish the long-term benefits of robotic thyroidectomy.

The Relationship Between the Expression of circFAT1 and Immune Cell in Patients with Non-Small Cell Lung Cancer.

Objective: To analyze the correlation between the expression of circFAT1 in serum and immune cells in patients with non-small cell lung cancer (NSCLC). Methods: A total of 96 patients with NSCLC admitted to our hospital from November 2019 to November 2022 were regarded as the study subjects. In the meantime, 96 volunteers who had physical examination in our hospital were regarded as the control group. The expression level of circFAT1 in serum was detected by real-time fluorescence quantitative PCR. NSCLC cancer tissue (NSCLC group) and paracancerous tissue (tissue ≥ 2cm away from the focus) (paracancerous group) were collected during the operation, the expression of CD4+, CD8+ and Foxp3+ in tissues was determined by immunohistochemistry; the expression level of circFAT1 mRNA in NSCLC tissue was analyzed using the Ualcan database. Spearman correlation was applied to analyze the correlation between the expression of circFAT1 and immune cells (CD4+, Foxp3+, CD8+). Results: The level of circFAT1 in NSCLC tissue was higher than that in normal tissue (P < 0.05). Compared with the control group, the expression level of circFAT1 in serum of NSCLC group was obviously higher (P < 0.05). The expression level of circFAT1 was related to lymph node metastasis, TNM stage and differentiation (P < 0.05). Compared with the paracancerous group, the positive expression rate of CD8+ in NSCLC group was obviously lower, and the positive expression rates of CD4+ and Foxp3+ were obviously higher (P < 0.05). The expression of CD4+, Foxp3+ and CD8+ in NSCLC patients' cancer tissue was related to lymph node metastasis, TNM stage and differentiation degree (P < 0.05). Spearman correlation analysis showed that circFAT1 was positively correlated with the expression of CD4+ and Foxp3+ and negatively correlated with the expression of CD8+ (P < 0.05). Conclusion: CircFAT1 is highly expressed in the serum of NSCLC patients and is closely related to immune cells.

Metronomic dosing of ovarian cancer cells with the ATR inhibitor AZD6738 leads to loss of CDC25A expression and resistance to ATRi treatment.

OBJECTIVE: ATR kinase inhibitors promote cell killing by inducing replication stress and through potentiation of genotoxic agents in gynecologic cancer cells. To explore mechanisms of acquired resistance to ATRi in ovarian cancer, we characterized ATRi-resistant ovarian cancer cells generated by metronomic dosing with the clinical ATR inhibitor AZD6738. METHODS: ATRi-resistant ovarian cancer cells (OVCAR3 and OV90) were generated by dosing with AZD6738 and assessed for sensitivity to Chk1i (LY2603618), PARPi (Olaparib) and combination with cisplatin or a CDK4/6 inhibitor (Palbociclib). Models were characterized by diverse methods including silencing CDC25A in OV90 cells and assessing impact on ATRi response. Serum proteomic analysis of ATRi-resistant OV90 xenografts was performed to identify circulating biomarker candidates of ATRi-resistance. RESULTS: AZD6738-resistant cell lines are refractory to LY2603618, but not to Olaparib or combinations with cisplatin. Cell cycle analyses showed ATRi-resistant cells exhibit G1/S arrest following AZD6738 treatment. Accordingly, combination with Palbociclib confers resistance to AZD6738. AZD6738-resistant cells exhibit altered abundances of G1/S phase regulatory proteins, including loss of CDC25A in AZD6738-resistant OV90 cells. Silencing of CDC25A in OV90 cells confers resistance to AZD6738. Serum proteomics from AZD6738-resistant OV90 xenografts identified Vitamin D-Binding Protein (GC), Apolipoprotein E (APOE) and A1 (APOA1) as significantly elevated in AZD6738-resistant backgrounds. CONCLUSIONS: We show that metronomic dosing of ovarian cancer cells with AZD6738 results in resistance to ATR/ Chk1 inhibitors, that loss of CDC25A expression represents a mechanism of resistance to ATRi treatment in ovarian cancer cells and identify several circulating biomarker candidates of CDC25A low, AZD6738-resistant ovarian cancer cells.

Activation of the Vascular Smooth Muscle GLP-1/NCX1 Pathway Regulates Cytoplasmic Ca2+ Homeostasis and Improves Blood Pressure Variability in Hypertension.

BACKGROUND: Hypertension is the most common cardiovascular disease, and its main harmful effect is chronic damage to target organs. In some patients with well-controlled blood pressure, target organ damage still occurs. GLP-1 agonists have significant cardiovascular benefits, but their antihypertensive effect is limited. The cardiovascular protective effect of GLP-1 is worth studying. METHODS: The ambulatory blood pressure of spontaneously hypertensive rats (SHRs) was detected by ambulatory blood pressure monitoring, and the characteristics of blood pressure and the effect of subcutaneous intervention with a GLP-1R agonist on blood pressure were observed. To explore the mechanism of the cardiovascular benefit of GLP-1R agonists in SHRs, we evaluated the effects of GLP-1R agonists on vasomotor function and calcium homeostasis in vascular smooth muscle cells (VSMCs) in vitro. RESULTS: Although the blood pressure of SHRs was significantly higher than that of WKY rats, the blood pressure variability of SHRs was also significantly higher than that of the control group. The GLP-1R agonist significantly reduced blood pressure variability in SHRs, but the antihypertensive effect was not obvious. GLP-1R agonists can significantly improve the cytoplasmic calcium overload of VSMCs in SHRs by upregulating the expression of NCX1, improving the systolic and diastolic functions of arterioles, and reducing blood pressure variability. CONCLUSIONS: Taken together, these results provide evidence that GLP-1R agonists improved VSMC cytoplasmic Ca2+ homeostasis through upregulated NCX1 expression in SHRs, which plays a key role in blood pressure stability and broad cardiovascular benefits.

Global Consensus Tracking Control for High-Order Nonlinear Multiagent Systems With Prescribed Performance.

In this article, we investigate the prescribed performance tracking control problem for high-order nonlinear multiagent systems (MASs) under directed communication topology and unknown control directions. Different from most existing prescribed performance consensus control methods where certain initial conditions are needed to be satisfied, here the restriction related to the initial conditions is removed and global tracking result irrespective of initial condition is established. Furthermore, output consensus tracking is achieved asymptotically with arbitrarily prescribed transient performance in spite of the directed topology and unknown control directions. Our development benefits from the performance function and prescribed-time observer. Both theoretical analysis and numerical simulation confirm the validity of the developed control scheme.

Values of serum neutrophil gelatinase-associated lipocalin and cystatin C after percutaneous coronary intervention for early diagnosis of contrast-induced nephropathy.

Objective: Serum creatinine (SCr) is not a sensitive and reliable index for the early diagnosis of acute kidney injury caused by contrast-induced nephropathy (CIN). The aim of this study was to explore the values of serum neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (Cys-C) after percutaneous coronary intervention (PCI) for the early diagnosis of CIN. Methods: Three hundred patients receiving PCI from January 2018 to December 2020 were assigned to a CIN group (n=25) and a non-CIN group (n=275), respectively. SCr, Cys-C and NGAL levels were measured, and their sensitivities for early CIN diagnosis were evaluated by the area under the receiver operating characteristic curve (AUC) values. Results: The NGAL and Cys-C levels of the CIN group began to rise 6 and 12 h after operation, respectively (P<0.05). The CIN group had higher NGAL and Cys-C levels than those of the non-CIN group 12, 24 and 48 h after operation (P<0.05). The AUC values of NGAL, Cys-C and SCr 24 h after operation were 0.885, 0.874 and 0.856, respectively. Conclusion: The serum NGAL and Cys-C levels of patients after PCI reflect the early changes of renal function, which are valuable for early CIN diagnosis.

A low-frequency multiple-band sound insulator without blocking ventilation along a pipe.

It is challenging to insulate sound transmission in low frequency-bands without blocking the air flow in a pipe. In this work, a small and light membrane-based cubic sound insulator is created to block acoustic waves in multiple low frequency-bands from 200 to 800 Hz in pipes. Due to distinct vibration modes of the membrane-type faces of the insulator and co-action of acoustic waves transmitting along different paths, large sound attenuation is achieved in multiple frequency-bands, and the maximum transmission loss reaches 25 dB. Furthermore, because the sound insulator with a deep subwavelength size is smaller than the cross-sectional area of the pipe, it does not block ventilation along the pipe.

Dual-emission fluorescent nanoprobe based on Ag nanoclusters for sensitive detection of Cu(II).

Noble metal nanoclusters have attracted much attention because of their excellent fluorescence properties. In this work, we demonstrated a dual-emission fluorescent nanocomposite based on silver nanoclusters. First, we synthesized positively charged His-AgNCs, which emits intense blue light, and then Ag nanoclusters with stable red emission were synthesized using DHLA as the ligand. Thus a dual-emission fluorescent nanoprobe was successfully obtained through electrostatic self-assembly, with the advantages of good water solubility and excellent stability. Based on the intensity ratio of the two emission peaks, the nanoprobe can be used for selective and sensitive detection of copper ions, and presents a good linear relationship within a certain concentration range. In addition, we also designed a polymer film, and our dual-emission nanoprobe was successfully loaded onto it, which means that the visual detection of copper ions is possible. This indicates that our dual-emission fluorescent nanoprobe has potential application prospects in environmental analysis, medical diagnosis, biological detection, etc.

The correlation between PLR-NLR and prognosis in acute myocardial infarction.

OBJECTIVE: To explore the correlation between the prognosis of acute myocardial infarction (AMI) and the platelet to lymphocyte ratio (PLR)-neutrophil to lymphocyte ratio (NLR). METHODS: A retrospective analysis was performed on the data of 300 patients with AMI admitted to our hospital between August 2016 and August 2019. The general data, data on the patients' major adverse cardiovascular and cerebrovascular events (MACCE), the global registry of acute coronary events (GRACE), and the different groups of patients' survival times were compared. RESULTS: The area under the curve (AUC) of PLR was 0.810 [95% CI (0.751, 0.869), P < 0.001]. The AUC value of NLR was 0.882 [95% CI (0.839, 0.925), P < 0.001]. In our study, 102 patients were placed in the high PLR group, 198 patients were placed in the low PLR group, 126 patients were placed in the high NLR group, 174 patients were placed in the low NLR group, 174 patients were placed in PLR-NLR group 0, 24 patients were placed in PLR-NLR group 1, and 102 patients were placed in PLR-NLR group 2. The heart rates (HR) and brain natriuretic peptide (BNP) levels in Group 0 were the lowest among the three groups (P < 0.05), and the cTnI levels were observably lower than they were in Group 2 (P < 0.05). The patients' HR and BNP ratios in Group 1 were notably lower than the HR and BNP ratios in Group 2 (P < 0.05). The lowest incidence of MACCE was found in PLR-NLR Group 0. The number of intermediate-risk of patients in Group 0 was the lowest among the three groups. The order of the overall survival (OS) and the progression-free survival (PFS) of the three PLR-NLR Groups 0 were Group 0 > Group 1 > Group 2 (P < 0.001). The survival rate (SR) of the patients in PLR-NLR Group 0 was 100% within 2 years, which was significantly greater than the survival rates in Group 1 and Group 2 (P < 0.05). The SR of the patients in Group 0 was 98.8% within five years, which was also significantly higher than the survival rates in Groups 1 and 2 (P < 0.05). CONCLUSION: The PLR-NLR combination has an essential effect on the prognostic analysis of AMI. The incidence of MACCE increases with an increase in PLR-NLR.

Multifocal neuroendocrine cell hyperplasia accompanied by tumorlet formation and pulmonary sclerosing pneumocytoma: A case report.

BACKGROUND: Pulmonary tumorlets are nodular hyperplastic neuroendocrine cells (NECs) that extend beyond the basement membrane. They often coexist with other lung diseases such as fibrosis and bronchiectasis, but rarely accompanied by pulmonary sclerosing pneumocytoma (PSP), which has not been reported in the literature. CASE SUMMARY: A 54-year-old woman was admitted to the hospital because she had symptoms of bloody sputum for more than 4 mo and hemoptysis for 1 wk. Computed tomography images showed atrophy accompanied by infections in the middle lobe of her right lung. Moreover, numerous nodules were identified in the middle lobe of the right lung. The patient underwent thoracoscopic pneumonectomy of the middle lobe of the right lung, and the resected mass was pathologically confirmed to have bronchiectasis, multifocal NEC hyperplasia accompanied by tumorlet, and PSP. CONCLUSION: Our report presents a rare clinical case of bronchiectasis complicated with multifocal NEC hyperplasia, tumorlet, and PSP.

Tanshinone IIA alleviates brain damage in a mouse model of neuromyelitis optica spectrum disorder by inducing neutrophil apoptosis.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD), an autoimmune astrocytopathic disease associated with the anti-aquaporin-4 (AQP4) antibody, is characterized by extensive necrotic lesions primarily located on the optic nerves and spinal cord. Tanshinone IIA (TSA), an active natural compound extracted from Salvia miltiorrhiza Bunge, has profound immunosuppressive effects on neutrophils. OBJECTIVE: The present study aimed to evaluate the effect of TSA on NMOSD mice and explore the underlying mechanisms. Mice were initially administered TSA (pre-TSA group, n = 20) or vehicle (vehicle group, n = 20) every 8 h for 3 days, and then NMOSD model was induced by intracerebral injection of NMOSD-immunoglobulin G (NMO-IgG) and human complement (hC). In addition, post-TSA mice (n = 10) were administered equal dose of TSA at 8 h and 16 h after model induction. At 24 h after intracerebral injection, histological analysis was performed to assess the inhibitory effects of TSA on astrocyte damage, demyelination, and neuroinflammation in NMOSD mice, and western blotting was conducted to clarify the effect of TSA on the NF-κB and MAPK signaling pathways. Furthermore, flow cytometry and western blotting were conducted to verify the proapoptotic effects of TSA on neutrophils in vitro. RESULTS: There was a profound reduction in astrocyte damage and demyelination in the pre-TSA group and post-TSA group. However, prophylactic administration of TSA induced a better effect than therapeutic treatment. The number of infiltrated neutrophils was also decreased in the lesions of NMOSD mice that were pretreated with TSA. We confirmed that prophylactic administration of TSA significantly promoted neutrophil apoptosis in NMOSD lesions in vivo, and this proapoptotic effect was mediated by modulating the caspase pathway in the presence of inflammatory stimuli in vitro. In addition, TSA restricted activation of the NF-κB signaling pathway in vivo. CONCLUSION: Our data provide evidence that TSA can act as a prophylactic agent that reduces NMO-IgG-induced damage in the mouse brain by enhancing the resolution of inflammation by inducing neutrophil apoptosis, and TSA may serve as a promising therapeutic agent for neutrophil-associated inflammatory disorders, such as NMOSD.

Distributed Secure State Estimation and Control for CPSs Under Sensor Attacks.

In this paper, we investigate the distributed secure state estimation and control problems for interconnected cyber-physical systems (CPSs) with some sensors being attacked. First, by exploring the distinct properties of the unidentifiable attacks to a CPS, an explicit sufficient condition that the secure state estimation problem can be solvable is established. Then distributed preselectors and observers are presented to solve the secure state estimation problems. Furthermore, with the obtained state estimation, fractional dynamic surface-based distributed secure controllers are also proposed for the secure control problem. Theoretical analysis shows that, with the proposed distributed secure observers and controllers, not only the state of the CPS under attacks can be obtained in a given finite time but also the dynamic surface can be achieved and maintained in a finite time. Finally, the results are applied to an islanded micro-grid system as an illustration, which verifies the effectiveness of the proposed schemes.

Jupiter microtubule-associated homolog 1 (JPT1): A predictive and pharmacodynamic biomarker of metformin response in endometrial cancers.

Preoperative use of metformin in obese women with endometrioid endometrial cancer (EEC) reduces tumor proliferation and inhibits the mammalian target of rapamycin pathway, though is only effective in select cases. This study sought to identify a predictive and/or pharmacodynamic proteomic signature of metformin response to tailor its pharmacologic use. Matched pre- and post-metformin-treated tumor tissues from a recently completed preoperative window trial of metformin in EEC patients (ClinicalTrials.gov: NCT01911247) were analyzed by mass spectrometry (MS)-based proteomic and immunohistochemical analyses. Jupiter microtubule-associated homolog 1 (JPT1) was significantly elevated in metformin responders (n = 13) vs nonresponders (n = 7), and found to decrease in abundance in metformin responders following treatment; observations that were verified by immunohistochemical staining for JPT1. Metformin response and loss of JPT1 were assessed in RL95-2 and ACI-181 endometrial cancer (EC) cell lines. We further identified that silencing of JPT1 abundance does not alter cellular response to metformin or basal cell proliferation, but that JPT1 abundance does decrease in response to metformin treatment in RL95-2 and ACI-181 EC cell lines. These data suggest that JPT1 represents a predictive and pharmacodynamic biomarker of metformin response that, if validated in larger patient populations, may enable preoperative EEC patient stratification to metformin treatment and the ability to monitor patient response.

Primary gastric melanoma: A case report with imaging findings and 5-year follow-up.

BACKGROUND: Most melanomas identified in the stomach are metastatic; primary gastric melanoma (PGM) is extremely rare, and the relevant studies are relatively scarce. PGM may be incorrectly diagnosed as other gastric malignant tumor types. CASE SUMMARY: We describe a rare case of PGM confirmed through long-term clinical observation and pathological diagnosis. A 67-year-old woman presented to our hospital with recurrent chest tightness and chest pain. Digital gastrointestinal radiography revealed a circular shadow in the gastric cardia. Computed tomography (CT) revealed a heterogeneous tumor with uneven enhancement. Enlarged lymph nodes were noted in the lesser curvature of the stomach. On magnetic resonance imaging (MRI), T1- and T2-weighted imaging revealed hyperintensity in and hypointensity in the tumor, respectively, both of which increased substantially after uneven enhancement. Near total gastrectomy was performed, and the tumor was pathologically confirmed to be a gastric melanoma. Because no other possible primary site of malignant melanoma was suspected, a clinical diagnosis of PGM was made. The patient was followed for nearly 5 years, during which she received CT reexamination, but no recurrence or metastasis was observed. CONCLUSION: Certain imaging characteristics could be revealed in PGM. Imaging examination can be of great value in preoperative diagnosis, differential diagnosis, and follow-up of patients with PGM.

Needles in a Haystack: Tracking City-Scale Moving Vehicles from Continuously Moving Satellite.

In recent years, the satellite videos have been captured by moving satellite platforms. In contrast to consumers, movies, and common surveillance videos, satellite videos can record the snapshots of city-scale scenes. In a broad fieldof-view of satellite videos, each moving target would be very tiny and usually composed of several pixels in frames. Even worse, the noise signals also exist in the video frames, and the background of the video frames subpixel-level and uneven moving thanks to the motion of satellites. We argue that it is a novel type of computer vision task since previous technologies are unable to detect such tiny moving vehicles efficiently. This paper proposes a novel framework that can identify small moving vehicles in satellite videos. In particular, we offer a novel detecting algorithm based on the local noise modeling. We differentiate the potential vehicle targets from noise patterns by an exponential probability distribution. Subsequently, a multi-morphologicalcue based discrimination strategy is designed to distinguish correct vehicle targets from the existing noises further. Another significant contribution is to introduce a series of evaluation protocols to measure the performance of tiny moving vehicle detection systematically. We annotate satellite videos manually to test our algorithms under different evaluation criterions. The proposed algorithm is also compared with the state-of-the-art baselines, which demonstrates the advantages of our framework over the benchmarks. Besides, the dataset would be downloaded from http://first.authour.github.com.

The application of a non-doped composite hole transport layer of [MoO3/CBP] n with multi-periodic structure for high power efficiency organic light-emitting diodes.

A non-doped multi-periodic structure of composite hole transport layer of [MoO3/CBP] n was applied to organic light-emitting diodes. All devices with such hole transport layers showed low turn-on voltage of about 3 V, ultra-high luminance of >110 000 cd m-2, high current efficiency of >50 cd A-1, and high EQE of more than 15%. The optimized device exhibited power efficiency increase of 66% and 18% relative to the single periodic and doped structure OLEDs. The achievement of the reduced driving voltage and improved power efficiency can be attributed to the significantly enhanced hole injection and transport induced by the multi-periodic structure of composite hole transport layer, which was demonstrated via a series of hole-only devices. For improved hole injection and transport mechanism, we also provided a detailed discussion in combination with atomic force microscopy measurements.

SGB-ELM: An Advanced Stochastic Gradient Boosting-Based Ensemble Scheme for Extreme Learning Machine.

A novel ensemble scheme for extreme learning machine (ELM), named Stochastic Gradient Boosting-based Extreme Learning Machine (SGB-ELM), is proposed in this paper. Instead of incorporating the stochastic gradient boosting method into ELM ensemble procedure primitively, SGB-ELM constructs a sequence of weak ELMs where each individual ELM is trained additively by optimizing the regularized objective. Specifically, we design an objective function based on the boosting mechanism where a regularization item is introduced simultaneously to alleviate overfitting. Then the derivation formula aimed at solving the output-layer weights of each weak ELM is determined using the second-order optimization. As the derivation formula is hard to be analytically calculated and the regularized objective tends to employ simple functions, we take the output-layer weights learned by the current pseudo residuals as an initial heuristic item and thus obtain the optimal output-layer weights by using the derivation formula to update the heuristic item iteratively. In comparison with several typical ELM ensemble methods, SGB-ELM achieves better generalization performance and predicted robustness, which demonstrates the feasibility and effectiveness of SGB-ELM.

Baicalein inhibits acinar-to-ductal metaplasia of pancreatic acinal cell AR42J via improving the inflammatory microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J. To investigate ADM and baicalein effects in vitro, AR42J were treated with recombinant rat Tumor Necrosis Factor alpha (rTNFα) with or without baicalein for 5 days. Results showed that rTNFα-induced AR42J cells switched their phenotype from dominantly amylase-positive acinar cells to dominantly cytokeratin 19-positive ductal cells. Moreover, expression of the transcripts for TNFα or Hes-1, a Notch target, was up-regulated in these cells. Interestingly, baicalein reduced the population of ADM as well as cytokines gene expression but not Hes-1. Baicalein inhibited NF-κB activation induced by rTNFα in AR42J, but no effect on Notch 1activation. Moreover, baicalein suppressed the secretion of TNFα and Nitric Oxide (NO) in macrophages stimulated with LPS and further inhibited ADM of conditional medium-treated AR42J cells. Baicalein also suppressed the inflammatory response of LPS-activated macrophages, thereby inhibited ADM of AR42J by altering their microenvironment. Taken together, our study indicates that baicalein reduces rTNFα-induced ADM of AR42J cells by inhibiting NF-κB activation. It also sheds new light on Chinese material medica therapy of pancreatitis and thereby prevention of PDAC.