A retrospective study of cumulative absolute reduction in axial length after photobiomodulation therapy.

BACKGROUND: To assess the age and timeline distribution of ocular axial length shortening among myopic children treated with photobiomodulation therapy in the real world situations. METHODS: Retrospective study of photobiomodulation therapy in Chinese children aged 4 to 13 years old where axial length measurements were recorded and assessed to determine effectiveness at two age groups (4 ∼ 8 years old group and 9 ∼ 13 years old group). Data was collected from myopic children who received photobiomodulation therapy for 6 ∼ 12 months. Effectiveness of myopia control was defined as any follow-up axial length ≤ baseline axial length, confirming a reduction in axial length. Independent t-test was used to compare the effectiveness of the younger group and the older group with SPSS 22.0. RESULTS: 342 myopic children were included with mean age 8.64 ± 2.20 years and baseline mean axial length of 24.41 ± 1.17 mm. There were 85.40%, 46.30%, 71.20% and 58.30% children with axial length shortening recorded at follow-up for 1 month, 3 months, 6 months and 12 months, respectively. With respect to the axial length shortened eyes, the mean axial length difference (standard deviation) was - 0.039 (0.11) mm, -0.032 (0.11) mm, -0.037 (0.12) mm, -0.028 (0.57) mm at 1, 3, 6, and 12-month follow-up, respectively. Greater AL shortening was observed among the older group who had longer baseline axial lengths than the younger group (P < 0.001). CONCLUSIONS: Overall myopia control effectiveness using photobiomodulation therapy was shown to be age and time related, with the maximum absolute reduction in axial elongation being cumulative.

Boosting Sodium Compensation Efficiency via a CNT/MnO2 Catalyst toward High-Performance Na-Ion Batteries.

The formation of a solid electrolyte interphase on carbon anodes causes irreversible loss of Na+ ions, significantly compromising the energy density of Na-ion full cells. Sodium compensation additives can effectively address the irreversible sodium loss but suffer from high decomposition voltage induced by low electrochemical activity. Herein, we propose a universal electrocatalytic sodium compensation strategy by introducing a carbon nanotube (CNT)/MnO2 catalyst to realize full utilization of sodium compensation additives at a much-reduced decomposition voltage. The well-organized CNT/MnO2 composite with high catalytic activity, good electronic conductivity, and abundant reaction sites enables sodium compensation additives to decompose at significantly reduced voltages (from 4.40 to 3.90 V vs Na+/Na for sodium oxalate, 3.88 V for sodium carbonate, and even 3.80 V for sodium citrate). As a result, sodium oxalate as the optimal additive achieves a specific capacity of 394 mAh g-1, almost reaching its theoretical capacity in the first charge, increasing the energy density of the Na-ion full cell from 111 to 158 Wh kg-1 with improved cycle stability and rate capability. This work offers a valuable approach to enhance sodium compensation efficiency, promising high-performance energy storage devices in the future.

Insulin resistance and osteocalcin associate with the incidence and severity of postoperative delirium in elderly patients undergoing joint replacement.

AIM: While insulin sensitivity plays an important role in maintaining glucose metabolic homeostasis and cognitive function, its impact on postoperative delirium (POD) remains unclear. This study aimed to investigate the association between POD and indicators of insulin sensitivity, including insulin resistance and osteocalcin. METHODS: A total of 120 elderly patients undergoing joint replacement were recruited and divided into delirium and non-delirium groups. Plasma and cerebrospinal fluid (CSF) samples were collected for the analysis of biomarkers, including insulin, uncarboxylated osteocalcin (ucOC), total osteocalcin (tOC), and glucose. Insulin resistance was assessed through the homeostatic model assessment of insulin resistance (HOMA-IR). MAIN RESULTS: Out of the total, 28 patients (23.3%) experienced POD within 5 days after surgery. Patients with delirium exhibited higher levels of preoperative HOMA-IR and ucOC in CSF and plasma, and of tOC in CSF (P = 0.028, P < 0.001, P = 0.005, P = 0.019). After adjusting for variables, including age, Mini-Mental State Examination score, surgical site and preoperative fracture, only preoperative ucOC in CSF and HOMA-IR were significantly linked to the incidence of delirium (OR = 5.940, P = 0.008; OR = 1.208, P = 0.046, respectively), both of which also correlated with the severity of delirium (P = 0.007, P < 0.001). Receiver operating curve analysis indicated that preoperative HOMA-IR and ucOC in CSF might partly predict POD (area under the curve [AUC] = 0.697, 95% confidence interval [CI] = 0.501-0.775, AUC = 0.745, 95% CI = 0.659-0.860). CONCLUSIONS: We observed that preoperative elevated HOMA-IR and ucOC in CSF were associated with the incidence and severity of POD. While these preliminary results need confirmation, they suggest a potential involvement of insulin resistance and osteocalcin in the pathological mechanism of POD. Geriatr Gerontol Int 2024; 24: 421-429.

The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice.

Extensive research has confirmed numerous advantages of exercise for promoting brain health. More recent studies have proposed the potential benefits of lactate, the by-product of exercise, in various aspects of brain function and disorders. However, there remains a gap in understanding the effects of lactate dosage and its impact on aged rodents. The present study first examined the long-term effects of three different doses of lactate intervention (2000 mg/kg, 1000 mg/kg, and 500 mg/kg) and high-intensity interval training (HIIT) on aging mice (20-22 months) as the 1st experiment. Subsequently, in the 2nd experiment, we investigated the long-term effects of 500 mg/kg lactate intervention and HIIT on brain neuroplasticity in aged mice (25-27 months). The results of the 1st experiment demonstrated that both HIIT and different doses of lactate intervention (500 mg/kg and 2000 mg/kg) positively impacted the neuroplasticity biomarker VEGF in the hippocampus of aging mice. Subsequently, the 2nd experiment revealed that long-term HIIT significantly improved the performance of mice in open-field, novel object recognition, and passive avoidance tests. However, lactate intervention did not significantly affect these behavioral tests. Moreover, compared to the control group, both HIIT and lactate intervention positively influenced the angiogenesis signaling pathway (p/t-AKT/ENOS/VEGF), mitochondrial biomarker (SDHA), and metabolic protein (p/t-CREB, p/t-HSL, and LDH) in the hippocampus of aged mice. Notably, only lactate intervention significantly elevated the BDNF (PGC-1α, SIRT1, and BDNF) signaling pathway and metabolic content (lactate and pyruvate). In the end, long-term HIIT and lactate intervention failed to change the protein expression of p/t-MTOR, iNOS, nNOS, HIF-1α, SYNAPSIN, SIRT3, NAMPT, CS, FNDC5 and Pan Lactic aid-Lysine in the hippocampus of aged mice. In summary, the present study proved that long-term HIIT and lactate treatment have positive effects on the brain functions of aged mice, suggesting the potential usage of lactate as a therapeutic strategy in neurodegenerative diseases in the elderly population.

RNNCon: Contribution Coverage Testing for Stacked Recurrent Neural Networks.

Recurrent Neural Networks (RNNs) are applied in safety-critical fields such as autonomous driving, aircraft collision detection, and smart credit. They are highly susceptible to input perturbations, but little research on RNN-oriented testing techniques has been conducted, leaving a threat to a large number of sequential application domains. To address these gaps, improve the test adequacy of RNNs, find more defects, and improve the performance of RNNs models and their robustness to input perturbations. We aim to propose a test coverage metric for the underlying structure of RNNs, which is used to guide the generation of test inputs to test RNNs. Although coverage metrics have been proposed for RNNs, such as the hidden state coverage in RNN-Test, they ignore the fact that the underlying structure of RNNs is still a fully connected neural network but with an additional "delayer" that records the network state at the time of data input. We use the contributions, i.e., the combination of the outputs of neurons and the weights they emit, as the minimum computational unit of RNNs to explore the finer-grained logical structure inside the recurrent cells. Compared to existing coverage metrics, our research covers the decision mechanism of RNNs in more detail and is more likely to generate more adversarial samples and discover more flaws in the model. In this paper, we redefine the contribution coverage metric applicable to Stacked LSTMs and Stacked GRUs by considering the joint effect of neurons and weights in the underlying structure of the neural network. We propose a new coverage metric, RNNCon, which can be used to guide the generation of adversarial test inputs. And we design and implement a test framework prototype RNNCon-Test. 2 datasets, 4 LSTM models, and 4 GRU models are used to verify the effectiveness of RNNCon-Test. Compared to the current state-of-the-art study RNN-Test, RNNCon can cover a deeper decision logic of RNNs. RNNCon-Test is not only effective in identifying defects in Deep Learning (DL) systems but also in improving the performance of the model if the adversarial inputs generated by RNNCon-Test are filtered and added to the training set to retrain the model. In the case where the accuracy of the model is already high, RNNCon-Test is still able to improve the accuracy of the model by up to 0.45%.

Hippocalcin-Like 1 blunts liver lipid metabolism to suppress tumorigenesis via directly targeting RUVBL1-mTOR signaling.

Rationale: Hepatocellular carcinoma (HCC) is one of the most severe cancers worldwide, with few effective targeted therapies for HCC. Lipid metabolic reprogramming is emerged as a hallmark of cancer metabolism that guides response to antitumoral therapies. Such lipid metabolic alteration in cancers is critically regulated by the mammalian target of rapamycin mTOR, which is considered as a promising therapeutic target. Despite efforts, mTOR inhibitors (mTORi) have produced limited response clinically, partly due to incomplete knowledge of mTORC1 addiction in cancers. Methods: CRISPR-Cas9 system was used to establish Hpcal1 null mice. The liver cancer model in mice was generated using Hpcal1-deficient mice with diethylnitrosamine (DEN) /CCL4 or MYC/Trp53-/- via hydrodynamic tail-vein injection. RNA-sequencing (RNA-seq) was used to identify potential signaling pathways. The expression of HPCAL1 and mTOR signaling were determined using quantitative polymerase chain reaction (qPCR), western blot and immunohistochemistry. The role of Hpcal1 in liver tumorigenesis and its response to mTORi was assessed by CCK-8 measurements, colony formation assay and in mouse model. Results: In this study, we identified hippocalcin-like protein 1 (HPCAL1) as an important negative regulator of de novo lipid biosynthesis and mTOR signaling activation, limiting liver tumorigenesis and establishing a metabolic vulnerability of HCC in mice. Genetic loss of HPCAL1 rendered HCC mTORC1-addicted and sensitive to mTORi AZD-8055 in vitro and in vivo. Importantly, HPCAL1 expression was inversely correlated with the levels of mTOR phosphorylation and several critical lipid biosynthesis enzymes in human specimens. Mechanistically, HPCAL1 directly bound to RuvB Like AAA ATPase 1 (RUVBL1), inhibiting the assembly of TEL2-TTI1-TTI2 (TTT)-RUVBL complex and subsequent leading the mTOR signaling suppression. Conclusion: We uncover a metabolic vulnerability and mTOR addiction in HCC with HPCAL1 loss that provides a selective therapeutic window for HCC with mTORC1 hyperactivation using mTORi.

Layered Oxide Cathode-Electrolyte Interface towards Na-Ion Batteries: Advances and Perspectives.

With the ever increasing demand for low-cost and economic sustainable energy storage, Na-ion batteries have received much attention for the application on large-scale energy storage for electric grids because of the worldwide distribution and natural abundance of sodium element, low solvation energy of Na+ ion in the electrolyte and the low cost of Al as current collectors. Starting from a brief comparison with Li-ion batteries, this review summarizes the current understanding of layered oxide cathode/electrolyte interphase in NIBs, and discusses the related degradation mechanisms, such as surface reconstruction and transition metal dissolution. Recent advances in constructing stable cathode electrolyte interface (CEI) on layered oxide cathode are systematically summarized, including surface modification of layered oxide cathode materials and formulation of electrolyte. Urgent challenges are detailed in order to provide insight into the imminent developments of NIBs.

From force chains to nonclassical nonlinear dynamics in cemented granular materials.

In this letter, we present evidence for a mechanism responsible for the nonclassical nonlinear dynamics observed in many cemented granular materials that are generally classified as mesoscopic nonlinear elastic materials. We demonstrate numerically that force chains are created within the complex grain-pore network of these materials when subjected to dynamic loading. The interface properties between grains along with the sharp and localized increase of the stress occurring at the grain-grain contacts leads to a reversible decrease of the elastic properties at macroscopic scale and peculiar effects on the propagation of elastic waves when grain boundary properties are appropriately considered. These effects are observed for relatively small amplitudes of the elastic waves, i.e., within tens of microstrain, and relatively large wavelengths, i.e., orders of magnitude larger than the material constituents. The mechanics are investigated numerically using the hybrid finite-discrete-element method and match those observed experimentally using nonlinear resonant ultrasound spectroscopy.

Competitive Doping Chemistry for Nickel-Rich Layered Oxide Cathode Materials.

Chemical modification of electrode materials by heteroatom dopants is crucial for improving storage performance in rechargeable batteries. Electron configurations of different dopants significantly influence the chemical interactions inbetween and the chemical bonding with the host material, yet the underlying mechanism remains unclear. We revealed competitive doping chemistry of Group IIIA elements (boron and aluminum) taking nickel-rich cathode materials as a model. A notable difference between the atomic radii of B and Al accounts for different spatial configurations of the hybridized orbital in bonding with lattice oxygen. Density functional theory calculations reveal, Al is preferentially bonded to oxygen and vice versa, and shows a much lower diffusion barrier than BIII . In the case of Al-preoccupation, the bulk diffusion of BIII is hindered. In this way, a B-rich surface and Al-rich bulk is formed, which helps to synergistically stabilize the structural evolution and surface chemistry of the cathode.

Agenesis of the dorsal pancreas with chronic suppurative pancreatitis: Case report and literature review.

RATIONALE: Agenesis of the dorsal pancreas (ADP) is a rare congenital anomaly of the pancreas. ADP is associated with some other medical problems such as diabetes mellitus, abdominal pain/bloating, pancreatitis, pancreatic neuroendocrine tumor and so on. In this study, we present a case of ADP with chronic suppurative pancreatitis, summarize the clinical characteristics of the reported cases in China and review the correlative literature. PATIENT CONCERNS: A 51-year-old Chinese man, with a history of impaired fasting glucose, presented with jaundice, pruritus and dark urine. Laboratory analysis showed abnormal liver function and elevated carbohydrate antigen 19-9. DIAGNOSES: Contrast-enhanced computed tomography demonstrated a mass located at the head of pancreas and complete absence of the body and tail of pancreas. Endoscopic retrograde cholangiopancreatography demonstrated an eccentric malignant stricture about 1.6cm of distal common bile duct. INTERVENTIONS: The patient underwent pancreaticoduodenectomy because of the suspicion of pancreatic tumor. The postoperative pathological result was chronic suppurative pancreatitis, with moderate hyperplasia in focal ductal epithelium. OUTCOMES: A long-term follow-up shows that the patient is asymptomatic with well-controlled diabetes mellitus and pancreatic exocrine insufficiency. LESSONS: ADP is a quite rare congenital malformation of the pancreas with poorly-understood pathogenesis. The diagnosis of ADP depends on the imaging examination. The therapeutic strategy varies from person to person due to the different accompanying conditions.

Computed tomography versus ultrasound/fine needle aspiration biopsy in differential diagnosis of thyroid nodules: a retrospective analysis / Tomografia computadorizada versus ultrassonografia/biópsia por aspiração com agulha fina no diagnóstico diferencial de nódulos tireoidianos: uma análise retrospectiva

Abstract Introduction Ultrasound sonography provides a quick method for determining which nodule to sample for fine needle aspiration biopsy in thyroid nodules. On the other hand, the computed tomography examination is not restricted by echo attenuation and distinguishes between benign and malignant nodules. Objective To compare computed tomography examinations against ultrasound/fine needle aspiration biopsy in the differential diagnosis of thyroid nodules. Methods Data regarding computed tomography examinations, sonographic finding following fine needle aspiration biopsy, and tumor histology of 953 nodules from 698 patients who underwent thyroidectomy were collected and analyzed. The beneficial score for detection of the malignant tumor for each adopted modality was evaluated. Results Ultrasound images did not show a well-circumscribed solid mass in 89 nodules, and ultimately did not detect nodules in fine needle aspiration biopsies (false positive non-malignant nodules). Ultrasound images showed parenchymatous disease (false positive malignant nodules) in several nodules. Computed tomography examinations demonstrated higher difficulty in detection of malignant nodules of 1.0-2.0 cm size than ultrasound examination following fine needle aspiration biopsies; compared to tumor histological data, computed tomography examinations had a sensitivity of 0.879. Conclusion Computed tomography examinations are a more reliable method for differential diagnosis of thyroid nodules than ultrasound examinations followed by fine needle aspiration biopsy. Level of Evidence III.

Resumo Introdução A ultrassonografia é um método rápido para determinar de qual nódulo se deve coletar uma amostra para biópsia por aspiração com agulha fina. Por outro lado, o exame de tomografia computadorizada não é restringido pela atenuação do eco e distingue entre nódulos benignos e malignos. Objetivo Comparar exames tomográficos versus biópsia por ultrassonografia/aspiração por agulha fina no diagnóstico diferencial de nódulos tireoidianos. Método Dados sobre exames tomográficos, achados ultrassonográficos após biópsia por aspiração com agulha fina e histologia tumoral de 953 nódulos de 698 pacientes submetidos à tireoidectomia foram coletados e analisados. O escore de benefício para detecção do tumor maligno para cada modalidade adotada foi avaliado. Resultados As imagens de ultrassom não mostraram uma lesão sólida bem circunscrita em 89 nódulos; e na análise final não foram detectados nódulos nas biópsias por aspiração com agulha fina (nódulos não malignos falsos positivos). As imagens ultrassonográficas mostraram doença parenquimatosa (nódulos malignos falsos positivos) em vários nódulos. Os exames de tomografia computadorizada apresentaram grandes dificuldades na detecção de nódulos malignos de 1,0-2,0 cm de tamanho em comparação com o exame de ultrassonografia após biópsias por aspiração com agulha fina; comparados aos dados histológicos do tumor, os exames de tomografia computadorizada apresentaram sensibilidade de 0,879. Conclusão Os exames de tomografia computadorizada são um método mais confiável para o diagnóstico diferencial de nódulos tireoidianos do que os exames de ultrassonografia, seguidos por biópsia por aspiração com agulha fina.

Platelet Distribution Width and Mortality in Hemodialysis Patients.

OBJECTIVES: The association between platelet distribution width (PDW) and mortality in hemodialysis (HD) patients has received little attention. METHODS: We retrospectively enrolled HD patients in a single center from January 1, 2008, to December 30, 2011. The primary and secondary endpoints were all-cause and cardiovascular mortality, respectively. The association between PDW and mortality was estimated by Cox regression model. RESULTS: Of 496 patients, the mean age was 52.5 ± 16.6 years, and the Charlson comorbidity index was 4.39 ± 1.71. During the follow-up period of 48.8 ± 6.7 months, 145 patients (29.2%) died, including 74 (14.9%) cardiovascular deaths. 258 (52.0%) with PDW < 16.31% were in the low group and 238 (48.0%) in those with PDW ≥ 16.31% according to cut-off for all-cause mortality by receiving-operator characteristics. After adjusting for confounding factors, high PDW values were independently associated with higher risk of all-cause (hazards ratio (HR) = 1.49, 95% confidence interval (CI) 1.15-6.82) and cardiovascular deaths (HR = 2.26, 95% CI 1.44-3.63) in HD patients. When comparing with quartile 1 of PDW, quartile 4 of PDW was independently associated with a higher risk of all-cause (HR = 1.59, 95% CI 1.18-5.30) and cardiovascular deaths (HR = 2.71, 95% CI 1.49-3.76) in HD patients. CONCLUSIONS: Baseline PDW was independently associated with all-cause and cardiovascular mortality in HD patients.

Computed tomography versus ultrasound/fine needle aspiration biopsy in differential diagnosis of thyroid nodules: a retrospective analysis.

INTRODUCTION: Ultrasound sonography provides a quick method for determining which nodule to sample for fine needle aspiration biopsy in thyroid nodules. On the other hand, the computed tomography examination is not restricted by echo attenuation and distinguishes between benign and malignant nodules. OBJECTIVE: To compare computed tomography examinations against ultrasound/fine needle aspiration biopsy in the differential diagnosis of thyroid nodules. METHODS: Data regarding computed tomography examinations, sonographic finding following fine needle aspiration biopsy, and tumor histology of 953 nodules from 698 patients who underwent thyroidectomy were collected and analyzed. The beneficial score for detection of the malignant tumor for each adopted modality was evaluated. RESULTS: Ultrasound images did not show a well-circumscribed solid mass in 89 nodules, and ultimately did not detect nodules in fine needle aspiration biopsies (false positive non-malignant nodules). Ultrasound images showed parenchymatous disease (false positive malignant nodules) in several nodules. Computed tomography examinations demonstrated higher difficulty in detection of malignant nodules of 1.0-2.0cm size than ultrasound examination following fine needle aspiration biopsies; compared to tumor histological data, computed tomography examinations had a sensitivity of 0.879. CONCLUSION: Computed tomography examinations are a more reliable method for differential diagnosis of thyroid nodules than ultrasound examinations followed by fine needle aspiration biopsy. LEVEL OF EVIDENCE: III.

Candidate genes mediated by estrogen-related receptor γ in pancreatic ß cells.

Recent studies have established the importance of estrogen-related receptor γ (ERRγ) as a required participant for insulin secretion in pancreatic ß cells. Key downstream genes of ERRγ remain unclear in the pancreatic ß cell. To understand the molecular role of ERRγ and elucidate potential key candidate genes involved in pancreatic ß cells, the eukaryotic expression plasmid containing mouse ERRγ was constructed and transfected into NIT-1 pancreatic ß cells. Overexpression of ERRγ was confirmed by quantitative real-time reverse-transcription polymerase chain reaction and Western blot analyses. RNA-seq was conducted to get the gene expression profiling between the overexpression group cells and control cells. Differentially expressed genes (DEGs) were identified by edgR and subsequently analyzed by gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. We found that overexpression of ERRγ in pancreatic ß cells enables regulation of the expression of certain genes involved in cell apoptosis and mitochondrial function, such as TFPT, Bcl7c, Dap, Thoc6, Ube2d3, ATP5H, MPV17, and NDUFA6. GO analysis revealed that the DEGs were mainly enriched in apoptotic process, cytoplasm, and protein binding. KEGG pathway analysis demonstrated that downregulated DEGs were mainly enriched in protein processing in endoplasmic reticulum, estrogen signaling pathway, and metabolic pathways. This study helps to further understand and reposition the molecular mechanisms of ERRγ in ß cells.

The Therapeutic Implications of Tea Polyphenols Against Dopamine (DA) Neuron Degeneration in Parkinson's Disease (PD).

: Accumulative evidence indicated that the pathologically accumulated metal ions (iron species and Mn3+) and abnormally up-regulated monoamine oxidase B (MAOB) activity induced oxidation of endogenous dopamine (DA) can lead to mitochondria impairment, lysosome dysfunction, proteasome inhibition, and selective DA neuron vulnerability, which is implicated in the pathogenesis of Parkinson's disease (PD). The DA oxidation can generate deleterious reactive oxygen species (ROS) and highly reactive DA quinones (DAQ) to induce DA-related toxicity, which can be alleviated by DA oxidation suppressors, ROS scavengers, DAQ quenchers, and MAOB inhibitors. On the other hand, the nuclear factor erythroid 2-related factor 2 (Nrf2)-Keap1 and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) anti-oxidative and proliferative signaling pathways play roles in anti-oxidative cell defense and mitochondria biogenesis, which is implicated in DA neuron protections. Therefore, agents with capabilities to suppress DA-related toxicity including inhibition of DA oxidation, scavenge of ROS, detoxification of DAQ, inhibition of MAOB, and modulations of anti-oxidative signaling pathways can be protective to DA neurons. Accumulative evidence shows that tea or coffee consumptions and smoking are related to deceased PD prevalence with unknown mechanisms. In this study, we investigate the protective capabilities of tea polyphenols and other PD relevant agents to inhibit DA-related toxicity and protect against environmental or genetic factors induced DA neuron degeneration in vitro and in vivo. We find that tea polyphenols can significantly suppress DA-related toxicity to protect DA neurons. The tea polyphenols can protect DA neurons via inhibition of DA oxidation, conjugation with DAQ, scavenge of ROS, inhibition of MAOB, and modulations of Nrf2-Keap1 and PGC-1α anti-oxidative signaling pathways. The tea polyphenols with more phenolic hydroxyl groups and ring structures have stronger protective functions. The protective capabilities of tea polyphenols is further strengthened by evidence that phenolic hydroxyl groups can directly conjugate with DAQ. However, GSH and other sulfhydyl groups containing agents have weaker capabilities to abrogate DA oxidation, detoxify ROS and DAQ and inhibit MAOB; whereas nicotine (NICO) and caffeine (CAF) can only modulate Nrf2-Keap1 and PGC-1α pathways to protect DA neurons weakly. The tea polyphenols are identified to protect against overexpression of mutant A30P α-synuclein (α-syn) induced DA neuron degeneration and PD-like symptoms in transgenic Drosophila. Based on achievements from current studies, the excellent and versatile protective capabilities of tea polyphenols are highlighted, which will contribute and benefit to future anti-PD therapy.

Simulation of crack induced nonlinear elasticity using the combined finite-discrete element method.

Numerical simulation of nonlinear elastic wave propagation in solids with cracks is indispensable for decoding the complicated mechanisms associated with the nonlinear ultrasonic techniques in Non-Destructive Testing (NDT). Here, we introduce a two-dimensional implementation of the combined finite-discrete element method (FDEM), which merges the finite element method (FEM) and the discrete element method (DEM), to explicitly simulate the crack induced nonlinear elasticity in solids with both horizontal and inclined cracks. In the FDEM model, the solid is discretized into finite elements to capture the wave propagation in the bulk material, and the finite elements along the two sides of the crack also behave as discrete elements to track the normal and tangential interactions between crack surfaces. The simulation results show that for cracked models, nonlinear elasticity is generated only when the excitation amplitude is large enough to trigger the contact between crack surfaces, and the nonlinear behavior is very sensitive to the crack surface contact. The simulations reveal the influence of normal and tangential contact on the nonlinear elasticity generation. Moreover, the results demonstrate the capabilities of FDEM for decoding the causality of nonlinear elasticity in cracked solid and its potential to assist in Non-Destructive Testing (NDT).

Directed elimination of senescent cells attenuates development of osteoarthritis by inhibition of c-IAP and XIAP.

Aging drives the accumulation of senescent cells (SnCs) by secreting factors that cause the senescence-associated secretory phenotype (SASP), including stem cells in the bone marrow, which contribute to aging-related bone degradation. Osteoarthritis (OA) is a serious chronic injury disease, and increasing age is a major risk factor. The accumulation of SnCs may accelerate the development of OA, and the accumulation of SnCs may benefit from its resistance to apoptotic stimuli. Therefore, local elimination of SnCs could be a promising treatment for OA. Apoptosis inhibitor protein (IAP) is an important antiapoptotic protein in vivo. AT-406 is a small molecule inhibitor of the IAP genes and also regulates the transcription of several genes. Here, we show that SnCs upregulate the antiapoptotic proteins c-IAP1, c-IAP2 and XIAP.The combined inhibition of c-IAP1, c-IAP2 and XIAP using siRNA or AT-406 specifically induce the apoptosis of SnCs.In addition, XIAP and STX17 bind to each other to regulate the fusion of autophagosomes and lysosomes in SnCs, which in turn, affects the fate of SnCs. It is worth noting that the clearance of SnCs attenuated the secretion of SASP and created a proregenerative environment. Most importantly, local clearance of SnCs significantly attenuated the progression of osteoarthritis in rats without significant toxic effects. Thus, local elimination of SnCs may be a potential treatment for OA. This is the first report of inhibition of IAPs for clearing SnCs and suggests that eradication of SnCs may be a new strategy for the treatment of age-related diseases.

[Cluster analysis of Dendrobium officinale from different populations through agronomy characterization].

Through resources investigation and sample collection,a total number of 392 Dendrobium officinale from 38 different populations,9 provinces were processed for measuring and observing.Fourteen agronomy characterizations like stem height,stem diameter,number of node in stem were selected for further classification.The cluster analysis was performed using Ward and Euclidean method.The results showed that the threshold of genetic distance was 2.77.Thirtyeight populations were divided into 6 groups.The factor analysis showed that,the leaf shape,stem shape,pitch length and leaf color were very important factors for classification.This study establish the foundation for analyzing the genetic relationship of D.officinale from different populations.

Nicotine downregulates microRNA-200c to promote metastasis and the epithelial-mesenchymal transition in human colorectal cancer cells.

BACKGROUND: Cigarette smoking is the most well-established risk factor for colorectal cancer (CRC). However, the mechanisms of smoking-associated colorectal carcinogenesis are poorly understood. METHODS: The effects of prediagnosis tobacco use on clinical characteristics, overall survival (OS), and recurrence-free survival (RFS) were analyzed in 396 patients with CRC. Associations between smoking status and OS and RFS were evaluated using Cox's proportional hazards regression. Furthermore, the effects of nicotine on the CRC cell lines SW620 and HT-29 were evaluated using in vitro assays. RESULTS: "Ever smoking" was associated with elevated serum carcinoembryonic antigen, American Joint Committee on Cancer T category, metastasis, and poorer OS and RFS in patients with CRC (OS: hazard ratio [HR] = 1.74, 95% confidence interval [CI], 1.07-2.81, p = 0.025; RFS: HR = 1.66, 95% CI: 1.18-2.34, p = 0.004). MicroRNA (miR)-200c was downregulated in CRC and tumor-adjacent tissues from ever smokers compared with the corresponding tissues from never smokers with CRC. Nicotine inhibited miR-200c expression in a dose- and time-dependent manner in SW620 and HT-29 CRC cell lines. Nicotine induced cell proliferation, migration, and invasion and promoted the epithelial-mesenchymal transition in SW620 and HT-29 cells, and these effects were attenuated by overexpression of miR-200c. CONCLUSION: Our findings support the adverse effects of prediagnosis cigarette smoking on prognosis and clinical behavior in CRC. We demonstrate a novel oncogenic mechanism by which nicotine promotes growth and metastasis in CRC by downregulating miR-200c.

Erythromycin combined with corticosteroid reduced inflammation and modified trauma-induced tracheal stenosis in a rabbit model.

BACKGROUND: Patients with endotracheal intubation or tracheostomy are subject to benign tracheal stenosis (TS), for which current therapies are unsatisfactory. We conducted a preliminary investigation of drugs and drug combinations for the prevention and treatment of TS in a rabbit model. METHODS: Fifty-four rabbits were apportioned into nine groups according to treatment: sham-operated control; untreated TS model; amikacin; budesonide; erythromycin; penicillin; amikacin + budesonide; erythromycin + budesonide; and penicillin + budesonide. TS was induced by abrasion during surgery. The drugs were applied for 7 days before and 10 days after the surgery. Rabbits were killed on the eleventh day. Tracheal specimens were processed for determining alterations in the thicknesses of tracheal epithelium and lamina propria via hematoxylin and eosin. The tracheal mRNA (assessed by real-time quantitative polymerase chain reaction) expressions of the following fibrotic-related factors were determined: transforming growth factor-ß1 (TGF- ß1), collagen type I (COL1A1), collagen type III (COL3A1), and interleukin-17 (IL-17). The protein levels of TGF-ß1, COL1A1, and COL3A1 were determined through immunohistochemistry and integrated optical densities. RESULTS: Compared with all other groups, the untreated TS model had significantly thicker tracheal epithelium and lamina propria, and higher mRNA and protein levels of all targeted fibrotic factors. The mRNA and protein levels of the targeted fibrotic factors in all the drug-treated groups were lower than those of the untreated TS model, and differences were most significant in the erythromycin + budesonide group. CONCLUSIONS: Erythromycin combined with budesonide may reduce inflammation and modify fibrosis progression in TS after tracheal injury.