Unique method for removal of knotted lumbar epidural catheter: A case report.

BACKGROUND: Combined spinal-epidural (CSE) anesthesia is the preferred anesthesia method for cesarean delivery. The use of an epidural catheter is essential for administering additional drugs intraoperatively and managing postoperative pain. However, the insertion of epidural catheters is associated with various complications, such as total spinal anesthesia, symptoms indicative of spinal nerve root irritation, and challenges in epidural catheter removal. CASE SUMMARY: We present a case report of a challenging epidural catheter removal due to knotting. The lumbar computed tomography scan results revealed that the catheter formed a tight knot in the epidural space. We used a novel extubation method and successfully removed the catheter. CONCLUSION: The operator can use opposite forces to "spiral" apart the spinal joints by positioning the patient's body in a specific position. The findings indicate that, when combined with imaging examination results, this method is effective for the removal of epidural catheters.

The combined effects of microplastics and bisphenol-A on the innate immune system response and intestinal microflora of the swimming crab Portunus trituberculatus.

Microplastics (MPs) and bisphenol-A (BPA) have been shown to have toxic effects on aquatic organisms. However, data on the combined effects of MPs and BPA on the innate immune system response and intestinal microorganisms of crabs are limited. Here, Portunus trituberculatus were exposed to BPA (at a concentration of 100 µg/L), MPs (microbeads of polystyrene with a particle size of 1 µm and at a concentration of 1 × 106 particles/L) or BPA+MPs for 21 days were tested at the tissue, cellular, and molecular levels. The results showed that neither the single nor combined exposure of MPs and BPA had a significant impact on the growth of crabs. However, intestinal histology study found that the intestinal villi of crabs in the BPA treated group, MP treated group and MP+BPA treated group appeared abnormal. Overall, compared with the control group and the single pollutant exposure group, co-exposure to the MP and BPA generally led to a significant increase in MDA and SOD activity and a significant decrease in CAT activity, and the activation of MyD88, Crustin-1, TARF6, Cu/Zn-SOD, Lyz, Toll-2 and NOX gene expression levels were significantly up-regulated. Co-exposure induced disorders of the intestinal microbial community of crabs, resulting in an increase in the abundance of harmful bacteria and a decrease in the abundance of beneficial bacteria. This study shows that the combined exposure of MPs and BPA can exacerbate the intestinal toxicity of a single pollutant to P. trituberculatus.

Plug-and-Play Model-Agnostic Counterfactual Policy Synthesis for Deep Reinforcement Learning-Based Recommendation.

Recent advances in recommender systems have proved the potential of reinforcement learning (RL) to handle the dynamic evolution processes between users and recommender systems. However, learning to train an optimal RL agent is generally impractical with commonly sparse user feedback data in the context of recommender systems. To circumvent the lack of interaction of current RL-based recommender systems, we propose to learn a general model-agnostic counterfactual synthesis (MACS) policy for counterfactual user interaction data augmentation. The counterfactual synthesis policy aims to synthesize counterfactual states while preserving significant information in the original state relevant to the user's interests, building upon two different training approaches we designed: learning with expert demonstrations and joint training. As a result, the synthesis of each counterfactual data is based on the current recommendation agent's interaction with the environment to adapt to users' dynamic interests. We integrate the proposed policy deep deterministic policy gradient (DDPG), soft actor critic (SAC), and twin delayed DDPG (TD3) in an adaptive pipeline with a recommendation agent that can generate counterfactual data to improve the performance of recommendation. The empirical results on both online simulation and offline datasets demonstrate the effectiveness and generalization of our counterfactual synthesis policy and verify that it improves the performance of RL recommendation agents.

Biological functions and research progress of eIF4E.

The eukaryotic translation initiation factor eIF4E can specifically bind to the cap structure of an mRNA 5' end, mainly regulating translation initiation and preferentially enhancing the translation of carcinogenesis related mRNAs. The expression of eIF4E is closely related to a variety of malignant tumors. In tumor cells, eIF4E activity is abnormally increased, which stimulates cell growth, metastasis and translation of related proteins. The main factors affecting eIF4E activity include intranuclear regulation, phosphorylation of 4EBPs, and phosphorylation and sumoylation of eIF4E. In this review, we summarize the biological functions and the research progress of eIF4E, the main influencing factors of eIF4E activity, and the recent progress of drugs targeting eIF4E, in the hope of providing new insights for the treatment of multiple malignancies and development of targeted drugs.

Estrogen receptor ß attenuates renal fibrosis by suppressing the transcriptional activity of Smad3.

Renal fibrosis (RF) is a common pathway leading to chronic kidney disease (CKD), which lacks effective treatment. While estrogen receptor beta (ERß) is known to be present in the kidney, its role in RF remains unclear. The present study aimed to investigate the role and underlying mechanism of ERß during RF progression in patients and animal models with CKD. We found that ERß was highly expressed in the proximal tubular epithelial cells (PTECs) in healthy kidneys but its expression was largely lost in patients with immunoglobin A nephropathy (IgAN) and in mice with unilateral ureter obstruction (UUO) and subtotal nephrectomy (5/6Nx). ERß deficiency markedly exacerbated, whereas ERß activation by WAY200070 and DPN attenuated RF in both UUO and 5/6Nx mouse models, suggesting a protective role of ERß in RF. In addition, ERß activation inhibited TGF-ß1/Smad3 signaling, while loss of renal ERß was associated with overactivation of the TGF-ß1/Smad3 pathway. Furthermore, deletion or pharmacological inhibition of Smad3 prevented the loss of ERß and RF. Mechanistically, activation of ERß competitively inhibited the association of Smad3 with the Smad-binding element, thereby downregulating the transcription of the fibrosis-related genes without altering Smad3 phosphorylation in vivo and in vitro. In conclusion, ERß exerts a renoprotective role in CKD by blocking the Smad3 signaling pathway. Thus, ERß may represent as a promising therapeutic agent for RF.

The Role of Nucleoporins in Cardiac Tissue Development and Disease.

Nuclear pore complexes (NPCs) are intricate intracellular structures composed of approximately 30 nuclear pore proteins (NUPs) that regulate the transport of materials between the nucleus and cytoplasm in eukaryotic cells. The heart is a crucial organ for sustaining the vital functions of the body, pumping blood rich in nutrients and energy to all organs and tissues. Recent studies have shown that NPCs play pivotal roles not only in normal cardiac physiological processes such as myocardial cell proliferation and differentiation but also in various pathological processes such as ischemic and hypoxic myocardial injury. Due to their mass and complicated nature, the structures of NPCs have been challenging to identify by the scientific community. With the development of cryo-electron microscopy and advanced sampling techniques, researchers have made significant progress in understanding the structures of NPCs. This review aims to summarize the latest research on the structural aspects of NPCs and their roles in cardiac physiology and pathology, increase the understanding of the intricate mechanisms of NPC actions, provide valuable insights into the pathogenesis of heart diseases and describe the development of potential novel therapeutic strategies.

1Progress, applications, challenges and prospects of protein purification technology.

Protein is one of the most important biological macromolecules in life, which plays a vital role in cell growth, development, movement, heredity, reproduction and other life activities. High quality isolation and purification is an essential step in the study of the structure and function of target proteins. Therefore, the development of protein purification technologies has great theoretical and practical significance in exploring the laws of life activities and guiding production practice. Up to now, there is no forthcoming method to extract any proteins from a complex system, and the field of protein purification still faces significant opportunities and challenges. Conventional protein purification generally includes three steps: pretreatment, rough fractionation, and fine fractionation. Each of the steps will significantly affect the purity, yield and the activity of target proteins. The present review focuses on the principle and process of protein purification, recent advances, and the applications of these technologies in the life and health industry as well as their far-reaching impact, so as to promote the research of protein structure and function, drug development and precision medicine, and bring new insights to researchers in related fields.

Phosphorylation of 17ß-hydroxysteroid dehydrogenase 13 at serine 33 attenuates nonalcoholic fatty liver disease in mice.

17ß-hydroxysteroid dehydrogenase-13 is a hepatocyte-specific, lipid droplet-associated protein. A common loss-of-function variant of HSD17B13 (rs72613567: TA) protects patients against non-alcoholic fatty liver disease with underlying mechanism incompletely understood. In the present study, we identify the serine 33 of 17ß-HSD13 as an evolutionally conserved PKA target site and its phosphorylation facilitates lipolysis by promoting its interaction with ATGL on lipid droplets. Targeted mutation of Ser33 to Ala (S33A) decreases ATGL-dependent lipolysis in cultured hepatocytes by reducing CGI-58-mediated ATGL activation. Importantly, a transgenic knock-in mouse strain carrying the HSD17B13 S33A mutation (HSD17B1333A/A) spontaneously develops hepatic steatosis with reduced lipolysis and increased inflammation. Moreover, Hsd17B1333A/A mice are more susceptible to high-fat diet-induced nonalcoholic steatohepatitis. Finally, we find reproterol, a potential 17ß-HSD13 modulator and FDA-approved drug, confers a protection against nonalcoholic steatohepatitis via PKA-mediated Ser33 phosphorylation of 17ß-HSD13. Therefore, targeting the Ser33 phosphorylation site could represent a potential approach to treat NASH.

New butanolide derivatives from the marine derived fungus Aspergillus terreus GZU-31-1 by chemical epigenetic manipulation.

Chemical epigenetic manipulation of Aspergillus terreus GZU-31-1 led to the discovery of five butanolide derivatives (1-5), including two new ones (1 and 2), and four known diphenyl ether derivatives (6-9). Compound 1 featured a Z-configuration double bond in the isoprenyl group was a potential anti-inflammatory bioactive group. Compound 2 was a new natural product. Moreover, compound 3 with a deacetylated group at C-4 was rarely reported as a butanolide analogue, which was isolated from the liquid culture treated with polyketide pathway inhibitor sodium citrate dihydrate. All of the isolates (1-9) were tested for their anti-inflammatory effects on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 1, 7, 8 and 9 exhibited more potent anti-inflammatory activity with IC50 values of 16.31, 20.16, 9.53 and 21.64 µM than the positive control (indomethacin, IC50, 24.0 µM).

Encoding category-level and context-specific phonological information at different stages: An EEG study of Mandarin third-tone sandhi word production.

Pronunciation of words or morphemes may vary systematically in different phonological contexts, but it remains unclear how different levels of phonological information are encoded in speech production. In this study, we investigated the online planning process of Mandarin Tone 3 (T3) sandhi, a case of phonological alternation whereby a low-dipping tone (T3) changes to a Tone 2 (T2)-like rising tone when followed by another T3. To examine the time course of the encoding of the abstract category-level (underlying form) and context-specific phonological form (surface form) of T3, we conducted an electroencephalographic (EEG) study with a phonologically-primed picture naming task and examined the event-related potentials (ERPs) time-locked to the stimulus onset as well as speech response onset. The behavioral results showed that targets primed by T3 or T2 primes yielded shorter naming latencies than those primed by control primes. Importantly, the EEG data revealed that T3 primes elicited larger positive amplitude over broad frontocentral regions roughly in the 320-550 ms time window of stimulus-locked ERP and -500 to -400 ms time window of response-locked ERP, whereas T2 primes elicited larger negative amplitude over left frontocentral regions roughly in the -240 to -100 ms time window of response-locked ERP. These results indicate that the underlying and the surface form are encoded at different processing stages. The former presumably occurs in the earlier phonological encoding stage, while the latter probably occurs in the later phonetic encoding or motor preparation stage. The current study offers important implications for understanding the processing of phonological alternations and tonal encoding in Chinese word production.

Diterpenoids with anti-inflammatory activity from the lateral root of Aconitum carmichaelii debeaux.

Five undescribed diterpenoids, including two ent-cleistanthane-type diterpenoids aconicleistanthanes A and B, a hetisine-type diterpenoid aconihetisine A, two aconitines-type diterpenoids aconicarmines A and B, and thirteen known diterpenoids alkaloids, were co-isolated from the lateral root of the Aconitum carmichaelii Debeaux (Ranunculaceae). Their structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and electronic circular dichroism (ECD) calculations. Among them, aconicleistanthanes A and B as ent-cleistanthane-type diterpenoid featuring a unique five-membered lactone D ring, is the first reported example of ent-cleistanthane-type diterpenoids in the Aconitum, which provided a new type of diterpene metabolites for Aconitum and enriched the chemical space of the plant of the Aconitum. In the bioassays, aconicleistanthane A significantly suppressed the production of pro-inflammatory mediators (IL-6, IL-1ß and COX-2) and the protein expression of the enzyme iNOS at the concentration of 6.25 µM.

Continuous Estimation of Human Knee Joint Angles by Fusing Kinematic and Myoelectric Signals.

Exoskeleton robot is an essential tool in active rehabilitation training for patients with lower limb motor dysfunctions. Accurate and real-time recognition in human motion intention is a great challenge in exoskeleton robot, which can be implemented by continues estimation of human joint angles. In this study, we innovatively proposed a novel feature-based convolutional neural network-bi-directional long-short term memory network (CNN-BiLSTM) model to predict the knee joint angles more accurately and in real time. We validated our method on a public dataset, including surface electromyography(sEMG) and inertial measurement unit (IMU) data of 10 healthy subjects during normal walking. Initially, features extraction from each modal data achieved feature-level fusion. Then the importance of each sEMG and IMU signal feature for knee joint angle prediction was quantified by ensemble feature scorer (EFS) and the number of features required for prediction while ensuring accuracy was simplified by profile likelihood maximization (PLM) algorithm. Finally, the CNN-BiLSTM model was created by using the determined simplest features to further fuse the spatio-temporal correlation of signals. The results indicated that the EFS and PLM algorithm could remove the feature redundancy perfectly and estimation performance would become better when bi-modal gait data were fused. For the estimation performance, the average root mean square error (RMSE), adjusted [Formula: see text] and pearson correlation coefficient (CC) of our algorithm were 4.07, 0.95, and 0.98, respectively, which was better than CNN, BiLSTM and other three traditional machine learning methods. In addition, the model test time was 62.47 ± 0.29 ms, which was less than the predicted horizon of 100 ms. The real-time performance and accuracy are satisfactory. Compared with previous works, our method has great advantages in feature selection and model design, which further improves the prediction accuracy. These promising results demonstrate that the proposed method has considerable potential to be applied to exoskeleton robot control.

Meroterpenoids from the fungus Penicillium sclerotiorum GZU-XW03-2 and their anti-inflammatory activity.

Seven undescribed meroterpenoids, peniscmeroterpenoids A - G, were isolated from the marine-derived fungus Penicillium sclerotiorum GZU-XW03-2. Their structures were established by the spectroscopic methods and the electronic circular dichroism (ECD) calculations. Peniscmeroterpenoid A possessed an unprecedented and highly oxidized 6/7/6/5/5 pentacyclic system, featuring a unique tetrahydrofuro [2,3-b]furan-2(3H)-one motif. Peniscmeroterpenoids B - E owned rare 6(D)/5(E) fused rings were not common in natural products, and peniscmeroterpenoid E is the first example of a berkeleyone analogue stripped of the methyl ester fragment. In bioassays, peniscmeroterpenoids A and D inhibited the production of nitric oxide (NO) in RAW264.7 cells with IC50 values of 26.60 ± 1.15 and 8.79 ± 1.22 µM. Moreover, peniscmeroterpenoid D significantly suppressed the production of pro-inflammatory mediators (COX-2, IL-1ß and IL-6) and the protein expression of the enzyme iNOS.

Linderasesterterpenoids A and B: Two 7-Cyclohexyldecahydroazulene Carbon Skeleton Sesterterpenoids Isolated from the Root of Lindera glauca.

Two novel sesterterpenoids linderasesterterpenoids A (1) and B (2) with an unprecedented 7-cyclohexyldecahydroazulene carbon skeleton isolated from the root of Lindera glauca. Their structures were elucidated by X-ray diffraction, quantum chemical calculations, and spectroscopic methods. The biogenetic pathway for 1 and 2 is proposed. In the bioassay, linderasesterterpenoids A and B showed good inhibitory activities against LPS-induced NO production in RAW 264.7 cells compared to a positive control.

Adversarial Robustness of Deep Reinforcement Learning Based Dynamic Recommender Systems.

Adversarial attacks, e.g., adversarial perturbations of the input and adversarial samples, pose significant challenges to machine learning and deep learning techniques, including interactive recommendation systems. The latent embedding space of those techniques makes adversarial attacks challenging to detect at an early stage. Recent advance in causality shows that counterfactual can also be considered one of the ways to generate the adversarial samples drawn from different distribution as the training samples. We propose to explore adversarial examples and attack agnostic detection on reinforcement learning (RL)-based interactive recommendation systems. We first craft different types of adversarial examples by adding perturbations to the input and intervening on the casual factors. Then, we augment recommendation systems by detecting potential attacks with a deep learning-based classifier based on the crafted data. Finally, we study the attack strength and frequency of adversarial examples and evaluate our model on standard datasets with multiple crafting methods. Our extensive experiments show that most adversarial attacks are effective, and both attack strength and attack frequency impact the attack performance. The strategically-timed attack achieves comparative attack performance with only 1/3 to 1/2 attack frequency. Besides, our white-box detector trained with one crafting method has the generalization ability over several other crafting methods.

mRNA expression level of CDH2, LEP, POSTN, TIMP1 and VEGFC modulates 5-fluorouracil resistance in colon cancer cells.

Drug resistance severely affects the clinical efficacy of therapeutic agents in patients with colon cancer. The aim of the present study was to identify genes involved in drug resistance in colon cancer using bioinformatics analysis and to identify the underlying mechanisms in vitro. Genes associated with cancer recurrence and chemotherapy resistance were identified using data mining. Immunohistochemistry was performed to analyze the protein expression level of genes of interest in human colon cancer tissues. Reverse transcription-quantitative PCR analysis was performed to analyze the gene expression level in patient samples and in colon cancer cell lines (HCT116 and LoVo). Cell viability was evaluated using the Cell Counting Kit-8 assay in the colon cancer cell lines. Apoptosis was measured using PI staining. The results from the present study revealed 602 genes using both 'cancer recurrence' and 'chemoresistance' terms on the GenCLiP3 website. Gene functional annotation was performed using the Database for Annotation, Visualization and Integrated Discovery then, the protein-protein interaction networks of the 602 genes were analyzed using STRING analysis. Further, in the GEPIA database, 14 genes (ATM, CDH2, CDKN2A, EPO, LEP, TGFB1, TIMP1, PGR, VEGFC, POSTN, BCL6, CYP19A1, NOTCH3 and XPA) were found to be upregulated in colon cancer tissue and were associated with poor prognosis in patients with colon cancer. Further analysis of 33 paired human colon cancer tissues revealed that 8 genes (ATM, CDH2, CDKN2A, LEP, PGR, TIMP1, POSTN and VEGFC) were significantly upregulated, which was consistent with the results obtained from the earlier analysis and 5 genes (CDH2, LEP, POSTN, TIMP1 and VEGFC) were associated with patient prognosis. Silencing of these 5 genes using small interfering RNAs significantly enhanced the sensitivity of colon cancer cells to the chemotherapeutic agent, 5-fluorouracil (5-FU). Taken together, the results suggested that CDH2, LEP, POSTN, TIMP1 and VEGFC might play a role in chemotherapeutic resistance in colon cancer and represent potential targets for overcoming 5-FU resistance in colon cancer.

Furanaspermeroterpenes A and B, two unusual meroterpenoids with a unique 6/6/6/5/5 pentacyclic skeleton from the Marine-derived fungus Aspergillus terreus GZU-31-1.

Furanaspermeroterpenes A (1) and B (2), with a unique 6/6/6/5/5 pentacyclic skeleton, and five new congeners aspermeroterpenes D-H (3-7) were co-isolated from the marine-derived fungus Aspergillus terreus GZU-31-1. Among them, compounds 1 and 2 with rare five-membered D/E coupling rings were the first example of DMOA-derived meroterpenoids. Moreover, compound 3 was the first reported 6/6/6/6/5 pentacyclic meroterpenoid featuring an unusual cis-fused A/B ring. In the bioassays, all of the isolates were evaluated on the inhibitory activities against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells, and compounds 3-7 exhibited significant anti-inflammatory activity with IC50 values ranging from 6.74 to 29.59 µM than positive control (Indomethacin, IC50 30.98 µM).

Momentum contrastive learning for few-shot COVID-19 diagnosis from chest CT images.

The current pandemic, caused by the outbreak of a novel coronavirus (COVID-19) in December 2019, has led to a global emergency that has significantly impacted economies, healthcare systems and personal wellbeing all around the world. Controlling the rapidly evolving disease requires highly sensitive and specific diagnostics. While RT-PCR is the most commonly used, it can take up to eight hours, and requires significant effort from healthcare professionals. As such, there is a critical need for a quick and automatic diagnostic system. Diagnosis from chest CT images is a promising direction. However, current studies are limited by the lack of sufficient training samples, as acquiring annotated CT images is time-consuming. To this end, we propose a new deep learning algorithm for the automated diagnosis of COVID-19, which only requires a few samples for training. Specifically, we use contrastive learning to train an encoder which can capture expressive feature representations on large and publicly available lung datasets and adopt the prototypical network for classification. We validate the efficacy of the proposed model in comparison with other competing methods on two publicly available and annotated COVID-19 CT datasets. Our results demonstrate the superior performance of our model for the accurate diagnosis of COVID-19 based on chest CT images.

On the predictive validity of various corpus-based frequency norms in L2 English lexical processing.

The predictive validity of various corpus-based frequency norms in first-language lexical processing has been intensively investigated in previous research, but less attention has been paid to this issue in second-language (L2) processing. To bridge the gap, in the present study we took English as a case in point and compared the predictive power of a large set of corpus-based frequency norms for the performance of an L2 English visual lexical decision task (LDT). Our results showed that, in general, the frequency norms from SUBTLEX-US and WorldLex-Blog tended to predict L2 performance better in reaction times, whereas the frequency norms from corpora with a mixture of written and spoken genres (CELEX, WorldLex-Blog, BNC, ANC, and COCA) tended to predict L2 accuracy better. Although replicated in both low- and high-proficiency L2 English learners, these patterns were not exactly the same as those found in LDT data from native English speakers. In addition, we only observed some limited advantages of the lemma frequency and contextual diversity measures over the wordform frequency measure in predicting L2 lexical processing. The results of the present study, especially the detailed comparisons among the different corpora, provide methodological implications for future L2 lexical research.

[Treatment of cerebral palsy children by integrative medical sequential method: a clinical efficacy observation].

OBJECTIVE: To observe the efficacy of integrative medical sequential method in treating cerebral palsy (CP) children's intelligence development, muscular tension, serum interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). METHODS: Totally 111 CP children were randomly assigned to the control group (50 cases) and the treatment group (61 cases). All patients received comprehensive rehabilitation training and intravenous dripping of Monosialotetrahexosylganglioside Sodium Injection for 10 days. But those in the treatment group additionally received Chinese medical enema for brain resuscitation, relieving rigidity of muscles and activating collaterals for 14 days. Then they started another medication cycle and lasted for a total of 6 cycles. Serum IL-6 levels and TNF-alpha contents were determined before treatment. Scoring for muscular tension, Gesell score for intelligence development, contents of serum IL-6 and TNF-alpha were assessed before and after treatment in the two groups. RESULTS: Compared with before treatment in this group, muscular tension, Gesell scores for intelligence development all decreased in the two groups (P < 0.05). As for inter-group comparison, the decrement was more obvious in the treatment group than in the control group (P < 0.05). The total effective rate was 86.9% in the treatment group and 76.0% in the control group (P < 0.05). The contents of IL-6 and TNF-alpha were obviously reduced in the treatment group and the control group after treatment (P < 0.01). The decrement was more obvious in the treatment group (P < 0.05). CONCLUSION: The two treatment methods were effective for CP children, but the efficacy was superior in the treatment group than in the control group, indicating integrative medical methods could play a synergistic effect and optimize the treatment program for CP.