Enantioselective Total Synthesis of (-)-Daphenylline.

A concise enantioselective total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira's Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens' photoredox-catalyzed hydrocarboxylation of olefin and CuBr2-catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische's Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens' photoredox-catalyzed hydrocarboxylation was used twice, and Friedel-Crafts acylation thrice.

Interfacial Electron Transfer in PbI2@Single-Walled Carbon Nanotube van der Waals Heterostructures for High-Stability Self-Powered Photodetectors.

Acquiring a deep insight into the electron transfer mechanism and applications of one-dimensional (1D) van der Waals heterostructures (vdWHs) has always been a significant challenge. Herein, through direct observation using aberration-corrected transmission electron microscopy (AC-TEM), we verify the stable formation of a high-quality 1D heterostructure composed of PbI2@single-walled carbon nanotubes (SWCNTs). The phenomenon of electron transfer between PbI2 and SWCNT is elucidated through spectroscopic investigations, including Raman and X-ray photoelectron spectroscopy (XPS). Electrochemical testing indicates the electron transfer and enduring stability of 1D PbI2 within SWCNTs. Moreover, leveraging the aforementioned electron transfer mechanism, we engineer self-powered photodetectors that exhibit exceptional photocurrent and a 3-order-of-magnitude switching ratio. Subsequently, we reveal its unique electron transfer behavior using Kelvin probe force microscopic (KPFM) tests. According to KPFM, the average surface potential of SWCNTs decreases by 80.6 mV after filling. Theoretical calculations illustrate a charge transfer of 0.02 e per unit cell. This work provides an effective strategy for the in-depth investigation and application of electron transfer in 1D vdWHs.

Direct α-Arylation of Benzo[b]furans Catalyzed by a Pd3 Cluster.

As an interim paradigm for the catalysts between those based on more conventional mononuclear molecular Pd complexes and Pdn nanoparticles widely used in organic synthesis, polynuclear palladium clusters have attracted great attention for their unique reactivity and electronic properties. However, the development of Pd cluster catalysts for organic transformations and mechanistic investigations is still largely unexploited. Herein, we disclose the use of trinuclear palladium (Pd3Cl) species as an active catalyst for the direct C-H α-arylation of benzo[b]furans with aryl iodides to afford 2-arylbenzofurans in good yields under mild conditions. With this method, broad substrate adaptability was observed, and several drug intermediates were synthesized in high yields. Mechanistic studies indicated that the Pd3 core most likely remained intact throughout the reaction course.

Biological functions of connexins in the development of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory diseases with unknown etiology. Gap junctions composed of connexins (Cxs) have been recently validated as an important factor in the development of IBD. Under IBD-induced inflammatory response in the gut, gap junctions connect multiple signaling pathways involved in the interaction between inflammatory cells with other intestinal cells, which altogether mediate the development of IBD. This paper is a narrative review aiming to comprehensively elucidate the biological function of connexins, especially the ubiquitously and predominantly expressed Cx43, in the pathogenesis of IBD.

Utility of enteral nutrition via percutaneous transhepatic cholangiography drainage catheterization in late-stage malignant obstructive jaundice.

Objective: The purpose of this study was to explore the clinical benefits of establishing an enteral nutrition (EN) pathway via percutaneous transhepatic cholangiography drainage (PTCD) catheterization in patients with late-stage malignant obstructive jaundice (MOJ).Methods: We selected 30 patients diagnosed as having late-stage MOJ with malnutrition. A dual-lumen biliary-enteral nutrition tube was placed via PTCD along with a biliary stent implantation. Postoperative EN was provided, and we observed the time taken for tube placement, its success rate, complications, and therapeutic efficacy.Results: Tube placement was successful in all 30 patients with an average procedural time of 5.7 ± 1.4 min with no tube placement complications. Compared to preoperative measures, there was a significant improvement in postoperative jaundice reduction and nutritional indicators one month after the procedure (p < 0.05). Post-placement complications included tube perileakage in 5 cases, entero-biliary reflux in 4 cases, tube blockage in 6 cases, tube displacement in 4 cases, accidental tube removal in 3 cases, and tube replacement due to degradation in 8 cases, with tube retention time ranging from 42 to 314 days, averaging 124.7 ± 37.5 days. All patients achieved the parameters for effective home-based enteral nutrition with a noticeable improvement in their quality of life.Conclusion: In this study, we found that the technique of establishing an EN pathway via PTCD catheterization was minimally invasive, safe, and effective; the tube was easy to maintain; and patient compliance was high. It is, thus, suitable for long-term tube retention in patients with late-stage MOJ.

Insight into Multiphase Interlayer Molecular Packing and Stepwise Phase Transition in 4-(Phenylazo)benzoate Anion-Intercalated Layered Zinc Hydroxide.

The properties of layered intercalation hybrids are closely related to interlayer molecular packing. To develop functional intercalation hybrids, it is essential to gain deep insights into interlayer molecular packing. This work reports a new comprehensive insight into the controllable multiphase interlayer molecular packing in 4-(phenylazo)benzoate anion-intercalated layered zinc hydroxide (LZH-4-PAB intercalation hybrids). The new insight breaks up the general understanding that the interlayer molecular packing of anions is usually single-phase, lacking diversity and controllability. Furthermore, it uncovers an interesting stepwise rather than the generally expected continuous phase transition of the interlayer molecular packing. The intercalated 4-PAB anions initially organize into the horizontal monolayer packing (θ = 0°, Phase I), which stepwise transforms to the tilted interdigitated antiparallel bilayer packing (θ ≈ 50°, Phase II) along with an increased intercalation loading and eventually to the vertical interdigitated antiparallel bilayer packing (θ = 90°, Phase III). The LZH-4-PAB hybrids exhibited a greatly enhanced interlayer molecular packing-dependent UV-vis absorption. This study provides helpful guidance for developing property-tailored intercalation hybrids. It may attract new interest in more layered intercalation hybrids. New and rich intercalation chemistry might be discovered in more functional intercalation hybrids beyond the 4-PAB anion-intercalated layered zinc hydroxide.

Transhiatal bilateral cervical approach for mediastinoscopy-assisted esophagectomy: A retrospective cohort study.

BACKGROUND: The McKeown minimally invasive esophagectomy (McMIE) procedure has various limitations, including surgical contraindications and a high rate of postoperative pulmonary complications. A novel mediastinoscopic esophagectomy procedure was described in this study by using esophageal invagination and a transhiatal and bilateral cervical approach (EITHBC). METHODS: According to the mode of operation, a total of 259 patients were divided into two groups, among which 106 underwent EITHBC and 153 underwent McMIE. The number of lymph nodes dissected, intraoperative outcomes, and postoperative outcomes were compared between the two groups of patients. RESULTS: The results revealed that the average number of resected lymph node in the EITHBC group was significantly higher in the recL106 and TbL106 stations (recL106: 1.75 vs. 1.51, p = 0.016, TbL106: 1.53 vs. 1.19, p = 0.016) and significantly lower in the 107 stations (1. 74 vs. 2. 07, p < 0.001) than in the McMIE group. The intraoperative blood loss in the EITHBC group was significantly lower than that in the McMIE group (63.30 vs. 80.45 mL, p < 0.001). The incidence of postoperative pulmonary complications in the EITHBC group was lower than that in the McMIE group (14.15% vs. 27.45%, p = 0.008). The incidence of recurrent laryngeal nerve paralysis in the EITHBC group was significantly higher than that in the McMIE group (26.41% vs. 10.46%, p = 0.003). CONCLUSION: Compared with the McMIE procedure, the EITHBC procedure has advantages in terms of removing the upper mediastinal lymph nodes and reducing postoperative pulmonary complications.

Three-Dimensional ERT Advanced Detection Method with Source-Position Electrode Excitation for Tunnel-Boring Machines.

Tunnel-boring machines (TBMs) are widely used in urban underground tunnel construction due to their fast and efficient features. However, shield-tunnel construction faces increasingly complex geological environments and may encounter geological hazards such as faults, fracture zones, water surges, and collapses, which can cause significant property damage and casualties. Existing geophysical methods are subject to many limitations in the shield-tunnel environment, where the detection space is extremely small, and a variety of advanced detection methods are unable to meet the required detection requirements. Therefore, it is crucial to accurately detect the geological conditions in front of the tunnel face in real time during the tunnel boring process of TBM tunnels. In this paper, a 3D-ERT advanced detection method using source-position electrode excitation is proposed. First, a source-position electrode array integrated into the TBM cutterhead is designed for the shield-tunnel construction environment, which provides data security for the inverse imaging of the anomalous bodies. Secondly, a 3D finite element tunnel model containing high- and low-resistance anomalous bodies is established, and the GREIT reconstruction algorithm is utilized to reconstruct 3D images of the anomalous body in front of the tunnel face. Finally, a physical simulation experiment platform is built, and the effectiveness of the method is verified by laboratory physical modeling experiments with two different anomalous bodies. The results show that the position and shape of the anomalous body in front of the tunnel face can be well reconstructed, and the method provides a new idea for the continuous detection of shield construction tunnels with boring.

Penisimplicins A and B: Novel Polyketide-Peptide Hybrid Alkaloids from the Fungus Penicillium simplicissimum JXCC5.

In this study, two previously undescribed nitrogen-containing compounds, penisimplicins A (1) and B (2), were isolated from Penicillium simplicissimum JXCC5. The structures of 1 and 2 were elucidated on the basis of comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS data. The absolute configuration of 2 was determined by Marfey's method, ECD calculation, and DP4+ analysis. Both structures of 1 and 2 feature an unprecedented manner of amino acid-derivatives attaching to a polyketide moiety by C-C bond. The postulated biosynthetic pathways for 1 and 2 were discussed. Additionally, compound 1 exhibited significant acetylcholinesterase inhibitory activity, with IC50 values of 6.35 µM.

Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities: a cross-sectional study with interrupted time series analysis.

BACKGROUND: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia. METHODS: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019. RESULTS: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding ≥ 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) ≥ 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0.87-0.97; p = 0.0019), duration of breastfeeding ≥ 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001). CONCLUSIONS: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.

Terahertz beam characterization by temporal-spatial mapping with a reflecting echelon.

A terahertz beam imaging method was proposed that involves scanning a reflecting echelon with temporal-spatial mapping inversion based on self-developed translation-scan and rotation-scan temporal-spatial mapping (TTSM and RTSM) algorithms. The beam characteristics of a terahertz time-domain spectroscopy (TDS) system, such as its size, shape, and energy distribution, were obtained. Besides the weak terahertz beam emitted from a TDS system, this scheme is also suitable for imaging large-size terahertz or laser beams in time-domain systems where existing beam imaging is impractical.

Multi-classification model incorporating radiomics and clinic-radiological features for predicting invasiveness and differentiation of pulmonary adenocarcinoma nodules.

PURPOSE: To develop a comprehensive multi-classification model that combines radiomics and clinic-radiological features to accurately predict the invasiveness and differentiation of pulmonary adenocarcinoma nodules. METHODS: A retrospective analysis was conducted on a cohort comprising 500 patients diagnosed with lung adenocarcinoma between January 2020 and December 2022. The dataset included preoperative CT images and histological reports of adenocarcinoma in situ (AIS, n = 97), minimally invasive adenocarcinoma (MIA, n = 139), and invasive adenocarcinoma (IAC, n = 264) with well-differentiated (WIAC, n = 99), moderately differentiated (MIAC, n = 84), and poorly differentiated IAC (PIAC, n = 81). The patients were classified into two groups (IAC and non-IAC) for binary classification and further divided into three and five groups for multi-classification. Feature selection was performed using the least absolute shrinkage and selection operator (LASSO) algorithm to identify the most informative radiomics and clinic-radiological features. Eight machine learning (ML) models were developed using these features, and their performance was evaluated using accuracy (ACC) and the area under the receiver-operating characteristic curve (AUC). RESULTS: The combined model, utilizing the support vector machine (SVM) algorithm, demonstrated improved performance in the testing cohort, achieving an AUC of 0.942 and an ACC of 0.894 for the two-classification task. For the three- and five-classification tasks, the combined model employing the one versus one strategy of SVM (SVM-OVO) outperformed other models, with ACC values of 0.767 and 0.607, respectively. The AUC values for histological subtypes ranged from 0.787 to 0.929 in the testing cohort, while the Macro-AUC and Micro-AUC of the multi-classification models ranged from 0.858 to 0.896. CONCLUSIONS: A multi-classification radiomics model combined with clinic-radiological features, using the SVM-OVO algorithm, holds promise for accurately predicting the histological characteristics of pulmonary adenocarcinoma nodules, which contributes to personalized treatment strategies for patients with lung adenocarcinoma.

Laparoscopic antireflux surgery or PPIs in the management of reflux-related esophageal stricture.

BACKGROUND: Gastroesophageal reflux disease (GERD) is often associated with esophageal stricture, particularly benign esophageal stricture. We aimed to evaluate the effects of balloon catheter dilation (BD) combined with laparoscopic fundoplication (LF) surgery and proton pump inhibitors (PPIs) in patients with reflux-induced esophageal strictures. METHODS: We retrospectively analyzed 116 patients with reflux-induced benign esophageal strictures who underwent balloon dilatation therapy combined with PPIs (BD-PPIs group, n = 58) and balloon dilatation combined with LF (BD-LF group, n = 58). Patients were followed up for 24 months. The outcomes of the patients were monitored, including clinical success, symptom improvement, adverse events, and the frequency of esophagitis. RESULTS: At the latest follow-up, the rate of clinical success was higher in BD-LF group than in BD-PPIs group (80.4% vs. 57.7%, P = 0.011). The patients in the BD-PPIs group required more dilation sessions to achieve successful dilation, as compared to those in the BD-LF group (2.1 ± 1.2 vs. 0.7 ± 0.8, P < 0.001). The DeMeester score, number of reflux episodes for which pH was < 4, and lower esophageal sphincter pressure were significantly better in the BD-LF group than in the BD-PPIs group (all P < 0.001). The incidence of reflux esophagitis was higher in the BD-PPIs group than in the BD-LF group, at 24 months (58.8% vs. 18.2%, P = 0.003). CONCLUSIONS: Balloon dilatation with concomitant LF is effective and safe for esophageal stricture secondary to GERD. Moreover, antireflux surgery techniques, such as Nissen or Toupet procedure, should be added for reflux-induced benign esophageal stricture.

A 7-Day Decitabine-Included Conditioning Regimen Accelerated Donor Hematopoietic Engraftment while Reduced the Occurrence of Mucositis without Interfering with Prognosis.

INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the standard and curative treatment strategy for patients with hematologic malignancies. Recently, decitabine-included regimens have been investigated by several studies including ours, which may prevent relapse of primary malignant diseases. METHODS: This study was to retrospectively evaluate a 7-day decitabine-included regimen with reduced dose of idarubicin for patients with hematologic malignancies who underwent allo-HSCT. RESULTS: A total of 84 patients were enrolled, including 24 cases in 7-day and 60 cases in 5-day decitabine groups, respectively. Patients conditioned with 7-day decitabine regimen showed accelerated neutrophil (12.05 ± 1.97 vs. 13.86 ± 3.15; u = 9.309, p < 0.001) and platelet (16.32 ± 6.27 vs. 21.37 ± 8.57; u = 8.887, p < 0.001) engraftment compared with those treated with 5-day decitabine regimen. Patients in the 7-day decitabine group showed a significantly lower incidence rate of total (50.00% [12/24] versus 78.33% [47/60]; χ2 = 6.583, p = 0.010) and grade III or above (4.17% [1/24] vs. 31.67% [19/60]; χ2 = 7.147, p = 0.008) oral mucositis compared to those in the 5-day decitabine group. However, the occurrence of other major complications post-allo-HSCT and outcomes of patients in these two groups were comparable. CONCLUSION: These results demonstrate that this 7-day decitabine-contained new conditioning regimen seems to be feasible and safe for patients with myeloid neoplasms who receive allo-HSCT, and a large-scale prospective study is needed to confirm the findings of this study.

The value of a dual-energy CT Iodine map radiomics model for the prediction of collagen fiber content in the ccRCC tumor microenvironment.

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) is a heterogeneous group of cancers. The collagen fiber content in the tumor microenvironment of renal cancer has an important role in tumor progression and prognosis. A radiomics model was developed from dual-energy CT iodine maps to assess collagen fiber content in the tumor microenvironment of ccRCC. METHODS: A total of 87 patients with ccRCC admitted to our hospital were included in this retrospective study. Among them, 59 cases contained large amounts of collagen fibers and 28 cases contained a small amount of collagen fibers. We established a radiomics model using preoperative dual-energy CT scan Iodine map (IV) imaging to distinguish patients with multiple collagen fibers from those with few collagen fibers in the tumor microenvironment of ccRCC. We extracted features from dual-energy CT Iodine map images to evaluate the effects of six classifiers, namely k-nearest neighbor (KNN), support vector machine (SVM), extreme gradient boosting (XGBoost), random forest (RF), logistic regression (LR), and decision tree (DT). The effects of the models built based on the dynamic and venous phases are also compared. Model performance was evaluated using quintuple cross-validation and area under the receiver operating characteristic curve (AUC). In addition, a clinical model was developed to assess the clinical factors affecting collagen fiber content. RESULTS: Compared to KNN, SVM, and LR classifiers, RF, DT, and XGBoost classifiers trained with higher AUC values, with training sets of 0.997, 1.0, and 1.0, respectively. In the validation set, the highest AUC was found in the SVM classifier with a size of 0.722. In the comparative test of the active and intravenous phase models, the SVM classifier had the best effect with its validation set AUC of 0.698 and 0.741. In addition, there was a statistically significant effect of patient age and maximum tumor diameter on the collagen fiber content in the tumor microenvironment of kidney cancer. CONCLUSION: Radionics features based on preoperative dual-energy CT IV can be used to predict the amount of collagen fibers in the tumor microenvironment of renal cancer. This study better informs clinical prognosis and patient management. Iodograms may add additional value to dual-energy CTs.

CCL3-CCR5 axis promotes cell migration and invasion of colon adenocarcinoma via Akt signaling pathway.

BACKGROUND: Infiltration of tumor-associated macrophages (TAMs) can promote tumorigenesis and development. C-C motif chemokine ligand 3 (CCL3) was reported to be derived from TAMs and tumor cells and facilitate the progression of several cancers. Nevertheless, whether CCL3 can be derived from TAMs and tumor cells of colon adenocarcinoma (COAD) is unclarified. METHODS: Peripheral blood monocytes-derived macrophages were polarized by the conditioned medium from COAD cells to establish TAM-like macrophages (TAM1/2). RT-qPCR and western blotting were used for detection of expression levels of CCL3 and its receptors C-C motif chemokine receptor 1 (CCR1) and CCR5 in TAM1/2 and COAD cells. Immunofluorescence staining was utilized for evaluating CCL3, CD163 and CCR5 expression. The Akt signaling pathway-associated protein levels were measured by western blotting. Transwell assays were used for assessing cell migration and invasiveness. RESULTS: CCL3 displayed a high level in TAMs and cancer cells of COAD. CCL3 activated the Akt signaling pathway by binding to CCR5. CCL3-CCR5 axis facilitated COAD cell migration and invasiveness by activating the Akt signaling. CCL3 derived from both TAMs and cancer cells contributed to the malignant behaviors of COAD cells. High expression of CCL3/CCR5 was closely associated with poor prognoses of COAD patients. CONCLUSION: CCL3-CCR5 interaction promotes cell migration and invasiveness, and functions as a prognostic biomarker for COAD.

Circular RNA MTCL1 promotes advanced laryngeal squamous cell carcinoma progression by inhibiting C1QBP ubiquitin degradation and mediating beta-catenin activation.

BACKGROUND: Circular RNAs (circRNAs) are involved in regulatory processes of ubiquitination and deubiquitination in various tumors at post-transcriptional epigenetic modification level. However, the underlying mechanism and its biological functions of circRNAs in the advanced laryngeal squamous cell carcinoma (LSCC) remain obscure. METHODS: RNA sequencing and quantitative real-time PCR (qRT-PCR) assays were applied to screen for circRNAs differentially expressed in LSCC tissues and cell lines. The candidate RNA-binding proteins and target signalling pathway were detected by RNA pull-down and mass spectrometry, in situ hybridization (ISH), immunohistochemistry (IHC), qRT-PCR assays, and bioinformatics analysis. The functional roles of these molecules were investigated using in vitro and in vivo experiments including EdU, transwell, wound healing, western blot assays, and the xenograft mice models. The molecular mechanisms were identified using RNA pull-down assays, RNA immunoprecipitation (RIP), Co-IP, ISH, Ubiquitination assay, bioinformatics analysis, and the rescue experiments. RESULTS: Here, we unveil that microtubule cross-linking factor 1 circRNA (circMTCL1, circ0000825) exerts its critical oncogenic functions by promoting complement C1q-binding protein (C1QBP)-dependent ubiquitin degradation and subsequently activating Wnt/ß-catenin signalling in laryngeal carcinoma initiation and development. Specifically, circMTCL1 was remarkably up-regulated in the paired tissues of patients with LSCC (n = 67), which predicted a worse clinical outcome. Functionally, circMTCL1 exerted oncogenic biological charactersistics by promoting cell proliferative capability and invasive and migrative abilities. Ectopic circMTCL1 augumented cell proliferation, migration, and invasion of LSCC cells, and this effect could be reversed by C1QBP knocking down in vitro and in vivo. Mechanistically, circMTCL1 directly recruited C1QBP protein by harboring the specific recognized sequence (+ 159 - + 210), thereby accelerating the translation of C1QBP expression by inhibiting its ubiquitin-proteasome-mediated degradation. Importantly, the direct interaction of C1QBP with ß-catenin protein was enhanced via suppressing the ß-catenin phosphorylation and accelerating its accumulation in cytoplasm and nucleus. CONCLUSION: Our findings manifested a novel circMTCL1-C1QBP-ß-catenin signaling axis involving in LSCC tumorigenesis and progression, which shed new light on circRNAs-ubiquitous acidic glycoprotein mediated ubiquitin degradation and provided strategies and targets in the therapeutic intervention of LSCC.

Zebrafish NIK Mediates IFN Induction by Regulating Activation of IRF3 and NF-κB.

Type I IFN mediates the innate immune system to provide defense against viral infections. NF-κB-inducing kinase (NIK) potentiates the basal activation of endogenous STING, which facilitates the recruitment of TBK1 with the ectopically expressed IRF3 to induce IFN production. Moreover, NIK phosphorylates IKKα and confers its ability to phosphorylate p100 (also known as NF-κB2) in mammals. Our study demonstrated that NIK plays a critical role in IFN production in teleost fish. It was found that NIK interacts with IKKα in the cytoplasm and that IKKα phosphorylates the NIK at the residue Thr432, which is different from the mammals. Overexpression of NIK caused the activation of IRF3 and NF-κB, which in turn led to the production of IFN and IFN-stimulated genes (ISGs). Furthermore, the ectopic expression of NIK was observed to be associated with a reduced replication of the fish virus, whereas silencing of endogenous NIK had an opposite effect in vitro. Furthermore, NIK knockdown significantly reduced the expression of IFN and key ISGs in zebrafish larvae after spring viremia of carp virus infection. Additionally, the replication of spring viremia of carp virus was enhanced in NIK knockdown zebrafish larvae, leading to a lower survival rate. In summary, our findings revealed a previously undescribed function of NIK in activating IFN and ISGs as a host antiviral response. These findings may facilitate the establishment of antiviral therapy to combat fish viruses.

Bacteria establish an aqueous living space in plants crucial for virulence.

High humidity has a strong influence on the development of numerous diseases affecting the above-ground parts of plants (the phyllosphere) in crop fields and natural ecosystems, but the molecular basis of this humidity effect is not understood. Previous studies have emphasized immune suppression as a key step in bacterial pathogenesis. Here we show that humidity-dependent, pathogen-driven establishment of an aqueous intercellular space (apoplast) is another important step in bacterial infection of the phyllosphere. Bacterial effectors, such as Pseudomonas syringae HopM1, induce establishment of the aqueous apoplast and are sufficient to transform non-pathogenic P. syringae strains into virulent pathogens in immunodeficient Arabidopsis thaliana under high humidity. Arabidopsis quadruple mutants simultaneously defective in a host target (AtMIN7) of HopM1 and in pattern-triggered immunity could not only be used to reconstitute the basic features of bacterial infection, but also exhibited humidity-dependent dyshomeostasis of the endophytic commensal bacterial community in the phyllosphere. These results highlight a new conceptual framework for understanding diverse phyllosphere-bacterial interactions.

Hydrogen sulfide as a potent scavenger of toxicant acrolein.

Acrolein (ACR) is a metabolic byproduct in vivo and a ubiquitous environmental toxicant. It is implicated in the initiation and development of many diseases through multiple mechanisms, including the induction of oxidative stress. Currently, our understanding of the body defense mechanism against ACR toxicity is still limited. Given that hydrogen sulfide (H2S) has strong antioxidative actions and it shares several properties of ACR scavenger glutathione (GSH), we, therefore, tested whether H2S could be involved in ACR detoxification. Taking advantage of two cell lines that produced different levels of endogenous H2S, we found that the severity of ACR toxicity was reversely correlated with H2S-producing ability. In further support of the role of H2S, supplementing cells with exogenous H2S increased cell resistance to ACR, whereas inhibition of endogenous H2S sensitized cells to ACR. In vivo experiments showed that inhibition of endogenous H2S with CSE inhibitor markedly increased mouse susceptibility to the toxicity of cyclophosphamide and ACR, as evidenced by the increased mortality and worsened organ injury. Further analysis revealed that H2S directly reacted with ACR. It promoted ACR clearance and prevented ACR-initiated protein carbonylation. Collectively, this study characterized H2S as a presently unrecognized endogenous scavenger of ACR and suggested that H2S can be exploited to prevent and treat ACR-associated diseases.