Triterpenoids from the leaves of Eleutherococcus sessiliflorus, and their antiproliferative activities in TNF-α induced HFLS-RA cells.

Five undescribed elesesterpenes L-U, along with nine known 3,4-seco-lupane-type triterpenoids were isolated from the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu. Elesesterpene L-S, and U were lupane-type triterpenoids, whereas elesesterpene T was an oleanane-type triterpenoid, probably artifact, as suggested by LC-MS analysis. Out of the nine known compounds, five were initially identified in E. sessiliflorus. Moreover, their structures were definitively determined using spectroscopic analyses, and the absolute configurations of elesesterpenes L-M and sachunogenin 3-O-glucoside were clarified using X-ray crystallographic techniques. The absolute configuration of elesesterpene T was determined by measuring and calculating its ECD. In addition, all compounds were tested to examine their ability to inhibit the proliferation of HFLS-RA cells induced by TNF-α in vitro. Elesesterpene M, chiisanogenin, chiisanoside, and 3-methylisochiisanoside significantly inhibited HFLS-RA proliferation.

Clinical Characteristics and Outcomes of the Phenotypes of COPD-Bronchiectasis Association.

INTRODUCTION: Although COPD may frequently co-exist with bronchiectasis [COPD-bronchiectasis associated (CBA)], little is known regarding the clinical heterogeneity. We aimed to identify the phenotypes and compare the clinical characteristics and prognosis of CBA. METHODS: We conducted a retrospective cohort study involving 2928 bronchiectasis patients, 5158 COPD patients, and 1219 patients with CBA hospitalized between July 2017 and December 2020. We phenotyped CBA with a two-step clustering approach and validated in an independent retrospective cohort with decision-tree algorithms. RESULTS: Compared with patients with COPD or bronchiectasis alone, patients with CBA had significantly longer disease duration, greater lung function impairment, and increased use of intravenous antibiotics during hospitalization. We identified five clusters of CBA. Cluster 1 (N=120, CBA-MS) had predominantly moderate-severe bronchiectasis, Cluster 2 (N=108, CBA-FH) was characterized by frequent hospitalization within the previous year, Cluster 3 (N=163, CBA-BI) had bacterial infection, Cluster 4 (N=143, CBA-NB) had infrequent hospitalization but no bacterial infection, and Cluster 5 (N=113, CBA-NHB) had no hospitalization or bacterial infection in the past year. The decision-tree model predicted the cluster assignment in the validation cohort with 91.8% accuracy. CBA-MS, CBA-BI, and CBA-FH exhibited higher risks of hospital re-admission and intensive care unit admission compared with CBA-NHB during follow-up (all P<0.05). Of the five clusters, CBA-FH conferred the worst clinical prognosis. CONCLUSION: Bronchiectasis severity, recent hospitalizations and sputum culture findings are three defining variables accounting for most heterogeneity of CBA, the characterization of which will help refine personalized clinical management.

A facile synthesis of α,ß-unsaturated imines via palladium-catalyzed dehydrogenation.

The dehydrogenation adjacent to an electron-withdrawing group provides an efficient access to α,ß-unsaturated compounds that serving as versatile synthons in organic chemistry. However, the α,ß-desaturation of aliphatic imines has hitherto proven to be challenging due to easy hydrolysis and preferential dimerization. Herein, by employing a pre-fluorination and palladium-catalyzed dehydrogenation reaction sequence, the abundant simple aliphatic amides are amendable to the rapid construction of complex molecular architectures to produce α,ß-unsaturated imines. Mechanistic investigations reveal a Pd(0)/Pd(II) catalytic cycle involving oxidative H-F elimination of N-fluoroamide followed by a smooth α,ß-desaturation of the in-situ generated aliphatic imine intermediate. This protocol exhibits excellent functional group tolerance, and even the carbonyl groups are compatible without any competing dehydrogenation, allowing for late-stage functionalization of complex bioactive molecules. The synthetic utility of this transformation has been further demonstrated by a diversity-oriented derivatization and a concise formal synthesis of (±)-alloyohimbane.

Experimental Study of Electroosmosis in Rock Cores Based on the Dual Pressure Sensor Method.

Electroosmotic experiments obtain the electroosmotic pressure coefficient of a rock sample by measuring the excitation voltage at both ends of the sample and the pressure difference caused by the excitation voltage. The electroosmotic pressure is very weak and buried in the background noise, which is the most difficult signal to measure in the dynamic-electric coupling experiment, so it is necessary to improve its signal-to-noise ratio. In this paper, for the low signal-to-noise ratio of electroosmotic pressure, the dual pressure sensor method is proposed, i.e., two pressure sensors of the same type are used to measure electroosmotic pressure. Two different data extraction methods, Fast Fourier Transform and Locked Amplification, are utilized to compare the dual pressure sensor method of this paper with the existing single pressure sensor method. The relationship between the electroosmotic pressure coefficient and the excitation frequency, mineralization, permeability, and porosity is analyzed and discussed.

Chemical constituents from the Saposhnikovia divaricata and their antiproliferative activity.

Nine compounds were isolated and identified from ethanolic extracts of Saposhnikovia divaricata, including one new alkaloid (1), one new pentacyclic triterpenoid (9), and seven known alkaloids (2-8). Structural elucidation of compounds 1 and 9 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. All compounds were evaluated for antiproliferative activity against two cancer cell lines (LN229, A549) in vitro. Compounds (1-9) showed no significant antiproliferative activity.

FOXS1 acts as an oncogene and induces EMT through FAK/PI3K/AKT pathway by upregulating HILPDA in prostate cancer.

Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.

Comparison of Sleeve Gastrectomy with Loop Duodenojejunal Bypass Versus One Anastomosis Gastric Bypass for Type 2 Diabetes: The Role of Pylorus Preservation.

BACKGROUND: One anastomosis gastric bypass (OAGB) is recognized as a standard procedure in metabolic surgery. However, concerns about postoperative bile reflux and nutritional risks are prevalent. Comparatively, sleeve gastrectomy with loop duodenojejunal bypass (SG + LoopDJB) bypasses an equivalent length of the foregut as OAGB while maintaining pyloric function. The role of pylorus function remains to be further elucidated regarding these metabolic procedures' therapeutic outcomes and side effects. METHOD: A retrospective study was conducted in our center to compare the surgical safety and 1-year outcomes of OAGB and SG + LoopDJB regarding type 2 diabetes mellitus (T2DM) remission, weight loss, gastrointestinal disorders, and nutritional status in T2DM patients matched by gender, age, and BMI. RESULTS: The baseline characteristics were comparable between groups. Compared with OAGB, SG + LoopDJB had longer operative time and length of stay (LOS) but similar major postoperative complications. At 1-year follow-up, OAGB has similar diabetes remission (both 91.9%), weight loss effect (28.1 ± 7.1% vs. 30.2 ± 7.0% for %TWL), and lipidemia improvement to SG + LoopDJB (P > 0.05). However, OAGB presented a higher incidence of hypoalbuminemia (11.9% vs. 2.4%, P = 0.026) but a low incidence of gastroesophageal reflux disease (GERD) symptoms (9.5% vs. 26.2%, P = 0.046) than SG + LoopDJB. There was no statistical difference regarding other gastrointestinal disorders and nutritional deficiencies between groups. CONCLUSION: Both OAGB and SG + LoopDJB show comparable, favorable outcomes in weight loss, T2DM remission, and lipidemia improvement at the 1-year follow-up. Pylorus preservation, while increasing surgical difficulty and the risk of de novo GERD, may reduce the risk of postoperative hypoalbuminemia.

GPR56, an Adhesion GPCR with Multiple Roles in Human Diseases, Current Status and Future Perspective.

Human G protein-coupled receptor 56 (GPR56) belongs to a member of the adhesion G-protein coupled receptor (aGPCR) family and widely exists in the central nervous system and various types of tumor tissues. Recent studies have shown that abnormal expression or dysfunction of GPR56 is closely associated with many physiological and pathological processes, including brain development, neuropsychiatric disorders, cardiovascular diseases and cancer progression. In addition, GPR56 has been proven to enhance the susceptibility of some antipsychotics and anticarcinogens in response to the treatment of neuropsychological diseases and cancer. Although there have been some reports about the functions of GPR56, the underlying mechanisms implicated in these diseases have not been clarified thoroughly, especially in depression and epilepsy. Therefore, in this review, we described the molecular structure and signal transduction pathway of GPR56 and carried out a comprehensive summary of GPR56's function in the development of psychiatric disorders and cancer. Our review showed that GPR56 deficiency led to depressive-like behaviors and an increase in resistance to antipsychotic treatment. In contrast, the upregulation of GPR56 contributed to tumor cell proliferation and metastasis in malignant diseases such as glioblastoma, colorectal cancer, and ovarian cancer. Moreover, we elucidated specific signaling pathways downstream of GPR56 related to the pathogenesis of these diseases. In summary, our review provides compelling arguments for an attractive therapeutic target of GPR56 in improving the therapeutic efficiency for patients suffering from psychiatric disorders and cancer.

Association between coffee and caffeine intake and risk of COPD: Findings based on NHANES 2007-2012.

BACKGROUND: The association between coffee and caffeine intake and the risk of COPD and lung function has not been thoroughly discussed in Americans, with subgroup and threshold effects remaining unclear. OBJECTIVES: This study investigated the association between coffee and caffeine consumption and the risk of chronic obstructive pulmonary disease (COPD) as well as lung function utilizing data from the NHANES 2007-2012. METHODS: We assessed the associations of coffee and caffeine consumption with the risk of COPD and lung function parameters, including FEV1 and FVC, adjusting for common demographic and disease characteristics in a cross-sectional analysis of NHANES data. RESULTS: A total of 9763 participants were included in the study, and 592 were diagnosed with COPD. Multivariate regression models revealed positive associations between coffee and caffeine consumption and the risk of COPD and lung function. Subgroup analyses stratified by sex, DM, hypertension status, and smoking habits identified potential effect modifiers as well as inflection points from threshold effect examinations. CONCLUSIONS: The results of this cross-sectional study indicated significant positive correlations between coffee and caffeine consumption and the risk of COPD. Additionally, positive correlations between exposure variables and FEV1 and FVC were detected. Among the stratification factors, smoking status exhibited the most potential for modifying effects. Future practices and research are needed to validate the results and explore the underlying mechanisms.

Management of renal sinus angiomyolipoma: modified robotic nephron-sparing surgery in a single center.

BACKGROUND: Renal sinus angiomyolipoma (RSAML) is a rare and typically complex renal tumor. The objective is to present our single-center experience with a modified technique of robotic nephron-sparing surgery (NSS) for treating RSAML. METHODS: We retrospectively evaluated 15 patients with RSAMLs who were treated with robotic NSS at the Department of Urology of Tongji hospital, ranging from November 2018 to September 2022. Renal vessels and ureter were dissected. The outer part of RSAML was resected. The rest of tumor was removed by bluntly grasp, curettage and suction. Absorbable gelatin sponges were filled in the renal sinus. The preoperative parameters, operative measures and postoperative outcomes were all collected. Follow-up was performed by ultrasonography and estimated glomerular filtration rate (eGFR). RESULTS: Robotic NSS was successfully performed in all the patients, without any conversion to open surgery or nephrectomy. The mean operation time was 134.13 ± 40.56 min. The mean warm ischemia time was 25.73 ± 3.28 min. The median estimated blood loss was 100 [50, 270] ml and 1 patient required blood transfusion. The mean drainage duration was 5.77 ± 1.98 days. The median postoperative hospital stay was 6.90 [5.80, 8.70] days. Two patients experienced postoperative urinary tract infection (Clavien-Dindo Grade II). During the median follow-up of 25.53 ± 15.28 months, patients received 91.18% renal function preservation. No local recurrence occurred in all the patients. CONCLUSIONS: Robotic NSS for RSAML is a complicated procedure that demands technical expertise and a well-designed strategy is critical in the operation. Treating RSAML with modified robotic NSS is safe, effective and feasible.

Fourteen undescribed steroidal saponins from Solanum capsicoides leaves and their neuroprotective effects.

A total of 14 previously undescribed steroidal saponins named capsicsaponins A-N were isolated from the leaves of Solanum capsicoides, encompassing various types, including cholesterol derivatives and pseudospirostanol saponins. The structures of all compounds were determined through comprehensive analysis of spectroscopic data (1D NMR and 2D NMR), along with physicochemical analysis methods (acid hydrolysis, OR, and UV). Moreover, in the H2O2-induced pheochromocytoma cell line model, compounds 1-14 were screened for their neuroprotective effects on cells. The bioassay results demonstrated compounds 8-14 were able to revive cell viability compared to the positive control edaravone. The damage neuroprotection of the most active compound was further explored.

A new 3,4-dihydroisocoumarin and an antiinflammatory coumarin from the roots of Saposhnikovia divaricata (Turcz.) Schischk.

Phytochemical investigation of the roots of Saposhnikovia divaricata (Turcz.) Schischk resulted in the isolation of twelve coumarin derivatives including one new 3,4-dihydroisocoumarin (1) and eleven known 3,4-unsubstituted coumarins (2-12). Structural elucidation of compounds 1-12 was established by 1D and 2D NMR spectra referring to the literature, together with high-resolution mass spectrometric analysis. LPS-induced RAW264.7 inflammatory cell model was used to determine the potential antiinflammation activity of all the isolated compounds in vitro. The results showed that compound 3 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages (IC50 = 4.54 ± 1.71 µM), more active than the positive control (L-NMMA).

An efficient and accurate multi-level cascaded recurrent network for stereo matching.

With the advent of Transformer-based convolutional neural networks, stereo matching algorithms have achieved state-of-the-art accuracy in disparity estimation. Nevertheless, this method requires much model inference time, which is the main reason limiting its application in many vision tasks and robots. Facing the trade-off problem between accuracy and efficiency, this paper proposes an efficient and accurate multi-level cascaded recurrent network, LMCR-Stereo. To recover the detailed information of stereo images more accurately, we first design a multi-level network to update the difference values in a coarse-to-fine recurrent iterative manner. Then, we propose a new pair of slow-fast multi-stage superposition inference structures to accommodate the differences between different scene data. Besides, to ensure better disparity estimation accuracy with faster model inference speed, we introduce a pair of adaptive and lightweight group correlation layers to reduce the impact of erroneous rectification and significantly improve model inference speed. The experimental results show that the proposed approach achieves a competitive disparity estimation accuracy with a faster model inference speed than the current state-of-the-art methods. Notably, the model inference speed of the proposed approach is improved by 46.0% and 50.4% in the SceneFlow test set and Middlebury benchmark, respectively.

A new triterpenoid saponin and a new natural saponin from the roots of Bupleurum scorzonerifolium willd.

Sixteen triterpenoid saponins were isolated from the roots of Bupleurum scorzonerifolium Willd., including a new triterpenoid saponin and new natural saponin that was characterised by NMR for the first time, along with 14 known triterpenoid saponins. The structures of the compounds were established by 1D and 2D NMR spectroscopy, HR-ESI-MS, and comparison with the literature. The cytotoxic activity of the compounds against 4T1 cells was determined using the CCK8 method. Compounds 9 and 6 showed the strongest cytotoxic activity with IC50 values of 2.75 ± 0.86 and 3.78 ± 0.50 µM, respectively. Compounds 2-5 and 8 showed potent cytotoxic activity. Compounds 14 and 16 showed moderate cytotoxicity.

Prognostic effect of DNA methylation of BTG2 gene in Chinese hepatocellular carcinoma.

Background: This study aims to develop a prognostic model for overall survival based on potential methylation sites within B-cell translocation gene 2 (BTG2) in Chinese patients with hepatocellular carcinoma (HCC). Methods: This is a retrospective study. The beta values of nine CpG sites and RSEM normalized count values of BTG2 gene were extracted from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) (TCGA-LIHC) dataset, with the beta value representing the methylation level by indicating the ratio of the intensity of the methylated bead type to the combined locus intensity. Pyrosequencing was performed to determine the range of methylation values surrounding cg01798157 site in BTG2 gene. A weighted linear model was developed to predict the overall survival (OS). Results: The beta value of cg01798157 was significantly negatively associated with the mRNA expression of BTG2 in the TCGA-LIHC dataset (Spearman's rho = -0.5306, P = 2.27 × 10-27). The methylation level of cg01798157 was significantly associated with OS in the cohort of 51 Chinese HCC patients (Hazard ratio = 0.597, 95% CI: 0.434-0.820, P = 0.001). Multivariate Cox regression analysis identified methylation level of cg01798157, cirrhosis, and microvascular invasion as independent prognostic factors. The prognostic efficiency of death risk score was superior to that of cirrhosis or microvascular invasion alone. Conclusions: The methylation level of cg01798157 in BTG2 may be an epigenetic biomarker in Chinese patients with resectable HCC.

Cytotoxicity phenylpropanoid amides from the seed of Cannabis sativa L.

Two novel phenylpropanoid amides, namely huomarenamide A (1) and huomarenamide B (2), along with twelve known compounds (3-14), were isolated from the seeds of Cannabis sativa L. The structures with absolute configurations of new compounds were unequivocally determined by spectroscopic analyses and the ECD method. The identification of the known compounds was based on a comparison of their 1D NMR data with literature references. All compounds were assessed for cytotoxic activity against LN229 cells, revealing that compounds 2, 13, and 14 exhibited significant cytotoxicity with IC50 values ranging from 9.02 to 21.26 µM.

Room-Temperature High-Performance Photodetector and Phototransistor Based on PdSe2/ZnIn2S4 Alloy Heterojunctions.

Various semiconductor devices have been developed based on 2D heterojunction materials owing to their distinctive optoelectronic properties. However, to achieve efficient charge transfer at their interface remains a major challenge. Herein, an alloy heterojunction concept is proposed. The sulfur vacancies in ZnIn2S4 are filled with selenium atoms of PdSe2. This chemically bonded heterojunction can significantly enhance the separation of photocarriers, providing notable advantages in the field of photoelectric conversion. As a demonstration, a two-terminal photodetector based on the PdSe2/ZnIn2S4 heterojunction materials is fabricated. The photodetector exhibits stable operation in ambient conditions, showcasing superior performance in terms of large photocurrent, high responsivity (48.8 mA W-1) and detectivity (1.98 × 1011 Jones). To further validate the excellent optoelectronic performance of the heterojunction, a tri-terminal phototransistor is also fabricated. Benefiting from gate voltage modulation, the photocurrent is amplified to milliampere level, and the responsivity is increased to 229.14 mA W-1. These findings collectively demonstrate the significant potential of the chemically bonded PdSe2/ZnIn2S4 alloy heterojunction for future optoelectronic applications.

Comparison of Copper-Tolerance Genes between Different Groups of Acidovorax citrulli.

Acidovorax citrulli populations exhibit genetic and phenotypic variations, particularly in terms of copper tolerance. Group I strains of A. citrulli generally exhibit higher copper tolerance compared to group II strains. This study aims to identify genes involved in copper tolerance to better understand the differences in copper tolerance between group I and group II strains. Representative strains pslb65 (group I) and pslbtw14 (group II) were selected for comparison. Deletion mutants of putative copper-tolerance genes and their corresponding complementary strains were constructed. The copper tolerance of each strain was evaluated using the minimum inhibitory concentration method. The results showed that the copA, copZ, cueR, and cueO genes played major roles in copper tolerance in A. citrulli, while cusC-like, cusA-like, and cusB-like genes had minor effects. The different expression levels of copper-tolerance-related genes in pslb65 and pslbtw14 under copper stress indicated that they had different mechanisms for coping with copper stress. Overall, this study provides insights into the mechanisms of copper tolerance in A. citrulli and highlights the importance of specific genes in copper tolerance.

Luteolin: A promising multifunctional natural flavonoid for human diseases.

Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti-convulsion, diabetes control, anti-inflammatory, neuroprotection, anti-oxidation, anti-cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF-κB, toll-like receptor, MAPK, Wnt/ß-catenin, PI3K/Akt, AMPK/mTOR, and Nrf-2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT.