Arenarialins A-F, Anti-inflammatory Meroterpenoids with Rearranged Skeletons from the Marine Sponge Dysidea arenaria.

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (1-6), were isolated from the marine sponge Dysidea arenaria collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A (1) features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (2-4) possess two rare secomeroterpene scaffolds. Arenarialins A-F showed inhibitory activity on the production of inflammatory cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages with arenarialin D regulating the NF-κB/MAPK signaling pathway.

Marcytoglobosins A and B, Cytochalasans From a Marine Sponge Associated Chaetomium globosum 162105 Fungus.

Two new cytochalasans, marcytoglobosins A (1) and B (2) were isolated from the marine sponge associated fungus Chaetomium globosum 162105, along with six known compounds (3-8). The complete structures of two new compounds were determined based on 1D/2D NMR and HR-MS spectroscopic analyses coupled with ECD calculations. All eight isolates were evaluated for their antibacterial activity. Among them, compounds 3-8 displayed antibacterial effects against Staphylococcus epidermidis, Bacillus thuringiensis, Pseudomonas syringae pv. Actinidiae, Vibrio alginolyticus, and Edwardsiella piscicida with minimum inhibitory concentration (MIC) values ranging from 10 to 25 µg/mL.

Study on fabrication of force transducer based on carbon nano-flake balls.

The purpose of this study was to fabricate a force sensor. A novel three-dimensional carbon-based material called a carbon nano-flake ball (CNFB) was used because it exhibits a large surface-area and high electrical conductivity. Moreover, CNFB can be easily fabricated using a one-step process via microwave plasma chemical vapor deposition. In the present study, two different methods, chemical and mechanical exfoliation, were used to fabricate the CNFB thin films. CNFEs were successfully synthesized on the silicon-based composite substrate. The substrate was constructed by the Si, SiO2, and Al2O3, where Al2O3played the role of the substrate for the force sensor while SiO2was the interface layer and was removed in the process by hydrogen fluoride (HF) solution to separate Al2O3from Silicon. The experiments showed that using sol-gel catalyst coating as pretreatment precursor, results in a larger ball-size but lower deposition density of CNFB on Al2O3substrate. By using mechanical exfoliation by polyimide (PI) tape, the CNFB grown on silicon substrate can be easily exfoliated from the substrate. PI/CNFB was successfully exfoliated from the substrate with a silver-grey color at the bottom of the CNFB which is likely to be silicon carbide (SiC) from the energy dispersive spectrometer analysis. The sheet resistance of PI/CNFB was 18.3 ± 1.0 Ω sq.-1PI/CNFB exhibits a good force sensing performance with good stability after 10 times of loading-unloading cycles and a good sensitivity of 11.6 Ω g-1.

Aspergetherins A-D, New Chlorinated Biphenyls with anti-MRSA Activity from the Marine Sponge Symbiotic Fungus Aspergillus terreus 164018.

Aspergetherins A-D (1-4), four new chlorinated biphenyls, were isolated from the rice fermentation of a marine sponge symbiotic fungus Aspergillus terreus 164018, along with seven known biphenyl derivatives (5-11). The structures of four new compounds were determined by a comprehensive analysis of the spectroscopic data, including HR-ESI-MS and 2D NMR data. All 11 isolates were evaluated for their anti-bacterial activity against two strains of methicillin-resistant Staphylococcus aureus (MRSA). Among them, compounds 1, 3, 8 and 10 showed anti-MRSA activity with MIC values of 1.0-128 µg/mL. Preliminary structure-activity relationship analysis unveiled that both chlorinated substitution and esterification of 2-carboxylic acid could impact the antibacterial activity of biphenyls.

Dysiscalarones A-E, scalarane sesterterpenoids with nitric oxide production inhibitory activity from marine sponge Dysidea granulosa.

Dysiscalarones A-E (1-5), five new scalarane-type bishomoscalarane sesterterpenoids, were isolated from marine sponge Dysidea granulosa collected from the South China Sea, together with two known ones, honulactone A (6) and phyllofolactone I (7). The new structures were determined by extensive spectroscopic analysis including HR-ESI-MS and 1D and 2D NMR data, and their absolute configurations were assigned by single crystal X-ray diffraction analyses. The inhibitory activity of all the seven isolates on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages was evaluated. Of these metabolites, dysiscalarones A-B (1-2), honulactone A (6), and phyllofolactone I (7) showed inhibitory activities with respective IC50 values of 16.4, 18.5, 2.6, and 3.7 µM, which suggested that the γ-methylated α,ß-unsaturated γ-lactone might be the functional group. In addition, all the seven metabolites showed no significant cytotoxicity against lung cancer PC9 cell line at the concentration of 20 µM.

Trichodermaloids A-C, Cadinane Sesquiterpenes from a Marine Sponge Symbiotic Trichoderma sp. SM16 Fungus.

Three new cadinane sesquiterpenes, trichodermaloids A (1), B (2), and C (5) were isolated from a symbiotic fungus Trichoderma sp. SM16 derived from the marine sponge Dysidea sp., together with three known ones, aspergilloid G (3), rhinomilisin E (4), and rhinomilisin G (6). The complete structures of three new compounds were determined by HR-MS and NMR spectroscopic analyses coupled with ECD calculations. The absolute configurations of two known compounds (4 and 6) were determined for the first time. The six isolates were inactive as antibacterial agents. However, trichodermaloids A and B have shown cytotoxicity on human NCIH-460 lung, NCIC-H929 myeloma, and SW620 colorectal cancer cell lines with IC50 values at the range of 6.8-12.7 µm.

HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis.

BACKGROUND: Dysregulation of pericellular proteolysis usually accounts for cancer cell invasion and metastasis. Isolation of a cell-surface protease system for lung cancer metastasis is an important issue for mechanistic studies and therapeutic target identification. METHODS: Immunohistochemistry of a tissue array (n = 64) and TCGA database (n = 255) were employed to assess the correlation between serine protease inhibitors (SPIs) and lung adenocarcinoma progression. The role of SPI in cell motility was examined using transwell assays. Pulldown and LC/MS/MS were performed to identify the SPI-modulated novel protease(s). A xenografted mouse model was harnessed to demonstrate the role of the SPI in lung cancer metastasis. RESULTS: Hepatocyte growth factor activator inhibitor-2 (HAI-2) was identified to be downregulated following lung cancer progression, which was related to poor survival and tumour invasion. We further isolated a serum-derived serine protease, plasmin, to be a novel target of HAI-2. Downregulation of HAI-2 promotes cell surface plasmin activity, EMT, and cell motility. HAI-2 can suppress plasmin-mediated activations of HGF and TGF-ß1, EMT and cell invasion. In addition, downregulated HAI-2 increased metastasis of lung adenocarcinoma via upregulating plasmin activity. CONCLUSION: HAI-2 functions as a novel inhibitor of plasmin to suppress lung cancer cell motility, EMT and metastasis.

Lidocaine lubricants for intubation-related complications: a systematic review and meta-analysis.

PURPOSE: Postoperative sore throat (POST) is a relatively common morbidity. Topical lidocaine lubricants have been proposed to prevent POST; however, their effectiveness remains uncertain. This meta-analysis aimed to evaluate the prophylactic effect of lidocaine lubrications against POST, cough, and hoarseness in adult patients after surgery. METHODS: Randomized-controlled trials from PubMed, Embase, the Cochrane Library, and the ClinicalTrials.gov registry that were published from inception until 26 March 2018 were included that compared the effectiveness of lidocaine lubricants with that of controls in preventing the incidence of overall POST and moderate to severe POST (POSTMS) at the first and 24th postoperative hour (POST-1h, POST-24h, POSTMS-1h, and POSTMS-24h). Postoperative cough and hoarseness at the 24th postoperative hour were also studied. Bias assessment and subgroup, sensitivity, and trial sequential analyses were also performed. RESULTS: Fourteen randomized-controlled trials (n = 2146) were selected. The incidences of POST-1h and POST-24h were 41.1 % and 22.6 % for the lidocaine group, and 41.9% and 23.5% for the control group, respectively. No effect was found on any of the outcome measurements. The overall risk ratios were 1.11 (95% confidence interval [CI], 0.82 to 1.51) and 1.06 (95% CI, 0.37 to 3.02) for the incidence of POST-1h and POSTMS-1h, respectively; 0.99 (95% CI, 0.83 to 1.17) and 0.49 (95% CI, 0.16 to 1.50) for POST-24h and POSTMS-24h, respectively; and, 1.09 (95% CI, 0.71 to 1.66) and 0.91 (95% CI, 0.66 to1.24) for postoperative cough (PC)-24h and postoperative hoarseness (PH)-24h, respectively. CONCLUSION: Lidocaine lubricants applied on the tips of endotracheal tube are not effective against the morbidities of POST, PC, and PH. TRIAL REGISTRATION: PROSPERO (CRD42017073259); registered 26 October, 2017.

RéSUMé: OBJECTIF: Les maux de gorge postopératoires sont une morbidité relativement fréquente. Les lubrifiants topiques à base de lidocaïne ont été proposés pour prévenir les maux de gorge postopératoires, mais leur efficacité demeure incertaine. Cette méta-analyse avait pour objectif d'évaluer l'effet prophylactique des lubrifications de lidocaïne contre les maux de gorge postopératoires, la toux et l'enrouement de la voix chez les patients adultes après une chirurgie. MéTHODE: Nous avons inclus les études randomisées contrôlées publiées sur PubMed, Embase, la Cochrane Library et le registre de ClinicalTrials.gov entre leur création et le 26 mars 2018 qui comparaient l'efficacité des lubrifiants à base de lidocaïne par rapport à l'absence de traitement pour prévenir l'incidence des maux de gorge postopératoires globaux et des maux de gorge postopératoires modérés à graves à la première et à la vingt-quatrième heure postopératoire (POST-1h, POST-24h, POSTMS-1h, et POSTMS-24h). La toux et l'enrouement à 24 heures postopératoires ont également été étudiés. Des analyses d'évaluation du biais et de sous-groupe, de sensibilité et des analyses séquentielles d'essais ont également été réalisées. RéSULTATS: Quatorze études randomisées contrôlées (n = 2146) ont été sélectionnées. Les incidences de POST-1h et de POST-24h étaient de 41,1 % et 22,6 % dans le groupe lidocaïne, et de 41,9 % et 23,5 % dans le groupe témoin, respectivement. Aucun effet n'a été observé pour aucun de nos critères d'évaluation. Les rapports de risque globaux étaient de 1,11 (intervalle de confiance [IC] 95 %, 0,82 à 1,51) et de 1,06 (IC 95 %, 0,37 à 3,02) pour l'incidence de POST-1h et de POSTMS-1h, respectivement; de 0,99 (IC 95 %, 0,83 à 1,17) et de 0,49 (IC 95 %, 0,16 à 1,50) pour les POST-24h et POSTMS-24h, respectivement; et de 1,09 (IC 95 %, 0,71 à 1,66) et 0,91 (IC 95 %, 0,66 à 1,24) pour la toux postopératoire (PC)-24h et l'enrouement postopératoire (PH)-24h, respectivement. CONCLUSION: Les lubrifiants à base de lidocaïne appliqués sur l'extrémité distale du tube endotrachéal ne sont pas efficaces pour prévenir les morbidités de maux de gorge, de toux et d'enrouement postopératoires. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42017073259); enregistrée le 26 octobre 2017.

Immobilization of Acidithiobacillus ferrooxidans on cotton gauze for biological oxidation of ferrous ions in a batch bioreactor.

The ability of Acidithiobacillus ferrooxidans to oxidize ferrous iron has been extensively studied in bioleaching to recover metal resources. Although immobilization of A. ferrooxidans is of great importance to achieve high bioleaching performance in practical application, the reported approaches of immobilization of A. ferrooxidans are still limited. This paper is attempting to develop a novel method to immobilize A. ferrooxidans by a less-costly effective carrier from zeolite, activated carbon, and cotton gauze. The results showed that cotton gauze was the most suitable carrier to immobilize A. ferrooxidans cells in comparison with zeolite and activated carbon. Acidithiobacillus ferrooxidans immobilized on the cotton gauze by gravity dehydration could achieve an average ferrous iron oxidation rate of 0.73 g/(L·h). Furthermore, the ferrous iron oxidation ratio attained in the bioreactor under batch operation was maintained above 97.83%. All results indicated that cotton gauze could be an efficient carrier for immobilizing A. ferrooxidans cells for the biooxidation of ferrous ions.

Ketamine Increases Permeability and Alters Epithelial Phenotype of Renal Distal Tubular Cells via a GSK-3ß-Dependent Mechanism.

Ketamine, a dissociative anesthetic, is misused and abused worldwide as an illegal recreational drug. In addition to its neuropathic toxicity, ketamine abuse has numerous effects, including renal failure; however, the underlying mechanism is poorly understood. The process called epithelial phenotypic changes (EPCs) causes the loss of cell-cell adhesion and cell polarity in renal diseases, as well as the acquisition of migratory and invasive properties. Madin-Darby canine kidney cells, an in vitro cell model, were subjected to experimental manipulation to investigate whether ketamine could promote EPCs. Our data showed that ketamine dramatically decreased transepithelial electrical resistance and increased paracellular permeability and junction disruption, which were coupled to decreased levels of apical junctional proteins (ZO-1, occludin, and E-cadherin). Consistent with the downregulation of epithelial markers, the mesenchymal markers N-cadherin, fibronectin, and vimentin were markedly upregulated following ketamine stimulation. Of the E-cadherin repressor complexes tested, the mRNA levels of Snail, Slug, Twist, and ZEB1 were elevated. Moreover, ketamine significantly enhanced migration and invasion. Ketamine-mediated changes were at least partly caused by the inhibition of GSK-3ß activity through Ser-9 phosphorylation by the PI3K/Akt pathway. Inhibiting PI3K/Akt with LY294002 reactivated GSK-3ß and suppressed ketamine-enhanced permeability, EPCs, and motility. These findings were recapitulated by the inactivation of GSK-3ß using the inhibitor 3F8. Taken together, these results provide evidence that ketamine induces renal distal tubular EPCs through the downregulation of several junction proteins, the upregulation of mesenchymal markers, the activation of Akt, and the inactivation of GSK-3ß.

The effects of narrow-band middle infrared radiation in enhancing the antitumor activity of paclitaxel.

Paclitaxel is used as an adjuvant to enhance the effectiveness of ionization radiation therapy; however, high-energy radiation often damages the healthy cells surrounding cancer cells. Low-energy, middle-infrared radiation (MIR) has been shown to prevent tissue damage, and recent studies have begun combining MIR with paclitaxel. However, the cytotoxic effects of this treatment combination remain unclear, and the mechanism underlying its effects on HeLa cells has yet to be elucidated. This study investigated the effectiveness of treating HeLa human cervical cancer cells with a combination of paclitaxel for 48 h in conjunction with narrow-band MIR from 3.0 to 5.0 µm. This combined treatment significantly inhibited the growth of HeLa cells. Specifically, results from Annexin V-FITC/PI apoptosis detection and cell mitochondrial membrane potential analyses revealed an increase in apoptotic cell death and a collapse of mitochondrial membrane potential. One possible mechanism underlying cellular apoptosis is an increase in oxidative stress. These preliminary findings provide evidence to support the combination of narrow-band MIR with paclitaxel as an alternative approach in the treatment of human cervical cancer.

Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells.

Breast cancer is one of the leading cancer-related causes of death worldwide. Treatment of triple-negative breast cancer (TNBC) is complex and challenging, especially when metastasis has developed. In this study, we applied infrared radiation as an alternative approach for the treatment of TNBC. We used middle infrared (MIR) with a wavelength range of 3-5 µm to irradiate breast cancer cells. MIR significantly inhibited cell proliferation in several breast cancer cells but did not affect the growth of normal breast epithelial cells. We performed iTRAQ-coupled LC-MS/MS analysis to investigate the MIR-triggered molecular mechanisms in breast cancer cells. A total of 1749 proteins were identified, quantified, and subjected to functional enrichment analysis. From the constructed functionally enriched network, we confirmed that MIR caused G2/M cell cycle arrest, remodeled the microtubule network to an astral pole arrangement, altered the actin filament formation and focal adhesion molecule localization, and reduced cell migration activity and invasion ability. Our results reveal the coordinative effects of MIR-regulated physiological responses in concentrated networks, demonstrating the potential implementation of infrared radiation in breast cancer therapy.

Simultaneous heavy metals removal and municipal sewage sludge dewaterability improvement in bioleaching processes by various inoculums.

The heavy metals content and dewaterability of municipal sewage sludge (MSS) are important parameters affecting its subsequent disposal and land application. Six kinds of inoculums were prepared to examine the characteristics of heavy metals removal and MSS dewaterability improvement in bioleaching processes. The results showed that Cu, Zn and Cd bioleaching efficiencies (12 days) were 81-91, 87-93 and 81-89%, respectively, which were significantly higher than those of Fe-S control (P < 0.05) and blank control (P < 0.01). The bioleaching boosted by the prepared inoculums could also significantly enhance MSS dewaterability (P < 0.01). The centrifugal dehydration efficiency of MSS rose from 73.00 to 90.00% at day 12. Microscopic observations and energy dispersive spectrum analysis demonstrated that the dewaterability improvement might be attributed to the changes of sludge structure from flocculent to obvious granular and the formation of secondary minerals mainly consisting of iron, oxygen and sulfur elements. The results above demonstrated that bacterial consortium enriched from acid mine drainage (AMD) was suitable to boost sludge bioleaching for heavy metals removal and dewaterability improvement. It also suggested that the synergy of sulfur/ferrous-oxidizing bacteria (SFOB) enriched from AMD and the cooperation of exogenous and indigenous SFOB significantly promoted bioleaching efficiencies.

Site-specific thrombus formation: advancements in photothrombosis-on-a-chip technology.

Thrombosis, characterized by blood clot formation within vessels, poses a significant medical challenge. Despite extensive research, the development of effective thrombosis therapies is hindered by substantial costs, lengthy development times, and high failure rates in medication commercialization. Conventional pre-clinical models often oversimplify cardiovascular disease, leading to a disparity between experimental results and human physiological responses. In response, we have engineered a photothrombosis-on-a-chip system. This microfluidic model integrates human endothelium, human whole blood, and blood flow dynamics and employs the photothrombotic method. It enables precise, site-specific thrombus induction through controlled laser irradiation, effectively mimicking both normal and thrombotic physiological conditions on a single chip. Additionally, the system allows for the fine-tuning of thrombus occlusion levels via laser parameter adjustments, offering a flexible thrombus model with varying degrees of obstruction. Additionally, the formation and progression of thrombosis noted on the chip closely resemble the thrombotic conditions observed in mice in previous studies. In the experiments, we perfused recalcified whole blood with Rose Bengal into an endothelialized microchannel and initiated photothrombosis using green laser irradiation. Various imaging methods verified the model's ability to precisely control thrombus formation and occlusion levels. The effectiveness of clinical drugs, including heparin and rt-PA, was assessed, confirming the chip's potential in drug screening applications. In summary, the photothrombosis-on-a-chip system significantly advances human thrombosis modeling. Its precise control over thrombus formation, flexibility in the thrombus severity levels, and capability to simulate dual physiological states on a single platform make it an invaluable tool for targeted drug testing, furthering the development of organ-on-a-chip drug screening techniques.

[Olecranon osteotomy approach for Dubberley type â ¢ coronal fractures of the distal humerus].

OBJECTIVE: To retrospectively analyze the clinical efficacy of olecranon osteotomy approach in the treatment of Dubberley type Ⅲ coronal fractures of the distal humerus and summarize the treatment experience. METHODS: From January 2016 to June 2020, 17 patients (5 males and 12 females) with Dubberley type Ⅲ coronal fractures of the distal humerus were treated by olecranon osteotomy approach. The age ranged from 37 to78 years old with an average of (58.5±12.9) years old. According to Dubberley classification, there were 5 cases of type Ⅲ A and 12 cases of type Ⅲ B. The curative effect was evaluated using the Borberg-Morrey elbow function score. The flexion, extension and rotation range of motion of the elbow joint, complications and postoperative imaging evaluation were recorded. RESULTS: All the 17 patients got bony union. The follow-up time ranged from 12 to 33 months with an average of (15.6±5.6) months. There was 1 case of ischemic necrosis of capitulum humeri, 2 cases of traumatic arthritis and 1 case of heterotopic ossification, 1 case of malunion of fracture. The range of motion was (114.80±19.50) °. The Broberg-Morrey score was 85.3±8.2, excellent in 5 cases, good in 9 cases, fair in 3 cases and poor in 0 case. CONCLUSION: Through olecranon osteotomy approach, the articular surface of distal humerus could be fully exposed, and the operation is convenient. Anatomical reduction and rigid fixation of the articular surface of distal humerus are the key factors for the succesful outcome.

PDMS/magnetic lignin sponge for oil/water separation.

Recyclable, non-toxic, and degradable biological substrates contribute significantly to super-wetting surfaces. In this work, we prepared magnetic micro-nano super-hydrophobic surfaces through a robust solution with magnetic modified lignin particles as the supporting structure. A novel PDMS (polydimethylsiloxane)/magnetic lignin particle (lignin@Fe3O4)/PDA sponge composite was fabricated. Through dopamine (DA) self-polymerization, covalent deposition of magnetic lignin (ML), and PDMS silane modification, the magnetic super-hydrophobic polyurethane sponge composite (Sponge-P) was synthesized so that the Fe3O4 nanoscale microspheres wrapped with microscale lignin magnetic particles adhered to the sponge surface tighter and were barely dislodged. The as-prepared Sponge-P displayed excellent flexibility and a water contact angle of up to 152.2°. The super-hydrophobic sponge prepared with the proposed method was acid-base stable (pH = 2-12), self-cleaning, and suitable for high-salinity seawater. The magnetic super-hydrophobic sponge has good oil-water separation ability and can absorb 43 times its own weight of oil. In the meantime, due to the introduction of magnetic materials into lignin, we not only constructed micro-nanostructures to improve the surface super-hydrophobicity, but also made Sponge-P have the function of magnetic recovery, which has a unique advantage in treating oily wastewater.