Hypoxia Postconditioning Attenuates Hypoxia-Induced Inflammation and Endothelial Barrier Dysfunction.

INTRODUCTION: In recent years, a number of studies have demonstrated that hypoxia reoxygenation (HR) induced by ischemia postconditioning (IPC) reduces endothelial barrier dysfunction and inflammation in various models. When HR occurs, the P38 mitogen-activated protein kinase (P38 MAPK) breaks down the endothelial barrier. But no study has clearly clarified the effect of hypoxia postconditioning (HPC) on P38 MAPK in human dermal microvascular endothelial cells. Therefore, we investigated the function of HPC on P38 MAPK during HR in vitro. METHODS: Human dermal microvascular endothelial cells were cultured in a hypoxic incubator for 8 h. Then cells were reperfused for 12 h (reoxygenation) or postconditioned by 5 min of reoxygenation and 5 min of re-hypoxia 3 times followed by 11.5 h reoxygenation. SB203580 was used as an inhibitor of P38 MAPK. Cell counting kit-8 assay kits were employed to detect cell activity. The corresponding levels of IL-6, IL-8 and IL-1ß were examined via Enzyme-Linked ImmunoSorbent Assay. The endothelial barrier was evaluated using fluorescein isothiocyanate-dextran leakage assay. Western blot was used to detect claudin-5, phosphorylation of P38 MAPK (P-P38 MAPK) and P38 MAPK expression. Claudin-5 localization was studied by immunofluorescence. RESULTS: HR induced endothelial barrier hyperpermeability, elevated inflammation levels, and increased the P-P38 MAPK. But HPC reduced cell injury and maintained the integrity of the endothelial barrier while inhibiting P-P38 MAPK and increasing expression of claudin-5. HPC redistributed claudin-5 in a continuous and linear pattern on the cell membrane. CONCLUSIONS: HPC protects against HR induced downregulation and redistribution of claudin-5 by inhibiting P-P38 MAPK.

Fast-track surgery with three-port versus conventional perioperative management of bladder cancer associated laparoscopic radical cystectomy and Ileal conduit diversion: Chinese experience.

OBJECTIVE: This study seeks to explore the impact of fast track surgery (FTS) with three-port in patients treated with laparoscopic radical cystectomy and ileal conduit on postoperative recovery, hospital stay and the complications. METHODS: This retrospective study analyzed 230 patients with invasive bladder cancer who underwent laparoscopic radical cystectomy at the Second Hospital of Anhui Medical University between December 2011 to January 2023. 50 patients received conventional surgery (CS) and 180 patients received FTS with three-port. Patients were assessed for time to normal diet consumption, time to passing first flatus, number of postoperative recovery days and complications. Trends of serum C-reactive protein levels were monitored preoperatively and on postoperative days 1, 3 and 7. RESULTS: Patients who underwent FTS with three-port had a shorter duration to first flatus (P < 0.05). And number of postoperative hospital days and the length of hospital stay were notably shorter in contrast to the CS group (P < 0.05). Serum CRP levels on postoperative day 7 were markedly reduced in those of the FTS group compared to the CS group (P < 0.05). Those of the CS group experienced more frequent rates of complications compared to those of the FTS with three-port group (P < 0.05). CONCLUSION: Our findings demonstrate that the FTS with three-port program hastens postoperative recovery and reduces duration of hospital stay. It is safer and more effective than the CS program in the Chinese population undergoing laparoscopic radical cystectomy.

(111) Facet-oriented Cu2Mg Intermetallic Compound with Cu3-Mg Sites for CO2 Electroreduction to Ethanol with Industrial Current Density.

The efficient ethanol electrosynthesis from CO2 is challenging with low selectivity at high CO2 electrolysis rates, due to the competition with H2 and other reduction products. Copper-based bimetallic electrocatalysts are potential candidates for the CO2-to-ethanol conversion, but the secondary metal has mainly been focused on active components (such as Ag, Sn) for CO2 electroreduction, which also promote selectivity of ethylene or other reduction products rather than ethanol. Limited attention has been given to alkali-earth metals due to their inherently active chemical property. Herein, we rationally synthesized a (111) facet-oriented nano Cu2Mg (designated as Cu2Mg(111)) intermetallic compound with high-density ordered Cu3-Mg sites. The in situ Raman spectroscopy and density function theory calculations revealed that the Cu3 - δ $_{^{\rm{{\rm \delta} }} }$ --Mg- δ $_{^{\rm{{\rm \delta} }} }$ + active sites allowed to increase *CO surface coverage, decrease reaction energy for *CO-CO coupling, and stabilize *CHCHOH intermediates, thus promoting the ethanol formation pathway. The Cu2Mg(111) catalyst exhibited a high FEC2H5OH of 76.2±4.8 % at 600 mA⋅cm-2, and a peak value of |jC2H5OH| of 720±34 mA⋅cm-2, almost 4 times of that using conventional Cu2Mg with (311) facets, comparable to the best reported values for the CO2-to-ethanol electroreduction.

Modified vein clamping technique for renal cell carcinoma complicated with level I-II IVC thrombi: a study at a single centre.

OBJECTIVES: To share our initial experience with the modified vein clamping technique for the treatment of renal cell carcinoma complicated with level I-II IVC thrombi. METHODS: From March 2018 to April 2021, 11 patients with renal cell carcinoma (RCC) involving an IVC tumour thrombus were admitted to our hospital. They all underwent laparoscopic radical nephrectomy and IVC thrombectomy (LRN-IVCTE) using a modified vein clamping technique. RESULTS: All procedures were successfully completed without conversion to open surgery. The median operative time was 185.00 min (145.00-216.00 min); the median estimated blood loss was 200.00 ml (155.00-300.00 ml), and four patients received an intraoperative transfusion. In addition, the median IVC clamping time was 18.00 min (12.00-20.00 min); the median postoperative hospital stay was 6.00 days (4.00-7.00 days), while the median follow-up period was 28.00 months (4.00-34.00 months). CONCLUSIONS: The modified vein clamping technique for the treatment of renal cell carcinoma complicated with level I-II IVC thrombi may be a safe and technically feasible alternative technique.

Monitored wet-etch removal of individual dielectric layers from high-finesse Bragg mirrors.

It is prohibitively expensive to deposit customized dielectric coatings on individual optics. One solution is to batch-coat many optics with extra dielectric layers, then remove layers from individual optics as needed. Here we present a low-cost, single-step, monitored wet etch technique for reliably removing individual SiO2 and Ta2O5 dielectric layers, in this case from a high-reflectivity fiber mirror. By immersing in acid and monitoring off-band reflected light, we show it is straightforward to iteratively (or continuously) remove six bilayers. At each stage, we characterize the coating performance with a Fabry-Pérot cavity, observing the expected stepwise decrease in finesse from 92,000 ± 3,000 to 3, 950 ± 50, finding no evidence of added optical losses. The etch also removes the fiber's sidewall coating after a single bilayer, and, after six bilayers, confines the remaining coating to a 60-µm-diameter pedestal at the center of the fiber tip. Vapor etching above the solution produces a tapered "pool cue" cladding profile, reducing the fiber diameter (nominally 125 µm) to 95 µm at an angle of ∼0.3° near the tip. Finally, we note that the data generated by this technique provides a sensitive estimate of the layers' optical depths. This technique could be readily adapted to free-space optics and other coatings.

Early Unclamping Laparoscopic Partial Nephrectomy for Complex Renal Tumor: Data from a Chinese Cohort.

OBJECTIVE: To evaluate the efficacy and safety of early unclamping laparoscopic partial nephrectomy (LPN) for complex renal tumor relative to the standard artery clamping technique (SCT). METHODS: Sixty-one patients with complex renal tumor (RENAL score ≥7) underwent LPN at our institution from January 2013 to April 2017. LPN was performed via SCT in 32 patients and via the early unclamping technique (EUT) in 29 patients. Operation time, warm ischemia time (WIT), blood loss, bleeding requiring transfusion, tumor volume, excisional volume loss (EVL), complications, and renal function before and after operation of the affected kidney were compared between the groups. RESULTS: All surgeries were successful without conversion to open or nephrectomy. EUT reduced the WIT (p < 0.001) but did not increase the complication rate (p = 0.322). Although the tumor volume and EVL were larger in the EUT than in the SCT group (p = 0.011, p = 0.001), glomerular filtration rate (GFR) reduction in the affected kidney did not significantly differ between the groups (p = 0.120). CONCLUSION: Early unclamping LPN for complex renal tumor is safe and efficient. Additionally, the EUT could expand the application of LPN in complex renal tumors, and make this challenging surgery easier and safer.

Curcumin inhibits bladder cancer stem cells by suppressing Sonic Hedgehog pathway.

Cancer stem cells (CSCs) is responsible for the recurrence of human cancers. Thus, targeting CSCs is considered to be a valid way for human cancer treatment. Curcumin is a major component of phytochemicals that exerts potent anticancer activities. However, the effect of curcumin on bladder cancer stem cells (BCSCs) remains to be elucidated. In this study, we investigated the mechanism of curcumin suppressing bladder cancer stem cells. In this study, UM-UC-3 and EJ cells were cultured in serum-free medium (SFM) to form cell spheres that was characterized as BCSCs. Then cell spheres were separately treated with different concentrations of curcumin and purmorphamine. Cell cycle analysis were used to determine the percentage of cells in different phases. Western blot and quantitative real-time PCR analysis were used to detect the expression of relative molecules. Immunofluorescence staining analysis were also utilized to measure the protein level of CD44. We found that CSC markers, including CD44, CD133, ALDH1-A1, OCT-4 and Nanog, were obviously highly expressed in cell spheres. Moreover, we observed that curcumin reduced the cell spheres formation, decreased the expression of CSC markers, suppressed cell proliferation and induced cell apoptosis. We also found that curcumin inhibited the activation of Shh pathway, while the inhibitory effects of curcumin on BCSCs could be weakened by upregulation of Sonic Hedgehog (Shh) pathway. Altogether, these data suggested that curcumin inhibited the activities of BCSCs through suppressing Shh pathway, which might be an effective chemopreventive agent for bladder cancer intervention.

Characteristics of tunneling nanotube-like structures formed by human dermal microvascular pericytes in vitro.

Tunneling nanotubes (TNTs) represent an innovative way for cells to communicate with one another, as they act as long conduits between cells. However, their roles in human dermal microvascular pericytes (HDMPCs) interaction remain elusive in vitro. In this work, we identified and characterized the TNT-like structures that connected two or more pericytes in two-dimensional cultures and formed a functional network in the human dermis. Immunofluorescence assay indicated that the F-actin was an essential element to form inter-pericyte TNT-like structures, as it decreased in actin polymer inhibitor-cytochalasin B treated groups, and microtubules were present in almost half of the TNT-like structures. Most importantly, we only found the presence of mitochondrial in TNT-like structures containing α-tubulin, and the application of microtubule assembly inhibitor-Nocodazole significantly reduced the percentage of TNT-like structures that contain α-tubulin, resulting in a sudden decrease in the positive rate of cytochrome c oxidase subunit 4 isoform 1 (COX IV, a marker of mitochondria) in TNT-like structures. In summary, we described a novel intercellular communication-TNT-like structures-between HDMPCs in vitro, and this work allows us to properly understand the cellular mechanisms of spreading materials between HDMPCs, shedding light on the role of HDMPCs.

Tube Formation Capability and Chemotaxis of Skin Pericytes.

BACKGROUND: Pericytes (PCs), the critical components of vessels, are implicated in wound repair. This study aimed to explore the roles of PCs in wound healing and angiogenesis. METHODS: Skin PCs and human dermal microvascular endothelial cells (HDMECs) were isolated from patients' upper eyelid skin. Immunofluorescence staining was used to characterize the morphology of PCs. Tube formation and transwell chemotaxis assays were performed to explore PC's tube-forming capability and chemotaxis. Finally, we investigated the effects of PCs and endothelial cells on wound repair using skin wound of a rat model. RESULTS: Skin PCs exhibited a double-protrusion structure and characteristic antigen expression of neural/glial antigen 2 (NG2)+/platelet-derived growth factor receptor-ß (PDGFR-ß)+/alpha-smooth muscle actin (α-SMA)+/CD31-. Skin PCs could directly form lumen-like structures in a two dimensional (2D) culture environment, and mild hypoxia and starvation promoted the lumen-like structure formation. Furthermore, skin PCs quickly formed more stable lumen-like structures than HDMECs in matrigel, and they recruited HDMECs in a three dimensional (3D) culture environment. Transwell chemotaxis assay showed that PCs and HDMECs were chemotactic to each other. PCs could develop lumen-like structures in the skin wounds of rat models. The number of PCs mounted in wounded skin was compared to normal skin. The ratio of PCs to endothelial cells gradually increased after skin injury and reached its maximum on the 3rd day. CONCLUSIONS: Skin PCs have an excellent tube-forming capability and chemotaxis to endothelial cells. PCs might promote wound repair by recruiting endothelial cells.

Sulfite-Assisted Acetate Conversion from CO Electroreduction.

The efficient acetate conversion from CO electroreduction is challenging due to the poor selectivity at high reaction rate, which requires the competition with H2 and other C2+ (i. e., ethylene, ethanol, n-propanol) reduction products. Electrolyte engineering is one of the efficient strategies to regulate the reaction microenvironment. In this work, the adding of sulfite (SO3 2-) with high nucleophilicity in KOH electrolytes was demonstrated to enable improving the CO-to-acetate conversion via generating a S-O chemical bond between SO3 2- and oxygenated *C2 intermediates (i. e., *CO-CO, *CO-COH) compared with that in pure KOH system on both synthesized Cu(200)- and normal commercial Cu(111)-facets-exposed metallic Cu catalysts. As a result, the prepared Cu(200)-facets-exposed metallic Cu catalyst with surface ions modification showed an superior Faradaic efficiency of 63.6 % at -0.6 A ⋅ cm-2, and extraordinary absolute value of peak partial current density as high as 1.52 A ⋅ cm-2 with adding SO3 2- in KOH electrolytes, compared to the best reported values in both CO and CO2 electroreduction. Our work suggests an attractive strategy to introduce the oxyanion with high nucleophilicity in electrolytes to regulate the microenvironment for industrial-current-density electrosynthesis of acetate from CO electroreduction.