Cutting-Edge HEK293T Protein-Integrated Lipid Nanostructures: Boosting Biocompatibility and Efficacy.

Recently, artificial exosomes have been developed to overcome the challenges of natural exosomes, such as production scalability and stability. In the production of artificial exosomes, the incorporation of membrane proteins into lipid nanostructures is emerging as a notable approach for enhancing biocompatibility and treatment efficacy. This study focuses on incorporating HEK293T cell-derived membrane proteins into liposomes to create membrane-protein-bound liposomes (MPLCs), with the goal of improving their effectiveness as anticancer therapeutics. MPLCs were generated by combining two key elements: lipid components that are identical to those in conventional liposomes (CLs) and membrane protein components uniquely derived from HEK293T cells. An extensive comparison of CLs and MPLCs was conducted across multiple in vitro and in vivo cancer models, employing advanced techniques such as cryo-TEM (tramsmission electron microscopy) imaging and FT-IR (fourier transform infrared spectroscopy). MPLCs displayed superior membrane fusion capabilities in cancer cell lines, with significantly higher cellular uptake. Additionally, MPLCs maintained their morphology and size better than CLs when exposed to FBS (fetal bovine serum), suggesting enhanced serum stability. In a xenograft mouse model using HeLa and ASPC cancer cells, intravenous administration of MPLCs MPLCs accumulated more in tumor tissues, highlighting their potential for targeted cancer therapy. Overall, these results indicate that MPLCs have superior tumor-targeting properties, possibly attributable to their membrane protein composition, offering promising prospects for enhancing drug delivery efficiency in cancer treatments. This research could offer new clinical application opportunities, as it uses MPLCs with membrane proteins from HEK293T cells, which are known for their efficient production and compatibility with GMP (good manufacturing practice) standards.

Organometal Halide Perovskite-Based Photoelectrochemical Module Systems for Scalable Unassisted Solar Water Splitting.

Despite achievements in the remarkable photoelectrochemical (PEC) performance of photoelectrodes based on organometal halide perovskites (OHPs), the scaling up of small-scale OHP-based PEC systems to large-scale systems remains a great challenge for their practical application in solar water splitting. Significant resistive losses and intrinsic defects are major obstacles to the scaling up of OHP-based PEC systems, leading to the PEC performance degradation of large-scale OHP photoelectrodes. Herein, a scalable design of the OHP-based PEC systems by modularization of the optimized OHP photoelectrodes exhibiting a high solar-to-hydrogen conversion efficiency of 10.4% is suggested. As a proof-of-concept, the OHP-based PEC module achieves an optimal PEC performance by avoiding major obstacles in the scaling up of the OHP photoelectrodes. The constructed OHP module is composed of a total of 16 OHP photoelectrodes, and a photocurrent of 11.52 mA is achieved under natural sunlight without external bias. The successful operation of unassisted solar water splitting using the OHP module without external bias can provide insights into the design of scalable OHP-based PEC systems for future practical application and commercialization.

Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma.

BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) play an immunosuppressive role in the tumor microenvironment (TME) of human cancers; however, their characteristics and role in hepatocellular carcinoma (HCC) remain to be elucidated. METHODS: Nine tumor and surrounding liver tissue samples from patients with HCC who underwent surgery were used to isolate patient-derived CAFs. Cell morphology was observed using an optical microscope after culture, and cell phenotypes were evaluated using flow cytometry and immunoblotting. Cytokines secreted by CAFs into culture medium were quantified using a multiplex cytokine assay. RESULTS: CAFs were abundant in the TME of HCC and were adjacent to immune cells. After culture, the CAFs and non-tumor fibroblasts exhibited spindle shapes. We observed a robust expression of alpha-smooth muscle actin and fibroblast activation protein in CAFs, whereas alpha-fetoprotein, epithelial cell adhesion molecule, platelet/endothelial cell adhesion molecule-1, and E-cadherin were not expressed in CAFs. Furthermore, CAFs showed high secretion of various cytokines, namely C-X-C motif chemokine ligand 12, interleukin (IL)-6, IL-8, and C-C motif chemokine ligand 2. CONCLUSIONS: CAFs are abundant in the TME of HCC and play a crucial role in tumor progression. These fibroblasts secrete cytokines that promote tumor growth and metastasis.

Photoelectrochemical Selective Oxidation of Glycerol to Glyceraldehyde with Bi-Based Metal-Organic-Framework-Decorated WO3 Photoanode.

The conversion of glycerol to high-value-added products via photoelectrochemical (PEC) oxidation has emerged as a promising approach for utilizing a sustainable and clean energy source with environmental and economic benefits. Moreover, the energy requirement for glycerol to produce hydrogen is lower than that for pure water splitting. In this study, we propose the use of WO3 nanostructures decorated with Bi-based metal-organic frameworks (Bi-MOFs) as the photoanode for glycerol oxidation with simultaneous hydrogen production. The WO3-based electrodes selectively converted glycerol to glyceraldehyde, a high-value-added product, with remarkable selectivity. The Bi-MOF-decorated WO3 nanorods enhanced the surface charge transfer and adsorption properties, thereby improving the photocurrent density and production rate (1.53 mA/cm2 and 257 mmol/m2·h at 0.8 VRHE). The photocurrent was maintained for 10 h, ensuring stable glycerol conversion. Furthermore, at 1.2 VRHE, the average production rate of glyceraldehyde reached 420 mmol/m2·h, with a selectivity of 93.6% between beneficial oxidized products over the photoelectrode. This study provides a practical approach for the conversion of glycerol to glyceraldehyde via the selective oxidation of WO3 nanostructures and demonstrates the potential of Bi-MOFs as a promising cocatalyst for PEC biomass valorization.

Preferential Expression of Programmed Death Ligand 1 Protein in Tumor-Associated Macrophages and Its Potential Role in Immunotherapy for Hepatocellular Carcinoma.

A predictive biomarker of immune checkpoint inhibitor (ICI)-based treatments in hepatocellular carcinoma (HCC) has not been clearly demonstrated. In this study, we focused on the infiltration and programmed death ligand 1 (PD-L1) expression of tumor-associated macrophages (TAMs) in the tumor microenvironment of HCC. Immunohistochemistry demonstrated that PD-L1 was preferentially expressed on CD68+ macrophages in the tumor microenvironment of HCC, suggestive of its expression in TAMs rather than in T cells or tumor cells (P < 0.05). A co-culture experiment using activated T cells and M2 macrophages confirmed a significant increase in T cell functionality after the pretreatment of M2 macrophages with anti-PD-L1. Syngeneic mouse model experiments demonstrated that TAMs expressed PD-L1 and tumors treated with anti-PD-L1 showed smaller diameters than those treated with IgG. In these mice, anti-PD-L1 treatment increased activation markers in intratumoral CD8+ T cells and reduced the size of the TAM population. Regarding nivolumab-treated patients, three of eight patients responded to the anti-PD-1 treatment. The percentage of Ki-67-positive CD4+ and CD8+ T cells was higher in responders than non-responders after nivolumab. Overall, PD-L1 expression on TAMs may be targeted by immune-based HCC treatment, and ICI treatment results in the reinvigoration of exhausted CD8+ T cells in HCC.

Direct In Situ Growth of Centimeter-Scale Multi-Heterojunction MoS2/WS2/WSe2 Thin-Film Catalyst for Photo-Electrochemical Hydrogen Evolution.

To date, the in situ fabrication of the large-scale van der Waals multi-heterojunction transition metal dichalcogenides (multi-TMDs) is significantly challenging using conventional deposition methods. In this study, vertically stacked centimeter-scale multi-TMD (MoS2/WS2/WSe2 and MoS2/WSe2) thin films are successfully fabricated via sequential pulsed laser deposition (PLD), which is an in situ growth process. The fabricated MoS2/WS2/WSe2 thin film on p-type silicon (p-Si) substrate is designed to form multistaggered gaps (type-II band structure) with p-Si, and this film exhibits excellent spatial and thickness uniformity, which is verified by Raman spectroscopy. Among various application fields, MoS2/WS2/WSe2 is applied to the thin-film catalyst of a p-Si photocathode, to effectively transfer the photogenerated electrons from p-Si to the electrolyte in the photo-electrochemical (PEC) hydrogen evolution. From a comparison between the PEC performances of the homostructure TMDs (homo-TMDs)/p-Si and multi-TMDs/p-Si, it is demonstrated that the multistaggered gap of multi-TMDs/p-Si improves the PEC performance significantly more than the homo-TMDs/p-Si and bare p-Si by effective charge transfer. The new in situ growth process for the fabrication of multi-TMD thin films offers a novel and innovative method for the application of multi-TMD thin films to various fields.

Effect of donor right hepatectomy on splenic volume and platelet count for living donor liver transplantation.

BACKGROUND: Donor hepatectomy for living donor liver transplantation accompanies physio-morphological changes of the liver and spleen. Therefore, the long-term consequences of these organs should be characterized to ensure donor's safety. METHODS: A total of 382 right liver harvests for liver transplantation were performed from October 2000 to February 2011. Clinical parameters across donor operations were compared, and the associations were investigated. RESULTS: The remaining liver grew continually, reaching 81.5 ± 11.2% of the entire liver until 6 months after donation. The spleen grew to 143.1 ± 28.8% of the pre-donation value within 1 week after surgery, and thereafter, its size decreased gradually to 130.6 ± 25.1% at 6 months. At 6 months post-donation, 48.1% (114/237) of donors showed an increase of ≥30% in splenic volume, and 15.9% (50/315) of donors exhibited a decrease of ≥30% in platelet count. However, patients with splenic enlargement and/or decrease in platelet count at 6 months post-donation were not different in liver function, liver regeneration, or overall complications. CONCLUSIONS: Although splenic enlargement and/or decrease in platelet count can persist for more than 6 months after donation in patient population after donor right hepatectomy, such a change did not impact donor's safety.

Surgical outcome of right liver donors in living donor liver transplantation: single-center experience with 500 cases.

BACKGROUND: With the increasing number of living donor liver transplantation (LDLT), concerns regarding morbidity and mortality of donors have become inevitable. Thus, the aim of the present study was to find ways to reduce the rate of morbidity and mortality of donors by analyzing our experience. METHODS: A retrospective clinicopathologic analysis was performed for 500 consecutive living donors who underwent donor right hepatectomy between May 1999 and February 2011. We chronologically divided those procedures into three periods: period A (n = 100), period B (n = 200), and period C (n = 200). Surgical outcomes according to each period were then compared. RESULTS: Over time, the following factors have decreased: the operative time, the amount of transfusions during surgery, hospital stay, and the incidence of biliary complications. No mortality developed. Even though the total complication rate was high (21.6 %, n = 108) including 10.6 % (n = 53) of biliary complications, the grade 3 complication rate was only 9.4 % (n = 47). In most patients with grade 3 complication, interventional therapies via radiologic or endoscopic approaches corrected these complications, and reoperation was required for ten patients (2 %). Whereas biliary complications were related with operation period (period B or C compared to period A; relative risk [RR] 2.10, P = 0.049, 95 % CI 1.01-4.39) and operative time (RR 1.01, P = 0.027, 95 % CI 1.00-1.02), postoperative hyperbilirubinemia (serum total bilirubin ≥ 5 mg/dL) was related with male gender (RR 2.68, P = 0.039, 95 % CI 1.05-6.85) and ≥ 25 % liver steatosis (RR 3.35, P = 0.053, 95 % CI 0.99-11.38). CONCLUSIONS: Optimization of donor selection as well as institutional experience is imperative to improve the surgical outcome. Even though donor hepatectomy was associated with relatively higher complication rate, most complications showed low-grade severity which could be corrected by interventional therapies.