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In the electrochemical CO 2 reduction reaction (CO 2 RR), Cu alloy electrocatalysts can control the CO 2 RR selectivity by modulating the intermediate binding energy. Here, we report the thermodynamic-based Cu-Sn bimetallic phase control in heterogeneous catalysts for selective CO 2 conversion. Starting from the thermodynamic understanding about Cu-Sn bimetallic compounds, we established the specific processing window for Cu-Sn bimetallic phase control. To modulate the Cu-Sn bimetallic phases, we controlled the oxygen partial pressure (pO 2 ) during the calcination of electrospun Cu and Sn ions-incorporated nanofibers (NFs). This resulted in the formation of CuO-SnO 2 NFs (full oxidation), Cu-SnO 2 NFs (selective reduction), Cu 3 Sn/CNFs, Cu 41 Sn 11 /CNFs, and Cu 6 Sn 5 /CNFs (full reduction). In the CO 2 RR, CuO-SnO 2 NFs exhibited formate (HCOO - ) production and Cu-SnO 2 NFs showed carbon monoxide (CO) production with the faradaic efficiency (FE) of 65.3% at -0.99 V ( vs. RHE) and 59.1% at -0.89 V ( vs. RHE) respectively. Cu-rich Cu 41 Sn 11 /CNFs and Cu 3 Sn/CNFs enhanced the methane (CH 4 ) production with the FE of 39.1% at -1.36 V ( vs. RHE) and 34.7% at -1.50 V ( vs. RHE). However, Sn-rich Cu 6 Sn 5 /CNFs produced HCOO - with the FE of 58.6% at -2.31 V ( vs. RHE). This study suggests the methodology for bimetallic catalyst design and steering the CO 2 RR pathway by controlling the active sites of Cu-Sn alloys.

Purpose: This study investigated the interfractional volume changes of large (≥ 10 cm 3 ) brain metastases (BMs) during fractionated gamma knife radiosurgery (FGKRS) to assess its predictive value for tumor control outcomes., Methods: The patients who underwent FGKRS for large BMs between January 2017 and December 2022 in our center were reviewed. The interfractional volume change was defined as the disparity in tumor volume (TV) measured between the magnetic resonance images acquired on the first treatment day and those obtained after 2 or 3 fractions during the course of FGKRS., Results: A total of 73 lesions in 70 patients with various primary pathologies were included. Over a median follow-up period of 11 months (range 1-77), the tumor control rate was 63%. Initial TV (cm 3 ) was associated with progression free survival (PFS) and overall survival (OS) in both univariate and multivariate analyses (p = 0.01). Interfractional TV changes revealed an increase in 13 (17.8%) lesions, no change in 14 (19.2%) lesions, and a decrease in 46 (63.0%) lesions, with a mean volume reduction of 5% ± 0.12. Three cut-offs (5%, 10% and 15% volume decrement) were established and patients were divided into two groups based on each reference point. However, there were no significant differences in PFS and OS between the two groups, irrespective of the chosen cut-off value used., Conclusion: Interfractional volume changes of large BMs were not found to be associated with tumor control outcomes. Neither significant interfractional volume reduction nor significant volume increase necessarily predicts the tumor control, making early close monitoring essential after FGKRS., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: The endoscopic transorbital approach (ETOA) has emerged as a promising minimally invasive technique for resection of lesions in the mediobasal temporal region (MTR) due to its potential to preserve the integrity of the optic radiation (OR). This study evaluated the safety and efficacy of ETOA using an OR-sparing surgical strategy for mediobasal temporal lesions., Methods: A retrospective review was conducted of the medical records of 15 patients (7 females and 8 males) who underwent ETOA for lesions in the MTR between November 2017 and November 2022. Preoperative diffusion tensor imaging (DTI) tractography of the OR was utilized in all cases for surgical planning to visualize the spatial relations between the OR and the target mediobasal temporal lesion., Results: The median age of the treated patients was 43 years (range 22-76 years), with a median follow-up duration of 12 months (range 6-35 months). Eleven lesions (73.3%) involved only the anterior segment of the MTR, while 4 lesions (26.7%) affected both the anterior and middle segments. Gross-total resection was achieved in 13 patients (86.7%) and subtotal resection in 2 (13.3%). The final pathologies included low-grade glioma (n = 5), cavernous malformation (n = 3), glioblastoma multiforme (n = 2), multinodular and vacuolating neuronal tumor (n = 1), pleomorphic xanthoastrocytoma (n = 1), anaplastic oligodendroglioma (n = 1), adenoid cystic carcinoma (n = 1), and metastatic renal cell carcinoma (n = 1). Postoperative neuro-ophthalmological examinations revealed that all patients maintained their previous visual function. Follow-up DTI tractography further confirmed the preservation of the preoperative ORs in the treated patients. No postoperative CSF leaks, infections, or cosmetic problems occurred in this series., Conclusions: The combined use of ETOA and OR tractography appears to be a feasible approach for resecting lesions involving the MTR, especially in the anterior segment. In the authors' experience, this surgical strategy enables maximal safe resection while minimizing the risk of postoperative visual dysfunction. Further studies with larger sample sizes are warranted to validate these findings and assess long-term outcomes.

T-cell activation is a multistep process requiring T-cell receptor engagement by peptide-major histocompatibility complexes (Signal 1) coupled with CD28-mediated costimulation (Signal 2). Tumors typically lack expression of CD28 ligands, so tumor-specific Signal 1 (e.g., neoepitope presentation) without costimulation may be ineffective or even induce T-cell anergy. We designed the bispecific antibody XmAb808 to co-engage the tumor-associated antigen B7-H3 with CD28 to promote T-cell costimulation within the tumor microenvironment. XmAb808 costimulation was measured by its ability to activate and expand T cells and enhance T cell-mediated cancer cell killing in cocultures of human peripheral blood mononuclear cells (PBMCs) and cancer cells, and in mice engrafted with human PBMCs and tumor xenografts. XmAb808 avidly bound cancer cells and stimulated interleukin (IL)2 and interferon (IFN)γ secretion from T cells cocultured with cancer cells engineered to deliver Signal 1 to T cells via a surface-expressed anti-CD3 antibody. XmAb808 enhanced expression of the anti-apoptotic factor Bcl-xL and CD25, promoting survival and IL2-dependent expansion of T cells coupled with increased T cell-mediated cytotoxicity in vitro. XmAb808 combined with a EpCAM×CD3 bispecific antibody to enhance target cell killing through IL2-dependent expansion of CD25+ T cells. This combination also suppressed pancreatic tumor xenograft growth in mice. Further, XmAb808 combined with an anti-PD1 antibody to suppress breast tumor xenograft growth in mice. XmAb808 as monotherapy and in combination with an anti-PD1 antibody is currently in clinical development in patients with advanced solid tumors. Our results suggest that XmAb808 may also combine with tumor antigen-targeted anti-CD3 (Signal 1) T-cell engagers.

Surface-enhanced Raman scattering (SERS) exploits localized surface plasmon resonances in metallic nanostructures to significantly amplify Raman signals and perform ultrasensitive analyses. A critical factor for SERS-based analysis systems is the formation of numerous electromagnetic hot spots within the nanostructures, which represent regions with highly concentrated fields emerging from excited localized surface plasmons. These intense hotspot fields can amplify the Raman signal by several orders of magnitude, facilitating analyte detection at extremely low concentrations and highly sensitive molecular identification at the single-nanoparticle level. In this study, mesoscopic star-shaped gold particles (gold mesostars) were synthesized using a three-step seed-mediated growth approach coupled with the addition of silver ions. Our study confirms the successful synthesis of gold mesostars with numerous sharp tips via the multi-directional growth effect induced by the underpotential deposition of silver adatoms (AgUPD) onto the gold surfaces. The AgUPD process affects the nanocrystal growth kinetics of the noble metal and its morphological evolution, thereby leading to intricate nanostructures with high-index facets and protruding tips or branches. Mesoscopic gold particles with a distinctive star-like morphology featuring multiple sharp projections from the central core were synthesized by exploiting this phenomenon. Sharp tips of the gold mesostars facilitate intense localized electromagnetic fields, which result in strong SERS enhancements at the single-particle level. Electromagnetic fields can be further enhanced by interparticle hot spots in addition to the intraparticle local field enhancements when arranged in multilayered arrays on substrates, rendering these arrays as highly efficient SERS-active substrates with improved sensitivity. Evaluation using Raman-tagged analytes revealed a higher SERS signal intensity compared to that of individual mesostars because of interparticle hot spots enhancements. These substrates enabled analyte detection at a concentration of 10 - 9 M, demonstrating their remarkable sensitivity for trace analysis applications., (© 2024. The Author(s).)

Fabricating nanoscale metal carbides is a great challenge due to them having higher Gibbs free energy of formation (Δ G° ) values than other metal compounds; additionally, these carbides have harsh calcination conditions, in which metal oxidation is preferred in the atmosphere. Herein, we report oxocarbon-mediated calcination for the predictive synthesis of nanoscale metal carbides. The thermochemical oxocarbon equilibrium of CO-CO 2 reactions was utilized to control the selective redox reactions in multiatomic systems of Mo-C-O, contributing to the phase-forming and structuring of Mo compounds. By harnessing the thermodynamically predicted processing window, we controlled a wide range of Mo phases (MoO 2 , α-MoC 1- x , and β-Mo 2 C) and nanostructures (nanoparticle, spike, stain, and core/shell) in the Mo compounds/C nanofibers. By inducing simultaneous reactions of C-O (selective C combustion) and Mo-C (Mo carbide formation) in the nanofibers, Mo diffusion was controlled in C nanofibers, acting as a template for the nucleation and growth of Mo carbides and resulting in precise control of the phases and structures of Mo compounds. The formation mechanism of nanostructured Mo carbides was elucidated according to the CO fractions of CO-CO 2 calcination. Moreover, tungsten (W) and niobium (Nb) carbides/C nanofibers have been successfully synthesized by CO-CO 2 calcination. We constructed the thermodynamic map for the predictive synthesis of transition metal carbides to provide universal guideline via thermochemical oxocarbon equilibrium. We revealed that our thermochemical oxocarbon-mediated gas-solid reaction enabled the structure and phase control of nanoscale transition metal compounds to optimize the material-property relationship accordingly.

Various electrocatalysts are extensively examined for their ability to selectively produce desired products by electrochemical CO 2 reduction reaction (CO 2 RR). However, an efficient CO 2 RR electrocatalyst doesn't ensure an effective co-catalyst on the semiconductor surface for photoelectrochemical CO 2 RR. Herein, Bi 2 S 3 nanorods are synthesized and electrochemically reduced to Bi nanoplates that adhere to the substrates for application in the electrochemical and photoelectrochemical CO 2 RR. Compared with commercial-Bi, the Bi 2 S 3 -derived Bi (S-Bi) nanoplates on carbon paper exhibit superior electrocatalytic activity and selectivity for formate (HCOO - ) in the electrochemical CO 2 RR, achieving a Faradaic efficiency exceeding 93%, with minimal H 2 production over a wide potential range. This highly selective S-Bi catalyst is being employed on the Si photocathode to investigate the behavior of electrocatalysts during photoelectrochemical CO 2 RR. The strong adhesion of the S-Bi nanoplates to the Si nanowire substrate and their unique catalytic properties afford exceptional activity and selectivity for HCOO - under simulated solar irradiation. The selectivity observed in electrochemical CO 2 RR using the S-Bi catalyst correlates with that seen in the photoelectrochemical CO 2 RR system. Combined pulsed potential methods and theoretical analyses reveal stabilization of the OCHO* intermediate on the S-Bi catalyst under specific conditions, which is critical for developing efficient catalysts for CO 2 -to-HCOO - conversion., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

(1) Background: The aim of this study was to investigate the circadian rhythms of tongue features according to the effects of physiological phases over a 24 h period. (2) Methods: Fifteen healthy participants aged 20 to 69 years were recruited. The participants did not have current chronic diseases or past diseases and had to meet the inclusion and exclusion criteria. The participants stayed at the Gil Hospital for a duration of 2 nights and 3 days. On the first day, at 18:00, they consumed their allocated portions of food and water and then completed a questionnaire. At approximately 21:00, their tongue images were acquired using a computerized tongue image acquisition system, following which they slept for 8 h, commencing at 23:00. Measurements were taken from 07:00 through 21:00 on the second day, and the final acquisition was taken at 07:00 on the following morning, resulting in a total of eight images. The circadian rhythm was authenticated and quantified utilizing the single cosinor analysis, a technique for periodic regression analysis for fitting a 24 h cosine curve. (3) Results: Cosinor analysis revealed that all tongue features were significantly related to circadian rhythm. (4) Conclusions: The results of this study may be important for considering the time of day at which the tongue is observed and tongue status is evaluated.

Although alternative splicing (AS) is a major mechanism that adds diversity to gene expression patterns, its precise role in generating variability in ribosomal proteins, known as ribosomal heterogeneity, remains unclear. The ribosomal protein S24 (RPS24) gene, encoding a ribosomal component, undergoes AS; however, in-depth studies have been challenging because of three microexons between exons 4 and 6. We conducted a detailed analysis of RPS24 AS isoforms using a direct approach to investigate the splicing junctions related to these microexons, focusing on four AS isoforms. Each of these isoforms showed tissue specificity and relative differences in expression among cancer types. Significant differences in the proportions of these RPS24 AS isoforms between cancerous and normal tissues across diverse cancer types were also observed. Our study highlighted a significant correlation between the expression levels of a specific RPS24 AS isoform and the epithelial-mesenchymal transition process in lung and breast cancers. Our research contributes to a better understanding of the intricate regulatory mechanisms governing AS of ribosomal protein genes and highlights the biological implications of RPS24 AS isoforms in tissue development and tumorigenesis., (© 2024. The Author(s).)

Patients with IDH-wild-type glioblastomas have a poor five-year survival rate along with limited treatment efficacy due to immune cell (glioma-associated microglia and macrophages) infiltration promoting tumour growth and resistance. To enhance therapeutic options, our study investigated the unique RNA-RNA-binding protein complex LOC-DHX15. This complex plays a crucial role in driving immune cell infiltration and tumour growth by establishing a feedback loop between cancer and immune cells, intensifying cancer aggressiveness. Targeting this complex with blood-brain barrier-permeable small molecules improved treatment efficacy, disrupting cell communication and impeding cancer cell survival and stem-like properties. Focusing on RNA-RNA-binding protein interactions emerges as a promising approach not only for glioblastomas without the IDH mutation but also for potential applications beyond cancer, offering new avenues for developing therapies that address intricate cellular relationships in the body., (© 2024. The Author(s).)

Purpose: Severe lymphopenia (SLP) has emerged as a significant prognostic factor in glioblastoma. Intensity-modulated radiation therapy (IMRT)-based radiation therapy (RT) is suggested to minimize the risk of SLP. This study aimed to evaluate SLP incidence based on multi-institutional database in patients with GBM treated with IMRT and develop a predictive nomogram., Patients and Methods: This retrospective study reviewed data from 348 patients treated with IMRT-based concurrent chemoradiation therapy (CCRT) at two major hospitals from 2016 to 2021. After multivariate regression analysis, a nomogram was developed and internally validated to predict SLP risk., Results: During treatment course, 21.0% of patients developed SLP and SLP was associated with poor overall survival outcomes in patients with GBM. A newly developed nomogram, incorporating gender, pre-CCRT absolute lymphocyte count, and brain mean dose, demonstrated fair predictive accuracy (AUC 0.723)., Conclusions: This study provides the first nomogram for predicting SLP in patients with GBM treated with IMRT-based CCRT, with acceptable predictive accuracy. The findings underscore the need for dose optimization and radiation planning to minimize SLP risk. Further external validation is crucial for adopting this nomogram in clinical practice., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that is commonly used for the treatment of type 2 diabetes mellitus (T2DM). CKD-370 was newly developed as a cocrystal formulation of empagliflozin with co-former L-proline, which has been confirmed to be bioequivalent in South Korea. This study aimed to quantify the differences in the absorption phase and pharmacokinetic (PK) parameters of two empagliflozin formulations in healthy subjects by using population PK analysis. The plasma concentration data of empagliflozin were obtained from two randomized, open-label, crossover, phase 1 clinical studies in healthy Korean subjects after a single-dose administration. A population PK model was constructed by using a nonlinear mixed-effects (NLME) approach (Monolix Suite 2021R1). Interindividual variability (IIV) and interoccasion variability (IOV) were investigated. The final model was evaluated by goodness-of-fit (GOF) diagnostic plots, visual predictive checks (VPCs), prediction errors, and bootstrapping. The PK of empagliflozin was adequately described with a two-compartment combined transit compartment model with first-order absorption and elimination. Log-transformed body weight significantly influenced systemic clearance (CL) and the volume of distribution in the peripheral compartment (V2) of empagliflozin. GOF plots, VPCs, prediction errors, and the bootstrapping of the final model suggested that the proposed model was adequate and robust, with good precision at different dose strengths. The cocrystal form did not affect the absorption phase of the drug, and the PK parameters were not affected by the different treatments.

Backgruound: Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity., Methods: A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared., Results: Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered., Conclusion: The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy of the illuminated chopper-assisted cataract surgery in terms of shortening the surgical time in eyes with miosis after femtosecond laser pretreatment., Methods: As retrospective study, three hundred thirty-six eyes of 336 consecutive patients who underwent the femtosecond laser and illuminated chopper-assisted cataract surgery were included. Cases with pupil less than 6 mm after femtosecond laser pretreatment were included in the miosis group. Pupil diameter, surgical time, and improved efficacy (100/surgical time×pupil size) were compared between eyes with and without miosis., Results: Of 336 eyes, 20 were included in the miosis group (6.0%). Pupil diameter was smaller in eyes with miosis than in those without miosis (5.23 ± 0.38 mm vs 7.35 ± 0.64 mm, p < 0.001); however, surgical time was not different (6.86 ± 0.73 min vs 6.60 ± 1.27 min, p = 0.071) between the two groups. Mechanical pupil dilations were not needed in any cases. As a result, improved efficacy was calculated to be higher in patients with miosis (2.83 vs 2.14, p < 0.001)., Conclusion: In terms of surgical time and improved efficacy, using the illuminated chopper simplified cataract surgery involving miosis after femtosecond laser pretreatment. The use of an illuminated chopper is expected to be a good solution for femtosecond laser-assisted cataract surgeries., Competing Interests: Declaration of conflicting interestsConflict of Interest Review Board of Gachon University thoroughly investigated the data collection and patient selection.

The electrochemical carbon dioxide (CO 2 ) reduction reaction (CO 2 RR) is considered a promising technology for converting atmospheric CO 2 into value-added compounds by utilizing renewable energy. The CO 2 RR has developed in various ways over the past few decades, including product selectivity, current density, and catalytic stability. However, its commercialization is still unsuitable in terms of economic feasibility. One of the major challenges in its commercialization is the low single-pass conversion efficiency (SPCE) of CO 2 , which is primarily caused by the formation of carbonate (CO 3 2- ) in neutral and alkaline electrolytes. Notably, the majority of CO 2 RRs take place in such media, necessitating significant energy input for CO 2 regeneration. Therefore, performing the CO 2 RR under conditions that minimize CO 3 2- formation to suppress reactant and electrolyte ion loss is regarded an optimal strategy for practical applications. Here, we introduce the recent progress and perspectives in the electrochemical CO 2 RR in acidic electrolytes, which receives great attention because of the inhibition of CO 3 2- formation. This includes the categories of nanoscale catalytic design, microscale microenvironmental effects, and bulk scale applications in electrolyzers for zero carbon loss reactions. Additionally, we offer insights into the issue of limited catalytic durability, a notable drawback under acidic conditions and propose guidelines for further development of the acidic CO 2 RR.

Purpose: This study aimed to evaluate the long-term cumulative survival rate (CSR) of dental implants with micro-threads in the neck over a 10-year follow-up period and to examine the factors influencing the survival rate of dental implants., Methods: This retrospective study was based on radiographic and dental records. In total, 151 patients received 490 Oneplant ® dental implants with an implant neck micro-thread design during 2006-2010 in the Department of Periodontology of Seoul National University Dental Hospital. Implant survival was evaluated using Kaplan-Meier analysis. Cox proportional hazard regression analysis was used to identify the factors influencing implant failure., Results: Ten out of 490 implants (2.04%) failed due to fixture fracture. The CSR of the implants was 97.9%, and no significant difference was observed in the CSR between external- and internal-implant types (98.2% and 97.6%, respectively, P =0.670). In Cox regression analysis, 2-stage surgery significantly increased the risk of implant failure (hazard ratio: 4.769, P =0.039). There were no significant differences in influencing factors, including sex, age, implant diameter, length, fixture type, location, surgical procedure, bone grafting, and restoration type., Conclusions: Within the limitations of this retrospective study, the micro-thread design of the implant neck was found to be favorable for implant survival, with stable clinical outcomes., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Academy of Periodontology.)

High-rate production of multicarbon chemicals via the electrochemical CO 2 reduction can be achieved by efficient CO 2 mass transport. A key challenge for C-C coupling in high-current-density CO 2 reduction is how to promote *CO formation and dimerization. Here, we report molecularly enhanced CO 2 -to-*CO conversion and *CO dimerization for high-rate ethylene production. Nanoconfinement of ascorbic acid by graphene quantum dots enables immobilization and redox reversibility of ascorbic acid in heterogeneous electrocatalysts. Cu nanowire with ascorbic acid nanoconfined by graphene quantum dots (cAA-CuNW) demonstrates high-rate ethylene production with a Faradaic efficiency of 60.7% and a partial current density of 539 mA/cm 2 , a 2.9-fold improvement over that of pristine CuNW. Furthermore, under low CO 2 ratio of 33%, cAA-CuNW still exhibits efficient ethylene production with a Faradaic efficiency of 41.8%. We find that cAA-CuNW increases *CO coverage and optimizes the *CO binding mode ensemble between atop and bridge for efficient C-C coupling. A mechanistic study reveals that ascorbic acid can facilitate *CO formation and dimerization by favorable electron and proton transfer with strong hydrogen bonding., (© 2024. The Author(s).)

For high-grade glioma (HGG) patients with old age or poor performance status, hypofractionated radiotherapy (hypoRT) in 10-15 fractions is recommended. Also, limited data exist on the impact of salvage treatment after progression in frail patients. We retrospectively analyzed the outcomes of dose-escalated hypoRT in 40 frail HGG patients who were treated with hypoRT between 2013 and 2021. With a median biologically effective dose of 71.7 Gy, a total dose of 56 Gy in 20 fractions was the most frequently used regimen (53.7%). The median age and Karnofsky Performance Status of patients were 74 years and 70, respectively. Most patients ( n = 31, 77.5%) were diagnosed with glioblastoma, IDH-wildtype, CNS WHO grade 4. Only 10 (25.0%) patients underwent surgical resection, and 28 (70.0%) patients received concurrent temozolomide during hypoRT. With a median follow-up of 9.7 months, the median overall survival (OS) was 12.2 months. Of the 30 (75.0%) patients with disease progression, only 12 patients received salvage treatment. The OS after progression differed significantly depending on salvage treatment (median OS, 9.6 vs. 4.6 months, p = 0.032). Dose-escalated hypoRT in 20 fractions produced survival outcomes outperforming historical data for frail patients.

Purpose: To introduce a new surgical technique with a beveled vitrectomy probe for the removal of peripheral vitreous cortex remnants (VCR) in primary rhegmatogenous retinal detachment (RRD)., Methods: This study was a retrospective case series. From September 2019 to June 2022, 54 patients with complete or partial posterior vitreous detachment who underwent vitrectomy for primary RRD by a single surgeon were enrolled., Results: After staining the vitreous with triamcinolone acetonide, the presence of VCR was assessed in detail. If VCR were present, the macular VCR were removed using surgical forceps, and then, a free flap of peripheral VCR was used as a handle for removing peripheral VCR using the beveled vitrectomy probe. Of the total patients, the presence of VCR was confirmed in 16 patients (29.6%). There were no intraoperative or postoperative complications, except for retinal redetachment caused by proliferative vitreoretinopathy, that occurred in only one eye (1.9%)., Conclusion: Using a beveled vitrectomy probe was a practical solution for removing VCR during RRD vitrectomy because additional instruments were not needed and risk of iatrogenic retinal damage was low.

Purpose: This study aimed to investigate changes in cytokine levels after intravitreal bevacizumab injection in patients with chronic central serous chorioretinopathy (CSC)., Methods: In a prospective interventional trial, 12 eyes from 12 patients with chronic CSC and six eyes from six patients who underwent cataract surgery were included as controls. Patients diagnosed as with CSC received a single intravitreal injection of bevacizumab (1.25 mg/0.05 mL). Aqueous humor samples were collected from the patients and controls. Best-corrected visual acuity and foveal thickness were evaluated, and aqueous samples were obtained before and 4 weeks after injection. The aqueous concentrations of interleukin (IL)-6, IL-8, interferon-induced protein (IP)-10, monocyte chemotactic protein (MCP)-1, platelet-derived growth factor (PDGF)-AA, and vascular endothelial growth factor (VEGF) were measured using a multiplex bead assay., Results: After injection, the foveal thickness decreased significantly from 328.08 μm (range, 210-477 μm) to 283.91 μm (range, 168-356 μm; p = 0.048), but the best-corrected visual acuity was not significantly different (p = 0.066). The aqueous levels of IL-8 increased significantly from 3.3 pg/mL (range, 1.5-8.3 pg/mL) to 4.7 pg/mL (range, 2.2-11.6 pg/mL) at 4 weeks after the injection (p = 0.046). The aqueous levels of VEGF decreased significantly from 31.4 pg/mL (range, 17.0-53.3 pg/mL) to 15.2 pg/mL (range, 7.7-21.5 pg/mL; p < 0.01). No significant changes in levels of IL-6 (p = 0.455), IP-10 (p = 0.055), MCP-1 (p = 0.076), and PDGF-AA (p = 0.339) were noted 4 weeks after injection., Conclusions: In this study we found intravitreal bevacizumab injection decreased VEGF and increased IL-8 in the eyes of patients with chronic CSC. This study suggests the possibility that the pathogenesis of CSC may be related to abnormal circulation of the choroidal blood vessels through VEGF and IL-8 cytokine level changes.

Articular cartilage lacks natural healing abilities and necessitates surgical treatments for injuries. While microfracture (MF) is a primary surgical approach, it often results in the formation of unstable fibrocartilage. Delivering hyaline cartilage directly to defects poses challenges due to the limited availability of autologous cartilage and difficulties associated with allogeneic cartilage delivery. We developed a decellularized allogeneic cartilage paste (DACP) using human costal cartilage mixed with a crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC) carrier. The decellularized allogeneic cartilage preserved the extracellular matrix and the nanostructure of native hyaline cartilage. The crosslinked HA-CMC carrier provided shape retention and moldability. In vitro studies confirmed that DACP did not cause cytotoxicity and promoted migration, proliferation, and chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. After 6 months of implantation in rabbit knee osteochondral defects, DACP combined with MF outperformed MF alone, demonstrating improved gait performance, defect filling, morphology, extracellular matrix deposition, and biomechanical properties similar to native cartilage. Thus, DACP offers a safe and effective method for articular cartilage repair, representing a promising augmentation to MF. STATEMENT OF SIGNIFICANCE: Directly delivering hyaline cartilage to repair articular cartilage defects is an ideal treatment. However, current allogeneic cartilage products face delivery challenges. In this study, we developed a decellularized allogeneic cartilage paste (DACP) by mixing human costal cartilage with crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC). DACP preserves extracellular matrix components and nanostructures similar to native cartilage, with HA-CMC ensuring shape retention and moldability. Our study demonstrates improved cartilage repair by combining DACP with microfracture, compared to microfracture alone, in rabbit knee defects over 6 months. This is the first report showing better articular cartilage repair using decellularized allogeneic cartilage with microfracture, without the need for exogenous cells or bioactive substances., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Glioblastoma (GBM) is the most lethal brain cancer with a dismal prognosis. Stem-like GBM cells (GSCs) are a major driver of GBM propagation and recurrence; thus, understanding the molecular mechanisms that promote GSCs may lead to effective therapeutic approaches. Through in vitro clonogenic growth-based assays, we determined mitogenic activities of the ligand molecules that are implicated in neural development. We have identified that semaphorin 3A (Sema3A), originally known as an axon guidance molecule in the CNS, promotes clonogenic growth of GBM cells but not normal neural progenitor cells (NPCs). Mechanistically, Sema3A binds to its receptor neuropilin-1 (NRP1) and facilitates an interaction between NRP1 and TGF-β receptor 1 (TGF-βR1), which in turn leads to activation of canonical TGF-β signaling in both GSCs and NPCs. TGF-β signaling enhances self-renewal and survival of GBM tumors through induction of key stem cell factors, but it evokes cytostatic responses in NPCs. Blockage of the Sema3A/NRP1 axis via shRNA-mediated knockdown of Sema3A or NRP1 impeded clonogenic growth and TGF-β pathway activity in GSCs and inhibited tumor growth in vivo. Taken together, these findings suggest that the Sema3A/NRP1/TGF-βR1 signaling axis is a critical regulator of GSC propagation and a potential therapeutic target for GBM.

Background: The standard of care for glioblastoma multiforme (GBM) is maximal surgical resection followed by conventional fractionated concurrent chemoradiotherapy (CCRT) with a total dose of 60 Gy. However, there is currently no consensus on the optimal boost technique for CCRT in GBM., Methods: We conducted a retrospective review of 398 patients treated with CCRT between 2016 and 2021, using data from two institutional databases. Patients were divided into two groups: those receiving sequential boost (SEB, N = 119) and those receiving simultaneous integrated boost (SIB, N = 279). The primary endpoint was overall survival (OS). To minimize differences between the SIB and SEB groups, we conducted propensity score matching (PSM) analysis., Results: The median follow-up period was 18.6 months. Before PSM, SEB showed better OS compared to SIB (2-year, 55.6% vs. 44.5%, p = 0.014). However, after PSM, there was no significant difference between two groups (2-year, 55.6% vs. 51.5%, p = 0.300). The boost sequence was not associated with inferior OS before and after PSM (all p-values > 0.05). Additionally, the rates of symptomatic pseudo-progression were similar between the two groups (odds ratio: 1.75, p = 0.055)., Conclusions: This study found no significant difference in OS between SEB and SIB for GBM patients treated with CCRT. Further research is needed to validate these findings and to determine the optimal boost techniques for this patient population., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification., Methods: In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005-2018) and an external validation site in South Korea (44 patients, 2013-2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines., Results: The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64-11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients., Conclusions: The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer., Competing Interests: M.P. has received honoraria for lectures, consultation, or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen, Adastra, Gan & Lee Pharmaceuticals, but declares no nonfinancial competing interests. G.L. holds shares in the company contextflow and has received honoraria for lectures from the following for-profit companies: Boehringer Ingelheim, Novartis, and declares no nonfinancial competing interests. All other authors declare no financial or nonfinancial conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Clonal evolution drives cancer progression and therapeutic resistance. Recent studies have revealed divergent longitudinal trajectories in gliomas, but early molecular features steering posttreatment cancer evolution remain unclear. Here, we collected sequencing and clinical data of initial-recurrent tumor pairs from 544 adult diffuse gliomas and performed multivariate analysis to identify early molecular predictors of tumor evolution in three diffuse glioma subtypes. We found that CDKN2A deletion at initial diagnosis preceded tumor necrosis and microvascular proliferation that occur at later stages of IDH-mutant glioma. Ki67 expression at diagnosis was positively correlated with acquiring hypermutation at recurrence in the IDH-wild-type glioma. In all glioma subtypes, MYC gain or MYC- target activation at diagnosis was associated with treatment-induced hypermutation at recurrence. To predict glioma evolution, we constructed CELLO2 (Cancer EvoLution for LOngitudinal data version 2), a machine learning model integrating features at diagnosis to forecast hypermutation and progression after treatment. CELLO2 successfully stratified patients into subgroups with distinct prognoses and identified a high-risk patient group featured by MYC gain with worse post-progression survival, from the low-grade IDH-mutant-noncodel subtype. We then performed chronic temozolomide-induction experiments in glioma cell lines and isogenic patient-derived gliomaspheres and demonstrated that MYC drives temozolomide resistance by promoting hypermutation. Mechanistically, we demonstrated that, by binding to open chromatin and transcriptionally active genomic regions, c-MYC increases the vulnerability of key mismatch repair genes to treatment-induced mutagenesis, thus triggering hypermutation. This study reveals early predictors of cancer evolution under therapy and provides a resource for precision oncology targeting cancer dynamics in diffuse gliomas.

Purpose: To compare patient experiences and cooperation and the clinical outcomes illuminated chopper vs conventional chopper during cataract surgery., Setting: 4 tertiary institutions in Korea., Design: Prospective, randomized, paired-eye, controlled pilot study., Methods: 152 eyes of 76 patients who underwent bilateral cataract surgeries were enrolled in this study. The surgical method was randomly assigned to each patient's eye (1 eye using the illuminated chopper with a light source and the other using the conventional chopper under the microscope light). Patient suffering scores (the degree of strong light perception, glare, inability to fixate, anxiety, discomfort, and fear) from 0 to 10 (10 being the most severe level); cooperation score from 0 to 3 (3 being the best cooperation); operating time; and corneal endothelial cell density (ECD) preoperatively and postoperatively were compared between the 2 groups., Results: The mean patient suffering score of all 6 parameters in the iChopper group was significantly smaller than those in the control group (all P < .05). The mean patient cooperation score of the iChopper group (2.3 ± 0.8) was significantly greater than that of the control (1.6 ± 0.9; P < .001). There was no significant difference in the mean operating time and corneal ECD at each visit between the groups, albeit the mean corneal ECD was significantly decreased from baseline to 1 month after cataract surgery in both groups., Conclusions: Phacoemulsification using the illuminated chopper provides less glare and anxiety and better cooperation during cataract surgery without increasing the operating time and damaging corneal endothelium compared with the conventional chopper., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of ASCRS and ESCRS.)

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Bevacizumab is a feasible option for treating cerebral radiation necrosis (RN). We investigated the clinical outcome of RN after treatment with bevacizumab and factors related to the initial response and the sustained effect., Methods: Clinical data of 45 patients treated for symptomatic RN between September 2019 and February 2021 were retrospectively collected. Bevacizumab (7.5 mg/kg) was administered at 3-week intervals with a maximum four-cycle schedule. Changes in the lesions magnetic resonance image (MRI) scans were examined for the response evaluation. The subgroup analysis was performed based on the initial response and the long-term maintenance of the effect., Results: Of the 45 patients, 36 patients (80.0%) showed an initial response, and eight patients (17.8%) showed delayed worsening of the corresponding lesion. The non-responders showed a significantly higher incidence of diffusion restriction on MRI than the responders (100.0% vs. 25.0%, p<0.001). The delayed worsening group showed a significantly higher proportion of glioma pathology than the maintenance group (87.5% vs. 28.6%, p=0.005). Cumulative survival rates with sustained effect were significantly higher in the groups with non-glioma pathology (p=0.019) and the absence of diffusion restriction (p<0.001). Pathology of glioma and diffusion restriction in MRI were the independent risk factors for non-response or delayed worsening after initial response., Conclusion: The initial response of RN to bevacizumab was favorable, with improvement in four-fifths of the patients. However, a certain proportion of patients showed non-responsiveness or delayed exacerbations. Bevacizumab may be more effective in treating RN in patients with non-glioma pathology and without diffusion restriction in the MRI.

Bacterial cellulose (BC) is a natural polysaccharide polymer hydrogel produced sustainably by the strain Gluconacetobacter hansenii under static conditions. Due to their biocompatibility, easy functionalization, and necessary physicochemical and mechanical properties, BC nanocomposites are attracting interest in therapeutic applications. In this study, we functionalized BC hydrogel with polydopamine (PDA) without toxic crosslinkers and used it in skin tissue engineering. The BC nanofibers in the hydrogel had a thickness of 77.8 ± 20.3 nm, and they could be used to produce hydrophilic, adhesive, and cytocompatible composite biomaterials for skin tissue engineering applications using PDA. Characterization techniques, namely Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), and Raman spectroscopy, were performed to investigate the formation of polydopamine on the BC nanofibers. The XRD peaks for BC occur at 2θ = 14.65°, 16.69°, and 22.39°, which correspond to the planes of (100), (010), and (110) of cellulose type Iα. Raman spectroscopy confirmed the formation of PDA, as indicated by the presence of bands corresponding to the vibration of aromatic rings and aliphatic C-C and C-O stretching at 1336 and 1567 cm -1 , respectively. FTIR confirmed the presence of peaks corresponding to PDA and BC in the BC/PDA hydrogel scaffolds at 3673, 3348, 2900, and 1052 cm -1 , indicating the successful interaction of PDA with BC nanofibers, which was further corroborated by the SEM images. The tensile strength, swelling ratio, degradation, and surface wettability characteristics of the composite BC biomaterials were also investigated. The BC/PDA hydrogels with PDA-functionalized BC nanofibers demonstrated excellent tensile strength and water-wetting ability while maintaining the stability of the BC fibers. The enhanced cytocompatibility of the BC/PDA hydrogels was studied using the PrestoBlue assay. Culturing murine NIH/3T3 fibroblasts on BC/PDA hydrogels showed higher metabolic activity and enhanced proliferation. Additionally, it improved cell viability when using BC/PDA hydrogels. Thus, these BC/PDA composite biomaterials can be used as biocompatible natural alternatives to synthetic substitutes for skin tissue engineering and wound-dressing applications.

Radiation therapy (RT) provides therapeutic benefits for patients with glioblastoma (GBM), but inevitably induces poorly understood global changes in GBM and its microenvironment (TME) that promote radio-resistance and recurrence. Through a cell surface marker screen, we identified that CD142 (tissue factor or F3) is robustly induced in the senescence-associated β-galactosidase (SA-βGal)-positive GBM cells after irradiation. F3 promotes clonal expansion of irradiated SA-βGal + GBM cells and orchestrates oncogenic TME remodeling by activating both tumor-autonomous signaling and extrinsic coagulation pathways. Intratumoral F3 signaling induces a mesenchymal-like cell state transition and elevated chemokine secretion. Simultaneously, F3-mediated focal hypercoagulation states lead to activation of tumor-associated macrophages (TAMs) and extracellular matrix (ECM) remodeling. A newly developed F3-targeting agent potently inhibits the aforementioned oncogenic events and impedes tumor relapse in vivo. These findings support F3 as a critical regulator for therapeutic resistance and oncogenic senescence in GBM, opening potential therapeutic avenues., Competing Interests: Declaration of interests H-M.J. and J.L. are co-inventors on a filed patent application for the use of truncated F7 recombinant protein to treat cancer., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the therapeutic efficacy of GC1118, a novel anti-epidermal growth factor receptor (EGFR) monoclonal antibody, in recurrent glioblastoma (GBM) patients with EGFR amplification., Methods: This study was a multicenter, open-label, single-arm phase II trial. Recurrent GBM patients with EGFR amplification were eligible: EGFR amplification was determined using fluorescence in situ hybridization analysis when a sample had both the EGFR/CEP7 ratio of ≥2 and a tight cluster EGFR signal in ≥10% of recorded cells. GC1118 was administered intravenously at a dose of 4 mg/kg once weekly. The primary endpoint was the 6-month progression-free survival rate (PFS6). Next-generation sequencing was performed to investigate the molecular biomarkers related to the response to GC1118., Results: Between April 2018 and December 2020, 21 patients were enrolled in the study and received GC1118 treatment. Eighteen patients were eligible for efficacy analysis. The PFS6 was 5.6% (95% confidence interval, 0.3%-25.8%, Wilson method). The median progression-free survival was 1.7 months (range: 28 days-7.2 months) and median overall survival was 5.7 months (range: 2-22.0 months). GC1118 was well tolerated except skin toxicities. Skin rash was the most frequent adverse event and four patients experienced Grade 3 skin-related toxicity. Genomic analysis revealed that the immune-related signatures were upregulated in patients with tumor regression., Conclusion: This study did not meet the primary endpoint (PFS6); however, we found that immune signatures were significantly upregulated in the tumors with regression upon GC1118 therapy, which signifies the potential of immune-mediated antitumor efficacy of GC1118., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Heteroatom-doped transition metal-oxides of high oxygen evolution reaction (OER) activities interfaced with metals of low hydrogen adsorption energy barrier for efficient hydrogen evolution reaction (HER) when uniformly embedded in a conductive nitrogen-doped carbon (NC) matrix, can mitigate the low-conductivity and high-agglomeration of metal-nanoparticles in carbon matrix and enhances their bifunctional activities. Thus, a 3D mesoporous heterostructure of boron (B)-doped cobalt-oxide/cobalt-metal nanohybrids embedded in NC and grown on a Ni foam substrate (B-CoO/Co@NC/NF) is developed as a binder-free bifunctional electrocatalyst for alkaline water-splitting via a post-synthetic modification of the metal-organic framework and subsequent annealing in different Ar/H 2 gas ratios. B-CoO/Co@NC/NF prepared using 10% H 2 gas (B-CoO/Co@NC/NF [10% H 2 ]) shows the lowest HER overpotential (196 mV) and B-CoO/Co@NC/NF (Ar), developed in Ar, shows an OER overpotential of 307 mV at 10 mA cm -2 with excellent long-term durability for 100 h. The best anode and cathode electrocatalyst-based electrolyzer (B-CoO/Co@NC/NF (Ar)(+)//B-CoO/Co@NC/NF (10% H 2 )(-)) generates a current density of 10 mA cm -2 with only 1.62 V with long-term stability. Further, density functional theory investigations demonstrate the effect of B-doping on electronic structure and reaction mechanism of the electrocatalysts for optimal interaction with reaction intermediates for efficient alkaline water-splitting which corroborates the experimental results., (© 2023 Wiley-VCH GmbH.)

In this work, the tunneling resistivity between neighboring nanosheets in grapheme-polymer nanocomposites is expressed by a simple equation as a function of the characteristics of graphene and tunnels. This expression is obtained by connecting two advanced models for the conductivity of graphene-filled materials reflecting tunneling role and interphase area. The predictions of the applied models are linked to the tested data of several samples. The impressions of all factors on the tunneling resistivity are evaluated and interpreted using the suggested equation. The calculations of tunneling resistivity for the studied examples by the model and suggested equation demonstrate the same levels, which confirm the presented methodology. The results indicate that the tunneling resistivity decreases by super-conductive graphene, small tunneling width, numerous contacts among nanosheets and short tunneling length., (© 2023. The Author(s).)

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in treating solid tumors, there are still challenges that need to be addressed. To overcome these limitations, other immune cells, such as natural killer (NK) cells and macrophages (M), have been developed as attractive options for efficient cancer immunotherapy of solid tumors. CAR-NK cells exhibit substantial clinical improvements with "off-the-shelf" availability and low toxicity. CAR-M cells have promising therapeutic potential because macrophages can infiltrate the TME of solid tumors. Here, we review the recent advances and future perspectives associated with engineered immune cell-based cancer immunotherapies for solid tumors. We also summarize ongoing clinical trials investigating the safety and efficacy of engineered immune cells, such as CAR-T, CAR-NK, and CAR-M, for targeting solid tumors.

Purpose: Glioblastoma (GBM) has a poor prognosis after standard treatment. Recently, metformin has been shown to have an antitumor effect on glioma cells. We performed the first randomized prospective phase II clinical trial to investigate the clinical efficacy and safety of metformin in patients with recurrent or refractory GBM treated with low-dose temozolomide., Methods: Included patients were randomly assigned to a control group [placebo plus low-dose temozolomide (50 mg/m 2 , daily)] or an experimental group [metformin (1000 mg, 1500 mg, and 2000 mg per day during the 1st, 2nd, and 3rd week until disease progression, respectively) plus low-dose temozolomide]. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), disease control rate, overall response rate, health-related quality of life, and safety., Results: Among the 92 patients screened, 81 were randomly assigned to the control group (43 patients) or the experimental group (38 patients). Although the control group showed a longer median PFS, the difference between the two groups was not statistically significant (2.66 versus 2.3 months, p = 0.679). The median OS was 17.22 months (95% CI 12.19-21.68 months) in the experimental group and 7.69 months (95% CI 5.16-22.67 months) in the control group, showing no significant difference by the log-rank test (HR: 0.78; 95% CI 0.39-1.58; p = 0.473). The overall response rate and disease control rate were 9.3% and 46.5% in the control group and 5.3% and 47.4% in the experimental group, respectively., Conclusions: Although the metformin plus temozolomide regimen was well tolerated, it did not confer a clinical benefit in patients with recurrent or refractory GBM. Trial registration NCT03243851, registered August 4, 2017., (© 2023. The Author(s).)