3D epigenomics and 3D epigenopathies.

Mammalian genomes are intricately compacted to form sophisticated 3-dimensional structures within the tiny nucleus, so called 3D genome folding. Despite their shapes reminiscent of an entangled yarn, the rapid development of molecular and next-generation sequencing technologies (NGS) has revealed that mammalian genomes are highly organized in a hierarchical order that delicately affects transcription activities. An increasing amount of evidence suggests that 3D genome folding is implicated in diseases, giving us a clue on how to identify novel therapeutic approaches. In this review, we will study what 3D genome folding means in epigenetics, what types of 3D genome structures there are, how they are formed, and how the technologies have developed to explore them. We will also discuss the pathological implications of 3D genome folding. Finally, we will discuss how to leverage 3D genome folding and engineering for future studies. [BMB Reports 2024; 57(5): 216-231].

Water-Ion Interaction Determines the Mobility of Ions in Highly Concentrated Aqueous Electrolytes.

Solvation engineering plays a critical role in tailoring the performance of batteries, particularly through the use of highly concentrated electrolytes, which offer heterogeneous solvation structures of mobile ions with distinct electrochemical properties. In this study, we employed spectroscopic techniques and molecular dynamics simulations to investigate mixed-cation (Li+/K+) acetate aqueous electrolytes. Our research unravels the pivotal role of water in facilitating ion transport within a highly viscous medium. Notably, Li+ cations primarily form ion aggregates, predominantly interacting with acetate anions, while K+ cations emerge as the principal charge carriers, which is attributed to their strong interaction with water molecules. Intriguingly, even at a concentration as high as 40 m, a substantial amount of water molecules persistently engages in hydrogen bonding with one another, creating mobile regions rich in K+ ions. Our observations of a redshift of the OH stretching band of water suggest that the strength of the hydrogen bond alone cannot account for the expansion of the electrochemical stability window. These findings offer valuable insights into the cation transfer mechanism, shedding light on the contribution of water-bound cations to both the ion conductivity and the electrochemical stability window of aqueous electrolytes for rechargeable batteries. Our comprehensive molecular-level understanding of the interplay between cations and water provides a foundation for future advances in solvation engineering, leading to the development of high-performance batteries with improved energy storage and safety profiles.

Effects of hormone therapy on the clinical outcomes of endoscopic intervention in patients with endometriosis-related ureteral obstruction.

PURPOSE: We investigated whether endoscopic interventions, including laser endoureterotomy and balloon dilatation following hormone therapy, are a good choice to treat ureteral obstruction due to ureteral endometriosis instead of laparoscopic or open surgery. MATERIALS AND METHODS: Patients with ureteral obstruction due to endometriosis who underwent endoscopic intervention between 2004 and 2021 were reviewed. Patients with other causes of ureteral obstruction or previous ureteral surgery were excluded from the study. The primary endpoint was the 3-month success rate of endoscopic intervention with or without hormone therapy. Secondary endpoints were the success rate of endoscopic intervention between the hormone-treated and hormone-untreated groups at 6 months and the success rate according to the hormone therapy response of endometriosis at 3 and 6 months. RESULTS: Eighteen patients with 19 ureter units were evaluated in this study, including 12 patients receiving hormone therapy and six patients not receiving hormone therapy. Among patients receiving hormone therapy, one patient had bilateral ureteral obstruction. The success rate of endoscopic intervention was higher in patients who received hormone therapy than in those who did not receive hormone therapy three months after endoscopic intervention (76.9% vs. 0.0%, p=0.003). The same result was also found 6 months after endoscopic intervention (75.0% vs. 0.0%, p=0.005). In addition, the success rates were higher in the hormone-responsive group than in the non-responsive group (100.0% vs. 57.1%), although the difference was not statistically significant (p=0.122). CONCLUSIONS: Ureteral obstruction caused by endometriosis can be effectively treated by endoscopic intervention with hormone therapy in select patients.

Injectable rapidly dissolving needle-type gelatin implant capable of delivering high concentrations of H2O2 through intratumoral injection.

Intratumoral injections can reduce systemic absorption and deliver large amounts of drugs to the tumor, thereby reducing side effects and exhibiting high therapeutic efficacy. Therefore, a variety of drug delivery systems, such as hydrogels, fine particles, and nanoparticles, have been studied. Although the sustained-release drug delivery system can effectively reduce systemic absorption due to the slow release of the drug from the site of intratumoral injection, it lacks the ability to deliver high concentrations of drugs to the tumor. In particular, the larger the tumor size, the lower the efficacy of the treatment. To address this problem, this study focused on the tumor structure. Owing to the three-dimensional structure of the dense tumor microenvironment (TME) and abnormal blood vessels, drugs administered directly into the tumor act as if they were encapsulated in a hydrogel. To evaluate whether the three-dimensional structure of the tumor affects the intratumoral distribution and systemic absorption of drugs, needle-type starch implants (GOD-NS implants) and needle-type gelatin implants (GOD-NG implants) containing glucose oxidase (GOD), a protein that exhibits anti-cancer effects through hydrogen peroxide (H2O2) generation, were prepared. Both GOD-NS and GOD-NG implants can be easily injected into tumors. GOD-NS implants released GOD slowly, whereas GOD-NG implants released most of the GOD within 1 h. When a GOD-NG implant that rapidly released GOD was also injected, a high concentration of GOD was maintained in the tumor for a long time as it was trapped in the three-dimensional structure of the tumor. This study demonstrated that intratumoral injection of a rapidly drug-releasing gelatin needle may be a novel drug delivery system capable of long-term retention of high drug concentrations in tumors, as the three-dimensional structure of the tumor affects drug delivery.

Effects of Complete Bladder Cuff Removal on Oncological Outcomes Following Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

PURPOSE: This study aimed to evaluate the effects of bladder cuff method on oncological outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma. MATERIALS AND METHODS: The records of 1,095 patients treated with RNU performed at our hospital between 1994 and 2018 were retrospectively reviewed; 856 patients with no bladder tumor history were enrolled in the present study. The management of bladder cuff was divided into two categories: extravesical ligation (EL) or transvesical resection (TR). Survival was analyzed using the Kaplan-Meier method and Cox regression analyses were performed to determine which factors were associated with intravesical recurrence (IVR)-free survival (IVRFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The mean patient age was 64.8 years and the median follow-up was 37.7 months. Among the 865 patients, 477 (55.7%) underwent the TR and 379 (44.3%) the EL. Significantly higher IVRFS (p=0.001) and OS (p=0.013) were observed in the TR group. In multivariable analysis, IVR, CSS, and OS were independently associated with the EL. Among 379 patients treated with the EL, eight underwent remnant ureterectomy. Based on radical cystectomy-free survival, significant difference was not observed between the two groups. However, significantly higher IVRFS was observed in the TR group when the tumor was located in the renal pelvis. CONCLUSION: Intramural complete excision of the distal ureter during RNU should be the gold standard approach compared with EL for the management of distal ureter in terms of oncological outcomes.

Prognostic Impact of Bone Metastasis on Survival Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated by First Line Tyrosine Kinase Inhibitors: A Propensity-Score Matching Analysis.

Purpose: To investigate the effect of bone metastasis (BM) on survival outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line tyrosine kinase inhibitors (TKI) by performing propensity-score matching (PSM) analysis. Materials & Methods: We retrospectively reviewed 1,151 patients with mRCC who were treated with first-line TKI from December 2006 to September 2016. After excluding 135 patients, 1,016 patients with mRCC were finally analyzed. The primary and secondary end points were overall survival (OS) and progression-free survival (PFS), respectively. After 1:1 PSM analysis, survival outcomes were compared between patients with BM (n=237) and without BM (n=237). Multivariate Cox regression analysis was used to determine predictors of survival. Results: Among 1,016 total patients, 27.5% (n=279) had BM. Before PSM, patients with BM had worse OS outcomes than those without BM. Even after PSM, OS was significantly poorer in patients with BM compared to those without BM. Of note, the presence of BM was identified as an independent predictor of OS (HR=1.36), in addition to prior nephrectomy, sarcomatoid differentiation, and IMDC risk group. However, there were no differences in PFS according to the presence of BM after PSM. In the subgroup analysis, only intermediate IMDC risk group showed significant differences in OS according to the presence of BM. Conclusion: Based on PSM analysis, the presence of BM negatively affected OS outcomes in patients with mRCC treated with first-line TKI, particularly in the IMDC intermediate risk group.

Pneumovesicoscopic bladder tumor resection in a young boy whose urethra was too small to use a resectoscope.

OBJECTIVE: To describe our experience with pneumovesicoscopic bladder tumor resection in a young boy whose urethra was too small to use a resectoscope. METHODS: An 11-year-old boy presented with gross hematuria. The patient was found to have a 2 cm-sized bladder tumor on ultrasound. The patient's urethra was too small to use a pediatric resectoscope, making it impossible to perform a transurethral resection of the bladder tumor. Therefore, pneumovesicoscopic bladder tumor resection was performed. En-bloc resection was performed successfully using 3 mm laparoscopic instruments, and the tumor was safely retrieved within an endo-bag made with a surgical glove. RESULTS: On postoperative day 1, the Foley catheter was removed and the patient was discharged. The pathology report described bladder papillary urothelial carcinoma, grade II/III without lamina propria invasion. The patient underwent follow-up with ultrasonography and urine cytology every three to six months. There was no recurrence for 21 months after surgery. CONCLUSION: This video demonstrates a pneumovesicoscopic approach for the treatment of bladder tumor in a young patient whose urethra was too small to use a resectoscope. Pneumovesicoscopic bladder tumor resection is technically feasible and safe.

Border Trap Extraction with Capacitance- Equivalent Thickness to Reflect the Quantum Mechanical Effect on Atomic Layer Deposition High-k/In0.53Ga0.47As on 300-mm Si Substrate.

This study presents a model to calculate the border trap density (Nbt) of atomic layer deposition high-k onto In0.53Ga0.47As on a 300-mm (001) Si substrate. This model considers the quantum confinement effect and band nonparabolicity. Capacitance-equivalent thickness (CET) was used to reflect the distance of the charge centroid from the oxide-semiconductor interface. The border trap values based on CET were found to be approximately 65% lower than the extracted values based on physical thickness in the In0.53Ga0.47As material. In an investigation of two different post-metal annealing effects on border traps, the border trap was more effectively passivated by N2-based forming gas annealing (FGA) compared with rapid thermal annealing (RTA), whereas a lower interface state density was observed in RTA-annealed samples compared with FGA-annealed samples. Nbt extraction at different bias voltages demonstrated that the applied frequencies travel deep into the oxide and interact with more traps as more the Fermi level passes the conduction band, thus creating tunneling with the carriers.

Characterization of Al Incorporation into HfO2 Dielectric by Atomic Layer Deposition.

This study presents the characteristics of HfAlO films for a series of Al incorporation ratios into a HfO2 dielectric by atomic layer deposition on a Si substrate. A small amount of Al doping into the HfO2 film can stabilize the tetragonal phase of the HfO2, which helps to achieve a higher dielectric constant (k) and lower leakage current density, as well as a higher breakdown voltage than HfO2 film on its own. Moreover, assimilation of Al2O3 into HfO2 can reduce the hysteresis width and frequency dispersion. These are indications of border trap reduction, which was also verified by the border trap extraction mechanism. X-ray photoelectron spectroscopy (XPS) analysis also verified the HfAlO microstructural properties for various Al compositions. In addition, higher amounts of Al2O3 in HfAlO resulted in better interface and dielectric behavior through trap minimization, although the equivalent-oxide-thickness (EOT) values show the opposite trend.

Nanometric Water Channels in Water-in-Salt Lithium Ion Battery Electrolyte.

Lithium-ion batteries (LIBs) have been deployed in a wide range of energy-storage applications and helped to revolutionize technological development. Recently, a lithium ion battery that uses superconcentrated salt water as its electrolyte has been developed. However, the role of water in facilitating fast ion transport in such highly concentrated electrolyte solutions is not fully understood yet. Here, femtosecond IR spectroscopy and molecular dynamics simulations are used to show that bulk-like water coexists with interfacial water on ion aggregates. We found that dissolved ions form intricate three-dimensional ion-ion networks that are spontaneously intertwined with nanometric water hydrogen-bonding networks. Then, hydrated lithium ions move through bulk-like water channels acting like conducting wires for lithium ion transport. Our experimental and simulation results indicate that water structure-breaking chaotropic anion salts with a high propensity to form ion networks in aqueous solutions would be excellent candidates for water-based LIB electrolytes. We anticipate that the present work will provide guiding principles for developing aqueous LIB electrolytes.

Electronic Effect on the Molecular Motion of Aromatic Amides: Combined Studies Using VT-NMR and Quantum Calculations.

Rotational barrier energy studies to date have focused on the amide bond of aromatic compounds from a kinetic perspective using quantum calculations and nuclear magnetic resonance (NMR). These studies provide valuable information, not only regarding the basic conformational properties of amide bonds but also the molecular gear system, which has recently gained interest. Thus, we investigate the precise motion of the amide bonds of two aromatic compounds using an experimental rotational barrier energy estimation by NMR experiments and a theoretical evaluation of the density functional theory calculation. The theoretical potential energy surface scan method combined with the quadratic synchronous transit 3 method and consideration of additional functional group rotation with optimization and frequency calculations support the results of the variable temperature ¹H NMR, with deviations of less than 1 kcal/mol. This detailed experimental and theoretical research strongly supports molecular gear motion in the aromatic amide system, and the difference in kinetic energy indicates that the electronic effect from the aromatic structure has a key role in conformational movements at different temperatures. Our study provides an enhanced basis for future amide structural dynamics research.