Modulating the Thermoresponsive Characteristics of PLGA-PEG-PLGA Hydrogels via Manipulation of PLGA Monomer Sequences.

Hydrogels are promising materials for biomedical applications, particularly in drug delivery and tissue engineering. This study highlights thermoresponsive hydrogels, specifically poly(lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA triblock copolymers, and introduces a feed rate-controlled polymerization (FRCP) method. By utilizing an organic catalyst and regulating the monomer feed rate, the sequence distribution of PLGA within the triblock copolymer is controlled. Various analyses, including 13C NMR and rheological measurements, were conducted to investigate the impact of sequence distribution. Results show that altering sequence distribution significantly influences the sol-gel transition, hydrophobicity-hydrophilicity balance, and drug release profile. Increased sequence uniformity lowers the glass transition temperature, raises the sol-gel transition temperature due to enhanced hydrophilicity, and promotes a more uniform drug (curcumin) distribution within the PLGA domain, resulting in a slower release rate. This study emphasizes the importance of PLGA sequence distribution in biomedical applications and the potential of FRCP to tailor thermoresponsive hydrogels for biomedical advancements.

Dynamical time scales of friction dynamics in active microrheology of a model glass.

Owing to the local/heterogeneous structures in supercooled liquids, after several decades of research, it is now clear that supercooled liquids are structurally different from their conventional liquid counterparts. Accordingly, an approach based on a local probe should provide a better understanding about the local mechanical properties as well as heterogeneous structures. Recently, the superiority of active microrheology over global rheology has been demonstrated [Yu et al., Sci. Adv., 2020, 6, 8766]. Here, we elaborate this new avenue of research and provide more evidence for such superiority. We report on the results of an extensive molecular dynamics simulation of active microrheology of a model glass. We identify several time scales in time series of friction, and detect a transition in dynamical behavior of friction. We discuss the possible relation to structural heterogeneities-a subject of considerable interest in glass physics.

Correction: Dynamical time scales of friction dynamics in active microrheology of a model glass.

Correction for 'Dynamical time scales of friction dynamics in active microrheology of a model glass' by A. Madanchi et al., Soft Matter, 2021, DOI: 10.1039/d0sm02039g.

Enhanced sampling of cylindrical microphase separation via a shell-averaged bond-orientational order parameter.

The formation of a hexagonal phase from disordered phase is one of the typical order-disorder transitions (ODTs) observed in asymmetric diblock copolymer systems. In order to drive this transition in a particle-based simulation, we introduce a shell-based bond-orientational order parameter that selectively responds to the mesoscopic order of the hexagonal cylinder phase. From metadynamics simulations in a bond-free particle model system, the characteristic pathway involved with the underlying free energy surface is deduced for the disordered-to-hexagonal transition. It is shown consecutively that the transition pathway and the metastable state are reproduced in dissipative particle dynamics simulations for the corresponding transition in a bulk asymmetric block copolymer melt system. These agreements suggest that efficient strategies for enhanced sampling with particle-based simulations of block copolymer systems can be devised using coarse-grained pictures of the mesoscopic order.

Combination of multiparametric magnetic resonance imaging and transrectal ultrasound-guided prostate biopsies is not enough for identifying patients eligible for hemiablative focal therapy for prostate cancer.

PURPOSE: To evaluate focal therapy (hemiablation) eligibility in men undergoing prostate biopsy and multiparametric magnetic resonance imaging (mpMRI) with reference to histopathology from radical prostatectomy (RP) specimens. METHODS: Subjects were selected among 810 men who underwent prostate biopsy, mpMRI, and RP from January 2016 to December 2017. Hemiablation eligibility criteria were biopsy-proven unilateral cancer, prostate-specific antigen ≤ 15 ng/ml, and Gleason score (GS) ≤ 3 + 4. Evidence of non-organ-confined disease or Prostate Imaging Reporting and Data System score ≥ 4 on the contralateral lobe on mpMRI was classified as ineligible for hemiablation. Of the 810, data for 185 who met the screening criteria were compared to final pathology findings. Significant cancer at RP was defined as any of the following: (1) GS 6 with tumor volume ≥ 0.5 ml; (2) GS ≥ 3 + 4; or (3) the presence of advanced stage (≥ pT3). RESULTS: Among the 185 candidates for hemiablation, 62 (33.5%) had unilateral cancer on final RP histopathology. Among the 123 bilateral cancers, 50 (27%) were organ confined and had GS ≤ 3 + 4 = 7 and bilateral multifocal tumor in which the index tumor was confined to one lobe and the secondary tumor in the contralateral lobe had tumor volume < 0.5 ml and GS ≤ 6. A total of 112 (60.5%) patients in this series were considered suitable for hemiablation. Significant cancer on biopsy and mpMRI-negative lobes were found in 72 (38.9%) of 185 lobes, including 1 (0.5%) with advanced stage. CONCLUSIONS: The combination of standard prostate biopsy and mpMRI did not accurately identify lobes that could be considered as non-treated regions.

Longitudinal recovery patterns of penile length and the underexplored benefit of long-term phosphodiesterase-5 inhibitor use after radical prostatectomy.

BACKGROUND: Penile length (PL) shortening is an underreported phenomenon following radical prostatectomy (RP) and risk factors are not fully explored. We aimed to describe longitudinal patterns of PL recovery and evaluate factors predicting complete return to baseline PL. METHODS: PL measurement was performed during a preoperative and postoperative follow-up visits at 7 days and 3, 6, 9, and 12 months. Patients who completely recovered (CR: N = 397) their preoperative stretched PL measured during at least one of their follow-up visits were compared to those with incomplete recovery (IR: N = 131). Recovery patterns were analyzed for both groups and were also compared in regards to demographics, nerve-sparing techniques, prostate size, cardiovascular risk profiles, and phosphodiesterase-5 inhibitor (PDE5i) uses. Logistic regression analyses were performed using age and other relevant clinicopathologic variables to predict PL recovery. RESULTS: 60.2% of the total study population regained their preoperative PL at 12 months. Average percent (length) differences from baseline were - 1.70% (- 0.25 cm) and - 16.42% (- 2.35 cm) in the CR and the IR groups, respectively (p < 0.001). Multivariate logistic regression demonstrated that younger age (OR 0.962; 95%CI 0.931-0.994; p = 0.019), high preoperative erectile function (EF) (OR 1.028; 95%CI 1.001-1.056; p = 0.046), and consistent PDE5i use (OR 1.998; 95%CI 1.166-3.425; p = 0.012) were independent predictors of CR. At 12-month follow up, PL difference for consistent PDE5iusers was statistically different from those who did not use PDE5i consistently (- 3.25%vs. -6.64%; P = 0.001). CONCLUSION: Age, preoperative EF, and consistent use of PDE5i were associated with complete recovery of baseline PL after RP. The therapeutic effect of PDE5i was most pronounced at 12-month visit, suggesting an added benefit with long-term use.

Assemblies of Colloidal CdSe Tetrapod Nanocrystals with Lengthy Arms for Flexible Thin-Film Transistors.

Herein, we report unique features of the assemblies of tetrapod-shaped colloidal nanocrystals (TpNCs) with lengthy arms applicable to flexible thin-film transistors. Due to the extended nature of tetrapod geometry, films made of the TpNC assemblies require reduced numbers of inter-NC hopping for the transport of charge carriers along a given channel length; thus, enhanced conductivity can be achieved compared to those made of typical spherical NCs without arms. Moreover, electrical conduction through the assemblies is tolerant against mechanical bending because interconnections between TpNCs can be well-preserved under bending. Interestingly, both the conductivity of the assemblies and their mechanical tolerance against bending are improved with an increase in the length of tetrapod arms. The arm length-dependency was demonstrated in a series of CdSe TpNC assemblies with different arm lengths (l = 0-90 nm), whose electrical conduction was modulated through electrolyte gating. From the TpNCs with the longest arm length included in the study (l = 90 nm), the film conductivity as high as 20 S/cm was attained at 3 V of gate voltage, corresponding to electron mobility of >10 cm2/(V s) even when evaluated conservatively. The high channel conductivity was retained (∼90% of the value obtained from the flat geometry) even under high bending (bending radius = 5 mm). The results of the present study provide new insights and guidelines for the use of colloidal nanocrystals in solution-processed flexible electronic device applications.

Two-Regime Conformation of Grafted Polymer on Nanoparticle Determines Symmetry of Nanoparticle Self-Assembly.

One of the key design factors that regulate the properties of grafted nanoparticles (GNPs) and their self-assembly is the conformation of the grafted polymer. On the curved surface of the GNP core, the conformation of the polymer chain is not uniform in the radial direction. The segment is a non-Gaussian chain in the concentrated polymer brush (CPB) regime near the interface between GNP core and grafted polymer, while it is less constrained in the semidilute polymer brush (SDPB) regime near the surface of GNP. Here, the property of polymer conformation showing crossover behavior at the CPB/SDPB threshold through the coarse-grain molecular dynamics simulation of nanoparticles with explicit grafted chains is explored. Moreover, the self-assembly structure depends on the effective softness, which is defined as a function of the threshold of two regimes estimated from the conformation of the polymer.

Anomalous Water Penetration in Al3+ Dissolution.

The physicochemical characterization of trivalent ions is limited due to a lack of accurate force fields. By leveraging the latest machine learning force field to model aqueous AlCl3, we discover that upon dissolution of Al3+, water molecules beyond the second hydration shell are involved in the hydration process. A combination of scissoring of coordinating water is followed by synchronized secondary motion of water in the second solvation shell due to hydrogen bonding. Consequently, the water beyond the second solvation penetrates through the second solvation shell and coordinates to the Al3+. Our study reveals a novel microscopic understanding of solvation dynamics for the trivalent ion.

Real-space imaging of nanoparticle transport and interaction dynamics by graphene liquid cell TEM.

Thermal motion of colloidal nanoparticles and their cohesive interactions are of fundamental importance in nanoscience but are difficult to access quantitatively, primarily due to the lack of the appropriate analytical tools to investigate the dynamics of individual particles at nanoscales. Here, we directly monitor the stochastic thermal motion and coalescence dynamics of gold nanoparticles smaller than 5 nm, using graphene liquid cell (GLC) transmission electron microscopy (TEM). We also present a novel model of nanoparticle dynamics, providing a unified, quantitative explanation of our experimental observations. The nanoparticles in a GLC exhibit non-Gaussian, diffusive motion, signifying dynamic fluctuation of the diffusion coefficient due to the dynamically heterogeneous environment surrounding nanoparticles, including organic ligands on the nanoparticle surface. Our study shows that the dynamics of nanoparticle coalescence is controlled by two elementary processes: diffusion-limited encounter complex formation and the subsequent coalescence of the encounter complex through rotational motion, where surface-passivating ligands play a critical role.

Active microrheology of a bulk metallic glass.

The glass transition remains unclarified in condensed matter physics. Investigating the mechanical properties of glass is challenging because any global deformation that might result in shear rejuvenation would require a prohibitively long relaxation time. Moreover, glass is well known to be heterogeneous, and a global perturbation would prevent exploration of local mechanical/transport properties. However, investigation based on a local probe, i.e., microrheology, may overcome these problems. Here, we establish active microrheology of a bulk metallic glass, via a probe particle driven into host medium glass. This technique is amenable to experimental investigations via nanoindentation tests. We provide distinct evidence of a strong relationship between the microscopic dynamics of the probe particle and the macroscopic properties of the host medium glass. These findings establish active microrheology as a promising technique for investigating the local properties of bulk metallic glass.

Histological characteristics of the largest and secondary tumors in radical prostatectomy specimens and implications for focal therapy.

BACKGROUND: Pathological features of prostate cancer in Korean men were analyzed to determine whether identification of tumor volume, Gleason score (GS), focality, and location using radical prostatectomy (RP) specimens can provide useful information for the application of focal therapy (hemiablation). METHODS: From January 2016 to December 2017, 913 patients who underwent RP at a single center were selected for analysis. Patients with prostate-specific antigen levels > 15 ng/mL or those who had received hormone therapy prior to surgery were excluded. Preoperative data and the number, volume, location, and GS of each tumor were recorded. RESULTS: Overall, 762 RP specimens were examined, and 1448 tumors were identified. The majority of the cases were multifocal (60.5%) and bilateral (82%) in nature. Among the 686 secondary tumors, 250 (36.4%) had a GS ≥7 and 122 (17.8%) had a tumor volume ≥ 0.5 mL. Among the 435 bilateral multifocal cases, secondary tumors on the lobes contralateral to the largest tumor were significant by volume (≥0.5 mL) in 91 (20.9%) cases and by grade (GS ≥7) in 179 (41.1%) cases. There were 102 (23.4%) tumors with a small tumor volume (< 0.5 mL) and Gleason pattern 4 on the lobe contralateral to the largest tumor. CONCLUSIONS: Bilateral and multifocal tumors are a common feature and secondary tumors frequently exhibit clinically significant prostate cancer on RP specimens in Korea. In many cases, secondary tumors on the lobe contralateral to the largest tumor had a high GS and small tumor volume.

The clinical usefulness of natural killer cell activity in patients with suspected or diagnosed prostate cancer: an observational cross-sectional study.

PURPOSE: To investigate the clinical usefulness of natural killer cell activity (NKA) for detection of prostate cancer (PCa) and prediction of Gleason grade. PATIENTS AND METHODS: We prospectively enrolled 221 patients who underwent transrectal ultrasound-guided prostate biopsy for suspected PCa due to elevated prostate-specific antigen (PSA) >2.5 ng/mL or abnormal findings on digital rectal examination (n=146), or who were diagnosed with PCa (n=75) between 2016 and 2017. The NKA was compared according to PCa and Gleason grade. Correlation analysis was used to evaluate associations among NKA, PCa, and Gleason grade, and expressed using distribution dot plots. The absolute risk and relative risk of PCa, and odds ratios at different cut-off values of NKA were calculated. RESULTS: Of the total 221 patients, PCa was identified in 135 (61.9%) patients. When patients were divided according to PCa, there was no significant difference in NKA (1,267.6 vs 1,198.9 pg/mL, P=0.491). Furthermore, in 135 patients with PCa, the NKA was not significantly different according to Gleason grade (P=0.893). These results were not changed when confined to the patients with PSA between 2.5 and 10.0 ng/mL (P=0.654 and P=0.672, respectively). In addition, there was no significant difference in the risk of PCa at different cut-off values of NKA. CONCLUSION: These results indicate that NKA does not appear to be very useful for detection of PCa and prediction of Gleason grade. Further large multi-institutional studies are required to verify the role of NKA in PCa detection and Gleason grade prediction.

Highly conductive, stretchable and biocompatible Ag-Au core-sheath nanowire composite for wearable and implantable bioelectronics.

Wearable and implantable devices require conductive, stretchable and biocompatible materials. However, obtaining composites that simultaneously fulfil these requirements is challenging due to a trade-off between conductivity and stretchability. Here, we report on Ag-Au nanocomposites composed of ultralong gold-coated silver nanowires in an elastomeric block-copolymer matrix. Owing to the high aspect ratio and percolation network of the Ag-Au nanowires, the nanocomposites exhibit an optimized conductivity of 41,850 S cm-1 (maximum of 72,600 S cm-1). Phase separation in the Ag-Au nanocomposite during the solvent-drying process generates a microstructure that yields an optimized stretchability of 266% (maximum of 840%). The thick gold sheath deposited on the silver nanowire surface prevents oxidation and silver ion leaching, making the composite biocompatible and highly conductive. Using the nanocomposite, we successfully fabricate wearable and implantable soft bioelectronic devices that can be conformally integrated with human skin and swine heart for continuous electrophysiological recording, and electrical and thermal stimulation.

High-Resolution Spin-on-Patterning of Perovskite Thin Films for a Multiplexed Image Sensor Array.

Inorganic-organic hybrid perovskite thin films have attracted significant attention as an alternative to silicon in photon-absorbing devices mainly because of their superb optoelectronic properties. However, high-definition patterning of perovskite thin films, which is important for fabrication of the image sensor array, is hardly accomplished owing to their extreme instability in general photolithographic solvents. Here, a novel patterning process for perovskite thin films is described: the high-resolution spin-on-patterning (SoP) process. This fast and facile process is compatible with a variety of spin-coated perovskite materials and perovskite deposition techniques. The SoP process is successfully applied to develop a high-performance, ultrathin, and deformable perovskite-on-silicon multiplexed image sensor array, paving the road toward next-generation image sensor arrays.

Neutrophil and Lymphocyte Counts as Clinical Markers for Stratifying Low-Risk Prostate Cancer.

UNLABELLED: Appropriate patient selection for active surveillance is challenging.Our study of 217 patients demonstrated that the preoperative absolute neutrophil and lymphocyte counts were better predictors of aggressive oncologic features than were the neutrophil-to-lymphocyte ratio in the assessment of low-risk prostate cancer patients. Our findings suggest that routine hematologic workup could be used to further stratify low-risk prostate cancer patients. INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) has emerged as a ubiquitous prognostic biomarker in cancer-related inflammation, specifically in patients with metastatic castration-resistant prostate cancer (PCa). We evaluated the clinical utility of the preoperative NLR, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) as a risk stratification tool for patients with low-risk PCa. MATERIALS AND METHODS: We identified 217 low-risk PCa patients with preoperative hematologic data who had met the criteria for active surveillance but had undergone robot-assisted radical prostatectomy at our institution from 2006 to 2015. Logistic regression models were constructed to determine whether the baseline NLR, ANC, and ALC were associated with upstaging, upgrading, and biochemical recurrence (BCR). Survival analyses were performed using the Kaplan-Meier method. RESULTS: On multivariate analysis, a higher prostate-specific antigen level (odds ratio [OR], 1.554; 95% confidence interval [CI], 1.148-2.104), a greater number of positive cores (OR, 2.098; 95% CI, 1.043-2.104), and a higher ALC (OR, 4.311; 95% CI, 1.258-14.770) were associated with upstaging. More importantly, the 5-year biochemical recurrence-free survival was significantly lower in the high ANC group (ANC > 4.0 × 10(9)/L) compared with that of the low ANC group (P = .011). The NLR was not associated with upstaging, upgrading, or BCR in our study cohort (P = .368, P = .573, and P = .504, respectively). The only significant association with upgrading was patient age (OR, 1.106; 95% CI, 1.043-1.173). CONCLUSION: NLR was not useful in predicting adverse pathologic outcomes in our patients with low-risk PCa. However, relative neutrophilia and lymphocytosis might indicate an early manifestation of harboring a more aggressive PCa.