Elucidating charge transfer process and enhancing electrochemical performance of laser-induced graphene via surface engineering with sustainable hydrogel membranes: An electrochemist's perspective.

Laser-induced graphene (LIG) has emerged as a promising solvent-free strategy for producing highly porous, 3D graphene structures, particularly for electrochemical applications. However, the unique character of LIG and hydrogel membrane (HM) coated LIG requires accounting for the specific conditions of its charge transfer process. This study investigates electron transfer kinetics and the electroactive surface area of LIG electrodes, finding efficient kinetics for the [Fe(CN)6]3-/4- redox process, with a high rate constant of 4.89 x 10-3 cm/s. The impact of polysaccharide HM coatings (cationic chitosan, neutral agarose and anionic sodium alginate) on LIG's charge transfer behavior is elucidated, considering factors like ohmic drop across porous LIG and Coulombic interactions/permeability affecting diffusion coefficient (D), estimated from amperometry.It was found that D of redox species is lower for HM-coated LIGs, and is the lowest for chitosan HM. Chitosan coating results in increased capacitive share in the total current while does not apparently reduce Faradaic current. Experimental findings are supported by ab-initio calculations showing an electrostatic potential map's negative charge distribution upon chitosan chain protonation, having an effect in over a two-fold redox current increase upon switching the pH from 7.48 to 1.73. This feature is absent for other studied HMs. It was also revealed that the chitosan's band gap was reduced to 3.07 eV upon acetylation, due to the introduction of a new LUMO state. This study summarizes the operating conditions enhanced by HM presence, impacting redox process kinetics and presenting unique challenges for prospective LIG/HM systems' electrochemical applications.

Polymerization of hydroxyethyl methacrylate (HEMA) under rotation to form core-annular hydrogels.

HYPOTHESIS: We propose to polymerize high water content hydroxyethyl methacrylate (HEMA) formulations in a rotating cylinder to explore the effect of the rotation on microstructure and critical parameters such as diffusivity of model proteins in porous poly-HEMA gels. EXPERIMENTS: Cylindrical molds were partially filled with water-HEMA-initiator-crosslinker mixtures and exposed to UV light while undergoing rotation to polymerize into a cylindrical tube. The process was repeated multiple times to manufacture a core annular rod with multiple concentric rings, in which at least one ring was porous. The porous gels were imaged by scanning electron microscopy to explore the microstructure. The transport of model proteins bovine serum albumin and human γ-globulin was measured and modeled, in radial and axial directions, to obtain the effective diffusivity and partition coefficient. Also, the true diffusivity of proteins was calculated by accounting for the effects of porosity and tortuosity. FINDINGS: The porous gels exhibited diffusion-controlled release of both model proteins. The hydrogels prepared with 55% water in the monomer mixture were porous with non-isotropic structure likely due to axially oriented pores with minimal radial connectivity. The gels with higher water content were isotropic with interconnected pores in both directions. The pore volume increased with water content, but the partition coefficient was relatively constant and less than one likely due to presence of isolated unconnected pores.

Cd/Pb behavior during combustion in a coal-fired power plant and their spatiotemporal impacts on soils: New insights from Cd/Pb isotopes.

Coal power plants annually generate quantities of byproducts that release environmentally hazardous heavy metals like Cd and Pb. Understanding the behavior and spatiotemporal impacts on soils of these releases is crucial for pollution control. This study investigated the concentrations and isotope ratios of Cd/Pb in combustion byproducts, depositions and soils collected from a coal-fired power plant or its surrounding area. The pulverized fuel ash (PFA) and desulfurized gypsum (DG) exhibited heavier Cd isotopes with Δ114Cd values of 0.304‰ and 0.269‰, respectively, while bottom ash (BA) showed lighter Cd isotopes (Δ114CdBA-coal = -0.078‰), compared to feed coal. We proposed a two-stage condensation process that governs the distribution of Cd/Pb, including accumulation on PFA and DG within electrostatic precipitators and desulfurization unit, as well as condensation onto fine particles upon release from the stack. Emissions from combustion and large-scale transport make a significant contribution to deposition, while the dispersion of Cd/Pb in deposition is primarily influenced by the prevailing wind patterns. However, the distribution of Cd/Pb in soils not only exhibit predominant wind control but is also potentially influenced by the resuspension of long-term storage byproducts. The power plant significantly contributes to soil in the NW-N-NE directions, even at a considerable distance (66%-79%), demonstrating its pervasive impact on remote regions along these orientations. Additionally, based on the vertical behavior in the profile, we have identified that Cd tends to migrate downward through leaching, while variations in Pb respond to the historical progression of dust removal.

Joint estimation of compartment-specific T2 relaxation and tumor microstructure using multi-TE IMPULSED MRI.

PURPOSE: This study aims to assess how T2 heterogeneity biases IMPULSED-derived metrics of tissue microstructure in solid tumors and evaluate the potential of estimating multi-compartmental T2 and microstructural parameters simultaneously. METHODS: This study quantifies the impact of T2 relaxation on IMPULSED-derived microstructural parameters using computer simulations and in vivo multi-TE IMPULSED MRI in five tumor models, including brain, breast, prostate, melanoma, and colon cancer. A comprehensive T2 + IMPULSED method was developed to fit multi-compartmental T2 and microstructural parameters simultaneously. A Bayesian model selection approach was carried out voxel-wisely to determine if the T2 heterogeneity needs to be included in IMPULSED MRI in cancer. RESULTS: Simulations suggest that T2 heterogeneity has a minor effect on the estimation of d in tissues with intermediate or high cell density, but significantly biases the estimation of v in $$ {v}_{in} $$ with low cell density. For the in vivo animal experiments, all IMPULSED metrics except v in $$ {v}_{in} $$ are statistically independent on TE. For B16 tumors, the IMPULSED-derived v in $$ {v}_{in} $$ exhibited a notable increase with longer TEs. For MDA-MB-231 tumors, IMPULSED-derived v in $$ {v}_{in} $$ showed a significant increase with increasing TEs. The T2 + IMPULSED-derived T 2 in $$ {T}_2^{in} $$ of all five tumor models are consistently smaller than T 2 ex $$ {T}_2^{ex} $$ . CONCLUSIONS: The findings from this study highlight two key observations: (i) TE has a negligible impact on IMPULSED-derived cell sizes, and (ii) the TE-dependence of IMPULSED-derived intracellular volume fractions used in T2 + IMPULSED modeling to estimate T 2 in $$ {T}_2^{in} $$ and T 2 ex $$ {T}_2^{ex} $$ . These insights contribute to the ongoing development and refinement of non-invasive MRI techniques for measuring cell sizes.

Adsorption of typical NDMA precursors by superfine powdered activated carbon: Critical role of particle size reduction.

Control of N-nitrosodimethylamine (NDMA) in drinking water could be achieved by removing its precursors as one practical way. Herein, superfine powdered activated carbons with a diameter of about 1 µm (SPACs) were successfully prepared by grinding powdered activated carbon (PAC, D50=24.3 µm) and applied to remove model NDMA precursors, i.e. ranitidine (RAN) and nizatidine (NIZ). Results from grain diameter experiments demonstrated that the absorption velocity increased dramatically with decreasing particle size, and the maximum increase in k2 was 26.8-folds for RAN and 33.4-folds for NIZ. Moreover, kinetic experiments explained that rapid absorption could be attributed to the acceleration of intraparticle diffusion due to the shortening of the diffusion path. Furthermore, performance comparison experiments suggested that the removal of RAN and NIZ (C0=0.5 mg/L) could reach 61.3% and 60%, respectively, within 5 min, when the dosage of SAPC-1.1 (D50=1.1 µm) was merely 5 mg/L, while PAC-24.3 could only eliminate 17.5% and 18.6%. The adsorption isotherm was well defined by Langmuir isotherm model, indicating that the adsorption of RAN/NIZ was a monolayer coverage process. The adsorption of RAN or NIZ by SAPC-1.1 and PAC-24.3 was strongly pH dependent, and high adsorption capacity could be observed under the condition of pH > pka+1. The coexistence of humic acid (HA) had no significant effect on the adsorption performance because RAN/NIZ may be coupled with HA and removed simultaneously. The coexistence of anions had little effect on the adsorption also. This study is expected to provide an alternative strategy for drinking water safety triggered by NDMA.

Improving diffusion kinetics of zinc ions/stabilizing zinc anode by molecular slip mechanism and anchoring effect in supramolecular zwitterionic hydrogels.

The severe hydrogen evolution reaction and parasitic side reaction on Zn anode are the key issues which hinder the development of aqueous Zn-based energy storage devices. Herein, a polyacrylamide/carboxylated cellulose nanofibers/betaine citrate supramolecular zwitterionic hydrogels with molecular slip effects are proposed for enhancing Zn2+ diffusion and protecting Zn anodes. Non-covalent interactions within supramolecular hydrogels forms the skeleton for molecular slip and the strong coordination of carboxyl and amino groups with Zn2+ further facilitates the rapid Zn2+ transfer. Additionally, anchoring carboxyl and amino groups at the anode promotes the uniform deposition of Zn2+and protects Zn anode. On the basis of molecular slip mechanism and anchoring effect in the supramolecular zwitterionic hydrogels, Zn||Zn symmetric batteries undergo 800 h of stable electroplating stripping at a depth of discharge of 80 %. Zn||Cu asymmetric batteries exhibit an impressive average coulombic efficiency of 99.4 % over a remarkable span of 900 cycles at a current density of 15 mA cm-2. Furthermore, Zn||NH4V4O10 batteries successfully undergo over 1,000 cycles at a current density of 0.5 A g-1. Intrinsic ion diffusion mechanism of supramolecular hydrogel electrolytes provides an original strategy for the application of high-performance Zn-based energy storage devices.

Comment on "Cellular aggregation dictates universal spreading behaviour of a whole-blood drop on a paper strip".

Laha et al. studied the diffusive behavior of a whole-blood drop on filter paper using the generalized capillary bundle model. However, some model parameters should be further refined to accurately reflect the physics involved in this diffusion process. Moreover, citations are missing for some key equations. Addressing these aspects will improve the model applicability to this application and benefit readers in accessing more accurate and detailed information.

Response to the comments on "Cellular aggregation dictates universal spreading behaviour of a whole-blood drop on a paper strip".

In 2023, we published a research article in the Journal of Colloidal and Interface Science, based on our experimental findings and substantiating scaling arguments leading to a simple theoretical insight on the effect of red blood cell (RBC) aggregation on the wicking behaviour of a finite volume of blood as it navigates through the porous passages of a paper matrix (Laha et al., 2023). Of late, we received comments from Li (2024), which offered certain suggestions regarding the possible improvement of the capillary bundle model as considered in our article for analyzing the transport of blood through the paper pores. Herein, we provide a detailed discussion on each of the points raised by Li (2024) and rationalize our views in further details in addition to the contents already provided in our concerned article.

White matter correlates of cognition: A diffusion magnetic resonance imaging study.

BACKGROUND: Our comprehension of the interplay of cognition and the brain remains constrained. While functional imaging studies have identified cognitive brain regions, structural correlates of cognitive functions remain underexplored. Advanced methods like Diffusion Magnetic Resonance Imaging (DMRI) facilitate the exploration of brain connectivity and White Matter (WM) tract microstructure. Therefore, we conducted connectometry method on DMRI data, to reveal WM tracts associated with cognition. METHODS: 125 healthy participants from the National Institute of Mental Health Intramural Healthy Volunteer Dataset were recruited. Multiple regression analyses were conducted between DMRI-derived Quantitative Anisotropy (QA) values within WM tracts and scores of participants in Flanker Inhibitory Control and Attention Test (attention), Dimensional Change Card Sort (executive function), Picture Sequence Memory Test (episodic memory), and List Sorting Working Memory Test (working memory) tasks from National Institute of Health toolbox. The significance level was set at False Discovery Rate (FDR)<0.05. RESULTS: We identified significant positive correlations between the QA of WM tracts within the left cerebellum and bilateral fornix with attention, executive functioning, and episodic memory (FDR=0.018, 0.0002, and 0.0002, respectively), and a negative correlation between QA of WM tracts within bilateral cerebellum with attention (FDR=0.028). Working memory demonstrated positive correlations with QA of left inferior longitudinal and left inferior fronto-occipital fasciculi (FDR=0.0009), while it showed a negative correlation with QA of right cerebellar tracts (FDR=0.0005). CONCLUSION: Our results underscore the intricate link between cognitive performance and WM integrity in frontal, temporal, and cerebellar regions, offering insights into early detection and targeted interventions for cognitive disorders.

Scale-Dependent Growth Modes of Selective Area Grown III-V Nanowires.

Due to their flexible geometry, in-plane selective area grown (SAG) nanowires (NWs) encompass the advantages of vapor-liquid-solid NWs and planar structures. The complex interplay of growth kinetics and NW dimensions provides new pathways for crystal engineering; however, their growth mechanisms remain poorly understood. We analyze the growth mechanisms of GaAs(Sb) and InGaAs/GaAs(Sb) in-plane SAG NWs using molecular beam epitaxy (MBE). While GaAs(Sb) NWs consistently follow a layer-by-layer growth, the InGaAs/GaAs(Sb) growth transitions from step-flow to layer-by-layer and layer-plus-island depending on the InGaAs thickness and the NW dimensions. We extract the diffusion lengths of Ga adatoms along the [11̅0] and [110] directions under As2 during GaAs(Sb) growth. Our results indicate that Sb may inhibit the layer-by-layer to step-flow transition. Our findings show that different growth modes can be achieved in the MBE of in-plane SAG NWs grown on the same substrate and highlight the importance of the interplay with NW dimensions.

Surface Self-Diffusion Induced Sintering of Nanoparticles.

Despite the critical role of sintering phenomena in constraining the long-term durability of nanosized particles, a clear understanding of nanoparticle sintering has remained elusive due to the challenges in atomically tracking the neck initiation and discerning different mechanisms. Through the integration of in situ transmission electron microscopy and atomistic modeling, this study uncovers the atomic dynamics governing the neck initiation of Pt-Fe nanoparticles via a surface self-diffusion process, allowing for coalescence without significant particle movement. Real-time imaging reveals that thermally activated surface morphology changes in individual nanoparticles induce significant surface self-diffusion. The kinetic entrapment of self-diffusing atoms in the gaps between closely spaced nanoparticles leads to the nucleation and growth of atomic layers for neck formation. This surface self-diffusion-driven sintering process is activated at a relatively lower temperature compared to the classic Ostwald ripening and particle migration and coalescence processes. The fundamental insights have practical implications for manipulating the morphology, size distribution, and stability of nanostructures by leveraging surface self-diffusion processes.

Longitudinal Evolution of the Brain Microstructure in Cirrhotic Patients on Diffusion Kurtosis Imaging.

BACKGROUND: Although improvement of cognitive function after liver transplantation has been demonstrated in several neuropsychological studies, there is limited research on longitudinal changes in the cirrhotic patients' brain structure before and after transplantation. PURPOSE: To investigate longitudinal changes of brain microstructure in cirrhotic patients using diffusion kurtosis imaging (DKI). STUDY TYPE: Prospective. SUBJECTS: A total of 153 cirrhosis patients, comprising 60 hepatic encephalopathy (HE) patients (16 females/44 males) and 93 no-HE patients (35 females/58 males), along with 93 healthy controls (HCs) (53 females/40 males) were enrolled. Subsequently, 58 recipients completed 1-month postoperative follow-up, 29 patients completed 1-, 3-months, and 17 patients completed 1-, 3-, 6-month follow-up. SEQUENCE: Spin-echo single-shot echo-planar sequence using a 3.0 T scanner. ASSESSMENT: Diffusion kurtosis estimator software was used to estimate the DKI parameter maps by a MR imaging physicist (Y.-Y.C. with 12 years of experience). STATISTICAL TESTS: The diffusion metrics (eg, radial kurtosis [RK], mean kurtosis, fractional anisotropy, mean diffusivity) of the patients before transplantation were compared with those of the HCs using voxel-wise analysis of variance (ANOVA), along with t tests for post hoc analysis. Linear mixed-effects models were applied to the longitudinal data. We imposed a cluster level Family Wise Error (FWE) correction rate of PFWE = 0.05 with voxel-wise cutoff of P = 0.001 together with a cluster-size cutoff of N ≥ 56, and generated smoothness estimates from the preprocessed data using the mixed-model autocorrelation function. RESULTS: The RK metrics of the patients decreased significantly in the anterior cingulate cortex (HE/no-HE < HC, ANOVA-F = 21.91). After transplantation, the RK of the pallidum showed a continuous upward trend (time effect T = 11.26); whereas the RK of the right postcentral gyrus showed a continuous downward trend (time effect T = -9.56). In addition, the RK in superior longitudinal fasciculus showed new-onset decrease after transplantation. DATA CONCLUSION: Longitudinal changes in DKI metrics reveal the course of brain microstructural changes before and after transplantation in cirrhotic patients, potentially associated with cognitive alterations after surgery. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Microstructural alterations of cerebellar peduncles in multiple sclerosis: a diffusion tensor imaging study.

BACKGROUND AND PURPOSE: Ataxia, tremors, dysarthria, and sometimes impaired cognition are the signs of cerebellum involvement in multiple sclerosis (MS). These symptoms affect up to 80% of patients and are usually hard to treat. To find the underlying involvement of the cerebellum in MS, we assessed the microstructural alterations with DTI in the cerebellar peduncles of the affected subjects. MATERIALS AND METHODS: We included 58 relapsing-remitting MS patients and 27 healthy controls. Patients were divided into 18 patients of relapsing-remitting MS with cerebellar impairment (RRMSc) and 40 without cerebellar impairment (RRMSnc). Using Diffusion Tensor Imaging (DTI), we calculated fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) metrics in all subjects. We also checked if there were associations between DTI metrics and clinical cerebellar measures (i.e., tremor severity and the scale for the assessment and rating of ataxia). RESULTS: ANOVA and post-hoc results showed significant differences in DTI metrics between RRMSc and HC and between RRMSnc and HC subjects. Inferior peduncle RD remained the only metric with a significant difference across all pairwise comparisons. The general linear model assessing the effects of the three study groups on the association between DTI metrics and clinical cerebellar measures yielded no significant result. CONCLUSIONS: Our study showed that DTI can mainly reveal significant differences between different MS groups and HCs. Our results imply the role of cerebellar peduncles in the pathophysiology of MS and that this role does not necessarily reflect the severity of cerebellar signs of the patients.

Assessment of training-associated changes of the lumbar back muscle using a multiparametric MRI protocol.

Adaptations in muscle physiology due to long-term physical training have been monitored using various methods: ranging from invasive techniques, such as biopsy, to less invasive approaches, such as electromyography (EMG), to various quantitative magnetic resonance imaging (qMRI) parameters. Typically, these latter parameters are assessed immediately after exercise. In contrast, this work assesses such adaptations in a set of qMRI parameters obtained at rest in the lumbar spine muscles of volunteers. To this end, we developed a multiparametric measurement protocol to extract quantitative values of (water) T2, fat fraction, T1, and Intra Voxel Incoherent Motion (IVIM) diffusion parameters in the lumbar back muscle. The protocol was applied to 31 healthy subjects divided into three differently trained cohorts: two groups of athletes (endurance athletes and powerlifters) and a control group with a sedentary lifestyle. Significant differences in muscle water T2, fat fraction, and pseudo-diffusion coefficient linked to microcirculatory blood flow in muscle tissue were found between the trained and untrained cohorts. At the same time, diffusion coefficients (resolved along different directions) provided additional differentiation between the two groups of athletes. Specifically, the strength-trained athletes showed lower axial and higher radial diffusion components compared to the endurance-trained cohort, which may indicate muscle hypertrophy. In conclusion, utilizing multiparametric information revealed new insights into the potential of quantitative MR parameters to detect and quantify long-term effects associated with training in differently trained cohorts, even at rest.

Changes in diffusion MRI and clinical motor function after physical/occupational therapies in toddler-aged children with spastic unilateral cerebral palsy.

Diffusion-weighted magnetic resonance imaging (DMRI) is a potential tool to assess changes in brain connectivity and microstructure resulting from physical and occupational therapy in young children with cerebral palsy. This works was carried out to assess whether DMRI can detect changes after 36 weeks of physical and occupational therapy in the microstructure and connectivity of the brains of children with cerebral palsy and determine whether imaging findings correlate with changes in clinical measures of motor function. Five children underwent anatomical MRI and DMRI and evaluations of motor function skills at baseline and after 36 weeks of intensive or once-weekly physical and occupational Perception-Action Approach therapies. Diffusion tensor imaging and constrained spherical deconvolution methods were used to calculate fractional anisotropy (FA) and fiber orientation distribution functions (fODFs), respectively. The fODFs were used to generate tractograms of the cerebrospinal tract (CST). After 36 weeks of physical and occupational therapy, all children showed increases in motor function. No changes were observed in anatomical MRI before and after therapy but CST tractography did show small differences indicating possible altered microstructure and connectivity in the brain. FA values along the CSTs, however, showed no significant changes. Reliable longitudinal DMRI can be employed in toddler-aged children with CP and DMRI has the potential to monitor neuroplastic changes in white matter microstructure. However, there is a high variability between subjects and clinical improvements were not always correlated with measures of FA along the CST.

Engineered AAV capsid transport mutants overcome transduction deficiencies in the aged CNS.

Adeno-associated virus (AAV)-based gene therapy has enjoyed great successes over the past decade, with Food and Drug Administration-approved therapeutics and a robust clinical pipeline. Nonetheless, barriers to successful translation remain. For example, advanced age is associated with impaired brain transduction, with the diminution of infectivity depending on anatomical region and capsid. Given that CNS gene transfer is often associated with neurodegenerative diseases where age is the chief risk factor, we sought to better understand the causes of this impediment. We assessed two AAV variants hypothesized to overcome factors negatively impacting transduction in the aged brain; specifically, changes in extracellular and cell-surface glycans, and intracellular transport. We evaluated a heparin sulfate proteoglycan null variant with or without mutations enhancing intracellular transport. Vectors were injected into the striatum of young adult or aged rats to address whether improving extracellular diffusion, removing glycan receptor dependence, or improving intracellular transport are important factors in transducing the aged brain. We found that, regardless of the viral capsid, there was a reduction in many of our metrics of transduction in the aged brain. However, the transport mutant was less sensitive to age, suggesting that changes in the cellular transport of AAV capsids are a key factor in age-related transduction deficiency.

Mesoporous Silica Microparticle-Protein Complexes: Effects of Protein Size and Solvent Properties on Diffusion and Loading Efficiency.

Oral administration of protein-based therapeutics is highly desirable due to lower cost, enhanced patient compliance, and convenience. However, the harsh pH environment of the gastrointestinal tract poses significant challenges. Silica-based carriers have emerged as potential candidates for the delivery of protein molecules, owing to their tuneable surface area and pore volume. We explored the use of a commercial mesoporous silica carrier, SYLOID, for the delivery of octreotide and bovine serum albumin (BSA) using a solvent evaporation method in three different solvents. The loading of proteins into SYLOID was driven by diffusion, as described by the Stokes-Einstein equation. Various parameters were investigated, such as protein size, diffusion, and solubility. Additionally, 3D fluorescence confocal imaging was employed to identify fluorescence intensity and protein diffusion within the carrier. Our results indicated that the loading process was influenced by the molecular size of the protein as octreotide exhibited a higher recovery rate (71%) compared to BSA (32%). The methanol-based loading of octreotide showed uniform diffusion into the silica carrier, whereas water and ethanol loading resulted in the drug being concentrated on the surface, as shown by confocal imaging, and further confirmed by scanning electron microscopy (SEM). Pore volume assessment supported these findings, showing that octreotide loaded with methanol had a low pore volume (1.2 cc/g). On the other hand, BSA loading was affected by its solubility in the three solvents, its tendency to aggregate, and its low solubility in ethanol and methanol, which resulted in dispersed particle sizes of 223 and 231 µm, respectively. This reduced diffusion into the carrier, as confirmed by fluorescence intensity and diffusivity values. This study underscores the importance of protein size, solvent properties, and diffusion characteristics when using porous carriers for protein delivery. Understanding these factors allows for the development of more effective oral protein-based therapeutics by enhancing loading efficiency. This, in turn, will lead to advances in targeted drug delivery and improved patient outcomes.

AptaDiff: de novo design and optimization of aptamers based on diffusion models.

Aptamers are single-stranded nucleic acid ligands, featuring high affinity and specificity to target molecules. Traditionally they are identified from large DNA/RNA libraries using $in vitro$ methods, like Systematic Evolution of Ligands by Exponential Enrichment (SELEX). However, these libraries capture only a small fraction of theoretical sequence space, and various aptamer candidates are constrained by actual sequencing capabilities from the experiment. Addressing this, we proposed AptaDiff, the first in silico aptamer design and optimization method based on the diffusion model. Our Aptadiff can generate aptamers beyond the constraints of high-throughput sequencing data, leveraging motif-dependent latent embeddings from variational autoencoder, and can optimize aptamers by affinity-guided aptamer generation according to Bayesian optimization. Comparative evaluations revealed AptaDiff's superiority over existing aptamer generation methods in terms of quality and fidelity across four high-throughput screening data targeting distinct proteins. Moreover, surface plasmon resonance experiments were conducted to validate the binding affinity of aptamers generated through Bayesian optimization for two target proteins. The results unveiled a significant boost of $87.9\%$ and $60.2\%$ in RU values, along with a 3.6-fold and 2.4-fold decrease in KD values for the respective target proteins. Notably, the optimized aptamers demonstrated superior binding affinity compared to top experimental candidates selected through SELEX, underscoring the promising outcomes of our AptaDiff in accelerating the discovery of superior aptamers.

Optimizing prostate cancer detection in transition zone: an analysis of apparent diffusion coefficient values in prostate magnetic resonance imaging evaluation with Prostate Imaging Reporting and Data System (PI-RADS) assessment.

Background: Multiparametric magnetic resonance imaging (mpMRI) is increasingly used for the early detection of clinically significant prostate cancer (csPCa). However, the achievement of accurate detection rates, particularly for transition zone (TZ) lesions, remains challenging. We investigated the relationship between apparent diffusion coefficient (ADC) values in Prostate Imaging Reporting and Data System (PI-RADS) 3-5 lesions and csPCa within the TZ. Methods: We retrospectively evaluated TZ lesions in patients who underwent 3.0 Tesla MRI followed by MRI-targeted/transrectal ultrasound fusion biopsies (MRI-FBx). Fusion biopsies were performed for potentially cancerous lesions, defined as lesions with PI-RADS scores 3-5. We analyzed 196 lesions for which fusion biopsies were performed. Results: The overall prostate cancer (PCa) detection rate was 53.6% (105/196); csPCa constituted 33.7% (66/196) of cases. The minimum ADC value was significantly lower for patients with csPCa (484.9±112.3 µm2/s) than for patients with benign histology or non-csPCa (P<0.001). Older age, higher initial prostate-specific antigen level, larger region of interest, and minimum and mean ADC values were associated with the presence of csPCa. Multivariate analysis indicated that only the minimum ADC value was an independent predictor of csPCa. Using a cutoff minimum ADC value <561 µm2/s to detect csPCa in TZ lesions increased the detection rate to 57.4% (54/94). Conclusions: The minimum ADC value provides substantial additional information regarding the presence of csPCa in the TZ, potentially improving the detection rates for lesions rated as PI-RADS 3-5 and informing the need for follow-up biopsies in areas that are initially cancer-free.

Large vessel occlusion mediated fluid attenuated inversion recovery signal intensity ratio is associated with stroke within 4.5 h.

Introduction: The primary objective was to investigate the value of the fluid attenuated inversion recovery (FLAIR) signal intensity ratio (SIR) in identifying stroke within 4.5 h. The secondary objective was to ascertain whether large vessel occlusion (LVO) mediated the relationship between the SIR and stroke within 4.5 h. Methods: We analyzed 633 acute stroke patients within 24 h of clear symptom onset. The SIR and DWI-FLAIR mismatch were evaluated. First, we determined whether demographic variables, vascular risk factors and LVO were related to stroke within 4.5 h with multivariate logistic regression analyses and stratified regression analysis. Next, we used mediation analysis to determine whether LVO explained the association between SIR and stroke within 4.5 h. Finally, we used receiver operating characteristic (ROC) analysis to assess the value of SIR, independent variable, and multiparameter models in identifying stroke within 4.5 h and compared with DWI-FLAIR mismatch. Results: Hyperlipemia, LVO and SIR were associated with stroke within 4.5 h. Mediation analysis revealed that LVO partially mediated the relationship between SIR and stroke within 4.5 h (p < 0.001). The multiparameter model (hyperlipemia, LVO and SIR) showed significantly improved performance (AUC 0.869) in identifying stroke within 4.5 h over DWI-FLAIR mismatch (0.684), hyperlipemia (0.632), LVO (0.667) and SIR (0.773) models. Conclusion: SIR is associated with stroke within 4.5 h, and LVO partially mediates this relationship. A multiparameter model combining hyperlipemia, LVO and SIR can more accurately identify stroke within 4.5 h than individual parameter models.