Anticancer peptides (ACPs) are a kind of bioactive peptides which could be used as a novel type of anticancer drug that has several advantages over chemistry-based drug, including high specificity, ...strong tumor penetration capacity, and low toxicity to normal cells. As the number of experimentally verified bioactive peptides has increased significantly, various of in silico approaches are imperative for investigating the characteristics of ACPs. However, the lack of methods for investigating the differences in physicochemical properties of ACPs. In this study, we compared the N- and C-terminal amino acid composition for each peptide, there are three major subtypes of ACPs that are defined based on the distribution of positively charged residues. For the first time, we were motivated to develop a two-step machine learning model for identification of the subtypes of ACPs, which classify the input data into the corresponding group before applying the classifier. Further, to improve the predictive power, the hybrid feature sets were considered for prediction. Evaluation by five-fold cross-validation showed that the two-step model trained with sequence-based features and physicochemical properties was most effective in discriminating between ACPs and non-ACPs. The two-step model trained with the hybrid features performed well, with a sensitivity of 86.75%, a specificity of 85.75%, an accuracy of 86.08%, and a Matthews Correlation Coefficient value of 0.703. Furthermore, the model also consistently provides the effective performance in independent testing set, with sensitivity of 77.6%, specificity of 94.74%, accuracy of 88.99% and the MCC value reached 0.75. Finally, the two-step model has been implemented as a web-based tool, namely iDACP, which is now freely available at http://mer.hc.mmh.org.tw/iDACP/ .
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. ...While various strategies, including local perfusion, molecular “uncaging”, or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the “turning assay” and “collapse assay”, which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo , which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically-controlled delivery technology a general and important tool in cell biology research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The optimization of reactant and product mass transfer within fuel cells stands as a critical determinant for achieving optimal fuel-cell performance. With a specific focus on stationary ...applications, this study delves into the comprehensive examination of fuel-cell mass transfer properties, employing a sophisticated blend of computational fluid dynamics (CFD) and the innovative design of a double-layered wire mesh (DLWM) as a flow field and gas diffusion layer. The investigation notably contrasts a meticulously developed 3D fine mesh flow field with a numerical model of the integrated DLWM implemented on the cathode end of a proton exchange membrane fuel cell (PEMFC). Evaluations reveal that the 3D fine mesh experiences a notable threefold increase in pressure drop compared to the DLWM flow field, indicative of the enhanced efficiency achieved by the DLWM configuration. Oxygen distribution analyses further underscore the promising performance of both the 3D fine mesh and the proposed DLWM, with the DLWM showcasing additional improvements in water removal capabilities within the cell. Impressively, the DLWM attains a remarkable maximum current density of 2137.17 mA/cm2 at 0.55 V, indicative of its superior performance over the 3D fine mesh, while also demonstrating the potential for cost-effectiveness and scalability in mass production.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
It has been unclear whether diabetes mellitus (DM) is positively associated with a risk of venous thromboembolism (VTE). In addition, whether the risk of VTE is altered in patients with type 1 ...diabetes (T1DM) has rarely been explored.
We investigated whether patients with T1DM are at a relatively high risk of VTE development.
We retrieved data from the National Health Insurance Research Database of Taiwan to conduct this retrospective cohort study. The T1DM group consisted of 4967 patients diagnosed as having T1DM before 2003. The non-T1DM group comprised 19 868 age- and sex-matched enrollees without T1DM. Cox proportional hazard regression analysis was used to investigate the hazard ratio of VTE in patients with T1DM relative to those without T1DM.
During a mean follow-up period of 8.61 years, the risk of VTE in the T1DM group was 5.33-fold higher than in the non-T1DM group after adjusting for dyslipidemia, hypertension, stroke, lower leg fracture or surgery, and obesity. Further stratified analysis revealed that the risk of VTE was significantly high in both sexes and in all age groups below the age of 60.
T1DM appears to be an independent risk factor for VTE development.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bacterial cellulose (BC) is a biocompatible material with high purity and robust mechanical strength used to fabricate desirable scaffolds for 3D cell culture and wound healing. However, the chemical ...resistance of BC and its insolubility in the majority of solutions make it difficult to manipulate using standard chemical methods. In this study, a microfluidic process is developed to produce hollow BC microspheres with desirable internal structures and morphology. Microfluidics is used to generate a core–shell structured microparticle with an alginate core and agarose shell as a template to encapsulate Gluconacetobacter xylinus for long‐term static culture. G. xylinus then secretes BC, which becomes entangled within the shell of the structured hydrogel microparticles and forms BC microspheres. The removal of the hydrogel template via thermal‐chemical treatments yields robust BC microspheres exhibiting a hollow morphology. These hollow microspheres spontaneously assemble as functional units to form a novel injectable scaffold. In vitro, a highly porous scaffold is created to enable effective 3D cell culture with a high cell proliferation rate and better depth distribution. In vivo, this injectable scaffold facilitates tissue regeneration, resulting in rapid wound‐healing in a Sprague Dawley rat skin model.
A microfluidics process is developed to fabricate hollow microspheres consisting of bacterial cellulose. The performance of the hollow bacterial cellulose microsphere scaffold is superior to a cellulose membrane and a normal cellulose microsphere scaffold in terms of cell proliferation, tissue regeneration, and wound healing promotion.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung ...cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and dacomitinib in this setting.
Between September 2020 and March 2023, we retrospectively recruited patients diagnosed with advanced-stage EGFR-mutant NSCLC who were treated with first-line irreversible EGFR-TKIs. The enrolled patients were assigned to two groups based on whether they received afatinib or dacomitinib.
A total of 101 patients were enrolled in the study (70 to afatinib and 31 to dacomitinib). The partial response rates (PR) for first-line treatment with afatinib and dacomitinib were 85.7 and 80.6% (p = 0.522). The median progression-free survival (PFS) (18.9 vs. 16.3 months, p = 0.975) and time to treatment failure (TTF) (22.7 vs. 15.9 months, p = 0.324) in patients with afatinib and dacomitinib treatment were similar. There was no significant difference observed in the median PFS (16.1 vs. 18.9 months, p = 0.361) and TTF (32.5 vs. 19.6 months, p = 0.182) between patients receiving the standard dose and those receiving the reduced dose. In terms of side effects, the incidence of diarrhea was higher in the afatinib group (75.8% vs. 35.5%, p < 0.001), while the incidence of paronychia was higher in the dacomitinib group (58.1% vs. 31.4%, p = 0.004). The PFS (17.6 vs. 24.9 months, p = 0.663) and TTF (21.3 vs. 25.1 months, p = 0.152) were similar between patients younger than 75 years and those older than 75 years.
This study showed that afatinib and dacomitinib had similar effectiveness and safety profiles. However, they have slightly different side effects. Afatinib and dacomitinib can be safely administered to patients across different age groups with appropriate dose reductions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The patient population with stage III non-small-cell lung cancer (NSCLC) is heterogeneous, with varying staging characteristics and diverse treatment options. Despite the potential practice-changing ...implications of randomized controlled trials evaluating the efficacy of perioperative epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), concerns have been raised due to conflicting overall survival (OS) results. Few real-world studies have examined the survival outcomes of patients with resected EGFR-mutant stage III adenocarcinoma receiving perioperative chemotherapy and EGFR-TKIs.
In this retrospective observational study, we enrolled patients with resected stage III adenocarcinoma with EGFR mutations between January 2011 and December 2021. Patients were classified into two groups: perioperative chemotherapy and perioperative EGFR-TKIs. Outcomes and prognostic factors were analyzed using Cox proportional hazards regression analysis.
Eighty-four patients were enrolled in the analysis. Perioperative EGFR-TKIs led to longer progression-free survival (PFS) than chemotherapy (38.6 versus 14.2 months; p = 0.019). However, only pathological risk factors predicted poor PFS in multivariate analysis. Patients receiving perioperative chemotherapy had longer OS than those receiving EGFR-TKIs (111.3 versus 50.2 months; p = 0.052). Multivariate analysis identified perioperative treatment with EGFR-TKIs as an independent predictor of poor OS (HR: 3.76; 95% CI: 1.22-11.54).
Our study demonstrates that chemotherapy should be considered in the perioperative setting for high-risk patients, when taking pathological risk factors into consideration, and that optimized sequencing of EGFR-TKIs might be the most critical determinant of OS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non‐small cell lung cancer cells to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors ...(TKIs). However, none of the PKC inhibitors has been approved for anticancer therapy yet due to the limited efficacy in clinical trials, and the underlying mechanisms remain unclear. l‐lactic acidosis, a common condition comprising high l‐lactate concentration and acidic pH in the tumor microenvironment, has been known to induce tumor metastasis and drug resistance. In this study, l‐lactic acid was found to reverse the inhibitory effects of pan‐PKC inhibitors GO6983 on PKC activity, cell migration, and EGFR‐TKI resistance, but these effects were not affected by the modulators of lactate receptor GPR81. Interestingly, blockade of lactate transporters, monocarboxylate transporter‐1 and ‐4 (MCT1 and MCT4), attenuated the intracellular level of GO6983, and its inhibitory effect on PKC activity, suggesting that lactic acid promotes the resistance to PKC inhibitors by competing for the uptake through these transporters rather than by activating its receptor, GPR81. Our findings explain the underlying mechanisms of the limited response of PKC inhibitors in clinical trials.
Targeting protein kinase C (PKC) family was found to repress the migration and resistance of non‐small cell lung cancer (NSCLC) cells to epidermal growth factor receptor tyrosine kinase inhibitors. The l‐lactic acidosis condition in the tumor microenvironment might be one of the factors that cause the resistance to PKC inhibitors by competing for the uptake via monocarboxylate transporters and limiting the response of NSCLC patients to this therapy
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Light‐directed forces have been widely used to pattern micro/nanoscale objects with precise control, forming functional assemblies. However, a substantial laser intensity is required to generate ...sufficient optical gradient forces to move a small object in a certain direction, causing limited throughput for applications. A high‐throughput light‐directed assembly is demonstrated as a printing technology by introducing gold nanorods to induce thermal convection flows that move microparticles (diameter = 40 µm to several hundreds of micrometers) to specific light‐guided locations, forming desired patterns. With the advantage of effective light‐directed assembly, the microfluidic‐fabricated monodispersed biocompatible microparticles are used as building blocks to construct a structured assembly (≈10 cm scale) in ≈2 min. The control with microscale precision is approached by changing the size of the laser light spot. After crosslinking assembly of building blocks, a novel soft material with wanted pattern is approached. To demonstrate its application, the mesenchymal stem‐cell‐seeded hydrogel microparticles are prepared as functional building blocks to construct scaffold‐free tissues with desired structures. This light‐directed fabrication method can be applied to integrate different building units, enabling the bottom‐up formation of materials with precise control over their internal structure for bioprinting, tissue engineering, and advanced manufacturing.
A novel high throughput light‐directed assembly methodon the microscale is investigated by suspending gold nanorods (GNRs), as photothermal transducers, in a fluidic medium to induce thermoplasmonic convections for the assembly of building blocks fabricated through microfluidics. Because significant local thermoplasmonic convections are generated by precisely controlling the low‐power infrared laser spot size and direction, effective building block assembly with high resolution enabled the desired patterns.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This paper presents the design of a continuous-time ΔΣ modulator (CTDSM) to be used in an ultrasound beamformer for biomedical imaging. To achieve better resolution, the prototype modulator operates ...at 1.2 GHz. It incorporates a digital excess loop delay (ELD) compensation to replace the active adder in front of the internal quantizer. A digitally controlled reference-switching matrix, combined with the data-weighted averaging (DWA) technique, results in a delay-free feedback path. A multi-bit FIR feedback DAC, along with its compensation path, is used to achieve lower clock jitter sensitivity and better loop filter linearity. The modulator achieves 79.4 dB dynamic range, 77.3 dB SNR, and 74.3 dB SNDR over a 15 MHz signal bandwidth. Fabricated in a 65 nm CMOS process, the core modulator occupies an area of only 0.16 mm 2 and dissipates 6.96 mW from a 1 V supply. A 58.6 fJ/conversion-step figure of merit is achieved.
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