The Rapidly Evolving Treatment Landscape of Metastatic Hormone-Sensitive Prostate Cancer.

The management of metastatic hormone-sensitive prostate cancer (mHSPC) or castration-sensitive prostate cancer (mCSPC) has become increasingly complex with the tremendous progress that has been made in this space within the past few decades. In the early days of androgen deprivation therapy (ADT), ADT monotherapy was the mainstay for treatment of advanced prostate cancer. However, novel hormone therapies in the form of androgen receptor pathway inhibitors (ARPI) have emerged; vaccine therapy, chemotherapy with docetaxel and cabazitaxel, and radioactive ligands have shaped the treatment of metastatic prostate cancer in the last decade. Following the initial approval of several drugs for use in metastatic castration-resistant prostate cancer (mCRPC) in combination with primary ADT, these agents were studied and subsequently approved for use in mCSPC. Therefore, ADT monotherapy no longer constitutes an optimal therapeutic option for otherwise fit patients who present with mCSPC. We focus on the treatment of first-line de novo mHSPC or mCSPC and explore frontline doublet and triplet therapy and the pivotal trials that led to their United States Food and Drug Administration approval.

Development of super-infective ternary vector systems for enhancing the Agrobacterium-mediated plant transformation and genome editing efficiency.

Agrobacterium-mediated transformation remains a cornerstone of plant biology, fueling advancements in molecular genetics, new genomic techniques (NGTs), and the biotech industry. However, recalcitrant crops and technical hurdles persist as bottlenecks. The goal was to develop super-infective ternary vector systems that integrate a novel salicylic acid-degrading enzyme, GABA, and ethylene-degrading enzymes, targeting the transformation of crops by neutralizing plant defense system on Agrobacterium. Firstly, both the effect and activity of introducing enzymes were validated in EHA105, an important Agrobacterium strain. Our study demonstrates that all ternary vector (Tv) system variants significantly enhance reporter expression in transient assays with Nicotiana benthamiana and Cannabis sativa. Specifically, incorporating a constitutive virG mutation with novel enzyme combinations increased GFP and RUBY expression in C. sativa by >5-fold and 13-fold, respectively. The Tv system, combined with a geminivirus replicon, markedly boosted GUS gene expression in tomato, enhancing genome editing efficiency. Notably, compared to controls, Tv-VS demonstrated up to 18-fold and 4.5-fold increases in genome editing efficiency in C. sativa and tomato, respectively. Additionally, stable transformation rates in tomato and Arabidopsis improved significantly, with Tv-VS showing a remarkable 2.5-fold increase in transformation efficiency compared to control strains. The research marks notable progress in Agrobacterium-mediated plant transformation. The innovative ternary vectors overcome plant defense mechanisms, enabling genetic manipulation in previously challenging plant species. This development is anticipated to broaden the applications of plant genetic engineering, contributing to advancements in crop genome editing.

Increased Scan Speed and Pitch on Ultra-Low-Dose Chest CT: Effect on Nodule Volumetry and Image Quality.

Background and Objectives: This study's objective was to investigate the influence of increased scan speed and pitch on image quality and nodule volumetry in patients who underwent ultra-low-dose chest computed tomography (CT). Material and Methods: One hundred and two patients who had lung nodules were included in this study. Standard-speed, standard-pitch (SSSP) ultra-low-dose CT and high-speed, high-pitch (HSHP) ultra-low-dose CT were obtained for all patients. Image noise was measured as the standard deviation of attenuation. One hundred and sixty-three nodules were identified and classified according to location, volume, and nodule type. Volume measurement of detected pulmonary nodules was compared according to nodule location, volume, and nodule type. Motion artifacts at the right middle lobe, the lingular segment, and both lower lobes near the lung bases were evaluated. Subjective image quality analysis was also performed. Results: The HSHP CT scan demonstrated decreased motion artifacts at the left upper lobe lingular segment and left lower lobe compared to the SSSP CT scan (p < 0.001). The image noise was higher and the radiation dose was lower in the HSHP scan (p < 0.001). According to the nodule type, the absolute relative volume difference was significantly higher in ground glass opacity nodules compared with those of part-solid and solid nodules (p < 0.001). Conclusion: Our study results suggest that HSHP ultra-low-dose chest CT scans provide decreased motion artifacts and lower radiation doses compared to SSSP ultra-low-dose chest CT. However, lung nodule volumetry should be performed with caution for ground glass opacity nodules.

Deep Learning-Based Reconstruction Algorithm With Lung Enhancement Filter for Chest CT: Effect on Image Quality and Ground Glass Nodule Sharpness.

OBJECTIVE: To assess the effect of a new lung enhancement filter combined with deep learning image reconstruction (DLIR) algorithm on image quality and ground-glass nodule (GGN) sharpness compared to hybrid iterative reconstruction or DLIR alone. MATERIALS AND METHODS: Five artificial spherical GGNs with various densities (-250, -350, -450, -550, and -630 Hounsfield units) and 10 mm in diameter were placed in a thorax anthropomorphic phantom. Four scans at four different radiation dose levels were performed using a 256-slice CT (Revolution Apex CT, GE Healthcare). Each scan was reconstructed using three different reconstruction algorithms: adaptive statistical iterative reconstruction-V at a level of 50% (AR50), Truefidelity (TF), which is a DLIR method, and TF with a lung enhancement filter (TF + Lu). Thus, 12 sets of reconstructed images were obtained and analyzed. Image noise, signal-to-noise ratio, and contrast-to-noise ratio were compared among the three reconstruction algorithms. Nodule sharpness was compared among the three reconstruction algorithms using the full-width at half-maximum value. Furthermore, subjective image quality analysis was performed. RESULTS: AR50 demonstrated the highest level of noise, which was decreased by using TF + Lu and TF alone (P = 0.001). TF + Lu significantly improved nodule sharpness at all radiation doses compared to TF alone (P = 0.001). The nodule sharpness of TF + Lu was similar to that of AR50. Using TF alone resulted in the lowest nodule sharpness. CONCLUSION: Adding a lung enhancement filter to DLIR (TF + Lu) significantly improved the nodule sharpness compared to DLIR alone (TF). TF + Lu can be an effective reconstruction technique to enhance image quality and GGN evaluation in ultralow-dose chest CT scans.

Fat Embolism Syndrome Mimicking Thrombotic Thrombocytopenic Purpura in a Patient With Hemoglobin S/Beta-Thalassemia.

Thrombotic microangiopathies cause ischemic organ damage and require urgent management for a favorable prognosis. Fat embolism syndrome from bone marrow necrosis is a rare and unique pathology that carries a high mortality rate. It can mimic thrombotic microangiopathies such as thrombotic thrombocytopenic purpura (TTP). Herein, we present a patient with sickle cell-beta-thalassemia who initially presented with a vaso-occlusive crisis, lab evidence of hemolysis, schistocytes and thrombocytopenia who developed acute encephalopathy with respiratory distress, consistent with TTP. She was found to have multiple infarcts in the brain. She was intubated and underwent plasma and red cell exchange. Bone marrow biopsy confirmed marrow necrosis from her vaso-occlusive crisis and subsequently, fat embolism syndrome. Here, we discuss the complex presentation and the complications of fat embolism from bone marrow necrosis and how it can mimic TTP.

Discovery and Characterization of Two Highly Divergent Variants of a Novel Potyvirus Species Infecting Madagascar Periwinkle (Catharanthus roseus).

During the summer of 2022, a cluster of Madagascar periwinkle plants with white and mauve flowers were observed with foliar mild yellow mosaic symptoms on a private property in Harlingen, Cameron County, Texas. The symptoms were reproduced on mechanically inoculated periwinkle and Nicotiana benthamiana plants. Virions of 776 to 849 nm in length and 11.7 to 14.8 nm in width were observed in transmission electron microscopy of leaf dip preparations made from symptomatic periwinkle leaves. High-throughput sequencing (HTS) analysis of total RNA extracts from symptomatic leaves revealed the occurrence of two highly divergent variants of a novel Potyvirus species as the only virus-like sequences present in the sample. The complete genomes of both variants were independently amplified via reverse transcriptase PCR, cloned, and Sanger sequenced. The 5' and 3' of the genomes were acquired using random amplification of cDNA ends methodology. The assembled virus genomes were 9,936 and 9,944 nucleotides (nt) long, and they shared 99.9 to 100% identities with the respective HTS-derived genomes. Each genome encoded hypothetical polyprotein of 3,171 amino acids (aa) (362.6 kilodaltons [kDa]) and 3,173 aa (362.7 kDa), respectively, and they shared 77.3/84.4% nt/aa polyprotein identities, indicating that they represent highly divergent variants of the same Potyvirus species. Both genomes also shared below-species-threshold polyprotein identity levels with the most closely phylogenetically related known potyviruses, thus indicating that they belong to a novel species. The name periwinkle mild yellow mosaic virus (PwMYMV) is given to the potyvirus with complete genomes of 9,936 nt for variant 1 (PwMYMV-1) and 9,944 nt for variant 2 (PwMYMV-2). We propose that PwMYMV be assigned into the genus Potyvirus (family Potyviridae).

Evaluating the effect of settlement services in South Korea: Focused on Korea Immigration & Integration Program.

To improve immigrants' integration, Korea Immigration & Integration Program (KIIP) has been delivered since 2009 in South Korea (hereafter Korea), yet little research has empirically estimated its net effect. Hence, the main aim of this study is to empirically and directly evaluate its net effect, using an Inverse-probability weighted analytical technique controlling selection bias that may distort its net effect. Utilizing the "Estimating social and economic effect of KIIP", published by the Ministry of Justice, Korea in 2017, this study selects immigrants including participants (n = 800) and nonparticipants (n = 214). The findings indicate that the effect of KIIP is dubious. Specifically, KIIP plays a role in raising the level of naturalization of immigrants, accepting Korean culture, and satisfying their lives. However, there are statistically non-significant differences in employment, monthly income, keeping home country's culture, social networks, Korean language skills, discrimination, and the sense of belonging to the Korean society between participants and nonparticipants. This shows both the effectiveness and ineffectiveness of KIIP. To find a way to improve integration, this study suggests strengthening advantages and offsetting disadvantages, in managing KIIP.

A processing-type active real-time traceable certification system.

In addition to substituting low-price and low-quality materials for high-quality materials at the food processing stage, many dishonest businesses risk adulterating chemical materials in products to reduce production costs or increase product flavor with chemical synthesis spices. As a result, the risks to food safety are increased. Most safety management and certification regulations proceed with on-site examination or sampling inspection. As current certification systems lack complete tracking and real-time certification processes, they cannot comprehensively check foods' processing and production processes and contents. Hence, food safety problems sway consumers' trust and confidence in certification systems. This study intends to improve the agricultural processing end's current food traceability certification system. Adding the design of raw material total quantity control provides a complete and sound real-time certification mechanism for citizens and businesses to assure consumer rights.

Sustained drug release behavior of captopril-incorporated chitosan/carboxymethyl cellulose biomaterials for antihypertensive therapy.

Captopril (CTP) is an oral drug widely used to treat high blood pressure and congestive heart failure. In this study, CTP-incorporated biomaterials for antihypertensive therapy were synthesized from chitosan, carboxymethyl cellulose, and plasticizers. The physicochemical properties of the prepared biomaterials were characterized using FE-SEM, FT-IR analysis, and physical properties. CTP release experiments were carried out in buffer solutions at various pH values and temperatures. Results indicated that above 99.0 % of CTP was released within 180 min. Optimization of the experimental conditions for CTP release was analyzed by using response surface methodology (RSM). Results of CTP release through artificial skin indicated that CTP was continuously released above 95.0 % from the prepared biomaterials for 36.0 h. The CTP release mechanisms into a buffer and through artificial skin followed pseudo-Fickian diffusion mechanism and non-Fickian diffusion mechanisms, respectively. Moreover, angiotensin-converting enzyme (ACE) inhibition (related to cardiovascular disease) via the released CTP clearly reveals that the prepared biomaterials have a high potential as a transdermal drug delivery agent in antihypertensive therapy.

On dosimetric characteristics of detectors for relative dosimetry in small fields: a multicenter experimental study.

Objective. In this multicentric collaborative study, we aimed to verify whether the selected radiation detectors satisfy the requirements of TRS-483 Code of Practice for relative small field dosimetry in megavoltage photon beams used in radiotherapy, by investigating four dosimetric characteristics. Furthermore, we intended to analyze and complement the recommendations given in TRS-483.Approach. Short-term stability, dose linearity, dose-rate dependence, and leakage were determined for 17 models of detectors considered suitable for small field dosimetry. Altogether, 47 detectors were used in this study across ten institutions. Photon beams with 6 and 10 MV, with and without flattening filters, generated by Elekta Versa HDTMor Varian TrueBeamTMlinear accelerators, were used.Main results. The tolerance level of 0.1% for stability was fulfilled by 70% of the data points. For the determination of dose linearity, two methods were considered. Results from the use of a stricter method show that the guideline of 0.1% for dose linearity is not attainable for most of the detectors used in the study. Following the second approach (squared Pearson's correlation coefficientr2), it was found that 100% of the data fulfill the criteriar2> 0.999 (0.1% guideline for tolerance). Less than 50% of all data points satisfied the published tolerance of 0.1% for dose-rate dependence. Almost all data points (98.2%) satisfied the 0.1% criterion for leakage.Significance. For short-term stability (repeatability), it was found that the 0.1% guideline could not be met. Therefore, a less rigorous criterion of 0.25% is proposed. For dose linearity, our recommendation is to adopt a simple and clear methodology and to define an achievable tolerance based on the experimental data. For dose-rate dependence, a realistic criterion of 1% is proposed instead of the present 0.1%. Agreement was found with published guidelines for background signal (leakage).

Mechanistic Insights on Localized to Metastatic Prostate Cancer Transition and Therapeutic Opportunities.

Prostate cancer is the most common non-cutaneous cancer among American men. Multiple mechanisms are involved in tumorigenesis and progression to metastases. While androgen deprivation therapy remains the cornerstone of treatment, progression to castration-resistant disease becomes inevitable. Aberrant pathway activations of PI3K/AKT due to PTEN loss, epithelial-mesenchymal transition pathways, homologous recombination repair, and DNA repair pathway mechanisms of resistance and cross-talk lead to opportunities for therapeutic targeting in metastatic castration-resistant prostate cancer. This review focuses on mechanisms of progression and key trials that evaluate the drugs and combinations that exploit these pathways.

Online Adaptive MRI-Guided Stereotactic Body Radiotherapy for Pancreatic and Other Intra-Abdominal Cancers.

A 1.5T MRI combined with a linear accelerator (Unity®, Elekta; Stockholm, Sweden) is a device that shows promise in MRI-guided stereotactic body radiation treatment (SBRT). Previous studies utilized the manufacturer's pre-set MRI sequences (i.e., T2 Weighted (T2W)), which limited the visualization of pancreatic and intra-abdominal tumors and organs at risk (OAR). Here, a T1 Weighted (T1W) sequence was utilized to improve the visualization of tumors and OAR for online adapted-to-position (ATP) and adapted-to-shape (ATS) during MRI-guided SBRT. Twenty-six patients, 19 with pancreatic and 7 with intra-abdominal cancers, underwent CT and MRI simulations for SBRT planning before being treated with multi-fractionated MRI-guided SBRT. The boundary of tumors and OAR was more clearly seen on T1W image sets, resulting in fast and accurate contouring during online ATP/ATS planning. Plan quality in 26 patients was dependent on OAR proximity to the target tumor and achieved 96 ± 5% and 92 ± 9% in gross tumor volume D90% and planning target volume D90%. We utilized T1W imaging (about 120 s) to shorten imaging time by 67% compared to T2W imaging (about 360 s) and improve tumor visualization, minimizing target/OAR delineation uncertainty and the treatment margin for sparing OAR. The average time-consumption of MRI-guided SBRT for the first 21 patients was 55 ± 15 min for ATP and 79 ± 20 min for ATS.

Manipulating the nonlinearity of transition-metal dichalcogenide polaritons.

The lithographically designed potential wells in monolayer WS2 microcavities are utilized to manipulate nonlinear transition-metal dichalcogenide polaritons and enhance the polariton-reservoir interaction strength.

Roles of Protein Post-Translational Modifications During Adipocyte Senescence.

Adipocytes are adipose tissues that supply energy to the body through lipids. The two main types of adipocytes comprise white adipocytes (WAT) that store energy, and brown adipocytes (BAT), which generate heat by burning stored fat (thermogenesis). Emerging evidence indicates that dysregulated adipocyte senescence may disrupt metabolic homeostasis, leading to various diseases and aging. Adipocytes undergo senescence via irreversible cell-cycle arrest in response to DNA damage, oxidative stress, telomere dysfunction, or adipocyte over-expansion upon chronic lipid accumulation. The amount of detectable BAT decreases with age. Activation of cell cycle regulators and dysregulation of adipogenesis-regulating factors may constitute a molecular mechanism that accelerates adipocyte senescence. To better understand the regulation of adipocyte senescence, the effects of post-translational modifications (PTMs), is essential for clarifying the activity and stability of these proteins. PTMs are covalent enzymatic protein modifications introduced following protein biosynthesis, such as phosphorylation, acetylation, ubiquitination, or glycosylation. Determining the contribution of PTMs to adipocyte senescence may identify new therapeutic targets for the regulation of adipocyte senescence. In this review, we discuss a conceptual case in which PTMs regulate adipocyte senescence and explain the mechanisms underlying protein regulation, which may lead to the development of effective strategies to combat metabolic diseases.

Role of human dural fibroblasts in the angiogenic responses of human endothelial cells: An in vitro dural model and the application of lab-on-a-chip for EDAS.

Encephaloduroarteriosynangiosis (EDAS), an indirect anastomosis procedure, is widely accepted as a primary treatment for moyamoya disease (MMD) to improve collateral blood flow. During surgical intervention, dural fibroblasts (DuF) are thought to produce various proteins that create an angiogenic microenvironment. However, the biophysiological evidence supporting the angiogenic properties of this surgical technique has not been thoroughly elucidated. The purpose of these studies was to determine whether DuF releases pro-angiogenic factors and chemokines and promotes angiogenic properties in human endothelial cells (ECs) under IL-1ß-mediated wound conditions, which are expected to occur during the process of neo-vascularization within the dura mater. Furthermore, a microfluidic chemotaxis platform was implemented to investigate the angiogenic activity of ECs in response to a reconstituted dura model. Transcriptome sequencing revealed that IL-1ß stimulation on DuF induced a significant upregulation of various pro-angiogenic genes, including IL-6, IL-8, CCL-2, CCL-5, SMOC-1, and SCG-2 (p < 0.05). Moreover, compared to ECs cultured in naïve media or naïve DuF media, those exposed to IL-1ß-DuF conditioned media expressed higher mRNA and protein levels of these pro-angiogenic factors (p < 0.001). ECs co-cultured with IL-1ß-DuF also exhibited considerable migration on the microfluidic chemotaxis platform. Furthermore, the chemotactic effects on the ECs were reduced upon neutralization of IL-8 or inhibition of NF-κB signaling. Our findings demonstrate that IL-1ß-DuFs release factors that activate and enhance the angiogenic properties of ECs. These results suggest a potential interaction between DuF and ECs following EDAS for MMD, and these components could be targeted for the development of therapeutic biomarkers.

The myosin and RhoGAP MYO9B influences osteocyte dendrite growth and responses to mechanical stimuli.

Introduction: Myosin IXB (MYO9B) is an unconventional myosin with RhoGAP activity and thus is a regulator of actin cytoskeletal organization. MYO9B was previously shown to be necessary for skeletal growth and health and to play a role in actin-based functions of both osteoblasts and osteoclasts. However, its role in responses to mechanical stimulation of bone cells has not yet been described. Therefore, experiments were undertaken to determine the role of MYO9B in bone cell responses to mechanical stress both in vitro and in vivo. Methods: MYO9B expression was knocked down in osteoblast and osteocyte cell lines using RNA interference and the resulting cells were subjected to mechanical stresses including cyclic tensile strain, fluid shear stress, and plating on different substrates (no substrate vs. monomeric or polymerized collagen type I). Osteocytic cells were also subjected to MYO9B regulation through Slit-Robo signaling. Further, wild-type or Myo9b -/- mice were subjected to a regimen of whole-body vibration (WBV) and changes in bone quality were assessed by micro-CT. Results: Unlike control cells, MYO9B-deficient osteoblastic cells subjected to uniaxial cyclic tensile strain were unable to orient their actin stress fibers perpendicular to the strain. Osteocytic cells in which MYO9B was knocked down exhibited elongated dendrites but were unable to respond normally to treatments that increase dendrite length such as fluid shear stress and Slit-Robo signaling. Osteocytic responses to mechanical stimuli were also found to be dependent on the polymerization state of collagen type I substrates. Wild-type mice responded to WBV with increased bone tissue mineral density values while Myo9b -/- mice responded with bone loss. Discussion: These results demonstrate that MYO9B plays a key role in mechanical stress-induced responses of bone cells in vitro and in vivo.

Ablation of the deubiquitinase USP15 ameliorates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) occurs due to the accumulation of fat in the liver, leading to fatal liver diseases such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Elucidation of the molecular mechanisms underlying NAFLD is critical for its prevention and therapy. Here, we observed that deubiquitinase USP15 expression was upregulated in the livers of mice fed a high-fat diet (HFD) and liver biopsies of patients with NAFLD or NASH. USP15 interacts with lipid-accumulating proteins such as FABPs and perilipins to reduce ubiquitination and increase their protein stability. Furthermore, the severity of NAFLD induced by an HFD and NASH induced by a fructose/palmitate/cholesterol/trans-fat (FPC) diet was significantly ameliorated in hepatocyte-specific USP15 knockout mice. Thus, our findings reveal an unrecognized function of USP15 in the lipid accumulation of livers, which exacerbates NAFLD to NASH by overriding nutrients and inducing inflammation. Therefore, targeting USP15 can be used in the prevention and treatment of NAFLD and NASH.

Effects of Uncertainty, Appraisal of Uncertainty, and Self-Efficacy on the Quality of Life of Elderly Patients with Lung Cancer Receiving Chemotherapy: Based on Mishel's Theory of Uncertainty.

Background and Objectives: The purpose of this study is to enhance the quality of life in elderly patients with lung cancer by understanding relations of uncertainty, appraisal of uncertainty, self-efficacy, and quality of life targeting elderly patients with lung cancer receiving anticancer therapy, and also analyzing the factors affecting the quality of life based on Mishel's theory. Materials and Methods: The subjects were a total of 112 lung cancer patients aged 65 or older receiving anticancer therapy. The data was collected by using self-report questionnaires targeting patients in hemato-oncology at Chungbuk National University Hospital. The data were analyzed using descriptive statistics, a t-test, an analysis of variance, Pearson's correlational coefficients, and hierarchical regression analysis. Results: In stage 1, anticancer therapy (chemotherapy) (ß = -0.34, p < 0.001), economic condition (low) (ß = -0.30, p < 0.001), the number of anticancer therapies (three times or more) (ß = -0.29, p < 0.001), and education (graduation from high school or higher) (ß = 0.18, p = 0.033) were influencing factors (F = 0.52, p < 0.001). In stage 2, self-efficacy (ß = 0.41, p < 0.001), appraisal of uncertainty: danger (ß = -0.29, p < 0.001), appraisal of uncertainty: opportunity (ß = 0.18, p = 0.018), the number of anticancer therapies (three times or more) (ß = -0.17, p = 0.006), and anticancer therapy (chemotherapy) (ß = -0.14, p = 0.031) were influencing factors, which showed 74.2% explanatory power (F = 26.17, p < 0.001). Conclusions: In order to improve the quality of life of subjects, it would be necessary to develop interventions for raising their self-efficacy by considering their degree of education, economic condition, the types and numbers of anticancer therapies, and understanding of the appraisal of uncertainty about the disease is assessed as an opportunity factor or a danger factor.

Nanograin network memory with reconfigurable percolation paths for synaptic interactions.

The development of memory devices with functions that simultaneously process and store data is required for efficient computation. To achieve this, artificial synaptic devices have been proposed because they can construct hybrid networks with biological neurons and perform neuromorphic computation. However, irreversible aging of these electrical devices causes unavoidable performance degradation. Although several photonic approaches to controlling currents have been suggested, suppression of current levels and switching of analog conductance in a simple photonic manner remain challenging. Here, we demonstrated a nanograin network memory using reconfigurable percolation paths in a single Si nanowire with solid core/porous shell and pure solid core segments. The electrical and photonic control of current percolation paths enabled the analog and reversible adjustment of the persistent current level, exhibiting memory behavior and current suppression in this single nanowire device. In addition, the synaptic behaviors of memory and erasure were demonstrated through potentiation and habituation processes. Photonic habituation was achieved using laser illumination on the porous nanowire shell, with a linear decrease in the postsynaptic current. Furthermore, synaptic elimination was emulated using two adjacent devices interconnected on a single nanowire. Therefore, electrical and photonic reconfiguration of the conductive paths in Si nanograin networks will pave the way for next-generation nanodevice technologies.

Intervertebral disc organ-on-a-chip: an innovative model to study monocyte extravasation during nucleus pulposus degeneration.

Degenerative cascades of the intervertebral disc (IVD) are characterized by the presence of immune cells like monocytes, macrophages, and leukocytes, which contribute to inflammation. Previous in vitro studies on monocyte chemotaxis in the presence of chemical or mechanical stimulation were unable to establish the effects of endogenous stimulating factors from resident IVD cells, or fully understand macrophage and monocyte differentiation pathways in IVD degeneration. Our study simulates monocyte extravasation using a fabricated microfluidic chemotaxis IVD organ-on-a-chip (IVD organ chip), which models the geometry of IVD, chemoattractant diffusion, and infiltration of immune cells. Additionally, the fabricated IVD organ chip mimics stepwise monocyte infiltration and differentiation into macrophages in the degenerative nucleus pulposus (NP) induced by IL-1ß. We find that naïve NP cells do not recruit THP-1 monocyte-like cells, but degenerative NP cells recruit and accumulate macrophages through chemo-gradient channels. Furthermore, the differentiated and migrated THP-1 cells show phagocytic activity around inflammatory NP cells. Our in vitro model of monocyte chemotaxis with degenerative NP on an IVD organ chip depicts the sequential processes of monocyte migration/infiltration, monocyte-to-macrophage differentiation, and accumulation. Using this platform to gain a deeper understanding of monocyte infiltration and differentiation processes can provide insights into the pathophysiology of the immune response in degenerative IVD.