Highly Selective and Reversible Detection of Simulated Breath Hydrogen Sulfide Using Fe-Doped CuO Hollow Spheres: Enhanced Surface Redox Reaction by Multi-Valent Catalysts.

The precise and reversible detection of hydrogen sulfide (H2 S) at high humidity condition, a malodorous and harmful volatile sulfur compound, is essential for the self-assessment of oral diseases, halitosis, and asthma. However, the selective and reversible detection of trace concentrations of H2 S (≈0.1 ppm) in high humidity conditions (exhaled breath) is challenging because of irreversible H2 S adsorption/desorption at the surface of chemiresistors. The study reports the synthesis of Fe-doped CuO hollow spheres as H2 S gas-sensing materials via spray pyrolysis. 4 at.% of Fe-doped CuO hollow spheres exhibit high selectivity (response ratio ≥ 34.4) over interference gas (ethanol, 1 ppm) and reversible sensing characteristics (100% recovery) to 0.1 ppm of H2 S under high humidity (relative humidity 80%) at 175 °C. The effect of multi-valent transition metal ion doping into CuO on sensor reversibility is confirmed through the enhancement of recovery kinetics by doping 4 at.% of Ti- or Nb ions into CuO sensors. Mechanistic details of these excellent H2 S sensing characteristics are also investigated by analyzing the redox reactions and the catalytic activity change of the Fe-doped CuO sensing materials. The selective and reversible detection of H2 S using the Fe-doped CuO sensor suggested in this work opens a new possibility for halitosis self-monitoring.

Highly Sensitive and Wide-Range Detection of Thiabendazole via Surface-Enhanced Raman Scattering Using Bimetallic Nanoparticle-Functionalized Nanopillars.

Thiabendazole (TBZ) is a benzimidazole; owing to its potent antimicrobial properties, TBZ is extensively employed in agriculture as a fungicide and pesticide. However, TBZ poses environmental risks, and excessive exposure to TBZ through various leakage pathways can cause adverse effects in humans. Therefore, a method must be developed for early and sensitive detection of TBZ over a range of concentrations, considering both human and environmental perspectives. In this study, we used silver nanopillar structures (SNPis) and Au@Ag bimetallic nanoparticles (BNPs) to fabricate a BNP@SNPi substrate. This substrate exhibited a broad reaction surface with significantly enhanced surface-enhanced Raman scattering hotspots, demonstrating excellent Raman performance, along with high reproducibility, sensitivity, and selectivity for TBZ detection. Ultimately, the BNP@SNPi substrate successfully detected TBZ across a wide concentration range in samples of tap water, drinking water, juice, and human serum, with respective limits of detection of 146.5, 245.5, 195.6, and 219.4 pM. This study highlights BNP@SNPi as a promising sensor platform for TBZ detection in diverse environments and contributes to environmental monitoring and bioanalytical studies.

Biomarkers in allergen immunotherapy: Focus on eosinophilic inflammation.

Asthma and allergic rhinitis (AR) are 2 of the most common chronic inflammatory disorders and they appear to be on the rise. Current pharmacotherapy effectively controls symptoms but does not alter the underlying pathophysiology. Allergen immunotherapy (AIT) is an evidence-based therapy for asthma and AR and has been recognized as the only therapeutic method that actually modifies the allergic disease process. There is a lack of objective markers that accurately and reliably reflect the therapeutic benefits of AIT. A biomarker indicating patients that would benefit most from AIT would be invaluable. Eosinophilic inflammation is a cardinal feature of many allergic diseases. Biomarkers that accurately reflect this inflammation are needed to better diagnose, treat, and monitor patients with allergic disorders. This review examines the current literature regarding AIT's effects on eosinophilic inflammation and biomarkers that may be used to determine the extent of these effects.

Risk factors of adjacent-segment disease after short-segment fusion in patients with de novo degenerative lumbar scoliosis.

OBJECTIVE: Short-segment fusion (SSF) is an effective surgical option for appropriately selected patients with de novo degenerative lumbar scoliosis (DNDLS). Considering that DNDLS is frequently accompanied by multisegment degeneration and potential instability across the entire lumbar segments, it is inevitable that unhealthy segments remain after SSF, thereby increasing the potential risk of adjacent-segment disease (ASD) occurrence. Therefore, the authors aimed to identify the risk factors for ASD in patients with DNDLS who underwent SSF. METHODS: This retrospective study included 80 patients with DNDLS (Cobb angle > 10°) who underwent SSF (1 or 2 levels) between December 2010 and July 2018 with a minimum follow-up duration of 5 years. The participants were divided into two groups: ASD and non-ASD. ASD was defined as clinical ASD rather than radiographic ASD. Various patient and operative variables were compared between the groups. Global and regional radiographic parameters (preoperatively and postoperatively) were also compared between the two groups using plain radiography and MRI. Consequently, univariate and multivariate analyses were conducted to identify the risk factors for ASD occurrence. The receiver operating characteristic (ROC) curve was used to calculate the cutoff values. RESULTS: The mean ± SD age was 67.7 ± 7.2 years at the time of SSF, and there were 62 women (77.5%) enrolled in the study. Thirty patients (37.5%) were in the ASD group and 50 patients (62.5%) were in the non-ASD group. The mean time from the surgery to ASD diagnosis was 34.9 ± 28.2 months in ASD group. Thirteen patients required revision surgery at a mean time of 8.8 ± 7.0 months after ASD occurrence. Multivariate logistic regression analysis demonstrated that preoperative disc wedging angle (OR 1.806, 95% CI 1.255-2.598, p = 0.001), presence of facet tropism (defined as ≥ 10° difference between the facet joint angles of the right and left sides) (OR 5.534, 95% CI 1.528-20.040, p = 0.009), and foraminal stenosis ≥ grade 2 (OR 5.935, 95% CI 1.253-28.117, p = 0.025) were significant risk factors for ASD development. The cutoff value of the preoperative disc wedging angle was calculated to be 2.5° using the ROC curve. CONCLUSIONS: Preoperative disc wedging angle ≥ 2.5°, presence of facet tropism, and foraminal stenosis ≥ grade 2 were identified as significant risk factors for ASD development after SSF in patients with DNDLS.

Enhanced selective discrimination of point-mutated viral RNA through false amplification regulatory direct insertion in rolling circle amplification.

Coronaviruses are single-stranded RNA viruses with high mutation rates. Although a diagnostic method for coronaviruses has been developed, variants appear rapidly. Low test accuracy owing to single-point mutations is one of the main factors in the failure to prevent the early spread of coronavirus infection. Although reverse transcription-quantitative polymerase chain reaction can detect coronavirus infection, it cannot exclude the possibility of false positives, and an additional multiplexing kit is needed to discriminate single nucleotide polymorphism (SNP) variants. Therefore, in this study, we introduced a new nucleic acid amplification method to determine whether an infected person has a SNP mutation using a lateral flow assay (LFA) as a point-of-care test. Unlike traditional DNA amplification methods, direct insertion into rolling circle amplification amplifies the target genes without false amplification. After SNP-selective nucleic acid amplification, nuclease enzymes are used to make double-stranded DNA fragments that the LFA can detect, where specific mismatched DNA is found and cleaved to show different signals when a SNP-type is present. Therefore, wild- and SNP-type variants can be selectively detected. In this study, the limit of detection was 400 aM for viral RNA, and we successfully identified a dominant SNP variant selectively. Clinical tests were also conducted.

Efficacy of leuprorelin in spinal and bulbar muscular atrophy: a 3-year observational study.

OBJECTIVE: This study aimed to investigate the long-term effects and functional outcomes of androgen suppression therapy using leuprorelin among Korean patients with spinal and bulbar muscular atrophy (SBMA). METHODS: This observational study enrolled patients with genetically confirmed SBMA who provided informed consent. Leuprorelin was administered via subcutaneous injection every 12 weeks. The primary outcome measure was the change in total Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) scores. RESULTS: A total of 48 SBMA patients were evaluated in this study. Among them, 39 patients underwent androgen suppression therapy over a 3-year period. The total SBMAFRS score decreased from 41.72 ± 5.55 to 36.74 ± 7.74 (p < 0.001) in patients who completed their treatment. The subgroup with a baseline SBMAFRS score of ≥ 42 had a significantly lower decline in SBMAFRS score than did those with a baseline SBMAFRS score of ≤ 41. We determined that at a baseline, SBMAFRS cutoff value of 41.5 could predict good prognosis, with a corresponding area under the curve of 0.689. CONCLUSION: Despite androgen suppression therapy, all enrolled participants exhibited a decrease in the overall SBMAFRS score. However, those with a baseline SBMAFRS of ≥ 42 showed a mild decrease in scores, indicating a more favorable prognosis. These findings suggest that a higher baseline motor function was a key prognostic indicator in SBMA treatment and that initiating early leuprorelin treatment in patients with high baseline function may lead to good clinical outcomes.

Identification and characterization of novel ERBB4 variant associated with sporadic amyotrophic lateral sclerosis (ALS).

Amyotrophic Lateral Sclerosis (ALS) is the most common type of motor neuron disease characterized by progressive motor neuron degeneration in brain and spinal cord. Most cases are sporadic in ALS and 5-10% of cases are familiar. >50 genes are known to be associated with ALS and one of them is ERBB4. In this paper, we report the case of a 53-year-old ALS patient with progressive muscle weakness and fasciculation, but he had no cognitive decline. We performed the next generation sequencing (NGS) and in silico analysis, it predicted a highly pathogenic variant, c.2116 A > G, p.Asn706Asp (N706D) in the ERBB4 gene. The amino acid residue is highly conserved among species. ERBB4 is a member of the ERBB family of receptor tyrosine kinases. ERBB4 has multiple tyrosine phosphorylation sites, including an autophosphorylation site at tyrosine 1284 residue. Autophosphorylation of ERBB4 promotes biological activity and it associated with NRG-1/ERBB4 pathway. It is already known that tyrosine 128 phosphorylation of ERBB4 is decreased in patients who have ALS-associated ERBB4 mutations. We generated ERBB4 N706D construct using site-directed mutagenesis and checked the phosphorylation level of ERBB4 N706D in NSC-34 cells. We found that the phosphorylation of ERBB4 N706D was decreased compared to ERBB4 wild-type, indicating a loss of function mutation in ERBB4. We report a novel variant in ERBB4 gene leading to ALS through dysfunction of ERBB4.

Whole-Body Muscle Magnetic Resonance Imaging in 81 Patients with Spinal and Bulbar Muscular Atrophy: A Prospective Study.

OBJECTIVE: Spinal and bulbar muscular atrophy (SBMA) is characterized by slow, progressive bulbar and limb muscle weakness; however, the pattern of progression of muscle fat infiltration remains unclear. We assessed the progression of muscle involvement in 81 patients with SBMA using whole-body muscle magnetic resonance imaging (MRI), alongside clinical and laboratory findings. METHODS: This prospective study included patients with genetically confirmed SBMA who underwent whole-body muscle MRI. We analyzed muscle fat infiltration and the pattern of involved muscles using cluster analysis, visualizing the sequential progression of fat infiltration. Muscle clusters demonstrated correlation with clinical scales and laboratory findings. Additionally, linear regression analysis was performed to identify the MRI section most strongly associated with 6-minute walk test (6MWT). RESULTS: We included 81 patients with SBMA (age = 54.3 years). After categorizing the patients into 6 clusters based on the pattern of muscle fat infiltration, we observed that muscle involvement began in the posterior calf and progressed to the posterior thigh, pelvis, trunk, anterior thigh, medial thigh, anterior calf, and upper extremity muscles. These muscle clusters correlated significantly with disease duration (τ = 0.47, p < 0.001), 6MWT (τ = -0.49, p < 0.001), and serum creatinine level (τ = -0.46, p < 0.001). The whole-body MRI indicated the thigh as the section most significantly correlated with 6MWT. INTERPRETATION: We used whole-body muscle MRI to determine the sequential progression of the fat infiltration in SBMA. Our findings may enable the identification of objective and reliable imaging outcome measures in the study of the natural history or future clinical trials of SBMA. ANN NEUROL 2024;95:596-606.

Predictor of Postoperative Ambulatory Recovery in Metastatic Spinal Cord Compression with Delayed Surgical Timing and Progressive Paraplegia.

OBJECTIVE: To analyze preoperative predictors of ambulatory recovery after surgical treatment in metastatic spinal cord compression (MSCC) patients with delayed surgical timing and progressive paraplegia. METHODS: We reviewed patients with a preoperative lower-extremity motor grade of ≤3 and surgical timing ≥48 hours after the nonambulatory status. The recovery group (group R) and nonrecovery group (group NR) were classified according to ambulation assessment during follow-up. The data on patient demographics, origin of the primary tumor, pre and postoperative chemotherapy and radiation therapy, surgical procedures, Tokuhashi score, Karnofsky score, preoperative lower-extremity motor grade, and surgical timing were collected for analyzing predictors of postoperative ambulatory recovery. RESULTS: Of the 55 patients, 24 (43.6%) were group R and 31 patients were group NR. The preoperative motor grade of the lower extremities was the only predictive factor (P < 0.05). The mean hip flexor and knee extensor motor grades in group R were 2.0 ± 1.0 and 2.4 ± 1.1 respectively, while in group NR, they were 1.2 ± 1.0 and 1.3 ± 1.0. The odds ratios for failing to regain ambulatory ability were 12.6 in the knee extensor and 4.8 in the hip flexor when the motor grades 0-2 and 3 groups were compared. The rescue ratio of the preoperative hip flexor and knee extensor motor grade 0-2 group were 34.1% and 21.2%, grades 3 group were 71.4% and 77.3%, respectively. CONCLUSIONS: The significant predictive factor for ambulatory recovery was the preoperative lower-extremity motor grade. The preoperative knee extensor motor grade was identified as a more important factor than hip flexor motor grade in predicting ambulatory recovery.

Clinical Significance of Lordosis Orientation on Proximal Junctional Kyphosis Development in Long-Segment Fusion Surgery for Adult Spinal Deformity.

OBJECTIVE: We sought to evaluate the clinical impact of lordosis orientation (LO) on proximal junctional kyphosis (PJK) development in adult spinal deformity surgery. METHODS: This study included 152 patients who underwent low thoracic (T9-T12) to pelvis fusion and were followed up for ≥2 years. In the literature, 6 radiographic parameters representing LO were introduced, such as uppermost instrumented vertebra (UIV) slope, UIV inclination, UIV-femoral angle (UIVFA), thoracolumbar tilt, thoracolumbar slope, and lordosis tilt. Various clinical and radiographic factors including 6 LO parameters were investigated using logistic regression analysis to identify risk factors for PJK. RESULTS: The mean age was 69.4 years, and 136 patients were females (89.5%). PJK developed in 65 patients (42.8%). Multivariate logistic regression analysis revealed that only small postoperative pelvic incidence (PI)-lumbar lordosis (LL) (odds ratio [OR] = 0.962, 95% confidence interval: 0.929-0.996, P = 0.030) and large UIVFA (OR = 1.089, 95% confidence interval: 1.028-1.154, P = 0.004) were significant for PJK development. UIVFA showed significantly positive correlation with pelvic tilt (CC = 0.509), thoracic kyphosis (CC = 0.384), and lordosis distribution index (CC = 0.223). UIVFA was also negatively correlated with sagittal vertical axis (CC = -0.371). However, UIVFA did not correlate with LL, PI-LL, or T1 pelvic angle. CONCLUSIONS: LO significantly increases the risk of PJK development in ASD surgery. Multivariate analysis revealed that smaller postoperative PI-LL and greater UIVFA were significant risk factors for PJK. Surgeons should avoid undercorrection and overcorrection to prevent PJK development.

Neurofilament light chain as a biomarker in neuromyelitis optica spectrum disorder: a comprehensive review and integrated analysis with glial fibrillary acidic protein.

BACKGROUND: In the context of neuromyelitis optica spectrum disorder (NMOSD), there are several measures that serve as a biomarker. However, each of the methods has the intrinsic limitations. While neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have emerged as an additional biomarker for NMOSD, a thorough investigation of their role remains incomplete. Our aim is to provide a comprehensive review of the current literature regarding NfL and GFAP as a biomarker and explore their potential utility in NMOSD. METHODS: We performed a comprehensive search using PubMed and Google Scholar to identify peer-reviewed articles investigating NfL and GFAP as a biomarker in NMOSD. RESULTS: Our search identified 13 relevant studies. NfL consistently showed promise in distinguishing NMOSD patients from healthy individuals, although it had limited specificity in distinguishing NMOSD from other demyelinating diseases. NfL offered certain advantages over GFAP, notably its ability to predict disability worsening during attacks. In contrast, GFAP provided valuable insight, particularly in distinguishing NMOSD from multiple sclerosis and identifying clinical relapses. In addition, GFAP showed predictive potential for future attacks. Some studies even suggested that NfL may serve as an indicator of treatment response in NMOSD. CONCLUSIONS: NfL and GFAP hold promise as biomarkers for NMOSD, demonstrating their usefulness in distinguishing patients from healthy individuals, assessing disease severity, and possibly reflecting treatment response. However, it is important to recognize that NfL and GFAP may, at some point, have different roles.

Proximal Junctional Failure after Corrective Surgery: Focusing on Elderly Patients with Severe Sagittal Imbalance.

Background: Previous reports with proximal junctional failure (PJF) included relatively young patients or deformity without sagittal imbalance. The present study focused on the two well-known risk factors for PJF, old age and severe sagittal imbalance. With these high-risk patients, the present study aimed to identify a strategy that could prevent PJF and to investigate whether the degree of correction would really affect the PJF occurrence. Methods: Patients who were ≥ 60 years of age and underwent long fusion (≥ 4) to the sacrum for severe sagittal imbalance (defined as pelvic incidence minus lumbar lordosis [PI-LL] ≥ 30°) were included. PJF was defined as a vertebral fracture at the uppermost instrumented vertebra (UIV) or UIV+1, failure of UIV fixation, myelopathy, or any need for proximal extension of fusion. Presumed risk factors were compared between the patients with and without PJF. Results: Total 146 patients (mean age, 68.4 years) with preoperative mean PI-LL of 46.8° were included. PJF developed in 39 patients (26.7%) at a mean of 18.1 months after surgery. Multivariate analysis showed that osteoporosis (odds ratio [OR], 2.812; p = 0.019) and UIV located below T10 (OR, 3.773; p = 0.010) were significant risk factors for developing PJF. However, the degree of correction did not affect PJF occurrence. Conclusions: The present study indicates that osteoporosis should be well corrected preoperatively and extending the fusion above T10 should be considered for severe imbalance in old patients. However, the amount of correction was not associated with PJF development.

Metallothionein Family Proteins as Regulators of Zinc Ions Synergistically Enhance the Anticancer Effect of Cannabidiol in Human Colorectal Cancer Cells.

Cannabidiol (CBD) is a chemical obtained from Cannabis sativa; it has therapeutic effects on anxiety and cognition and anti-inflammatory properties. Although pharmacological applications of CBD in many types of tumors have recently been reported, the mechanism of action of CBD is not yet fully understood. In this study, we perform an mRNA-seq analysis to identify the target genes of CBD after determining the cytotoxic concentrations of CBD using an MTT assay. CBD treatment regulated the expression of genes related to DNA repair and cell division, with metallothionein (MT) family genes being identified as having highly increased expression levels induced by CBD. It was also found that the expression levels of MT family genes were decreased in colorectal cancer tissues compared to those in normal tissues, indicating that the downregulation of MT family genes might be highly associated with colorectal tumor progression. A qPCR experiment revealed that the expression levels of MT family genes were increased by CBD. Moreover, MT family genes were regulated by CBD or crude extract but not by other cannabinoids, suggesting that the expression of MT family genes was specifically induced by CBD. A synergistic effect between CBD and MT gene transfection or zinc ion treatment was found. In conclusion, MT family genes as novel target genes could synergistically increase the anticancer activity of CBD by regulating the zinc ions in human colorectal cancer cells.

EBP50 is a key molecule for the Schwann cell-axon interaction in peripheral nerves.

Peripheral nerve injury disrupts the Schwann cell-axon interaction and the cellular communication between them. The peripheral nervous system has immense potential for regeneration extensively due to the innate plastic potential of Schwann cells (SCs) that allows SCs to interact with the injured axons and exert specific repair functions essential for peripheral nerve regeneration. In this study, we show that EBP50 is essential for the repair function of SCs and regeneration following nerve injury. The increased expression of EBP50 in the injured sciatic nerve of control mice suggested a significant role in regeneration. The ablation of EBP50 in mice resulted in delayed nerve repair, recovery of behavioral function, and remyelination following nerve injury. EBP50 deficiency led to deficits in SC functions, including proliferation, migration, cytoskeleton dynamics, and axon interactions. The adeno-associated virus (AAV)-mediated local expression of EBP50 improved SCs migration, functional recovery, and remyelination. ErbB2-related proteins were not differentially expressed in EBP50-deficient sciatic nerves following injury. EBP50 binds and stabilizes ErbB2 and activates the repair functions to promote regeneration. Thus, we identified EBP50 as a potent SC protein that can enhance the regeneration and functional recovery driven by NRG1-ErbB2 signaling, as well as a novel regeneration modulator capable of potential therapeutic effects.

Long-term cargo tracking reveals intricate trafficking through active cytoskeletal networks in the crowded cellular environment.

A eukaryotic cell is a microscopic world within which efficient material transport is essential. Yet, how a cell manages to deliver cellular cargos efficiently in a crowded environment remains poorly understood. Here, we used interferometric scattering microscopy to track unlabeled cargos in directional motion in a massively parallel fashion. Our label-free, cargo-tracing method revealed not only the dynamics of cargo transportation but also the fine architecture of the actively used cytoskeletal highways and the long-term evolution of the associated traffic at sub-diffraction resolution. Cargos frequently run into a blocked road or experience a traffic jam. Still, they have effective strategies to circumvent those problems: opting for an alternative mode of transport and moving together in tandem or migrating collectively. All taken together, a cell is an incredibly complex and busy space where the principle and practice of transportation intriguingly parallel those of our macroscopic world.

Incidence and Risk Factors for Wound Revision after Surgical Treatment of Spinal Metastasis: A National Population-Based Study in South Korea.

Wound complications are commonly seen after surgeries for metastatic spine tumors. While numerous studies have pinpointed various risk factors, there is ongoing debate. Therefore, this study aimed to verify various factors that are still under debate utilizing the comprehensive Korean National Health Insurance Service database. We identified and retrospectively reviewed a cohort of 3001 patients who underwent one of five surgical treatments (corpectomy, decompression and instrumentation, instrumentation only, decompression only, and vertebroplasty) for newly diagnosed spinal metastasis between 2009 and 2017. A Cox regression analysis was performed to determine the risk factors. A total of 197 cases (6.6%) of wound revision were found. Only the surgical method and Charlson comorbidity index were significantly different between the group that underwent wound revision and the group that did not. Regarding surgical methods, the adjusted hazard ratios for decompression only, corpectomy, instrumentation and decompression, and instrumentation only were 1.3, 2.2, 2.2, and 2.4, with these ratios being compared to the vertebroplasty group (p for trend = 0.02). In this regard, based on a sizable South Korean cohort, both surgical methods and medical comorbidity were found to be associated with the wound revision rate among spinal surgery patients for spinal metastasis.

Natural history of eosinophil­derived neurotoxin levels and the onset of allergic airway disease in preschool children.

'Atopic march' is the progression of allergic conditions through infancy and childhood. The present study investigated the association between blood eosinophil-derived neurotoxin (EDN) levels in preschool children with food allergy (FA) or atopic dermatitis (AD) and the onset of allergic airway disease [bronchial asthma (BA), allergic rhinitis (AR)]. A total of 123 children below the age of 1 year were enrolled in the present study, along with controls (n=37). Blood specimens were taken, serum EDN levels were measured and immunoglobulin E was quantified. Finally, a total of 86 subjects were analyzed. EDN values were measured at 3 time-points: before 1 year of age, before 2 years of age and before 3 years of age. The EDN levels were initially similar between those patients who did and those who did not develop allergic airway disease but then markedly diverged at the 2-year time-point (226.6 vs. 65.0 ng/ml; P<0.01) and remained divergent at the 3-year time-point (173.9 vs. 62.7 ng/ml; P<0.01). EDN levels prior to diagnosis were compared between the two groups and they were much higher in the Onset group (n=10) compared to the Non-onset group (n=67) (171.2±34.28 vs. 81.3±10.02 ng/ml; P=0.003), with 4 cases of BA and 6 cases of AR in the Onset group. After diagnosis, EDN levels were compared twice: i) At 1 and 2 years of age; and ii) 1 and 3 years of age. A significant difference was found only in the comparison at 2 years (P=0.001). In conclusion, young children with elevated EDN levels during the FA/AD disease period were more likely to develop allergic airway disease (BA, AR) in their first three years of life. A factor leading to this progression may be increased eosinophil activity.

Cell death induction and intracellular vesicle formation in human colorectal cancer cells treated with Δ9-Tetrahydrocannabinol.

BACKGROUND: Δ9-Tetrahydrocannabinol (Δ9-THC) is a principal psychoactive extract of Cannabis sativa and has been traditionally used as palliative medicine for neuropathic pain. Cannabidiol (CBD), an extract of hemp species, has recently attracted increased attention as a cancer treatment, but Δ9-THC is also requiring explored pharmacological application. OBJECTIVE: This study evaluated the pharmacological effects of Δ9-THC in two human colorectal cancer cell lines. We investigated whether Δ9-THC treatment induces cell death in human colorectal cancer cells. METHODS: We performed an MTT assay to determine the pharmacological concentration of Δ9-THC. Annxein V and Western blot analysis confirmed that Δ9-THC induced apoptosis in colorectal cancer cells. Metabolic activity was evaluated using MitoTracker staining and ATP determination. We investigated vesicle formation by Δ9-THC treatment using GW9662, known as a PPARγ inhibitor. RESULTS: The MTT assay showed that treatment with 40 µM Δ9-THC and above inhibited the proliferation of colorectal cancer cells. Multiple intracytoplasmic vesicles were detected upon microscopic observation, and fluorescence-activated cell sorting analysis showed cell death via G1 arrest. Δ9-THC treatment increased the expression of cell death marker proteins, including p53, cleaved PARP-1, RIP1, and RIP3, suggesting that Δ9-THC induced the death of colorectal cancer cells. Δ9-THC treatment also reduced ATP production via changes in Bax and Bcl-2. Δ9-THC regulated intracytoplasmic vesicle formation by modulating the expression of PPARγ and clathrin, adding that antiproliferative activity of Δ9-THC was also affected. CONCLUSION: In conclusion, Δ9-THC regulated two functional mechanisms, intracellular vesicle formation and cell death. These findings can help to determine how cannabinoids can be used most effectively to improve the efficacy of cancer treatment.

Epitaxially Grown Silicon Nanowires with a Gold Molecular Adhesion Layer for Core/Shell Structures with Compact Mie and Plasmon Resonances.

Noble-metal plasmonic nanostructures have attracted much attention because they can support deep-subwavelength optical resonances, yet their performance tends to be limited by high Ohmic absorption losses. In comparison, high-index dielectric materials can support low-loss optical resonances but do not tend to yield the same subwavelength optical confinement. Here, we combine these two approaches and examine the dielectric-plasmonic resonances in dielectric/metal core/shell nanowires. Si nanowires were grown epitaxially from (111) substrates, and direct deposition of Au on these structures by physical vapor deposition yielded nonconformal Au islands. However, by introduction of a molecular adhesion layer prior to deposition, cylindrical Si/Au core/shell nanostructures with conformal metal shells were successfully fabricated. Examining these structures as optical cavities using both optical simulations and experimental extinction measurements, we found that the structures support Mie resonances with quality factors enhanced up to ∼30 times compared with pure dielectric structures and plasmon resonances with optical confinement enhanced up to ∼5 times compared with pure metallic structures. Interestingly, extinction spectra of both Mie and plasmon resonances yield Fano line shapes, whose manifestation can be attributed to the combination of high quality factor resonances, Mie-plasmon coupling, and phase delay of the background optical field. This work demonstrates a bottom-up synthetic method for the production of freestanding, cylindrically symmetric semiconductor/metal core/shell nanowires that enables the efficient trapping of light on deep-subwavelength length scales for varied applications in photonics and optoelectronics.