TASL mediates keratinocyte differentiation by regulating intracellular calcium levels and lysosomal function.

Maintaining epidermal homeostasis relies on a tightly organized process of proliferation and differentiation of keratinocytes. While past studies have primarily focused on calcium regulation in keratinocyte differentiation, recent research has shed light on the crucial role of lysosome dysfunction in this process. TLR adaptor interacting with SLC15A4 on the lysosome (TASL) plays a role in regulating pH within the endo-lysosome. However, the specific role of TASL in keratinocyte differentiation and its potential impact on proliferation remains elusive. In our study, we discovered that TASL deficiency hinders the proliferation and migration of keratinocytes by inducing G1/S cell cycle arrest. Also, TASL deficiency disrupts proper differentiation process in TASL knockout human keratinocyte cell line (HaCaT) by affecting lysosomal function. Additionally, our research into calcium-induced differentiation showed that TASL deficiency affects calcium modulation, which is essential for keratinocyte regulation. These findings unveil a novel role of TASL in the proliferation and differentiation of keratinocytes, providing new insights into the intricate regulatory mechanisms of keratinocyte biology.

Optimization of treatment workflow for 0.35T MR-Linac system.

PURPOSE: This study presents a novel and comprehensive framework for evaluating magnetic resonance guided radiotherapy (MRgRT) workflow by integrating the Failure Modes and Effects Analysis (FMEA) approach with Time-Driven Activity-Based Costing (TDABC). We assess the workflow for safety, quality, and economic implications, providing a holistic understanding of the MRgRT implementation. The aim is to offer valuable insights to healthcare practitioners and administrators, facilitating informed decision-making regarding the 0.35T MRIdian MR-Linac system's clinical workflow. METHODS: For FMEA, a multidisciplinary team followed the TG-100 methodology to assess the MRgRT workflow's potential failure modes. Following the mitigation of primary failure modes and workflow optimization, a treatment process was established for TDABC analysis. The TDABC was applied to both MRgRT and computed tomography guided RT (CTgRT) for typical five-fraction stereotactic body RT (SBRT) treatments, assessing total workflow and costs associated between the two treatment workflows. RESULTS: A total of 279 failure modes were identified, with 31 categorized as high-risk, 55 as medium-risk, and the rest as low-risk. The top 20% risk priority numbers (RPN) were determined for each radiation oncology care team member. Total MRgRT and CTgRT costs were assessed. Implementing technological advancements, such as real-time multi leaf collimator (MLC) tracking with volumetric modulated arc therapy (VMAT), auto-segmentation, and increasing the Linac dose rate, led to significant cost savings for MRgRT. CONCLUSION: In this study, we integrated FMEA with TDABC to comprehensively evaluate the workflow and the associated costs of MRgRT compared to conventional CTgRT for five-fraction SBRT treatments. FMEA analysis identified critical failure modes, offering insights to enhance patient safety. TDABC analysis revealed that while MRgRT provides unique advantages, it may involve higher costs. Our findings underscore the importance of exploring cost-effective strategies and key technological advancements to ensure the widespread adoption and financial sustainability of MRgRT in clinical practice.

Commissioning and Assessment of Radiation Field and Dose Inhomogeneity for a Dual X-ray Tube Cabinet Irradiator: To Ensure Accurate Dosimetry in Radiation Biology Experiments.

Purpose: Standardization of x-ray cabinet irradiator dose, geometry, and calibration reporting is an ongoing process. Multi-tube designs have been introduced into the preclinical market and give a theoretical benefit but have not been widely assessed for use in preclinical irradiation conditions. The aim of this study was to report our experience commissioning a dual x-ray source cabinet irradiator (CIXD, Xstrahl Limited, United Kingdom) and assess the dose distribution for various experimental conditions. Methods and Materials: Half-value layer (HVL) measurement, profile measurements, and output calibration were performed using a calibrated ion chamber. Constancy measurements were performed twice daily over 2 weeks to assess output fluctuations. Film measurements were completed using solid water to assess percent depth dose and homogeneity within the field and within variable thicknesses of solid water and phosphate-buffered saline solution. Film measurements were repeated for various arrangements of petri dishes filled with phosphate-buffered saline or water and in a 3D-printed mouse phantom. Results: The x-ray tubes had a measured in-air output of 1.27 Gy/min. The HVL was 1.7 mm Cu. The upper and lower tubes both exhibited the heel effect, but when operated simultaneously, the effect was reduced. Ion chamber measurements revealed a 15% dose inhomogeneity within the tray area (18 × 18 cm2). Film measurements in the petri dishes indicated minor nonuniformities in the arrangements of the experimental apparatus. Measurements from the mouse phantom with film agreed with ion chamber measurements for various phantom placements and orientations. Conclusions: X-ray cell culture and animal irradiation with dual tube cabinet irradiation is efficient and robust when using established dosimetric tools to confirm output and homogeneity. The conditions assumed for calibrations are often not maintained during experiments. We have confirmed that inhomogeneities are present for single-tube use; however, they are reduced with simultaneous tube use. Additional dosimetric monitoring should be performed for each unique irradiation setup.

Rectal deformation management with IGRT in prostate radiotherapy: Can it be managed with rigid alignment alone?

PURPOSE: It is challenging to achieve appropriate target coverage of the prostate with Image Guided Radiation Therapy (IGRT) while simultaneously constraining rectal doses within planned values when there is significant variability in rectal filling and shape. We investigated if rectum planning goals can be fulfilled using rigid CBCT-based on-board alignment to account for interfraction rectal deformations. METHODS: Delivered rectal doses corresponding to prostate alignment ("PR") and anterior rectum alignment ("AR") for 239 daily treatments from 13 patients are reported. Rectal doses were estimated by rigidly mapping the planned dose on the daily CT derived from the daily CBCT according to respective alignment shifts. Rectum V95% (rV95%) was used for analyses. RESULTS: Compared to "PR", "AR" alignment increased rV95% for an average of 34.4% across all patients. rV95% (cc) averaged over all fractions was significant from planning values for 10/13 patients for "PR" and for 9/13 for "AR". 3/13 patients had reproducible anatomy. Of patients with non-reproducible anatomy, three had dosimetrically more favorable, while seven had less favorable anatomies. Most shift differences (82.3%) between the "PR" and "AR" alignments larger than 2 mm resulted in rV95% changes larger than 2 cc. Most shift differences (82.2%) of 2 mm or less between the "PR" and "AR" alignments resulted in rV95% changes less than 2 cc. The average percentage of fractions among patients in which anterior or posterior shifts for "AR" and "PR" alignment was larger than the PTV margins was 9.1% (0.0%-37.5%) and 1.3% (0%-10%). CONCLUSION: Rectal deformation and subsequent inconsistent interfraction separation between prostate and rectal wall translate into anatomical changes that cannot always be mitigated with rigid alignment. If systematic differences exist due to a non-reproducible planning anatomy, attempts to restore the planned rectal doses through anterior rectum alignment produce rather small improvements and may result in unacceptable target underdosage.

Generation of tissues outside the field of view (FOV) of radiation therapy simulation imaging based on machine learning and patient body outline (PBO).

BACKGROUND: It is not unusual to see some parts of tissues are excluded in the field of view of CT simulation images. A typical mitigation is to avoid beams entering the missing body parts at the cost of sub-optimal planning. METHODS: This study is to solve the problem by developing 3 methods, (1) deep learning (DL) mechanism for missing tissue generation, (2) using patient body outline (PBO) based on surface imaging, and (3) hybrid method combining DL and PBO. The DL model was built upon a Globally and Locally Consistent Image Completion to learn features by Convolutional Neural Networks-based inpainting, based on Generative Adversarial Network. The database used comprised 10,005 CT training slices of 322 lung cancer patients and 166 CT evaluation test slices of 15 patients. CT images were from the publicly available database of the Cancer Imaging Archive. Since existing data were used PBOs were acquired from the CT images. For evaluation, Structural Similarity Index Metric (SSIM), Root Mean Square Error (RMSE) and Peak signal-to-noise ratio (PSNR) were evaluated. For dosimetric validation, dynamic conformal arc plans were made with the ground truth images and images generated by the proposed method. Gamma analysis was conducted at relatively strict criteria of 1%/1 mm (dose difference/distance to agreement) and 2%/2 mm under three dose thresholds of 1%, 10% and 50% of the maximum dose in the plans made on the ground truth image sets. RESULTS: The average SSIM in generation part only was 0.06 at epoch 100 but reached 0.86 at epoch 1500. Accordingly, the average SSIM in the whole image also improved from 0.86 to 0.97. At epoch 1500, the average values of RMSE and PSNR in the whole image were 7.4 and 30.9, respectively. Gamma analysis showed excellent agreement with the hybrid method (equal to or higher than 96.6% of the mean of pass rates for all scenarios). CONCLUSIONS: It was first demonstrated that missing tissues in simulation imaging could be generated with high similarity, and dosimetric limitation could be overcome. The benefit of this study can be significantly enlarged when MR-only simulation is considered.

Shallow kinetics induced by a metronome (SKIM): A novel contactless respiratory motion management.

OBJECTIVES: As an alternative to conventional compression amidst the COVID-19 pandemic, we developed a contactless motion management strategy. By increasing the patient's breathing rate to induce shallow breathing with the aid of a metronome, our hypothesis is that the motion magnitude of the target may be minimized without physical contact or compression. METHODS: Fourteen lung stereotactic body radiation therapy (SBRT) patients treated under fast shallow-breathing (FSB) were selected for inclusion in this retrospective study. Our proposed method is called shallow kinetics induced by a metronome (SKIM). We induce FSB by setting the beats-per-minute (BPM) high (typically in the range of 50-60). This corresponded to a patient breathing rate of 25-30 (breathing) cycles per minute. The magnitude of target motion in 3D under SKIM was evaluated using 4DCT datasets. Comparison with free breathing (FB) 4DCT was also made for a subset for which FB data available. RESULTS: The overall effectiveness of SKIM was evaluated with 18 targets (14 patients). Direct comparison with FB was performed with 12 targets (10 patients). The vector norm mean ± SD value of motion magnitude under SKIM for 18 targets was 8.2 ± 4.1 mm. The mean ± SD metronome BPM was 54.9 ± 4.0 in this group. The vector norm means ± SD values of target motion for FB and SKIM in the 12 target sub-group were 14.6 ± 8.5 mm and 9.3 ± 3.7 mm, respectively. The mean ± SD metronome BPM for this sub-group was 56.3 ± 2.5. CONCLUSION: Compared with FB, SKIM can significantly reduce respiratory motion magnitude of thoracic targets. The difference in maximum motion reduction in the overall vector norm, S-I, and A-P directions was significant (p = 0.033, 0.042, 0.011). Our proposed method can be an excellent practical alternative to conventional compression due to its flexibility and ease of implementation.

Silibinin induces oral cancer cell apoptosis and reactive oxygen species generation by activating the JNK/c-Jun pathway.

Background: Oral cancer is one of the most prevalent malignant tumors worldwide. Silibinin has been reported to exert therapeutic effects in various cancer models. However, its mechanism of action in oral cancer remains unclear. We aimed to examine the molecular processes underlying the effects of silibinin in oral cancer in vitro and in vivo as well as its potential anticancer effects. Next, we investigated the molecular processes underlying both in vitro and in vivo outcomes of silibinin treatment on oral cancer. Methods: To investigate the effects of silibinin on the growth of oral cancer cells, cell proliferation and anchorage-independent colony formation tests were conducted on YD10B and Ca9-22 oral cancer cells. The effects of silibinin on the migration and invasion of oral cancer cells were evaluated using transwell assays. Flow cytometry was used to examine apoptosis, cell cycle distribution, and accumulation of reactive oxygen species (ROS). The molecular mechanism underlying the anticancer effects of silibinin was explored using immunoblotting. The in vivo effects of silibinin were evaluated using a Ca9-22 xenograft mouse model. Results: Silibinin effectively suppressed YD10B and Ca9-22 cell proliferation and colony formation in a dose-dependent manner. Moreover, it induced cell cycle arrest in the G0/G1 phase, apoptosis, and ROS generation in these cells. Furthermore, silibinin inhibited the migration and invasion abilities of YD10B and Ca9-22 cells by regulating the expression of proteins involved in the epithelial-mesenchymal transition. Western blotting revealed that silibinin downregulated SOD1 and SOD2 and triggered the JNK/c-Jun pathway in oral cancer cells. Silibinin significantly inhibited xenograft tumor growth in nude mice, with no obvious toxicity. Conclusions: Silibinin considerably reduced the development of oral cancer cells by inducing apoptosis, G0/G1 arrest, ROS generation, and activation of the JNK/c-Jun pathway. Importantly, silibinin effectively suppressed xenograft tumor growth in nude mice. Our findings indicate that silibinin may be a promising option for the prevention or treatment of oral cancer.

A comprehensive quality assurance procedure for 4D CT commissioning and periodic QA.

PURPOSE: The 4D computed tomography (CT) simulation is an essential procedure for tumors exhibiting breathing-induced motion. However, to date there are no established guidelines to assess the characteristics of existing systems and to describe meaningful performance. We propose a commissioning quality assurance (QA) protocol consisting of measurements and acquisitions that assess the mechanical and computational operation for 4D CT with both phase and amplitude-based reconstructions, for regular and irregular respiratory patterns. METHODS: The 4D CT scans of a QUASAR motion phantom were acquired for both regular and irregular breathing patterns. The hardware consisted of the Canon Aquilion Exceed LB CT scanner used in conjunction with the Anzai laser motion monitoring system. The nominal machine performance and reconstruction were demonstrated with measurements using regular breathing patterns. For irregular breathing patterns the performance was quantified through the analysis of the target motion in the superior and inferior directions, and the volume of the internal target volume (ITV). Acquisitions were performed using multiple pitches and the reconstructions were performed using both phase and amplitude-based binning. RESULTS: The target was accurately captured during regular breathing. For the irregular breathing, the measured ITV exceeded the nominal ITV parameters in all scenarios, but all deviations were less than the reconstructed slice thickness. The mismatch between the nominal pitch and the actual breathing rate did not affect markedly the size of the ITV. Phase and normalized amplitude binning performed similarly. CONCLUSIONS: We demonstrated a framework for measuring and quantifying the initial performance of 4D CT simulation scans that can also be applied during periodic QAs. The regular breathing provided confidence that the hardware and the software between the systems performs adequately. The irregular breathing data suggest that the system may be expected to capture in excess the target motion and geometry, but the deviation is expected to be within the slice thickness.

Development of a Real-Time Thermoplastic Mask Compression Force Monitoring System Using Capacitive Force Sensor.

Purpose: Thermoplastic masks keep patients in an appropriate position to ensure accurate radiation delivery. For a thermoplastic mask to maintain clinical efficacy, the mask should wrap the patient's surface properly and provide uniform pressure to all areas. However, to our best knowledge, no explicit method for achieving such a goal currently exists. Therefore, in this study, we intended to develop a real-time thermoplastic mask compression force (TMCF) monitoring system to measure compression force quantitatively. A prototype system was fabricated, and the feasibility of the proposed method was evaluated. Methods: The real-time TMCF monitoring system basically consists of four force sensor units, a microcontroller board (Arduino Bluno Mega 2560), a control PC, and an in-house software program. To evaluate the reproducibility of the TMCF monitoring system, both a reproducibility test using a micrometer and a setup reproducibility test using a head phantom were performed. Additionally, the reproducibility tests of mask setup and motion detection tests were carried out with a cohort of six volunteers. Results: The system provided stable pressure readings in all 10 trials during the sensor unit reproducibility test. The largest standard deviation (SD) among trials was about 36 gf/cm2 (∼2.4% of the full-scale range). For five repeated mask setups on the phantom, the compression force variation of the mask was less than 39 gf/cm2 (2.6% of the full-scale range). We were successful in making masks together with the monitoring system connected and demonstrated feasible utilization of the system. Compression force variations were observed among the volunteers and according to the location of the sensor (among forehead, both cheekbones, and chin). The TMCF monitoring system provided the information in real time on whether the mask was properly pressing the human subject as an immobilization tool. Conclusion: With the developed system, it is possible to monitor the effectiveness of the mask in real time by continuously measuring the compression force between the mask and patient during the treatment. The graphical user interface (GUI) of the monitoring system developed provides a warning signal when the compression force of the mask is insufficient. Although the number of volunteers participated in the study was small, the obtained preliminary results suggest that the system could ostensibly improve the setup accuracy of a thermoplastic mask.

20 (S)-ginsenoside Rh2 inhibits colorectal cancer cell growth by suppressing the Axl signaling pathway in vitro and in vivo.

Background: Colorectal cancer (CRC) has a high morbidity and mortality worldwide. 20 (S)-ginsenoside Rh2 (G-Rh2) is a natural compound extracted from ginseng, which exhibits anticancer effects in many cancer types. In this study, we demonstrated the effect and underlying molecular mechanism of G-Rh2 in CRC cells in vitro and in vivo. Methods: Cell proliferation, migration, invasion, apoptosis, cell cycle, and western blot assays were performed to evaluate the effect of G-Rh2 on CRC cells. In vitro pull-down assay was used to verify the interaction between G-Rh2 and Axl. Transfection and infection experiments were used to explore the function of Axl in CRC cells. CRC xenograft models were used to further investigate the effect of Axl knockdown and G-Rh2 on tumor growth in vivo. Results: G-Rh2 significantly inhibited proliferation, migration, and invasion, and induced apoptosis and G0/G1 phase cell cycle arrest in CRC cell lines. G-Rh2 directly binds to Axl and inhibits the Axl signaling pathway in CRC cells. Knockdown of Axl suppressed the growth, migration and invasion ability of CRC cells in vitro and xenograft tumor growth in vivo, whereas overexpression of Axl promoted the growth, migration, and invasion ability of CRC cells. Moreover, G-Rh2 significantly suppressed CRC xenograft tumor growth by inhibiting Axl signaling with no obvious toxicity to nude mice. Conclusion: Our results indicate that G-Rh2 exerts anticancer activity in vitro and in vivo by suppressing the Axl signaling pathway. G-Rh2 is a promising candidate for CRC prevention and treatment.

Protective Effect of GIP against Monosodium Glutamate-Induced Ferroptosis in Mouse Hippocampal HT-22 Cells through the MAPK Signaling Pathway.

The effect of glucose-dependent insulinotropic polypeptide (GIP) on cells under oxidative stress induced by glutamate, a neurotransmitter, and the underlying molecular mechanisms were assessed in the present study. We found that in the pre-treatment of HT-22 cells with glutamate in a dose-dependent manner, intracellular ROS were excessively generated, and additional cell damage occurred in the form of lipid peroxidation. The neurotoxicity caused by excessive glutamate was found to be ferroptosis and not apoptosis. Other factors (GPx-4, Nrf2, Nox1 and Hspb1) involved in ferroptosis were also identified. In other words, it was confirmed that GIP increased the activity of sub-signalling molecules in the process of suppressing ferroptosis as an antioxidant and maintained a stable cell cycle even under glutamate-induced neurotoxicity. At the same time, in HT-22 cells exposed to ferroptosis as a result of excessive glutamate accumulation, GIP sustained cell viability by activating the mitogen-activated protein kinase (MAPK) signalling pathway. These results suggest that the overexpression of the GIP gene increases cell viability by regulating mechanisms related to cytotoxicity and reactive oxygen species production in hippocampal neuronal cell lines.

[6]-Gingerol Suppresses Oral Cancer Cell Growth by Inducing the Activation of AMPK and Suppressing the AKT/mTOR Signaling Pathway.

BACKGROUND/AIM: [6]-Gingerol, a compound extracted from ginger, has been studied for its therapeutic potential in various types of cancers. However, its effects on oral cancer remain largely unknown. Here, we aimed to investigate the potential anticancer activity and underlying mechanisms of [6]-gingerol in oral cancer cells. MATERIALS AND METHODS: We analyzed the antigrowth effects of [6]-gingerol in oral cancer cell lines by cell proliferation, colony formation, migration, and invasion assays. We detected cell cycle and apoptosis with flow cytometry and further explored the mechanisms of action by immunoblotting. RESULTS: [6]-Gingerol significantly inhibited oral cancer cell growth by inducing apoptosis and cell cycle G2/M phase arrest. [6]-Gingerol also inhibited oral cancer cell migration and invasion by up-regulating E-cadherin and down-regulating N-cadherin and vimentin. Moreover, [6]-gingerol induced the activation of AMPK and suppressed the AKT/mTOR signaling pathway in YD10B and Ca9-22 cells. CONCLUSION: [6]-Gingerol exerts anticancer activity by activating AMPK and suppressing the AKT/mTOR signaling pathway in oral cancer cells. Our findings highlight the potential of [6]-gingerol as a therapeutic drug for oral cancer treatment.

Overexpression of Lin28a Aggravates Psoriasis-Like Phenotype by Regulating the Proliferation and Differentiation of Keratinocytes.

PURPOSE: Psoriasis is a common and well-studied autoimmune skin disease, which is characterized by plaques. The formation of psoriasis plaques occurs through the hyperproliferation and abnormal differentiation of keratinocytes, infiltration of numerous immune cells into the dermis, increased subepidermal angiogenesis, and various autoimmune-associated cytokines and chemokines. According to previous research, Lin28 regulates the let-7 family, and let-7b is associated with psoriasis. However, the link between Lin28 and psoriasis is unclear. In this study, an association was identified between Lin28a and psoriasis progression, which promoted the pathological characteristic of psoriasis in epidermal keratinocytes. PATIENTS AND METHODS: This study aims to investigate the role of Lin28a and its underlying mechanism in psoriasis through in vivo and in vitro models, which include the Lin28a-overexpressing transgenic (TG) mice and Lin28a-overexpressing human keratinocyte (HaCaT) cell lines, respectively. RESULTS: In vivo and in vitro results revealed that overexpression of Lin28a downregulated microRNA let-7 expression levels and caused hyperproliferation and abnormal differentiation in keratinocytes. In imiquimod (IMQ)-induced psoriasis-like inflammation, Lin28a overexpressing transgenic (TG) mice exhibited more severe symptoms of psoriasis. CONCLUSION: Mechanistically, Lin28a exacerbated psoriasis-like inflammation through the activation of the extracellular-signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 signaling (STAT 3) by targeting proinflammatory cytokine interleukin-6 (IL-6).

JAZF1 heterozygous knockout mice show altered adipose development and metabolism.

BACKGROUND: Juxtaposed with another zinc finger protein 1 (JAZF1) is associated with metabolic disorders, including type 2 diabetes mellitus (T2DM). Several studies showed that JAZF1 and body fat mass are closely related. We attempted to elucidate the JAZF1 functions on adipose development and related metabolism using in vitro and in vivo models. RESULTS: The JAZF1 expression was precisely regulated during adipocyte differentiation of 3T3-L1 preadipocyte and mouse embryonic fibroblasts (MEFs). Homozygous JAZF1 deletion (JAZF1-KO) resulted in impaired adipocyte differentiation in MEF. The JAZF1 role in adipocyte differentiation was demonstrated by the regulation of PPARγ-a key regulator of adipocyte differentiation. Heterozygous JAZF1 deletion (JAZF1-Het) mice fed a normal diet (ND) or a high-fat diet (HFD) had less adipose tissue mass and impaired glucose homeostasis than the control (JAZF1-Cont) mice. However, other metabolic organs, such as brown adipose tissue and liver, were negligible effect on JAZF1 deficiency. CONCLUSION: Our findings emphasized the JAZF1 role in adipocyte differentiation and related metabolism through the heterozygous knockout mice. This study provides new insights into the JAZF1 function in adipose development and metabolism, informing strategies for treating obesity and related metabolic disorders.

Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects multiple organs. Recent studies suggest relevance between cysteine protease cathepsin S (CTSS) expression and SLE. To investigate the mechanism of CTSS in SLE, CTSS-overexpressing transgenic (TG) mice were generated, and induced lupus-like symptoms. Eight months later, the TG mice spontaneously developed typical SLE symptoms regardless of the inducement. Furthermore, we observed increased toll-like receptor 7 (TLR7) expression with increased monocyte and neutrophil populations in the TG mice. In conclusion, overexpression of CTSS in mice influences TLR7 expression, autoantibodies and IFN-α, which leads to an autoimmune reaction and exacerbates lupus-like symptoms.

Autoencoder-Inspired Convolutional Network-Based Super-Resolution Method in MRI.

OBJECTIVE: To introduce an MRI in-plane resolution enhancement method that estimates High-Resolution (HR) MRIs from Low-Resolution (LR) MRIs. METHOD & MATERIALS: Previous CNN-based MRI super-resolution methods cause loss of input image information due to the pooling layer. An Autoencoder-inspired Convolutional Network-based Super-resolution (ACNS) method was developed with the deconvolution layer that extrapolates the missing spatial information by the convolutional neural network-based nonlinear mapping between LR and HR features of MRI. Simulation experiments were conducted with virtual phantom images and thoracic MRIs from four volunteers. The Peak Signal-to-Noise Ratio (PSNR), Structure SIMilarity index (SSIM), Information Fidelity Criterion (IFC), and computational time were compared among: ACNS; Super-Resolution Convolutional Neural Network (SRCNN); Fast Super-Resolution Convolutional Neural Network (FSRCNN); Deeply-Recursive Convolutional Network (DRCN). RESULTS: ACNS achieved comparable PSNR, SSIM, and IFC results to SRCNN, FSRCNN, and DRCN. However, the average computation speed of ACNS was 6, 4, and 35 times faster than SRCNN, FSRCNN, and DRCN, respectively under the computer setup used with the actual average computation time of 0.15 s per [Formula: see text].

Rhein Suppresses Colorectal Cancer Cell Growth by Inhibiting the mTOR Pathway In Vitro and In Vivo.

Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. Rhein has demonstrated therapeutic effects in various cancer models. However, its effects and underlying mechanisms of action in CRC remain poorly understood. We investigated the potential anticancer activity and underlying mechanisms of rhein in CRC in vitro and in vivo. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of rhein on CRC cells. Wound-healing and Transwell assays were conducted to assess cell migration and invasion capacity. Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. A tissue microarray was used to detect mTOR expression in CRC patient tissues. Gene overexpression and knockdown were done to analyze the function of mTOR in CRC. The anticancer effect of rhein in vivo was assessed in a CRC xenograft mouse model. The results show that rhein significantly inhibited CRC cell growth by inducing S-phase cell cycle arrest and apoptosis. Rhein inhibited CRC cell migration and invasion through the epithelial-mesenchymal transition (EMT) process. mTOR was highly expressed in CRC cancer tissues and cells. Overexpression of mTOR promoted cell growth, migration, and invasion, whereas mTOR knockdown diminished these phenomena in CRC cells in vitro. In addition, rhein directly targeted mTOR and inhibited the mTOR signaling pathway in CRC cells. Rhein promoted mTOR degradation through the ubiquitin-proteasome pathway. Intraperitoneal administration of rhein inhibited HCT116 xenograft tumor growth through the mTOR pathway. In conclusion, rhein exerts anticancer activity in vitro and in vivo by targeting mTOR and inhibiting the mTOR signaling pathway in CRC. Our results indicate that rhein is a potent anticancer agent that may be useful for the prevention and treatment of CRC.

Overexpression of hepatic serum amyloid A1 in mice increases IL-17-producing innate immune cells and decreases bone density.

Serum amyloid A (SAA) is an acute-phase protein produced primarily in the liver that plays a key role in both the initiation and maintenance of inflammation. Rapidly secreted SAA induces neutrophilia at inflammatory sites, initiating inflammation and inducing the secretion of various cytokines, including TNF-α, IL-6, and IL-17. IL-17 is expressed in several inflammatory cells, including innate immune cells such as γδT cells, ILC3 cells, and neutrophils. Increased IL-17 levels exacerbate various inflammatory diseases. Among other roles, IL-17 induces bone loss by increasing receptor activator of nuclear factor-κB ligand (RANKL) secretion, which stimulates osteoclast differentiation. Several studies have demonstrated that chronic inflammation induces bone loss, suggesting a role for SAA in bone health. To test this possibility, we observed an increase in IL-17-producing innate immune cells, neutrophils, and γδT cells in these mice. In 6-month-old animals, we detected increased osteoclast-related gene expression and IL-17 expression in bone lysates. We also observed an increase in neutrophils that secreted RANKL in the bone marrow of TG mice. Finally, we demonstrated decreased bone mineral density in these transgenic (TG) mice. Our results revealed that the TG mice have increased populations of IL-17-producing innate immune cells, γδT cells, and neutrophils in TG mice. We additionally detected increased RANKL and IL-17 expression in the bone marrow of 6-month-old TG mice. Furthermore, we confirmed significant increases in RANKL-expressing neutrophils in TG mice and decreased bone mineral density. Our results provide evidence that chronic inflammation induced by SAA1 causes bone loss via IL-17-secreting innate immune cells.

Jazf1 acts as a regulator of insulin-producing ß-cell differentiation in induced pluripotent stem cells and glucose homeostasis in mice.

Genetic susceptibility of type 2 diabetes and Juxtaposed with another zinc finger protein 1 (Jazf1) has been reported; however, the precise role of Jazf1 in metabolic processes remains elusive. In this study, using Jazf1-knockout (KO)-induced pluripotent stem cells (iPSC), pancreatic beta cell line MIN6 cells, and Jazf-1 heterozygous KO (Jazf1+/- ) mice, the effect of Jazf1 on gradual differentiation was investigated. We checked the alterations of the genes related with ß-cell specification, maturation, and insulin release against glucose treatment by the gain and loss of the Jazf1 gene in the MIN6 cells. Because undifferentiated Jazf1-KO iPSC were not significantly different from wild-type (WT) iPSC, the size and endoderm marker expression after embryoid body (EB) and teratoma formation were investigated. Compared to EB and teratomas formed with WT iPSC, the EB and teratomas from with Jazf1-KO iPSC were smaller, and in teratomas, the expression of proliferation markers was reduced. Moreover, the expression of the gene sets for ß-cell differentiation and the levels of insulin and C-peptide secreted by insulin precursor cells were notably reduced in ß-cells differentiated from Jazf1-KO iPSC compared with those differentiated from WT iPSC. A comparison of Jazf1+/- and WT mice showed that Jazf1+/- mice had lower levels of serum insulin, pancreatic insulin expression, and decreased pancreatic ß-cell size, which resulted in defects in the glucose homeostasis. These findings suggest that Jazf1 plays a pivotal role in the differentiation of ß-cells and glucose homeostasis.

An efficient planning technique for low dose whole lung radiation therapy for covid-19 pandemic patients.

This study aimed to establish an efficient planning technique for low dose whole lung treatment that can be implemented rapidly and safely. The treatment technique developed here relied only on chest radiograph and a simple empirical monitor unit calculation formula. The 3D dose calculation in real patient anatomy, including both nonCOVID and COVID-19 patients, which took into account tissue heterogeneity showed that the dose delivered to lungs had reasonable uniformity even with this simple and quick setup.