Three-dimensional heavily T2-weighted FLAIR in the detection of blood-labyrinthine barrier leakage in patients with sudden sensorineural hearing loss: comparison with T1 sequences and application of deep learning-based reconstruction.

OBJECTIVE: Blood-labyrinthine barrier leakage has been reported in sudden sensorineural hearing loss (SSNHL). We compared immediate post-contrast 3D heavily T2-weighted fluid-attenuated inversion recovery (FLAIR), T1 spin echo (SE), and 3D T1 gradient echo (GRE) sequences, and heavily T2-weighted FLAIR (hvT2F) with and without deep learning-based reconstruction (DLR) in detecting perilymphatic enhancement. METHODS: Fifty-four patients with unilateral SSNHL who underwent ear MRI with three sequences were included. We compared asymmetry scores, confidence scores, and detection rates of perilymphatic enhancement among the three sequences and obtained 3D hvT2F with DLR from 35 patients. The above parameters and subjective image quality between 3D hvT2F with and without DLR were compared. RESULTS: Asymmetry scores and detection rate of 3D hvT2F were significantly higher than 3D GRE T1 and SE T1 (respectively, 1.37, 0.11, 0.19; p < 0.001). Asymmetry scores significantly increased with DLR compared to 3D hvT2F for experienced and inexperienced readers (respectively, 1.77 vs. 1.40, p = 0.036; 1.49 vs. 1.03, p = 0.012). The detection rate significantly increased only for the latter (57.1% vs. 31.4%, p = 0.022). Patients with perilymphatic enhancement had significantly higher air conduction thresholds on initial (77.96 vs. 57.79, p = 0.002) and 5 days after presentation (63.38 vs. 41.85, p = 0.019). CONCLUSION: 3D hvT2F significantly increased the detectability of perilymphatic enhancement compared to 3D GRE T1 and SE T1. DLR further improved the conspicuity of perilymphatic enhancement in 3D hvT2F. 3D hvT2F and DLR are useful for evaluating blood-labyrinthine barrier leakage; furthermore, they might provide prognostic value in the early post-treatment period. CLINICAL RELEVANCE STATEMENT: Ten-minute post-contrast 3D heavily T2-weighed FLAIR imaging is a potentially efficacious sequence in demonstrating perilymphatic enhancement in patients with sudden sensorineural hearing loss and may be further improved by deep learning-based reconstruction. KEY POINTS: • 3D heavily T2-weighted FLAIR (3D hvT2F) is a sequence sensitive in detecting low concentrations of contrast in the perilymphatic space. • 3D hvT2F sequences properly demonstrated perilymphatic enhancement in sudden sensorineural hearing loss compared to T1 sequences and were further improved by deep learning-based reconstruction (DLR). • 3D hvT2F and DLR are efficacious sequences in detecting blood-labyrinthine barrier leakage and with potential prognostic information.

Deciphering the Role of ERBB3 Isoforms in Renal Cell Carcinoma: A Comprehensive Genomic and Transcriptomic Analysis.

ERBB3, a key member of the receptor tyrosine kinase family, is implicated in the progression and development of various human cancers, affecting cellular proliferation and survival. This study investigated the expression of ERBB3 isoforms in renal clear cell carcinoma (RCC), utilizing data from 538 patients from The Cancer Genome Atlas (TCGA) Firehose Legacy dataset. Employing the SUPPA2 tool, the activity of 10 ERBB3 isoforms was examined, revealing distinct expression patterns in RCC. Isoforms uc001sjg.3 and uc001sjh.3 were found to have reduced activity in tumor tissues, while uc010sqb.2 and uc001sjl.3 demonstrated increased activity. These variations in isoform expression correlate with patient survival and tumor aggressiveness, indicating their complex role in RCC. The study, further, utilizes CIBERSORTx to analyze the association between ERBB3 isoforms and immune cell profiles in the tumor microenvironment. Concurrently, Gene Set Enrichment Analysis (GSEA) was applied, establishing a strong link between elevated levels of ERBB3 isoforms and critical oncogenic pathways, including DNA repair and androgen response. RT-PCR analysis targeting the exon 21-23 and exon 23 regions of ERBB3 confirmed its heightened expression in tumor tissues, underscoring the significance of alternative splicing and exon utilization in cancer development. These findings elucidate the diverse impacts of ERBB3 isoforms on RCC, suggesting their potential as diagnostic markers and therapeutic targets. This study emphasizes the need for further exploration into the specific roles of these isoforms, which could inform more personalized and effective treatment modalities for renal clear cell carcinoma.

Tuning Proton Insertion Chemistry for Sustainable Aqueous Zinc-Ion Batteries.

Rechargeable aqueous zinc-ion batteries (ZIBs) have emerged as an alternative to lithium-ion batteries due to their affordability and high level of safety. However, their commercialization is hindered by the low mass loading and irreversible structural changes of the cathode materials during cycling. Here, a disordered phase of a manganese nickel cobalt dioxide cathode material derived from wastewater via a coprecipitation process is reported. When used as the cathode for aqueous ZIBs , the developed electrode delivers 98% capacity retention at a current density of 0.1 A g-1 and 72% capacity retention at 1 A g-1 while maintaining high mass loading (15 mg cm-2 ). The high performance is attributed to the structural stability of the Co and Ni codoped phase; the dopants effectively suppress Jahn-Teller distortion of the manganese dioxide during cycling, as revealed by operando X-ray absorption spectroscopy. Also, it is found that the Co and Ni co-doped phase effectively inhibits the dissolution of Mn2+ , resulting in enhanced durability without capacity decay at first 20 cycles. Further, it is found that the performance of the electrode is sensitive to the ratio of Ni to Co, providing important insight into rational design of more efficient cathode materials for low-cost, sustainable, rechargeable aqueous ZIBs.

Angle-resolving spectral ellipsometry using structured light for direct measurement of ellipsometric parameters.

We propose a compact angle-resolving spectral ellipsometry. Using the structured light generated from a digital micro-mirror device (DMD), what we believe to be a novel pattern is illuminated to the back focal plane of the high numerical aperture (NA) objective lens. As a result, ellipsometric parameters with fine resolution of both the wavelength and incidence angle domain can be directly measured. The incidence angle can be resolved by resolution under 1° ranging from 35° to 59° by the radius of the projected images. A spectrometer as a detector enables acquisition by the resolution of 0.7 nm from 410 to 700 nm, and the fiber reduces measurement spot size to a single micrometer. Additionally, the measurement process does not require any rotating optical components or moving parts, needing only digital modification of the projected image. This simplifies the sequences and reduces the measurement time. The 2D (angle of incidence and spectral domain) ellipsometric parameter plane measured by the proposed method was used to measure the thickness of various samples. The measurement result was verified in comparison with a commercial ellipsometer. The accuracy and precision of the result show that the proposed method is capable of precise measurement of thin films.

Radiologic findings associated with mucoid degeneration of the anterior cruciate ligament.

INTRODUCTION: Mucoid degeneration (MD) of the anterior cruciate ligament (ACL) is a well-recognized pathology characterized by the degradation of collagen fibers and infiltration of a mucoid-like substance. This study is to determine the anatomical associated factors for MD-ACL using radiographic and magnetic resonance imaging (MRI). MATERIALS AND METHODS: This was a retrospective study on patients who had undergone knee arthroscopy between 2011 and 2020. The patients with MD-ACL were defined and enrolled by the MRI and arthroscopy. Eventually, 52 patients in the MD-ACL group (group 1) and 52 patients in the control group (group 2) were enrolled, following sex and age matching. Radiologic evaluation included the assessment of Kellgren-Lawrence (K-L) grade, mechanical hip-knee-ankle (HKA) angle, posterior tibial slope (PTS) angle, and Insall-Salvati ratio. The notch width index and transverse notch angle were measured on MRI, and the grade of trochlear dysplasia was defined. Logistic regression analysis, receiver operating characteristic (ROC) curves, and area under curve (AUC) were performed. RESULTS: The ROM was significantly decreased in group 1, whereas the PTS angle was significantly larger in group 1. Combined ganglion cysts of ACL were found in 42/52 patients (80.7%) in group 1. The risk of MD-ACL was associated with a steeper PTS angle, increased Insall-Salvati ratio, male sex, higher K-L grade, and decreased transverse notch angle and notch width index. The cutoff values in ROC analysis were found to be ≤ 28.27% for the notch width index (AUC, 0.849; p < 0.001), > 12.2° for the PTS angle (AUC, 0.765; p < 0.001), and ≤ 47.4° for the transverse notch angle (AUC, 0.711; p < 0.001), but not significant for Insall-salvati ratio. CONCLUSION: A steeper PTS angle, decreased notch width index, and transverse notch angle are significantly associated with the presence of MD-ACL. These factors should be considered during diagnosis or when determining the treatment strategy for symptomatic MD-ACL patients. LEVEL OF EVIDENCE: Level IIIb.

Patterns of Occult Metastasis to Level Va and Vb in Clinically Lateral Node-Positive Papillary Thyroid Carcinoma.

BACKGROUND: The optimal extent of therapeutic lateral neck dissection (ND) in papillary thyroid carcinoma (PTC) continues to be debated. We analyzed the frequency, patterns, and predictive factors of occult level Va and Vb metastasis in clinically lateral node-positive PTC patients. METHODS: We reviewed the data of PTC patients who underwent thyroidectomy and therapeutic lateral ND from level II to V between May 2008 and August 2020. In our study, 46 patients without clinically positive metastatic lymph nodes (LNs) at level V on the preoperative evaluation were included to analyze occult metastasis at level Va and Vb, respectively. Patient demographics, including age, sex, distribution of pathologic LNs, and characteristics of the primary tumors, were reviewed. In addition, clinicopathologic factors associated with occult level Va and Vb metastasis were analyzed. RESULTS: Of the 46 patients, 14 (30.4%) patients had occult metastases at level Vb. No occult metastases were found at level Va. Clinically positive level II metastasis (p = 0.015) and simultaneous level II, III, and IV metastases (p = 0.010) in the preoperative evaluation were significantly associated with occult level Vb metastasis. Patients without LN metastasis at level IV or with three or fewer metastatic LNs in the lateral neck never had occult LN metastases at level Vb. CONCLUSIONS: Occult metastasis at level Va is rare in PTC with lateral LN metastasis. Occult metastasis at level Vb may occur in PTC patients with multilevel involvement, including level II and/or four or more lateral LN metastases.

STAT3 maintains skin barrier integrity by modulating SPINK5 and KLK5 expression in keratinocytes.

Skin barrier dysfunction induces skin inflammation. Signal transducer and activator of transcription 3 (STAT3) is known to be involved in Th17-mediated immune responses and barrier integrity in the cornea and intestine; however, its role in the skin barrier remains largely unknown. In this study, we elucidated the potential role of STAT3 in the skin barrier and its effect on kallikrein-related peptidase 5 (KLK5) and serine protease inhibitor Kazal-type 5 (SPINK5) expression using a mouse model with keratinocyte-specific ablation of STAT3. Keratinocyte-specific loss of STAT3 induced a cutaneous inflammatory phenotype with pruritus and intense scratching behaviour in mice. Transcriptomic analysis revealed that the genes associated with impaired skin barrier function, including KLK5, were upregulated. The effect of STAT3 on KLK5 expression in keratinocytes was not only substantiated by the increase in KLK5 expression following treatment with STAT3 siRNA but also by its decreased expression following STAT3 overexpression. Overexpression and IL-17A-mediated stimulation of STAT3 increased the expression of SPINK5, which was blocked by STAT3 siRNA. These results suggest that the expression of SPINK5 and KLK5 in keratinocytes could be dependent on STAT3 and that STAT3 might play an essential role in the maintenance of skin barrier homeostasis.

Performance Analysis of NB-IoT Uplink in Low Earth Orbit Non-Terrestrial Networks.

The 3rd Generation Partnership Project (3GPP) narrowband Internet of Things (NB-IoT) over non-terrestrial networks (NTN) is the most promising candidate technology supporting 5G massive machine-type communication. Compared to geostationary earth orbit, low earth orbit (LEO) satellite communication has the advantage of low propagation loss, but suffers from high Doppler shift. The 3GPP proposes Doppler shift pre-compensation for each beam region of the satellite. However, user equipment farther from the beam center has significant residual Doppler shifts even after pre-compensation, which degrades link performance. This study proposes residual Doppler shift compensation by adding demodulation reference signal symbols and reducing satellite beam coverage. The block error rate (BLER) data are obtained using link-level simulation with the proposed technique. Since the communication time provided by a single LEO satellite moving fast is short, many LEO satellites are necessary for seamless 24-h communication. Therefore, with the BLER data, we analyze the link budget for actual three-dimensional orbits with a maximum of 162 LEO satellites. We finally investigate the effect of the proposed technique on performance metrics such as the per-day total service time and maximum persistent service time, considering the number of satellites and the satellite spacing. The results show that a more prolonged and continuous communication service is possible with significantly fewer satellites using the proposed technique.

Anti-Inflammatory Effect of Protopine through MAPK and NF-κB Signaling Regulation in HepG2 Cell.

Protopine is a substance used for hemostasis with an anti-inflammatory action and is one of the substances that are actively undergoing experiments to confirm their utility as anticancer agents. This study examined the molecular changes in the cellular signaling pathways associated with inflammatory responses in phorbol 12-myristate 13 acetate (PMA)-induced human hepatocellular carcinoma cell line (Hep G2). The inhibition of PMA-induced phosphorylation of I-κB in HepG2, the effect of protopine on the MAPK signals, the inhibition of COX-2 activity, and the inhibition of MMP-9 as a medium of inflammatory response were evaluated by Western blot and qPCR. The effect of protopine on the survival rates in HepG2 cells was evaluated and found to be stable to a processing concentration of up to 40µM. Subsequent Western blot analyses showed that protopine blocks the transfer of the MAPKs cell signals induced by PMA and the transfer of the subunit of the nuclear factor-kappa B (NF-κB) to the nucleolus. Protopine inhibited the kappa alpha (I-κBα) phosphorylation in the cytosol and blocked PMA-induced inflammation via COX-2 activity inhibition. The expression of MMP-9 at the gene and protein levels, which is associated with cell migration and metastasis, was reduced by protopine.

Use of iliac screw associated with more correction of lumbar lordosis than S2-alar-iliac screw for adult spinal deformity.

BACKGROUND: To date, there is a paucity of reports clarifying the change of spinopelvic parameters in patients with adult spinal deformity (ASD) who underwent long segment spinal fusion using iliac screw (IS) and S2-alar-iliac screw (S2AI) fixation. METHODS: A retrospective review of consecutive patients who underwent deformity correction surgery for ASD between 2013 and 2017 was performed. Patients were divided into two groups based on whether IS or S2AI fixation was performed. All radiographic parameters were measured preoperatively, immediately postoperatively, and the last follow-up. Demographics, intraoperative and clinical data were analyzed between the two groups. Additionally, the cohort was subdivided according to the postoperative change in pelvic incidence (PI): subgroup (C) was defined as change in PI ≥5° and subgroup (NC) with change < 5°. In subgroup analyses, the 2 different types of postoperative change of PI were directly compared. RESULTS: A total of 142 patients met inclusion criteria: 111 who received IS and 31 received S2AI fixation. The IS group (65.6 ± 26°, 39.8 ± 13.8°) showed a significantly higher change in lumbar lordosis (LL) and upper lumbar lordosis (ULL) than the S2AI group (54.4 ± 17.9°, 30.3 ± 9.9°) (p < 0.05). In subgroup (C), PI significantly increased from 53° preoperatively to 59° postoperatively at least 50% of IS cohort, with a mean change of 5.8° (p < 0.05). The clinical outcomes at the last follow-up were significantly better in IS group than in S2AI group in terms of VAS scores for back and leg. The occurrence of sacroiliac joint pain and pelvic screw fracture were significantly greater in S2AI group than in IS group (25.8% vs 9%, p < 0.05) and (16.1% vs 3.6%, p < 0.05). CONCLUSIONS: Compared with the S2AI technique, the IS technique usable larger cantilever force demonstrated more correction of lumbar lordosis, and possible increase in pelvic incidence. Further study is warranted to clarify the clinical impaction of these results.

Low-Asymmetry Interface for Multiuser VR Experiences with Both HMD and Non-HMD Users.

We propose a low-asymmetry interface to improve the presence of non-head-mounted-display (non-HMD) users in shared virtual reality (VR) experiences with HMD users. The low-asymmetry interface ensures that the HMD and non-HMD users' perception of the VR environment is almost similar. That is, the point-of-view asymmetry and behavior asymmetry between HMD and non-HMD users are reduced. Our system comprises a portable mobile device as a visual display to provide a changing PoV for the non-HMD user and a walking simulator as an in-place walking detection sensor to enable the same level of realistic and unrestricted physical-walking-based locomotion for all users. Because this allows non-HMD users to experience the same level of visualization and free movement as HMD users, both of them can engage as the main actors in movement scenarios. Our user study revealed that the low-asymmetry interface enables non-HMD users to feel a presence similar to that of the HMD users when performing equivalent locomotion tasks in a virtual environment. Furthermore, our system can enable one HMD user and multiple non-HMD users to participate together in a virtual world; moreover, our experiments show that the non-HMD user satisfaction increases with the number of non-HMD participants owing to increased presence and enjoyment.

Exercise Pills for Drug Addiction: Forced Moderate Endurance Exercise Inhibits Methamphetamine-Induced Hyperactivity through the Striatal Glutamatergic Signaling Pathway in Male Sprague Dawley Rats.

Physical exercise reduces the extent, duration, and frequency of drug use in drug addicts during the drug initiation phase, as well as during prolonged addiction, withdrawal, and recurrence. However, information about exercise-induced neurobiological changes is limited. This study aimed to investigate the effects of forced moderate endurance exercise training on methamphetamine (METH)-induced behavior and the associated neurobiological changes. Male Sprague Dawley rats were subjected to the administration of METH (1 mg/kg/day, i.p.) and/or forced moderate endurance exercise (treadmill running, 21 m/min, 60 min/day) for 2 weeks. Over the two weeks, endurance exercise training significantly reduced METH-induced hyperactivity. METH and/or exercise treatment increased striatal dopamine (DA) levels, decreased p(Thr308)-Akt expression, and increased p(Tyr216)-GSK-3ß expression. However, the phosphorylation levels of Ser9-GSK-3ß were significantly increased in the exercise group. METH administration significantly increased the expression of NMDAr1, CaMKK2, MAPKs, and PP1 in the striatum, and exercise treatment significantly decreased the expression of these molecules. Therefore, it is apparent that endurance exercise inhibited the METH-induced hyperactivity due to the decrease in GSK-3ß activation by the regulation of the striatal glutamate signaling pathway.

Implication of COVID-19 outbreak on ship survey and certification.

The COVID-19 pandemic is having a significant implication on shipping industry causing disruption to smooth operation of ships. In particular, it has been difficult to arrange ship surveys due to a restriction on surveyors' travel to reach ports for the surveys. However, to keep ships to continue operating, all ships must be surveyed and have relevant certificates renewed in a timely manner. In response, Classification Societies and flag Administrations have come up with temporary measure by granting 3-month extension of ship surveys. The rationale for granting extension up to 3 months can be found in Class rules and IMO instruments in force majeure clauses and extension clauses respectively. However, the real test is just beginning for further extension beyond 3 months as the COVID-19 pandemic seems to prolong globally, and there is no legal ground for this further extension in both Class rules and IMO instruments. Thus, granting such extension beyond 3 months of statutory maximum would leave uncertainty about the legal exposure of all parties involved in case a ship were victimized during the extension period. To ease the legal uncertainty, this paper suggests that the force majeure clause in Class rules should be amended to cover the COVID-19 pandemic. It is also suggested that IMO should embark the discussion to amend the extension clause, to cover the possibility of not being able to find a port in which a ship can be surveyed within 3 months in the wake of world-wide pandemic like the COVID-19 outbreak.

Inositol polyphosphate multikinase in adipocytes is dispensable for regulating energy metabolism and whole body metabolic homeostasis.

Adipose tissue plays a central role in regulating whole body energy and glucose homeostasis at both organ and systemic levels. Inositol polyphosphates, such as 5-diphosphoinositol pentakisphosphate, reportedly control adipocyte functions and energy expenditure. However, the physiological roles of the inositol polyphosphate (IP) pathway in the adipose tissue are not yet fully defined. The aim of the present study was to test the hypothesis that inositol polyphosphate multikinase (IPMK), a key enzyme in the IP metabolism, plays a critical role in adipose tissue biology and obesity. We generated adipocyte-specific IPMK knockout (Ipmk AKO) mice and evaluated metabolic phenotypes by measuring fat accumulation, glucose homeostasis, and insulin sensitivity in adult mice fed either a regular-chow diet or high-fat diet (HFD). Despite substantial reduction of IPMK, Ipmk AKO mice exhibited normal glucose tolerance and insulin sensitivity and did not show changes in fat accumulation in response to HFD-feeding. In addition, loss of IPMK had no major impact on thermogenic processes in response to cold exposure. Collectively, these findings suggest that adipocyte IPMK is dispensable for normal adipose tissue and its physiological functions in whole body metabolism, suggesting the complex roles that inositol polyphosphate metabolism has in the regulation of adipose tissue.

Angle-resolved spectral reflectometry with a digital light processing projector.

We describe a novel approach for angle-resolved spectral reflectometry using a digital light processing (DLP) projector. Here, the DLP generates ring patterned images which are projected on the back focal plane of an objective lens. This way, the proposed method quickly changes the angle of incidence with ease based on the relation between the radius of the back focal plane and the angle of incidence. As a result, a detector captures the intensity of the image plane based on the angular and spectral axis. As the proposed method detects the interesting spot of a sample image, it can easily locate the measurement spot with viewing the full field of view, and the spot size is reduced by adopting the fiber. This method is verified by comparing the measurement output of the thin-film samples with a commercial ellipsometer. The result shows that our the proposed method enables the high accuracy of the thin-film inspection.

Radiographic and clinical evidence: osteoarthritic knee can change surgical result for lumbar degenerative disease patient undergone surgery for 3-year follow-up: a retrospective comparative clinical study.

BACKGROUND: There is a paucity of reports clarifying the implication of knee osteoarthritis (OA) on spinal sagittal alignment of patients undergone surgery for lumbar spine. This study aimed to analyze how osteoarthritic knee affects radiographic and clinical results of degenerative lumbar disease patients undergone lumbar fusion. METHODS: We retrospectively reviewed the medical records and radiographs of 74 consecutive degenerative lumbar disease patients who underwent posterior instrumentation and fusion surgery between May 2016 and June 2017 and were followed up for minimum 3 years postoperatively. The patients were divided into 2 groups according to the severity of knee OA by Kellgren-Lawrence grading (KLG) scale (group I, KLG 1 or 2 [n = 39]; group II, KLG 3 or 4 [n = 35]). Patient demographic data, comorbidities, spinal sagittal parameters and clinical scores were extracted and compared at preoperative, postoperative 1 month and the ultimate follow-up between the groups. In radiographic assessment, sagittal alignment parameters and sagittal balance were used. In clinical assessment, the scores of Oswestry disability index (ODI) and Scoliosis Research Society questionnaire (SRS-22) were used. For the frequency analysis of categorical variables across the groups, chi-square test was used and student t tests was used to compare the differences of continuous variables. RESULTS: In radiographic assessment, TLK (thoracolumbar kyphosis), LL (lumbar lordosis), PT (pelvic tilt), C7 SVA (sagittal vertical axis) in both groups improved significantly after surgery (p <  0.05). However, LL, PT, C7SVA improved at postoperative 1 month in the group II were not maintained at the ultimate postoperative follow-up. In clinical assessment, preoperative Oswestry disability index (ODI, %) and all SRS-22 subscores of the group I and II were not different (p > 0.05). There were significant differences between the groups at the ultimate follow-up in ODI (- 25.6 vs - 12.1, p <  0.001), SRS total score (%) (28 vs 20, p = 0.037), function subscore (1.4 vs 0.7, p = 0.016), and satisfaction subscore (1.6 vs 0.6, p < 0.001). CONCLUSION: Osteoarthritic knee with KLG 3 or 4 have a negative influence on maintaining postoperative spinal sagittal alignment, balance, and the clinical outcomes achieved immediately by posterior instrumentation and fusion for lumbar degenerative disease. TRIAL REGISTRATION: This study was retrospectively registered with approval by the institutional review board (IRB) of our institution (approval number: 2018-11-007).

Inositol Pyrophosphates: Signaling Molecules with Pleiotropic Actions in Mammals.

Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP7) are inositol metabolites containing high-energy phosphoanhydride bonds. Biosynthesis of PP-IPs is mediated by IP6 kinases (IP6Ks) and PPIP5 kinases (PPIP5Ks), which transfer phosphate to inositol hexakisphosphate (IP6). Pleiotropic actions of PP-IPs are involved in many key biological processes, including growth, vesicular remodeling, and energy homeostasis. PP-IPs function to regulate their target proteins through allosteric interactions or protein pyrophosphorylation. This review summarizes the current understanding of how PP-IPs control mammalian cellular signaling networks in physiology and disease.

RIP4 upregulates CCL20 expression through STAT3 signalling in cultured keratinocytes.

The receptor-interacting protein kinase 4 (RIP4), a serine/threonine kinase, is an important modulator of epidermal growth and cutaneous inflammation. We found that RIP4 expression was significantly increased in the lesional skin of psoriasis. However, the role and regulatory mechanism of RIP4 in psoriasis have not been characterized. After treatment with IL-17, RIP4 mRNA and protein levels were increased in HaCaT cells. IL-17 also activated the RIP4 promoter. To understand the functional role of RIP4 in keratinocyte and to investigate the genes regulated by RIP4, RNA-based microarray analysis was performed. Among immune response-related genes, CCL20 expression was significantly changed by RIP4. To identify RIP4-interacting protein, an immunoprecipitation assay was performed. As a result, STAT3 was identified as a new protein that interacts with RIP4. The interaction of RIP4 and STAT3 enhanced STAT3 phosphorylation. In addition, the transcriptional activity of STAT3 induced by RIP4 regulated IL-17-mediated CCL20 expression in HaCaT cells. Taken together, these findings indicate that IL-17 increased RIP4-mediated STAT3 phosphorylation by directly interacting with STAT3. Thus, transcriptional activation of STAT3 promotes the expression of CCL20. Thus, activations of these signalling pathways by RIP4 may contribute to epithermal inflammation in psoriatic keratinocytes.

A Study on Immersion and Presence of a Portable Hand Haptic System for Immersive Virtual Reality.

This paper proposes a portable hand haptic system using Leap Motion as a haptic interface that can be used in various virtual reality (VR) applications. The proposed hand haptic system was designed as an Arduino-based sensor architecture to enable a variety of tactile senses at low cost, and is also equipped with a portable wristband. As a haptic system designed for tactile feedback, the proposed system first identifies the left and right hands and then sends tactile senses (vibration and heat) to each fingertip (thumb and index finger). It is incorporated into a wearable band-type system, making its use easy and convenient. Next, hand motion is accurately captured using the sensor of the hand tracking system and is used for virtual object control, thus achieving interaction that enhances immersion. A VR application was designed with the purpose of testing the immersion and presence aspects of the proposed system. Lastly, technical and statistical tests were carried out to assess whether the proposed haptic system can provide a new immersive presence to users. According to the results of the presence questionnaire and the simulator sickness questionnaire, we confirmed that the proposed hand haptic system, in comparison to the existing interaction that uses only the hand tracking system, provided greater presence and a more immersive environment in the virtual reality.