Channel Degradation Research Articles

Multistep Fabrication of OECTs via Direct Ink Writing, With Performance Analysis Based on a Novel Measurement Protocol

AbstractOrganic electrochemical transistors (OECTs) have been proven beneficial for bioelectronic applications. However, the demand for reliable and fast fabrication methods has not yet been fully met. In this work, OECTs are fabricated using direct ink writing (DIW). This method is cleanroom‐free and can be done without using lithography techniques. These devices are characterized and benchmarked against devices fabricated using spin‐coating and drop‐casting deposition approaches. Response time as well as the product of carrier charge mobility and volumetric capacitance are found to be higher using the DIW fabrication approach compared to standard deposition techniques. In addition, a testing process is designed to systematically evaluate the operational degradation of the semiconductor channel. This test enables identical conditions for all tested devices while providing comparable output. Thicker channels show better stability, while thinner channels are proved to be better transistors. Finally, the degradation issues and instability of these devices are discussed.

N6-methyladenosine modification of SPOP relieves ferroptosis and diabetic cardiomyopathy by enhancing ubiquitination of VDAC3

Understanding the pathogenesis of diabetic cardiomyopathy (DCM), a common microvascular complication affecting the heart, is crucial for identifying new therapeutic targets and intervention strategies for DCM. Our study revealed a significant downregulation in Speckle-type POZ protein (SPOP) expression in DCM, while the overexpression of SPOP improved DCM-induced myocardial dysfunction, injury, fibrosis, hypertrophy, and ferroptosis. Mechanistically, SPOP facilitated the degradation of voltage-dependent anion channel 3 (VDAC3) by enhancing its ubiquitination. M6A demethylase AlkB homolog 5 (ALKBH5) reduced the mRNA stability of SPOP by decreasing m6A modification in its 3′UTR. The m6A reader insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) enhanced the stability of SPOP mRNA through recognition of m6A-modified SPOP 3′UTR. Furthermore, ALKBH5 promoted ferroptosis by inhibiting SPOP-induced VDAC3 degradation, while IGF2BP2 inhibited ferroptosis via activation of SPOP-induced VDAC3 degradation in high glucose-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Overall, our study has unveiled a novel role of SPOP in the pathogenesis of ferroptosis and DCM, thereby significantly advancing our understanding of the involvement of ferroptosis during the progression of DCM. Moreover, this discovery offers promising potential therapeutic interventions targeting DCM.

Chelerythrine triggers the prolongation of QT interval and induces cardiotoxicity by promoting the degradation of hERG channels

Cardiotoxicity is a serious adverse reaction during drug treatment. The cardiac hERG channels play a crucial role in driving cardiac action potential repolarization and are a key target for drug-induced cardiac toxicity. Chelerythrine has anti-cancer effects on various human cancer cells. But little is known about its drug safety currently. The purpose of this study is to explore the key mechanism of cardiac toxicity induced by Chelerythrine under pathological conditions. Chelerythrine and hypoxia prolonged QT interval and action potential duration compared with control group in guinea pigs, as measured by BL-420S biological acquisition and processing system in conjunction with optical mapping technology. HERG current was measured by patch-clamp technique and the interaction between ubiquitin molecules and hERG channels was assessed using immunoprecipitation method at the molecular level. The co-localization of proteins and the function of lysosomes were determined via confocal laser scanning microscopy. Further research indicates that Chelerythrine enhances the ubiquitination process of hERG proteins by catalyzing the formation of K63 ubiquitin chains, the ubiquitination modification disrupts hERG channel homeostasis and promotes the degradation of the channel. Mechanistically, Chelerythrine accelerates the degradation of hERG channels through lysosomes via HDAC6, which may easily induce cardiotoxicity caused by prolonged QT interval under hypoxic conditions.

Numerical modeling of graded sediment transport with limited bed material supply – A case study in the Middle Yangtze River

Suspended sediment concentration in the Middle Yangtze River (MYR) has reduced sharply below the Three Gorges Dam since 2003, and led to significant channel degradation and riverbed coarsening. However, the complex interaction between riverbed coarsening and sediment transport is essential for channel evolution processes but is poorly understood. This paper presents a one-dimensional model for simulating graded sediment transport when the bed material supply is limited. The model takes account of the effect of bed material composition (BMC) and threshold probability on graded sediment transport, and thus improve the accuracy of recovery coefficient. The modeling results of graded sediment concentrations was calibrated and then satisfactorily verified using field observations in the JingJiang Reach from 2015 to 2016. The results showed bed material composition affect the simulated fine, medium, and coarse sediment concentrations, and the improvements of normalized errors are 17.6%, 45.9%, and 330.7%, respectively. With the BMC effect considered, the recovery factor of fine and medium were far less than coarse sediment in the MYR. In addition, the recovery ratios of medium and coarse sediment concentrations along the MYR were improved by 88.6%-265.4% and 75.1%-105.9% respectively, owing to the bed material supply after the TGD operation; however, there was no significant effect on fine sediment, with a low recovery ratio of 8.3%-8.6%. Therefore, the effect of bed material composition on graded sediment transport and channel evolution needs to be considered for higher simulation accuracy in the MYR.

Error performance of DF cooperative SMTs with I/Q imbalance over Beckmann fading channels

The direct down-conversion principle, which has generally been used in the design of multiple-input multiple-output (MIMO) schemes, including space modulation techniques (SMTs), is attractive to researchers because of its low cost, low power consumption with fewer components, flexible and simple structure. However, hardware imperfections such as in-phase (I) and quadrature-phase (Q) imbalance (IQI) negatively affect the performance of the systems with direct down-conversion in practice. On the other hand, cooperative communication is a promising technology that can be utilized in the design of future wireless networks due to its significant advantages such as increasing system reliability, extending network coverage, reducing channel degradation, and providing high quality of service. In this study, SMT-based methods are integrated into cooperative systems, and a flexible and comprehensive model is presented that is applicable to many channel structures. Specifically, the error performance analysis of space shift keying (SSK), spatial modulation (SM), and quadrature SM (QSM) systems in the presence of IQI in decode-and-forward (DF) cooperative communication is carried out by analytical derivations and computer simulations over generalized Beckmann fading channels. The obtained results show that the performance of SMT-based DF cooperative systems is superior to the conventional schemes, and the effects of receiver IQI can be eliminated by optimal detector designs.

Simultaneous enhanced antibiotic pollutants removal and sustained permeability of the membrane involving CoFe2O4/MoS2 catalyst initiated with simple H2O2 backwashing

Membranes for wastewater treatment should ideally exhibit sustainable high permeate production, enhanced pollutant removal, and intrinsic physical rejection. In this study, CoFe2O4/MoS2 serves as a non-homogeneous phase catalyst; it is combined with polyether sulfone membranes via liquid-induced phase separation to simultaneously sustain membrane permeability and enhance antibiotic pollutant degradation. The prepared catalytic membranes have higher pure water flux (329.34 L m−2 h−1) than pristine polyethersulfone membranes (219.03 L m−2 h−1), as well as higher mean pore size, porosity, and hydrophilicity. Under a moderate transmembrane pressure (0.05 MPa), tetracycline (TC) in synthetic and real wastewater was degraded by the optimal catalytic membrane by 72.7 % and 91.2 %, respectively. Owing to the generation of the reactive oxygen species (ROS) during the Fenton-like reaction process, the catalytic membrane could exclude the natural organics during the H2O2 backwash step and selectively promote fouling degradation in the membrane channel. The irreversible fouling ratio of the catalyzed membrane was significantly reduced, and the flux recovery rate increased by up to 91.6 %. A potential catalytic mechanism and TC degradation pathways were proposed. This study offers valuable insights for designing catalytic membranes with enhanced filtration performance.

Ubiquitination is involved in PKC-mediated degradation of cell surface Kv1.5 channels

The voltage-gated Kv1.5 potassium channel, conducting the ultra-rapid delayed rectifier K+ current (IKur) in human cells, plays important roles in the repolarization of atrial action potentials and regulation of the vascular tone. We previously reported that activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) induces endocytic degradation of cell-surface Kv1.5 channels, and a point mutation removing the phosphorylation site, T15A, in the N terminus of Kv1.5 abolished the PMA-effect. In the present study, using mutagenesis, patch clamp recording, Western blot analysis, and immunocytochemical staining, we demonstrate that ubiquitination is involved in the PMA-mediated degradation of mature Kv1.5 channels. Since the expression of the Kv1.4 channel is unaffected by PMA treatment, we swapped the N- and/or C-termini between Kv1.5 and Kv1.4. We found that the N-terminus alone did not but both N- and C-termini of Kv1.5 did confer PMA sensitivity to mature Kv1.4 channels, suggesting the involvement of Kv1.5 C-terminus in the channel ubiquitination. Removal of each of the potential ubiquitination residue Lysine at position 536, 565, and 591 by Arginine substitution (K536R, K565R, and K591R) had little effect, but removal of all three Lysine residues with Arginine substitution (3K-R) partially reduced PMA-mediated Kv1.5 degradation. Furthermore, removing the cysteine residue at position 604 by Serine substitution (C604S) drastically reduced PMA-induced channel degradation. Removal of the three Lysines and Cys604 with a quadruple mutation (3K-R/C604S) or a truncation mutation (Δ536) completely abolished the PKC activation-mediated degradation of Kv1.5 channels. These results provide mechanistic insight into PKC activation-mediated Kv1.5 degradation.

Effectiveness of stormwater control measures in protecting stream channel stability

AbstractWhile research on the hydrologic impact of different types of stormwater control measures (SCMs) is extensive, little research exists linking urbanization, widespread implementation of SCMs and channel stability in headwater streams. This study evaluated whether the unified stormwater sizing criteria (USSC) regulations in the state of Maryland, USA, which require the use of both end‐of‐pipe and distributed, small‐scale SCMs, protect channel stability. To achieve this goal, a coupled hierarchical modelling approach utilizing the Storm Water Management Model (SWMM) and the Hydrologic Engineering Center River Analysis System 6.3 (HEC‐RAS) was developed to predict changes in streamflow and sediment transport dynamics in a first‐order gravel‐bed, riffle‐pool channel. Storm event discretization revealed that 88% of observed storm events during the 16 years (2004–2020) had durations less than 18 h and that the greatest peak flows resulted from storm events with durations less than 24 h. HEC‐RAS simulation results also showed that both channel degradation and aggradation, as high as 1.2 m, will likely occur due to regulations which require the use of 24 h duration design storms with a target stormwater detention time rather than bed material sediment transport limits. Overall, this study provides valuable insights into the complex interactions between SCM practises, flow regimes and sediment transport dynamics in heavily urbanized watersheds. It is recommended that SCMs be designed using a continuous simulation model with at least 10 years of continuous rainfall data. Furthermore, to protect channel stability, the SCM design goal should focus on maintaining pre‐development sediment transport regimes across a range of flows.

An intelligent wireless channel corrupted image-denoising framework using symmetric convolution-based heuristic assisted residual attention network

ABSTRACT Image denoising is one of the significant approaches for extracting valuable information in the required images without any errors. During the process of image transmission in the wireless medium, a wide variety of noise is presented to affect the image quality. For efficient analysis, an effective denoising approach is needed to enhance the quality of the images. The main scope of this research paper is to correct errors and remove the effects of channel degradation. A corrupted image denoising approach is developed in wireless channels to eliminate the bugs. The required images are gathered from wireless channels at the receiver end. Initially, the collected images are decomposed into several regions using Adaptive Lifting Wavelet Transform (ALWT) and then the “Symmetric Convolution-based Residual Attention Network (SC-RAN)” is employed, where the residual images are obtained by separating the clean image from the noisy images. The parameters present are optimized using Hybrid Energy Golden Tortoise Beetle Optimizer (HEGTBO) to maximize efficiency. The image denoising is performed over the obtained residual images and noisy images to get the final denoised images. The numerical findings of the developed model attain 31.69% regarding PSNR metrics. Thus, the analysis of the developed model shows significant improvement.

An adaptive frequency-hopping detection for slowly-varying fading dispersive channels.

Frequency hopping (FH) signals have been widely used to improve performance against frequency selective fading phenomenon of underwater channels. However, the channel is slowly varying in regard to changes in weather conditions, and thus the conventional FH detection transmitting signals with fixed frequency cannot guarantee good detection performance in the dynamic underwater environment. To overcome the performance degradation in slowly-varying fading dispersive channels, this paper proposes an adaptive frequency-hopping (AFH) target detection method. Compared with conventional FH detection methods, the AFH can adaptively select the optimal detection frequency based on premeasured background noise and channel frequency response measured from previous experiments. Numerical simulations and lake trials are conducted to verify the effectiveness of the AFH. The simulation results show that the AFH has better detection performance than the conventional FH. The lake trial results have also verified the validity and feasibility of AFH. Importantly, AFH also achieves a better output signal-to-noise ratio under actual noise interference.

Temporal change in channel form and hydraulic behaviour of a tropical river due to natural forcing and anthropogenic interventions

ABSTRACT Assessing the degradation of river channels is crucial in the Anthropocene era, particularly in the deltaic areas worldwide. The present study aims to investigate the degradation of the Mathabhanga-Churni River giving emphasis on the temporal change of channel morphology and hydraulic behaviour and comparing the current situation with the historical past based on planform morphology and meander geometry of 118 meander loops, and width, depth, cross-sectional area, and hydraulic behaviour (velocity, discharge, stream power) at 47 cross-sections. The absence of lateral dynamicity, the static character of channel sinuosity during the last century (1913–2018), and the constant meander morphology reflects the static meander geometry and degradation of the river. The reduction of average channel width, depth, and cross-sectional area supports the falling trend of channel forms. Findings on hydraulic behaviour indicate declining discharge (~50% reduction during 1915–2018) that induces the present-day downscaled velocity and lowered stream power. Neotectonics (eastward tilting of the Bengal delta) and anthropogenic stressors such as stream crossings, agriculture on river beds, brickfields, and urbanisation have a severe impact on the hydromorphology of the channel, turning the active river into a stagnant and polluted channel.

River bed degradation in a compound channel after base level fall

The bed degradation of a compound channel induced by a base level fall can significantly impact the flood conveyance capability and stability of riverine structures. This study found that severe compound channel degradation is due to the coupled effects of flood discharge and base level fall. Laboratory experiments examined the impact of base level fall on the grain size distribution at the bed surface, flow discharge in the main channel and floodplains, and longitudinal profile of the bed elevation. Two riverbed degradation patterns of a compound channel after base level fall were clarified. Relative to the original bed slope, degradation pattern (I) had a higher bed slope, but degradation pattern (II) had a lower one. A calculation method was proposed to determine the critical conditions for identifying these two riverbed degradation types. Both experimental and published data confirmed that the proposed method is valid for identifying these two compound channel degradation patterns.

Computational insights into the mechanisms underlying structural destabilization and recovery in trafficking-deficient hERG mutants.

Cardiovascular diseases are a major global health concern, responsible for a significant number of deaths each year, often linked to cardiac arrhythmias resulting from dysfunction in ion channels. Hereditary Long QT Syndrome (LQTS) is a condition characterized by a prolonged QT interval on ECG, increasing the risk of sudden cardiac death. The most common type of LQTS, LQT2, is caused by mutations in the hERG gene, affecting a potassium ion channel. The majority of these mutations disrupt the channel's trafficking to the cell membrane, leading to intracellular retention. Specific high-affinity hERG blockers (e.g., E-4031) can rescue this mutant phenotype, but the exact mechanism is unknown. This study used accelerated molecular dynamics simulations to investigate how these mutations affect the hERG channel's structure, folding, endoplasmic reticulum (ER) retention, and trafficking. We reveal that these mutations induce structural changes in the channel, narrowing its central pore and altering the conformation of the intracellular domains. These changes expose internalization signals that contribute to ER retention and degradation of the mutant hERG channels. Moreover, the study found that the trafficking rescue drug E-4031 can inhibit these structural changes, potentially rescuing the mutant channels. This research offers valuable insights into the structural issues responsible for the degradation of rescuable transmembrane trafficking mutants. Understanding the defective trafficking structure of the hERG channel could help identify binding sites for small molecules capable of restoring proper folding and facilitating channel trafficking. This knowledge has the potential to lead to mechanism-based therapies that address the condition at the cellular level, which may prove more effective than treating clinical symptoms, ultimately offering hope for individuals with hereditary Long QT Syndrome.

Quercetin is a foe in the heart by targeting the hERG potassium channel.

Quercetin is a plant flavonoid known for its pharmacological activities, such as antioxidant, anti-inflammatory, and anti-cancer properties. However, there is limited information available regarding its potential toxicities. A previous study showed that quercetin can inhibit human ether-a-go-related gene (hERG, also named KCNH2) currents, which may lead to long QT syndrome, torsade de pointes (TdP), and even sudden cardiac death. This study aimed to investigate the effects of quercetin on hERG and its potential mechanism. hERG currents and action potential duration (APD) were assessed using the patch clamp technique. Molecular docking was employed to elucidate the binding sites between quercetin and hERG. Transfection of wild-type or mutant plasmids was used to verify the results of molecular docking. Western blot was performed to determine the expression levels of hERG, transcription factor SP1, molecular chaperones HSP70 and HSP90, phosphorylated E3 ubiquitin ligase p-Nedd4-2, serum- and glucocorticoid-inducible kinase (SGK1), and phosphatidylinositol 3-kinase (PI3K). Immunoprecipitation was conducted to evaluate hERG ubiquitination. Quercetin acutely blocked hERG current by binding to F656 amino acid residue, subsequently accelerating channel inactivation. Long-term incubation of quercetin accelerates Nedd4-2-mediated ubiquitination degradation of hERG channels by inhibiting the PI3K/SGK1 signaling pathway. Moreover, the APD of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) is significantly prolonged by 30 μM quercetin. Quercetin has a potential risk of proarrhythmia, which provided useful information for the usage and development of quercetin as a medication.

Hydrodynamic and Morphological Adaptation of Two Consecutive Sharp Bends of the Middle Yangtze River to Upstream Damming

AbstractIt remains an open question how the hydrodynamics and morphology in sharp meander bends adapt to the changes in flow and sediment conditions induced by upstream damming. This study reports a comprehensive investigation into the morphological changes, patterns of mean and secondary flows and sediment transport around two consecutive sharp bends in the Middle Yangtze River (MYR), and explains these changes from the viewpoint of flow‐sediment transport‐morphology interaction based on field measurements. With the Three Gorges Project operation, the MYR suffered a remarkable channel degradation due to a sudden decrease of incoming sediment discharge. The point bars were removed, and outer‐bank benches (OBB) formed upstream of the bend apices, which resulted in quite different flow and sediment transport patterns in the bends. The highest velocity zones and center‐region cells of secondary flow were more toward the inner bank due to the lack of point bars, and the outward migration of momentum was delayed. Flow recirculation zones were observed over the OBBs, covering 12%–58% of the channel width. The transport rates of suspended load accounted for 98% of the total sediment load, and the outward shift of the highest transport rate zone was confined by the OBBs, which reduced the effective width of sediment transport. These changes in flow and sediment transport re‐inforced the morphological changes around the sharp bends: the velocity redistribution and evolution of scour factor lagged more behind planform curvature, which further promoted the erosion of point bars and the development of OBB.

Demonstration of 120 Gbit/s turbulence-resilient coherent optical communication employing cylindrical vector beam multiplexing

Free space optical (FSO) communication has gained widespread attention due to its advantages, including high confidentiality, high communication capacity, and no limitation of spectrum. One of the great challenges in FSO communication is the transmission performance degradation in atmospheric turbulence channel due to wavefront distortion and scintillation. Here, we proposed and experimentally demonstrated a 120 Gbit/s vector beam multiplexed coherent optical communication system with turbulence-resilient capacity. Four multiplexed vector beams, each carrying a 30 Gbit/s quadrature phase-shift keying signal, propagate through different turbulence conditions. The influence of turbulence channel on the vector beam impairments is experimentally investigated. Under the weaker turbulence conditions, the system bit error rates are below the forward error correction threshold of 3.8 × 10−3. In comparison with the Gaussian mode, the communication interruption probability of the vector beams system decreases from 36% to 12%-18% under stronger turbulence conditions.

Cardiovascular phenotype of the duchenne muscular dystrophy carrier female rat

Abstract Background Duchenne muscular dystrophy (DMD) is a lethal, severely progressive muscle-wasting disease. It is an X-linked recessive disease caused by mutations in the DMD gene encoding dystrophin protein and consequently the absence of dystrophin protein synthesis. Besides the skeletal muscle abnormalities, DMD patients are often suffering cardiovascular symptoms include cardiac fibrosis, dilated cardiomyopathy, arrhythmia, and congestive heart failure. Heterozygous female DMD carriers rarely acquire skeletal muscle symptoms, however the cardiac abnormalities are often underrepresented. There are few studies to date characterizing cardiovascular abnormalities in female DMD carriers and the mechanisms underlying the cardiac manifestations are still not fully known. Aims and Methods: Therefore, the aim of this study was to investigate the cardiovascular phenotype of 9 months old female DMD carrier rats and compare with age-matched wildtype rats. Objectives included assessment of cardiac function via transthoracic echocardiography, vascular function using wire myography, cardiac fibrosis and dystrophin via histology, mRNA expression of inflammatory markers via RT-qPCR, measurements of ACE1 and ACE2 activity, as well as expression of dystrophin, SERCA, sarcolipin, BAG3, and Connexin43 (Cx43) using western blotting. The cardiac function, vascular endothelial function, ACE1 and ACE2 activity, and collagen deposition in cardiac tissue were similar between the female DMD carrier and wildtype rats. The echocardiography data revealed thinning of the left-ventricular posterior wall indicating trend towards cardiac atrophy and dysfunction (p<0.05). Wire myography data showed trends of impaired endothelium-independent relaxation and hypercontractility, suggesting the potential vascular abnormalities. Histological analysis showed thickening of intima-media layer in coronary arteries, addition to reduced dystrophin staining, further affirming dystrophin loss impairs smooth muscle cell function (p<0.05, respectively). Protein expression of dystrophin, SERCA2, and BAG3 was decreased in female DMD carrier rats in the myocardium. We also found decreased levels of Cx43 at the intercalated discs, with a concomitant increase in the phosphorylation of Serine368 on Cx43 that very often precedes ubiquitination and degradation of Cx43 channels. In agreement, higher levels of the ubiquitin ligase Nedd4 were observed in hearts of female DMD carrier rats, implicating Cx43 degradation in cardiac dysfunction observed in these animals. Conclusions These findings indicate that female DMD carrier rats do not develop severe cardiac systolic dysfunction nor dilated cardiomyopathy at the age of 9 months unlike male DMD rats as previously described(1). However, the female DMD carrier rats begin to manifest tendencies towards cardiac and vascular dysfunction in association with a changes of calcium handling protein and Cx 43 expression in the heart.

The Migration of the Erosion Center Downstream of the Three Gorges Dam, China, and the Role Played by Underlying Gravel Layer

AbstractRivers disrupted by sediment cutoff often experience degradation, but the migration of the erosion center, defined as the location with the greatest degradation rates, has not been thoroughly understood. This paper focuses on the streamwise migration of the erosion center along the ∼400‐km‐long Yichang to Chenglingji reach (YCR) downstream of the Three Gorges Dam (TGD), China. We analyzed channel morphological adjustment based on water, sediment and channel geometry data collected during 2002–2020. Based on the location and time for the occurrence of relatively large channel degradation, a clustering algorithm was used to identify the location of the erosion center. Characteristics and morphodynamic controls of the erosion centers were studied based on the migration of incisional and coarsening waves simulated by a one‐dimensional morphodynamic model for nonuniform sediment. Results show that the erosion center migrated downstream along the Yichang‐Zhicheng reach with gravel‐sand bed during 2002–2012, the migration rate was rapid after the dam closure then decreased with time. After ∼2012, large cascade dams started to operate along the upper Yangtze River, sediment load further decreased and degradation accelerated at the YCR. Correspondingly, the erosion center migrated to the sand‐bedded upper Jingjiang reach with faster rates. The erosion center migrated for a total of over 200 km with an average rate of ∼14 km/yr during 2002–2020. The underlying gravel layer was exposed due to degradation, which enhanced bed coarsening and resulted in the propagation of the erosion center downstream of the TGD.

FRI355 Hypokalemia-induced Nephrogenic Diabetes Insipidus In A Patient With Medullary Thyroid Carcinoma And Paraneoplastic Cushing’s Syndrome

Abstract Disclosure: S. Jhawar: None. S. Jumani: None. Y. Sterrett: None. H. Elenius: None. P. Veeraraghavan: None. C. Ryan: None. J. Del Rivero: None. S.M. Sadowski: None. N. Nilubol: None. J.G. Verbalis: None. L.K. Nieman: None. E. Globa: None. M.S. Zemskova: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Introduction: Nephrogenic diabetes insipidus (NDI) is commonly associated with the use of medications such as lithium, antibiotics, and chemotherapeutic agents or with renal disorders. Rarely, NDI can be a manifestation of paraneoplastic conditions. We describe a case of NDI caused by severe hypokalemia in a patient with metastatic medullary thyroid cancer (MTC) and paraneoplastic Cushing’s syndrome (CS). Clinical Case: A 47-year-old male with sporadic, metastatic MTC (RET M918T pathogenic variant) was referred to our institution for further management. The patient had florid metastases to the liver, lungs, and skeleton, with a calcitonin of 158,535 pg/mL [normal (NL): <14.3], and a CEA of 3,634 pg/mL (NL: 0.8-3.4), but surprisingly, without an intrathyroidal primary tumor. Vandetanib and octreotide were previously trialed but discontinued due to financial constraints. The patient had diarrhea, but no other symptoms. Physical exam revealed cervical lymphadenopathy, facial plethora, dorsocervical fat pad, and a single purple stria on the chest. Further work up revealed markedly elevated 24-hr urine free cortisol (12,460 mcg/24hr; NL: 35-45), ACTH 116 pg/mL (normal 5.0-46.0), and an undetectable serum aldosterone and plasma renin activity, raising suspicion for paraneoplastic ectopic-CS. Immunostaining of the MTC biopsy specimen showed ACTH positivity. During the inpatient admission, polyuria of >3L/day was noted on two consecutive 24-hour urine measurements. Laboratory investigations revealed hypernatremia (serum sodium: 147 mmol/L; NL: 136-145), elevated serum osmolality (303 mOsm/Kg; NL: 278-298), and a low urine osmolality (215 mOsm/kg; NL: 300-900), thus establishing the diagnosis of DI. A simultaneous, elevated plasma copeptin (36.3 pmol/L; NL: <13.1) further suggested NDI. Also noted was severe hypokalemia (serum potassium: 1.7 mmol/L; NL: 3.5-5.1), with normal serum magnesium and calcium. A thorough review of patient’s medication list did not reveal any culprit drug for hypokalemia or NDI. Hypokalemia was managed with aggressive oral and intravenous potassium repletion. A bilateral adrenalectomy was performed to treat the ectopic-CS, which improved the hypokalemia and resolved the NDI. Three months later, the patient unfortunately died due to progression of MTC. Conclusion: Severe hypokalemia causes autophagic degradation of aquaporin-2 channels in the renal tubules and is an under-recognized cause of NDI. Profound hypercortisolism in ectopic-CS may result in cortisol-mediated overactivation of mineralocorticoid receptors that can cause renal potassium loss leading to NDI. Only 0.6% of MTCs are associated with ectopic-CS (PMID: 16029131). Our report highlights hypokalemia-induced NDI as a manifestation of paraneoplastic CS resulting from MTC. Presentation: Friday, June 16, 2023

IEEE 802.11ax Meet Edge Computing: AP Seamless Handover for Multi-Service Communications in Industrial WLAN

IEEE 802.11ax, as a new generation of wireless local area network (WLAN) standard, has great development potential for multi-service access in industrial WLAN with its characteristics of low-cost, quick-deployment and high-efficiency. However, it still faces the problem of quick and efficient access point (AP) seamless handover for multi-service communications due to terminal mobility and channel degradation. To solve the problem, combining the characteristics of orthogonal frequency division multiple access (OFDMA) technology and multi-user multiple-input multiple-output (MU-MIMO) technology, this paper firstly proposes an edge computing based IEEE 802.11ax multi-service bearer mechanism by dynamically allocating channel resource units (RUs). Secondly, a multi-service AP seamless handover mechanism based on edge computing is proposed, which consists of a channel scanning delay optimization method based on virtual AP sentinel, a handover trigger judgment algorithm considering mobility and RU reallocation, a multi-objective optimized AP handover model considering load balancing, transmission rate optimization and handover cost minimization with service attributes. Finally, we propose a multi-service AP seamless handover algorithm based on improved particle swarm optimization (PSO) to get optimized handover making-decision. Simulation results show that the proposed handover mechanism can reduce the handover delay significantly while realizing seamless handover accurately in multi-service industrial WLAN.