Search

Although all herpesviruses utilize a highly conserved replication machinery to amplify their viral genomes, different members may have unique strategies to modulate the assembly of their replication components. Herein, we characterize the subcellular localization of seven essential replication proteins of varicella-zoster virus (VZV) and show that several viral replication enzymes such as the DNA polymerase subunit ORF28, when expressed alone, are localized in the cytoplasm. The nuclear import of ORF28 can be mediated by the viral DNA polymerase processivity factor ORF16. Besides, ORF16 could markedly enhance the protein abundance of ORF28. Noteworthily, an ORF16 mutant that is defective in nuclear transport still retained the ability to enhance ORF28 abundance. The low abundance of ORF28 in transfected cells was due to its rapid degradation mediated by the ubiquitin-proteasome system. We additionally reveal that radicicol, an inhibitor of the chaperone Hsp90, could disrupt the interaction between ORF16 and ORF28, thereby affecting the nuclear entry and protein abundance of ORF28. Collectively, our findings imply that the cytoplasmic retention and rapid degradation of ORF28 may be a key regulatory mechanism for VZV to prevent untimely viral DNA replication, and suggest that Hsp90 is required for the interaction between ORF16 and ORF28.

IntroductionAtherosclerotic cardiovascular disease is associated with a high mortality rate due to vascular calcification. The role of fetuin-A in aortic arch calcification (AAC) is less well understood.MethodsAn analysis of secondary biomarkers was performed on 800 individuals from the biobank using the community database. AAC was defined by radiologists based on imaging. Multiple variables logical analysis was used for risk analysis.ResultsA total of 736 individual samples were collected based on age and gender. The average age is 65 ± 10 years, and half the population comprises men. In spite of similar body weight, renal function, and hepatic function, the AAC group had higher blood pressure and fetuin-A levels independently: systolic blood pressure (SBP) index ≥130 mmHg [adjusted odds ratio (aOR) 1.85, 95% confidence interval (CI) 1.34–2.57, p = 0.002] and fetuin-A (aOR 0.62, 95% CI 0.50–0.76, p

Abstract This study showcases a method for achieving high-performance yellow and red micro-LEDs through precise control of indium content within quantum wells. By employing a hybrid quantum well structure with our six core technologies, we can accomplish outstanding external quantum efficiency (EQE) and robust stripe bandwidth. The resulting 30 μm × 8 micro-LED arrays exhibit maximum EQE values of 11.56% and 5.47% for yellow and red variants, respectively. Notably, the yellow micro-LED arrays achieve data rates exceeding 1 Gbit/s for non-return-to-zero on–off keying (NRZ-OOK) format and 1.5 Gbit/s for orthogonal frequency-division multiplexing (OFDM) format. These findings underscore the significant potential of long-wavelength InGaN-based micro-LEDs, positioning them as highly promising candidates for both full-color microdisplays and visible light communication applications.

Abstract Charge density waves (CDWs) involved with electronic and phononic subsystems simultaneously are a common quantum state in solid-state physics, especially in low-dimensional materials. However, CDW phase dynamics in various dimensions are yet to be studied, and their phase transition mechanism is currently moot. Here we show that using the distinct temperature evolution of orientation-dependent ultrafast electron and phonon dynamics, different dimensional CDW phases are verified in CuTe. When the temperature decreases, the shrinking of c-axis length accompanied with the appearance of interchain and interlayer interactions causes the quantum fluctuations (QF) of the CDW phase until 220 K. At T

With the increasing reliance on unmanned logistics through drone technology, the challenge of efficiently transporting heavy cargo has emerged. The study delves into the complexities of multi-drone cargo transportation, focusing on the stability of transported goods. To address the limitations of single drones in carrying heavy loads, we propose the integration of a disturbance observer-based (DOB) controller to effectively estimate disturbances without intricate calculations or additional sensors and specific knowledge of the cargo’s characteristics, thereby enhancing cargo movement stability. This estimated disturbance is countered by dynamically adjusting the drone’s inclination, reducing the cargo swing angle, and maintaining formation to ensure a balanced weight distribution during transportation. In addition, we investigate the impact of positional accuracy on overall performance and find that a PID controller combined with the DOB controller outperforms both standalone PID control and the combination of PID and formation control relative to the desired reference. Real-world experiments, which have rigorously validated the efficacy of our proposed method, demonstrate its ability to neutralize disturbances and stabilize drones within constrained areas quickly, instilling confidence in its reliability and effectiveness.

Abstract Transition metal dichalcogenides, by virtue of their two-dimensional structures, could provide the largest active surface for reactions with minimal materials consumed, which has long been pursued in the design of ideal catalysts. Nevertheless, their structurally perfect basal planes are typically inert; their surface defects, such as under-coordinated atoms at the surfaces or edges, can instead serve as catalytically active centers. Here we show a reaction probability > 90 % for adsorbed methanol (CH3OH) on under-coordinated Pt sites at surface Te vacancies, produced with Ar+ bombardment, on layered PtTe2 — approximately 60 % of the methanol decompose to surface intermediates CHxO (x = 2, 3) and 35 % to CHx (x = 1, 2), and an ultimate production of gaseous molecular hydrogen, methane, water and formaldehyde. The characteristic reactivity is attributed to both the triangular positioning and varied degrees of oxidation of the under-coordinated Pt at Te vacancies.

Abstract The monitoring of physiological parameters is a crucial topic in promoting human health and an indispensable approach for assessing physiological status and diagnosing diseases. Particularly, it holds significant value for patients who require long-term monitoring or with underlying cardiovascular disease. To this end, Visual Contactless Physiological Monitoring (VCPM) is capable of using videos recorded by a consumer camera to monitor blood volume pulse (BVP) signal, heart rate (HR), respiratory rate (RR), oxygen saturation (SpO2) and blood pressure (BP). Recently, deep learning-based pipelines have attracted numerous scholars and achieved unprecedented development. Although VCPM is still an emerging digital medical technology and presents many challenges and opportunities, it has the potential to revolutionize clinical medicine, digital health, telemedicine as well as other areas. The VCPM technology presents a viable solution that can be integrated into these systems for measuring vital parameters during video consultation, owing to its merits of contactless measurement, cost-effectiveness, user-friendly passive monitoring and the sole requirement of an off-the-shelf camera. In fact, the studies of VCPM technologies have been rocketing recently, particularly AI-based approaches, but few are employed in clinical settings. Here we provide a comprehensive overview of the applications, challenges, and prospects of VCPM from the perspective of clinical settings and AI technologies for the first time. The thorough exploration and analysis of clinical scenarios will provide profound guidance for the research and development of VCPM technologies in clinical settings.

Abstract Free-space optical communications hold promising advantages, including a large bandwidth, access to license-free spectrum, high data rates, quick and simple deployment, low power consumption, and relaxed quality requirements. Nevertheless, key technical challenges remain, such as a higher transmission efficiency, a lower transmission loss, and a smaller form factor of optical systems. Here, we demonstrate the viability of circular-polarization-multiplexed multi-channel optical communication using metasurfaces alongside a photonic-crystal surface-emitting laser (PCSEL) light source at wavelength of 940 nm. Through the light manipulation with metasurface, we split the linearly polarized incidence into left and right circular polarizations with desired diffraction angles. Such orthogonal polarization states provide a paradigm of polarization division multiplexing technique for light communication. The PCSEL light source maintains a low divergence angle of about 0.373 degrees after passing through an ultra-thin metasurface without further bulky collimator or light guide, making end-to-end (E2E) and device-to-device (D2D) communications available in a compact form. Both light source and modulated polarized light exhibit a − 3 dB bandwidth over 500 MHz, with successful 1 Gbit/s transmission demonstrated in eye diagrams. Our results affirm that metasurface effectively boosts transmission capacity without compromising the light source's inherent properties. Future metasurface designs could expand channel capacity, and its integration with PCSEL monolithically holds promise for reducing interface losses, thereby enhancing efficiency.

Diabetic nephropathy, a leading cause of end-stage renal disease, accounts for significant morbidity and mortality. It is characterized by microinflammation in the glomeruli and myofibroblast activation in the tubulointerstitium. Salvia miltiorrhiza Bunge, a traditional Chinese medicine, is shown to possess anti-inflammatory and anti-fibrotic properties, implying its renal-protective potential. This study investigates which type of component can reduce the damage caused by diabetic nephropathy in a single setting. The ethyl acetate (EtOAc) layer was demonstrated to provoke peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ activities in renal mesangial cells by dual luciferase reporter assay. In a high glucose (HG)-cultured mesangial cell model, the EtOAc layer substantially inhibited HG-induced elevations of interleukin-1β, transforming growth factor-β1 (TGF-β1), and fibronectin, whereas down-regulated PPAR-γ was restored. In addition, among the extracts of S. miltiorrhiza, the EtOAc layer effectively mitigated TGF-β1-stimulated myofibroblast activation. The EtOAc layer also showed a potent ability to attenuate renal hypertrophy, proteinuria, and fibrotic severity by repressing diabetes-induced proinflammatory factor, extracellular matrix accumulation, and PPAR-γ reduction in the STZ-induced diabetes mouse model. Our findings, both in vitro and in vivo, indicate the potential of the EtOAc layer from S. miltiorrhiza for future drug development targeting diabetic nephropathy.

Abstract The scaling of transistors with thinner channel thicknesses has led to a surge in research on two-dimensional (2D) and quasi-2D semiconductors. However, modulating the threshold voltage (V T) in ultrathin transistors is challenging, as traditional doping methods are not readily applicable. In this work, we introduce a optical-thermal method, combining ultraviolet (UV) illumination and oxygen annealing, to achieve broad-range V T tunability in ultrathin In2O3. This method can achieve both positive and negative V T tuning and is reversible. The modulation of sheet carrier density, which corresponds to V T shift, is comparable to that obtained using other doping and capacitive charging techniques in other ultrathin transistors, including 2D semiconductors. With the controllability of V T, we successfully demonstrate the realization of depletion-load inverter and multi-state logic devices, as well as wafer-scale V T modulation via an automated laser system, showcasing its potential for low-power circuit design and non-von Neumann computing applications.

Abstract In this study, we have demonstrated the potential of InGaN-based red micro-LEDs with single quantum well (SQW) structure for visible light communication applications. Our findings indicate the SQW sample has a better crystal quality, with high-purity emission, a narrower full width at half maximum, and higher internal quantum efficiency, compared to InGaN red micro-LED with a double quantum wells (DQWs) structure. The InGaN red micro-LED with SQW structure exhibits a higher maximum external quantum efficiency of 5.95% and experiences less blueshift as the current density increases when compared to the DQWs device. Furthermore, the SQW device has a superior modulation bandwidth of 424 MHz with a data transmission rate of 800 Mbit/s at an injection current density of 2000 A/cm2. These results demonstrate that InGaN-based SQW red micro-LEDs hold great promise for realizing full-color micro-display and visible light communication applications.

This study introduces a novel approach for fabricating vertically stacked mini-LED arrays, integrating InGaN yellow and blue epitaxial layers with a stress buffer layer to enhance optoelectronic characteristics and structural stability. This method significantly simplifies the LED design by reducing the need for RGB configurations, thus lowering costs and system complexity. Employing vertical stacking integration technology, the design achieves high-density, efficient white light production suitable for multifunctional applications, including automotive lighting and outdoor signage. Experimental results demonstrate the exceptional performance of the stacked yellow and blue mini-LEDs in terms of luminous efficiency, wavelength precision, and thermal stability. The study also explores the performance of these LEDs under varying temperature conditions and their long-term reliability, indicating that InGaN-based yellow LEDs offer superior performance over traditional AlGaInP yellow LEDs, particularly in high-temperature environments. This technology promises significant advancements in the design and application of lighting systems, with potential implications for both automotive and general illumination markets.

Background: Spheroids generated by tumor cells collected from malignant pleural effusion (MPE) were shown to retain the characteristics of the original tumors. This ex vivo model might be used to predict the response of non-small cell lung cancer (NSCLC) to anticancer treatments. Methods: The characteristics, epidermal growth factor receptor (EGFR) mutation status, and clinical response to EGFR-TKIs treatment of enrolled patients were recorded. The viability of the spheroids generated from MPE of enrolled patients were evaluated by visualization of the formazan product of the MTT assay. Results: Spheroids were generated from 14 patients with NSCLC-related MPE. Patients with EGFR L861Q, L858R, or Exon 19 deletion all received EGFR-TKIs, and five of these seven patients responded to treatment. The viability of the spheroids generated from MPE of these five patients who responded to EGFR-TKIs treatment was significantly reduced after gefitinib treatment. On the other hand, gefitinib treatment did not reduce the viability of the spheroids generated from MPE of patients with EGFR wild type, Exon 20 insertion, or patients with sensitive EGFR mutation but did not respond to EGFR-TKIs treatment. Conclusion: Multicellular spheroids generated from NSCLC-related MPE might be used to predict the response of NSCLC to treatment.

Diabetes is not solely a metabolic disorder but also involves inflammatory processes. The immune response it incites is a primary contributor to damage in target organs. Research indicates that during the initial phases of diabetic nephropathy, macrophages infiltrate the kidneys alongside lymphocytes, initiating a cascade of inflammatory reactions. The interplay between macrophages and other renal cells is pivotal in the advancement of kidney disease within a hyperglycemic milieu. While M1 macrophages react to the inflammatory stimuli induced by elevated glucose levels early in the disease progression, their subsequent transition to M2 macrophages, which possess anti-inflammatory and tissue repair properties, also contributes to fibrosis in the later stages of nephropathy by transforming into myofibroblasts. Comprehending the diverse functions of macrophages in diabetic kidney disease and regulating their activity could offer therapeutic benefits for managing this condition.

Abstract Background Little research has been done on ischemic outcomes related to left ventricular ejection fraction (EF) in acute decompensated heart failure (ADHF). Methods A retrospective cohort study was conducted between 2001 and 2021 using the Chang Gung Research Database. ADHF Patients discharged from hospitals between January 1, 2005, and December 31, 2019. Cardiovascular (CV) mortality and heart failure (HF) rehospitalization are the primary outcome components, along with all-cause mortality, acute myocardial infarction (AMI) and stroke. Results A total of 12,852 ADHF patients were identified, of whom 2,222 (17.3%) had HFmrEF, the mean (SD) age was 68.5 (14.6) years, and 1,327 (59.7%) were males. In comparison with HFrEF and HFpEF patients, HFmrEF patients had a significant phenotype comorbid with diabetes, dyslipidemia, and ischemic heart disease. Patients with HFmrEF were more likely to experience renal failure, dialysis, and replacement. Both HFmrEF and HFrEF had similar rates of cardioversion and coronary interventions. There was an intermediate clinical outcome between HFpEF and HFrEF, but HFmrEF had the highest rate of AMI (HFpEF, 9.3%; HFmrEF, 13.6%; HFrEF, 9.9%). The AMI rates in HFmrEF were higher than those in HFpEF (AHR, 1.15; 95% Confidence Interval, 0.99 to 1.32) but not in HFrEF (AHR, 0.99; 95% Confidence Interval, 0.87 to 1.13). Conclusion Acute decompression in patients with HFmrEF increases the risk of myocardial infarction. The relationship between HFmrEF and ischemic cardiomyopathy, as well as optimal anti-ischemic treatment, requires further research on a large scale.

ABSTRACT Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes six highly conserved core replication proteins essential for the viral lytic DNA synthesis, including ORF6 (single-stranded DNA-binding protein), ORF9 (DNA polymerase), ORF40/41 (primase-associated factor), ORF44 (helicase), ORF56 (primase), and ORF59 (polymerase processivity factor). Since the protein-protein interactions among KSHV core replication proteins are largely unknown, this study aimed to decipher their interrelationships. Herein, we propose a protein-protein interaction network of these six core replication proteins according to the results obtained from confocal fluorescence microscopy, coimmunoprecipitation, and mammalian two-hybrid (GAL4/VP16) reporter assays. In this interaction network, ORF40/41 plays a central role in the connection of different replication subcomplexes. In addition to the well-conserved helicase-primase subcomplex (consisting of ORF44, ORF56, and ORF40/41) and the replisome subcomplex (consisting of ORF9 and ORF59), our data also suggest that several discrete, stable subcomplexes exist in the cell nucleus. Among these replication subcomplexes in the nucleus, the tetrameric subcomplex composed of ORF44, ORF56, ORF40/41, and ORF6 exhibited the ability to trigger a DNA damage response. By using an established GAL4/VP16-based reporter system and confocal fluorescence microscopy, we additionally found that the heat shock protein 90 (Hsp90) inhibitor, radicicol, significantly inhibited the formation of both the helicase-primase subcomplex and the replisome subcomplex in a dose-dependent manner. Collectively, these data not only provide further insights into the interaction and assembly of KSHV-encoded core replication proteins but also suggest a critical role of Hsp90 in assisting the construction of the viral core replication machinery. IMPORTANCE Eukaryotic DNA replication is a highly regulated process that requires multiple replication enzymes assembled onto DNA replication origins. Due to the complexity of the cell’s DNA replication machinery, most of what we know about cellular DNA replication has come from the study of viral systems. Herein, we focus our study on the assembly of the Kaposi’s sarcoma-associated herpesvirus core replication complex and propose a pairwise protein-protein interaction network of six highly conserved viral core replication proteins. A detailed understanding of the interaction and assembly of the viral core replication proteins may provide opportunities to develop new strategies against viral propagation.

Abstract Defects to popular two-dimensional (2D) transition metal dichalcogenides (TMDs) seriously lower the efficiency of field-effect transistor (FET) and depress the development of 2D materials. These atomic defects are mainly identified and researched by scanning tunneling microscope (STM) because it can provide precise measurement without harming the samples. The long analysis time of STM for locating defects in images has been solved by combining feature detection with convolutional neural networks (CNN). However, the low signal-noise ratio, insufficient data, and a large amount of TMDs members make the automatic defect detection system hard to be applied. In this study, we propose a deep learning-based atomic defect detection framework (DL-ADD) to efficiently detect atomic defects in molybdenum disulfide (MoS2) and generalize the model for defect detection in other TMD materials. We design DL-ADD with data augmentation, color preprocessing, noise filtering, and a detection model to improve detection quality. The DL-ADD provides precise detection in MoS2 (F2-scores is 0.86 on average) and good generality to WS2 (F2-scores is 0.89 on average).

Myelodysplastic syndrome (MDS) immunity plays an important role in the proliferation and apoptosis of aberrant cells. Immune dysregulation has been studied in various prognostic subgroups. This study analyzed 60 patients with MDS via multidimensional flow cytometry to evaluate the expression of aberrant markers, such as CD7 and cytoplasmic CD3 on lymphocytes. The Revised International Prognostic Scoring System (IPSS-R) scores were used to classify the patients into risk groups. The results showed a significant downregulation of CyCD3− T cells in low–intermediate versus high-risk patients (p = 0.013). This study is the first to show that a significant decrease in cyCD3− T cells in patients with a lower IPSS-R score may indicate microenvironmental changes conducive to transformation in MDS.

Hospital revisits significantly contribute to financial burden. Therefore, developing strategies to reduce hospital revisits is crucial for alleviating the economic impacts. However, this critical issue among peritoneal dialysis (PD) patients has not been explored in previous research. This single-center retrospective study, conducted at Chang Gung Memorial Hospital, Chiayi branch, included 1373 PD patients who visited the emergency room (ER) between Jan 2002 and May 2018. The objective was to predict hospital revisits, categorized into 72-h ER revisits and 14-day readmissions. Of the 1373 patients, 880 patients visiting the ER without subsequent hospital admission were analyzed to predict 72-h ER revisits. The remaining 493 patients, who were admitted to the hospital, were studied to predict 14-day readmissions. Logistic regression and decision tree methods were employed as prediction models. For the 72-h ER revisit study, 880 PD patients had a revisit rate of 14%. Both logistic regression and decision tree models demonstrated a similar performance. Furthermore, the logistic regression model identified coronary heart disease as an important predictor. For 14-day readmissions, 493 PD patients had a readmission rate of 6.1%. The decision tree model outperformed the logistic model with an area under the curve value of 79.4%. Additionally, a high-risk group was identified with a 36.4% readmission rate, comprising individuals aged 41 to 47 years old with a low alanine transaminase level ≤15 units per liter. In conclusion, we present a study using regression and decision tree models to predict hospital revisits in PD patients, aiding physicians in clinical judgment and improving care.

Abstract Recently, inductive power transfer (IPT) system has been used for wireless charging of electric vehicles (EVs). However, most of them only treat the issue of single directional wireless power transfer (WPT). This research proposes a novel bi‐directional IPT (BD‐IPT) scheme EVs, which can simultaneously transmit power/data via magnetic field when the mutual inductance changes. For power transmission, resonant inverters with phase‐shift pulse width modulation (PSPWM) are used to generate carrier waves and alternating current. As for data transmission, a dedicated communication method with the accompanied protocol is proposed. Binary phase shift keying (BPSK) is used to simulate the two‐quadrature amplitude modulation (QAM), which generates digital signals for data transmission without the need of extra communication links. Hamming codes are combined with single‐error correction and double‐error detection (SECDED) to ensure communication quality.

Abstract Plumbene, with a structure similar to graphene, is expected to possess a strong spin–orbit coupling and thus enhances its superconducting critical temperature (Tc). In this work, a buckled plumbene‐Au Kagome superstructure grown by depositing Au on Pb(111) is investigated. The superconducting gap monitored by temperature‐dependent scanning tunneling microscopy/spectroscopy shows that the buckled plumbene‐Au Kagome superstructure not only has an enhanced Tc with respect to that of a monolayer Pb but also possesses a higher value than what owned by a bulk Pb substrate. By combining angle‐resolved photoemission spectroscopy with density functional theory, the monolayer Au‐intercalated low‐buckled plumbene sandwiched between the top Au Kagome layer and the bottom Pb(111) substrate is confirmed and the electron–phonon coupling‐enhanced superconductivity is revealed. This work demonstrates that a buckled plumbene‐Au Kagome superstructure can enhance superconducting Tc and Rashba effect, effectively triggering the novel properties of a plumbene.

Sleep-related problems are widespread. Numerous devices for sleep monitoring are increasingly available, including smartwatches, sleep monitoring rings, etc. These devices accumulate and analyze a substantial quantity of physiological data. In this study, we develop a smart air-mattress system that can effectively aid health measurements. The proposed system adopts an air-mattress system to detect subtle changes in pressure and thereby collect micro physiological signals, including ballistocardiography (BCG) and breathing signals. The system uses ultrasonic signals to detect the subject's turning movements. To increase the signal recognition accuracy, the BCG signal is processed effectively to reduce noise interference engendered by the body movement during sleep and is processed using regression analysis for heart rate and breathing rate estimation. Accordingly, the proposed system is unconstrained and can be used to collect micro BCG signals, breathing signals, heart rate signals, and turning movements for the long-term health-care.

Abstract Recently, facial recognition has been extensively adopted in various fields. Wide applications are associated with a large amount of data transmission so that edge computing is inspired accordingly. In this research task, the major goal of edge computing is to handover a part of the computing work to the terminal equipment; the server only needs to process the results of final return. The IoT configuration proposed includes a perception layer, a transmission layer, and an application layer to fulfil a complete IoT system. In the perception layer, the facial authentication mechanism is adopted. This system is equipped with a highly robust anti‐spoofing function, which can avoid criminal access from photos or electronic screens. Finally, the IoT transmission system is realised as the transmission layer. Combined with such a transmission mechanism, one can distribute user facial features to user's electronic devices instead of storing it in the server. This not only saves storage resources and transmission costs, but also allows users to complete data transmission and face authentication easily.

Abstract With the increasing demand of silicon carbide (SiC) power devices that outperform the silicon-based devices, high cost and low yield of SiC manufacturing process are the most urgent issues yet to be solved. It has been shown that the performance of SiC devices is largely influenced by the presence of so-called killer defects, formed during the process of crystal growth. In parallel to the improvement of the growth techniques for reducing defect density, a post-growth inspection technique capable of identifying and locating defects has become a crucial necessity of the manufacturing process. In this review article, we provide an outlook on SiC defect inspection technologies and the impact of defects on SiC devices. This review also discusses the potential solutions to improve the existing inspection technologies and approaches to reduce the defect density, which are beneficial to mass production of high-quality SiC devices.

Vaccine-related immune responses are one of the causes of encephalitis. Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) have been administered worldwide due to the ongoing global pandemic; cases of SARS-CoV-2 vaccination-related encephalitis were scarcely reported. An 82-year-old female was diagnosed with acute encephalitis following her first dose of vaccination with mRNA-1273 against SARS-CoV-2. The patient presented with fever and headache five days after vaccination, followed by behavior change 17 days after vaccination. Electroencephalographic recordings revealed focal slow waves in the right frontoparietal regions. Brain MRI revealed the signal change in the right middle and posterior temporal lobe. Cerebrospinal fluid analysis showed mildly elevated protein. She responded well to steroid pulse therapy and made a full recovery. The severity of the immune response following COVID-19 vaccination may be alleviated if adequate treatment is achieved. Physicians must be alert for encephalitis after vaccination to help ensure a favorable outcome.

As people are accustomed to the popularization of information services, immersive experiences are emphasized, which drives the vigorous development of virtual reality. In practice, devices are limited by their computing capabilities and rely on cloud computing to complete the overall service provided. As a result, technologies of the Internet of Things (IoT) emerge to respond to this demand. As an ideal IoT, in addition to lightweight, it is ideally to possess the following features: easy installation of devices, intelligent networking capability, multi-field equipment sharing, and customizable to meet various needs. However, most of the current IoTs are “Internet of Targets” rather than “Internet of Things”. The Internet of Targets is lacking interoperability because of incompatible communication protocols and interface features among a variety of “devices” leading to different barriers thus hindering its applicability. This research task proposes two new ideas-refactor and feedback. The former meant that the system is able to change transmission path intelligently. The later enables the system reacts and acts appropriately in real time when receiving a stimulation. On the basis of the two factors we construct a conscious system served as the core of the “ideal IoT”. For the practical operating framework, we build a service model that integrates different data formations with feedback. We demonstrate the presented design by realizing a compact IoT system for long-term health care.

Type 1 diabetes is an inflammatory state. Myeloid-derived suppressive cells (MDSCs) originate from immature myeloid cells and quickly expand to control host immunity during infection, inflammation, trauma, and cancer. This study presents an ex vivo procedure to develop MDSCs from bone marrow cells propagated from granulocyte–macrophage-colony-stimulating factor (GM-CSF), interleukin (IL)-6, and IL-1β cytokines expressing immature morphology and high immunosuppression of T-cell proliferation. The adoptive transfer of cytokine-induced MDSCs (cMDSCs) improved the hyperglycemic state and prolonged the diabetes-free survival of nonobese diabetic (NOD) mice with severe combined immune deficiency (SCID) induced by reactive splenic T cells harvested from NOD mice. In addition, the application of cMDSCs reduced fibronectin production in the renal glomeruli and improved renal function and proteinuria in diabetic mice. Moreover, cMDSCs use mitigated pancreatic insulitis to restore insulin production and reduce the levels of HbA1c. In conclusion, administering cMDSCs propagated from GM-CSF, IL-6, and IL-1β cytokines provides an alternative immunotherapy protocol for treating diabetic pancreatic insulitis and renal nephropathy.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to inadequate insulin secretion, resistance, or both. The cardiovascular complications of DM are the leading cause of morbidity and mortality in diabetic patients. There are three major types of pathophysiologic cardiac remodeling including coronary artery atherosclerosis, cardiac autonomic neuropathy, and DM cardiomyopathy in patients with DM. DM cardiomyopathy is a distinct cardiomyopathy characterized by myocardial dysfunction in the absence of coronary artery disease, hypertension, and valvular heart disease. Cardiac fibrosis, defined as the excessive deposition of extracellular matrix (ECM) proteins, is a hallmark of DM cardiomyopathy. The pathophysiology of cardiac fibrosis in DM cardiomyopathy is complex and involves multiple cellular and molecular mechanisms. Cardiac fibrosis contributes to the development of heart failure with preserved ejection fraction (HFpEF), which increases mortality and the incidence of hospitalizations. As medical technology advances, the severity of cardiac fibrosis in DM cardiomyopathy can be evaluated by non-invasive imaging modalities such as echocardiography, heart computed tomography (CT), cardiac magnetic resonance imaging (MRI), and nuclear imaging. In this review article, we will discuss the pathophysiology of cardiac fibrosis in DM cardiomyopathy, non-invasive imaging modalities to evaluate the severity of cardiac fibrosis, and therapeutic strategies for DM cardiomyopathy.

Chronic kidney disease (CKD) is a serious public health problem. Due to a high variability in the speed of CKD progression to end-stage renal disease (ESRD) and the critical involvement of Wnt/β-catenin signaling in CKD, we investigated the role of the Wnt antagonist Dickkopf-1 (DKK1) in CKD progression. Our data revealed that patients with CKD stages 4–5 had higher DKK1 levels in their serum and renal tissues than the control subjects. In an 8-year follow-up, the serum DKK1-high group in the enrolled CKD patients showed a faster progression to ESRD than the serum DKK1-low group. Using a rat model of 5/6 nephrectomy (Nx)-induced CKD, we consistently detected elevated serum levels and renal production of DKK1 in 5/6 Nx rats compared to sham-operated rats. Importantly, the knockdown of the DKK1 levels in the 5/6 Nx rats markedly attenuated the CKD-associated phenotypes. Mechanistically, we demonstrated that the treatment of mouse mesangial cells with recombinant DKK1 protein induced not only the production of multiple fibrogenic proteins, but also the expression of endogenous DKK1. Collectively, our findings suggest that DKK1 acts as a profibrotic mediator in CKD, and elevated levels of serum DKK1 may be an independent predictor of faster disease progression to ESRD in patients with advanced CKD.

Abstract Diabetic nephropathy (DN) is one of the major leading cause of kidney failure. To identify the progression of chronic kidney disease (CKD), renal function/fibrosis is playing a crucial role. Unfortunately, lack of sensitivities/specificities of available clinical biomarkers are key major issues for practical healthcare applications to identify the renal functions/fibrosis in the early stage of DN. Thus, there is an emerging approach such as therapeutic or diagnostic are highly desired to conquer the CKD at earlier stages. Herein, we applied and examined the application of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted imaging (DWI) to identify the progression of fibrosis between wild type (WT) and miR29a transgenic (Tg) mice during streptozotocin (STZ)-induced diabetes. Further, we also validate the potential renoprotective role of miR29a to maintain the renal perfusion, volume, and function. In addition, Ktrans values of DCE-MRI and apparent diffusion coefficient (ADC) of DWI could significantly reflect the level of fibrosis between WT and Tg mice at identical conditions. As a result, we strongly believed that the present non-invasive MR imaging platforms have potential to serveas an important tool in research and clinical imaging for renal fibrosis in diabetes, and that microenvironmental changes could be identified by MR imaging acquisition prior to histological biopsy and diabetic podocyte dysfunction.

Arteriovenous graft (AVG) is an important vascular access route in hemodialysis patients. The optimal waiting time between AVG creation and the first cannulation is still undetermined, therefore the current study investigated the association between ideal timing for cannulation and AVG survival. This retrospective cohort study used data from the Taiwan National Health Insurance Database, which included 6,493 hemodialysis patients with AVGs between July 1st 2008 and June 30th 2012. The waiting cannulation time was defined as the time from the date of shunt creation to the first successful cannulation. Patients were categorized according to the waiting cannulation time of their AVGs as follows: ≤30 days, between 31 and 90 days, between 91 and 180 days, and >180 days. The primary outcome was functional cumulative survival, measured as the time from the first cannulation to shunt abandonment. The AVGs which were cannulated between 31 and 90 days (reference group) after construction had significantly superior functional cumulative survival compared with those cannulated ≤30 days (adjusted HR = 1.651 with 95% CI 1.482–1.839; p 180 days (adjusted HR = 1.197 with 95% CI 1.012–1.417; p = 0.0363) after construction. An analysis of the hazard ratios in patients with different demographic characteristics, revealed that the functional cumulative survival of AVGs in most groups was better when they received cannulation >30 days after construction. Consequently, in order to achieve the best long-term survival, AVGs should be cannulated at least 1 month after construction, but you should avoid waiting for >3 months.

Redox is a constant phenomenon in organisms. From the signaling pathway transduction to the oxidative stress during the inflammation and disease process, all are related to reduction-oxidation (redox). Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor targeting many antioxidant genes. In non-stressed conditions, NRF2 maintains the hemostasis of redox with housekeeping work. It expresses constitutively with basal activity, maintained by Kelch-like-ECH-associated protein 1 (KEAP1)-associated ubiquitination and degradation. When encountering stress, it can be up-regulated by several mechanisms to exert its anti-oxidative ability in diseases or inflammatory processes to protect tissues and organs from further damage. From acute kidney injury to chronic kidney diseases, such as diabetic nephropathy or glomerular disease, many results of studies have suggested that, as a master of regulating redox, NRF2 is a therapeutic option. It was not until the early termination of the clinical phase 3 trial of diabetic nephropathy due to heart failure as an unexpected side effect that we renewed our understanding of NRF2. NRF2 is not just a simple antioxidant capacity but has pleiotropic activities, harmful or helpful, depending on the conditions and backgrounds.

The monolithic integration of InGaN-based micro-LEDs is being of interest toward developing full-color micro-displays. However, the color stability in InGaN red micro-LED is an issue that needs to be addressed. In this study, the modified distributed Bragg reflectors (DBRs) were designed to reduce the transmission of undesired spectra. The calculated optical properties of the InGaN red micro-LEDs with conventional and modified DBRs have been analyzed, respectively. The CIE 1931 color space and the encoded 8-bit RGB values are exhibited for the quantitative assessment of color stability. The results suggest the modified DBRs can effectively reduce the color shift, paving the way for developing full-color InGaN-based micro-LED displays.

Diabetic nephropathy is a complication of diabetes that leads to end-stage kidney disease and is a major health burden worldwide. Prenylflavonoid compounds extracted from Macaranga tanarius (MTE) exhibit anti-inflammation, anti-oxidant, and anti-bacterial properties. However, the effects of these compounds on diabetic nephropathy remain unclear. The effects of MTE on diabetic nephropathy were investigated in vitro by using mouse renal mesangial cells and in vivo by using a db/db knockout mouse model. No overt alteration in proliferation was observed in mouse renal mesangial cells treated with 0–1 μg/mL MTE. Western blot analysis indicated that MTE dose-dependently attenuated the expression of fibronectin, α-smooth muscle actin, and collagen IV. Administration of MTE ameliorated renal albumin loss in db/db mice. Immunohistochemical staining revealed that MTE mitigated diabetes-induced fibronectin and collagen IV expression. Periodic acid–Schiff (PAS) and trichrome staining also showed that administration of MTE reduced the renal fibrosis phenomenon. MTE significantly ameliorated diabetes-induced nephropathy.

Unmanned aerial vehicles (UAVs) are becoming popular in various applications. However, there are still challenging issues to be tackled, such as effective obstacle avoidance, target identification within a crowd, and specific target tracking. This paper focuses on dynamic target following and obstacle avoidance to realize a prototype of a quadcopter drone to serve as an autonomous object follower. An adaptive target identification system is proposed to recognize the specific target in the complicated background. For obstacle avoidance during flight, we introduce an idea of space detection and use it to develop a so-called contour and spiral convolution space detection (CASCSD) algorithm to evade obstacles. Thanks to the low architecture complexity, it is appropriate for implementation on onboard flight control systems. The target prediction is integrated with fuzzified flight control to fulfill an autonomous target tracker. When this series of technical research and development is completed, this system can be used for applications such as personal security guard and criminal detection systems.

ABSTRACT The open reading frame 50 (ORF50) protein of Kaposi’s sarcoma-associated herpesvirus (KSHV) is the master regulator essential for initiating the viral lytic cycle. Previously, we have demonstrated that the ORF50 protein can cooperate with Sp3 to synergistically activate a set of viral and cellular gene promoters through highly conserved ORF50-responsive elements that harbor a Sp3-binding motif. Herein, we show that Sp3 undergoes proteolytic cleavage during the viral lytic cycle, and the cleavage of Sp3 is dependent on caspase activation. Since similar cleavage patterns of Sp3 could be detected in both KSHV-positive and KSHV-negative lymphoma cells undergoing apoptosis, the proteolytic cleavage of Sp3 could be a common event during apoptosis. Mutational analysis identifies 12 caspase cleavage sites in Sp3, which are situated at the aspartate (D) positions D17, D19, D180, D273, D275, D293, D304 (or D307), D326, D344, D530, D543, and D565. Importantly, we noticed that three stable Sp3 C-terminal fragments generated through cleavage at D530, D543, or D565 encompass an intact DNA-binding domain. Like the full-length Sp3, the C-terminal fragments of Sp3 could still retain the ability to cooperate with ORF50 protein to activate specific viral and cellular gene promoters synergistically. Collectively, our findings suggest that despite the proteolytic cleavage of Sp3 under apoptotic conditions, the resultant Sp3 fragments may retain biological activities important for the viral lytic cycle or for cellular apoptosis. IMPORTANCE The ORF50 protein of Kaposi’s sarcoma-associated herpesvirus (KSHV) is the key viral protein that controls the switch from latency to lytic reactivation. It is a potent transactivator that can activate target gene promoters via interacting with other cellular DNA-binding transcription factors, such as Sp3. In this report, we show that Sp3 is proteolytically cleaved during the viral lytic cycle, and up to 12 caspase cleavage sites are identified in Sp3. Despite the proteolytic cleavage of Sp3, several resulting C-terminal fragments that have intact zinc-finger DNA-binding domains still retain substantial influence in the synergy with ORF50 to activate specific gene promoters. Overall, our studies elucidate the caspase-mediated cleavage of Sp3 and uncover how ORF50 utilizes the cleavage fragments of Sp3 to transactivate specific viral and cellular gene promoters.

Objective: Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.Methods: The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994–2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.Results: Low cholesterol (LDL-C

Diabetic kidney disease (DKD) frequently leads to end-stage renal disease and other life-threatening illnesses. The dysregulation of glomerular cell types, including mesangial cells, endothelial cells, and podocytes, appears to play a vital role in the development of DKD. Myeloid-derived suppressor cells (MDSCs) exhibit immunoregulatory and anti-inflammatory properties through the depletion of L-arginine that is required by T cells, through generation of oxidative stress, interference with T-cell recruitment and viability, proliferation of regulatory T cells, and through the promotion of pro-tumorigenic functions. Under hyperglycemic conditions, mouse mesangial cells reportedly produce higher levels of fibronectin and pro-inflammatory cytokines. Moreover, the number of MDSCs is noticeably decreased, weakening inhibitory immune activities, and creating an inflammatory environment. In diabetic mice, immunotherapy with MDSCs that were induced by a combination of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-1β, and IL-6, reduced kidney to body weight ratio, fibronectin expression, and fibronectin accumulation in renal glomeruli, thus ameliorating DKD. In conclusion, MDSCs exhibit anti-inflammatory activities that help improve renal fibrosis in diabetic mice. The therapeutic targeting of the proliferative or immunomodulatory pathways of MDSCs may represent an alternative immunotherapeutic strategy for DKD.

ABSTRACT The human norovirus (HuNV)-encoded nucleoside-triphosphatase (NTPase) is a multifunctional protein critically involved in viral replication and pathogenesis. Previously, we have shown that the viral NTPase is capable of forming vesicle clusters in cells, interacting with other viral proteins such as P22, and promoting cellular apoptosis. Herein, we demonstrate that NTPase-associated vesicle clusters correspond to lipid droplets (LDs) wrapped by the viral protein and show that NTPase-induced apoptosis is mediated through both caspase-8- and caspase-9-dependent pathways. Deletion analysis revealed that the N-terminal 179-amino-acid (aa) region of NTPase encompasses two LD-targeting motifs (designated LTM-1 and LTM-2), two apoptosis-inducing motifs, and multiple regulatory regions. Interestingly, the identified LTM-1 and LTM-2, which are located from aa 1 to 50 and from aa 51 to 90, respectively, overlap with the two apoptosis-inducing motifs. Although there was no positive correlation between the extent of LD localization and the degree of cellular apoptosis for NTPase mutants, we noticed that mutant proteins defective in LD-targeting ability could not induce cellular apoptosis. In addition to LD targeting, the amphipathic LTM-1 and LTM-2 motifs could have the potential to direct fusion proteins to the endoplasmic reticulum (ER). Furthermore, we found that the LTM-1 motif is a P22-interacting motif. However, P22 functionally augmented the proapoptotic activity of the LTM-2 fusion protein but not the LTM-1 fusion protein. Overall, our findings propose that NTPase may participate in multiple cellular processes through binding to LDs or to the ER via its N-terminal amphipathic helix motifs. IMPORTANCE Human noroviruses (HuNVs) are the major agent of global gastroenteritis outbreaks. However, due to the lack of an efficient cell culture system for HuNV propagation, functions of the viral-encoded proteins in host cells are still poorly understood. In the current study, we present that the viral NTPase is a lipid droplet (LD)-associated protein, and we identify two LD-targeting motifs, LTM-1 and LTM-2, in its N-terminal domain. In particular, the identified LTM-1 and LTM-2 motifs, which contain a hydrophobic region and an amphipathic helix, are also capable of delivering the fusion protein to the endoplasmic reticulum (ER), promoting cellular apoptosis, and physically or functionally associating with another viral protein P22. Since LDs and the ER have been linked to several biological functions in cells, our study therefore proposes that the norovirus NTPase may utilize LDs or the ER as replication platforms to benefit viral replication and pathogenesis.

Diabetic kidney disease (DKD) can cause inflammation and fibrosis, in addition to being the main complication of diabetes. Among many factors, epigenetic alterations in aberrant histone modifications play a key role in causing DKD. In this study, the mechanism of GSK-J4, a histone demethylase KDM6A inhibitor, was evaluated in streptozotocin-induced diabetic mice. It was confirmed that GSK-J4, via dickkopf-1 (DKK1) modulation, could significantly reduce proteinuria and glomerulosclerosis in diabetic mice. The mRNA accumulation levels of DKK1, TGF-β1, fibronectin, and collagen IV were significantly elevated in diabetic mice. In contrast, the mRNA accumulations of those genes were significantly reduced in diabetic mice treated with GSK-J4 compared to those in diabetic mice, relatively speaking. The protein accumulation levels of fibronectin and collagen IV were significantly elevated in diabetic mice. Furthermore, GSK-J4 attenuated the high glucose-induced expression of profibrotic factors in mesangial cells via DKK1. In conclusion, our study provides a novel strategy to eliminate fibrosis in the kidneys of DKD mice. Using GSK-J4 reduces DKK1 expression, thereby ameliorating renal insufficiency, glomerulosclerosis morphological abnormalities, inflammation, and fibrosis in diabetic mice.

Nowadays, the flurry of autonomous vehicles is in full swing regarding light detection and ranging (LiDAR) and depth perception. For such visual perception, light plays an important role. We human beings recognize and distinguish surrounding details when the eye focuses light on the retina. For the LiDAR system, pulsed lasers are employed to measure the relevant range. Thus, appropriate light sources with high performance are in urgent demand. Auspiciously, a revolutionary semiconductor laser technology, namely the photonic-crystal surface-emitting laser (PCSEL), emerges over the past two decades. PCSEL exhibits not only a symmetric beam profile with narrow beam divergence but also a high-power operation with controllability. Therefore, it may be the holy grail for an ultracompact time-of-flight (ToF) LiDAR system. Hereupon, comprehensive analyses of PCSEL-relevant scientific publications and patent documents are conducted. We thereby review the development progress of PCSEL technology. Moreover, a systematic simulation is performed, providing real-time visualization of relevant point clouds with different beam divergence. PCSEL technology with unprecedented merits indeed turns a new leaf and a paradigm shift in LiDAR application is ongoing. It is believed that a lens-free and adjustment-free ultracompact apparatus in simplicity can be expected.

Diabetes-induced chronic kidney disease leads to mortality and morbidity and thus poses a great health burden worldwide. Krüppel-like factor 10 (KLF10), a zinc finger-containing transcription factor, regulates numerous cellular functions, such as proliferation, differentiation, and apoptosis. In this study, we explored the effects of KLF10 on diabetes-induced renal disease by using a KLF10 knockout mice model. Knockout of KLF10 obviously diminished diabetes-induced tumor growth factor-β (TGF-β), fibronectin, and type IV collagen expression, as evidenced by immunohistochemical staining. KLF10 knockout also repressed the expression of Dickkopf-1 (DKK-1) and phosphorylated β-catenin in diabetic mice, as evidenced by immunohistochemical staining and Western blot analysis. Quantitative reverse transcriptase–polymerase chain reaction (RT-PCR) revealed that significantly decreased type IV collagen, fibronectin, and DKK-1 existed in KLF10 knockout diabetic mice compared with control diabetic mice. Moreover, knockout of KLF10 reduced the renal fibrosis, as shown by Masson’s Trichrome analysis. Overall, the results indicate that depletion of KLF10 ameliorated diabetic renal fibrosis via the downregulation of DKK-1 expression and inhibited TGF-β1 and phosphorylated β-catenin expression. Our findings suggest that KLF10 may be a promising therapeutic choice for the treatment of diabetes-induced renal fibrosis.

Treatment for glomerular diseases has been extrapolated from the experience of other autoimmune disorders while the underlying pathogenic mechanisms were still not well understood. As the classification of glomerular diseases was based on patterns of juries instead of mechanisms, treatments were typically the art of try and error. With the advancement of molecular biology, the role of the immune agent in glomerular diseases is becoming more evident. The four-hit theory based on the discovery of gd-IgA1 gives a more transparent outline of the pathogenesis of IgA nephropathy (IgAN), and dysregulation of Treg plays a crucial role in the pathogenesis of minimal change disease (MCD). An epoch-making breakthrough is the discovery of PLA2R antibodies in the primary membranous nephropathy (pMN). This is the first biomarker applied for precision medicine in kidney disease. Understanding the immune system’s role in glomerular diseases allows the use of various immunosuppressants or other novel treatments, such as complement inhibitors, to treat glomerular diseases more reasonable. In this era of advocating personalized medicine, it is inevitable to develop precision medicine with mechanism-based novel biomarkers and novel therapies in kidney disease.

Abstract Background Synthesis of a variety of biological circuits for specific functional purposes has made a tremendous progress in recent years. The ultimate goal of combining molecular biology and engineering is to realize a functional biocomputer. To address this challenge, all previous efforts work toward building up the bio-computer as the ultimate goal. To this aim, there should be a key module, named control unit (CU), to direct a serious of logic or arithmetic operations within the processor. Methods This research task develops a bio-CU to work with a bio-ALU, which is realized from the combination of previously developed genetic logic gates to fulfill the kernel function of CPU as those done in the silicon computer. Results A possible framework of the bio-CPU has demonstrated how to connect a bio-CU with a bio-ALU to conduct a fetch-decode-execute cycle of a macro instruction. It presents not only capability of 4-bit full adder but coordination of related modules in biocomputer. Conclusions We have demonstrated computer simulation for applications of the genetic circuits in biocomputer construction. It’s expected to inspire follow-up study to synthesize potential configurations of the future biocomputer.

Abstract Background Diabetes is a proinflammatory state. Fibrosis of the renal glomerulus is the most common cause of end-stage renal disease. Glomerulosclerosis is caused by the accumulation of extracellular matrix (ECM) proteins in the mesangial interstitial space. Mesangial cells are unique stromal cells in the renal glomerulus that form the vascular pole of the renal corpuscle along with the mesangial matrix. Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature myeloid cells that rapidly expand to regulate host immunity during inflammation, infection, and cancer. High concentrations of granulocyte–macrophage colony-stimulating factor (GM-CSF) alone or in combination with other molecules represent the most common ex-vivo protocol for differentiating MDSCs from bone marrow or from peripheral blood mononuclear cells. In this study, we analyzed and characterized the functions of MDSCs under the influence of mouse mesangial cells (MMCs) in a hyperglycemic environment and investigated whether cytokine-induced MDSCs ameliorated renal glomerulosclerosis in diabetic mice. Methods Cytokine-induced MDSCs were propagated from bone marrow cells cultured with mouse recombinant GM-CSF, IL-6, and IL-1β. Diabetic mice were induced with streptozotocin (STZ) and maintained at a blood glucose concentration exceeding 350 mg/dl. The ECM of the renal cortex and fibronectin expression of MMCs were analyzed through immunohistochemistry and western blotting. Arginase 1 and inducible NO synthase expressions of MDSCs were evaluated using quantitative reverse-transcriptase PCR. Cytokines released from MMCs were examined using a cytokine array assay. Results MDSCs in the diabetic mice were redistributed from the bone marrow into peripheral organs. An increase in fibronectin production was also observed in the renal glomerulus. MMCs in vitro produced more fibronectin and proinflammatory cytokines, such as macrophage inflammatory protein-2, RANTES, and stromal-cell-derived factor-1, under hyperglycemic conditions. The adoptive transfer of cytokine-induced MDSCs into STZ-induced mice normalized the glomerular filtration rate to reduce the kidney to body weight ratio and decrease fibronectin production in the renal glomerulus, ameliorating renal fibrosis. These results demonstrate the anti-inflammatory properties of cytokine-induced MDSCs and offer an alternative immunotherapy protocol for the management of diabetic nephropathy. Conclusions The application of cytokine-induced MDSCs provides a promising treatment for renal fibrosis and the prevention of diabetic nephropathy.

Abstract Background Breast cancer is the most common cancer in women and affects 1.38 million women worldwide per year. Antiestrogens such as tamoxifen, a selective estrogen receptor (ER) modulator, are widely used in clinics to treat ER-positive breast tumors. However, remissions of breast cancer are often followed by resistance to tamoxifen and disease relapse. Despite the increasing understanding of the resistance mechanisms, effective regimens for treating tamoxifen-resistant breast cancer are limited. Antrodia cinnamomea is a traditional medicinal mushroom native only to Taiwan. In this study, we aimed to examine in vitro effect of antrodia cinnamomea in the tamoxifen-resistant cancer. Methods Antrodia cinnamomea was studied for its biological activity against proliferation of tamoxifen-resistant breast cancer by XTT assay. Next, the underlying mechanism was studied by flow cytometry, qPCR and Western’s blotting assay. Results Our results revealed that the ethanol extract of antrodia cinnamomea (AC) can inhibit the growth of breast cancer cells, including MCF-7 cell and tamoxifen-resistant MCF-7 cell lines. Combination treatment with AC and 10− 6 M tamoxifen have the better inhibitory effect on the proliferation of tamoxifen-resistant MCF-7 cells than only AC did. AC can induce apoptosis in these breast cancer cells. Moreover, it can suppress the mRNA expression of skp2 (S-phase kinase-associated protein 2) by increasing the expressions of miR-21-5p, miR-26-5p, and miR-30-5p in MCF-7 and tamoxifen-resistant MCF-7 cells. Conclusions These results suggest that the ethanol extract of antrodia cinnamomea could be a novel anticancer agent in the armamentarium of tamoxifen-resistant breast cancer management. Moreover, we hope to identify additional pure compounds that could serve as promising anti-breast cancer candidates for further clinical trials.

Abstract Background Radiotherapy plays an important role in the treatment of prostate cancer. Despite that sophisticated techniques of radiotherapy and radiation combined with chemotherapy were applied to the patients, some tumors may recur. Therefore, the study investigated the effect of dihydroisotanshinone I (DT) and the combination treatment of 5 μM DT and 5Gy irradiation (IR) against the migration ability of prostate cancer cells. Methods DT and the combination treatment were studied for its biological activity against migration ability of prostate cancer cells with transwell migration assay. Subsequently, we tried to explore the underlying mechanism with ELISA, flow cytometry and Western’s blotting assay. Results The results showed that DT and the combination treatment substantially inhibited the migration ability of prostate cancer cells. DT and the combined treatment can decrease the ability of macrophages to recruit prostate cancer cells. Mechanistically, DT and the combination treatment reduced the secretion of chemokine (C-C Motif) Ligand 2 (CCL2) from prostate cancer cells. We also found that DT treatment induced the cell cycle of prostate cancer cells entering S phase and increased the protein expression of DNA damage response proteins (rH2AX and phosphorylated ataxia telangiectasia-mutated [ATM]) in DU145 cells and PC-3 cells. Conclusions DT displays radiosensitization and antimigration effects in prostate cancer cells by inducing DNA damage and inhibiting CCL2 secretion. We suggest that DT can be used as a novel antimetastatic cancer drug or radiosensitizer in the armamentarium of prostate cancer management.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease. The natural history of DKD includes glomerular hyperfiltration, progressive albuminuria, declining estimated glomerular filtration rate, and, ultimately, kidney failure. It is known that DKD is associated with metabolic changes caused by hyperglycemia, resulting in glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Hyperglycemia is also known to cause programmed epigenetic modification. However, the detailed mechanisms involved in the onset and progression of DKD remain elusive. In this review, we discuss recent advances regarding the pathogenic mechanisms involved in DKD.

An increasing number of people are undergoing vaccination for COVID-19 because of the ongoing pandemic. The newly developed, genetically engineered mRNA vaccines are critical for controlling the epidemic disease. However, major adverse effects, including neuroimmunological disorders, are being attributed to this vaccine. For instance, several cases of acute transverse myelitis (ATM) after COVID-19 vaccination have been reported in clinical trials. Here, we report an exceedingly rare case of longitudinally extensive transverse myelitis (LETM), a rare subtype of ATM involving three or more vertebral segments, that occurred shortly after vaccination with the Moderna COVID-19 (mRNA-1273) vaccine, with a comorbidity of vitamin B12 deficiency. The findings of subsequent investigations suggest the possibility that autoimmune responses are triggered by the reactions between anti-SARS-CoV-2 spike protein antibodies and tissue proteins, as well as the interaction between spike proteins and angiotensin-converting enzyme 2 receptors.

The unfolded protein response (UPR) is an intracellular signaling pathway essential for alleviating the endoplasmic reticulum (ER) stress. To support the productive infection, many viruses are known to use different strategies to manipulate the UPR signaling network. However, it remains largely unclear whether the UPR signaling pathways are modulated in the lytic cycle of Epstein-Barr virus (EBV), a widely distributed human pathogen. Herein, we show that the expression of GRP78, a central UPR regulator, is up-regulated during the EBV lytic cycle. Our data further revealed that knockdown of GRP78 in EBV-infected cell lines did not substantially affect lytic gene expression; however, GRP78 knockdown in these cells markedly reduced the production of virus particles. Importantly, we identified that the early lytic protein BMLF1 is the key regulator critically contributing to the activation of the grp78 gene promoter. Mechanistically, we found that BMLF1 can trigger the proteolytic cleavage and activation of the UPR senor ATF6, which then transcriptionally activates the grp78 promoter through the ER stress response elements. Our findings therefore provide evidence for the connection between the EBV lytic cycle and the UPR, and implicate that the BMLF1-mediated ATF6 activation may play critical roles in EBV lytic replication.