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Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT‐driven LIF/LIFR signaling induces brain‐derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration‐resistant PCa (CRPC) and a positive correlation with programmed death‐ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.

The finite penetration depth of light in biological tissues is a practical constraint in light‐induced therapies, such as antimicrobial light therapy, photothermal therapy, and photodynamic cancer therapy. Herein, a biocompatible and implantable device, termed hydrogel planar waveguide with lens‐microneedles, for light delivery in deep tissue is demonstrated. The prototype device, integrated planar waveguide and lens‐microneedles, is fabricated by press‐molding polyethylene glycol diacrylate polymers. The optical beams through the lens‐microneedles are focused at a specific point to realize the optimal intensity profile in the tissue. The adequate treatment depth and region for the hydrogel planar waveguide with five lens‐microneedles are extended to 24 mm and 3.1 cm2. The photoswitchable chemotherapeutic against colorectal cancer cells is switched by using different hydrogel waveguides. The performances of hydrogel‐waveguide‐enabled photoswitching are characterized by the dose responses from the optical microscope, crystal violet staining, and MTT assays. The anticancer drug activated by the hydrogel planar waveguide with five lens‐microneedles is shown to be twice as effective as the other fibers and waveguides in causing cancer cell death. The proposed biodegradable waveguide can be utilized for long‐term light delivery and does not require to be removed as it is gradually resorbed by the tissue. The results point to a new paradigm for widespread use in photomedicine.

Background: Extrauterine growth restriction (EUGR) is common in very-low-birth-weight-infants and may be associated with poor neurodevelopment. The growth velocity of preterm infants is increasing over decades, but the relationship between growth velocity, EUGR, and morbidities of preterm infants remains unknown. Methods: A total of 263 infants born between 2012 and 2020, with birthweight

Mercury (Hg) is a toxic element which impacts on biological systems and ecosystems. Because the toxicity of Hg species is highly dependent on their concentration levels and chemical forms, the sensitive identification of the chemical forms of Hg—i.e., Hg speciation—is of major significance in providing meaningful information about the sources of Hg exposure. In this study, a microfluidic-based device made of high-clarity poly(methyl methacrylate) (PMMA) was fabricated. Then, titanium dioxide nanoparticles (nano-TiO2s) were attached to the treated channel’s interior with the aid of poly(diallyldimethylammonium chloride) (PDADMAC). After coupling the nano-TiO2-coated microfluidic-based photocatalyst-assisted reduction device (the nano-TiO2-coated microfluidic-based PCARD) with high-performance liquid chromatography (HPLC) and inductively coupled plasma mass spectrometry (ICP-MS), a selective and sensitive, hyphenated system for Hg speciation was established. Validation procedures demonstrated that the method could be satisfactorily applied to the determination of mercury ions (Hg2+) and methylmercury ions (CH3Hg+) in both human urine and water samples. Remarkably, the zeta potential measured clearly indicated that the PDADMAC-capped nano-TiO2s with a predominance of positive charges indeed provided a steady force for firm attachment to the negatively charged device channel. The cause of the durability of the nano-TiO2-coated microfluidic-based PCARD was clarified thus.

PurposeOur study aimed to explore the correlation between Sjögren syndrome, sociodemographic factors, comorbid conditions, and optic neuritis.MethodsThis retrospective, nationwide, population-based, matched case–control investigation involved 33,190 individuals diagnosed with optic neuritis, identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes 377.30 for optic neuritis or 377.32 for retrobulbar neuritis. Patient data were extracted from the Taiwan National Health Insurance Research Database. Demographic characteristics, the presence of Sjögren syndrome, and pre-existing comorbid conditions were analyzed using univariate logistic regression. Continuous variables were assessed with a paired t-test. Adjusted logistic regression was employed to compare the prognosis odds ratio (OR) of patients with optic neuritis to controls.ResultsAfter adjusting for confounding variables, individuals with Sjögren syndrome exhibited a significantly higher likelihood of developing optic neuritis compared to controls (adjusted OR, 9.79; 95% confidence interval [CI], 7.28–12.98; p

Abstract Background Pancreatic ductal adenocarcinoma (PDA) is a pernicious disease characterized by an immunosuppressive milieu that is unresponsive to current immunotherapies. Interleukin-1 receptor antagonist (IL-1Ra) is a natural anti-inflammatory cytokine; however, its contribution to cancer pathogenesis and immunosuppression remains elusive. In this research, we investigated the role and mechanism of IL-1Ra in malignant progression of PDA. Results Through analyzing clinical dataset and examining the pathological tumor tissues and serum samples, we have demonstrated that IL-1Ra expression is elevated in human PDA and positively associated with malignant progression of PDA. To study the biological function of IL-1Ra in tumors, we generated a set of mouse pancreatic cancer cell lines with a knockout (KO) of the Il1rn gene, encoding IL-1Ra, and compared the tumor growth rates in immune-competent and immune-deficient mice. We found that the Il1rn KO cells exhibited greater tumor inhibition in immune-competent mice, highlighting the crucial role of a functional immune system in Il1rn KO-mediated anti-tumor response. Consistently, we found an increase in CD8+ T cells and a decrease in CD11b+Ly6G− immunosuppressive mononuclear population in the tumor microenvironment of Il1rn KO-derived tumors. To monitor the inhibitory effects of IL-1Ra on immune cells, we utilized a luciferase-based reporter CD4+ T cell line and splenocytes, which were derived from transgenic mice expressing ovalbumin-specific T cell receptors in CD8+ T cells, and mice immunized with ovalbumin. We showed that IL-1Ra suppressed T cell receptor signaling and inhibited antigen-specific interferon-γ (IFN-γ) secretion and cytolytic activity in splenocytes. Conclusions Our findings illustrate the immunosuppressive properties of the natural anti-inflammatory cytokine IL-1Ra, and provide a rationale for considering IL-1Ra-targeted therapies in the treatment of PDA.

Abstract Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.

Abstract Current treatment options for prostate cancer focus on targeting androgen receptor (AR) signaling. Inhibiting effects of AR may activate neuroendocrine differentiation and lineage plasticity pathways, thereby promoting the development of neuroendocrine prostate cancer (NEPC). Understanding the regulatory mechanisms of AR has important clinical implications for this most aggressive type of prostate cancer. Here, we demonstrated the tumor-suppressive role of the AR and found that activated AR could directly bind to the regulatory sequence of muscarinic acetylcholine receptor 4 (CHRM4) and downregulate its expression. CHRM4 was highly expressed in prostate cancer cells after androgen-deprivation therapy (ADT). CHRM4 overexpression may drive neuroendocrine differentiation of prostate cancer cells and is associated with immunosuppressive cytokine responses in the tumor microenvironment (TME) of prostate cancer. Mechanistically, CHRM4-driven AKT/MYCN signaling upregulated the interferon alpha 17 (IFNA17) cytokine in the prostate cancer TME after ADT. IFNA17 mediates a feedback mechanism in the TME by activating the CHRM4/AKT/MYCN signaling-driven immune checkpoint pathway and neuroendocrine differentiation of prostate cancer cells. We explored the therapeutic efficacy of targeting CHRM4 as a potential treatment for NEPC and evaluated IFNA17 secretion in the TME as a possible predictive prognostic biomarker for NEPC.

Purpose: In this study, we aimed to assess the geographic distribution and molecular characteristics of β-lactamases among Enterobacterales isolates causing intra-abdominal infections (IAIs) from 2015 to 2018 in the Asia–Pacific region. Method: Isolates were investigated for extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases using multiplex PCR assays and full-gene DNA sequencing. Result: A total of 832 Enterobacterales isolates from 8 different countries with β-lactamase genes were analysed. Plasmid-mediated ESBLs and AmpC β-lactamases were encoded in 598 (71.9 %) and 314 (37.7 %) isolates, respectively. In 710 (85.3 %) carbapenemase-negative isolates, positivity for both AmpC β-lactamases and ESBLs was identified in 51 (8.5 %) Escherichia coli and 24 (3.4 %) Klebsiella pneumoniae isolates. The most prevalent countries were Taiwan and Vietnam, and the co-occurrence of CMY/CTX-M in E. coli and DHA-1/ESBLs in K. pneumoniae was predominant. All isolates showed high susceptibility to colistin, but susceptibility to carbapenems varied among different resistance mechanism combinations. Among 122 (14.7 %) isolates encoding carbapenemase, NDM (n = 67, including 64.2 % NDM-1) was the most common, followed by the OXA-48-type (n = 49), KPC (n = 24) and IMP (n = 4). The most prevalent country was Thailand (n = 44), followed by Vietnam (n = 35) and the Philippines (n = 21). Twenty-two isolates were found to encode multiple carbapenemases, 16 of which were collected from Thailand and harbored NDM-1, OXA-232 and CTX-M-15. Despite high susceptibility to amikacin, susceptibility to colistin was only 56 %. Conclusion: The emergence of carbapenem-non-susceptible AmpC/ESBL co-occurring Enterobacterales and colistin non-susceptible carbapenemases co-occurring K. pneumoniae highlights potential therapeutic challenges in the Asia–Pacific region.

Background: In Taiwan, there were only 799 confirmed COVID-19 cases in 2020. The unique backdrop amidst a pandemic and promotion of nonpharmaceutical interventions generated some distinct changes in the epidemiology of common respiratory pathogens. In this study, we aimed to investigate the dynamic changes in respiratory pathogens in children during 2020. Methods: We performed a retrospective cohort study at a tertiary hospital in southern Taiwan during 2020. Patients aged 0–18 years who visited the pediatric emergency department were enrolled. Children who presented with clinical symptoms (fever or respiratory illness) and received nasopharyngeal swabs for multiplex polymerase chain reaction (PCR) were included in our analysis. We also compared respiratory syncytial virus (RSV) trends from previous years by PCR and lateral flow immunochromatographic assays from 2017 to 2020. Results: A total of 120 children were tested. The overall detection rate was 55%. With strengthened restrictions, the detection rate dropped from 70% to 30%. However, non-enveloped viruses (rhinovirus/enterovirus and adenovirus) were in constant circulation. Upon easing prevention measures, the detection rate remained above 60%, and an outbreak of an enveloped virus (RSV and parainfluenza virus) was noted. Compared with 2017–2019, the cyclical RSV epidemic was delayed, with a large surge in late 2020. Conclusions: We observed a constant circulation of non-enveloped viruses when strict nonpharmaceutical interventions were employed and a delayed surge of enveloped viruses during the easing of restrictions. Continuous surveillance and monitoring of the evolutionary dynamics of respiratory viruses is important, while easing restrictions requires balanced judgment.

LaFexNi1−xO3 perovskite oxides were prepared by the sol–gel method under various conditions, including different pH values (pH 0 and pH 7) and different calcination temperatures (500–800 °C) as well as different Fe/Ni ratios (1/9, 3/7, 5/5, 7/3, 9/1). The samples were examined by XRD, DRS, BET, and SEM to reveal their crystallinity, light-absorption ability, specific surface area, and surface features, respectively. The photocatalytic Fenton reaction was conducted using various LaFexNi1−xO3 perovskite oxides to decompose the methylene blue molecules. Accordingly, the synthesis condition of pH 0, calcination temperature at 700 °C, and Fe/Ni ratio = 7/3 could form LaFe0.7Ni0.3O3 perovskite oxides as highly efficient photocatalysts. Moreover, various conditions during the photocatalytic degradation were verified, such as pH value, catalyst dosage, and the additional amount of H2O2. LaFe0.7Ni0.3O3 perovskite oxides could operate efficiently under pH 3.5, catalyst dosage of 50 mg/150 mL, and H2O2 concentration of 133 ppm to decompose the MB dye in the 1st order kinetic rate constant of 0.0506 s−1.

Conventional treatment of prostate cancer (PCa) uses androgen-deprivation therapy (ADT) to inhibit androgen receptor (AR) signaling-driven tumor progression. ADT-induced PCa recurrence may progress to an AR-negative phenotype with neuroendocrine (NE) histologic features, which are associated with metabolic disturbances and poor prognoses. However, the metabolic pathways that regulate NE differentiation (NED) in PCa remain unclear. Herein, we show a regulatory mechanism in NED-associated metabolism dysfunction induced by ADT, whereby overexpression of pyruvate kinase L/R (PKLR) mediates oxidative stress through upregulation of reactive oxygen species modulator 1 (ROMO1), thereby promoting NED and aggressiveness. ADT mediates the nuclear translocation of PKLR, which binds to the MYCN/MAX complex to upregulate ROMO1 and NE-related genes, leading to altered mitochondrial function and NED of PCa. Targeting nuclear PKLR/MYCN using bromodomain and extra-terminal motif (BET) inhibitors has the potential to reduce PKLR/MYCN-driven NED. Abundant ROMO1 in serum samples may provide prognostic information in patients with ADT. Our results suggest that ADT resistance leads to upregulation of PKLR/MYCN/ROMO1 signaling, which may drive metabolic reprogramming and NED in PCa. We further show that increased abundance of serum ROMO1 may be associated with the development of NE-like PCa.

This study explores the synergistic impact of Programmed Death Ligand 1 (PD-L1) and Protein Kinase B (Akt) overexpression in adipose-derived mesenchymal stem cells (AdMSCs) for ameliorating cardiac dysfunction after myocardial infarction (MI). Post-MI adult Wistar rats were allocated into four groups: sham, MI, ADMSC treatment, and ADMSCs overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) treatment. MI was induced via left anterior descending coronary artery ligation, followed by intramyocardial AdMSC injections. Over four weeks, cardiac functionality and structural integrity were assessed using pressure–volume analysis, infarct size measurement, and immunohistochemistry. AdMSC-PDL1-Akt exhibited enhanced resistance to reactive oxygen species (ROS) in vitro and ameliorated MI-induced contractile dysfunction in vivo by improving the end-systolic pressure–volume relationship and preload-recruitable stroke work, together with attenuating infarct size. Molecular analyses revealed substantial mitigation in caspase3 and nuclear factor-κB upregulation in MI hearts within the AdMSC-PDL1-Akt group. Mechanistically, AdMSC-PDL1-Akt fostered the differentiation of normal T cells into CD25+ regulatory T cells in vitro, aligning with in vivo upregulation of CD25 in AdMSC-PDL1-Akt-treated rats. Collectively, PD-L1 and Akt overexpression in AdMSCs bolsters resistance to ROS-mediated apoptosis in vitro and enhances myocardial protective efficacy against MI-induced dysfunction, potentially via T-cell modulation, underscoring a promising therapeutic strategy for myocardial ischemic injuries.

Abstract Background Dry eye disease (DED) is a common disease in ophthalmology, affecting millions of people worldwide. Recent studies have shown that inflammation is the core mechanism of DED. IL-20 is a proinflammatory cytokine involved in various inflammatory diseases. Therefore, we aimed to explore the role of this cytokine in the pathogenesis of DED and evaluate the therapeutic potential of the anti-IL-20 monoclonal antibody (mAb) 7E for DED treatment. Methods Clinical tear samples from patients with DED and non-DED controls were collected and their IL-20 protein levels were determined. We established three DED animal models to explore the role of IL-20 and the efficacy of IL-20 antibody in DED. Benzalkonium chloride (BAC)-induced over-evaporative DED, extra-orbital lacrimal gland excision (LGE)-induced aqueous tear-deficient DED, and desiccating stress (DS)-induced combined over-evaporative and aqueous tear-deficient DED animal models were established to investigate the role of IL-20. The anti-IL-20 antibody 7E was established to neutralize IL-20 activity. The effects of IL-20 or 7E on human corneal epithelial cells and macrophages under hyperosmotic stress were analyzed. 7E was topically applied to eyes to evaluate the therapeutic effects in the DED animal models. Results IL-20 was significantly upregulated in the tears of patients with DED and in the tears and corneas of DED animal models. Under hyperosmotic stress, IL-20 expression was induced via NFAT5 activation in corneal epithelial cells. 7E suppressed hyperosmotic stress-induced activation of macrophages. IL-20 induced cell death in corneal epithelial cells and 7E protected cells from hyperosmotic stress-induced cell death. Blocking IL-20 signaling with 7E protected mice from BAC-induced, LGE-induced, and DS-induced DED by reducing DED symptoms and inhibiting inflammatory responses, macrophage infiltration, apoptosis, and Th17 populations in the conjunctiva and draining lymph nodes. Conclusions Our results demonstrated the functions of IL-20 in DED and presented a potential therapeutic option for this condition. Graphical Abstract

Abstract Neuroendocrine differentiation (NED) frequently occurs in androgen-deprivation therapy (ADT)-resistant prostate cancer (PCa) and is typically associated with metabolic pathway alterations, acquisition of lineage plasticity, and malignancy. There is no conventional therapeutic approach for PCa patients with NED pathologic features because the molecular targets are unknown. Here, we evaluated the regulatory mechanism of NED-associated metabolic reprogramming induced by ADT. We detected that the loss of the androgen-responsive transcription factor, zinc finger, and BTB domain containing 10 (ZBTB10), can activate pyruvate kinase L/R (PKLR) to enhance a NED response that is associated with glucose uptake by PCa cells. PKLR exhibits a tumor-promoting effect in PCa after ADT, but ZBTB10 can compensate for the glucose metabolism and NED capacity of PKLR through the direct transcriptional downregulation of PKLR. Targeting PKLR by drug repurposing with FDA-approved compounds can reduce the aggressiveness and NED of ADT-resistant PCa. We demonstrated that PKLR acts as a modulator to activate NED in PCa enhancement by loss of ZBTB10, thereby enabling PCa cells to mount a glycolysis response essential for therapeutic resistance. Our findings highlight the broad relation between NED and metabolic dysfunction to provide gene expression-based biomarkers for NEPC treatment.

Cell-free massive multiple-input multiple-output (CF-mMIMO) systems are expected to provide faster and more robust connections to user equipments by cooperation of a massive number of distributed access points (APs), and to be one of the key technologies for beyond 5G (B5G). CF-mMIMO systems with multiple-antenna APs have been investigated from various viewpoints recently. However, no comprehensive analysis of the impact of antenna distribution on CF-mMIMO system performance has been done so far, which is important for practical deployment. Besides spectral efficiency, in B5G, energy efficiency of user equipments is one of the key indicators because various kinds of battery-limited devices connect to the network. Thus, this paper provides a comprehensive performance analysis of the impact of antenna distribution on the performance indicators, while considering several combining/precoding schemes and transmit power control algorithms. For uplink maximal-ratio combining, the concentrated deployment has the best performance thanks to the channel hardening and favorable propagation phenomena. On the other hand, the concentrated deployment prominently suffers from shadowing effects. For uplink/downlink minimum mean-square error combining with transmit power control, the semi-distributed deployments show the best performance, and it implies that we can reduce the number of APs to 1/4 for uplink and to 1/2 for downlink while keeping the same performance as the fully-distributed deployment.

Abstract Neuroendocrine differentiation (NED) is associated with WNT signaling activation and can be significantly observed after failure of androgen-deprivation therapy (ADT) for prostatic adenocarcinomas. Cytokine signaling is stimulated in NED prostate cancer; however, how ADT-upregulated WNT signaling promotes activation of cytokine signaling and contributes to NED of prostate cancer is poorly understood. In this study, we identified ADT-mediated upregulation of transcription factor 7 like 1 (TCF7L1), which increases the cytokine response and enhances NED of prostate cancer through interleukin (IL)-8/C-X-C motif chemokine receptor type 2 (CXCR2) signaling activation. ADT induced the secretion of WNT4 which upon engagement of TCF7L1 in prostate cancer cells, enhanced IL-8 and CXCR2 expressions. TCF7L1 directly binds to the regulatory sequence region of IL-8 and CXCR2 through WNT4 activation, thus upregulating IL-8/CXCR2 signaling-driven NED and cell motility. Analysis of prostate tissue samples collected from small-cell neuroendocrine prostate cancer (SCPC) and castration-resistant prostate cancer (CRPC) tumors showed an increased intensity of nuclear TCF7L1 associated with CXCR2. Our results suggest that induction of WNT4/TCF7L1 results in increased NED and malignancy in prostate cancer that is linked to dysregulation of androgen receptor signaling and activation of the IL-8/CXCR2 pathway.

Foot and root rot caused by Phytophthora parasitica is a substantial threat to citrus cultivation, affecting both yield and quality. Thus, rapid and accurate detection of P. parasitica plays an important role in disease management. The aim of this study was to develop a simple diagnostic method to detect P. parasitica infection by combining recombinase polymerase amplification and lateral flow strips (LF-RPA). To establish the LF-RPA assay of P. parasitica, the primers and probe designed based on the Ypt1 gene were tested for specificity to P. parasitica, which showed no cross-reactivity with DNAs of other related oomycete species. The LF-RPA assay detected the amount of genomic DNA of P. parasitica which was as low as 1 pg. To make the LF-RPA assay useful in low-resource settings, four simplified DNA extraction methods were compared, after which the LF-RPA assay was applied, with no specialized equipment, to analyze a diverse range of citrus tissues by using a simplified PEG-NaOH method for DNA extraction. This method was successful in detecting P. parasitica in infected plant samples within 30 min. Combining the LF-RPA assay and a simplified DNA extraction method could be a potential detection test for P. parasitica, especially in areas with limited resources.

We report 4 cases of neonatal sepsis caused by Streptococcus gallolyticus. The clinical course was quite similar to early-and late-onset group B streptococcus disease. None of the mothers had group B streptococcus (GBS) colonization on prenatal screening nor received intrapartum antibiotics. We proposed the sporadic distribution of S. gallolyticus sepsis among neonates was partly due to relatively low colonization rate in adults compared with GBS. Species determination of S. gallolyticus may not be available using conventional microbiological methods and may contribute to underestimation or misclassification. In our series, we highlighted the importance of S. gallolyticus as an important pathogen in neonatal sepsis deserving further surveillance.

In this study, a multi-objective H2/H∞ observer-based fault-tolerant control (FTC) design with reverse-order multi-objective evolution algorithm (MOEA) is proposed to deal with the FTC problem of Takagi-Sugeno (T-S) fuzzy systems. To achieve the optimal robust FTC design for the T-S fuzzy systems under the sensor and actuator faults, as well as external disturbance and measurement noise, the multi-objective H2/H∞ observer-based FTC scheme is proposed to efficiently estimate the system state and the fault signals based on a proposed smoothed fault signal model. Then, multi-objective H2/H∞ FTC performance can be achieved by an estimated state and fault signal feedback scheme to efficiently compensate the effect of fault signals and attenuate the effect of external disturbance. By using the proposed indirect method, the multi-objective H2/H∞ observer-based FTC design problem is transformed into linear matrix inequalities (LMIs)-constrained multi-objective optimization problem (MOP). Besides, to overcome the difficulties in searching large fuzzy parameters of observer-based FTC design for solving the LMIs-constrained MOP, a reverse-order MOEA is proposed to overcome the bottleneck to efficiently solve the MOP for multi-objective H2/H∞ observer-based FTC of T-S fuzzy system by searching feasible objective vectors in the objective space instead of searching fuzzy design parameters in the parametric space. Two practical examples are considered for the performance validation with (i) H2/H∞ observer-based FTC design for the missile guidance system with the actuator and sensor fault signals due to the sudden cheating side-step maneuvering and the hostile jamming interference and (ii) H2/H∞ observer-based FTC design for inverted pendulum system which effected by the constant actuator fault.

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.

Here, the authors discover that NGF, upregulated by transcription factor ZBTB46 in prostate cancer exposed to androgen therapy, promotes neuroendocrine differentiation. They show that NGF interacts with the GPCR CHRM4, that both NGF and CHRM4 are upregulated in highly metastatic prostate cancer and that targeting NGF reduces therapy resistance in a mouse xenograft model.

In order to increase the performance of tool or mold/die, there are a lot of micro features on the surface to provide special functions, such as anti-adhesion or lubrication. The MPB (Micro Particle Bombarding) process provides a powerful technology to enhance the surface quality without damaging the micro features. The effect of MPB parameters were investigated by bombarding the surface with extremely small particles (20~200 µm in diameter) at a high velocity and pressure to obtain a better surface integrity. -The MPB has two functions, one is micro blasting for cleaning purposes and the other is micro shot peening for surface strengthening. The regression relationship between particle bombarding time and micro hardness is established to predict the surface hardness after MPB process. The experimental results reveal that the surface hardness of cermet is increased 14~66% (HV2167~HV3163) by micro particle bombarding. The micro shot peening provides a good surface integrity due to thebetter surface roughness of 0.1 μmRa and higher compress residual stress of −1393.7 MPa, which is up to 26% enhancement compared with the base material cermet. After micro shot peening, the surface hardness of the SKD11 tool steel increased from HV 686 to HV 739~985. The surface roughness of SKD 11 after micro shot peening was 0.31–0.48 μmRa, while the surface roughness after micro blasting was 0.77–1.15 μmRa. It is useful to predict the residual stress for micro blasting by surface roughness, and to estimate the residual stress after micro shot peening by surface hardness by applying the MPB process in industry in the case of SKD 11 tool steel.

We report a 7-year-old girl who got Mycoplasma pneumoniae infection with prolonged fever. Macrolide was used on day 14 of illness but fever persisted with progressive lung consolidation. Oral prednisolone was administered on day 33 then fever subsided with dramatically clinical improvement (decreased CRP and resolution of lung consolidation). In this case, delayed effective antibiotic treatment with inflammation may be the major factor contributing to the fever rather than ongoing infection.

The pro-inflammatory cytokine IL-20 promotes tumor growth in several cancer types. Here, the authors show that high levels of IL-20 are associated with poor survival in patients with pancreatic ductal adenocarcinoma (PDAC) and that IL-20 blockade reduces tumor growth and alleviates cachexia symptoms in mouse models of PDAC.

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided. Keywords: Clostridium difficile, Diarrhea, CDI, Infectious diarrhea

Summary: Various populations of cancer stem cells (CSCs) have been identified in hepatocellular carcinoma (HCC). Wnt signaling is variably activated in HCC and regulates CSCs and tumorigenesis. We explored cell-to-cell Wnt and stemness heterogeneity in HCC by labeling freshly isolated cancer cells with a Wnt-specific reporter, thereby identifying a small subset (0.4%–8.9%) of Wnt-activityhigh cells. Further cellular subset analysis identified a refined subset of Wnt-activityhighALDH1+EpCAM+ triple-positive (TP) cells as the most stem-like, phenotypically plastic, and tumorigenic among all putative CSC populations. These TP “superpotent CSCs” (spCSCs) specifically upregulate the expression of dishevelled 1 (DVL1) through the antagonism between abnormal spindle-like microcephaly-associated (ASPM) and the ubiquitin ligase complex Cullin-3/KLHL-12. Subsequent functional and molecular studies revealed the role of DVL1 in controlling spCSCs and their tumorigenic potential. These findings provide the mechanistic basis of the Wnt and stemness heterogeneity in HCC and highlight the important role of DVL1high spCSCs in tumor progression. : In this article, Tsai and colleagues investigated the Wnt and stemness heterogeneity in HCC and identified a novel subset of Wnt-activityhigh “superpotent cancer stem cells” (spCSCs). The existence of spCSCs is independent of β-catenin mutations and its proportion correlates with poor prognosis in patients with HCC. Mechanistically, spCSCs are positively regulated by the Wnt-ASPM-DVL1 signaling axis through protein-protein interactions. Keywords: Dishevelled-1, Wnt, cancer stem cells, hepatocellular carcinoma, heterogeneity, ASPM, ubiquitin ligase, prognostic marker

Failure to thrive is one of the most common complaints in the endocrinology and genetics clinic. An 8-month-old girl with presentation of motor developmental delay, failure to thrive, and midline facial defects, with history of hypoglycemia at birth and central congenital hypothyroidism (CCH), was brought to our genetic clinic. Hormone test demonstrated combined pituitary hormone deficiency with growth hormone deficiency (GHD), central hypothyroidism, and hypoprolactinemia. Brain magnetic resonance imaging (MRI) showed anterior pituitary hypoplasia (APH), abnormal pituitary stalk, and preserved posterior pituitary lobe. Whole exome sequence (WES) identified a compound heterozygous mutation of the POU1F1 gene: c.649C>T (p.Arg217Ter) and c.662T>C (p.Ile221Thr), which are de novo mutation and inherited from mother, respectively. The patient's phenotype was consistent clinically with congenital hypopituitarism due to the POU1F1 gene mutation. Based on our literature review, this is the first report of the c.662T>C mutation, to the best of our knowledge. Our study demonstrates the power of WES for early diagnosis of congenital hypopituitarism with its relative phenotype for improving prognosis and preventing irreversible deficit.

In this study, we propose a novel design of triangular mesoscale Janus prisms for the generation of the long photonic hook. Numerical simulations based on the finite-difference time-domain method are used to examine the formation mechanism of the photonic hook. The electric intensity distributions near the micro-prisms are calculated for operation at different refractive indices and spaces of the two triangular micro-prisms. The asymmetric vortices of intensity distributions result in a long photonic hook with a large bending angle. The length and the bending angle of the photonic hook are efficiently modulated by changing the space between the two triangular micro-prisms. Moreover, the narrow width of the photonic hook is achieved beyond the diffraction limit. The triangular Janus micro-prisms have high potential for practical applications in optical tweezers, nanoparticle sorting and manipulation and photonic circuits.

Frozen-sectioned hematoxylin–eosin (H&E) image evaluation is the current method for intraoperative breast cancer metastasis assessment through ex vivo sentinel lymph nodes (SLNs). After frozen sectioning, the sliced fatty region of the frozen-sectioned specimen is easily dropped because of different freezing points for fatty tissues and other tissues. Optical-sectioned H&E images provide a nondestructive method for obtaining the insight en face image near the attached surface of the dissected specimen, preventing the freezing problem of fatty tissue. Specimens from 29 patients at Wanfang Hospital were collected after excision and were analyzed at the pathology laboratory, and a fluorescence-in-built optical coherence microscopic imaging system (OCMIS) was then used to visualize the pseudo-H&E (p-H&E) images of the SLNs for intraoperative breast cancer metastasis assessment, and the specificity, sensitivity, and accuracy were 100%, 88.9%, and 98.8% (n = 83), respectively. Compared with gold-standard paraffin-sectioned H&E images, the specificity, sensitivity, and accuracy obtained with the frozen-sectioned H&E images (n = 85) of the specimens were the same as those obtained with the p-H&E images (n = 95). Thus, OCMIS is a useful noninvasive image-assisted tool for breast cancer metastasis assessment based on SLN images.

The kidney epithelial barrier has multifaceted functions in body fluids, electrolyte homeostasis, and urine production. The renal epithelial barrier (REB) frequently faces and challenges osmotic dynamics, which gives rise to osmotic pressure (a physical force). Osmotic pressure overloading can crack epithelial integrity and damage the REB. The endurance of REB to osmotic pressure forces remains obscure. LMO7 (LIM domain only 7) is a protein associated with the cell–cell junctional complex and cortical F-actin. Its upregulation was observed in cells cultured under hypertonic conditions. LMO7 is predominantly distributed in renal tubule epithelial cells. Hypertonic stimulation leads to LMO7 and F-actin assembly in the cortical stress fibers of renal epithelial cells. Hypertonic-isotonic alternation, as a pressure force pushing the plasma membrane inward/outward, was set as osmotic disturbance and was applied to test FAK signaling and LMO7 functioning in maintaining junctional integrity. LMO7 depletion in cells resulted in junctional integrity loss in the epithelial sheet-cultured hypertonic medium or hypertonic-isotonic alternation. Conversely, FAK inhibition by PF-573228 led to failure in robust cortical F-actin assembly and LMO7 association with cortical F-actin in epithelial cells responding to hypertonic stress. Epithelial integrity against osmotic stress and LMO7 and FAK signaling are involved in assembling robust cortical F-actin and maintaining junctional integrity. LMO7 elaborately manages FAK activation in renal epithelial cells, which was demonstrated excessive FAK activation present in LMO7 depleted NRK-52E cells and epithelial integrity loss when cells with LMO7 depletion were exposed to a hypertonic environment. Our data suggests that LMO7 regulates FAK activation and is responsible for maintaining REB under osmotic disturbance.

Appendiceal mucinous tumors are rare, with variable malignant potential, and they are usually found incidentally. Clinical symptoms are nonspecific. Rarely, appendiceal mucinous neoplasm causes bowel obstruction and makes diagnosis more difficult. We present a case of an 84-year-old female who came to our emergency department having had abdominal fullness and constipation for 5 days. Ileus, due to an affected adhesion band, was diagnosed initially, and symptoms improved gradually under conservative treatment. However, 3 months later she presented to the emergency department again with abdominal pain and distension; small bowel obstruction due to adhesion was again diagnosed. Recurrent bowel obstruction prompted emergent surgery. Operative findings showed a whitish appendiceal tumor adhering to and directly invading the adjacent ileum, with a segment of herniated small bowel wedged in between, causing the obstruction. Upon reviewing the initial computed tomography scan, the dilated tubular structure of appendiceal tumor was misrecognized as small bowel loop; there was no surrounding inflammatory sign, leading to diagnosis difficulty. Instead of a common cause of bowel obstruction, such as adhesion band, this case revealed bowel obstruction can be caused by the direct invasion of an appendiceal tumor. Awareness of this condition with careful image evaluation of small bowel obstruction is essential for diagnosis.

The Tactile Internet enables physical touch to be transmitted over the Internet. In the context of electronic medicine, an authenticated key agreement for the Tactile Internet allows surgeons to perform operations via robotic systems and receive tactile feedback from remote patients. The fifth generation of networks has completely changed the network space and has increased the efficiency of the Tactile Internet with its ultra-low latency, high data rates, and reliable connectivity. However, inappropriate and insecure authentication key agreements for the Tactile Internet may cause misjudgment and improper operation by medical staff, endangering the life of patients. In 2021, Kamil et al. developed a novel and lightweight authenticated key agreement scheme that is suitable for remote surgery applications in the Tactile Internet environment. However, their scheme directly encrypts communication messages with constant secret keys and directly stores secret keys in the verifier table, making the scheme vulnerable to possible attacks. Therefore, in this investigation, we discuss the limitations of the scheme proposed by Kamil scheme and present an enhanced scheme. The enhanced scheme is developed using a one-time key to protect communication messages, whereas the verifier table is protected with a secret gateway key to mitigate the mentioned limitations. The enhanced scheme is proven secure against possible attacks, providing more security functionalities than similar schemes and retaining a lightweight computational cost.

Summary: Urbanization is a pressing challenge for earth’s humans because it is changing not only natural environments but also agricultural lands. Yet, the consequences of cropland loss on pest insect populations that largely depend on these habitats remain largely unclear. We used a 17-year data set to investigate the dynamics of three moth pest species (i.e., striped stem borer, yellow stem borer, and pink stem borer) and their driving forces across the largest mega-urban region of China. Total abundance of three pest species is declined by about 80%, which was strongly associated with cropland loss during rapid urbanization. Our findings indicate that not only the increasing conversion of natural areas to human-dominated landscapes but also that of agricultural lands to urban landscapes can be critical to insect populations. It is therefore essential to monitor and understand the insect dynamics in rapidly urbanizing regions, which are currently found in many developing countries worldwide.

This study develops a multi-functional hydrogel with a dual injection system based on the adhesive and self-healing properties of the byssus excretion found in mussels. Through precisely controlling the composite cross-linking hydrophobic association (HA) structure composed of A and B solutions, a high-strength, temperature-sensitive injectable hydrogel can be obtained, and it has good self-healing properties. The main composition of A solution contains the surfactant SDS, which can form amphiphilic micelles, the strength increasing component stearyl methacrylate (C18), and NIPAAm, which provides thermo-sensitivity. Solution B contains dopamine acrylate (DAA), which has self-healing properties, and ferric chloride (FeCl3), which is a connecting agent. The rheological behavior shows that when the temperature is increased from 25 °C to 32 °C, the gel can be completed in seven minutes to form a composite hydrogel of NIPAAm-DAA-HA. When NMR identification was conducted on composite DAA, it was found that when comparing DAA and dopamine hydrochloride there were new peaks with specific characteristics, which confirm that this study successfully prepared DAA; swelling tests found that swelling could surpass a rate of 100%, and a higher ratio of crosslinking agent decreased the amount of moisture absorbed; the results of the compression test showed that the addition of hydrophobic micelles C18 effectively enhanced the mechanical properties of hydrogel, allowing it to withstand increased external stress; the adhesiveness results show that an increase in the catechol-Fe3+ concentration of the NIPAAm-DAA-HA hydrogel results in an increased adhesiveness of 0.0081 kg/cm2 on pig skin; the self-healing tests show that after taking damage, NIPAAm-DAA-HA hydrogel can be reactivated with catechol-Fe3+ and self-heal at a rate of up to 70% after 24 h; antibacterial tests show that hydrogel has good bacterial resistance to against E. coli, staphylococcus epidermidis, and bacillus cereus; through in vitro transdermal absorption, it can be seen that the release ability of drugs within the hydrogel can reach up to 8.87 μg/cm2. The NIPAAm-DAA-HA hydrogel prepared by this study performed excellently in both adhesion and self-healing tests. The thermo-sensitive and antibacterial properties can be applied to the treatment of deep wounds and address some of the flaws of traditional wound dressings.

Chemosensitivity to cisplatin derivatives varies among individual patients with intractable malignancies including ovarian cancer, while how to unlock the resistance remain unknown. Ovarian cancer tissues were collected the debulking surgery in discovery- (n = 135) and validation- (n = 47) cohorts, to be analyzed with high-throughput automated immunohistochemistry which identified cystathionine γ-lyase (CSE) as an independent marker distinguishing non-responders from responders to post-operative platinum-based chemotherapy. We aimed to identify CSE-derived metabolites responsible for chemoresistant mechanisms: gold-nanoparticle (AuN)-based surface-enhanced Raman spectroscopy (SERS) was used to enhance electromagnetic fields which enabled to visualize multiple sulfur-containing metabolites through detecting scattering light from Au–S vibration two-dimensionally. Clear cell carcinoma (CCC) who turned out less sensitive to cisplatin than serous adenocarcinoma was classified into two groups by the intensities of SERS intensities at 480 cm−1; patients with greater intensities displayed the shorter overall survival after the debulking surgery. The SERS signals were eliminated by topically applied monobromobimane that breaks sulfane-sulfur bonds of polysulfides to result in formation of sulfodibimane which was detected at 580 cm−1, manifesting the presence of polysulfides in cancer tissues. CCC-derived cancer cell lines in culture were resistant against cisplatin, but treatment with ambroxol, an expectorant degrading polysulfides, renders the cells CDDP-susceptible. Co-administration of ambroxol with cisplatin significantly suppressed growth of cancer xenografts in nude mice. Furthermore, polysulfides, but neither glutathione nor hypotaurine, attenuated cisplatin-induced disturbance of DNA supercoiling. Polysulfide detection by on-tissue SERS thus enables to predict prognosis of cisplatin-based chemotherapy. The current findings suggest polysulfide degradation as a stratagem unlocking cisplatin chemoresistance.

Background: Asthma is a common pediatric chronic respiratory disease worldwide. Previous studies showed the prevalence of childhood asthma increased in developed countries as well as in Taiwan in the late 20th century. Recently, several reports from different parts of the world showed a reversed trend in this epidemic of childhood asthma prevalence. This study investigated the trend of childhood asthma through serial cross-section questionnaire surveys in the southern part of Taiwan, and identified associated factors related to this trend in elementary school children. Methods: We used the Chinese version of the International Study of Asthma and Allergies in Childhood (ISAAC)29 questionnaire to assess the asthma status of elementary school students aged 6–12 years in Tainan city in 3 independent study periods, namely, 2008–2009, 2010–2012, and 2017–2018. We assessed the trend of “asthma” and “related respiratory symptoms” across 3 study periods. Results: Of the 19,633 respondents, 17,545 (89.4%) completed the questionnaires. After adjustment for covariates, the prevalence of asthma and related respiratory symptoms was significantly lower in 2017–2018 than in the 2 earlier periods. Among the protective factors, the increasing rate of breastfeeding might be partly responsible for the observed reduced prevalence of current asthma and exercise-induced wheeze, but not physician-diagnosed asthma. The presence of pets in the house was the risk factor that correlated with the prevalence of nocturnal cough. Pearson correlation analysis showed a significant correlation of the prevalence of physician-diagnosed asthma, current asthma, and exercise-induced wheezing with the concentrations of air pollutant particles with aerodynamic diameter ≤10 μM (PM10) (r = 0.84, 0.77 and 0.81, respectively). Conclusion: The prevalence of asthma and related respiratory symptoms has declined in elementary school-age children in southern Taiwan. The increased prevalence of breastfeeding, decreased rate of the presence of pets in the house, and improvement in outdoor air pollution seem to be related to this decreasing trend of asthma in school children. Our findings will provide the scientific base to empower prevention policy to reverse the trend of childhood asthma prevalence. Trial registration: N/A

Abstract Background Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality. The mechanisms remain unclear. We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure. Methods and results The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13). Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks. After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses. Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected. Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation. Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR. In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues. The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin. Conclusions Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes. Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.

Executive Summary: Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia. Keywords: Pneumonia, Guidelines, Treatment, Taiwan

Skin is an important organ that mainly functions as a barrier. Skin diseases can damage a person’s self-confidence and reduce their willingness to socialize, as well as their social behavior and willingness. When the skin appearance is abnormal, in addition to affecting the quality of life, it often leads to personal, social, and psychological dysfunction and even induces depression. Psoriasis and atopic dermatitis are common chronic skin diseases. Their prevalence in the world is 3–10%, and there is an increasing trend year by year. These congenital or acquired factors cause the dysfunction of the immune system and then destroy the barrier function of the skin. Because these patients are flooded with a variety of inflammatory mediators, this causes skin cells to be in chronic inflammation. Therefore, psoriasis and atopic dermatitis are also considered systemic chronic inflammatory diseases. In the healthcare systems of developed countries, it is unavoidable to spend high costs to relieve symptoms of psoriasis and atopic dermatitis patients, because psoriasis and atopic dermatitis have a great influence on individuals and society. Giving a lot of attention and developing effective treatment methods are the topics that the medical community must work on together. Therefore, we used a narrative review manuscript to discuss pathogenesis, clinical classification, incidence, and treatment options, including topical medication, systemic therapeutics, immunosuppressive medication for psoriasis, and atopic dermatitis, as well as also comparing the differences between these two diseases. We look forward to providing readers with comprehensive information on psoriasis and atopic dermatitis through this review article.

During the rotary machine operation process, seemingly small amounts of abnormal vibration can often cause serious damage to the machinery over time and even increase the risk of accidents. Although professional vibration engineers can determine the current health status of a machine by interpreting the vibration spectrum information and predicting which components will fail, if even ordinary operators can send feedback regarding the vibration signals reaching the human–machine interface through a system when an abnormality is detected in the machine, the abnormality can be made known and processed in time. This can prevent the magnified impact of rotary inertia, thereby lowering the risk of major damage and the failure of machinery and equipment, as well as effectively saving on equipment maintenance costs. This study mainly adopted LabVIEW and Arduino IDE to develop a control program and human–machine monitoring interface. As the initial experiment on rotary machine vibration monitoring and smart balance correction, the measurement system setup in this study was applied to determine vibration abnormality as well as to carry out continuous online automatic balance correction. Experimental verification was carried out using active correction and smart correction. In terms of active online balance correction, the amplitude correction rate was 96%, the double-frequency correction rate was 102.9%, and the correction process was performed in 5 min. In terms of smart balance correction, the amplitude correction rate was 103.8%, the double-frequency correction rate was 103.3%, and the correction process was performed in 3 min. Through feedback signaling, the operator can effectively learn the current health status of the mechanical equipment from the human–machine interface.

Abstract Background Degenerative lumbar spondylolisthesis (DLS) is a major cause of spinal canal stenosis and is often related to lower back pain. IL-20 is emerging as a potent angiogenic, chemotactic, and proinflammatory cytokine related to several chronic inflammatory bone disorders likes intervertebral disc herniation, rheumatoid arthritis (RA), osteoporosis, and bone fracture. IL-19 also acts as a proinflammatory cytokine in RA. The aim of the present study was to investigate whether IL-19 and IL-20 are involved in DLS and compare three different tissues including disc, facet joint, and ligamentum flavum of patients with DLS to verify which tissue is affected more by inflammation. Methods Disc, facet joint and ligamentum flavum from 13 patients with DLS was retrieved, and the expression pattern of IL-19, IL-20, IL-20R1, IL-20R2, TNF-α, IL-1β, and MCP-1 was evaluated using immunohistochemical staining with specific antibodies. The disc cells were isolated and incubated with IL-19 and IL-20 under CoCl2-mimicked hypoxic conditions to analyze the proinflammatory cytokine expression pattern using real-time quantitative PCR with specific primers. Results IL-19 and IL-20 were positively stained and accompanied by abundant expression of TNF-α, IL-1β, and MCP-1 in facet joints of DLS patients. IL-19 and IL-20’s receptors (IL-20R1 and IL-20R2) were expressed on chondrocytes and fibrocytes/fibroblasts in facet joint and ligamentum flavum tissues from patients with DLS. There was a significant correlation between the expression of IL-20 and IL-1β in facet joint. In vitro assay, IL-19 and IL-20 upregulated the expression of IL-1β, IL-6, TNF-α, IL-8, VEGF, and MCP-1 in primary cultured DLS disc cells under CoCl2-mimicked hypoxic conditions. Conclusions IL-19, IL-20, and their receptors as well as proinflammatory cytokines (TNF-α, IL-1β, and MCP-1) were expressed more in facet joints than the other tissues in patients with DLS; therefore, the etiology of inflammation might be more facet-centric. IL-19 and IL-20 induced proinflammatory cytokine expression in disc cells and might play a role in the pathogenesis of DLS.

Abstract. Breast cancer metastasis is the root cause of deaths from breast cancer. Currently, endocrine therapy resistance in estrogen receptor (ER)-positive (ER+) breast cancer remains a major clinical issue. Moreover, ER-negative (ER−) breast cancer is often associated with distant recurrence and death. G-protein-coupled ER (GPER1) participates in endocrine therapy resistance and is involved in the malignant progression of breast cancer. However, the underlying detailed mechanisms remain obscure. Here we investigated the role and mechanism of GPER1 in the activation of focal adhesion kinase (FAK) using ER+ or ER− breast cancer cell lines. In SK-Br-3 cells (ERα−/β−/GPER1+), both 17β-estradiol (E2) and the GPER1 agonist G1 resulted in rapid FAK phosphorylation. This action is due to GPER1 interaction with the non-receptor tyrosine kinase c-Src and subsequent activation of nuclear factor kappa B (NF-κB) signaling. Silencing of GPER1, c-Src or the nuclear factor kappa B p65 subunit blocked E2- or G1-induced SK-Br-3 cell migration and invasion. In MCF-7 cells (ERα+/β+/GPER1+), silencing of GPER1, but not ERα or ERβ, abolished FAK phosphorylation induced by E2 or G1. In MDA-MB-231 cells (ERα−/β+/GPER1−), E2 or G1 was also unable to stimulate E2-induced FAK phosphorylation. However, E2 and G1 regained the ability to induce FAK phosphorylation under conditions of overexpression of GPER1. In conclusion, we demonstrated that GPER1, but not ERα or ERβ, mediates FAK phosphorylation induced by E2 via the c-Src/p65 signaling pathway, which enhances cell migration and invasion. These findings may shed light on novel therapeutic strategies based on GPER1/FAK signaling pathways in suppression of breast cancer metastasis.

Interleukin (IL)-33, a member of the IL-1 family of cytokines, is involved in innate and adaptive immune responses via interaction with its receptor, ST2. Activation of ST2 signalling by IL-33 triggers pleiotropic immune functions in multiple ST2-expressing immune cells, including macrophages, neutrophils, eosinophils, basophils, mast cells, type 2 helper T cells, regulatory T cells, and group 2 innate lymphoid cells. IL-33-mediated effector functions contribute to the tissue inflammatory and reparative responses in various organs including lung, skin, kidney, central nerve system, cardiovascular system, and gastrointestinal system. Endogenous IL-33/ ST2 signaling exhibits diverse immune regulatory functions during progression of different diseases. IL-33 likely functions as a disease sensitizer and plays pathological roles in inflamed tissues in allergic disorders that involve hyperreactive immune responses in the context of skin and pulmonary allergy. However, IL-33 also mediates tissue-protective functions during the recovery phase following tissue injury in the central nerve system and gastrointestinal system. Modulation of the IL-33/ST2 axis, therefore, represents a promising strategy for treating immune disorders that involve dysregulation of the cytokine signalling. In the past two decades, therapeutic strategies blocking IL-33/ST2 have been extensively studied for the treatment of diseases in animal models. In this review, the current progress on the development of therapeutic biologics for targeting IL-33/ST2 signalling in inflammatory diseases is summarized.

Urology: Tracking a trigger for kidney damage An inflammatory signaling protein may play an important role in kidney damage associated with urinary tract blockage. Untreated obstructive nephropathy can lead to kidney injury, particularly in younger patients. Taiwanese researchers led by Wei-Yu Chen at the Kaohsiung Chang Gung Memorial Hospital and Ya-Jen Chang at the Academia Sinica, Taipei, homed in on a signaling pathway that apparently contributes to the pathology of this condition. Using an animal model of surgically induced obstructive nephropathy, the researchers observed a post-injury spike in production of an immunity-activating protein called interleukin (IL)-33. This protein subsequently activates a host of immune cell types, and also stimulates abnormal growth in a subset of urinary tract epithelial cells. This excessive growth may directly contribute to subsequent damage and functional impairment of the kidney, although more research will be needed to confirm this.