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Slowly adapting receptors (SARs), vagal mechanosensitive receptors located in the lung, play an important role in regulating the breathing pattern and Hering-Breuer inflation reflex (HBIR). Inhalation of high concentration of sulfur dioxide (SO 2 ), a common environmental and occupational air pollutant, has been shown to selectively block the SAR activity in rabbits, but the mechanism underlying this inhibitory effect remained a mystery. We carried out this study to determine if inhalation of SO 2 can inhibit the HBIR and change the eupneic breathing pattern, and to investigate further a possible involvement of voltage-gated K + channels in the inhibitory effect of SO 2 on these vagal reflex-mediated responses. Our results showed 1 ) inhalation of SO 2 (600 ppm; 8 min) consistently abolished both the phasic activity of SARs and their response to lung inflation in anesthetized, artificially ventilated mice, 2 ) inhalation of SO 2 generated a distinct inhibitory effect on the HBIR and induced slow deep breathing in anesthetized, spontaneously breathing mice, and these effects were reversible and reproducible in the same animals, 3 ) This inhibitory effect of SO 2 was blocked by pretreatment with 4-aminopyridine (4-AP), a nonselective blocker of voltage-gated K + channel, and unaffected by pretreatment with its vehicle. In conclusion, this study suggests that this inhibitory effect on the baseline breathing pattern and the HBIR response was primarily mediated through the SO 2 -induced activation of voltage-gated K + channels located in the vagal bronchopulmonary SAR neurons. NEW & NOTEWORTHY This study demonstrated that inhaled sulfur dioxide completely and reversibly abolished the activity of vagal bronchopulmonary slowly adapting receptors, significantly inhibited the apneic response to lung inflation, and induced slow deep breathing in anesthetized mice. More importantly, our results further suggested that this inhibitory effect was mediated through an action of sulfur dioxide and its derivatives on the voltage-gated potassium channels expressed in the slowly adapting receptor sensory neurons innervating the lung.

Zika virus (ZIKV) is a mosquito-borne flavivirus that causes severe neurological disorders, such as microcephaly in fetuses. Most recently, an outbreak of ZIKV started in Brazil in 2015. To date, no therapeutic agents have been approved to treat ZIKV infection in the clinic. Here, we screened a small molecule inhibitor that can inhibit the function of ZIKV non-structural protein 2B (NS2B)-NS3 protease (ZIKV NS2B-NS3 protease), thereby interfering with viral replication and spread. First, we identified the half maximal inhibitory concentration (IC 50 ) of compound 3 (14.01 μM), 8 (6.85 μM), and 9 (14.2 μM) and confirmed that they are all non-competitive inhibitors. In addition, we have used the blind molecular docking method to simulate the inhibition area of three non-competitive inhibitors (compound 3, 8, and 9) with the ZIKV NS2B-NS3 protease. The results indicated that the four allosteric binding residues (Gln139, Trp148, Leu150, and Val220) could form hydrogen bonds or non-bonding interactions most frequently with the three compounds. The interaction might induce the reaction center conformation change of NS2B-NS3 protease to reduce catalyzed efficiency. The concentration of compounds required to reduce cell viability by 50% (CC 50 ), and the concentration of compounds required to inhibit virus-induced cytopathic effect by 50% (EC 50 ) of three potential compounds are >200 μM, 2.15 μM (compound 3), > 200 μM, 0.52 μM (compound 8) and 61.48 μM, 3.52 μM (compound 9), and Temoporfin are 61.05 μM, 2 μM, respectively. To select candidate compounds for further animal experiments, we analyzed the selectivity index (SI) of compound 3 (93.02), 8 (384.61), 9 (17.46), and Temoporfin (30.53, FDA-approved drug against cancer). Compound 8 has the highest SI value. Therefore, compound 8 was selected for verification in animal models. In vivo, compound 8 significantly delayed ZIKV-induced lethality and illness symptoms and decreased ZIKV-induced weight loss in a ZIKV-infected suckling mouse model. We conclude that compound 8 is worth further investigation for use as a potential future therapeutic agent against ZIKV infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Four new alkaloids, hippobrines A-D ( 1 - 4 ), along with three new polyacetylenes, hippobrenes A-C ( 5 - 7 ), were isolated from Hippobroma longiflora . Compounds 1 - 3 possess an unprecedented carbon skeleton. All of the new structures were determined by analyzing their mass and NMR spectroscopic data. The absolute configurations of 1 and 2 were confirmed by single-crystal X-ray analyses, and the absolute configurations of 3 and 7 were deduced using their ECD spectra. Plausible biogenetic pathways of 1 and 4 were proposed. In regard to bioactivities, all compounds ( 1 - 7 ) exhibited weak antiangiogenic activity against human endothelial progenitor cells, with IC 50 values ranging from 21.1 ± 1.1 to 44.0 ± 2.3 μg/mL.

A tunable metamaterial nanograting coupler (MNC) is presented that is composed of a one-dimensional surface nanograting coupler with a bottom reflector and the metamaterial atop. For a single nanograting coupler, by introducing a reflector and optimizing nanograting parameters, the spatial coupling efficiency exceeds 97% around near-infrared wavelength of 1.43 μm. The metamaterial can be tuned by using micro-electro-mechanical system (MEMS) technique. The relative height or lateral offset between metamaterial and coupling nanograting can be controlled, that the light-emitting efficiency can be separated into two different directions. In addition, the coupling efficiency is as high as 91% at the optical C-band communication window. Therefore, the proposed MEMS-based MNC not only has the possibility of coupling optical fibers with high-density integrated optoelectronic chips, but also has potential application prospects in light path switching, variable optical attenuation, and optical switch., (© 2023. The Author(s).)

Introduction: Beta-blockers are widely prescribed to manage hypertension and cardiovascular diseases and have been suggested as an attractive therapy to improve the prognosis of sepsis. Herein, we investigated the potential benefits of premorbid selective beta-blocker use in sepsis with a real-world database and explored the underlying mechanism by in vivo and in vitro experiments., Methods: A total of 64,070 sepsis patients and 64,070 matched controls who were prescribed at least one anti-hypertensive drug for more than 300 days within 1 year were selected for the nested case-control study. Female C57BL/6 J mice and THP-1 cells stimulated with lipopolysaccharide (LPS) were used for studying systemic responses during sepsis to validate our clinical findings., Results: The risk of sepsis was lower in current selective beta-blocker users than in non-users (adjusted OR (aOR), 0.842; 95% CI, 0.755-0.939), and in recent users than in non-users (aOR, 0.773; 95% CI, 0.737-0.810). A mean daily dose of ≥0.5 DDD was associated with a lower risk of sepsis (aOR, 0.7; 95% CI, 0.676-0.725). Metoprolol, atenolol, and bisoprolol users had lower risk of sepsis than non-users. In a LPS-induced sepsis mouse model, mice pre-fed with atenolol had significantly reduced mortality. While atenolol had some mild effects on LPS-induced release of inflammatory cytokines in septic mice, it significantly reduced serum soluble PD-L1 levels. Notably, atenolol treatment reversed the negative correlation of sPD-L1 with inflammatory cytokines in septic mice. Moreover, atenolol markedly downregulated the PD-L1 expression on LPS-stimulated THP-1 monocytes/macrophages via targeting ROS-induced NF-κB and STAT3 activation., Conclusion: Atenolol pretreatment can reduce sepsis mortality in mice, and in vivo and in vitro studies of PD-L1 expression suggest a role for atenolol in the modulation of immune homeostasis. These findings may contribute to the reduced incidence of sepsis in hypertensive patients with premorbid treatment with selective beta-blockers, especially atenolol., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hong, Lai, Teng, Chen, Hsu, Chan, Wang, Wang, Lin and Chen.)

For decades, studies of snake venoms focused on the venom-ome-specific toxins (VSTs). VSTs are dominant soluble proteins believed to contribute to the main venomous effects and emerged into gene clusters for fast adaptation and diversification of snake venoms. However, the conserved minor venom components, such as snake venom phosphodiesterase (svPDE), remain largely unexplored. Here, we focus on svPDE by genomic and transcriptomic analysis across snake clades and demonstrate that soluble svPDE is co-opted from the ancestral membrane-attached ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase 3) gene by replacing the original 5' exon with the exon encoding a signal peptide. Notably, the exons, promoters, and transcription/translation starts have been replaced multiple times during snake evolution, suggesting the evolutionary necessity of svPDE. The structural and biochemical analyses also show that svPDE shares the similar functions with ENPP family, suggesting its perturbation to the purinergic signaling and insulin transduction in venomous effects., Competing Interests: CP, CL, IL, KC, YL, HC, WW No competing interests declared, (© 2023, Pan et al.)

Metastasis is the main cause of death in many cancers including colorectal cancer (CRC); however, the underlying mechanisms responsible for metastatic progression remain largely unknown. We found that nuclear TYRO3 receptor tyrosine kinase is a strong predictor of poor overall survival in patients with CRC. The metastasis-promoting function of nuclear TYRO3 requires its kinase activity and matrix metalloproteinase-2 (MMP-2)-mediated cleavage but is independent of ligand binding. Using proteomic analysis, we identified bromodomain-containing protein 3 (BRD3), an acetyl-lysine reading epigenetic regulator, as one of nuclear TYRO3's substrates. Chromatin immunoprecipitation-sequencing data reveal that TYRO3-phosphorylated BRD3 regulates genes involved in anti-apoptosis and epithelial-mesenchymal transition. Inhibition of MMP-2 or BRD3 activity by selective inhibitors abrogates nuclear TYRO3-induced drug resistance and metastasis in organoid culture and in orthotopic mouse models. These data demonstrate that MMP-2/TYRO3/BRD3 axis promotes the metastasis of CRC, and blocking this signaling cascade is a promising approach to ameliorate CRC malignancy.

Chip-scale photonic systems that manipulate free-space emission have recently attracted attention for applications such as free-space optical communications and solid-state LiDAR. Silicon photonics, as a leading platform for chip-scale integration, needs to offer more versatile control of free-space emission. Here we integrate metasurfaces on silicon photonic waveguides to generate free-space emission with controlled phase and amplitude profiles. We demonstrate experimentally structured beams, including a focused Gaussian beam and a Hermite-Gaussian TEM 10 beam, as well as holographic image projections. Our approach is monolithic and CMOS-compatible. The simultaneous phase and amplitude control enable more faithful generation of structured beams and speckle-reduced projection of holographic images.

Background: Neoadjuvant systemic therapy (NST) is conducted in increased number of patients with breast cancer overexpressing human epidermal growth factor receptor 2 (HER2). Whether the intensity of HER2 protein expression determines response to treatment is challenged. This study aims to analyze the impact of HER2 immunohistochemical (IHC) scores on NST response and survival outcome., Methods: We analyzed a total of 197 patients with HER2-positive breast cancer receiving NST and definite surgery from a prospectively collected database. The analyzed endpoints included pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). More patients with IHC 2+/ in situ hybridization (ISH)-positive tumors presented positive for hormonal receptors, compared with those with IHC 3+ tumors. No clinicopathological features except tumor necrosis were significantly associated with pCR., Results: Both positive hormone receptors and IHC scores stood on the borderline in statistical analysis. IHC 3+ group tends to present a higher pCR rate than IHC 2+/ISH+ groups (52.5% vs. 34.3%). Patients who achieved pCR had better survival outcome than that of non-pCR group. The impact of pCR on survival reached the statistical significance in the IHC 3+ group both in DFS (90.9% vs. 76.5%; p = 0.004) and OS (97.4% vs. 83.2%; p = 0.002). Multivariate analysis demonstrated IHC scores as an independent predictor of survival outcome with the adjustment of tumor staging and pCR., Conclusion: HER2 IHC score is an independent predictor for outcome. IHC 3+ tumors presented a trend of higher pCR rate and better outcome in HER2-positive breast cancer patients who receive NST., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: An esophageal defect usually resulted from surgical ablation of tumors or corrosive injury. Staged reconstructions are required usually in extensive defects., Aim and Objectives: This study aimed to present a rare iatrogenic complication of total esophageal avulsion injury during upper gastrointestinal endoscopic treatment and to perform staged reconstructions to create a neoesophagus., Materials and Methods: In the presented case, staged reconstructions with a tubed deltopectoral flap and a supercharged colon interposition flap were performed to reconstruct the hypopharynx and esophagus. However, recurrent choking occurred because of the extent of injury involving the epiglottis. A tubed free radial forearm flap connected to the lower buccogingival sulcus was used to create a new route for food passage., Results: The patient resumed oral intake after rehabilitation., Conclusions: The avulsion injury of the total esophagus is rare and devastating. Staged reconstructions with a tubed deltopectoral flap, a supercharged colon interposition flap, and a tubed free radial forearm flap would be a safe and reliable method., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The family Fulgoridae belongs to the order Hemiptera, superfamily Fulgoridea, with approximately 770 described species worldwide. Their extraordinary appearance attracts the attention of both entomologists and the public. In addition to the evolutionary issue of their special appearance, certain species are also considered notorious pests ( e.g. , Lycorma delicatula ). Several issues widely exist in previous taxonomic studies of lanternflies: (1) application of uncertain morphological characters leads to synonymy or misidentification; (2) descriptions of male genitalia are incomplete; (3) information of nymphal morphology is insufficient. Therefore, this study aims to provide a comprehensive taxonomic study of Fulgoridae from Taiwan. In this study, eight species in six genera from Taiwan were reported, of which Limois westwoodii was recorded for the first time from Taiwan. Lycorma olivacea was proposed as a new junior synonym of L. meliae . The fifth-instar nymph of Saiva formosana was described for the first time. Detailed descriptions of these lanternflies and an identification key to adults of Fulgoridae from Taiwan were also included.

In this study, we propose a novel high-concentration photovoltaic (HCPV) cell by considering both the light leakage characteristics of the Fresnel-lens-based solar cell modules and the performance issues arising from cloud shading in practical use. We use our self-constructed systems to conduct field measurements for up to half a year under various environmental conditions. According to the acquired results, it was surprising to know that in the area other than the focusing area, the so-called light leakage region, there always bears illuminance of about 20,000-40,000 lx whether it is a sunny day or a cloudy day with different cloud conditions. Such an interesting result is caused by the light scattering of the clouds and the inherent leakage characteristic of a Fresnel lens. To prove this important finding, we simulated the illuminance of the Fresnel lens structure used in the measurement with apertures of different sizes to determine the detected area. In the laboratory, the diffuse plates were used to mimic the situation of varying cloud layer thicknesses. The trend of calculated and measured results fitted well with the field measurements. Also, the experimental and simulation results show that the round angle and draft facet of the Fresnel lens were responsible for light leakage. This finding prompted us to propose a hybrid high-concentration solar module in which more cost-effective polycrystalline silicon solar cells are placed around the high-efficiency wafer of HCPV to capture the dissipated light leakage and convert it into usable electricity., (© 2023. The Author(s).)

Indium oxide (In 2 O 3 ) is a widely used n-type semiconductor for detection of pollutant gases; however, its gas selectivity and sensitivity have been suboptimal in previous studies. In this work, zinc-doped indium oxide nanowires with appropriate morphologies and high crystallinity were synthesized using chemical vapor deposition (CVD). An accurate method for electrical measurement was attained using a single nanowire microdevice, showing that electrical resistivity increased after doping with zinc. This is attributed to the lower valence of the dopant, which acts as an acceptor, leading to the decrease in electrical conductivity. X-ray photoelectron spectroscopy (XPS) analysis confirms the increased oxygen vacancies due to doping a suitable number of atoms, which altered oxygen adsorption on the nanowires and contributed to improved gas sensing performance. The sensing performance was evaluated using reducing gases, including carbon monoxide, acetone, and ethanol. Overall, the response of the doped nanowires was found to be higher than that of undoped nanowires at a low concentration (5 ppm) and low operating temperatures. At 300 °C, the gas sensing response of zinc-doped In 2 O 3 nanowires was 13 times higher than that of undoped In 2 O 3 nanowires. The study concludes that higher zinc doping concentration in In 2 O 3 nanowires improves gas sensing properties by increasing oxygen vacancies after doping and enhancing gas molecule adsorption. With better response to reducing gases, zinc-doped In 2 O 3 nanowires will be applicable in environmental detection and life science.

Dengue virus (DENV) infection can induce life-threatening dengue hemorrhagic fever/dengue shock syndrome in infected patients. DENV is a threat to global health due to its growing numbers and incidence of infection in the last 50 years. During infection, DENV expresses ten structural and nonstructural proteins modulating cell responses to benefit viral replication. However, the lack of knowledge regarding the cellular proteins and their functions in enhancing DENV pathogenesis impedes the development of antiviral drugs and therapies against fatal DENV infection. Here, we identified that integrin-linked kinase (ILK) is a novel enhancing factor for DENV infection by suppressing type I interferon (IFN) responses. Mechanistically, ILK binds DENV NS1 and NS3, activates Akt and Erk, and induces NF-κB-driven suppressor of cytokine signaling 3 (SOCS3) expression. Elevated SOCS3 in DENV-infected cells inhibits phosphorylation of STAT1/2 and expression of interferon-stimulated genes (ISGs). Inhibiting ILK, Akt, or Erk activation abrogates SOCS3 expression. In DENV-infected mice, the treatment of an ILK inhibitor significantly reduces viral loads in the brains, disease severity, and mortality rate. Collectively, our results show that ILK is a potential therapeutic target against DENV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Singlet oxygen ( 1 O 2 ) is a type of reactive oxygen species (ROS), playing a vital role in the physiological and pathophysiological processes. Specific probes for monitoring intracellular 1 O 2 still remain challenging. In this study, we develop a ratiometric fluorescent probe for the real-time intracellular detection of 1 O 2 using o-phenylenediamine-derived carbonized polymer dots (o-PD CPDs). The o-PD CPDs possessing dual-excitation-emission properties (blue and yellow fluorescence) were successfully synthesized in a two-phase system (water/acetonitrile) using an ionic liquid tetrabutylammonium hexafluorophosphate as a supporting electrolyte through the electrolysis of o-PD. The o-PD CPDs can act as a photosensitizer to produce 1 O 2 upon white LED irradiation, in turn, the generated 1 O 2 selectively quenches the yellow emission of the o-PD CPDs. This quenching behavior is ascribed to the specific cycloaddition reaction between 1 O 2 and alkene groups in the polymer scaffolds on o-PD CPDs. The interior carbon core can be a reliable internal standard since its blue fluorescence intensity remains unchanged in the presence of 1 O 2 . The ratiometric response of o-PD CPDs is selective toward 1 O 2 against other ROS species. The developed o-PD CPDs have been successfully applied to monitor the 1 O 2 level in the intracellular environment. Furthermore, in the inflammatory neutrophil cell model, o-PD CPDs can also detect the 1 O 2 and other ROS species such as hypochlorous acid after phorbol 12-myristate 13-acetate (PMA)-induced inflammation. Through the dual-channel fluorescence imaging, the ratiometric response of o-PD CPDs shows great potential for detecting endogenous and stimulating 1 O 2 in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Rare-earth element-free fluorescent materials are eco-friendlier than other traditional fluorescent precursors, such as quantum dots and phosphors. In this study, we explore a simple and facile solution-based technique to prepare fluorescent films, which are highly stable under ordinary room conditions and show hydrophobic behaviour. The proposed hybrid material was designed with hybrid composites that use polyvinyl butyral (PVB) as a host doped with organic dyes. The red and green fluorescent films exhibited quantum yields of 89% and 80%, respectively, and both are very uniform in thickness and water resistant. Additionally, PVB was further compared with another polymeric host, such as polyvinylpyrrolidone (PVP), to evaluate their binding ability and encapsulation behaviour. Next, the effect of PVB on the optical and chemical properties of the fluorescent materials was studied using UV spectroscopy and Fourier transform infrared spectroscopy. The analysis revealed that no new bond was formed between the host material and fluorescent precursor during the process, with intermolecular forces being present between different molecules. Moreover, the thickness of the fluorescent film and quantum yield relation were evaluated. Finally, the hydrophobic nature, strong binding ability, and optical enhancement by PVB provide a powerful tool for fabricating a highly efficient fluorescent film with enhanced stability in an external environment based on its promising encapsulation properties. These efficient fluorescent films have a bright potential in colour conversion for next-generation display applications.

Background: The echocardiographic parameter E/e' has been associated with cardiovascular (CV) events. However, few studies have analyzed multiple associated CV outcomes using E/e' in a diverse population of both inpatients and outpatients with and without cardiac diseases and risk factors., Methods: Medical records of 75,393 patients without atrial fibrillation (AF) with first available E/e' were retrieved from our hospital database. Patients with mitral valve disease were excluded, and the remainder were studied in protocol 1 (70,819 patients). Patients with hypertension, diabetes mellitus, hyperlipidemia, CV diseases, prior CV events, CV surgeries, and left ventricular ejection fraction <50% or missing left ventricular ejection fraction were further excluded, and the remaining patients were studied in protocol 2 (14,665 patients). The study outcomes are major adverse CV events (MACE), which included myocardial infarction (MI), AF, ischemic and hemorrhagic stroke (IHS), hospitalization for heart failure (HHF), and cardiac death. The primary outcomes were MACE and each of the MACE components., Results: At the end of maximal 5-year follow-up (median 22.18 months with interquartile range 7.20-49.08 months for MACE in protocol 1 and 23.46 months with interquartile range 8.15-49.02 months for MACE in protocol 2), compared with an E/e' value of <8, an intermediate value of E/e' 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and cardiac death in protocol 1 (all P < .0001). In protocol 2, an intermediate E/e' value of 8 to 15 and a high value of E/e' >15 were significantly associated with MACE, MI, AF, IHS, HHF, and CV death (all P < .05), except an intermediate value E/e' 8 to 15 was not associated with AF., Conclusions: In a diverse population of inpatients and outpatients with and without cardiac diseases and risk factors, the echocardiographic parameter E/e' was associated with CV events and is a useful marker of risk., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Rice protein was used as a starting material to provide rice protein hydrolysates (RPH) through enzyme-assisted extraction. RPH was further fractionated using ultrafiltration membrane (UF) and classified by molecular weight (MW; MW < 1 kDa, MW 1-10 kDa, and MW > 10 kDa). Peptides with MW < 1 kDa possessed superior antioxidant properties (p < 0.05). Therefore, UF demonstrated great efficacy in selectively separating antioxidant peptides. A Pearson correlation analysis revealed that the total phenolic concentration was correlated with oxygen radical absorbance capacity (ORAC; r = 0.999, p < 0.05). Amino acid contents had negative correlations with the scavenging activity (specifically, IC50) of 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (r =  - 0.986 to - 1.000). Reducing power was related to aromatic amino acid contents (r = 0.997, p < 0.05). In this study, enzymatic hydrolysis was discovered to be an effective method of extracting and isolating natural antioxidant proteins from broken rice, thus preserving the nutritional quality of rice and making those proteins more accessible in future applications., (© 2023. The Author(s).)

Three new alkaloids, hipporidine A (1: ), hipporidine B (2: ), and (-)-lobeline N -oxide (3: ), were discovered from the whole plant of Hippobroma longiflora together with five known compounds (4: -8: ). Their 2,6-disubstituted piperidine structures were established based on the HRESIMS, NMR (COSY, HMBC, HSQC, NOESY), and UV spectroscopic data. Hipporidines A (1: ) and B (2: ) possess a rare 1,3-oxazinane moiety. Compound 3: is the N -oxide derivative of (-)-lobeline (6: ). Moreover, the absolute configuration of norlobeline (5: ) was established by single-crystal X-ray diffraction analysis. Three major secondary metabolites (6: -8: ) were evaluated for their neuroprotective effect against paclitaxel-induced neurotoxicity. Consequently, pretreatment with compound 8: at a concentration of 1.0 µM displayed significant attenuation on paclitaxel-damaged neurite outgrowth of dorsal root ganglion neurons without interfering with the cytotoxicity of paclitaxel on cervical cancer SiHa cells., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Nanomedicine has garnered significant interest owing to advances in drug delivery, effectively demonstrated in the treatment of certain diseases. Here, smart supermagnetic nanocomposites based on iron oxide nanoparticles (MNPs) coated with Pluronic F127 (F127) were developed for the delivery of doxorubicin (DOX) to tumor tissues. The XRD patterns for all samples revealed peaks consistent with Fe 3 O 4 , as shown by their indices (220), (311), (400), (422), (511), and (440), demonstrating that the structure of Fe 3 O 4 did not change after the coating process. After loading with DOX, the as-prepared smart nanocomposites demonstrated drug-loading efficiency and drug-loading capacity percentages of 45 ± 0.10 and 17 ± 0.58% for MNP-F127-2-DOX and 65 ± 0.12 and 13 ± 0.79% for MNP-F127-3-DOX, respectively. Moreover, a better DOX release rate was observed under acidic conditions, which may be credited to the pH sensitivity of the polymer. In vitro analysis demonstrated the survival rate of approximately 90% in HepG2 cells treated with PBS and MNP-F127-3 nanocomposites. Furthermore, after treatment with MNP-F127-3-DOX, the survival rate decreased, confirming cellular inhibition. Hence, the synthesized smart nanocomposites showed great promise for drug delivery in liver cancer treatment, overcoming the limitations of traditional therapies.

The development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors is described. First, selectivity for mutant EGFR was accomplished by replacing the ( S )-2-phenylglycinol moiety of 12 with either an ethanol or an alkyl substituent. Then, the cellular potency and physicochemical properties were optimized through insights from molecular modeling studies by implanting various solubilizing groups in phenyl rings A and B. Optimized lead 52 shows 8-fold selective inhibition of H1975 (EGFR L858R/T790M overexpressing) cancer cells over A431 (EGFR WT overexpressing) cancer cells; western blot analysis further confirmed EGFR mutant-selective target modulation inside the cancer cells by 52 . Notably, 52 displayed in vivo antitumor effects in two different mouse xenograft models (BaF3 transfected with mutant EGFR and H1975 tumors) with TGI = 74.9 and 97.5% after oral administration ( F = 27%), respectively. With an extraordinary kinome selectivity ( S (10) score of 0.017), 52 undergoes detailed preclinical development.

Here in this study we adopted genome-wide association studies (GWAS) to investigate the genetic components of the personality constructs in the Chinese Personality Assessment Inventory 2 (CPAI-2) in Taiwanese Hakka populations, who are likely the descendants of a recent admixture between a group of Chinese immigrants with high emigration intention and a group of the Taiwanese aboriginal population generally without it. A total of 279 qualified participants were examined and genotyped by an Illumina array with 547,644 SNPs to perform the GWAS. Although our sample size is small and that unavoidably limits our statistical power (Type 2 error but not Type 1 error), we still found three genomic regions showing strong association with Enterprise, Diversity, and Logical vs. Affective Orientation, respectively. Multiple genes around the identified regions were reported to be nervous system related, which suggests that genetic variants underlying the certain personalities should indeed exist in the nearby areas. It is likely that the recent immigration and admixture history of the Taiwanese Hakka people created strong linkage disequilibrium between the emigration intention-related genetic variants and their neighboring genetic markers, so that we could identify them despite with only limited statistical power., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Dual pH-sensitive smart nanocarriers based on silica nanoparticles (SNPs) extracted from rice husk ashes (RHAs) to effectively inhibit liver cancer cell proliferation were investigated. The SNPs were coated with chitosan (CH) and loaded with doxorubicin (DOX), then functionalized with cell membrane (CM) for homologous targeting ability. The FTIR spectra showed an absorption wave number at 1083 cm -1 which confirmed the existence of the SiOSi group, ratifying that the nanocarriers belong to silica species. The Korsmeyer-Peppas kinetic model reported R 2 values of 0.996 and 0.931 for pH = 5.4 and pH = 7.4, respectively, demonstrating pH-responsive behavior of the nanocarriers. The cytotoxicity test confirmed that the HepG2 cell line treated with different SNP-CH-CM concentrations had no detectable significant cell toxicity, however, SNP-CH-DOX-CM induced greater cell death. In vivo tests revealed that SNP-CH-DOX-CM suppressed liver cancer growth in nude mice, demonstrating high pharmaceutical capability. Histological examination of vital organs showed that the targeted drug delivery system (DDS) had minor in vivo toxicity. In the light of its high treatment efficacy and minimal side effects, the investigated DDS is promising for the therapy of liver cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

To improve the color conversion performance, we study the nanoscale-cavity effects on the emission efficiency of a colloidal quantum dot (QD) and the Förster resonance energy transfer (FRET) from quantum well (QW) into QD in a GaN porous structure (PS). For this study, we insert green-emitting QD (GQD) and red-emitting QD (RQD) into the fabricated PSs in a GaN template and a blue-emitting QW template, and investigate the behaviors of the photoluminescence (PL) decay times and the intensity ratios of blue, green, and red lights. In the PS samples fabricated on the GaN template, we observe the efficiency enhancements of QD emission and the FRET from GQD into RQD, when compared with the samples of surface QDs, which is attributed to the nanoscale-cavity effect. In the PS samples fabricated on the QW template, the FRET from QW into QD is also enhanced. The enhanced FRET and QD emission efficiencies in a PS result in an improved color conversion performance. Because of the anisotropic PS in the sample surface plane, the polarization dependencies of QD emission and FRET are observed.

Respiratory oscillometry is widely explored in asthma management; however, there is currently no consensus on its routine work-up in patients with difficult-to-treat asthma. We conducted a retrospective, cross-sectional study involving patients with difficult-to-treat asthma at Asia University Hospital between January 2017 and October 2020. We aimed to correlate clinical significance of respiratory oscillometry and asthma treatment outcomes including symptoms control and exacerbation in patients with difficult-to-treat asthma. Among the 69 patients enrolled in the study, a total of 26.1% of the patients experienced at least one severe or two moderate exacerbations. Patients with ACT < 20 presented a higher prevalence of higher frequency-dependent resistance (FDR; the difference in resistance at 5 Hz and 20 Hz) and frequency of resonance (Fres) than those with ACT ≥ 20. In the multivariable analysis, comorbidities, COPD or allergic rhinitis, and FDR were independent factors in increasing the odds ratio in poorly controlled asthma. (FDR ≥ 0.10 vs. < 0.10, adjusted ORR = 5.05, P = 0.037) There was a higher proportion of frequent exacerbations in patients with higher FDR (FDR ≥ 0.10 vs. < 0.10 = 30.0%:20.7%), but IOS parameters failed to predict frequent exacerbations on further analysis. FDR may be a potential clinical parameter for predicting symptom control in patients with difficult-to-treat asthma., (© 2023. The Author(s).)

Background: This study was performed to compare clinical characteristics and outcomes between patients with bloodstream infections (BSIs) caused by Candida auris and those with BSIs caused by other Candida spp., Methods: A multicenter retrospective case-control study was performed at 3 hospitals in Brooklyn, New York, between 2016 and 2020. The analysis included patients ≥18 years of age who had a positive blood culture for any Candida spp. and were treated empirically with an echinocandin. The primary outcome was the 30-day mortality rate. Secondary outcomes were 14-day clinical failure, 90-day mortality rate, 60-day microbiologic recurrence, and in-hospital mortality rate., Results: A total of 196 patients were included in the final analysis, including 83 patients with candidemia caused by C. auris. After inverse propensity adjustment, C. auris BSI was not associated with increased 30-day (adjusted odds ratio, 1.014 [95% confidence interval, .563-1.828]); P = .96) or 90-day (0.863 [.478-1.558]; P = .62) mortality rates. A higher risk for microbiologic recurrence within 60 days of completion of antifungal therapy was observed in patients with C. auris candidemia (adjusted odds ratio, 4.461 [95% confidence interval, 1.033-19.263]; P = .045)., Conclusions: C. auris BSIs are not associated with a higher mortality risk than BSIs caused by other Candida spp. The rate of microbiologic recurrence was higher in the C. auris group., Competing Interests: Potential conflicts of interest. S. P. S. is currently an employee and shareholder at Accelerate Diagnostics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to determine the impact on hearing prognosis of the coherent frequency with high magnitude-squared wavelet coherence (MSWC) in video head impulse test (vHIT) among patients with sudden sensorineural hearing loss with vertigo (SSNHLV) undergoing high-dose steroid treatment. This study was a retrospective cohort study. SSNHLV patients treated at our referral center from December 2016 to December 2020 were examined. The cohort comprised 64 patients with SSNHLV undergoing high-dose steroid treatment. MSWC was measured by calculating the wavelet coherence analysis (WCA) at various frequencies from a vHIT. The hearing prognosis were analyzed using a multivariable Cox regression model and convolution neural network (CNN) of WCA. There were 64 patients with a male-to-female ratio of 1:1.67. The greater highest coherent frequency of the posterior semicircular canal (SCC) was associated with the complete recovery (CR) of hearing. After adjustment for other factors, the result remained robust (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.86-2.35). In the feature extraction with Resnet-50 and proceeding SVM in the horizontal image cropping style, the classification accuracy [STD] for (CR vs. partial + no recovery [PR + NR]), (over-sampling of CR vs. PR + NR), (extensive data extraction of CR vs. PR + NR), and (interpolation of time series of CR vs. PR + NR) were 83.6% [7.4], 92.1% [6.8], 88.9% [7.5], and 91.6% [6.4], respectively. The high coherent frequency of the posterior SCC was a significantly independent factor that was associated with good hearing prognosis in the patients who have SSNHLV. WCA may be provided with comprehensive ability in vestibulo-ocular reflex (VOR) evaluation. CNN could be utilized to classify WCA, predict treatment outcomes, and facilitate vHIT interpretation. Feature extraction in CNN with proceeding SVM and horizontal cropping style of wavelet coherence plot performed better accuracy and offered more stable model for hearing outcomes in patients with SSNHLV than pure CNN classification. Clinical and Translational Impact Statement-High coherent frequency in vHIT results in good hearing outcomes in SSNHLV and facilitates AI classification.

Background: Acute myocardial infarction (AMI) and colon cancer share similar risk factors. Studies have suggested an association between AMI and colon cancer; however, evidence is conflicting. Whether sex disparities exist in this association in the real world remains unknown., Methods: In this population-based retrospective cohort study, 94,780 and 97,987 male patients and 38,697 and 72,007 female patients with and without new-onset AMI, respectively, from January 1, 2001, to December 31, 2012, were enrolled from Taiwan's National Health Insurance Research Database. Inverse probability of treatment weighting (IPTW) was used to balance covariates across study groups. The primary outcome was a new diagnosis of colon cancer., Results: The incidence rate of colon cancer was 1.54 (95% confidence interval [CI] = 1.46-1.62) and 1.40 (95% CI = 1.32-1.48) per 1000 person-years in the male patients and 1.62 (95% CI = 1.50-1.74) and 1.22 (95% CI = 1.13-1.32) in the female patients, in the AMI and non-AMI groups, respectively. AMI was associated with a significantly higher risk of colon cancer in the female patients (hazard ratio [HR] = 1.31, 95% CI = 1.06-1.61) but not in the male patients (HR = 1.09, 95% CI = 0.95-1.26). In the subgroup analysis, the association between AMI and colon cancer in the female patients was stronger in those aged ≥65 years (HR = 1.28, 95% CI = 1.13-1.44)., Conclusions: An increased risk of colon cancer was observed only in the female patients with AMI. The association between AMI and colon cancer in the female patients was the most evident in those aged ≥65 years., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Trastuzumab, a potent anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody, is conditionally reimbursed by the Taiwan National Health Insurance (NHI) for HER2-positive breast cancer (BC). Trastuzumab-induced cardiotoxicity studies have well characterized heart failure (HF) but fewer addressed arrhythmia, particularly the association of potential life threatening atrial fibrillation (Af) is poorly characterized. We aimed to study the trastuzumab-related risk of Af and HF using the claimed data of Taiwan NHI., Methods: A nationwide retrospective cohort of patients with BC from the Taiwan NHI reimbursement database from January 2007 to December 2016 was analyzed. Propensity score matching and competing risk model analysis were used for adjusting confounding concurrent medication or comorbidities and competing events. The HF study was used to validate the method used., Results: For Af, 12,472 trastuzumab users were matched with 12,472 non-trastuzumab users. For HF, 12,241 trastuzumab users and 12,241 non-users were enrolled. We found that trastuzumab users had significantly worse HF-free survival but not Af-free survival than non-trastuzumab users. In the competing risk analysis, the use of trastuzumab did not increase the risk of Af (hazard ratio [HR] 0.76, P = 0.0006) but was associated with HF (HR 1.19, P = 0.0052). The risk trends among stratifications by comorbidities and concurrent medication remained in similar directions for both Af and HF., Conclusion: Trastuzumab in real-world practice was associated with an increased risk of HF, but was not associated with an increased risk of Af in BC patients. Trastuzumab-induced arrhythmogenic effects may be masked by concurrent heart-protecting measures, more prominent roles of comorbidities or concurrent medications under real-world settings. Further studies are required., (© 2022. The Author(s).)

Aim: The study examined the differences in nursing student empathy, caring behavior and competence between the experimental and control groups before and after educational intervention and to predict the factors affecting their core competencies., Background: Educating nursing students in empathy and caring behaviors before entering clinical practice is challenging., Design: We used a two-group pretest and post-test quasi-experimental design., Methods: First-year nursing students from medical schools in Taiwan participated in our study. Data were collected between March and May 2022. The learning method used with the intervention group was role-playing with videos and guided reflection. The control group was exposed to traditional curriculum. Empathy, caring behavior and competence were measured using the Jefferson Scale of Empathy- Healthcare Providers, the Caring Behaviors Scale and the Nursing Student Competence Scale., Result: A total of 72 participants (40 in the experimental group and 32 in the control group) were included in the final statistical analysis. The response rate was 92%. Statistically significant differences in nursing student empathy, caring behavior and competence were observed between the experimental and control groups (p < .05). The η 2 effect levels were 0.083, 0.223 and 0.270. Higher caring behavior scores were significantly associated with higher nursing student competence scores (β = 0.81, 95% CI:0.66-0.97)., Conclusions: Education based on video role-play and guided reflection improved empathy, caring behavior and nursing competence in first-year nursing students., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A new drug delivery system (DDS) type complexing magnetic nanoparticles (MNP) along with boron nanosheets (BNN) coated with a pH-responsive polymer-polyethylene glycol (PEG) for the manageable loading/release of the anti-cancerous drug, doxorubicin (DOX), was created (MNP-BNN-PEG-DOX). The X-ray diffraction patterns of the nanocomposites displayed wide diffraction peaks for BNN at 25.1° and 42.3°, belonging to the (002) and (100) planes, correspondingly. Additionally, the characteristic peaks of Fe 3 O 4 appeared at 30.5°, 35.9°, 43.6°, 54.1°, 57.5°, and 63.2°, belonging to the (220), (311), (400), (422), (511), and (440) crystal planes, correspondingly. Moreover, the magnetic properties of the nanocomposites revealed that the MNP-BNN remained magnetic after coating with PEG. The saturation magnetization (Ms) of the uncoated-MNP-BNN and MNP-BNN-PEG-1 were 49.4 and 42.3 emu g -1 , respectively. Both in vitro and in vivo analyses shown that DDS might inhibit tumor growth, provoke cancer cell apoptosis, and reduce the cytotoxic effects of DOX. In vivo analysis demonstrated that after treatment with phosphate-buffered saline (PBS), MNP-BNN-PEG-1, free DOX, and MNP-BNN-PEG-1-DOX, the average tumor growth and weight were 1906, 1997, 1188, and 1043 nm and 0.17, 0.20, 0.13, and 0.07 g, respectively. The MNP-BNN-PEG-DOX nanoparticles could be an effective treatment and potential alternative for liver cancer therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Group A Streptococcus (GAS) is a strict human pathogen possessing a unique pathogenic trait that utilizes the cooperative activity of NAD + -glycohydrolase (NADase) and Streptolysin O (SLO) to enhance its virulence. How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracellular survival is a long-standing question. Here, the structure and dynamic nature of the NADase/SLO complex are elucidated by X-ray crystallography and small-angle scattering, illustrating atomic details of the complex interface and functionally relevant conformations. Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection. Furthermore, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated in a murine infection model. Overall, this work delivers the structure-functional relationship of the NADase/SLO complex and pinpoints the key interacting residues that are central to the coordinated actions of NADase and SLO in the pathogenesis of GAS infection., (© 2023. The Author(s).)

Light-emitting diodes (LEDs) are used widely, but when operated at a low-voltage direct current (DC), they consume unnecessary power because a converter must be used to convert it to an alternating current (AC). DC flow across devices also causes charge accumulation at a high current density, leading to lowered LED reliability. In contrast, gallium-nitride-based LEDs can be operated without an AC-DC converter being required, potentially leading to greater energy efficiency and reliability. In this study, we developed a multicolor AC-driven light-emitting device by integrating a WSe 2 monolayer and AlGaInP-GaInP multiple quantum well (MQW) structures. The CVD-grown WSe 2 monolayer was placed on the top of an AlGaInP-based light-emitting diode (LED) wafer to create a two-dimensional/three-dimensional heterostructure. The interfaces of these hybrid devices are characterized and verified through transmission electron microscopy and energy-dispersive X-ray spectroscopy techniques. More than 20% energy conversion from the AlGaInP MQWs to the WSe 2 monolayer was observed to boost the WSe 2 monolayer emissions. The voltage dependence of the electroluminescence intensity was characterized. Electroluminescence intensity-voltage characteristic curves indicated that thermionic emission was the mechanism underlying carrier injection across the potential barrier at the Ag-WSe 2 monolayer interface at low voltage, whereas Fowler-Nordheim emission was the mechanism at voltages higher than approximately 8.0 V. These multi-color hybrid light-emitting devices both expand the wavelength range of 2-D TMDC-based light emitters and support their implementation in applications such as chip-scale optoelectronic integrated systems, broad-band LEDs, and quantum display systems.

Acute caffeine intake has been found to increase working memory (WM)-related brain activity in healthy adults without improving behavioral performances. The impact of daily caffeine intake-a ritual shared by 80% of the population worldwide-and of its discontinuation on working memory and its neural correlates remained unknown. In this double-blind, randomized, crossover study, we examined working memory functions in 20 young healthy non-smokers (age: 26.4 ± 4.0 years; body mass index: 22.7 ± 1.4 kg/m 2 ; and habitual caffeine intake: 474.1 ± 107.5 mg/day) in a 10-day caffeine (150 mg × 3 times/day), a 10-day placebo (3 times/day), and a withdrawal condition (9-day caffeine followed by 1-day placebo). Throughout the 10th day of each condition, participants performed four times a working memory task (N-Back, comprising 3- and 0-back), and task-related blood-oxygen-level-dependent (BOLD) activity was measured in the last session with functional magnetic resonance imaging. Compared to placebo, participants showed a higher error rate and a longer reaction time in 3- against 0-back trials in the caffeine condition; also, in the withdrawal condition we observed a higher error rate compared to placebo. However, task-related BOLD activity, i.e., an increased attention network and decreased default mode network activity in 3- versus 0-back, did not show significant differences among three conditions. Interestingly, irrespective of 3- or 0-back, BOLD activity was reduced in the right hippocampus in the caffeine condition compared to placebo. Adding to the earlier evidence showing increasing cerebral metabolic demands for WM function after acute caffeine intake, our data suggest that such demands might be impeded over daily intake and therefore result in a worse performance. Finally, the reduced hippocampal activity may reflect caffeine-associated hippocampal grey matter plasticity reported in the previous analysis. The findings of this study reveal an adapted neurocognitive response to daily caffeine exposure and highlight the importance of classifying impacts of caffeine on clinical and healthy populations., (© 2023. The Author(s).)

Ultraviolet-C AlGaN resonant-cavity light-emitting diodes with top and bottom pipe-AlGaN-distributed Bragg reflectors (DBRs) have been demonstrated. For the top/bottom DBR structures, 20 pairs of n + -AlGaN:Si/n-AlGaN:Si stack structures were transformed into the pipe-AlGaN:Si/n-AlGaN:Si DBRs through a doping-selective electrochemical wet etching process. The reflectivity of the pipe-AlGaN DBR structure was measured as 90% at 276.7 nm with a 20.9 nm flat stopband width. The anisotropic optical properties of the pipe-AlGaN DBR structure had been analyzed through the polarization-dependent reflectance spectra. For temperature-dependent reflectance spectra, the central wavelengths were slightly redshifted from 275 nm (100 K) to 281 nm (600 K) due to thermal expansion, refractive index increase, and partial strain release phenomena in the pipe-DBR structure. High photoluminescence emission intensity and line-width reducing phenomena were observed at 10 K in the UVC-LED with the resonant-cavity structure, which has potential for high-efficiency UV-C light source applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

To further enhance the color conversion from a quantum-well (QW) structure into a color-converting colloidal quantum dot (QD) through Förster resonance energy transfer (FRET), we designed and implemented a device structure with QDs inserted into a GaN nano-porous structure near the QWs to gain the advantageous nanoscale-cavity effect. Additionally, surface Ag nanoparticles were deposited for inducing surface plasmon (SP) coupling with the QW structure. Based on the measurements of time-resolved and continuous-wave photoluminescence spectroscopies, the FRET efficiency from QW into QD is enhanced through the SP coupling. In particular, performance in the polarization perpendicular to the essentially extended direction of the fabricated pores in the nano-porous structure is more strongly enhanced when compared with the other linear polarization. A numerical simulation study was undertaken, and showed consistent results with the experimental observations.

In this study, a tunable terahertz (THz) metamaterial using the micro-electro-mechanical system (MEMS) technique is proposed to demonstrate pressure sensing application. This MEMS-based tunable metamaterial (MTM) structure is composed of gold (Au) split-ring resonators (SRRs) on patterned silicon (Si) substrate with through Si via (TSV). SRR is designed as a cantilever on the TSV structure. When the airflow passes through the TSV from bottom to up and then bends the SRR cantilever, the SRR cantilever will bend upward. The electromagnetic responses of MTM show the tunability and polarization-dependent characteristics by bending the SRR cantilever. The resonances can both be blue-shifted from 0.721 THz to 0.796 THz with a tuning range of 0.075 THz in transverse magnetic (TM) mode and from 0.805 THz to 0.945 THz with a tuning range of 0.140 THz in transverse electric (TE) mode by changing the angle of SRR cantilever from 10° to 45°. These results provide the potential applications and possibilities of MTM design for use in pressure and flow rate sensors.

Eggshells offer many advantages as adsorbents, such as affordability without special preparations other than pulverization and calcination. However, the manufacturing industry generally has a severe problem with high concentrations of heavy metals in wastewater. The purpose of this study was to use eggshell byproducts and calcined eggshell treatment for the adsorption of copper in an aqueous solution. The reaction time, metal concentration, adsorbent dose, temperature, and pH were evaluated using primary factors followed by the response surface method (RSM) to investigate the optimum conditions for eggshell byproducts and calcined eggshell adsorption treatment. The results of the one-factor-at-a-time experiment showed that the optimal adsorption rate was obtained from treatment at 24 h, 25 mg/L, 10 mg, and 25 °C. In addition, the effect of pH on the adsorption rates of eggshells and eggshells with membrane were detected at pH values of 5 and 5.9 and found to be 95.2, 90.5, and 73.3%. The reaction surface experiment showed that the best adsorption rate reached 99.3% after calcination at 900 °C for 2 h and a 20 min reaction. The results showed that eggshells, eggshell membranes, eggshells with membrane, and calcined eggshells could be applied to remove copper ions from industrial wastewater. The adsorption capacity of the calcined eggshell is better than that of the non-calcined eggshell and has good neutrality in acidic industrial wastewater. Therefore, it is convenient and practical for practical production and application. Likewise, this study conveys promising findings in the context of improving wastewater treatment based on a circular economy approach to waste reuse in the food industry and represents a valuable direction for future research., (© 2023. The Author(s).)

Background: Postoperative urinary retention (POUR) is a common complication following orthopaedic surgery. Previous studies attempted to establish the preventative role of α1-antagonist in POUR in the general surgical population; however, there is still no consensus regarding its use in orthopaedic surgery due to limited evidence., Methods: Electronic databases of Cochrane Library, Embase, MEDLINE, and ClinicalTrials.gov were searched by two independent investigators from inception to 1 March 2022 to identify relevant randomized clinical trials. Two reviewers independently completed a critical appraisal of included trials by using the Cochrane Risk of Bias tool version 2.0 and extracted data from included articles. Risk of POUR was summarized as risk ratio (RR) with 95 per cent confidence intervals (c.i.). Mean difference (MD) was used for meta-analysis of continuous outcomes., Results: Five randomized clinical trials involving 878 patients (α1-antagonist, 434; placebo, 444) undergoing hip/knee arthroplasty and spine surgeries were included. One study was assessed as high risk of bias from the randomization process and was excluded from the final meta-analysis. There was no difference in the risk of POUR between patients taking α1-antagonist and the placebo in arthroplasty (RR, 0.64; 95 per cent c.i., 0.36 to 1.14) and in spine surgeries (RR, 1.03; 95 per cent c.i., 0.69 to 1.55). There was no difference in length of stay (MD, -0.14 days; 95 per cent c.i., -0.33 to 0.05). Use of α1-antagonist was associated with a higher risk of adverse events (RR, 1.97; 95 per cent c.i., 1.27 to 3.06), with a composite of dizziness, light-headedness, fatigue, altered mental status, and syncope being the most commonly reported symptoms., Conclusion: In patients undergoing spinal surgery and joint arthroplasty, routine administration of perioperative α1-antagonist does not decrease risk of POUR but does increase perioperative dizziness, light-headedness, and syncope., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Amyloidogenesis, self-propagation of protein or peptide monomers to amyloid fibrils, has been linked to incurable pathogenesis of neurodegenerative diseases such as Alzheimer's disease and prion diseases. Investigations of amyloid structures and how monomers are transformed through seeding are therefore crucial for developing therapeutics toward these diseases. Here we describe a cross-seeding method to explore the amyloid core in prion fibrils that uses preformed amyloid fibrils as a seed to induce the transformation of other protein or peptide monomers to amyloid fibrils., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Mycotoxins are secondary metabolites produced by various kinds of fungi that can induce disease in humans. The fungal species Penicillium expansum produces patulin (C 7 H 6 O 4 ), a polyketide lactone mycotoxin found in fruits. Patulin is classified as noncarcinogen; however, recently, it has been associated with harmful effects on the central nervous system. Patulin's toxic action has been established in various brain models; however, its effect on human glioblastoma remains elusive. This study explores whether patulin induces cytotoxicity through oxidative stress in DBTRG-05MG human glioblastoma cells. This study also evaluates whether the antioxidant N-acetylcysteine (NAC) protects against patulin-induced cytotoxicity. In DBTRG-05MG cells, patulin concentration (10-60 μM) dependently induced cytotoxicity. Concerning oxidative stress, patulin (10 and 20 μM) increased the production of intracellular reactive oxygen species (ROS) but depleted reduced glutathione (GSH) contents and regulated the expressions of antioxidant-related proteins (Nrf2 and HO-1). Furthermore, patulin induced cytotoxicity via modulation of apoptosis-related protein expressions (Bax, cleaved caspase-9, and cleaved caspase-3). These cytotoxic responses were partially reversed via pretreatment with NAC (10 μM). In summary, these data help us understand the toxicology of patulin in human glioblastoma and evaluate whether NAC could clinically reduce patulin-affected brain damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with both systematic inflammation and renal dysfunction. Reports have suggested that anti-inflammatory properties of vitamin D may provide protection against renal injury. This cross-sectional study tested the hypothesis that serum 25-hydroxyvitamin D [25(OH)D] moderates the inflammation and albuminuria associated with PAH exposure. Data were obtained from 5,982 subjects aged 20-79 years in the National Health and Nutrition Examination Survey (2001-2010). PAH exposure was estimated by urinary PAH metabolites. Inflammation was defined as serum C-reactive protein (CRP) > 3 mg/L and albuminuria as urinary albumin-to-creatinine ratio > 30 mg/g. The results found that greater PAH exposure was linked with inflammation and albuminuria. Individuals with PAH exposure also tended to have lower 25(OH)D and lower vitamin D was associated with both elevated CRP (Odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.07-1.54) and urinary albumin (1.35, 95%CI = 1.03-1.77) for any given PAH exposure. Those with lower serum 25(OH)D-to-urinary PAH ratios were likewise at a greater risk of elevated CRP and albuminuria. The findings support prior suggestions that exposure to PAHs is associated with inflammation and albuminuria but suggests further that the risk is higher when vitamin D is lower. Thus, nutritional status becomes an important variable in PAH risk assessment.

Background: Little is known about the effect that different time sequences for coronary ligation and reperfusion have on ischemic-reperfusion (IR) injury., Objective: To investigate the relationship between the extent of IR injury and the timeframe for coronary ligation/reperfusion in three animal models., Methods: Three rat models were used: normal Sprague-Dawley rats, diabetes mellitus (DM) rats, and fat rats. The rats in each model were divided into four groups based on the coronary ligation period (L): 30, 60, 120, and 180 min, and then divided into seven sub-groups based on the reperfusion period (R): 0, 30, 60, 120, 180, 270, and 360 min. R0 was the IR injury baseline for each sub-group. The hearts were harvested and stained with Evans blue and 2,3,5-triphenyl tetrazolium chloride dye to distinguish the different myocardial injury areas: area at risk (AAR) and myocardial necrosis. The difference between each subgroup and baseline (R0) for the necrotic area/AAR was calculated., Results: In the normal rats, the highest IR injury differences compared with the baseline group occurred at L120, with a reperfusion time of > 180 min. The highest IR injury difference compared to the baseline group occurred at L30, with a reperfusion time of > 180 min in the DM rats and at L60R270, L120R180 in the fat rats., Conclusions: IR injury, as induced by different coronary ligation and reperfusion time intervals, had diverse expression profiles in the different animal models. Optimal animal models with optimal coronary ligation/reperfusion protocols to achieve maximal IR injury will affect the results and interpretation of future studies.

Background: In China, the current status of clinical treatment of eLVO and the factors affecting its long-term prognosis are unclear., Objective: This study aims to explore the predictive factors of functional outcomes at one year in patients of acute ischemic stroke with emergent large vessel occlusion (eLVO)., Methods: We retrospectively collected 536 patients who underwent treatments for eLVO. Primary outcomes included one-year functional outcomes and delayed functional independence (DFI). The logistic regression was performed to predict the primary outcome., Results: 431 (85%) survivors participated in the one-year follow-up. In the multivariate logistic analysis adjusted for baseline characteristics, the following factors were found to be significant predictors of functional dependence at one year: old age (aOR = 1.042, 95% CI=1.01-1.076, p = 0.011), low Alberta stroke program early CT score (ASPECTS) (aOR = 0.791, 95% CI=0.671-0.933, p = 0.005), unsuccessful reperfusion (aOR = 0.168, 95% CI=0.048-0.586, p = 0.005), poor medication compliance (aOR = 0.022, 95% CI=0.007-0.072, p < 0.001), and complicated with stroke-associated pneumonia (SAP) (aOR = 2.269, 95% CI=1.103-4.670, p = 0.026). We also found that men (aOR = 3.947, 95% CI=1.15-13.549, p = 0.029) had better medication adherence (aOR = 14.077, 95% CI=1.736-114.157, p = 0.013), and going to rehabilitation centers (aOR = 5.197, 95% CI=1.474-18.327, p = 0.010) were independent predictors of DFI., Conclusion: The significant predictors of functional dependence at one year were: old age, low ASPECTS, unsuccessful reperfusion, poor medication adherence, and combination with SAP. Men, good medication adherence, and going to rehabilitation centers contributed to getting delayed functional independence.

Aims: Mineralocorticoid receptor antagonists (MRAs) have been shown to provide survival benefits in patients with heart failure; however, MRA use in patients with chronic kidney disease has been limited by safety concerns. The effects of MRAs on outcomes in patients with end-stage renal disease (ESRD) and heart failure remain unknown. The aim of this study was to evaluate the effects of MRAs on cardiovascular outcomes in patients with heart failure under maintenance dialysis in a real-world setting., Methods and Results: A retrospective cohort study was conducted by collecting data from the Taiwan National Health Insurance Research Database (NHIRD). Patients diagnosed with heart failure and ESRD and who started maintenance dialysis between 1 January 2001 and 31 December 2013 were identified. Patients were grouped according to MRA prescription. The outcomes of interest included cardiovascular (CV) death, hospitalization for heart failure (HHF), all-cause mortality, acute myocardial infarction (AMI), ischaemic stroke, any coronary revascularization procedures, and new-onset hyperkalaemia. Propensity score matching was performed at a 1:3 ratio between MRA users and non-users to minimize selection bias. A total of 50 872 patients who satisfied our inclusion and exclusion criteria were identified. After 1:3 matching, 2176 patients were included in the MRA group, and 6528 patients were included in the non-MRA group. The risk of CV death was significantly lower among patients who received MRAs than those who did not (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.80-0.95), as was the risk of all-cause mortality (HR 0.88, 95% CI 0.83-0.94). Reductions in the risks of CV death and all-cause mortality were more prominent among patients undergoing haemodialysis and those with coronary artery disease., Conclusions: In patients undergoing regular dialysis who are diagnosed with heart failure, the use of MRAs is associated with lower risks of all-cause mortality and CV death. The benefits of MRA treatment in heart failure may persist in patients with ESRD. Further investigations through randomized controlled trials are needed to assess the efficacy and safety of MRAs in this high-risk population., (© 2022 European Society of Cardiology.)

Introduction: Regular physical exercise is believed to counteract the adverse physiological consequences of aging. However, smart fitness equipment specifically designed for older adults is quite rare. Here we designed an exergame-integrated internet of things (IoT)-based ergometer system (EIoT-ergo) that delivers personalized exercise prescriptions for older adults. First, physical fitness was evaluated using the Senior Fitness Test (SFT) application. Then, radio frequency identification (RFID) triggered the EIoT-ergo to deliver the corresponding exercise session based on the individual level of physical fitness. The exercise intensity during each workout was measured to generate the next exercise session. Further, EIoT-ergo provides an exergame to help users control and maintain their optimal cadence while engaging in exercise., Methods: This was a randomized controlled trial with 1:1 randomization. Participants were older adults, 50+ years of age (N = 35), who are active in their community. Participants in the EIoT-ergo group received a 12-week personalized exercise program delivered by EIoT-ergo for 30 min per session, with 2 sessions per week. Participants in the control group continued with their usual activities. A senior's fitness test and a health questionnaire were assessed at baseline and at a 13-week reassessment. The Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) was used to evaluate the satisfaction of EIoT-ergo., Results: Compared with the control group, the EIoT-ergo group showed significant improvements in muscle strength (time-by-group interaction, sit-to-stand: β = 5.013, p < 0.001), flexibility (back stretch: β = 4.008, p = 0.005; and sit-and-reach: β = 4.730, p = 0.04), and aerobic endurance (2-min step: β = 9.262, p = 0.03). The body composition was also improved in the EIoT-ergo group (body mass index: β = -0.737, p < 0.001; and skeletal muscle index: β = 0.268, p = 0.03). Satisfaction with EIoT-ergo was shown in QUEST, with an average score of 4.4 ± 0.32 (5 for very satisfied). The percentage maximum heart rate in each session also indicated that EIoT-ergo can gradually build up the exercise intensity of users., Conclusions: EIoT-ergo was developed to provide personal identification, exergames, intelligent exercise prescriptions, and remote monitoring, as well as to significantly enhance the physical fitness of the elderly individuals under study., (© 2023 S. Karger AG, Basel.)

Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD., Competing Interests: The authors declare no conflict of interest.

Tumour metabolomics and transcriptomics co-expression network as related to biological folate alteration and cancer malignancy remains unexplored in human non-small cell lung cancers (NSCLC). To probe the diagnostic biomarkers, tumour and pair lung tissue samples (n = 56) from 97 NSCLC patients were profiled for ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS)-analysed metabolomics, targeted transcriptionomics, and clinical folate traits. Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Tumour lactate was identified as the top VIP marker to predict advance NSCLC (AUC = 0.765, Sig = 0.017, CI 0.58-0.95). Low folate (LF)-tumours vs. adjacent lungs displayed higher glycolytic index of lactate and glutamine-associated amino acids in enriched biological pathways of amino sugar and glutathione metabolism specific to advance NSCLCs. WGCNA classified the green module for hub serine-navigated glutamine metabolites inversely associated with tumour and RBC folate, which module metabolites co-expressed with a predominant up-regulation of LF-responsive metabolic genes in glucose transport ( GLUT1 ), de no serine synthesis ( PHGDH , PSPH , and PSAT1 ), folate cycle ( SHMT1/2 and PCFR ), and down-regulation in glutaminolysis ( SLC1A5 , SLC7A5 , GLS , and GLUD1 ). The LF-responsive WGCNA markers predicted poor survival rates in lung cancer patients, which could aid in optimizing folate intervention for better prognosis of NSCLCs susceptible to folate malnutrition.