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Ya-Chun Liao,1 Yao-Ting Huang,2,* Chien-Hao Tseng,1 Chia-Wei Liu,1 Po-Yu Liu1,3,4,* 1Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Computer Science and Information Engineering, National Chung Cheng University, Chiayi, Taiwan; 3Department of Post-Baccalaureate Medicine, National Chung Hsing University, Taichung, Taiwan; 4Genome Center for Infectious Diseases, Taichung Veterans General Hospital, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Po-Yu Liu, Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Blvd., Xitun District, Taichung, Taiwan, Tel +886-4-2359-2525, Fax +886-4-2359-5046, Email pyliu@vghtc.gov.twPurpose: Burkholderia cepacia complex (Bcc) is a known significant opportunistic pathogen causing morbidity and mortality, particularly in those with cystic fibrosis, chronic granulomatous disease, or immunocompromising host. Mortality of Bcc bloodstream infections among non-cystic fibrosis patients remained high. The antibiotic treatment for Bcc infection is quite challenging due to its intrinsic resistance to most antibiotics, and the resistance to carbapenems was the biggest concern among them. We aimed to realize the mechanism of carbapenem resistance in Bcc.Patients and Methods: Ten strains of Bcc were identified by the MALDI-TOF MS, and the drug susceptibility test was using VITEK 2 system. The Burkholderia cepacia complex genomes were sequenced via Nanopore GridIon. We also downloaded another ninety-five strains of Bcc from the National Center for Biotechnology Information database to evaluate the divergence between carbapenem-resistance and carbapenem-sensitive strains.Results: The genetic organization between carbapenem-sensitive and carbapenem-resistant strains of Bcc showed no difference. However, in the carbapenem-sensitive strain, E151V substitution in PenR was detected. In addition, a novel specific OXA family subgroup, blaOXA-1043 in Burkholderia cenocepacia was discovered.Conclusion: The E151V substitution in PenR may be associated with carbapenem-sensitive in Bcc. Moreover, the V151E mutation in PenR may be related to the activation of PenB, leading to Bcc resistance to carbapenems. Besides, a novel OXA family subgroup, blaOXA-1043, was found in Burkholderia cenocepacia, which differs from the previous OXA family.Keywords: Burkholderia cepacia complex, Burkholderia cenocepacia, carbapenem-resistant, whole-genome sequencing

Po-Hsiu Huang,1,* Yao-Ting Huang,2,* Po-Hsin Lee,3– 6 Chien-Hao Tseng,7 Po-Yu Liu,5– 7 Chia-Wei Liu7 1Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Computer Science and Information Engineering, National Chung Cheng University, Chia-Yi, Taiwan; 3Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 4College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 6Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 7Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan*These authors contributed equally to this workCorrespondence: Po-Yu Liu; Chia-Wei Liu, Tel +886 4 2359 2525, Fax +886 4 2359 2525 2111, Email pyliu@vghtc.gov.tw; chiaweiliu35@gmail.comAbstract: Coinfection in COVID-19 patients is associated with worsening outcome. Among patients with COVID-19, Legionella pneumophila, a common cause of pneumonia, has been reported as a co-occurring respiratory infection. A nonspecific clinical presentation, however, makes an early diagnosis difficult. Bronchoalveolar lavage fluid was collected from a patient suffering from COVID-19 and presenting with pneumonia and sent for metagenomic analysis. Differential abundance analysis was carried out by comparing each taxon reads per million between the bronchoalveolar lavage fluid sample and the negative control. Two replicates of metagenomic sequencing were conducted on bronchoalveolar lavage fluid samples. Within each replicated sequencing, one negative control was sequenced for comparison of taxon abundance in the BALF sample. In both replicates, Legionella pneumophila was the only taxon with significantly higher abundance when compared with the negative control. PCR of the bronchoalveolar further confirmed the presence of L. pneumophila. Several studies have estimated that the incidence of Legionnaires’ disease co-infection in patients with COVID-19 infection is approximately 0% to 1.5%. There are some common characteristics of COVID-19 and co-infection with Legionnaires’ disease, making it difficult to diagnose bacterial infection early. The diagnosis of these cases is important due to the different treatments used. Current diagnostic tests for Legionnaires’ disease include conventional culture, urinary antigen for L. pneumophila serogroup 1, polymerase chain reaction, direct fluorescent antibody stain, and paired serology. The current study demonstrated that metagenomics is a promising approach that facilitated the diagnosis of Legionnaires’ disease.Keywords: Legionnaires’ disease, COVID-19, co-infection, next-generation sequencing

Jen-Yu Hsu,1 Po-Yu Liu,1 Chien-Hao Tseng,1 Chia-Wei Liu,1 Wan-Ting Yang,1 Wei-Hsuan Huang,1 Shu-Yuan Li,1 Ya-Chun Liao,1 Ming-Ju Wu2 1Division of Infectious Diseases, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, 407, Taiwan; 2Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan & College of Medicine, National Chung Hsing University, Taichung, 402, TaiwanCorrespondence: Ming-Ju WuDepartment of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Sec. 4, Taiwan Blvd, Xitun Dist, Taichung City, 407219, TaiwanTel +886-4-23592525Email wmj530@gmail.comPurpose: The COVID-19 pandemic poses a serious threat to healthcare workers and hospitalized patients. Early detection of COVID-19 cases is essential to control the spread in healthcare facilities. However, real-world data on the screening criteria for hospitalized patients remain scarce. We aimed to explore whether patients with negative results of pre-hospital screening for COVID-19 should be rescreened after admission in a low-prevalence (less than 3% of the world average) setting.Patients and Methods: We retrospectively included patients in central Taiwan who were negative at the first screening but were newly diagnosed with pneumonia or had a body temperature above 38 degrees Celsius during their hospitalization. Each patient might be included as an eligible case several times, and the proportions of cases who were rescreened for COVID-19 and those diagnosed with COVID-19 were calculated. A logistic regression model was constructed to identify factors associated with rescreening. Reverse transcription-polymerase chain reaction tests were used to confirm the diagnosis of COVID-19.Results: A total of 3549 cases eligible for COVID-19 rescreening were included. There were 242 cases (6.8%) who received rescreening. In the multivariable analysis, cases aged 75 years or older, those with potential exposure to SARS-CoV-2, or patients visiting specific departments, such as the Cardiovascular Center and Department of Neurology, were more likely to be rescreened. None was diagnosed with COVID-19 after rescreening. There was no known cluster infection outbreak in the hospital or in the local community during the study period and in the following two months.Conclusion: In Taiwan, a country with a low COVID-19 prevalence, it was deemed safe to rescreen only high-risk hospitalized patients. This strategy was effective and reduced unnecessary costs.Keywords: fever, pneumonia, risk, SARS-CoV-2, screen

Shih-Wei Lee,1,* Yu-Chen Huang,2,3,* Chun-Yu Lin,2,3 Hung-Yu Huang,2,3 Chi-Wei Liu,1 Ming-Tsuen Hsieh,4 Chon-Lin Lee,4– 7 Wen-Yu Chung,8 Kian Fan Chung,9 Chun-Hua Wang,2,3 Han-Pin Kuo10,11 1Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 2Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 3College of Medicine, Chang Gung Memorial University, Taoyuan, Taiwan; 4Department of Marine Environment and Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Aerosol Science and Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan; 6Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Department of Applied Chemistry, Providence University, Taichung, Taiwan; 8Department of Computer Science and Information Engineering, National Kaohsiung University of Science and Technology, Kaohsiung, Taiwan; 9Experimental Studies, National Heart and Lung Institute, Imperial College London and Royal Brompton Hospital, London, UK; 10Pulmonary Medicine Research Center, Taipei Medical University, Taipei, Taiwan; 11Department of Thoracic Medicine, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Chun-Hua WangDepartment of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa North Road, Taipei 10507, TaiwanTel +886 3 321 1200 ext 8467Email wchunhua@ms7.hinet.netHan-Pin KuoDepartment of Medicine, Taipei Medical University School of Medicine, 250 Wu-Xing Street, Taipei 11031, TaiwanEmail q8828@ms11.hinet.netPurpose: Exposure to polycyclic aromatic hydrocarbons (PAHs) associated with ambient air particulate matter (PM) poses significant health concerns. Increased acute exacerbation (AE) frequency in asthmatic patients has been associated with ambient PAHs, but which subgroup of patients are particularly susceptible to ambient PAHs is uncertain. We developed a new model to simulate grid-scale PM2.5-PAH levels in order to evaluate whether the severity of asthma as measured by the Global Initiative of Asthma (GINA) levels of treatment is related to cumulative exposure of ambient PAHs.Methods: Patients with asthma residing in the northern Taiwan were reviewed retrospectively from 2014 to 2017. PM2.5 were sampled and analysed for PAHs twice a month over a 72-hour period, in addition to collecting the routinely monitored air pollutant data from an established air quality monitoring network. In combination with correlation analysis and principal component analysis, multivariate linear regression models were performed to simulate hourly grid-scale PM2.5-PAH concentrations (ng/m3). A geographic information system mapping approach with ordinary kriging interpolation method was used to calculate the annual exposure of PAHs (ng/m).Results: Among the 387 patients with asthma aged 18 to 93 (median 62), 97 subjects were treated as GINA step 5 (24%). Asthmatics in GINA 5 subgroup with high annual PAHs exposure were likely to have a higher annual frequency of any AE (1 (0– 12), p< 0.0001). Annual PAHs exposure was correlated with the annual frequency of any exacerbation (r=0.11, p=0.02). This was more significant in the GINA 5 subgroup (r=0.29, p=0.005) and in the GINA 5 subgroup with severe acute exacerbations (r=0.51, p=0.002). Annual PAHs exposure, severe acute exacerbation and GINA steps were independent variables that predict annual frequency of any exacerbation.Conclusion: Asthmatic patients in the GINA 5 subgroup with acute exacerbations were more susceptible to the effect of environmental PAHs on their exacerbation frequency. Reducing environmental levels of PAHs will have the greatest impact on the more severe asthma patients.Keywords: polycyclic aromatic hydrocarbons, asthma acute exacerbation, GINA, hourly grid-scale model

Chunrui Wang,1 Zhe Yuan,1 Wenxiang Huang,1 Li Yan,2 Jun Tang,3 Cheng-wei Liu3 1Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 3Department of Infectious Diseases, Key Laboratory of Infectious and Parasitic Diseases in Chongqing, Chongqing 400016, People’s Republic of China Background: Klebsiella pneumoniae (KP) is the most common pathogen isolated in intensive care units (ICUs) and the most frequently encountered carbapenemase-producing Enterobacteriaceae. Increasing antimicrobial drug resistance, especially in carbapenem-resistant KP (CRKP), can limit the choice of antibiotics used for the treatment of infectious diseases and further poses a negative impact on patient outcome. However, the reason behind this increasing resistance is not well known. Patients and methods: A retrospective analysis of laboratory records and clinical cases of KP infection in the ICUs of a hospital from January 2013 to December 2017 was conducted. The disk diffusion method and double-paper synergy test were used to test drug sensitivity for extended-spectrum β-lactamase (ESBL) detection. WHONET5.6 and SPSS 21.0 software were used for statistical analysis. Results: A total of 64.8% (570/847) of patients with KP infection were older than 60 years. The lower respiratory tract was the main infection site, accounting for 70.84% (600/847); the highest rate of ICU admission was for neurosurgery, accounting for 28.69% (243/847). Some 444 multidrug-resistant KP strains were detected, including 69 CRKP and 299 ESBL-producing strains. In the past 5 years, the resistance rate of detected strains to common antibiotics increased to various degrees, particularly carbapenem-resistant strains which increased from 4.76% (9/189) in 2013 to 16.00% (28/175) in 2017. All carbapenem-resistant isolates were resistant to β-lactam antibiotics, and no isolates were resistant to tigecycline. Conclusion: CRKP and ESBLKP prevalence and resistance rates gradually increased in our ICUs in the past 5 years. The reasons for this are manifold. Regular surveillance of resistance, rational use of antibiotics, and other effective infection control measures need to be strengthened to slow down the production of multidrug-resistant bacteria and prevent their spread in ICU settings. Keywords: Klebsiella pneumoniae, antibiotic resistance, carbapenem resistance, intensive care units

Chia Wen Liu,1,2 Wen Jen Lin11Graduate Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei; 2Drug Delivery Department, Biomedical Engineering Research Laboratories, Industrial Technology Research Institute, Hsinchu, TaiwanBackground: This study was performed to develop a functional poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG)-bearing amino-active end group for peptide conjugation.Methods and results: PLGA was preactivated following by copolymerization with PEG diamine. The resulting amphiphilic PLGA-PEG copolymer bearing 97.0% of amino end groups had a critical micelle concentration of 3.0 × 10-8 mol/L, and the half-effective inhibition concentration (IC50) of the prepared PLGA-PEG nanoparticles was >100 mg/mL, which was much higher than that of PLGA nanoparticles (1.02 ± 0.37 mg/mL). The amphiphilic properties of PLGA-PEG spontaneously formed a core-shell conformation in the aqueous environment, and this special feature provided the amino group on the PEG chain scattered on the surface of PLGA-PEG nanoparticles for efficient peptide conjugation. The peptide-conjugated PLGA-PEG nanoparticles showed three-fold higher uptake than peptide-free PLGA-PEG nanoparticles in a SKOV3 cell line with high expression of epidermal growth factor receptor. Both peptide-conjugated and peptide-free PLGA-PEG nanoparticles were used as nanocarriers for delivery of doxorubicin. Although the rate of release of doxorubicin from both nanoparticles was similar, drug release at pH 4.0 (500 U lipase) was faster than at pH 7.4. The IC50 of doxorubicin-loaded peptide-conjugated PLGA-PEG nanoparticles in SKOV3 cells (0.05 ± 0.03 µg/mL) was much lower (by 62.4-fold) than that of peptide-free PLGA-PEG nanoparticles (3.12 ± 1.44 µg/mL).Conclusion: This in vivo biodistribution study in SKOV3 tumor-bearing mice was further promising in that accumulation of doxorubicin in tumor tissue was in the order of peptide-conjugated PLGA-PEG nanoparticles > peptide-free PLGA-PEG nanoparticles > doxorubicin solution.Keywords: amphiphilic copolymer, peptide, nanoparticles, SKOV3 cell, doxorubicin

The morphological evolutions of chemical dissolution fronts have attracted increasing interest in the field of the geological sciences and in industrial applications. Extensive research based on numerical simulations has been conducted to understand how various mechanisms and processes influence the morphological evolution of chemical dissolution fronts within geological media. Most researchers in previous studies have assumed the medium permeability to be isotropic for developing numerical models, despite isotropic geological media being uncommon in the real world. This study investigates the effect of medium permeability anisotropy on the morphological evolutions of two non-uniformities with higher permeability in a geochemical dissolution system. A series of numerical simulations are performed to evaluate the effect of medium permeability anisotropy on the morphological evolution of a chemical dissolution front. The simulation results indicate that the patterns of the dissolution reaction front are substantially affected by medium permeability anisotropy. An increase in the permeability anisotropy ratio, which is defined as the ratio of the permeability in the transverse direction to that in the longitudinal direction, enhances the dominance of the flow-focusing effect over the stabilizing or merging effect induced by diffusion/dispersion mechanism. Therefore, an increase in the permeability anisotropy ratio can increase the fingering length of the dissolution front or cause the dissolution front to have a more unstable pattern. By contrast, a reduction in the permeability anisotropy ratio will weaken the flow-focusing effect, thereby reducing the fingering length of the dissolution front or changing the front morphology such that it has a more stable status. The effect of the permeability anisotropy ratio on the morphological evolution tends to decrease when the Zhao number (negative dimensionless upstream pressure gradient) of the system increases. The consideration of medium permeability anisotropy in the geochemical dissolution model renders the simulation of the morphological evolutions of dissolution reaction fronts more realistic.

This article aims to present a numerical study of the behavior of engine main bearings under dynamic load. The coupling performance characteristics of oil film between crankshaft and engine block are analyzed. The film pressure is solved numerically with Reynolds boundary conditions when various bearing characteristics are calculated. Hydrodynamic lubrication is analyzed with finite difference method for solving the Reynolds equation for thermo effect. The other models, such as engine block and crankshaft-connecting rod system, are processed by utilizing the finite element method. Above this system, model applied in this paper is simulated by employing multi-body dynamic method to capture the dynamic characteristics of engine dynamic simulation. Through the methods mentioned above, the performance characteristics of engine main bearings under hydrodynamic loads in a six-cylinder in-line diesel engine were received. And the orbit movement, minimum oil film thickness, and power loss in the bearing were estimated over the wide range of engine operation. [ABSTRACT FROM PUBLISHER]

Liquiritigenin (LQ) is a non-toxic dietary flavonoid with chemopreventive and anticancer properties. However, the mechanism of its antiangiogenesis remains unclear. Hypoxia-inducible factor-1[alpha] (HIF-1[alpha]) and its downstream target, vascular endothelial growth factor (VEGF), play a critical role in tumour angiogenesis and represent an attractive chemotherapeutic target. In this study, we investigated the effect of LQ on the molecular mechanism of angiogenesis. We found that LQ inhibited VEGF expression at both mRNA and protein levels. Liquiritigenin did not affect HIF-1[alpha] expression at the mRNA level, but it dramatically inhibited both serum- and mimicked hypoxic-induced HIF-1[alpha] protein accumulation in HeLa cells. Furthermore, we showed that LQ inhibited serum-induced expression of HIF-1[alpha] by reducing its stability and decreased the synthesis in a dose-dependent manner. Mechanistically, we demonstrated that LQ inhibited HIF-1[alpha] and VEGF expression involved in blocking the protein kinase B (PKB/Akt) signalling pathway, and the mechanisms correlated with dephosphorylation of the mammalian target of rapamycin (mTOR) and its effector ribosomal protein S6 kinase (p70S6K). In addition, LQ inhibited VEGF-induced formation of capillary-like structures in human umbilical vein endothelial cells (HUVEC). Taken together, our study provided valuable insights into the mechanism of antiangiogenic effect of LQ. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Contents The survival and development of pre-implantation embryos are determinant factors affecting the outcome of animal reproduction. It is essential to transfer the expression of the genetic material from maternal sources, that is the ovum to the zygote before implantation to ensure successful development. Differentiation and transformation of blastomeres initiated during the morula and blastocyst stages is an important step of the embryonic development prior to implantation. We collected morula and early blastocyst samples from pure-bred Landrace pigs in vivo to study the differential gene expression patterns at these two stages. Total RNA was extracted from individual embryos and two rounds of amplification were employed. Two micrograms of antisense RNA, targets, were prepared and hybridized with each of four custom made oligo microarrays representing 24 000 porcine genes. The analyses of replicate hybridizations showed that among the 24 000 genes, 162 genes were expressed fivefold or greater in the morula compared to early blastocysts and 2126 genes were expressed fivefold or greater in early blastocysts compared to the morula. Of these differentially expressed genes, 1429 genes were functionally annotated with related human Gene Ontology terms. In addition to basic metabolic processes, genes related to signal transduction, transportation and cell differentiation were found in both stages and were up-regulated as embryo development proceeded. Real time polymerase chain reaction was utilized to quantify 12 genes differentially expressed in the 2 embryonic stages and validated the reliability of major evidences shown in microarrays. In conclusion, we have obtained a preliminary landscape of genes differentially expressed during the transition from morula to early blastocysts in pigs and showed a generally increased transcriptional activity, perhaps in preparation for implantation. Our results provide an opportunity to study the functions of these genes in relation to the development and survival of pre-implantation porcine embryos. [ABSTRACT FROM AUTHOR]

An essential feature of coinage metal nanoclusters (NCs) is their photoluminescence (PL), which spans a wide range of wavelengths from visible to near-infrared regions (NIR-I/II). A key challenge for synthetic chemists is to develop materials capable of efficient spectral change with maximum efficiency. Herein, we report novel dithiolate-protected bimetallic Pd-Ag NCs of the type [PdAg 16 S 2 {S 2 P(OR) 2 } 12 ] (R = i Pr, 1Pr and i Bu, 1Bu) and [Pd 6 Ag 14 S{S 2 P(O i Bu) 2 } 12 ] (2Bu). Sulfide-mediated expansions of NCs result in unique PL in the NIR-I region for 1Pr and 1Bu ( λ max = 808 and 811 nm) and the NIR-II region for 2Pr ( λ max = 1007) at 77 K. NIR PL enhancement largely depends on structural modification with the sulfide anions at the central position. DFT calculations indicate that the PL properties are associated with 4d π (Pd)/3p π (S) → 5s/5p(Ag) excitation, resulting from the existence of S-Pd(0)-S motifs in both 1 and 2. The electrochemical gaps of 1Pr, 1Bu, and 2Bu are recorded by SWV.

Objective: The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA). Methods: This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up. Results: All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M (IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions: MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

Objective: This study investigated the impact of a 12-week remote interaction intervention on loneliness, quality of life, and social support for seniors living in a community during the COVID-19 pandemic., Methods: This study adopted a randomized controlled trial design. Participants in the intervention group received a 12-week bidirectional remote interaction intervention, while participants in the control group received a 12-week unidirectional remote interaction intervention. The study's primary assessment tools were the UCLA Loneliness Scale (UCLA) and the World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF)., Results: The main findings indicate that the intervention group scored significantly higher than the control group on the WHOQOL-BREF in the physical health and social relationships domains after the intervention. In addition, intervention group participants with low loneliness scored significantly higher than their control group counterparts in the physical health and social relationships domains of the WHOQOL-BREF. Similarly, intervention group participants with high loneliness scored significantly higher than their control group counterparts in the social relationships domain of the WHOQOL-BREF. However, there was no significant difference in loneliness scores between the intervention and control groups., Conclusions: This result confirms that providing intensive bidirectional interaction benefits seniors' quality of life during the COVID-19 pandemic.

Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article.

Background: Growing awareness of social inequities and injustices in education highlights the urgent need to address harmful mechanisms, policies, and norms within health education curricula and systems., Purpose: This study examines inclusivity and exclusivity content in four fundamental nursing textbooks and contributes to the broader discourse on fostering equitable health education., Methods: A Directed Qualitative Content Analysis on 32 chapters from four fundamental nursing textbooks was systematically conducted. Seven codes within inclusivity and exclusivity themes were deductively developed from the literature. Inclusivity codes included equity language and contextualized race-based prevalence. Exclusivity codes included normalizing Whiteness in assessment, stigmatizing and negative descriptors, race-based prevalence without context, cisgenderism, and othering. Two trained analysts independently reviewed the chapters, assigning texts to these codes. Discrepancies were resolved by team consensus., Results: A total of 118 inclusivity instances: equity language (n = 109) and race-based prevalence with context (n = 9). Exclusivity codes were more prevalent (n = 642), including normalizing Whiteness (n = 398), stigmatizing descriptors (n = 106), cisgenderism (n = 59), and othering (n = 32)., Conclusion: The study highlights inclusive language in fundamental nursing textbooks but reveals significant exclusive language perpetuating negative generalizations, including marginalized identities and race prevalence without context. This content undermines person-centered care and hinders understanding the complex interplay between intersectionality, social justice, and social determinants of health., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Recombinant human hepatocyte growth factor (HGF) plasmids are novel alternatives to salvage limbs in patients with chronic limb threatening ischaemia (CLTI). A systematic review and meta-analysis of data was conducted to assess the therapeutic efficacy of HGF plasmids in patients with CLTI., Data Sources: Randomised controlled studies evaluating HGF plasmid efficacy in patients with CLTI were identified using MEDLINE, Embase, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov databases., Review Methods: Meta-analyses of the reported relative risk (RR) or mean difference (MD) were conducted. Subgroup analyses were performed to determine the efficacy of HGF plasmids in cohorts excluding Buerger's disease. Certainty of evidence for each outcome was assessed., Results: Seven studies (n = 655 participants) were included. Based on low certainty evidence, patients treated with HGF had a significantly higher complete ulcer healing rate (RR 1.99, 95% confidence interval [CI] 1.30 - 3.04; p = .002) than patients treated with placebo. HGF treatment was associated with reduced visual analogue scale (VAS) scores of pain severity (MD -1.56, 95% CI -2.12 - -1.00; p < .001) vs. placebo in patients with CLTI assessed at three month follow up (low certainty evidence); no significant differences were observed in major amputation (RR 0.91, 95% CI 0.48 - 1.73; p = .77) (low certainty evidence) or all cause mortality rate (RR 0.93, 95% CI 0.38 - 2.27; p = .87) (low certainty evidence) between patients treated with HGF and placebo. Low certainty evidence suggested no significant differences in change in ankle brachial index at six months (MD 0.00, 95% CI -0.09 - 0.09; p = 1.0) between patients treated with HGF and placebo. The complete ulcer healing rate and improved three month VAS scores of pain severity benefits persisted in subgroup analyses (low certainty evidence)., Conclusion: Low certainty evidence suggested that HGF treatment is associated with an increased complete ulcer healing rate and reduced ischaemic pain in patients with CLTI., (Copyright © 2024. Published by Elsevier B.V.)

Infection is a known cause of abdominal aortic aneurysm (AAA), and matrix metalloproteases-2 (MMP-2) secreted by vascular smooth muscle cells (SMCs) plays a key role in the structural disruption of the middle layer of the arteries during AAA progression. The periodontal pathogen Porphyromonas gingivalis is highly associated with the progression of periodontitis. GroEL protein of periodontal pathogens is an important virulence factor that can invade the body through either the bloodstream or digestive tract and is associated with numerous systemic diseases. Although P. gingivalis aggravates AAA by increasing the expression of MMP-2 in animal studies, the molecular mechanism through which P. gingivalis regulates the expression of MMP-2 is still unknown and requires further investigation. In this study, we first confirmed through animal experiments that P. gingivalis GroEL promotes MMP-2 secretion from vascular SMCs, thereby aggravating Ang II-induced aortic remodeling and AAA formation. In addition, rat vascular SMCs and A7r5 cells were used to investigate the underlying mechanisms in vitro. The results demonstrated that GroEL can promote the interaction between the K639 site of MMP-2 and SUMO-1, leading to MMP-2 SUMOylation, which inhibits the reoccurrence of non-K639-mediated monoubiquitylation. Hence, the monoubiquitylation-mediated lysosomal degradation of MMP-2 is inhibited, consequently promoting MMP-2 stability and production. SUMOylation may facilitate intra-endoplasmic reticulum (ER) and Golgi trafficking of MMP-2, thereby enhancing its transport capacity. In conclusion, this is the first report demonstrating the presence of a novel posttranslational modification, SUMOylation, in the MMP family, suggesting that P. gingivalis GroEL may exacerbate AAA formation by increasing MMP-2 production through SUMOylation in vascular SMCs. This study also provides a novel perspective on the role of SUMOylation in MMP-2-induced systemic diseases., (© 2024 The Author(s). Molecular Oral Microbiology published by John Wiley & Sons Ltd.)

Introduction: Existing evidence suggests that exposure to phthalates is higher among younger age groups. However, limited knowledge exists on how phthalate exposure, as well as exposure to replacement plasticizers, di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) and di-2-ethylhexyl terephthalate (DEHTP), change from infancy through early childhood., Methods: Urine samples were collected across the first 5 years of life from typically developing infants and young children enrolled between 2017 and 2020 in the longitudinal UNC Baby Connectome Project. From 438 urine samples among 187 participants, we quantified concentrations of monobutyl phthalate (MnBP), mono-3-carboxypropyl phthalate (MCPP), monoisobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), and metabolites of di(2-ethylhexyl) phthalate (DEHP), diisonoyl phthalate (DiNP), DINCH and DEHTP. Specific gravity (SG) adjusted metabolite and molar sum concentrations were compared across age groups. Intraclass correlation coefficients (ICCs) were calculated among 122 participants with multiple urine specimens (373 samples)., Results: Most phthalate metabolites showed high detection frequencies (>80% of samples). Replacement plasticizers DINCH (58-60%) and DEHTP (>97%) were also commonly found. DiNP metabolites were less frequently detected (<10%). For some metabolites, SG-adjusted concentrations were inversely associated with age, with the highest concentrations found in the first year of life. ICCs revealed low to moderate reliability in metabolite measurements (ρ = 0.10-0.48) suggesting a high degree of within-individual variation in exposure among this age group. The first 6 months (compared to remaining age groups) showed an increased ratio of carboxylated metabolites of DEHP and DEHTP, compared to other common metabolites, but no clear age trends for DINCH metabolite ratios were observed., Conclusion: Metabolites of phthalates and replacements plasticizers were widely detected in infancy and early childhood, with the highest concentrations observed in the first year of life for several metabolites. Higher proportions of carboxylated metabolites of DEHP and DEHTP in younger age groups indicate potential differences in metabolism during infancy., 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 © 2024. Published by Elsevier Inc.)

Background: Non/low-caloric artificial sweeteners (NAS) are recognized as chemical additives substituting sugars to avoid caloric intake and subsequent sugar-derived diseases such as diabetes and hyperglycemia. Six NAS have been claimed safe and are authorized by the US Food and Drug Administration (FDA) for public use, with acceptable daily intake information available: aspartame, acesulfame-K, saccharin, sucralose, neotame, and advantame. However, the impacts of NAS on the gut microbiome have raised potential concerns, since sporadic research revealed NAS-induced microbial changes in the gastrointestinal tracts and alterations in the microbiome-host interactive metabolism., Methods: Given the fact that the gut microbiome influences kaleidoscopic physiological functions in host health, this review aimed to decipher the impacts of NAS on the gut microbiome by implementing a comprehensive two-stage literature analysis based on each NAS., Results: This review documented disturbed microbiomes due to NAS exposure to a maximal resolution of species level using taxonomic clustering analysis, and recorded metabolism alterations involved in gut microbiome-host interactions., Conclusions: The results elucidated that specific NAS exhibited discrepant impacts on the gut microbiome, even though overlapping on the genera and species were identified. Some NAS caused glucose tolerance impairment in the host, but the key metabolites and their underlying mechanisms were different. Furthermore, this review embodied the challenges and future directions of current NAS-gut microbiome research to inspire advanced examination of the NAS exposure-gut microbiome-host metabolism axis.

The scientific community actively pursuits novel compounds with biological activities. In this context, our study utilized the predicted data mining approach (PDMA), which can efficiently screen out biotransformable precursor candidates to produce new bioactive compounds. The PDMA was applied to Bacillus megaterium tyrosinase ( Bm TYR) to form new bioactive hydroxyl compounds from isoxsuprine hydrochloride (isoxsuprine). The results show that isoxsuprine could be biotransformed by BmTYR to form a new compound, 3''-hydroxyisoxsuprine. 3''-Hydroxyisoxsuprine exhibited 40- fold and 10-fold higher potent antioxidant and anti-inflammation activities than the precursor, isoxsuprine. The 3''-hydroxyisoxsuprine effectively mitigates the hyperimmune response in RAW 264.7 macrophages by inhibiting the upregulation of pro-inflammatory cytokine (IL-1β and IL-6) and inflammatory enzyme COX-2 gene expression triggered by LPS stimulation. This study illustrates that PDMA is an effective strategy for screening known natural and chemical compounds and for generating new bioactive compounds through biotransformation. Our newly produced compound has potential future applications in pharmacology and biotechnology.

Herpes zoster (HZ) is a painful, vesicular, cutaneous eruption from reactivation of varicella zoster virus (VZV), which can lead to potentially debilitating complications. The lifetime risk of HZ is estimated to be 20%-30% in the general population, with an increased risk in the elderly and immunocompromised populations. The most effective strategy to prevent HZ and its complications is by vaccination. Two types of HZ vaccines, zoster vaccine live and recombinant zoster vaccine, have been approved for use. This guidance offers recommendations and suggestions for HZ vaccination in adults, aiming to reduce the disease burden of HZ and its complications. It is intended as a guide to first-line healthcare providers, but does not supersede clinical judgement when assessing risk and providing recommendations to individuals. The Working Group on Adult Immunization Practice was appointed by the Infectious Diseases Society of Taiwan (IDST) and recommendations were drafted after a full literature review, using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. The recommendations were reviewed and revised by expert review panels during a series of consensus meetings and endorsed by the IDST, Taiwan Association of Family Medicine, the Taiwanese Dermatological Association, the Taiwan Oncology Society, the Taiwan Society of Blood and Marrow Transplantation, the Transplantation Society of Taiwan, the Taiwan AIDS Society, and the Taiwan College of Rheumatology. This guidance describes the epidemiology of HZ and provides recommendations for HZ vaccination in adults with varying levels of risk, differing history of previous VZV infection and past varicella or zoster vaccinations., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with regards to the research, authorship, or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

The ability to fabricate bimetallic clusters with atomic precision offers promising prospects for elucidating the correlations between their structures and properties. Nevertheless, achieving precise control at the atomic level in the production of clusters, including the quantity of dopant, characteristic of ligands, charge state of precursors, and structural transformation, have remained a challenge. Herein, we report the synthesis, purification, and characterization of a new bimetallic hydride cluster, [AuCu 11 (H){S 2 P(O i Pr) 2 } 6 (C≡CPh) 3 ] ( AuCu 11 H ). The hydride position in AuCu 11 H was determined using DFT calculations. AuCu 11 H comprises a ligand-stabilized defective fcc Au@Cu 11 cuboctahedron. AuCu 11 H is metastable and undergoes a spontaneous transformation through ligand exchange into the isostructural [AuCu 11 (Cl){S 2 P(O i Pr) 2 } 6 (C≡CPh) 3 ] ( AuCu 11 Cl ) and into the complete cuboctahedral [AuCu 12 {S 2 P(O i Pr) 2 } 6 (C≡CPh) 4 ] + ( AuCu 12 ) through an increase in nuclearity. These structural transformations were tracked by NMR and mass spectrometry.

Background/aim: Skin and soft tissue infections (SSTIs) can be life-threatening, but the conventional bacterial cultures have low sensitivity and are time-consuming. Metagenomic next-generation sequencing (mNGS) is widely used as a diagnostic tool for detecting pathogens from infection sites. However, the use of mNGS for pathogen detection in SSTIs and related research is still relatively limited., Patients and Methods: From January 2020 to October 2021, 19 SSTI samples from 16 patients were collected in a single center (Taichung Veterans General Hospital, Taichung, Taiwan). The clinical samples were simultaneously subjected to mNGS and conventional bacterial culture methods to detect pathogens. Clinical characteristics were prospectively collected through electronic chart review. The microbiological findings from conventional bacterial culture and mNGS were analyzed and compared., Results: The mNGS method detected a higher proportion of multiple pathogens in SSTIs compared to conventional bacterial culture methods. Pseudomonas spp. was among the most commonly identified Gram-negative bacilli using mNGS. Additionally, the mNGS method identified several rare pathogens in patients with SSTIs, including Granulicatella adiacens, Bacillus thuringiensis, and Bacteroides fragilis. Antimicrobial resistance genes were detected in 10 samples (52.6%) using the mNGS method, including genes for extended-spectrum beta-lactamase, Ambler class C β-lactamases, and carbapenemase., Conclusion: mNGS not only plays an important role in the detection of pathogens in soft tissue infections, but also informs clinical professionals about the presence of additional microbes that may be important for treatment decisions. Further studies comparing conventional pathogen culture with the mNGS method in SSTIs are required., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A testlet-based visual analogue scale (VAS) is a doubly bounded scaling approach (e.g., from 0% to 100% or from 0 to 1) composed of multiple adjectives, nouns, or sentences (statements/items) within testlets for measuring individuals' attitudes, opinions, or career interests. While testlet-based VASs have many advantages over Likert scales, such as reducing response style effects, the development of proper statistical models for analyzing testlet-based VAS data lags behind. This paper proposes a novel beta copula model and a competing logit-normal model based on the item response theory framework, assessed by Bayesian parameter estimation, model comparison, and goodness-of-fit statistics. An empirical career interest dataset based on a testlet-based VAS design was analyzed using the proposed models. Simulation studies were conducted to assess the two models' parameter recovery. The results show that the beta copula model had superior fit in the empirical data analysis, and also exhibited good parameter recovery in the simulation studies, suggesting that it is a promising statistical approach to testlet-based doubly bounded responses., (© 2023. The Psychonomic Society, Inc.)

The assembly of discrete superatomic nanoclusters into larger constructs is a significant stride towards developing a new set of artificial/pseudo-elements. Herein, we describe a novel series of 16-electron supermolecules derived from the combination of discrete 8-electron superatomic synthons containing interstitial hydrides as vertex-sharing building blocks. The symmetric (RhH) 2 Ag 33 [S 2 P(OPr) 2 ] 17 (1) and asymmetric PtHPtAg 32 [S 2 P(OPr) 2 ] 17 (2) are characterized by ESI-MS, SCXRD, NMR, UV-vis absorption spectra, electrochemical and computational methods. Cluster 1 represents the first group 9-doped 16-electron supermolecule, composed of two icosahedral (RhH)@Ag 12 8-electron superatoms sharing a silver vertex. Cluster 2 results from the assembly of two distinct icosahedral units, Pt@Ag 12 , and (PtH)@Ag 12 . In both cases, the presence of the interstitial hydrides is unprecedented. The stability of the supermolecules is investigated, and 2 spontaneously transforms into Pt 2 Ag 33 [S 2 P(OPr) 2 ] 17 (3) with thermal treatment. The lability of the hydride within the icosahedral framework in solution at low-temperature was confirmed by the VT-NMR., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

To understand the karst groundwater hydrochemical characteristics and ion sources of the Jinan Baotu Spring area, this study focused on the three functional zones as an indirect recharge area, direct recharge area, and discharge area. Through water sample collection and testing, the spatial variability of groundwater chemical characteristics in different functional zones and the formation mechanism were analyzed using hydrochemistry parameter statistics, multivariate statistics, self-organizing map, hydrochemistry graphical analysis, ion ratios, and other methods, guided by the theory of groundwater flow system and combined with regional physical geography and hydrogeological conditions. The results showed that： the groundwater of each functional zone was alkaline as is typical in the dissolution of carbonate minerals. Owing to the different groundwater runoff pathways, the variability of water chemistry parameters in different functional areas was obvious. The groundwater of the discharge area was recharged by both the direct recharge area and the indirect recharge area. The hydrochemistry type changed from HCO 3 -Ca type to HCO 3 ·SO 4 -Ca type through the indirect recharge area to the discharge area. The presence of a small amount of gypsum dissolution within the aquifer generated Ca 2+ and SO 4 2- . The ions in groundwater mainly came from the dissolution and filtration of aquifer rock minerals, and at the same time, they were affected by cation exchange, mineral dissolution equilibrium, and the combined effects of human activities. The groundwater in the Baotu Spring area was greatly influenced by human activities, which to some extent affected the evolution of groundwater hydrochemistry in the spring area.

Neuronal loss is a hallmark of stroke and other neurodegenerative diseases, and as such, neuronal loss caused by microglia has been thought to be a contributing factor to disease progression. Here, we show that microglia indeed contribute significantly to neuronal loss in a mouse model of stroke, but this microglial-dependent process of neuronal clearance specifically targets stressed and degenerating neurons in the ischemic cortical region and not healthy non-ischemic neurons. Nonspecific stimulation of microglia decreased the density of neurons in the ischemic cortical region, whereas specific inhibition of MFG-E8 signaling, which is required for microglial phagocytosis of neurons, had the opposite effect. In both scenarios, the effects were microglia specific, as the same treatments had no effect in mice whose microglia were depleted prior to stroke. Finally, even though the inhibition of MFG-E8 signaling increased neuronal density in the ischemic brain region, it substantially exacerbated the development of cortical infarction. In conclusion, microglia through MFG-E8 signaling contribute to the loss of ischemic neurons and, in doing so, minimize the development of cortical infarction after stroke., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang 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.)