Fu Jen Catholic University

Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis-as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels-but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that G. lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals.

[Ag(Et2-Bimy)2][AgBr2] (1; Et2-Bimy = diethylbenzimidazol-2-ylidene) was obtained readily from the reaction of [Et2-BimyH]Br with Ag2O. Compound 2, [Ag(Et2-Bimy)2]PF6, was prepared by the reaction of [Et2-Bimy]PF6 with Ag2O under basic phase transfer catalysis conditions. Both compounds 1 and 2 are good carbene transfer agents. Thus, Pd(Et2-Bimy)2Cl2, Au(Et2-Bimy)Br, and [Au(Et2-Bimy)2]PF6 were obtained in high yields using 1 and 2 as carbene sources. The byproduct AgBr or AgCl can be reused to generate 1 under basic phase transfer catalysis conditions. The crystal structure of compound 1 revealed that linear [Ag(Et2-Bimy)2]+ and [AgBr2]- groups were associated through a short AgI−AgI contact (2.956 Å). FAB/mass spectrometry and molar conductivity measurements indicate the existence of ligand-unsupported AgI−AgI interactions in the gas phase and acetonitrile solution. 13C NMR studies suggest that the two Bimy ligands in 1 are fluxional in solution.

Since the emergence of coronavirus disease 2019 (COVID-19) (formerly known as the 2019 novel coronavirus [2019-nCoV]) in Wuhan, China in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more than 75,000 cases have been reported in 32 countries/regions, resulting in more than 2000 deaths worldwide. Despite the fact that most COVID-19 cases and mortalities were reported in China, the WHO has declared this outbreak as the sixth public health emergency of international concern. The COVID-19 can present as an asymptomatic carrier state, acute respiratory disease, and pneumonia. Adults represent the population with the highest infection rate; however, neonates, children, and elderly patients can also be infected by SARS-CoV-2. In addition, nosocomial infection of hospitalized patients and healthcare workers, and viral transmission from asymptomatic carriers are possible. The most common finding on chest imaging among patients with pneumonia was ground-glass opacity with bilateral involvement. Severe cases are more likely to be older patients with underlying comorbidities compared to mild cases. Indeed, age and disease severity may be correlated with the outcomes of COVID-19. To date, effective treatment is lacking; however, clinical trials investigating the efficacy of several agents, including remdesivir and chloroquine, are underway in China. Currently, effective infection control intervention is the only way to prevent the spread of SARS-CoV-2.

This study examined whether mesenchymal stem cells (MSCs), which are stem cells originated from embryonic mesoderm, are able to differentiate into functional hepatocyte-like cells in vitro. MSCs were isolated from human bone marrow and umbilical cord blood, and the surface phenotype and the mesodermal multilineage differentiation potentials of these cells were characterized and tested. To effectively induce hepatic differentiation, we designed a novel 2-step protocol with the use of hepatocyte growth factor and oncostatin M. After 4 weeks of induction, cuboidal morphology, which is characteristic of hepatocytes, was observed, and cells also expressed marker genes specific of liver cells in a time-dependent manner. Differentiated cells further demonstrated in vitro functions characteristic of liver cells, including albumin production, glycogen storage, urea secretion, uptake of low-density lipoprotein, and phenobarbital-inducible cytochrome P450 activity. In conclusion, human MSCs from different sources are able to differentiate into functional hepatocyte-like cells and, hence, may serve as a cell source for tissue engineering and cell therapy of hepatic tissues. Furthermore, the broad differentiation potential of MSCs indicates that a revision of the definition may be required.

This review article aims to anatomize sources of the healthy worker effect (HWE) and to summarize advantages and limitations of several approaches frequently proposed to eliminate the HWE. Although the HWE is frequently addressed in the context of selection bias, our review suggests that the selection of occupational cohorts with advantageous health status would preferably be addressed as a source of confounding biases. The authors also conclude that the exclusion of unhealthy workers at employment and the study of active workers are the two main sources of HWE, and that the use of the general population as a comparison group in occupational epidemiology should be avoided if possible. The authors encourage investigators to make distinctions between the underlying factors related to the use of the general population as the comparison group in occupational epidemiology.

Gross spreads received by underwriters on initial public offerings (IPOs) in the United States are much higher than in other countries. Furthermore, in recent years more than 90 percent of deals raising $20–80 million have spreads of exactly seven percent, three times the proportion of a decade earlier. Investment bankers readily admit that the IPO business is very profitable, and that they avoid competing on fees because they ‘don't want to turn it into a commodity business.’ We examine several features of the IPO underwriting business that result in a market structure where spreads are high.

Objective The medicinal fungus Ophiocordyceps sinensis and its anamorph Hirsutella sinensis have a long history of use in traditional Chinese medicine for their immunomodulatory properties. Alterations of the gut microbiota have been described in obesity and type 2 diabetes. We examined the possibility that H. sinensis mycelium (HSM) and isolated fractions containing polysaccharides may prevent diet-induced obesity and type 2 diabetes by modulating the composition of the gut microbiota. Design High-fat diet (HFD)-fed mice were treated with HSM or fractions containing polysaccharides of different molecular weights. The effects of HSM and polysaccharides on the gut microbiota were assessed by horizontal faecal microbiota transplantation (FMT), antibiotic treatment and 16S rDNA-based microbiota analysis. Results Fraction H1 containing high-molecular weight polysaccharides (>300 kDa) considerably reduced body weight gain (∼50% reduction) and metabolic disorders in HFD-fed mice. These effects were associated with increased expression of thermogenesis protein markers in adipose tissues, enhanced gut integrity, reduced intestinal and systemic inflammation and improved insulin sensitivity and lipid metabolism. Gut microbiota analysis revealed that H1 polysaccharides selectively promoted the growth of Parabacteroides goldsteinii , a commensal bacterium whose level was reduced in HFD-fed mice. FMT combined with antibiotic treatment showed that neomycin-sensitive gut bacteria negatively correlated with obesity traits and were required for H1’s anti-obesogenic effects. Notably, oral treatment of HFD-fed mice with live P. goldsteinii reduced obesity and was associated with increased adipose tissue thermogenesis, enhanced intestinal integrity and reduced levels of inflammation and insulin resistance. Conclusions HSM polysaccharides and the gut bacterium P. goldsteinii represent novel prebiotics and probiotics that may be used to treat obesity and type 2 diabetes.

Abstract Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3–6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

RATIONALE: The biological mechanisms linking air pollution to cardiovascular events still remain largely unclear. OBJECTIVES: To investigate whether biological mechanisms linking air pollution to cardiovascular events occurred concurrently in human subjects exposed to urban air pollutants. METHODS: We recruited a panel of 76 young, healthy students from a university in Taipei. Between April and June of 2004 or 2005, three measurements were made in each participant of high-sensitivity C-reactive protein (hs-CRP), 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasminogen activator fibrinogen inhibitor-1 (PAI-1), tissue-type plasminogen activator (tPA) in plasma, and heart rate variability (HRV). Gaseous air pollutants were measured at one air-monitoring station inside their campus, and particulate air pollutants were measured at one particulate matter supersite monitoring station 1 km from their campus. We used linear mixed-effects models to associate biological endpoints with individual air pollutants averaged over 1- to 3-day periods before measurements were performed. MEASUREMENTS AND MAIN RESULTS: We found that increases in hs-CRP, 8-OHdG, fibrinogen, and PAI-1, and decreases in HRV indices were associated with increases in levels of particles with aerodynamic diameters less than 10 microm and 2.5 microm, sulfate, nitrate, and ozone (O(3)) in single-pollutant models. The increase in 8-OHdG, fibrinogen, and PAI-1, and the reduction in HRV remained significantly associated with 3-day averaged sulfate and O(3) levels in two-pollutant models. There were moderate correlations (r = -0.3) between blood markers of hs-CRP, fibrinogen, PAI-1, and HRV indices. CONCLUSIONS: Urban air pollution is associated with inflammation, oxidative stress, blood coagulation and autonomic dysfunction simultaneously in healthy young humans, with sulfate and O(3) as two major traffic-related pollutants contributing to such effects.

Environmental pollution brought on by xenobiotics and other related recalcitrant compounds have recently been identified as a major risk to both human health and the natural environment. Due to their toxicity and non-biodegradability, a wide range of pollutants, such as heavy metals, polychlorinated biphenyls, plastics, and various agrochemicals are present in the environment. Bioremediation is an effective cleaning technique for removing toxic waste from polluted environments that is gaining popularity. Various microorganisms, including aerobes and anaerobes, are used in bioremediation to treat contaminated sites. Microorganisms play a major role in bioremediation, given that it is a process in which hazardous wastes and pollutants are eliminated, degraded, detoxified, and immobilized. Pollutants are degraded and converted to less toxic forms, which is a primary goal of bioremediation. Ex situ or in situ bioremediation can be used, depending on a variety of factors, such as cost, pollutant types, and concentration. As a result, a suitable bioremediation method has been chosen. This review focuses on the most recent developments in bioremediation techniques, how microorganisms break down different pollutants, and what the future holds for bioremediation in order to reduce the amount of pollution in the world.

PURPOSE: Oral squamous cell carcinoma (OSCC), like many solid tumors, contains a heterogeneous population of cancer cells. Recent data suggest that a rare subpopulation of cancer cells, termed cancer stem cells (CSC), is capable of initiating, maintaining, and expanding the growth of tumor. Identification and characterization of CSC from OSCC facilitates the monitoring, therapy, or prevention of OSCC. EXPERIMENTAL DESIGN: We enriched oral cancer stem-like cells (OC-SLC) through sphere formation by cultivating OSCC cells from established OSCC cell lines or primary cultures of OSCC patients within defined serum-free medium. Differential expression profile of stemness genes between enriched OC-SLC and parental OSCC was elucidated. Furthermore, immunohistochemical staining of stemness markers on OSCC patient tissues was examined to evaluate the association between stemness genes and prognosis of OSCC. RESULTS: Enriched OC-SLC highly expressed the stem/progenitor cell markers and ABC transporter gene (Oct-4, Nanog, CD117, Nestin, CD133, and ABCG2) and also displayed induced differentiation abilities and enhanced migration/invasion/malignancy capabilities in vitro and in vivo. Elevated expression of CD133 was shown in the enriched OC-SLC from OSCC patients' tumors. Positive correlations of Oct-4, Nanog, or CD133 expression on tumor stage were shown on 52 OSCC patient tissues. Kaplan-Meier analyses exhibited that Nanog/Oct-4/CD133 triple-positive patients predicted the worst survival prognosis of OSCC patients. CONCLUSION: We enriched a subpopulation of cancer stem-like cell from OSCC by sphere formation. The enriched OC-SLC possesses the characteristics of both stem cells and malignant tumors. Additionally, expression of stemness markers (Nanog/Oct-4/CD133) contradicts the survival prognosis of OSCC patients.

OBJECTIVE: To evaluate our experience with the diagnosis and treatment of Cesarean scar pregnancy. METHODS: During a 6-year period, 12 cases of Cesarean scar pregnancy were diagnosed using transvaginal color Doppler sonography and treated conservatively to preserve fertility. Incidence, gestational age, sonographic findings, beta-human chorionic gonadotropin ( beta-hCG) levels, flow profiles of transvaginal color Doppler ultrasound, and methods of treatment were recorded. RESULTS: The incidence of Cesarean scar pregnancy was 1:2216 and its rate was 6.1% in women with an ectopic pregnancy and at least one previous Cesarean section. Gestational age at diagnosis ranged from 5 + 0 to 12 + 4 weeks. The time interval from the last Cesarean section to the diagnosis of Cesarean scar pregnancy ranged from 6 months to 12 years. High-velocity and low-impedance subtrophoblastic flow (resistance index, 0.38) persisted until beta-hCG declined to normal. Patients were treated as follows: transvaginal ultrasound-guided injection of methotrexate into the embryo or gestational sac (n = 3), transabdominal ultrasound-guided injection of methotrexate (n = 2), transabdominal ultrasound-guided injection of methotrexate followed by systemic methotrexate administration (n = 2), systemic methotrexate administration alone (n = 2), dilatation and curettage (n = 2), or local resection of the gestation mass (n = 1). Eleven of the 12 patients preserved their reproductive capacity; the remaining patient, treated by dilatation and curettage, underwent a hysterectomy because of profuse vaginal bleeding. The Cesarean scar mass regressed from 2 months to as long as 1 year after treatment. Uterine rupture occurred in one patient during the following pregnancy at 38 + 3 weeks' gestational age. CONCLUSION: Ultrasound-guided methotrexate injection emerges as the treatment of choice to terminate Cesarean scar pregnancy. Surgical or invasive techniques, including dilatation and curettage are not recommended for Cesarean scar pregnancy due to high morbidity and poor prognosis.

We report the observation of two narrow structures in the mass spectra of the ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}\ensuremath{\Upsilon}(nS)$ ($n=1$, 2, 3) and ${\ensuremath{\pi}}^{\ifmmode\pm\else\textpm\fi{}}{h}_{b}(mP)$ ($m=1$, 2) pairs that are produced in association with a single charged pion in $\ensuremath{\Upsilon}(5S)$ decays. The measured masses and widths of the two structures averaged over the five final states are ${M}_{1}=(10\text{ }607.2\ifmmode\pm\else\textpm\fi{}2.0)\text{ }\text{ }\mathrm{MeV}/{c}^{2}$, ${\ensuremath{\Gamma}}_{1}=(18.4\ifmmode\pm\else\textpm\fi{}2.4)\text{ }\text{ }\mathrm{MeV}$, and ${M}_{2}=(10\text{ }652.2\ifmmode\pm\else\textpm\fi{}1.5)\text{ }\text{ }\mathrm{MeV}/{c}^{2}$, ${\ensuremath{\Gamma}}_{2}=(11.5\ifmmode\pm\else\textpm\fi{}2.2)\text{ }\text{ }\mathrm{MeV}$. The results are obtained with a $121.4\text{ }\text{ }{\mathrm{fb}}^{\ensuremath{-}1}$ data sample collected with the Belle detector in the vicinity of the $\ensuremath{\Upsilon}(5S)$ resonance at the KEKB asymmetric-energy ${e}^{+}{e}^{\ensuremath{-}}$ collider.

In the original version of this manuscript, an error was introduced on pp352. '2.7nb:1.6nb' has been corrected to '2.4nb:1.3nb' in the current online and printed version. doi:10.1093/ptep/ptz106.

An intelligent battery equalization scheme based on fuzzy logic control is presented to adaptively control the equalizing process of series-connected lithium-ion batteries. The proposed battery equalization scheme is a bidirectional dc-dc converter with energy transferring capacitor that can be used to design the bidirectional nondissipative equalizer for a battery balancing system. Furthermore, it can be designed as a ripple-free converter for improving the input current distortion of the battery charge supply power system. A fuzzy-logic-controlled strategy is constructed with a set of membership functions to prescribe the cells equalizing behavior within a safe equalizing region for rapid cell voltage balancing. The simulation and experimental results show the advantage of the predicted equalizing performance of the lithium-ion battery stacks. The proposed fuzzy logic control battery equalization controller can abridge the equalization time about 32%. The proposed method maintains safe operation during the charge/discharge state in each lithium-ion cell of the battery strings.

Co-infection has been reported in patients with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, but there is limited knowledge on co-infection among patients with coronavirus disease 2019 (COVID-19). The prevalence of co-infection was variable among COVID-19 patients in different studies, however, it could be up to 50% among non-survivors. Co-pathogens included bacteria, such as Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, Chlamydia pneumonia, Legionella pneumophila and Acinetobacter baumannii; Candida species and Aspergillus flavus; and viruses such as influenza, coronavirus, rhinovirus/enterovirus, parainfluenza, metapneumovirus, influenza B virus, and human immunodeficiency virus. Influenza A was one of the most common co-infective viruses, which may have caused initial false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory and imaging findings alone cannot help distinguish co-infection from SARS-CoV-2 infection. Newly developed syndromic multiplex panels that incorporate SARS-CoV-2 may facilitate the early detection of co-infection among COVID-19 patients. By contrast, clinicians cannot rule out SARS-CoV-2 infection by ruling in other respiratory pathogens through old syndromic multiplex panels at this stage of the COVID-19 pandemic. Therefore, clinicians must have a high index of suspicion for coinfection among COVID-19 patients. Clinicians can neither rule out other co-infections caused by respiratory pathogens by diagnosing SARS-CoV-2 infection nor rule out COVID-19 by detection of non-SARS-CoV-2 respiratory pathogens. After recognizing the possible pathogens causing co-infection among COVID-19 patients, appropriate antimicrobial agents can be recommended.

A comparative study of work-family stressors, work hours and well-being was described contrasting 3 culturally distinct regions: Anglo (Australia, Canada, England, New Zealand, and U.S.), China (Hong Kong, People’s Republic of China, and Taiwan) and Latin America(Argentina, Brazil, Colombia, Ecuador, Mexico, Peru, and Uruguay). Samples of managers were surveyed in each country, and country data were combined for the 3 regions. Support was found for the hypothesis that Anglos would demonstrate a stronger positive relation between work hours and work-family stressors than Chinese and Latins. In all 3 samples, work-family stressors related to increased job satisfaction and reduced well-being. Latins were found to work the most hours, have the most children, and report the highest job satisfaction. China was the only region in which being married and having more children related positively to all measures of well-being.

PURPOSE: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. METHODS: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. RESULTS: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. CONCLUSION: A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.

This paper presents the first successful application of vinyl polymer/graphene-based nanocomposites in corrosion protection. Well-dispersed polystyrene (PS)/modified-GO nanocomposites were successfully prepared using in situ miniemulsion polymerisation. The as-prepared nanocomposites exhibit superior anti-corrosion properties compared with pure PS, in which the corrosion protection efficiency increased from 37.90% to 99.53% with the incorporation of 2 wt% modified GO in the PS polymer matrix. The thermal stability and mechanical properties also greatly improved compared with pure PS. The incorporation of 2 wt% modified GO in the PS polymer matrix increased the thermal decomposition temperature (Td) from approximately 298 to 372 °C, and the storage modulus increased from 1808.76 to 2802.36 MPa. This paper attributes the substantially improved properties to the nearly complete exfoliation of the modified-GO dispersion, which greatly enhanced the modified-GO/PS interfacial bond strength and gas barrier properties.