Dysregulated lipid metabolism is associated with kidney allograft fibrosis.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IF/TA), a histologic feature of kidney allograft destruction, is linked to decreased allograft survival. The role of lipid metabolism is well-acknowledged in the area of chronic kidney diseases; however, its role in kidney allograft fibrosis is still unclarified. In this study, how lipid metabolism contributes to kidney allografts fibrosis was examined. METHODS: A comprehensive bioinformatic comparison between IF/TA and normal kidney allograft in the Gene Expression Omnibus (GEO) database was conducted. Further validations through transcriptome profiling or pathological staining of human recipient biopsy samples and in rat models of kidney transplantation were performed. Additionally, the effects of enhanced lipid metabolism on changes in the fibrotic phenotype induced by TGF-ß1 were examined in HK-2 cell. RESULTS: In-depth analysis of the GEO dataset revealed a notable downregulation of lipid metabolism pathways in human kidney allografts with IF/TA. This decrease was associated with increased level of allograft rejection, inflammatory responses, and epithelial mesenchymal transition (EMT). Pathway enrichment analysis showed the downregulation in mitochondrial LC-fatty acid beta-oxidation, fatty acid beta-oxidation (FAO), and fatty acid biosynthesis. Dysregulated fatty acid metabolism was also observed in biopsy samples from human kidney transplants and in fibrotic rat kidney allografts. Notably, the areas affected by IF/TA had increased immune cell infiltration, during which increased EMT biomarkers and reduced CPT1A expression, a key FAO enzyme, were shown by immunohistochemistry. Moreover, under TGF-ß1 induction, activating CPT1A with the compound C75 effectively inhibited migration and EMT process in HK-2 cells. CONCLUSIONS: This study reveal a critical correlation between dysregulated lipid metabolism and kidney allograft fibrosis. Enhancing lipid metabolism with CPT1A agonists could be a therapeutic approach to mitigate kidney allografts fibrosis.

Ionomer degradation in catalyst layers of anion exchange membrane fuel cells.

Anion exchange membrane fuel cells (AEMFCs) that operate at high pH, offer the advantage of enabling the use of abundant 3d-transition metal-based electrocatalysts. While they have shown remarkable improvement in performance, their long-term durability remains insufficient for practical applications with the alkaline polymer electrolytes (APEs) being the limiting factor. The stability of APEs is generally evaluated in concentrated alkaline solutions, which overlooks/oversimplifies the complex electrochemical environment of the catalyst layer in membrane electrode assembly (MEA) devices. Herein, we report a study of the degradation of the membrane and ionomer independently under realistic H2-air (CO2 free) fuel cell operation, using proton nuclear magnetic resonance (1H-NMR), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and X-ray photoelectron spectroscopy (XPS). While the membrane degradation was minimal after the AEMFC stability test, the ionomer in the catalyst layers degraded approximately 20% to 30% with the cathode being more severely affected than the anode. The ionomer degradation decreased the catalyst utilization and significantly increased the ionic resistance, leading to significant performance degradation in the AEMFC stability test. These findings emphasize the importance of ionomer stability and the need to consider the electrochemical environments of MEAs when evaluating the stability of APEs.

Fibroblasts in heart scar tissue directly regulate cardiac excitability and arrhythmogenesis.

After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.

Design and synthesis of guaianolide-germacranolide heterodimers as novel anticancer agents against hepatocellular carcinoma.

Inspired by our previous finding that disesquiterpenoids showed more potent antihepatoma cytotoxicity than their corresponding parent monomers, natural product-like guaianolide-germacranolide heterodimers were designed and synthesized from guaianolide diene and germacranolides via a biomimetic Diels-Alder reaction to provide three antihepatoma active dimers with novel scaffolds. To explore the structure-activity relationship, 31 derivatives containing ester, carbamate, ether, urea, amide, and triazole functional groups at C-14' were synthesized and evaluated for their cytotoxic activities against HepG2, Huh7, and SK-Hep-1 cell lines. Among them, 25 compounds were more potent than sorafenib against HepG2 cells, 15 compounds were stronger than sorafenib against Huh7 cells, and 17 compounds were stronger than sorafenib against SK-Hep-1 cells. Compound 23 showed the most potent cytotoxicity against three hepatoma cell lines with IC50 values of 4.4 µM (HepG2), 3.7 µM (Huh7), and 3.1 µM (SK-Hep-1), which were 2.7-, 2.2-, and 2.8-fold more potent than sorafenib, respectively. The underlying mechanism study demonstrated that compound 23 could induce cell apoptosis, prevent cell migration and invasion, cause G2/M phase arrest in SK-Hep-1 cells. Network pharmacology analyses predicted PDGFRA was one of the potential targets of compound 23, and surface plasmon resonance (SPR) assay verified that 23 had strong affinity with PDGFRA with a dissociatin constant (KD) value of 90.2 nM. These promising findings revealed that structurally novel guaianolide-germacranolide heterodimers might provide a new inspiration for the discovery of antihepatoma agents.

Direct Insertion Polymerization of Ionic Monomers: Rapid Production of Anion Exchange Membranes.

The limited number of methods to directly polymerize ionic monomers currently hinders rapid diversification and production of ionic polymeric materials, namely anion exchange membranes (AEMs) which are essential components in emerging alkaline fuel cell and electrolyzer technologies. Herein, we report a direct coordination-insertion polymerization of cationic monomers, providing the first direct synthesis of aliphatic polymers with high ion incorporations and allowing facile access to a broad range of materials. We demonstrate the utility of this method by rapidly generating a library of solution processable ionic polymers for use as AEMs. We investigate these materials to study the influence of cation identity on hydroxide conductivity and stability. We found that AEMs with piperidinium cations exhibited the highest performance, with high alkaline stability, hydroxide conductivity of 87 mS cm-1 at 80 °C, and a peak power density of 730 mW cm-2 when integrated into a fuel cell device.

Drift of sparse and dense spiral waves under joint external forces.

Many methods have been employed to investigate the drift behaviors of spiral waves in an effort to understand and control their dynamics. Drift behaviors of sparse and dense spirals induced by external forces have been investigated, yet they remain incompletely understood. Here we employ joint external forces to study and control the drift dynamics. First, sparse and dense spiral waves are synchronized by the suitable external current. Then, under another weak current or heterogeneity, the synchronized spirals undergo a directional drift, and the dependence of their drift velocity on the strength and frequency of the joint external force is studied.

Pseudo-Pt Monolayer for Robust Hydrogen Oxidation.

Heteroepitaxial core-shell structure is conducive to combining the advantages of the epilayer and the substrate, creating a novel multifunctionality for catalysis application. Herein, we report a pseudomorphic-Pt atomic layer (PmPt) epitaxially growing on an IrPd-core matrix (PmPt@IrPd/C) as an efficient and stable catalyst for alkaline hydrogen oxidation reaction that exhibits ∼29.2 times more mass activity enhancement than that of benchmark Pt/C. The PmPt@IrPd/C catalyst also gives rise to ∼25.0 times more enhancement than Pt/C during a 50,000-cycle accelerated stability test. This robust stability originates from the resistance to carbon corrosion owing to the stronger H2O interaction instead of carbon oxide (COx) poison species, and the modulated hydroxyl (OH*) adsorption could inhibit the OH* species from shuffling the surface Pt atoms away from the substrate. Moreover, the anion-exchange membrane fuel cells assembled by PmPt@IrPd/C with an ultralow Pt loading of 0.009 mgPt cm-2 in the anode can deliver a power density of 1.27 W cm-2.

Dynamic distribution and potential transmission of antibiotic resistance genes in activated sludge.

Public concerns are increasing regarding the prevalence and transmission of antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs), especially ARG persistence and dissemination in activated sludge (AS). However, the temporal dynamics of ARGs in the AS of WWTPs over a long period of time and their transfer potential after the treatment process upgrade (e.g., total nitrogen reduction from 20 to 15 mg/L in effluent) remain poorly explored. Here, metagenomic sequencing was performed to quantify the ARGs in AS samples from two WWTPs with different treatment processes over a 2-year period. A total of 368 and 426 ARG subtypes affiliated with 20 ARG types were identified separately in the two WWTPs and the similar core ARGs were shared by all 54 samples. There were significant differences in ARG composition in different treatment processes, yet the abundance and diversity of ARGs in the AS samples demonstrated no distinct seasonal patterns. Notably, after the treatment process upgrade, the relative abundance of sulfonamide, beta-lactam, and aminoglycoside resistance genes was reduced by more than 10%, and the transfer potential of ARGs in bacterial pathogens decreased greatly, which suggested that an upgrade could limit the prevalence and transmission of ARGs. Variation partitioning analysis showed that metal resistance genes rather than bacterial community represented the significantly influential factor in shaping ARGs, and some key genera correlated with ARGs were identified through network analysis. These results will deepen our understanding of the dynamic changes in ARG profiles in AS systems and guide wastewater treatment plant upgrades. KEY POINTS: • The potential transfer of ARGs decreased after the treatment process upgrade • Metal resistance genes were the most influential factor in shaping ARG composition • Co-occurrence networks displayed potential hosts of beta-lactam resistance genes.

Plastisphere showing unique microbiome and resistome different from activated sludge.

Plastisphere (the biofilm on microplastics) in wastewater treatment plants (WWTPs) may enrich pathogens and antibiotic resistance genes (ARGs) which can cause risks to the ecological environment by discharging into receiving waters. However, the microbiome and resistome of plastisphere in activated sludge (AS) systems remain inconclusive. Here, metagenome was applied to investigate the microbial composition, functions and ARGs of the Polyvinyl chloride (PVC) plastisphere in lab-scale reactors, and revealed the effects of tetracycline (TC) and/or Cu(II) pressures on them. The results indicated that the plastisphere provided a new niche for microbiota showing unique functions distinct from the AS. Particularly, various potentially pathogenic bacteria tended to enrich in PVC plastisphere. Moreover, various ARGs were detected in plastisphere and AS, but the plastisphere had more potential ARGs hosts and a stronger correlation with ARGs. The ARGs abundances increased after exposure to TC and/or Cu(II) pressures, especially tetracycline resistance genes (TRGs), and the results further showed that TRGs with different resistance mechanisms were separately enriched in plastisphere and AS. Furthermore, the exogenous pressures from Cu(II) or/and TC also enhanced the association of potential pathogens with TRGs in PVC plastisphere. The findings contribute to assessing the potential risks of spreading pathogens and ARGs through microplastics in WWTPs.

Control of spiral waves in optogenetically modified cardiac tissue by periodic optical stimulation.

Resonant drift of nonlinear spiral waves occurs in various types of excitable media under periodic stimulation. Recently a novel methodology of optogenetics has emerged, which allows to affect excitability of cardiac cells and tissues by optical stimuli. In this paper we study if resonant drift of spiral waves in the heart can be induced by a homogeneous weak periodic optical stimulation of cardiac tissue. We use a two-variable and a detailed model of cardiac tissue and add description of depolarizing and hyperpolarizing optogenetic ionic currents. We show that weak periodic optical stimulation at a frequency equal to the natural rotation frequency of the spiral wave induces resonant drift for both depolarizing and hyperpolarizing optogenetic currents. We quantify these effects and study how the speed of the drift and its direction depend on the initial conditions. We also derive analytical formulas based on the response function theory which correctly predict the drift velocity and its trajectory. We conclude that optogenetic methodology can be used for control of spiral waves in cardiac tissue and discuss its possible applications.

Glycated modification of the protein from Rana chensinensis eggs by Millard reaction and its stability analysis in curcumin encapsulated emulsion system.

Forest frog (Rana chensinensis) eggs contain high-quality protein but have not been well utilized. In this study, the total protein of forest frog eggs was extracted and 4491 protein/peptides were identified by HPLC-MS/MS. The egg protein was glycated using monosaccharides (lactose, fructose, xylose and glucose). The xylose modified egg protein showed excellent emulsifying ability, high viscosity and uniform structure under the laser confocal microscope in a concentration dependent way (1-3%, w/v). We next used xylose glycated egg protein to encapsulate curcumin to determine the stability of its emulsion system. This emulsion system showed low particle size (< 400 nm) and high Zeta-potential (> 30 mV with absolute value) at pH > 6. The system was stable under 4 °C, 25℃ and 37 °C after seven weeks' storage, especially for the emulsions at 3% and 5% concentrations. Therefore, the glycated frog egg protein can be used to encapsulate hydrophobic nutrients.

Electrocatalysis in Alkaline Media and Alkaline Membrane-Based Energy Technologies.

Hydrogen energy-based electrochemical energy conversion technologies offer the promise of enabling a transition of the global energy landscape from fossil fuels to renewable energy. Here, we present a comprehensive review of the fundamentals of electrocatalysis in alkaline media and applications in alkaline-based energy technologies, particularly alkaline fuel cells and water electrolyzers. Anion exchange (alkaline) membrane fuel cells (AEMFCs) enable the use of nonprecious electrocatalysts for the sluggish oxygen reduction reaction (ORR), relative to proton exchange membrane fuel cells (PEMFCs), which require Pt-based electrocatalysts. However, the hydrogen oxidation reaction (HOR) kinetics is significantly slower in alkaline media than in acidic media. Understanding these phenomena requires applying theoretical and experimental methods to unravel molecular-level thermodynamics and kinetics of hydrogen and oxygen electrocatalysis and, particularly, the proton-coupled electron transfer (PCET) process that takes place in a proton-deficient alkaline media. Extensive electrochemical and spectroscopic studies, on single-crystal Pt and metal oxides, have contributed to the development of activity descriptors, as well as the identification of the nature of active sites, and the rate-determining steps of the HOR and ORR. Among these, the structure and reactivity of interfacial water serve as key potential and pH-dependent kinetic factors that are helping elucidate the origins of the HOR and ORR activity differences in acids and bases. Additionally, deliberately modulating and controlling catalyst-support interactions have provided valuable insights for enhancing catalyst accessibility and durability during operation. The design and synthesis of highly conductive and durable alkaline membranes/ionomers have enabled AEMFCs to reach initial performance metrics equal to or higher than those of PEMFCs. We emphasize the importance of using membrane electrode assemblies (MEAs) to integrate the often separately pursued/optimized electrocatalyst/support and membranes/ionomer components. Operando/in situ methods, at multiscales, and ab initio simulations provide a mechanistic understanding of electron, ion, and mass transport at catalyst/ionomer/membrane interfaces and the necessary guidance to achieve fuel cell operation in air over thousands of hours. We hope that this Review will serve as a roadmap for advancing the scientific understanding of the fundamental factors governing electrochemical energy conversion in alkaline media with the ultimate goal of achieving ultralow Pt or precious-metal-free high-performance and durable alkaline fuel cells and related technologies.

Topological charge-density method of identifying phase singularities in cardiac fibrillation.

Spiral waves represent the key motifs of typical self-sustained dynamical patterns in excitable systems such as cardiac tissue. The motion of phase singularities (PSs) that lies at the center of spiral waves captures many qualitative and, in some cases, quantitative features of their complex dynamics. Recent clinical studies suggested that ablating the tissue at PS locations may cure atrial fibrillation. Here, we propose a different method to determine the location of PSs. Starting from the definition of the topological charge of spiral waves, we obtain the expression of the topological charge density in a discrete case. With this expression, we can calculate the topological charge at each grid in the space directly, so as to accurately identify the position of PSs.

A phycocyanin derived eicosapeptide attenuates lung fibrosis development.

Pulmonary fibrosis (PF) is a progressive respiratory disease. Phycocyanin derived eicosapeptide (PP20) is a novel peptide derived from active protein C-phycocyanin in Cyanobacteria. The aim of our study was to explore the anti-fibrotic activity of the PP20 and its underlying mechanism. Characteristic features of pulmonary fibrosis in oleic acid (OA)-induced mice and epithelial-mesenchymal transition (EMT) in TGF-ß1-exposed A549 and HFL-1 cells with or without PP20 and the change of TGF-ß/Smad and MAPK signaling pathways were examined. Smad and MAPK agonists were used to explore the role of TGF-ß/Smad and MAPK signaling in TGF-ß1- induced collagen I expression in A549 cells and α-SMA expression in HFL-1 cells when treated with PP20. Our results showed that PP20 significantly alleviated the inflammatory response and tissue destruction, inhibited EMT, restored the imbalance of TIMP-1/MMP-9 and reduced collagen fiber deposition. Moreover, PP20 inhibited TGF-ß1-induced EMT and collagen I expression in A549 cells. PP20 could also inhibit the proliferation, and decrease TGF-ß1-induced the expression of collagen I and transformation of fibroblasts into myofibroblasts in HFL-1 cells. Additionally, animal experiments and cell experiments combined with pathway agonists have shown that PP20 can negatively regulate TGF-ß/Smad and MAPK pathways and show anti-fibrotic properties. PP20 may be a promising drug candidate for protection against pulmonary fibrosis.

Clinical and Pathologic Feature of Patients With Early Versus Late Active Antibody-Mediated Rejection After Kidney Transplantation: A Single-Center Experience.

OBJECTIVE: Active antibody-mediated rejection (aABMR), particularly late aABMR, remains a major challenge for long-term renal allograft survival. This single-center retrospective study aimed to compare clinical features between early vs late aABMR and to identify risk factors for allograft failure among patients with aABMR. METHOD: Forty-one patients diagnosed with aABMR at our hospital were included and were divided into 2 groups: early aABMR (≤6 months; n = 10) vs late aABMR (>6 months; n = 31) based on the time from transplant to diagnosis. Their clinical and pathologic data were compared. This study was performed in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Of 10 patients with early aABMR, none had allograft failure, whereas 8 of 31 patients with late aABMR had developed allograft failure at the time of follow-up (25.8%). At the time of biopsy, patients with early aABMR had higher positive grade in urine occult blood test than patients with late aABMR (P = .01); however, the late aABMR group displayed more intensive interstitial fibrosis and tubular atrophy (P = .03) and more frequent HLA-DQ-type donor-specific antibodies. Interestingly, donor-specific antibody conversion from positive to negative was not associated with C4d grade but was correlated with time from transplant to biopsy. Multivariate Cox regression analysis indicated that high levels of serum creatinine or proteinuria and concomitant T-cell-mediated rejection were independent risk factors for allograft failure in patients with aABMR. CONCLUSION: These data not only confirm that early aABMR has better clinical outcomes than late aABMR but highlight the importance of early diagnostic biopsy and early therapeutic interventions in ABMR, particularly in patients with high levels of serum creatinine or proteinuria in the early posttransplant phase.

Finding type and location of the source of cardiac arrhythmias from the averaged flow velocity field using the determinant-trace method.

Life threatening cardiac arrhythmias result from abnormal propagation of nonlinear electrical excitation waves in the heart. Finding the locations of the sources of these waves remains a challenging problem. This is mainly due to the low spatial resolution of electrode recordings of these waves. Also, these recordings are subjected to noise. In this paper, we develop a different approach: the AFV-DT method based on an averaged flow velocity (AFV) technique adopted from the analysis of optical flows and the determinant-trace (DT) method used for vector field analysis of dynamical systems. This method can find the location and determine all important types of sources found in excitable media such as focal activity, spiral waves, and waves rotating around obstacles. We test this method on in silico data of various wave excitation patterns obtained using the Luo-Rudy model for cardiac tissue. We show that the method works well for data with low spatial resolutions (up to 8×8) and is stable against noise. Finally, we apply it to two clinical cases and show that it can correctly identify the arrhythmia type and location. We discuss further steps on the development and improvement of this approach.

The Comparability of Pt to Pt-Ru in Catalyzing the Hydrogen Oxidation Reaction for Alkaline Polymer Electrolyte Fuel Cells Operated at 80 °C.

The Pt-catalyzed hydrogen oxidation reaction (HOR) for alkaline polymer electrolyte fuel cells (APEFCs) has been one of the focus subjects in current fuel-cell research. The Pt catalyst is inferior for HOR in alkaline solutions, and alloying with Ru is an effective promotion strategy. APEFCs with Pt-Ru anodes have provided a performance benchmark over 1 W cm-2 at 60 °C. The Pt anode is now found to be in fact as good as the Pt-Ru anode for APEFCs operated at elevated conditions. At 80 °C with appropriate gas back-pressure, the cell with a Pt anode exhibits a peak power density of about 1.9 W cm-2 , which is very close to that with a Pt-Ru anode. Even by decreasing the anode Pt loading to 0.1 mg cm-2 , over 1.5 W cm-2 can still be achieved at 80 °C. This finding alters the previous understanding about the Pt catalyzed HOR in alkaline media and casts a new light on the development of practical and high-power APFEC technology.

Resonance of scroll rings with periodic external fields in excitable media.

By direct numerical simulations of a chemical reaction-diffusion system coupled to a periodic external AC electric field with frequency equal to double frequency of the scroll wave rotation, we find that scroll rings resonate with the electric field and exhibit various dynamical behaviors, for example, their reversals, collapses, or growths, depending both on the initial phase of AC electric fields and on the initial phase of scroll rings. A kinematical model characterizing the drift velocity of the scroll rings along their radial directions as well as that of the scroll rings along their symmetry axes is proposed, which can effectively account for the numerical observations and predict the behaviors of the scroll rings. Besides, the existence of the equilibrium state of a scroll ring under the AC electric fields is predicted by the kinematical model and the predictions agree well with the simulations.

A nickel nanocatalyst within a h-BN shell for enhanced hydrogen oxidation reactions.

The development of low-cost and high-performance electrocatalysts remains a challenge for the hydrogen oxidation reaction (HOR) in alkaline membrane fuel cells. Here, we have reported novel Ni@h-BN core-shell nanocatalysts consisting of nickel nanoparticles encapsulated in few-layer h-BN shells. The Ni@h-BN catalysts exhibit an improved HOR performance compared with the bare Ni nanoparticles. In situ characterization experiments and density functional theory calculations indicate that the interactions of the O, H, and OH species with the Ni surface under the h-BN shell are weakened, which helps to maintain the active metallic Ni phase both in air and in the electrolyte and strengthen the HOR processes occurring at the h-BN/Ni interfaces. These results suggest a new route for designing high-performance non-noble metal electrocatalysts with encapsulating two-dimensional material overlayers for HOR reactions.

Clinical evaluation of oral levofloxacin 500 mg once-daily dosage for treatment of lower respiratory tract infections and urinary tract infections: a prospective multicenter study in China.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.