Discharged sewage is the dominant source of urban river pollution. Macrolide antibiotics have emerged as prominent contaminants, which are frequently detected in sewage and rivers and pose a threat to aquatic microbial community. As a typical primary producer, periphyton is crucial for maintaining the biodiversity and functions of aquatic ecosystem. However, effects of antibiotic exposure time as well as the recovery process of periphyton remain undetermined. In the present study, five exposure scenarios of two typical macrolides, erythromycin (ERY) and roxithromycin (ROX) were investigated at 50 µg/L, dose to evaluate their potential detrimental effects on the structure and function of periphyton and the subsequent recovery process in 14 days. Results revealed that the composition of periphytic community returned to normal over the recovery period, except for a few sensitive species. The antibiotics-caused significant photodamage to photosystem II, leading to continuous inhibition of the photosynthetic capacity of periphyton. Furthermore, no significant difference in carbon metabolism capacity was observed after direct antibiotic exposure, while the amine carbon utilization capacity of periphyton remarkably increased during the recovery process. These results indicated that periphyton community was capable of coping with the periodic exposure of antibiotic pollutants and recovering on its own. However, the ecological functions of periphyton can be permanently disturbed due to macrolide exposure. Overall, this study sheds light on the influence of macrolide exposure on the development, structure and function of the periphytic microbial community in rivers.

The utilization of micronano composite scaffolds has been extensively demonstrated to confer the superior advantages in bone repair compared to single nano- or micron-sized scaffolds. Nevertheless, the enhancement of bioactivities within these composite scaffolds remains challenging. In this study, we propose a novel approach to combine melt electrowriting (MEW) and solution electrospinning (SES) techniques for the fabrication of a composite scaffold incorporating hydroxyapatite (HAP), an osteogenic component, and roxithromycin (ROX), an antibacterial active component. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) confirmed the hierarchical architecture of the nanofiber-microgrid within the scaffold, as well as the successful loading of HAP and ROX. The incorporation of HAP enhanced the water absorption capacity of the composite scaffold, thus promoting cell adhesion and proliferation, as well as osteogenic differentiation. Furthermore, ROX resulted in effective antibacterial capability without any observable cytotoxicity. Finally, the scaffolds were applied to a rat calvarial defect model, and the results demonstrated that the 20% HAP group exhibited superior new bone formation without causing adverse reactions. Therefore, our findings present a promising strategy for designing and fabricating bioactive scaffolds for bone regeneration.

The detection of antibiotics is crucial for safeguarding the environment, ensuring food safety, and promoting human health. However, developing a rapid, convenient, low-cost, and sensitive method for antibiotic detection presents significant challenges. Herein, an aptamer-free biosensor was successfully constructed using upconversion nanoparticles (UCNPs) coated with silk fibroin (SF), based on Förster resonance energy transfer (FRET) and the charge-transfer effect, for detecting roxithromycin (RXM). A synergistic FRET efficiency was achieved by utilizing alizarin red and RXM complexes as energy acceptors, with UCNP as the energy donor, and immobilizing an ultrathin SF protein corona within 10 nm. The biosensor detects RXM in deionized water with high sensitivity primarily through monolayer adsorption, with a detection range of 1.0 nM-141.6 nM and a detection limit as low as 0.68 nM. The performance of this biosensor was compared with the ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method for detecting antibiotics in river water separately and a strong correlation between the two methods was observed. The biosensor exhibited long-term stability in aqueous solutions (up to 60 d) with no attenuation of fluorescence intensity. Furthermore, the biosensor\'s applicability extended to the highly sensitive detection of other antibiotics, such as azithromycin. This study introduces a low-cost, eco-friendly, and highly sensitive method for antibiotic detection, with broad potential for future applications in environmental, healthcare, and food-related fields.

Roxithromycin (ROX), a commonly used macrolide antibiotic, is extensively employed in human medicine and livestock industries. Due to its structural stability and resistance to biological degradation, ROX persists as a resilient environmental contaminant, detectable in aquatic ecosystems and food products. However, our understanding of the potential health risks to humans from continuous ROX exposure remains limited. In this study, we used the zebrafish as a vertebrate model to explore the potential developmental toxicity of early ROX exposure, particularly focusing on its effects on locomotor functionality and CaP motoneuron development. Early exposure to ROX induces marked developmental toxicity in zebrafish embryos, significantly reducing hatching rates (n=100), body lengths (n=100), and increased malformation rates (n=100). The zebrafish embryos treated with a corresponding volume of DMSO (0.1%, v/v) served as vehicle controls (veh). Moreover, ROX exposure adversely affected the locomotive capacity of zebrafish embryos, and observations in transgenic zebrafish Tg(hb9:eGFP) revealed axonal loss in motor neurons, evident through reduced or irregular axonal lengths (n=80). Concurrently, abnormal apoptosis in ROX-exposed zebrafish embryos intensified alongside the upregulation of apoptosis-related genes (bax, bcl2, caspase-3a). Single-cell sequencing further disclosed substantial effects of ROX on genes involved in the differentiation of motor neuron progenitor cells (ngn1, olig2), axon development (cd82a, mbpa, plp1b, sema5a), and neuroimmunity (aplnrb, aplnra) in zebrafish larvae (n=30). Furthermore, the CaP motor neuron defects and behavioral deficits induced by ROX can be rescued by administering ngn1 agonist (n=80). In summary, ROX exposure leads to early-life abnormalities in zebrafish motor neurons and locomotor behavior by hindering the differentiation of motor neuron progenitor cells and inducing abnormal apoptosis.

Background: Prior research has raised concerns regarding the use of macrolides and their association with an increased risk of cardiovascular events. Methods: We conducted a cohort study, where we explored the cardiovascular risks associated with the treatment of COPD patients using macrolide antibiotics-namely azithromycin, clarithromycin, and roxithromycin-with amoxicillin serving as a reference. The study focused on COPD patients in an outpatient setting and included a thorough 3-year follow-up. Patients were categorized into four groups based on their treatment. The primary analysis utilized an adjusted Cox model, supplemented by sensitivity analysis through inverse probability of treatment weighting. Results: No significant differences were found in major adverse cardiovascular events (MACE-stroke, acute myocardial infarction, cardiovascular death) between the macrolide groups, and the amoxicillin/hazard ratios (HR) were azithromycin HR = 1.01, clarithromycin HR = 0.99, and roxithromycin HR = 1.02. Similarly, sensitivity analysis showed no disparities in all-cause mortality and cardiovascular death among the groups. Conclusions: Overall, the study revealed no evidence of increased risk of MACE, all-cause mortality, or cardiovascular death in COPD patients treated with these macrolides compared to amoxicillin over a 3-year period.

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Bioadsorption, bioaccumulation and biodegradation processes in algae, play an important role in the biomagnification of antibiotics, or other organic pollutants, in aquatic food chains. In this study, the bioadsorption, bioaccumulation and biodegradation of norfloxacin [NFX], sulfamethazine [SMZ] and roxithromycin [RTM]) is investigated using a series of culture experiments. Chlorella vulgaris was exposed to these antibiotics with incubation periods of 24, 72, 120 and 168 h. Results show the bioadsorption concentration of antibiotics in extracellular matter increases with increasing alkaline phosphatase activity (AKP/ALP). The bioaccumulation concentrations of NFX, SMZ and RTM within cells significantly increase after early exposure, and subsequently decrease. There is a significant positive antibiotics correlation to superoxide dismutase (SOD), the photosynthetic electron transport rate (ETR) and maximum fluorescence after dark adaptation (Fv/Fm), while showing a negative correlation to malondialdehyde (MDA). The biodegradation percentages (Pb) of NFX, SMZ and RTM range from 39.3 - 97.2, 41.3 - 90.5, and 9.3 - 99.9, respectively, and significantly increase with increasing Fv/Fm, density and chlorophyll-a. The accumulation of antibiotics in extracellular and intracellular substances of C. vulgaris is affected by antibiotic biodegradation processes associated with cell physiological state. The results succinctly explain relationships between algal growth during antibiotics exposure and the bioadsorption and bioaccumulation of these antibiotics in cell walls and cell matter. The findings draw an insightful understanding of the accumulation of antibiotics in algae and provide a scientific basis for the better utilization of algae treatment technology in antibiotic contaminated wastewaters. Under low dose exposures, the biomagnification of antibiotics in algae is affected by bioadsorption, bioaccumulation and biodegradation.

BACKGROUND: The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma.
METHODS: Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides.
RESULTS: Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo.
CONCLUSIONS: Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a segmental, progressive, and fatal vascular disorder, and the current strategy for small AAAs is close observation alone.The purpose of this study is to summarize the available evidence to assess the effects of antibiotics on small abdominal aortic aneurysms (AAA).
METHODS: We searched PubMed, EMBASE, Web of Science, and Scopus from inception to September 29, 2023, and included randomized controlled trials (RCTs) that evaluated the effects of antibiotics on small AAAs in humans. We first performed a meta-analysis to assess the effects of antibiotics on small AAAs. Afterward, network pharmacology analysis was applied to investigate the optimal drug generated from the meta-analysis results. We searched Pharmmapper and GeneCards to obtain the common potential targets of the selected drug and AAA-related targets. The protein-protein interaction network and functional enrichment analysis were performed by the STRING database, Cytoscape 3.7.2 software, and R, respectively. Docking studies were carried out for validation.
RESULTS: We incorporated data from six RCTs involving a total of 997 patients. The results of this meta-analysis revealed that roxithromycin exhibited a modest yet statistically significant protective effect in terms of slowing down the AAA expansion rate. Furthermore, our subsequent bioinformatics analysis pinpointed MMP-2, MMP-9, ALB, MMP-3, and CCL-5 as potential therapeutic targets that could be explored for the treatment of AAA using roxithromycin.
CONCLUSIONS: In conclusion, the study indicates roxithromycin is a promising drug for treating small AAAs and supports its underlying clinical use in small AAAs.

Solid-phase extraction (SPE) coupled with capillary electrophoresis (CE) for the determination of macrolide antibiotics (azithromycin, clarithromycin, roxithromycin, tylosin) and tiamulin in water samples was described in this article. These compounds were extracted with different types of sorbents ( Oasis HLB, C18, C8, SDB, and Strata-X) and different masses of sorbents (60 mg, 200 mg, and 500 mg) using different organic solvents (methanol, ethanol, and acetonitrile) and different pH values of water samples (pH 7.00, 8.00, and 9.00). It was found that the highest extraction efficiency of the studied compounds was obtained with 200 mg/3 mL C18 cartridges with methanol as eluent at pH 9.00 of the water sample. The developed SPE-CE method for macrolide antibiotics and tiamulin was validated for linearity, precision, repeatability, the limit of detection (LOD), the limit of quantification (LOQ), and recovery. Good linearity was obtained in the range of 0.3-30 mg L-1 depending on the drug, with correlation coefficients higher than 0.9958 in all cases except clarithromycin (0.9873). Expanded measurement uncertainties were calculated for each pharmaceutical, accounting for 20.31 % (azithromycin), 38.33 % (tiamulin), 28.95 % (clarithromycin), 26.99 % (roxithromycin), and 21.09 % (tiamulin). Uncertainties associated with precision and calibration curves contributed the most to the combined measurement uncertainty. The method was successfully applied to the analysis of production waste-water from the pharmaceutical industry.