Search Results (59)

Integrated optical waveguide amplifiers, with their compact footprint, low power consumption, and scalability, are the basis for optical communications. The realization of high gain in such integrated devices is made more challenging by the tight optical constraints. In this work, we present efficient amplification in an erbium–ytterbium-based hybrid slot waveguide consisting of a silicon nitride waveguide and a thin-film active layer/electron-beam resist. The electron-beam resist as the upper cladding layer not only possesses the role of protecting the waveguide but also has tighter optical confinement in the vertical cross-section direction. On this basis, an accurate and comprehensive dynamic model of an erbium–ytterbium co-doped amplifier is realized by introducing quenched ions. A modal gain of above 20 dB is achieved at the signal wavelength of 1530 nm in a 1.4 cm long hybrid slot waveguide, with fractions of quenched ions f_q = 30%. In addition, the proposed hybrid waveguide amplifiers exhibit higher modal gain than conventional air-clad amplifiers under the same conditions. Endowing silicon nitride photonic integrated circuits with efficient amplification enriches the integration of various active functionalities on silicon. Full article

Background/Objectives: Mycobacterium avium, a member of Mycobacterium avium complex (MAC), is an emerging opportunistic pathogen causing MAC-pulmonary disease (PD). Fluoroquinolones (FQs), along with ethambutol (EMB) and rifampicin, are recommended for macrolide-resistant MAC-PD; however, FQ-resistant M. avium have been reported worldwide. WQ-3810 is an FQ with high potency against FQ-resistant pathogens; however, its activity against M. avium has not yet been studied. Methods: In this study, we conducted a DNA supercoiling inhibitory assay to evaluate the inhibitory effect of WQ-3810 on recombinant wild-type (WT) and four mutant DNA gyrases of M. avium and compared the IC₅₀s of WQ-3810 with those of ciprofloxacin (CIP), levofloxacin (LVX), and moxifloxacin (MXF). In addition, we examined WQ-3810’s antimicrobial activity against 11 M. avium clinical isolates, including FQ-resistant isolates, with that of other FQs. Furthermore, we assessed the synergistic action of WQ-3810 with the combination of either EMB or isoniazid (INH). Results: In a DNA supercoiling inhibitory assay, WQ-3810 showed 1.8 to 13.7-fold higher efficacy than LVX and CIP. In the MIC assay, WQ-3810 showed 4 to 8-fold, 2 to 16-fold, and 2 to 4-fold higher antimicrobial activity against FQ-resistant isolates than CIP, LVX, and MXF, respectively. The combination of WQ-3810 and INH exhibited a synergistic relationship. Conclusions: The overall characteristics of WQ-3810 demonstrated greater effectiveness than three other FQs, suggesting that it is a promising option for treating FQ-resistant M. avium infections. Full article

The presence of fluoroquinolone (FQ) residues in food-producing animals has raised concerns regarding antimicrobial resistance. This study evaluated the occurrence of FQ residues in the liver and kidneys of piglets and their association with resistance patterns in Escherichia coli and Enterococcus species from piglets’ intestinal microbiota. FQ residues were found in 44% of livers and 23% of kidneys. Among 340 E. coli isolates from feces, resistance to ciprofloxacin (CIP) (43.2%) and multidrug resistance (MDR) (82.7%) were prominent. The presence of FQ in kidneys significantly increased the odds of CIP-resistant E. coli (OR = 2.94, p = 0.0013) and MDR (OR = 2.70, p = 0.0047). Enterococci (n = 130) were evenly distributed among the species E. faecalis, E. faecium, and Enterococcus spp. and presented resistance to CIP (34.6%). FQ in kidneys were associated with higher odds of CIP-resistant enterococci (OR = 3.78, p = 0.015). Interaction models revealed species-dependent responses, with Enterococcus spp. showing high resistance in the presence of FQ in kidneys (OR = 18, p = 0.006), while E. faecium exhibited lower resistance compared to E. faecalis. These findings emphasize the role of FQ residues in promoting bacterial resistance and underscore the need for the stricter regulation and routine surveillance of antimicrobial use in livestock to curb the spread of bacterial resistance to clinical drugs, and mitigate public health risks—One Health. Full article

Drought is one of the major abiotic stresses that inhibits plant growth and development. Therefore, it is critical to explore drought resistance genes in crops to obtain high-quality breeding materials. In this study, the drought-sensitive tomato line “FQ118” and the resistant line “FQ119” were treated with PEG-6000 and, at 0 h (CK), 6 h, 24 h, 36 h and 48 h, the plants were evaluated for growth and physiological indicators, and leaf tissues were collected for RNA-seq. The growth indicators (growth trend, dry and fresh weights above- and below-ground, etc.) and the antioxidant enzyme system reflect that “FQ119” has stronger drought tolerance. Through RNA-seq analysis, a total of 68,316 transcripts (37,908 genes) were obtained. The largest number of significant differentially expressed genes (DEGs) in the comparison of “FQ118” and “FQ119” was observed at 6 h and 48 h. KEGG analysis demonstrated the significant enrichment of certain pathways associated with drought stress, such as glycerolipid metabolism and galactose metabolism. Co-expression analysis revealed that 7 hub DEGs, including genes encoding a photosystem reaction center subunit protein, chlorophyll a-b binding protein, glyceraldehyde-3-phosphate dehydrogenase A (GAPDH), and others, were coenriched in both comparisons. In addition, three hub genes specific to the comparison during the 6-h processing stage, encoding oxygen-evolving enhancer protein 1, receptor-like serine/threonine-protein kinase and calcium-transporting ATPase, were identified. The above hub genes were related to plant resistance to drought stress, and RT‒qPCR verified that the overall magnitudes of the differences in expression between the two lines gradually increased over time. Virus-induced gene silencing (VIGS) experiments have demonstrated that GAPDH plays a relevant role in the drought resistance pathway. In addition, the differences in expression of 7 DEGs encoding transcription factors, including Dofs, WRKYs, MYBs, and MYCs, also tended to increase with increasing duration of drought treatment, as determined via qPCR. In summary, this study identified several valuable genes related to plant drought resistance by screening genes with differential transcription under drought stress. This in-depth gene mining may provide valuable references and resources for future breeding for drought resistance in tomato. Full article

Spontaneous bacterial peritonitis (SBP) is the most common bacterial infection in cirrhotic patients. Historically, the bacterial spectrum was dominated by Gram-negative bacteria. However, recent studies showed that fluoroquinolone (FQ)-based prophylaxis promotes the intestinal overgrowth of Gram-positive bacteria and contributes to the selection of quinolone-resistant Gram-negative bacteria, increasing multidrug-resistant (MDR) organism infections. FQ resistance rates reach up to nearly one-third in community-acquired cases and 50% in hospital-acquired cases, raising concerns about FQ efficacy. Moreover, rare but serious side effects further limit FQ use. Predictive factors of FQ treatment failure have been identified, guiding management strategies. Rifaximin has emerged as a promising alternative for SBP prophylaxis, with encouraging results. This review aims to explore the shifting role of FQ-based SBP prophylaxis, focusing on the emerging concerns, side effects, and alternative strategies. While norfloxacin remains a first-line prophylactic in cirrhotic patients with low ascitic protein levels, its efficacy appears to be reduced in those with advanced liver failure or additional risk factors for MDR organisms. In these subgroups, alternative prophylactics, such as trimethoprim–sulfamethoxazole or rifaximin, may be preferable. We propose a risk-stratification approach to guide treatment selection, with further studies needed to refine these criteria. Full article

The fluoroquinolone (FQ) class of antibiotics includes the world’s most prescribed antibiotics such as ciprofloxacin, levofloxacin, and ofloxacin that are known for their low bacterial resistance. This is despite their potential to trigger severe side effects, such as myopathy, hearing loss, tendinopathy, and tendon rupture. Thus, healthcare organizations around the world have recommended limiting the prescription of FQs. Tendinopathy is a common name for maladies that cause pain and degeneration in the tendon tissue, which can result in tendon rupture. Whilst there are several identified effects of FQ on tendons, the exact molecular mechanisms behind FQ-mediated tendon rupture are unclear. Previous research studies indicated that FQ-mediated tendinopathy and tendon rupture can be induced by changes in gene expression, metabolism, and function of tendon resident cells, thus leading to alterations in the extracellular matrix. Hence, this review begins with an update on FQs, their mode of action, and their known side effects, as well as summary information on tendon tissue structure and cellular content. Next, how FQs affect the tendon tissue and trigger tendinopathy and tendon rupture is explored in detail. Lastly, possible preventative measures and promising areas for future research are also discussed. Specifically, follow-up studies should focus on understanding the FQ-mediated tendon changes in a more complex manner and integrating in vitro with in vivo models. With respect to in vitro systems, the field should move towards three-dimensional models that reflect the cellular diversity found in the tissue. Full article

Campylobacteriosis is a leading cause of infectious diarrhea and foodborne illness worldwide. Campylobacter infection is primarily transmitted through the consumption of contaminated food, especially uncooked meat, or untreated water; contact with infected animals or contaminated environments; poultry is the primary reservoir and source of human transmission. The clinical spectrum of Campylobacter jejuni/coli infection can be classified into two distinct categories: gastrointestinal and extraintestinal manifestations. Late complications are reactive arthritis, Guillain–Barré syndrome, and Miller Fisher syndrome. In the pediatric population, the 0–4 age group has the highest incidence of campylobacteriosis. Regarding the use of specific antimicrobial therapy, international guidelines agree in recommending it for severe intestinal infections. Host factors, including malnutrition, immunodeficiency, and malignancy, can also influence the decision to treat. The Centers for Disease Control and Prevention (CDC) has identified antibiotic resistance in Campylobacter as a ‘significant public health threat’ due to increasing resistance to FQs or macrolides. Although numerous vaccines have been proposed in recent years to reduce the intestinal colonization of poultry, none have shown sufficient efficacy to provide a definitive solution. Full article

Background: Rotary Ni-Ti files are susceptible to sudden intra-canal separation due to cyclic fatigue stress, particularly in curved canals. To increase resistance to cyclic fatigue, new heat-treated files have been introduced. This study aimed to compare the performance of four heat-treated Ni-Ti files in two simulated curved root canals by evaluating the effect of the alloy, rotation speed, and diameter of the files on their resistance to cyclic fatigue. Methods: The Ni-Ti files included in the study were the ProTaper Gold^® (Dentsply Sirona) F2, ProTaper Ultimate^® (Dentsply Sirona) F2, FQ^® (Komet) 25.06, and Blueshaper^® (Zarc4Endo) Z4 25.06. Two groups of 30 files were selected for each system and were tested in two simulated canals milled in a specific metal template. One group was tested in a 60° curved canal and the other in a 90° curved canal. Results: In the 60° simulated canal, there were no instrument fractures within the 15 min time limit. In the 90° simulated canal, the Blueshaper Z4 demonstrated a lower resistance to cyclic fatigue, while FQ 25.06 showed statistically higher fatigue resistance based on both the Kruskal–Wallis and Games–Howell tests (p < 0.05). Conclusions: No differences were found between files when tested in a 60° curved canal for up to 15 min. However, in a 90° canal, the FQ^® files showed significantly higher resistance to cyclic fatigue, especially compared to the Blueshaper^® Z4. The ProTaper Ultimate and ProTaper Gold produced intermediate results, with the ProTaper Ultimate F2 slightly outperforming the ProTaper Gold F2. Full article

This study identified a salt-tolerant GH11 xylanase, Xyn^st, which was isolated from a soil bacterium Bacillus sp. SC1 and can resist as high as 4 M NaCl. After rational design and high-throughput screening of site-directed mutant libraries, a double mutant W6F/Q7H with a 244% increase in catalytic activity and a 10 °C increment in optimal temperature was obtained. Both Xyn^st and W6F/Q7H xylanases were stimulated by high concentrations of salts. In particular, the activity of W6F/Q7H was more than eight times that of Xyn^st in the presence of 2 M NaCl at 65 °C. Kinetic parameters indicated they have the highest affinity for beechwood xylan (K_m = 0.30 mg mL⁻¹ for Xyn^st and 0.18 mg mL⁻¹ for W6F/Q7H), and W6F/Q7H has very high catalytic efficiency (K_cat/K_m = 15483.33 mL mg⁻¹ s⁻¹). Molecular dynamic simulation suggested that W6F/Q7H has a more compact overall structure, improved rigidity of the active pocket edge, and a flexible upper-end alpha helix. Hydrolysis of different xylans by W6F/Q7H released more xylooligosaccharides and yielded higher proportions of xylobiose and xylotriose than Xyn^st did. The conversion efficiencies of Xyn^st and W6F/Q7H on all tested xylans exceeded 20%, suggesting potential applications in the agricultural and food industries. Full article

The increase in fluoroquinolone (FQ)-resistant Escherichia coli (EC) is a serious global problem. In addition, much of acute uncomplicated cystitis (AUC) cases are caused by EC. FQs have been selected for the treatment of cystitis in outpatients, and there is concern about treatment failure. It is therefore necessary to select appropriate antimicrobials to spare FQs. However, there are few reported effective antimicrobial stewardship programs (ASPs) for outpatients. We aimed to establish the effective ASP for outpatients diagnosed with AUC caused by EC, to spare the use of FQs, and to explore optimal oral antimicrobials for AUC. The study subjects were outpatients treated for AUC caused by extended-spectrum β-lactamase-non-producing EC (non-ESBL-EC). Based on the antibiogram results, we recommended cefaclor (CCL) as the initial treatment for AUC, and educated clinical pharmacists who also worked together to advocate for CCL or cephalexin (CEX) prescriptions. FQ usages decreased, and cephalosporin (Ceph) prescriptions increased in all medical departments. The Ceph group (n = 114; CCL = 60, CEX = 54) in the non-FQ group had fewer treatment failures than the FQ group (n = 86) (12.3% vs. 31.4%). Cephs, including CCL and CEX, were effective treatments for AUC caused by non-ESBL-EC. Antimicrobial selection based on antibiogram results and the practice of an ASP in collaboration with clinical pharmacists were useful for optimizing antimicrobial therapy in outpatients. Full article

Background/Objectives: Mycoplasma genitalium (MG) infections and antibiotic resistance are increasing in prevalence while treatment options are limited. Limited data exist regarding MG resistance in Israel. Our aim was to study the prevalence of MG resistance in a sexually transmitted infection (STI) clinic in Israel. Methods: We performed a single-center retrospective study among patients attending an STI clinic during 2019–2020. MG isolates were tested to detect their resistance to azithromycin and fluoroquinolones (FQs) using commercial kits (Allplex™ MG & AziR Assay, Allplex™ MG & MoxiR Assay). We collected patient data regarding the risk factors for STIs and resistance. A multivariate logistic regression model was used to identify the risk factors for resistance. Results: Of the 142 patients who tested positive for MG, 50 (35.2%) and 22 (15.5%) had resistant mutations to azithromycin and FQ, respectively, and 13 (9.2%) showed resistance to both agents. In a multivariate logistic regression model, men who have sex with men (RR 7.01 95% CI 3.00–16.33) and past STIs (RR 2.33 95% CI 1.01–5.34) were independent risk factors for azithromycin resistance. Conclusions: We found a high prevalence of azithromycin resistance and, to a lesser degree, FQ resistance. These findings may help design the treatment guidelines and support routine resistance testing in high-risk populations. Full article

Struvite (MgNH₄PO₄·6H₂O) is a precipitation product that can be obtained in municipal wastewater treatment plants (WWTPs) and represents a promising fertilizer and technical solution for phosphorus recovery. Struvite can be recovered from the wastewater stream, during sludge digestion or by accelerated acid leaching from sludge followed by solid–liquid separation and struvite precipitation from the liquid phase. Moreover, struvite can be precipitated from industrial effluents or agricultural wastes. The resulting products are of different purity. Antibiotic residues are a relevant class of contaminants as already traces can induce or promote the development of antibiotic resistance in the environment. The aim of the current study was a screening of struvite raw materials precipitated by different processes in German WWTPs for their contamination by selected antibiotics out of the classes of sulfonamides (SAs), fluoroquinolones (FQs) and tetracyclines (TCs). Slightly higher antibiotic residues were detected when struvite was precipitated from the solid phase with a maximum of 133 µg TCs, 484 µg FQs and 8 µg SAs compared to 8 µg TCs, 86 µg FQs and 9 µg SAs per kg dry weight (DW) when struvite was obtained from the liquid phase. FQs were most frequently found in low but quantifiable concentrations in almost all struvite raw materials. Yet, the contamination level of struvite from WWTPs can generally be regarded as low compared to sewage sludge. Products received from effluents from the food industry were found to be almost free of antibiotic residues. Full article

In this study, we measured the growth performance and intramuscular fat (IMF) content of the Longissimus dorsi (LD) of Fuqing goats (FQs) and Nubian goats (NBYs), which exhibit extreme phenotypic differences in terms of their production and meat quality traits. RNA-Seq analysis was performed, and transcriptome data were obtained from the LD tissue of 3-month fetuses (E3), 0-month lambs (0M), 3-month lambs (3M), and 12-month lambs (12M) to reveal the differences in the molecular mechanisms regulating the muscle development and IMF deposition between FQs and NBYs. The results showed that a higher body weight and average daily gain were observed in the NBYs at three developmental stages after birth, whereas a higher IMF content was registered in the FQs at 12M. Additionally, transcriptome profiles during the embryonic period and after birth were completely different for both FQs and NBYs. Moreover, DEGs (KIF23, CCDC69, CCNA2, MKI67, KIF11, RACGAP1, NUSAP1, SKP2, ZBTB18, NES, LOC102180034, CAPN6, TUBA1A, LOC102178700, and PEG10) significantly enriched in the cell cycle (ko04110) at E3 (FQs vs. NBYs), and DEGs (MRPS7, RPS8, RPL6, RPL4, RPS11, RPS10, RPL5, RPS6, RPL8, RPS13, RPS24, RPS15, RPL23) significantly enriched in ribosomes (ko03010) at 0M (FQs vs. NBYs) related to myogenic differentiation and fusion were identified. Meanwhile, the differences in glucose and lipid metabolism began at the E3 timepoint and continued to strengthen as growth proceeded in FQs vs. NBYs. DEGs (CD36, ADIROQR2, ACACA, ACACB, CPT1A, IGF1R, IRS2, LDH-A, PKM, HK2, PFKP, PCK1, GPI, FASN, FADS1, ELOVL6, HADHB, ACOK1, ACAA2, and ACSL4) at 3M (FQs vs. NBYs) and 12M (FQs vs. NBYs) significantly enriched in the AMPK signaling pathway (ko04152), insulin resistance (ko04931), the insulin signaling pathway (ko04910), fatty acid metabolism (ko01212), and glycolysis/gluconeogenesis (ko00010) related to IMF deposition were identified. Further, the results from this study provide the basis for future studies on the mechanisms regulating muscle development and IMF deposition in different breeds of goats, and the candidate genes identified could be used in the selection process. Full article

Fluoroquinolones (FQs) have achieved significant success in both human and veterinary medicine. However, regulatory authorities have recommended limiting their use, firstly because they can have disabling side effects; secondly, because of the need to limit the spread of antibiotic resistance. This review addresses another concerning consequence of the excessive use of FQs: the freshwater environments contamination and the impact on non-target organisms. Here, an overview of the highest concentrations found in Europe, Asia, and the USA is provided, the sensitivity of various taxa is presented through a comparison of the lowest EC_50s from about a hundred acute toxicity tests, and primary mechanisms of FQ toxicity are described. A risk assessment is conducted based on the estimation of the Predicted No Effect Concentration (PNEC). This is calculated traditionally and, in a more contemporary manner, by constructing a normalized Species Sensitivity Distribution curve. The lowest individual HC5 (6.52 µg L⁻¹) was obtained for levofloxacin, followed by ciprofloxacin (7.51 µg L⁻¹), sarafloxacin and clinafloxacin (12.23 µg L⁻¹), and ofloxacin (17.12 µg L⁻¹). By comparing the calculated PNEC with detected concentrations, it is evident that the risk cannot be denied: the potential impact of FQs on freshwater ecosystems is a further reason to minimize their use. Full article

Background: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. Methods: Between January 2012 and December 2022, all Hr-TB patients’ information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients’ clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. Results: A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). Conclusion: The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment. Full article