Antimicrobial peptides (AMPs) are essential components of the innate immune system in animals, playing crucial roles in defending against microbial infections. Hydrogen sulfide (H2S), a vital gasotransmitter, is involved in regulating a wide array of physiological functions. However, the role of H₂S in the anti-infective actions of AMPs remains poorly understood. Here, we demonstrate the crucial role of H2S in mediating the anti-infective functions of AMPs across diverse animal species. LL-37/CRAMP, the human cathelicidin family AMP and its mouse homolog, induce H2S production predominantly through 3-mercaptopyruvate sulfurtransferase (3MST) in Escherichia coli and Clostridium perfringens. The generated H₂S further participates in reactive oxygen species (ROS) accumulation, leading to bacterial death by oxidative damage. Additionally, LL-37 activates the Akt signaling pathway, upregulating cystathionine γ-lyase (CSE) expression to generate H2S in macrophages. This process plays a potential role in facilitating the immunomodulatory activity of LL-37/CRAMP and we confirmed that H2S is involved in their in vivo anti-infective activity of LL-37. Moreover, besides LL-37/CRAMP, we reveal that AMPs from various animal species also induce H2S production in bacteria and macrophages. Overall, our findings highlight a previously unrecognized role of H2S in AMP anti-infective function, which is ubiquitous across AMPs from different animals.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis characterized by eosinophilic inflammation and necrotizing vasculitis. Benralizumab, an anti-IL-5Rα monoclonal antibody that directly targets eosinophils, was approved for EGPA in China in December 2025. We report an early real-world experience of benralizumab combined with corticosteroids in a patient with severe ANCA-negative EGPA. A 73-year-old male with a history of childhood asthma, chronic rhinosinusitis, CKD stage 4 presented with recurrent pulmonary infiltrates, progressive interstitial lung disease, severe eosinophilia (peak 12.90×109/L), diffuse skin lesion and new-onset arrhythmia. After systematic differential diagnosis, EGPA was diagnosed according to the 2022 ACR/EULAR criteria (score 7). BALF and blood testing detected nucleic acids of Pneumocystis jirovecii and CMV. He was treated with methylprednisolone 40 mg/day and subcutaneous benralizumab 30 mg every 4 weeks. Concurrently, empirical preemptive anti-infective therapy (caspofungin for Pneumocystis jirovecii, ganciclovir for CMV) was initiated. At 4-week follow-up, prednisone was tapered to 30 mg/day; dyspnea and rash markedly improved, eosinophils decreased to 0, IgE fell from 1,860 to 519 IU/mL, chest CT showed significant resolution of infiltrates, and pulmonary function improved from severe to mild restrictive impairment. At 3 months, prednisone was further tapered to 25 mg/day in combination with benralizumab, and the patient remained stable without disease relapse or acute infection. This case represents an early real-world application of benralizumab in a high-risk ANCA-negative EGPA patient following its approval in China. The findings suggest that benralizumab, used as an adjunctive steroid-sparing agent, may facilitate rapid corticosteroid tapering in selected vulnerable patients with infection risk. Long-term follow-up and studies are needed to validate these findings.
Necrotizing fasciitis (NF) is a rare but life-threatening soft-tissue infection characterized by rapidly progressive necrosis of the fascia and subcutaneous tissue. Early manifestations are often nonspecific, and delayed diagnosis is associated with substantial mortality. Early recognition and immediate intervention are critical to improving outcomes. A 34-year-old man presented with progressive left lower abdominal pain and persistent perianal discomfort 5 days after radical drainage of a perianal abscess combined with internal hemorrhoid ligation. Despite initial treatment with antibiotics, glycemic control, and fluid resuscitation, his condition continued to deteriorate, and he was subsequently transferred to our hospital for definitive treatment. Emergency debridement demonstrated extensive spread of infection from the ischiorectal fossa through the obturator and abdominal fascial planes to the contralateral gluteal region and mediastinal/para-mediastinal fascial planes. Microbiological cultures confirmed type I polymicrobial infection involving Escherichia coli, Enterococcus raffinosus, and Candida albicans. Postoperatively, the patient developed early hypoxemic respiratory failure requiring invasive mechanical ventilation. The lowest documented PaO₂/FiO₂ ratio was 98.6 mmHg, and oxygenation improved after ventilatory optimization, increased PEEP, fluid restriction, and diuretic therapy. He was successfully extubated on postoperative day 3 and subsequently transitioned to high-flow nasal oxygen. Following combined anti-infective therapy, organ support, and nutritional management, the patient recovered and was discharged. NF can affect any body region, with the perineum, lower limbs, and postoperative wounds being most common. The disease can rapidly progress to systemic infection, sepsis, and multiple organ dysfunction syndrome. Early diagnosis, urgent surgical intervention, and multidisciplinary management are crucial for favorable outcomes.
A woman in her early 20s underwent bilateral photorefractive keratectomy (PRK) for correction of myopia. She developed bilateral central corneal melt 3 weeks post-operatively. There was no response to oral antivirals (for presumed necrotising stromal keratitis) and oral steroids (for presumed immune-mediated melt). She gradually developed pigmented corneal infiltrates and microbiology revealed a fungal infection. Despite intensive antifungal therapy, she developed corneal perforations. After applying tissue adhesive as a temporary measure, she was referred for further management. Bilateral Tenon's patch grafts (TPG) were performed and the infection resolved with antifungal therapy. Three months later, her vision improved to 20/40, which was maintained even at the 1-year follow-up.Bilateral corneal melt following PRK is uncommon. A high index of suspicion is required to identify microbial keratitis as a potential cause, especially since sterile infiltrates are also known post-PRK. TPG serves as an effective option in such a situation.
In this study, the abundance and conjugation capacity of mobile genetic elements (MGEs) carrying resistance genes such as vanA, tet(M) and erm(B) were investigated to enhance our understanding of antimicrobial resistance (AMR) dissemination across the One Health continuum in high-priority, highly prevalent enterococcal pathogens. The abundance of MGEs was estimated using replicon typing and both reference-based and reference-free clustering approaches. Conjugation potential was assessed using agar plate mating between Enterococcus faecium donors and E. faecium, Enterococcus faecalis and Enterococcus hirae recipients, with conjugated MGE verified via long-read sequencing. Key findings include the identification of a vanA gene cluster from E. faecium VRE0008 associated with a Tn1546-like transposon embedded in a RepA_N-type putative plasmid (232,902 bp). This plasmid successfully conjugated with E. faecium, E. faecalis and E. hirae recipients from clinical, environmental and agricultural sources. The transfer predominantly involved the modular movement of a 46-kb region surrounding the vanA gene cluster, with E. hirae of agricultural origin (i.e. 0093A) being the exception, as it retained the entire plasmid. The tet(M) gene from E. faecium Ent0189 was located on a putative Rep_Trans-like plasmid, with features of Tn916 integrative conjugative elements. The entire plasmid from Ent0189 was successfully transferred to intra-species recipients from clinical and environmental sources, but transfer to E. faecalis and E. hirae was less common. Attempts to transfer tet(M) associated with Tn916 from bovine E. hirae to any of the E. hirae, E. faecium and E. faecalis isolates were unsuccessful. Additionally, the erm(B) gene from E. faecium NS0794 was carried by an MGE matching the RepA_N-type plasmid, but lacking the vanA gene cluster. Successful conjugative transfer of this plasmid was observed with E. faecium, E. faecalis and E. hirae of various origins, except one clinical E. faecalis isolate. These findings highlight the broad conjugation capabilities and modular mobility of MGEs carrying ARGs in enterococci, enhancing our understanding of dynamic MGE-mediated ARG dissemination and informing strategies to address the spread of AMR between species and habitats.
Periodontitis is a chronic infectious disease caused by bacteria, which leads to destruction of periodontal tissues, tooth loss, and systemic complications. Conventional treatments often fail to counteract the suppression of periodontal tissue regeneration caused by the persistent inflammatory microenvironment. This review focuses on the application of functionalized nanozymes in the treatment of periodontitis, covering the classification of nanozymes, their mechanisms of action, and recent advances in nanozyme-based therapeutic strategies. Functionalized nanozymes, with their multiple bioactivities including antibacterial, antioxidant, and osteogenic stimulation, represent a promising complement to existing therapeutic approaches. Their sophisticated designs enhance biofilm eradication, modulate immune responses, and facilitate tissue regeneration, thereby overcoming key limitations of existing periodontal treatments.  Functionalized nanozymes, particularly motor-based composite nanozymes, show great promise for periodontitis treatment due to their self-propulsion and multifunctional design (antibacterial, antioxidant, osteogenic). However, long-term biosafety, especially metal-ion accumulation, remains the key bottleneck for clinical translation. With continued optimization and standardized safety evaluation, these nanozyme platforms may open a new precision therapy avenue for drug-resistant refractory periodontitis.
Ischemia-reperfusion injury (IRI) following thrombolytic therapy significantly influences the ischemic stroke outcomes. Here, we develop M@EFE NPs, a biomimetic nanomedicine, to alleviate the reperfusion injury. This nanomedicine is constructed by encapsulating Edaravone into the metal-phenolic nanoparticles self-assembled from epigallocatechin gallate (EGCG) and iron ions (Fe3+), and further coating with macrophage membranes. This design integrates the antioxidant and anti-lipid peroxidation properties of the EGCG-Fe3+ nanoparticles with the inflammatory targeting capacity of macrophage membranes. Following systemic administration, M@EFE NPs are able to penetrate the blood-brain barrier and target the ischemic regions, thereby inhibiting oxidative damage, protecting neurons, and ultimately improving stroke outcomes. In vitro, the nanomedicine can effectively scavenge reactive oxygen species, inhibit lipid peroxidation, and enhance cell survival. In murine middle cerebral artery occlusion models, M@EFE NPs could reduce infarct volume, attenuate neuronal apoptosis and neuroinflammation, and improve motor recovery and long-term survival. This study presents a promising combinatorial nanotherapeutic strategy for ischemic stroke, providing insights into biomimetic nanomedicine for treating cerebral IRI.
People diagnosed with advanced HIV disease (AHD) are at high risk for mortality even after starting antiretroviral therapy (ART). We determined characteristics, clinical outcomes, and risks of mortality among children and adolescents diagnosed with AHD in western Uganda. We conducted a retrospective cohort analysis of routinely collected program data of children and adolescents living with HIV (CALHIV) aged 0-19 years, from outpatient HIV clinic electronic medical records in 48 high-volume health facilities in two regions of western Uganda (Fort Portal and Hoima). Data for clients who initiated ART during January 2016-July 2023 were analysed. AHD was defined as a CD4 cell count <200 cells/μL, or WHO stage 3 or 4, or any child younger than 5 years of age living with HIV who had been on ART for more than 12 months and virally non-suppressed (≥1,000 copies). We used descriptive statistics (i.e., frequencies and percentages) to summarise characteristics and treatment outcomes. Kaplan-Meier curves were used to estimate survival overall and by clients' characteristics; log-rank tests were used to compare survival functions. A gamma-shared frailty model was used to determine factors associated with the rate of mortality. Effect measures were summarized using adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals (95%CI). A total of 5,143 CALHIV, including 3,067 (59.6%) females, with a median (interquartile range [IQR]) age of 10 (9) years were assessed. Overall, AHD was high (18.1%) and varied by age-0-4 years (68.4%), 5-9 years (12.6%), 10-14 years (13.2%), and lowest among adolescents, 15-19 years (7.7%). Just over half of the CALHIV with AHD were active in care (51.5% [480/932]), about a quarter (26.4% [264/932]) had transferred out, 13.8% (129/932) were lost to follow-up, and 8.3% (77/932) had died. Survival was significantly higher in CALHIV who were not malnourished compared to those with malnutrition (p = 0.001). Overall mortality rate per 100 person-years among CALHIV with AHD was 4.1 (95%CI:3.2-5.2) and was significantly higher among those who had been on ART for 3 months or less (27.3; 95%CI: 20.6-36.2) compared to 6 months or more (1.0; 95%CI: 0.6-1.7). Advanced HIV Disease among CALHIV in western Uganda was consistent with what has been published elsewhere. Risk of death differed by nutrition status and was high among those on ART three months or less. Early screening and management of malnutrition, as well as early ART initiation and adherence initiatives, might improve outcomes and reduce AHD-related mortality among CALHIV.
Antivirals for mild-to-moderate coronavirus disease 2019 (COVID-19) were adopted for use based on trials in unvaccinated adults during the pre-Omicron period. In today's broadly immune populations, where the risk of hospitalisation and death has decreased substantially, there is a lack of high-quality contemporary evidence to support routine antiviral use for mild-to-moderate disease. Comparing the Australian and New Zealand experiences in the evolving COVID-19 landscape highlights differences in policy and prescribing practice. Treatment guidelines should be informed by systematic evaluation of emerging data, given uncertainty regarding antiviral effectiveness in a context of widespread immunity and milder disease, which have altered the balance of risks and benefits.
A girl with very early-onset inflammatory bowel disease due to a loss-of-function IL10RA mutation (c.611G>A p.Trp204*) presented in infancy with severe Crohn's disease-like colitis requiring colectomy. Two matched-sibling allogeneic haematopoietic stem cell transplantations using treosulfan-based conditioning engrafted transiently but ultimately failed with autologous recovery and immune cytopenias. A third transplant from the same donor with busulfan/fludarabine/melphalan plus serotherapy and peripheral blood stem cells achieved durable engraftment. Acute skin and gut graft-versus-host disease responded to corticosteroids and etanercept. On long-term follow-up, the patient remained off immunosuppression with stable donor chimerism, normal immunoglobulins, nutritional catch-up (weight), preserved puberty and regular menses though short stature persisted.
Vibrio bacteria, including pathogens like Vibrio vulnificus (V. vulnificus) and Vibrio cholerae (V. cholerae) (typical for tropical regions), are increasingly reported in the Baltic Sea, with rising infections linked to climate change. In our study, we examined the presence of Vibrio species on waste materials floating in the coastal zone. Seventy-five waste items were collected. Samples were rinsed, homogenized, and cultured on CHROMagar Vibrio and thiosulfate-citrate-bile salts-sucrose (TCBS) agar. Vibrio isolates were tested for their tolerance to salinity and susceptibility to antibiotics. Vibrio contamination was most common on medical waste (46.15%), followed by plastic film (16%), and both cigarette butts and other waste (14.28%). No Vibrio was detected on food packaging. Two of the 25 Vibrio isolates (V. cholerae/mimicus) showed resistance to cefotaxime (CTX), piperacillin-tazobactam (TZP), trimethoprim-sulfamethoxazole (SXT), and imipenem (IMP). Salinity strongly influenced growth: all isolates grew best at 2% salinity, with reduced growth at 5% and minimal growth at 10-15%. The detection of V. vulnificus on medical waste such as band-aids raises concerns for individuals with open wounds, who should avoid seawater exposure during summer and replace wound dressings after swimming. Additionally, the presence of antibiotic-resistant V. cholerae/mimicus underscores the need for ongoing monitoring and further research into environmental reservoirs of pathogenic and drug-resistant Vibrio species.
Even after long-term nucleos(t)ide analogue (NA) therapy achieves hepatitis B virus (HBV) DNA suppression in patients with chronic hepatitis B (CHB), serum HBV RNA may remain detectable. HBV RNA reflects intrahepatic viral transcriptional activity. This study identified baseline traits and predictors of persistent HBV RNA positivity during NA therapy after sustained HBV DNA suppression. This retrospective study included 155 CHB patients who underwent liver biopsy before initiating NA therapy, subsequently achieved sustained HBV DNA suppression on continuous NA therapy. Patients were classified into two groups according to HBV RNA status during therapy. Baseline clinical, virological and histological variables were assessed by multivariate logistic regression. Correlations between HBV RNA and serological markers were also assessed. The diagnostic performance of the model was analyzed using area under the receiver operating characteristic (AUC) and boostrap internal validation. Overall, 47.7% achieved undetectable serum HBV RNA. Higher baseline HBV DNA and absence of intrahepatic hepatitis B core antigen (HBcAg) independently predicted persistent HBV RNA positivity (both P < 0.001). The combined assessment of HBcAg with HBV DNA improved predictive accuracy (AUC = 0.780), outperforming either marker alone. The AUC value of bootstrap internal validation was 0.756. Across the cohort, HBV RNA showed moderate correlation with hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B e antibody (HBeAb). Correlations were minimal in HBeAg-negative patients and most evident in HBeAg-positive patients. Incorporating HBcAg histology with baseline HBV DNA may enable more individualized treatment strategies during antiviral therapy. Correlations between HBV RNA and traditional markers are primarily observed in HBeAg-positive patients.
We describe the case of a 38-year-old patient who developed a delayed localized cutaneous hypersensitivity reaction after she underwent lumbar trigger point injections (TPIs). This patient had undergone numerous TPIs in the past without adverse reactions. Notably, she had one prior similar episode; in both episodes, a larger volume of chlorhexidine was used during skin preparation. These findings suggest that the combined effects of a longer dry time and inadvertent subcutaneous chlorhexidine exposure were the likely drivers of these reactions. This case presents a unique manifestation of chlorhexidine hypersensitivity via subcutaneous introduction.
Intestinal tuberculosis (TB) most commonly involves the ileo-caecal region. Isolated involvement of the jejunum without concomitant ileo-caecal or colonic disease is exceptionally rare. We report the case of a woman in her early 60s who presented with a 2-year history of postprandial abdominal pain, intermittent constipation, anorexia and weight loss, followed by acute-onset vomiting suggestive of small bowel obstruction. Contrast-enhanced CT demonstrated a short-segment jejunal stricture with proximal dilatation. Enteroscopy confirmed luminal narrowing. Ileo-colonoscopy showed no ileo-caecal involvement. The patient underwent laparoscopy-assisted segmental jejunal resection. Histopathology revealed necrotising epithelioid granulomatous inflammation consistent with TB. Cartridge-based nucleic acid amplification test (GeneXpert MTB/RIF assay system, Cepheid, Sunnyvale, California, USA) was negative. She was commenced on standard antitubercular therapy with a good clinical response. This case highlights the importance of considering TB in isolated small bowel strictures in endemic regions, even in the absence of ileo-caecal disease or systemic features.
Synthetic anthelmintics widely used in livestock production are largely excreted unchanged in faeces, where they can exert sublethal and lethal effects on non-target organisms such as dung beetles. Phytochemical compounds, including thymol (THY), have been proposed as environmentally compatible alternatives; however, information on their ecotoxicological safety across different dung beetle taxa remains limited. We assessed the sublethal effects of dietary thymol on Thorectes lusitanicus (Coleoptera: Geotrupidae), a flightless tunneller dung beetle considered functionally sensitive to veterinary drug residues. Antennal sensory responses were evaluated using electroantennography, and immune function was assessed by measuring haemolymph total protein content, phenoloxidase and prophenoloxidase activities. Ivermectin was included as a reference compound due to its well-documented ecotoxic effects on dung beetles. Thymol ingestion did not affect antennal olfactory responses or immune parameters across a wide range of concentrations, and no neurotoxic symptoms were observed. Significant inhibitory effects were detected only at concentrations substantially higher than thymol residues measured in cattle dung following dietary supplementation. In contrast, ivermectin significantly impaired olfactory function and induced clear neurotoxic symptoms. Overall, these results indicate that thymol is unlikely to cause ecotoxicologically relevant sublethal effects in tunneller dung beetles under the exposure scenarios evaluated. Our findings suggest that thymol-based phytochemical anthelmintics may represent environmentally compatible alternatives to conventional veterinary drugs.
Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic antibiotic resistance and ability to form biofilms, primarily regulated by the redox-active compound, pyocyanin. The transcriptional activator (Multidrug efflux regulator L) MexL plays a crucial role in the biosynthesis of pyocyanin by upregulating key genes such as phz1, phz2, and phzM. Targeting MexL may serve as a novel anti-virulence strategy by suppressing pyocyanin production and attenuating pathogenicity of P. aeruginosa. This study aimed to identify potential inhibitors of MexL using in silico approaches to disrupt its regulatory function and reduce pyocyanin synthesis. The findings suggest that the selected compounds could serve as effective inhibitors of MexL, offering a promising strategy to suppress pyocyanin biosynthesis and reduce P. aeruginosa virulence. For this purpose, molecular docking was conducted between the binding pocket of the MexL protein and compounds selected based on pharmacokinetic properties from the FooDB, NPASS, and LOTUS databases. Furthermore, molecular dynamics simulations were performed on the selected MexL-ligand complexes to evaluate the stability of the protein-ligand complex within a simulated solvated environment under defined conditions. The virtual screening by molecular docking identified four top-scoring ligands FDB000380, LTS0012415, and NPC253096 and ZINC14780782 with binding energies of -8.6, -7.5, -7.1, and -8.8 kcal/mol respectively, showing strong affinities toward the MexL binding pocket. These ligands demonstrated key molecular interactions with residues critical for regulatory function of MexL protein. Molecular dynamics simulations (300 ns) of the three lead MexL-ligand complexes (FDB000380, LTS0012415, and NPC253096) revealed exceptional structural stability, with low backbone RMSD values (0.240-0.309 nm), minimal residue fluctuations, stable radius of gyration, and consistent solvent-accessible surface area profiles. Persistent protein-ligand hydrogen bond networks (occupancy 72.1-100%) confirmed stable polar interactions throughout the trajectories. MM-GBSA and MM-PBSA binding free energy calculations demonstrated superior affinities over the endogenous ligand pyocyanin (ΔG =  - 15.30 to - 21.75 kcal/mol versus - 12.57 kcal/mol). Principal component analysis further revealed restricted conformational dynamics and compound-specific free energy landscapes, collectively supporting these three compounds as thermodynamically stable lead inhibitors of MexL-mediated pyocyanin biosynthesis in Pseudomonas aeruginosa.
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa strains remain a major threat in clinical settings, yet no contemporary genomic data are available from the Olomouc region, Czech Republic. We performed whole-genome sequencing of 157 MDR isolates obtained from 133 patients hospitalized at two tertiary-care hospitals in Olomouc between April 2020 and April 2024. The aim of this study was to delineate the clonal structure, resistance and virulence repertoires shaping the local epidemiology. Of the 157 isolates, 81 (51.6%) met XDR criteria, most commonly exhibiting susceptibility to colistin (37/81, 45.7%). Four dominant high-risk sequence types (STs) were identified: ST175 (n = 53), ST357 (n = 49), ST233 (n = 25), and ST235 (n = 11). ST357 comprised two phylogenetically and functionally distinct sublineages: a major cluster (43/49) carrying bla IMP-7 and bla OXA-2, and a smaller bla VIM-2-positive cluster (5/49) lacking bla OXA-2, oprD, soxR, and the pvc operon, correlating with an XDR phenotype and reduced biofilm-associated virulence potential. All ST357 isolates carried the cytotoxic exoU gene. Both bla IMP-7 and bla VIM-2 were chromosomally encoded. ST175 isolates lacked acquired carbapenemase genes, except for a single bla VIM-2-positive isolate. This lineage carried the highest number of virulence genes, dominated by adherence- and biofilm-associated determinants together with the characteristic exoS +/exoT +/exoY + type III secretion system profile. All ST233 isolates carried bla VIM-2 and exhibited an XDR phenotype, consistent with globally disseminated VIM-2 lineages. ST235 displayed the greatest diversity of carbapenemase genes, including bla GES-14 (5/11), bla GES-29 (1/11), and bla VIM-1 (1/11). This represented the first identification of a bla VIM-1-positive ST235 isolate in Olomouc University Hospital, and, to our knowledge, the first documented occurrence of a VIM-1-producing ST235 strain in the Czech Republic. All ST235 isolates were exoU-positive. This study provides a recent whole-genome analysis of MDR/XDR P. aeruginosa in the Czech Republic, integrating resistome, virulome and molecular epidemiology. Our findings demonstrate that the local population is shaped by multiple high-risk lineages with distinct resistance-virulence profiles, underscoring their clinical relevance and the necessity of genomic surveillance to guide therapy and prevent hospital transmission.
The widespread use of antibiotics in human and veterinary medicine has led to the presence of their residues in aquatic environments, primarily due to their high-water solubility and poor bioavailability. As a result, fish, being a crucial part of the aquatic ecosystem, are continually exposed to the risk of antibiotic toxicity, which can significantly disrupt their normal physiological functions. Therefore, the aim of the study was to assess the impact of the antibiotic Norfloxacin (NOR) on the edible fish species Heteropneustes fossilis. Fish were treated with four different concentrations (mg/L) of NOR (0.0025, 0.1, 4 and 160) for 7 days, and different hematological and serum biochemical changes were examined. The result of the present study revealed that fish exposed to 160 mg/l had significant changes in their blood and serum biochemical parameters relative to the control. These changes include fluctuations in RBC count, WBC count, Hb content, Ht%, and O₂ carrying capacity of blood, as well as levels of AST, ALP, ALT, and LDH. Additionally, the exposed fish exhibited variations in the levels of cholesterol, triglycerides, glucose, total protein, albumin, globulin, bilirubin, and creatinine in their serum. Nevertheless, the treatment of fish with 0.0025 mg/l resulted in the least impact on the above-mentioned parameters. Structural changes, including membrane and nuclear disintegration along with deformation and vacuolation of cells, were also observed in the RBCs of NOR-exposed fishes. Changes in the structure and percentage of deposited and circulating immune cells in spleenic smears were also observed in NOR-exposed group. As a result, our study provides valuable insights into the potential ecotoxicity of NOR on aquatic organisms.
In response to the situation where it is not allowed to stick CFRP cloth at the bottom of a concrete beam and stick it on both sides of the beam, this article analyzes the factors that affect the ultimate flexural bearing capacity of reinforced concrete beams reinforced with CFRP on the side, and provides a calculation method for the flexural bearing capacity of reinforced concrete beams reinforced with CFRP on the side; At the same time, for the convenience of calculation, this paper explores the comprehensive consideration of the tensile force of carbon fiber cloth pasted on the side and the corresponding correction factor ηf of the force arm, and analyzes it by fitting a quadratic trend function with the ratio of CFRP pasting height to beam height (hf/h). Based on this, the calculation methods for the bending capacity of carbon fiber cloth pasted on the bottom surface according to the "Code" and the bending capacity of carbon fiber cloth pasted on the bottom surface according to the quadratic trend function are proposed. Research has shown that using CFRP to reinforce reinforced concrete beams on the side can effectively improve the flexural bearing capacity. After comparative analysis, the calculation results of three calculation methods are in good agreement with the experimental values; The correction coefficient ηf increases with the increase of the ratio of the bonding height to the beam height (hf/h). When the ratio of the bonding height to the beam height (hf/h) exceeds 0.25, the value of the correction coefficient ηf increases significantly; Especially when the ratio of the pasting height to the beam height (hf/h) exceeds 0.5, it is recommended to calculate the flexural bearing capacity of carbon fiber cloth pasted on the bottom surface according to the proposed quadratic trend function for ηf; At the same time, it is recommended to consider the reduction of the cross-sectional area of carbon fiber cloth as compensation when determining the flexural bearing capacity of reinforced concrete beams with carbon fiber cloth pasted on the side according to the calculation of the beam bottom. In order to reduce errors, the utilization coefficient of ψf is no longer limited. Theoretical analysis shows that there are critical values for the bonding height and thickness of carbon fiber cloth used for reinforcement. When these exceed the critical value, the effect on enhancing load-bearing capacity becomes insignificant or even declines.
Colonic diverticulitis is a common and costly disease, with a lifetime risk of 3%-5%, that drives substantial healthcare use. This guideline provides practical, evidence-based recommendations for the management of diverticulitis in the outpatient gastroenterology setting. Consultations should address diagnosis, typical clinical course, risk factors, the role of antibiotics, and prevention. Computed tomography imaging is essential to confirm the diagnosis of diverticulitis, particularly at the first presentation and in severe cases. After recovery, colonoscopy is recommended for patients with complicated diverticulitis and suggested for those with uncomplicated disease who have alarm symptoms or are not up to date with colorectal cancer screening to rule out an underlying malignancy. Patients treated nonoperatively remain at substantial risk for recurrence, which increases with each episode, whereas complicated diverticulitis most often occurs at the initial presentation. For patients with a history of diverticulitis, lifestyle measures-including a healthy diet (without avoiding nuts, seeds, corn, or popcorn), regular physical activity, achieving or maintaining a healthy weight, avoidance of smoking and heavy alcohol use, and limiting nonsteroidal anti-inflammatory drugs use when possible-may help reduce the recurrence risk. Because randomized trials show little or no benefit, we suggest against routine antibiotics for low-risk patients with acute uncomplicated diverticulitis. Antibiotic use is appropriate for patients with high-risk features, immunocompromise, frailty, or inability to ensure safe outpatient management. Patients with recurrent, uncomplicated diverticulitis that significantly affects quality of life should be referred for surgical consultation to discuss the risks and benefits of elective colon resection.