Mild hyperthermia enhanced synergistic uric acid degradation and multiple ROS elimination for an effective acute gout therapy.

BACKGROUND: Acute gouty is caused by the excessive accumulation of Monosodium Urate (MSU) crystals within various parts of the body, which leads to a deterioration of the local microenvironment. This degradation is marked by elevated levels of uric acid (UA), increased reactive oxygen species (ROS) production, hypoxic conditions, an upsurge in pro-inflammatory mediators, and mitochondrial dysfunction. RESULTS: In this study, we developed a multifunctional nanoparticle of polydopamine-platinum (PDA@Pt) to combat acute gout by leveraging mild hyperthermia to synergistically enhance UA degradation and anti-inflammatory effect. Herein, PDA acts as a foundational template that facilitates the growth of a Pt shell on the surface of its nanospheres, leading to the formation of the PDA@Pt nanomedicine. Within this therapeutic agent, the Pt nanoparticle catalyzes the decomposition of UA and actively breaks down endogenous hydrogen peroxide (H2O2) to produce O2, which helps to alleviate hypoxic conditions. Concurrently, the PDA component possesses exceptional capacity for ROS scavenging. Most significantly, Both PDA and Pt shell exhibit absorption in the Near-Infrared-II (NIR-II) region, which not only endow PDA@Pt with superior photothermal conversion efficiency for effective photothermal therapy (PTT) but also substantially enhances the nanomedicine's capacity for UA degradation, O2 production and ROS scavenging enzymatic activities. This photothermally-enhanced approach effectively facilitates the repair of mitochondrial damage and downregulates the NF-κB signaling pathway to inhibit the expression of pro-inflammatory cytokines. CONCLUSIONS: The multifunctional nanomedicine PDA@Pt exhibits exceptional efficacy in UA reduction and anti-inflammatory effects, presenting a promising potential therapeutic strategy for the management of acute gout.

Effects of low-flux and high-flux hemodialysis on the survival of elderly maintenance hemodialysis patients.

BACKGROUND: Elderly hemodialysis (HD) patients have a high risk of death. The effect of different types of HD membranes on survival is still controversial. The purpose of this study was to determine the relationship between the use of low-flux or high-flux membranes and all-cause and cardiovascular mortality in elderly hemodialysis patients. METHODS: This was a retrospective clinical study involving maintenance hemodialysis patients which were categorized into low-flux and high-flux groups according to the dialyzer they were using. Propensity score matching was used to balance the baseline data of the two groups. Survival rates were compared between the two groups, and the risk factors for death were analyzed by multivariate Cox regression. RESULTS: Kaplan-Meier survival analysis revealed no significant difference in all-cause mortality between the low-flux group and the high-flux group (log-rank test, p = 0.559). Cardiovascular mortality was significantly greater in the low-flux group than in the high-flux group (log-rank test, p = 0.049). After adjustment through three different multivariate models, we detected no significant difference in all-cause mortality. Patients in the high-flux group had a lower risk of cardiovascular death than did those in the low-flux group (HR = 0.79, 95% CI, 0.54-1.16, p = 0.222; HR = 0.58, 95% CI, 0.37-0.91, p = 0.019). CONCLUSIONS: High-flux hemodialysis was associated with a lower relative risk of cardiovascular mortality in elderly MHD patients. High-flux hemodialysis did not improve all-cause mortality rate. Differences in urea distribution volume, blood flow, and systemic differences in solute clearance by dialyzers were not further analyzed, which are the limitations of this study.

The crystal structures of a chloride-pumping microbial rhodopsin and its proton-pumping mutant illuminate proton transfer determinants.

Microbial rhodopsins are versatile and ubiquitous retinal-binding proteins that function as light-driven ion pumps, light-gated ion channels, and photosensors, with potential utility as optogenetic tools for altering membrane potential in target cells. Insights from crystal structures have been central for understanding proton, sodium, and chloride transport mechanisms of microbial rhodopsins. Two of three known groups of anion pumps, the archaeal halorhodopsins (HRs) and bacterial chloride-pumping rhodopsins, have been structurally characterized. Here we report the structure of a representative of a recently discovered third group consisting of cyanobacterial chloride and sulfate ion-pumping rhodopsins, the Mastigocladopsis repens rhodopsin (MastR). Chloride-pumping MastR contains in its ion transport pathway a unique Thr-Ser-Asp (TSD) motif, which is involved in the binding of a chloride ion. The structure reveals that the chloride-binding mode is more similar to HRs than chloride-pumping rhodopsins, but the overall structure most closely resembles bacteriorhodopsin (BR), an archaeal proton pump. The MastR structure shows a trimer arrangement reminiscent of BR-like proton pumps and shows features at the extracellular side more similar to BR than the other chloride pumps. We further solved the structure of the MastR-T74D mutant, which contains a single amino acid replacement in the TSD motif. We provide insights into why this point mutation can convert the MastR chloride pump into a proton pump but cannot in HRs. Our study points at the importance of precise coordination and exact location of the water molecule in the active center of proton pumps, which serves as a bridge for the key proton transfer.

The treatment landscape of advanced angiosarcoma in Asia-A multi-national collaboration from the Asian Sarcoma Consortium.

Angiosarcoma (AS) is a rare disease with a dismal prognosis. The treatment landscape and prognostic factors for advanced AS, including locally advanced, unresectable, and metastatic disease remain elusive. The Asian Sarcoma Consortium is an international collaborative effort to understand the sarcoma treatment landscape in Asia. We undertook a retrospective chart review of AS patients seen in 8 sarcoma academic centers across Asia. Patients with complete clinical, treatment, and follow-up data were enrolled. Overall, 276 advanced AS patients were included into this study; 84 (30%) of the patients had metachronous metastatic AS. The median age was 67 y; primary sites of AS was cutaneous in 55% and visceral in 45% of patients. In total, 143 (52%) patients received at least 1 line of systemic chemotherapy. The most common first-line chemotherapy regimen used was paclitaxel (47.6%) followed by liposomal doxorubicin (19.6%). The median overall survival (OS) was 7.8 mo. Significant prognostic factors for OS included age > 65 (hazard ratio (HR) 1.54, P = .006), male gender (HR 1.39, P = .02), and a cutaneous primary AS site (HR 0.63, P = .004). The median progression-free survival (PFS) for first-line chemotherapy was 3.4 mo. PFS for single vs combination or paclitaxel vs liposomal doxorubicin chemotherapy regimens were comparable. This study provides an insight into the treatment patterns and prognostic factors of advanced AS patients in Asia. Prognosis of advanced AS remains poor. Data from this study serve as a benchmark for future clinical study design.

Efficient Modulation of ß-Amyloid Peptide Fibrillation with Polymer Nanoparticles Revealed by Super-Resolution Optical Microscopy.

ß-Amyloid peptide (Aß) aggregation is the essential hallmark of neurodegenerative disorders such as Alzheimer's disease. Efficient inhibitors are highly desired for the prevention of Aß assembly that has been considered as the primary therapeutic strategy for neurodegenerative diseases. Apart from this, visualization of the aggregates and morphology at high spatial resolution is widely considered of crucial significance on biological treatment. In this work, we have developed small-sized (with diameter of ∼4.7 nm) and positively charged fluorescent conjugated polymer nanoparticles (CPNPs) with strong inhibition effect on Aß1-40 peptides fibrillation. Interestingly, the CPNPs also possess excellent photophysical properties, including high photon counts, robust blinking, and repetitive fluorescence switching, that are especially suitable for localization-based super-resolution imaging. Spatial resolution of ∼20 nm for these blinking CPNPs is readily achieved. According to the optical microscopic results, it was found that binding of CPNPs to the terminal of seed fibrils can effectively inhibit the fibrillation process. Owing to these attractive biological and unique photophysical properties, the small-sized CPNPs show high potential in a variety of super-resolution based biological applications.

Single-Particle Enumeration-Based Sensitive Glutathione S-Transferase Assay with Fluorescent Conjugated Polymer Nanoparticle.

Glutathione S-transferase (GST) is a group of multifunctional enzyme and participates in many physiological processes, such as xenobiotic biotransformation, drug metabolism, and degradation of toxic products. Herein, we demonstrate a label-free fluorescent conjugated polymer nanoparticle (FCPNPs)-based single-particle enumeration (SPE) method for the sensitive GST assay. Fluorescence resonance energy transfer (FRET) is formed between the glutathione-modified FCPNPs (FCPNPs-GSH) and polyethylenimine-capped gold nanoparticles (GNPs@PEI). Therefore, the fluorescence of FCPNPs-GSH is quenched remarkably. In the presence of GST, GNPs@PEI stay away from FCPNPs-GSH due to the specific interaction between FCPNPs-GSH and GST, leading to the inhibition of FRET. As a result, the fluorescence emission of FCPNPs-GSH is restored, which is reflected as the increase of the number of fluorescent particles in the microscopic image. By statistically counting the target concentration-dependent fluorescent particle number, accurate quantification of GST is achieved. The linear range from 0.01 to 6 µg/mL is obtained for GST assay and the limit-of-detection (LOD) is 1.03 ng/mL, which is much lower than the ensemble fluorescence spectra measurements in bulk solution. In urine sample assay, satisfactory recoveries in the range of 97.5-106.5.0% are achieved. Because of the high sensitivity and excellent specificity, this method can be extended to the detection of other disease-related biomolecules in the future.

Surface Coassembly of Polymer Brushes and Polymer-Protein Bioconjugates: An Efficient Approach to the Purification of Bioconjugates under Mild Conditions.

Well-defined polymer-protein bioconjugates are widely used in therapeutics and biocatalysis. One of the challenges in the synthesis of bioconjugates is the efficient separation of the target conjugate molecules from reaction systems. In this research, surface coassembly of polymer brushes and polymer-protein bioconjugates is investigated, and it is demonstrated that the coassembly approach can be applied in the purification of polymer-protein bioconjugates. Bovine serum albumin-poly( N-isopropylacrylamide) (BSA-PNIPAM) bioconjugates were synthesized by the "grafting from" approach, and PNIPAM brushes on silica particles were prepared by the "grafting to" approach. PNIPAM brushes on silica particles are able to coassemble with BSA-PNIPAM at a temperature above the lower critical solution temperature of PNIPAM. Two-layer surface structures with collapsed PNIPAM in the inner layers and BSA in the outer layers are formed on the silica particles. The size of the silica particles and molecular weight of PNIPAM on the bioconjugates exert influences on the coassembly. The coassembly approach can be used in the purification of bioconjugates. After repeated coassembly centrifugation-release cycles, all the BSA-PNIPAM bioconjugates can be removed from the reaction solutions, and the purified bioconjugates are obtained.

An In†Situ Depot for Continuous Evolution of Gaseous H2 Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis.

Inflammation is involved in many human pathologies, including osteoarthritis (OA). Hydrogen (H2 ) is known to have anti-inflammatory effects; however, the bioavailability of directly administered H2 gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H2 at inflamed tissues is proposed. The delivery system comprises poly(lactic-co-glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra-muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes.

Single Particle Tracking of Peptides-Modified Nanocargo on Lipid Membrane Revealing Bulk-Mediated Diffusion.

Understanding the detailed diffusion behavior of the nanocargo on lipid membrane can afford deep insight into the surface chemistry controlled translocation mechanism for the rational design of an efficient delivery system. By tracking the diffusion trajectory of transacting activator of transcription (TAT, a cell penetrating peptide) peptides-modified nanocargo on lipid membrane, bulk-mediated (intermittent hopping) diffusion was observed for the first time after a blended modification of TAT peptides and polyethylene glycol (PEG) molecules onto the nanoparticle surface. In contrast to random walk or confined diffusion, the nanoparticles could be temporarily confined for random waiting times between surface displacements produced by excursions through the bulk fluid, which was not noted before. Non-Gaussian distributed step length (with a stretched power law like tail) was observed, making large displacements much more probable than one would predict for regular Gaussian decay. This kind of larger displacement would therefore significantly facilitate a kinetically controlled surface searching process like heterogeneous penetration site recognition on a fluidic membrane with suitable spatial orientation.

Signal transduction and regulation of IbpreproHypSys in sweet potato.

Hydroxyproline-rich glycopeptides (HypSys) are small signalling peptides containing 18-20 amino acids. The expression of IbpreproHypSys, encoding the precursor of IbHypSys, was induced in sweet potato (Ipomoea batatas cv. Tainung 57) through wounding and IbHypSys treatments by using jasmonate and H2 O2 . Transgenic sweet potatoes overexpressing (OE) and silencing [RNA interference (RNAi)] IbpreproHypSys were created. The expression of the wound-inducible gene for ipomoelin (IPO) in the local and systemic leaves of OE plants was stronger than the expression in wild-type (WT) and RNAi plants after wounding. Furthermore, grafting experiments indicated that IPO expression was considerably higher in WT stocks receiving wounding signals from OE than from RNAi scions. However, wounding WT scions highly induced IPO expression in OE stocks. These results indicated that IbpreproHypSys expression contributed towards sending and receiving the systemic signals that induced IPO expression. Analysing the genes involved in the phenylpropanoid pathway demonstrated that lignin biosynthesis was activated after synthetic IbHypSys treatment. IbpreproHypSys expression in sweet potato suppressed Spodoptera litura growth. In conclusion, wounding induced the expression of IbpreproHypSys, whose protein product was processed into IbHypSys. IbHypSys stimulated IbpreproHypSys and IPO expression and enhanced lignin biosynthesis, thus protecting plants from insects.

Folate and TAT peptide co-modified liposomes exhibit receptor-dependent highly efficient intracellular transport of payload in vitro and in vivo.

PURPOSE: Using different chain lengths of PEG as linkers to develop a novel folate (FA) and TAT peptide co-modified doxorubicin (DOX)-loaded liposome (FA/TAT-LP-DOX) and evaluate its potential for tumor targeted intracellular drug delivery. METHODS: FA/TAT-LP-DOX was prepared by pH gradient method and post-insertion method and the optimal ligand density was screened by MTT assay. In vitro evaluation was systematically performed through cytotoxicity assay, cellular uptake studies, subcellular localization and cellular uptake mechanism in folate receptor (FR) over-expressing KB tumor cells. In vivo tumor targeted delivery of FA/TAT-LP-DOX was also studied by in vivo fluorescence imaging in a murine KB xenograft model. RESULTS: The particle size and zeta potential determination indicated that FA and TAT were successfully inserted into the liposome and cationic TAT peptide was completely shielded. With the optimal ligand density (5% of FA and 2.5% TAT), the FA/TAT-LP-DOX exhibited improved cytotoxity and cellular uptake efficiency compared with its single-ligand counterparts (FA-LP-DOX and PEG/TAT-LP-DOX). Competitive inhibition and uptake mechanism experiments revealed that FA and TAT peptide played a synergistic effect in facilitating intracellular transport of the liposome, and association between FA and FA receptors activated this transport process. In vivo imaging further demonstrated the superiority of FA/TAT-LP in tumor targeting and accumulation. CONCLUSIONS: Folate and TAT peptide co-modified liposome using different chain lengths of PEG as linkers may provide a useful strategy for specific and efficient intracellular drug delivery.

[Preparation of solid dispersion of triterpenoid acids from Eriobotrya japonica leaf and study on their dissolution in vitro].

UNLABELLED: To prepare the solid dispersion of Eriobotrya japonica leaf triterpenoid acids(EJA) in order to enhance their dissolution characteristics in vitro. METHODS: Taking ursolic acid and oleanolic acid in vitro dissolution as an indicator, the influence of factors including different water-soluble carriers (PEG 6000, PVPk30 and P188) and the drug/carrier weight ratio for the preparation of solid dispersion were examined using single factor experiment. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) were used to describe the characterization of solid dispersion. RESULTS: P188 was used as appropriate carrier for the preparation of solid dispersion and the drug/carrier weight ratio was 1:5. The X-RD and DSC showed EJA existed in the solid dispersion as the way of amorphous. The dissolution rate of EJA solid dispersion was significantly higher than physical mixture and EJA. CONCLUSION: The solid dispersion prepared with P188 can significantly increase the solubility and dissolution of EJA in vitro. This study provides the scientific evidence for further preparation of solid dispersion tablet.

Revealing symptom profiles: A pre-post analysis of docetaxel therapy in individuals with breast cancer.

PURPOSE: This study aimed to explore the symptom profiles and predominant symptoms in newly diagnosed breast cancer women before and after receiving docetaxel chemotherapy. METHODS: A pre-post study recruited adult women with stage I-III breast cancer undergoing docetaxel chemotherapy using convenience sampling. The 13-item symptom severity subscale of the M. D. Anderson Symptom Inventory-Taiwan Form was used to measure symptoms. The study employed latent profile analysis to identify subgroups based on symptom severity before and after docetaxel chemotherapy. Descriptive statistics, including mean and frequency, were used to compare and contrast the most prevalent and severe symptoms within each subgroup to confirm the predominant symptoms. RESULTS: The study identified four and two symptom profiles before and after docetaxel treatment, respectively. Disturbed sleep was identified as a prevalent symptom for all participants, regardless of their chemotherapy status. The predominant symptoms before treatment were disturbed sleep, dry mouth, difficulty remembering, and fatigue, while disturbed sleep and numbness were the predominant symptoms after treatment. CONCLUSION: The findings of this study are significant, as they contribute to the current understanding of the symptom experience of breast cancer individuals undergoing docetaxel chemotherapy. Healthcare professionals should prioritize assessing and managing these symptoms, including identifying contributing factors to poor sleep. Addressing symptom profiles related to sleep can improve the quality of life of breast cancer individuals undergoing docetaxel chemotherapy.

Association between prosthesis contour and peri-implantitis in patients compliant with supportive periodontal therapy: A retrospective cohort study.

PURPOSE: Poor contour of the implant restoration causes plaque accumulation and increases the risk of peri-implantitis. This study aimed to investigate whether the prosthodontic components of dental implants were associated with the prevalence of peri-implantitis. METHODS: We enrolled 185 patients with 348 implants who underwent at least 1-year follow-up after the delivery of the prosthesis from February 2010 to January 2021. Demographic data of the patients and implants and the follow-up period were recorded. The emergence angle, type of cervical crown contour, and contour angle were analyzed using annual bite-wing radiographs. Peri-implantitis in this study was diagnosed if the peri-implant bone loss was greater than 2 mm between the bite-wing radiographs taken at baseline and the latest. Chi-square test, two-sample t-test, and multivariate logistic regression were used to investigate the differences and odds ratios between the peri-implantitis and non-peri-implantitis groups. RESULTS: The incidence of peri-implantitis was 14.9% during a follow-up period of 1509 days after the delivery of the prosthesis for at least 1-year. Based on the prevalence of non-peri-implantitis and after adjusting for confounding factors, the risk factors identified were bone types for implants (native bone vs. alveolar ridge preservation: adjusted odds ratio = 2.43, P = 0.04). Sex, arch, and guided bone regeneration vs. alveolar ridge preservation have the potential for a statistical difference. CONCLUSIONS: Compared with implants at alveolar ridge preservation sites, implants in the native bone were more prone to peri-implantitis. Further randomized controlled trials are required to determine these associations.

Liposomes encapsulation by pH driven improves the stability, bioaccessibility and bioavailability of urolithin A: A comparative study.

Urolithin A (UroA) is gut metabolites of ellagitannins possessing a vast range of biological activities, but its poor water solubility and low bioavailability hinder its potential applications. This study utilized the pH dependent dissolution characteristics of UroA and employed a simple pH-driven method to load UroA into liposomes. The characterization and stability of obtained liposomes under different conditions were evaluated, and their oral bioavailability was tested by pharmacokinetics, and compared with UroA liposomes prepared using traditional thin film dispersion (TFM-ULs). Results indicated that liposomes could effectively encapsulate UroA. The UroA liposomes prepared by the pH-driven method (PDM-ULs) showed lower particle size, polydispersity index, zeta potential, and higher encapsulation efficiency than TFM-ULs. Interestingly, better thermal stability, storage stability, in vitro digestion stability, and higher bioaccessibility were also found on PDM-ULs. Moreover, pharmacokinetic experiments in rats demonstrated that PDM-ULs could significantly improve the bioavailability of UroA, with an absorption efficiency 1.91 times that of TFM-ULs. Therefore, our findings suggest that liposomes prepared by pH-driven methods have great potential in improving the stability and bioavailability of UroA.

Electrospinning of amphipathic chitosan nanofibers for surgical implants application.

Novel amphipathic derivative of chitosan (carboxymethyl-hexanoyl chitosan, CHC) was made into mats of nanofibers (approximately 100 nm) via electrospinning. The resulting mats were further cross-linked with genipin. The morphology of CHC nanofibers was examined using a field emission scanning electron microscope (FESEM). The optimum parameters of CHC nanofiber was achieved when the CHC concentration was 4 wt% and electrospinning was conducted with a voltage of 20 kV over a distance of 10 cm. The characterizations of biocompatibility, hemocompatibility, and anti-bacterial activity of the nanofibers were also investigated. The results show that CHC nanofibers still preserved antibacterial activity and thrombogeneicity owing to those residual amino groups of chitosan and exhibit high biocompatibility for L929 fibroblast test. Thus CHC exhibited the potential to serve as a novel wound dressing and surgical implants application by these advanced features.

[Impact of liver steatosis on antiviral effects of pegylated interferon-alpha in patients with chronic hepatitis B].

OBJECTIVE: To investigate the impact of hepatic steatosis on virologic response in chronic hepatitis B (CHB) patients treated with pegylated interferon-alpha (PEG-IFNa). METHODS: Ninety-six naive patients positive for hepatitis B e antigen (HBeAg) and with biopsy-proven CHB were administered PEG-IFNa-2a or PEG-IFNa-2b for 48 weeks. Virologic response (HBeAg clearance and hepatitis B virus (HBV) DNA less than 5 log10 copies/ml) and biochemical response (alanine transaminase (ALT) normalization) were compared between patients with (n=34) and without (n=62) steatosis. RESULTS: The HBV DNA titer in the steatosis group was significantly lower than that of the non-steatosis group (6.961.27 vs. 7.541.28 log10 copies/ml; t=2.161, P=0.033). After 48 weeks of PEG-IFNa treatments, there was no significant difference in HBeAg seroconversion or the percentage of undetectable HBV DNA (less than 3 log10 copies/ml) between steatosis and non-steatosis patients. However, the steatosis patients presented with a significantly lower complete response rate (virologic response plus biochemical response) compared to non-steatosis patients (26.5% vs. 48.4%; x² =4.373, P=0.037). Of the 45 CHB patients with undetectable HBV DNA after 48 weeks of treatment, seven did not achieve ALT normalization. The rate of patients with non-biochemical response was significantly higher in the steatosis group than in the non-steatosis group (33.3% vs. 6.67%; P=0.032). CONCLUSION: Hepatic steatosis does not affect the virologic response, but does affect the biochemical response in CHB patients treated with PEG-IFNa for 48 weeks.

Crown ether enabled enhancement of ionic-electronic properties of PEDOT:PSS.

Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) based organic electrochemical transistors (OECTs) have proven to be one of the most versatile platforms for various applications including bioelectronics, neuromorphic computing and soft robotics. The use of PEDOT:PSS for OECTs originates from its ample mixed ionic-electronic conductivity, which in turn depends on the microscale phase separation and morphology of the polymer. Thus, modulation of the microstructure of PEDOT:PSS film enables us to tune the operation and device characteristics of the resulting OECT. Herein we report enhanced transconductance (20 mS), fast switching (32 µs) and stable operation (10 000 cycles) of modified PEDOT:PSS based OECTs using 15-crown-5 as an additive. Four probe measurements reveal an increased electronic conductivity of the modified PEDOT:PSS film (∼450 S cm-1) while tapping mode atomic force microscopy shows an increased phase separation. Further detailed characterization using spectroelectrochemistry, X-ray photoelectron spectroscopy (XPS) and grazing incidence wide-angle X-ray diffraction (GIWAXS) provides insight into the microstructural changes brought about by the crown ether additive that result in the desirable characteristics of the modified PEDOT:PSS film.

[Effect of Antibiotic-Degrading Bacteria on Maturity and Bacterial Community Succession During Pig Manure Composting].

The inoculation of antibiotic-degrading bacteria into manure could promote the removal of antibiotics during composting. However, knowledge on the impact of inoculating these antibiotic-degrading bacteria on the composting process and indigenous microbial community succession is still limited. This study assessed the antibiotic removal efficiency in pig manure after inoculating a microbial inoculum with antibiotic-degrading bacteria as the key component. The effect of inoculating this microbial inoculum on the physicochemical dynamics and the succession of the manure bacterial community during composting was also analyzed. The results showed that the antibiotic degradation in pig manure reached 81.95% after inoculating the microbial inoculum. When compared with that in the control, the total concentration of antibiotic residues in manure with the microbial agent inoculated was decreased by 42.18%. During composting, inoculating the microbial inoculum accelerated the temperature rise of compost, favored water loss, and alleviated the release of NH3 and H2S. Moreover, the total nutrient content (nitrogen, phosphorus, and potassium) in the final compost and the germination index of radish seeds increased by 6.80% and 68.33%, respectively, after inoculating this microbial inoculum. Furthermore, inoculating the microbial inoculum increased the content of stable organic carbon in the final compost and decreased the content of recalcitrant substances such as cellulose and hemicellulose. The analysis of the manure bacterial community showed that inoculating the microbial inoculum increased the relative abundances of Actinomycetes and Firmicutes in the compost. In particular, the thermophilic bacteria that was positively related to the compost temperature was increased significantly (P<0.01) after inoculating the microbial inoculum, whereas the relative abundance of pathogenic bacteria was correspondingly decreased. Network analysis of the bacterial coexistence pattern showed that inoculating this microbial inoculum also changed the interaction pattern of indigenous manure bacterial communities, which greatly reduced the complexity and connectivity of the bacterial interaction and improved the ecological relationship between beneficial bacteria and other bacterial communities. The effect of this microbial inoculum on the interaction with manure bacterial community laid a foundation for the establishment of a new and healthier composting bacterial community. This study provides a scientific basis for the application and development of multifunctional antibiotic-degrading microbial agents in manure treatments.