The RNA binding protein EHD6 recruits the m6A reader YTH07 and sequesters OsCOL4 mRNA into phase-separated ribonucleoprotein condensates to promote rice flowering.

N6-methyladenosine (m6A) is one of the most abundant modifications in eukaryotic mRNA, but the comprehensive biological functionality continues to be a subject for exploration. In this study, we identified and characterized a new flowering-promoting gene EARLY HEADING DATE6 (EHD6) in rice. EHD6 encodes an RNA recognition motif (RRM)-containing RNA binding protein that is localized in the non-membranous cytoplasm ribonucleoprotein (RNP) granules and can bind both m6A-modified RNA and unmodified RNA indiscriminately. We found that EHD6 can physically interact with YTH07, a YTH (YT521-B homology) domain containing m6A reader, and their interaction enhances the binding of m6A-modified RNA and triggers relocation of a part of YTH07 from the cytoplasm into RNP granules through phase-separated condensation. Within these condensates, the mRNA of a rice flowering repressor, CONSTANS-like 4 (OsCOL4), becomes sequestered, leading to a reduction in its protein abundance and thus affect flowering through the Early heading date 1 pathway. Our results not only shed new light on the molecular mechanism of efficient m6A recognition by the collaboration between the RNA binding protein and YTH family m6A reader, but also uncovers a potential m6A mediated translation regulation through phase-separated ribonucleoprotein condensation in rice.

Astaxanthin prevents bone loss in osteoporotic rats with palmitic acid through suppressing oxidative stress.

OBJECTIVES: The study aimed to assess the role of Astaxanthin (ATX) in palmitic acid(PA) -induced bone loss in Ovariectomized(OVX) rats. METHODS: In the OVX rat model, we observed that PA affects bone metabolism and accelerates bone loss. Additionally, treatment with ATX was able to suppress the deleterious effects of PA and a simultaneous decrease in serum MDA levels and an increase in SOD was observed. RESULTS: In addition, rats treated with ATX were observed to have significantly increased bone mass and elevated activity of SIRT1 and SOD2 in bone tissue. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclast differentiation, the ATX intervention was able to significantly restore the restriction of osteogenic differentiation and the up-regulation of osteoclast differentiation with PA therapy. Furthermore, we confirm that PA damage to cells is caused by increased oxidative stress, and that ATX can target and modulate the activity of SIRT1 to regulate the levels of oxidative stress in cells. CONCLUSION: Summarizing, ATX may inhibit PA-induced bone loss through its antioxidant properties via the SIRT1 signaling pathway.

Comparison of [18F]FDG and [68 Ga]pentixafor PET/CT in Nasopharyngeal Carcinoma.

PURPOSE: This study aimed to explore the feasibility of [68 Ga]pentixafor positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma (NPC). PROCEDURES: This prospective study included patients with NPC who underwent [68 Ga]pentixafor PET/CT and 2-[18F]fuoro-2-deoxy-D-glucose ([18F]FDG) PET/CT within one week between November 2022 and March 2023. The [68 Ga]pentixafor and [18F]FDG uptakes in primary and metastatic lesions were measured and compared. RESULTS: Twenty-five participants (21 patients for initial stage and four patients for recurrence detection) were enrolled in our study. The participants underwent [18F]FDG PET/CT and [68 Ga]pentixafor PET/CT. [68 Ga]pentixafor PET/CT had the same detection rate as [18F]FDG for primary tumor (96% vs. 96%). The [68 Ga]pentixafor maximum standard uptake value (SUVmax) and target-to-background ratio (TBR) of primary tumors were lower than those of [18F]FDG (SUVmax: 8.13 ± 2.78 vs. 14.25 ± 6.45; P < 0.01; TBR: 5.17 ± 2.14 vs. 9.81 ± 5.30, P < 0.01). The difference between tumor volume of [68 Ga]pentixafor (TVpentixafor) and tumor volume of [18F]FDG (TVFDG) showed no significance (median: 16.01 vs. 9.56, P = 0.332). In the detection of suspected metastatic cervical lymph nodes (CLNs), [68 Ga]pentixafor PET possessed a lower SUVmax than [18F]FDG PET/CT (SUVmax: 6.86 ± 2.63 vs. 10.39 ± 5.28, P < 0.01), but there was no significant difference in the detection rate between [68 Ga]pentixafor and [18F]FDG PET/CT (96 vs. 98, P = 0.613). CONCLUSIONS: [68 Ga]pentixafor is a promising imaging tracer for detecting primary and metastatic NPC. [68 Ga]pentixafor PET/CT is comparable to [18F]FDG PET/CT in the detection rate of primary tumors and metastatic cervical lymph nodes in nasopharyngeal carcinoma, but [68 Ga]pentixafor uptake was heterogeneous. [68 Ga]pentixafor PET/CT may help select patients most likely to benefit from CXCR4-directed endoradiotherapy. CLINICAL TRIAL REGISTRATION NO: ChiCTR2200065902.

Parametric net influx rate imaging of 68Ga-DOTATATE in patients with neuroendocrine tumors: assessment of lesion detectability.

OBJECTIVES: There has been developed a clinical dynamic total-body 68Ga-DOTATATE PET/CT imaging protocol that allows quantitative imaging of net influx rate (Ki). Using qualitative and quantitative analyses of clinical studies, this retrospective study aims to assess whether parametric Ki images improve lesion detectability. METHODS: Using a 194-cm axial field-of-view PET/CT scanner, 52 patients with neuroendocrine tumors underwent a 60-min dynamic total-body 68Ga-DOTATATE scan. Parametric Ki images and static standardized uptake value (SUV) images were generated. In addition to visual inspection of both sets of images, a quantitative analysis of 249 individual lesions was conducted using the target-to-background (TBR) metric. RESULTS: There were 52 patients who underwent dynamic total-body 68Ga-DOTATATE PET/CT scans. A total of 249 lesions were evaluated, of which 66 lesions were biopsy-proven and 183 lesions were unproven. Ki images produced two fewer false positives than the SUV images. Overall, our results from 66 proven NET lesions suggested similar sensitivity (98.5%) but improved accuracy (from 95.6 to 97.1%) and potentially enhanced specificity with Ki over SUV imaging. Besides, there was no difference in the number of pathological lesions identified visually in both images. However, Ki TBR was significantly higher than SUV TBR quantitatively (P < 0.001). CONCLUSIONS: Patlak Ki imaging provides nuclear physicians with a PET image with higher tumor contrast which may enhance confidence in diagnosis with possibly reduced false positive results, albeit an equivalent detectability, compared to static SUV image.

Favorable osteogenic activity of vericiguat doped in ß-tricalcium phosphate: In vitro and in vivo studies.

Recently, more and more studies have shown that guanylate cyclase, an enzyme that synthesizes cyclic guanosine monophosphate (cGMP), plays an important role in bone metabolism. Vericiguat (VIT), a novel oral soluble guanylate cyclase stimulator, directly generates cyclic guanosine monophosphate and reduce the death incidence from cardio-vascular causes or hospitalization. Recent studies have shown beneficial effects of VIT in animal models of osteoporosis, but very little is currently known about the effects of VIT on bone defects in the osteoporotic states. Therefore, in this study, ß-tricalcium phosphate (ß-TCP) was used as a carrier to explore the effect of local VIT administration on the repair of femoral metaphyseal bone defects in ovariectomized (OVX) rats. When MC3T3-E1 was cultured in the presence of H2H2, VIT, similar to Melatonin (MT), therapy could increase the matrix mineralization and ALP, SOD2, SIRT1, and OPG expression, reduce ROS and Mito SOX production, RANKL expression, Promote the recovery of mitochondrial membrane potential. In the OVX rat model, VIT increases the osteogenic effect of ß-TCP and better results were obtained at a dose of 5 mg. Local use of VIT can inhibit increased OC, BMP2 and RUNX2 expressions in bone tissue, while decreased SOST and TRAP expressions by RT-PCR and immunohistochemistry. Thereby, VIT stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis.

Comparison of 18F-MFBG PET/CT and 18F-FDG PET/CT Images of Metastatic Neuroblastoma.

ABSTRACT: Two children with neuroblastoma underwent tumor resection and postoperative chemotherapy. After treatment, they participated in a clinical trial and received 18F-MFBG and 18F-FDG PET/CT examinations. Although similar lesions were found in the 2 examinations, the uptake pattern was different. The lymph nodes and bone lesions had intense 18F-MFBG activity, whereas 18F-FDG uptake was not very impressive. The uptake of bone marrow by 18F-MFBG was significantly stronger than that by 18F-FDG. This case emphasizes that 18F-MFBG PET/CT is superior to 18F-FDG PET/CT in detecting the metastases of neuroblastoma.

Monoaxial Screws Versus Polyaxial Screws Osteosynthesis for Unstable Atlas Fractures: A Retrospective, Comparative Study With a Minimum Follow-Up of 3 years.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The study aimed to compare the radiological parameters, clinical outcomes, and long-term effects of the posterior osteosynthesis with polyaxial screw-rod system and the monoaxial screw-rod system in the treatment of unstable atlas fractures. METHODS: We retrospectively analyzed the clinical data of 33 patients with posterior ORIF for unstable atlas fractures in our hospital from August 2013 to June 2020, with a minimum of 3 years of follow-up. Polyaxial screws (group A) were used in 12 patients and monoaxial screws (group B) in 21 patients. Perioperative data, radiological parameters, and clinical outcomes were collected and compared between the 2 surgical approaches. RESULTS: The operative time, blood loss, time of screw-rod system placement, and hospital stay were significantly lower in group A than in group B. At the last follow-up, the visual analog scale (VAS) score and anterior arch reduction rate of the atlas in group A were lower than those in group B, while the lateral mass displacement (LMD) in group A was higher than that in group B. There was no significant difference between Group A and Group B in terms of the anterior atlantodental interval (AADI), posterior arch reduction rate of the atlas, range of motion (ROM), and neck disability index (NDI). CONCLUSIONS: Monoaxial screws can achieve better reduction results for unstable atlas fractures, especially for the anterior arch of atlas. However, the surgical operation of monoaxial screws is more complicated than that of polyaxial screws and has more complications. Appropriate implants should be selected for the treatment of unstable atlas fractures based on the type of atlas fracture, the experience of surgeons, and the demands of patients.

Screening of potential biomarkers in propofol-induced neurotoxicity via bioinformatics prediction and experimental verification.

OBJECTIVES: To identify hub genes and biological processes of propofol-induced neurotoxicity and promote the development of pediatric anesthesiology. METHODS: We downloaded the GSE106799 dataset from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened, then Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment analyses were performed on all DEGs. We identified potential ferroptosis genes in the pathogenesis of propofol-induced neurotoxicity. A key module was obtained after performing weighted gene co-expression network analysis (WGCNA) on the GSE106799 dataset. Hub genes were identified after the least absolute shrinkage and selection operator (LASSO) regression analysis of the intersection of DEGs and genes from the key module. We established a competing endogenous RNA network and predicted potential drugs according to the hub genes. Total RNA and proteins were extracted for real-time quantitative polymerase chain reaction and Western blotting, respectively. RESULTS: A total of 112 DEGs, including 76 upregulated and 36 downregulated ones were screened out. Propofol-induced neurotoxicity involved processes such as nervous system development, activation of JAK/STAT and MAPK signaling pathways, vascular regeneration, and oxidative stress. The results of WGCNA suggested that the tan module was the most strongly associated with propofol-induced neurotoxicity. We identified 4 hub genes (EGR4, HAO1, ITK and GM14446) after LASSO regression analysis. Animal experiments demonstrated that propofol caused overexpression of the protein levels of HAO1, ITK and inflammatory factors in the brain, as well as the mRNA levels of HAO1, ITK and GM14446. Propofol inhibited expression of EGR4 at mRNA and protein levels. CONCLUSIONS: Previous studies have demonstrated that EGR4, HAO1, ITK and GM14446 play a role in intellectual development, neuroinflammation and neuronal differentiation. These hub genes may help us to find new preventive and therapeutic targets for propofol-induced neurotoxicity.

Diagnostic value of serum COMP and ADAMTS7 for intervertebral disc degeneration.

OBJECTIVE: Intervertebral disc degeneration (IVDD) is a major cause of morbidity and disability. Our study aimed to investigate the potential of cartilage oligomeric matrix protein (COMP) and ADAMTS7 (A disintegrin and metalloproteinases with thrombospondin motifs 7) as biomarkers for IVDD together with their functional relationship. METHODS: IVD tissues and peripheral blood samples were collected from IVDD rabbit models over 1-4 weeks. Tissues and blood samples were also collected from clinical patients those were stratified into four equal groups according to Pfirrmann IVDD grading (I-V) with baseline data collected for each participant. COMP and ADAMTS7 expression were analyzed and biomarker characteristics were assessed using linear regression and receiver operating curve (ROC) analyses. RESULTS: COMP and ADAMTS7 expression increased in tissues and serum during IVDD progression. Serum COMP (sCOMP) and serum ADAMTS7 (sADAMTS7) levels increased in a time-dependent manner following IVD damage in the rabbit model while significant positive correlations were detected between sCOMP and sADAMTS7 and Pfirrmann grade in human subjects. ROC analysis showed that combining sCOMP and sADAMTS7 assay results produced an improved diagnostic measure for IVDD compared to individual sCOMP or sADAMTS7 tests. In vitro assays conducted on human cell isolates revealed that COMP prevented extracellular matrix degradation and antagonized ADAMTS7 expression although this protective role was uncoupled under microenvironmental conditions mimicking IVDD. CONCLUSIONS: Increases in circulating COMP and ADAMTS7 correlate with IVDD progression and may play regulatory roles. Assays for sCOMP and/or sADAMTS7 levels can discriminate between healthy subjects and IVDD patients, warranting further clinical assessment.

Costunolide mitigates inflammation and promotes extracellualr matrix integrity of thoracic aortic dissection by inhibiting NF-κB signaling.

BACKGROUND: Thoracic aortic dissection (TAD) is one of the most fatal cardiovascular diseases. One of its important pathological characteristics is the local inflammatory response. Many studies have found that Macrophage polarization plays an extremely critical role in the inflammatory progression and tissue remodeling of TAD. Costunolide (CTD) has an improving effect on oxidative stress and inflammation in the body. However, whether it can promote the integrity of extracellular matrix in Aortic dissection and its mechanism are still unclear. METHODS: The male C57BL/6J mice were used to construct an animal model of TAD with ß-aminopropionitrile (BAPN) (100 mg/kg/day, lasting for 28 days), and then CTD (10 mg/kg or 100 mg/kg) was injected intraperitoneally for 28 days to check the survival rate, TAD incidence, aortic morphology and other indicators of the mice. Using hematoxylin-eosin (HE), Masson, Elastin van Gieson (EVG) staining, immunofluorescence (IF), and immunohistochemical staining, the study aimed to determine the therapeutic effects of CTD on an animal model with BAPN-induced TAD. To enhance the examination of the regulatory mechanism of CTD, we conducted transcriptome sequencing on arterial tissues of mice in both the BAPN group and the BAPN + CTD100 group. Next, ANG II were used to construct TAD model in vascular smooth muscle cells (VMSCs). The effects of CTD on the proliferation, migration, invasion, and apoptosis of ANG II-induced cells are to be detected. The expression of MMP2, MMP9, P65, and p-P65 in each group will be examined using Western blot. Finally, the overexpression of IκB kinaseß (IKKß) will be established in VMSCs cells to further explore the protective function of CTD. RESULTS: The result showed that CTD significantly inhibited BAPN induced mortality and TAD incidence in the animal model, improved aortic vascular morphology, promoted the integrity of extracellular matrix in TAD, reduced tissue inflammation, reduced the accumulation of M1 macrophage, promoted M2 macrophage polarization, and reduced the expression of NF-κB pathway related proteins. Mechanistically, CTD significantly weakened the proliferation, migration, invasion, and apoptosis. p-P65 protein expression of TAD cells were induced by ANG II and IKK-ß. CONCLUSION: CTD has the potential to alleviate inflammation, VSMC apoptosis, MMP2/9 levels, and enhance extracellular matrix integrity in TAD by inhibiting the NF-κB signaling pathway.

Tomatidine activates autophagy to improve lung injury and inflammation in sepsis by inhibiting NF-κB and MAPK pathways.

Sepsis-induced acute lung injury (ALI) is a life-threatening medical condition with high mortality and morbidity. Autophagy is involved in the pathophysiological process of sepsis-induced ALI, including inflammation, which indicates that regulating autophagy may be beneficial for this disease. Tomatidine, a natural compound abundant in unripe tomatoes, has been reported to have anti-inflammatory, anti-tumorigenic, and lipid-lowering effects. However, the biological functions and mechanisms of tomatidine in sepsis-induced ALI remain unknown. The principal objective of this study was to investigate the effect of tomatidine on sepsis-induced ALI. Cecal ligation and puncture (CLP) was used to induce septic lung injury in mice, and 10 mg/kg tomatidine was intraperitoneally injected into mice 2 h after the operation. The results of hematoxylin and eosin staining and assessment of lung edema and total protein levels in bronchoalveolar lavage fluid (BALF) demonstrated that tomatidine alleviated CLP-induced severe lung injuries such as hemorrhage, infiltration of inflammatory cells, and interstitial and alveolar edema in mice. Additionally, the levels of proinflammatory cytokines in BALF and lung tissues were measured by enzyme-linked immunosorbent assay (ELISA), and the results showed that tomatidine inhibited CLP-induced inflammatory damage to lungs. Moreover, the results of western blotting showed that tomatidine promoted autophagy during CLP-induced ALI. Mechanistically, immunofluorescence staining and western blotting were used to measure the protein levels of TLR4, phosphorylated NF-κB, phosphorylated IκBα, and phosphorylated MAPKs, showing that tomatidine inactivated NF-κB and MAPK signaling in lung tissues of CLP-induced ALI mice. In conclusion, tomatidine exerts protective effects against sepsis-induced severe damage to the lungs by inhibiting inflammation and activating autophagy in CLP-treated mice through inactivating the NF-κB and MAPK pathways, which may be an effective candidate for treating septic ALI.

Cutaneous Metastasis of Ovarian Cancer on 68 Ga-FAPI PET/CT.

ABSTRACT: Ovarian cancer with cutaneous metastases is quite rare. We report the findings of cutaneous metastases from ovarian cancer on 68 Ga-FAPI PET/CT imaging. A 53-year-old woman with cutaneous metastases from ovarian cancer was enrolled in 68 Ga-FAPI PET/CT clinical trial. The images showed intense FAPI activity in the known cutaneous metastases.

FSTL1 Accelerates Nucleus Pulposus Cell Senescence and Intervertebral Disc Degeneration Through TLR4/NF-κB Pathway.

Intervertebral disc degeneration (IVDD) is a major contributor to low back pain (LBP), and inflammatory factors play crucial roles in its pathogenesis. Follistatin-like 1 (FSTL1) has been reported to induce an inflammatory response in chondrocytes, microglia and preadipocytes, but its role in the pathogenesis of nucleus pulposus cell (NPC) degeneration remains unclear. In this study, we mainly utilized an acidosis-induced NPC degeneration model and a rabbit puncture IVDD model to investigate the role of FSTL1 in IVDD both in vitro and in vivo. We confirmed that FSTL1 expression significantly increased in nucleus pulposus (NP) tissues from IVDD patients and rabbit puncture IVDD models. The expression levels of FSTL1 were significantly increased in all three models of NPC degeneration under harsh microenvironments. In addition, recombinant human FSTL1 (rh-FSTL1) was found to upregulate the expression of p16 and p21, increase the number of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells, induce senescence-related secretory phenotypes (SASP), and downregulate extracellular matrix (ECM) protein expressions, leading to an imbalance in ECM metabolism destructions. Conversely, silencing of FSTL1 by small interfering RNA (siRNA) ameliorated senescence of NPCs associated with inflammation in IVDD. Furthermore, Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway plays a crucial role in regulating NPC senescence through FSTL1 regulation. Inhibition of TLR4 expression partly reversed the effects of rh-FSTL1 on NPC senescence-associated inflammation. Finally, rabbit IVDD model experiments demonstrated that the specific FSTL1 siRNA markedly repressed the development of IVDD. These findings may offer a therapeutic approach for mitigating inflammation-induced senescence associated with IVDD.

FDG Uptake Caused by Right Varicocele.

ABSTRACT: A 67-year-old man underwent 18 F-FDG PET/CT for lung cancer staging. Interestingly, the PET scan revealed strip-shaped FDG uptake in the right inguinal contoured area, which was later confirmed as a right varicocele through ultrasound imaging.

MALT Lymphoma in Histologic Transformation: FDG-Avid but Pentixafor-Negative.

ABSTRACT: An 81-year-old woman experienced compression symptoms due to diffuse enlargement of the thyroid gland. The cytopathological results of thyroid fine-needle suggested malignancy. Therefore, she underwent bilateral thyroidectomy. Postoperative pathology indicated mucosa-associated lymphoid tissue (MALT) lymphoma. Three months later, she found a progressively enlarged mass in her neck. The biopsy showed MALT lymphoma with highly aggressive B-cell lymphoma transformation. 18F-FDG PET/CT showed increased metabolism in multiple lymph nodes. However, some of these lymph nodes were negative in 68Ga-pentxafor PET/CT. Our case demonstrated that 68Ga-pentixafor may have limited value in evaluating MALT lymphoma transformation.

Non­synchronous bilateral metastatic ovarian cancer originating from small bowel adenocarcinoma with multidisciplinary treatment: A case report.

Primary small bowel adenocarcinoma (SBA) is a rare gastrointestinal cancer with a low incidence of ovarian metastasis. Differential diagnosis of metastatic and primary ovarian cancer is often challenging. The present study reported the case of a 45-year-old woman with jejunal adenocarcinoma who presented with right ovarian, left ovarian, abdominopelvic implant and local recurrent bowel wall metastases successively after primary tumor resection. The ovarian masses of the patient originated from SBA, which was confirmed by immunohistochemical results. Following four comprehensive evaluations by an experienced multidisciplinary team (MDT) during the disease period, the patient underwent four operations, 28 cycles of chemotherapy, 24 cycles of targeted therapy and maintenance therapy for 8 months. As of February 2023, the patient has survived for 73 months and has a high quality of life. It is suggested that when a patient with SBA presents with an ovarian mass, the differential diagnosis between metastatic ovarian cancer and primary ovarian cancer mainly relies on immunohistochemistry. After a comprehensive evaluation by an experienced MDT, surgical resection is the primary treatment for advanced SBA, thus demonstrating some benefits for patients.

Comparative assessment of the feasibility and validity of daily activity space in urban and non-urban settings.

Activity space research explores the behavioral impact of the spaces people move through in daily life. This research has focused on urban settings, devoting little attention to non-urban settings. We examined the validity of the activity space method, comparing feasibility and data quality in urban and non-urban contexts. Overall, we found that the method is easily implemented in both settings. We also found location data quality was comparable across residential and activity space settings. The major differences in GPS (Global Positioning System) density and accuracy came from the operating system (iOS versus Android) of the device used. The GPS-derived locations showed high agreement with participants' self-reported locations. We further validated GPS data by comparing at-home time allocation with the American Time Use Survey. This study suggests that it is possible to collect daily activity space data in non-urban settings that are of comparable quality to data from urban settings.

Characterization and risk assessment of novel SXT/R391 integrative and conjugative elements with multidrug resistance in Proteus mirabilis isolated from China, 2018-2020.

Proteus mirabilis can transfer transposons, insertion sequences, and gene cassettes to the chromosomes of other hosts through SXT/R391 integrative and conjugative elements (ICEs), significantly increasing the possibility of antibiotic resistance gene (ARG) evolution and expanding the risk of ARGs transmission among bacteria. A total of 103 strains of P. mirabilis were isolated from 25 farms in China from 2018 to 2020. The positive detection rate of SXT/R391 ICEs was 25.2% (26/103). All SXT/R391 ICEs positive P. mirabilis exhibited a high level of overall drug resistance. Conjugation experiments showed that all 26 SXT/R391 ICEs could efficiently transfer to Escherichia coli EC600 with a frequency of 2.0 × 10-7 to 6.0 × 10-5. The acquired ARGs, genetic structures, homology relationships, and conservation sequences of 26 (19 different subtypes) SXT/R391 ICEs were investigated by high-throughput sequencing, whole-genome typing, and phylogenetic tree construction. ICEPmiChnHBRJC2 carries erm (42), which have never been found within an SXT/R391 ICE in P. mirabilis, and ICEPmiChnSC1111 carries 19 ARGs, including clinically important cfr, blaCTX-M-65, and aac(6')-Ib-cr, making it the ICE with the most ARGs reported to date. Through genetic stability, growth curve, and competition experiments, it was found that the transconjugant of ICEPmiChnSCNNC12 did not have a significant fitness cost on the recipient bacterium EC600 and may have a higher risk of transmission and dissemination. Although the transconjugant of ICEPmiChnSCSZC20 had a relatively obvious fitness cost on EC600, long-term resistance selection pressure may improve bacterial fitness through compensatory adaptation, providing scientific evidence for risk assessment of horizontal transfer and dissemination of SXT/R391 ICEs in P. mirabilis.IMPORTANCEThe spread of antibiotic resistance genes (ARGs) is a major public health concern. The study investigated the prevalence and genetic diversity of integrative and conjugative elements (ICEs) in Proteus mirabilis, which can transfer ARGs to other hosts. The study found that all of the P. mirabilis strains carrying ICEs exhibited a high level of drug resistance and a higher risk of transmission and dissemination of ARGs. The analysis of novel multidrug-resistant ICEs highlighted the potential for the evolution and spread of novel resistance mechanisms. These findings emphasize the importance of monitoring the spread of ICEs carrying ARGs and the urgent need for effective strategies to combat antibiotic resistance. Understanding the genetic diversity and potential for transmission of ARGs among bacteria is crucial for developing targeted interventions to mitigate the threat of antibiotic resistance.