Targeted Light-Induced Immunomodulatory Strategy for Implant-Associated Infections via Reversing Biofilm-Mediated Immunosuppression.

The clinical treatment efficacy for implant-associated infections (IAIs), particularly those caused by Methicillin-resistant Staphylococcus aureus (MRSA), remains unsatisfactory, primarily due to the formation of biofilm barriers and the resulting immunosuppressive microenvironment, leading to the chronicity and recurrence of IAIs. To address this challenge, we propose a light-induced immune enhancement strategy, synthesizing BSA@MnO2@Ce6@Van (BMCV). The BMCV exhibits precise targeting and adhesion to the S. aureus biofilm-infected region, coupled with its capacity to catalyze oxygen generation from H2O2 in the hypoxic and acidic biofilm microenvironment (BME), promoting oxygen-dependent photodynamic therapy efficacy while ensuring continuous release of manganese ions. Notably, targeted BMCV can penetrate biofilms, producing ROS that degrade extracellular DNA, disrupting the biofilm structure and impairing its barrier function, making it vulnerable to infiltration and elimination by the immune system. Furthermore, light-induced reactive oxygen species (ROS) around the biofilm can lyse S. aureus, triggering bacterium-like immunogenic cell death (ICD), releasing abundant immune costimulatory factors, facilitating the recognition and maturation of antigen-presenting cells (APCs), and activating adaptive immunity. Additionally, manganese ions in the BME act as immunoadjuvants, further amplifying macrophage-mediated innate and adaptive immune responses and reversing the immunologically cold BME to an immunologically hot BME. We prove that our synthesized BMCV elicits a robust adaptive immune response in vivo, effectively clearing primary IAIs and inducing long-term immune memory to prevent recurrence. Our study introduces a potent light-induced immunomodulatory nanoplatform capable of reversing the biofilm-induced immunosuppressive microenvironment and disrupting biofilm-mediated protective barriers, offering a promising immunotherapeutic strategy for addressing challenging S. aureus IAIs.

Neutrophil Function Conversion Driven by Immune Switchpoint Regulator against Diabetes-Related Biofilm Infections.

Reinforced biofilm structures and dysfunctional neutrophils induced by excessive oxidative stress contribute to the refractoriness of diabetes-related biofilm infections (DRBIs). Herein, in contrast to traditional antibacterial therapies, an immune switchpoint-driven neutrophil immune function conversion strategy based on a deoxyribonuclease I loaded vanadium carbide MXene (DNase-I@V2 C) nanoregulator is proposed to treat DRBIs via biofilm lysis and redirecting neutrophil functions from NETosis to phagocytosis in diabetes. Owing to its intrinsic superoxide dismutase/catalase-like activities, DNase-I@V2 C effectively scavenges reactive oxygen species (ROS) in a high oxidative stress microenvironment to maintain the biological activity of DNase-I. By increasing the depth of biofilm penetration of DNase-I, DNase-I@V2 C thoroughly degrades extracellular DNA and neutrophil extracellular traps (NETs) in extracellular polymeric substances, thus breaking the physical barrier of biofilms. More importantly, as an immune switchpoint regulator, DNase-I@V2 C can skew neutrophil functions from NETosis toward phagocytosis by intercepting ROS-NE/MPO-PAD4 and activating ROS-PI3K-AKT-mTOR pathways in diabetic microenvironment, thereby eliminating biofilm infections. Biofilm lysis and synergistic neutrophil function conversion exert favorable therapeutic effects on biofilm infections in vitro and in vivo. This study serves as a proof-of-principle demonstration of effectively achieving DRBIs with high therapeutic efficacy by regulating immune switchpoint to reverse neutrophil functions.

Hsa_circ_0079557 Promotes the Proliferation of Colorectal Cancer Cells Through the hsa_circ_0079557/miR-502-5p/CCND1 Axis.

BACKGROUND/AIM: Recent studies have demonstrated the crucial regulatory roles of circular RNAs (circRNAs) in cancer initiation and progression. The sponge mechanism of circRNAs has been shown to be widely active in various types of tumors. However, many circRNAs still have not been verified to function through this mechanism. This study aimed to investigate the regulatory mechanism of hsa_circ_0079557 in colorectal cancer (CRC) and its role in CRC progression. MATERIALS AND METHODS: Raw gene expression profile datasets were downloaded from Gene Expression Omnibus (GEO) and combined to form a new dataset. Hsa_circ_0079557 was found to be highly expressed in CRC. Its role was evaluated in vitro and in vivo through a series of experiments, including quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, colony formation, cell counting kit-8 (CCK-8), transwell assays, scratch wound healing assays, nude mice experiments, and immunohistochemistry (IHC). The association between hsa_circ_0079557 and the identified target microRNAs (miRNA) was confirmed through fluorescence in situ hybridization (FISH) and dual-luciferase reporter assays. The downstream target proteins were predicted using the web-based tool "TargetScan," and their expressions were determined using Western blot (WB). RESULTS: Hsa_circ_0079557 was found to be relatively up-regulated in CRC tissues and cell lines. Suppression of hsa_circ_0079557 expression inhibited cell proliferation in vitro and in vivo. Additionally, hsa_circ_0079557 acted as a "molecular sponge" for miR-502-5p, up-regulating the expression of Cyclin D1 (CCND1). CONCLUSION: In this study, we identify a highly expressed circRNA in CRC and propose a novel pathway of hsa_circ_0079557/miR-502-5p/CCND1 in CRC.

New Mouse Models of Roux-en Y Gastric Bypass and One Anastomosis Gastric Bypass for Type 2 Diabetes.

BACKGROUND: Current bariatric surgery models primarily utilize mice with obesity, overlooking those with type 2 diabetes (T2DM). These models have limitations in replicating clinical procedures accurately and achieving broad applicability. This study aimed to develop novel mouse models of Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) surgeries specifically designed for T2DM research, utilizing simplified surgical techniques closely resembling clinical procedures. METHODS: Eight-week-old C57/Bl6 mice, except for the Blank-Control group, were induced with T2DM by combining a high-fat diet and streptozotocin injection. RYGB involved creating a 10% gastric pouch, a 4-cm biliopancreatic limb (BL), and a 4-cm Roux limb (RL). Similarly, OAGB maintained a 10% gastric pouch and a 4-cm BL. To assess the efficacy of these models, we measured the body weight and fasting blood glucose (FBG) and conducted intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), and liver B-ultrasound, as well as a histopathological analysis of multiple organs 12 weeks post-operation. RESULTS: The survival rates in the Blank-Control, T2DM-Sham, T2DM-RYGB, and T2DM-OAGB groups were 100% (6/6), 100% (6/6), 85.7% (6/7), and 100% (6/6), respectively. Both RYGB and OAGB surgeries similarly led to sustained weight loss, reduced the FBG levels, improved the IPGTT and ITT results, and alleviated the histopathological manifestations in multiple organs. CONCLUSION: The innovative mouse models of RYGB and OAGB surgeries effectively improve T2DM. Both surgeries demonstrate comparable efficacy in ameliorating T2DM, even when utilizing a gastric pouch of the same size and the same length of BL in OAGB.

Trends in microbiological epidemiology of orthopedic infections: a large retrospective study from 2008 to 2021.

BACKGROUND: This study assessed the distribution characteristics of pathogens isolated from cases of orthopedic infections and focused on the antimicrobial susceptibility of the main pathogens. METHODS: This retrospective study involved patients with orthopedic infection in a tertiary medical center located in Shanghai, China, from 2008 to 2021.Pathogen information and the basic information of patients were identified from clinical microbiology laboratory data and the institutional medical record system. RESULTS: In total, the pathogen information of 2821 patients were enrolled in the study. S. aureus (37.71%) was the main causative pathogen responsible for orthopedic infection. Gender, pathogens distribution and polymicrobial infection rates were significantly different (P < 0.05) among patients with different orthopedic infection diseases.The trends in the distribution of pathogens in the total cohort, implant-related infection group (Group A), non-implant-related infection group (Group B), and the sub-group of cases with arthroplasty showed significant linear changes over time. And the polymicrobial infection rates of the total cohort (from 17.17% to 11.00%), Group B(from 24.35% to 14.47%), and the sub-group of cases with internal fixation (from 10.58% to 4.87%) decreased significantly. The antimicrobial susceptibility showed changing trends with time for some main pathogens, especially for S.aureus and Enterobacter spp. CONCLUSIONS: Our research indicated that the pathogen distribution and antimicrobial susceptibility in orthopedic infections changed over time. And the distribution of pathogens varied significantly among different types of orthopedic infectious diseases. These findings may serve as a reference for prophylaxis and empirical treatment strategies of orthopedic infection.

Repurposed Fenoprofen Targeting SaeR Attenuates Staphylococcus aureus Virulence in Implant-Associated Infections.

Implant-associated infections (IAIs) caused by S. aureus can result in serious challenges after orthopedic surgery. Due to biofilm formation and antibiotic resistance, this refractory infection is highly prevalent, and finding drugs to attenuate bacterial virulence is becoming a rational alternative strategy. In S. aureus, the SaeRS two-component system (TCS) plays a key role in the production of over 20 virulence factors and the pathogenesis of the bacterium. Here, by conducting a structure-based virtual screening against SaeR, we identified that fenoprofen, a USA Food and Drug Administration (FDA)-approved nonsteroid anti-inflammatory drug (NSAID), had excellent inhibitory potency against the response regulator SaeR protein. We showed that fenoprofen attenuated the virulence of S. aureus without drug resistance. In addition, it was helpful in relieving osteolysis and restoring the walking ability of mice in vitro and in implant-associated infection models. More importantly, fenoprofen treatment suppressed biofilm formation and changed the biofilm structure, which caused S. aureus to form loose and porous biofilms that were more vulnerable to infiltration and elimination by leukocytes. Our results reveal that fenoprofen is a potent antivirulence agent with potential value in clinical applications and that SaeR is a drug target against S. aureus implant-associated infections.

Identification of Staphylococcus aureus virulence-modulating RNA from transcriptomics data with machine learning.

The virulence factors of Staphylococcus aureus are tightly controlled by two-component systems (TCSs) and small RNA (sRNA). TCSs have been well studied over the past several decades, but our understanding of sRNA functions lags far behind that of TCS functions. Here, we studied the biological role of sRNA from 506 S. aureus RNA-seq datasets using independent component analysis (ICA). We found that a previously neglected sRNA, Sau-41, functions in the Agr system. Sau-41 is located within the PSMα operon and controlled by the Agr system. It was predicted to share 22-base complementarity with RNAIII, a major regulator of S. aureus virulence. The EMSA results demonstrated that Sau-41 directly binds to RNAIII. Furthermore, our results found that Sau-41 is capable of repressing S. aureus haemolysin activity by downregulating α-haemolysin and δ-toxin. The repression of α-haemolysin was attributed to the competition between the 5' UTR of hla and Sau-41 for binding RNAIII. We observed that Sau-41 mitigated S. aureus virulence in an orthopaedic implant infection mouse model and alleviated osteolysis. Together, our results indicate that Sau-41 is a virulence-regulating RNA and suggest that Sau-41 might be involved in a negative feedback mechanism to control the Agr system. This work is a demonstration of using ICA in sRNA identification by mining high-throughput data and could be extended to other organisms as well.

High-precision micro-displacement sensing based on an optical filter and optoelectronic oscillators.

High-precision micro-displacement sensing based on an optical filter and optoelectronic oscillators (OEOs) is proposed and experimentally demonstrated. In this scheme, an optical filter is utilized to separate the carriers of the measurement and reference OEO loops. Through the optical filter, the common path structure can be consequently achieved. The two OEO loops share all optical/electrical components, except for the micro-displacement to be measured. Measurement and reference OEOs are alternately oscillated by using a magneto-optic switch. Therefore, self-calibration is achieved without additional cavity length control circuits, greatly simplifying the system. A theoretical analysis of the system is developed, and this analysis is then demonstrated with experiments. Regarding the micro-displacement measurements, we achieved a sensitivity of 312.058 kHz/mm and a measurement resolution of 356 pm. The measurement precision is less than 130 nm over a measurement range of 19 mm.

Evaluation of early liquid drinking after radical gastrectomy in gastric cancer: a Chinese multicenter propensity score matching analysis.

Background: Enhanced recovery after surgery is used in gastrointestinal surgery. This study aimed to access the effects of early liquid drinking (ELD) on gastrointestinal function recovery in patients with gastric cancer (GC) who underwent radical gastrectomy, as high-quality evidence on the outcomes of ELD after gastrectomy is currently lacking. Methods: Clinicopathological data of patients with GC from 11 centers were retrospectively analysed. Clinical outcomes were investigated in 555 patients, including 225 who started drinking liquid within 48 h (ELD group) of surgery and 330 who started drinking liquid after flatus resumption (traditional liquid drinking [TLD] group). Propensity score matching (PSM) analysis was performed using a match ratio of 1:1 and 201 patients were selected from each group for the analysis. Primary outcome was time to first passage of flatus. Secondary outcomes included time to first defecation, post-operative hospitalization days, occurrence of short-term post-operative complications, and hospitalization costs. Results: After PSM, baseline characteristics were not significantly different between the two groups. The time to first flatus (2.72 ± 1.08 vs 3.36 ± 1.39 days), first defecation (4.34 ± 1.85 vs 4.77 ± 1.61 days), and post-operative hospital stay (8.27 ± 4.02 vs 12.94 ± 4.43 days) were shorter in the ELD group than in the TLD group (all P < 0.05). The ELD group had lower hospitalization costs than the TLD group ([7.83 ± 2.44 vs 8.78 ± 3.41] × 104 RMB, P = 0.041). No significant differences were observed in the incidence of post-operative complications. Conclusions: Compared with TLD, post-operative ELD could promote rapid recovery of gastrointestinal function and reduce hospitalization costs; moreover, ELD does not increase the risk of post-operative complications.

The role of the microbiota-gut-brain axis and intestinal microbiome dysregulation in Parkinson's disease.

Parkinson's disease (PD) is a complex progressive neurodegenerative disease associated with aging. Its main pathological feature is the degeneration and loss of dopaminergic neurons related to the misfolding and aggregation of α-synuclein. The pathogenesis of PD has not yet been fully elucidated, and its occurrence and development process are closely related to the microbiota-gut-brain axis. Dysregulation of intestinal microbiota may promote the damage of the intestinal epithelial barrier, intestinal inflammation, and the upward diffusion of phosphorylated α-synuclein from the enteric nervous system (ENS) to the brain in susceptible individuals and further lead to gastrointestinal dysfunction, neuroinflammation, and neurodegeneration of the central nervous system (CNS) through the disordered microbiota-gut-brain axis. The present review aimed to summarize recent advancements in studies focusing on the role of the microbiota-gut-brain axis in the pathogenesis of PD, especially the mechanism of intestinal microbiome dysregulation, intestinal inflammation, and gastrointestinal dysfunction in PD. Maintaining or restoring homeostasis in the gut microenvironment by targeting the gut microbiome may provide future direction for the development of new biomarkers for early diagnosis of PD and therapeutic strategies to slow disease progression.

Cx43-Delivered miR-181b Negatively Regulates Sirt1/FOXO3a Signalling Pathway-Mediated Apoptosis on Intestinal Injury in Sepsis.

INTRODUCTION: Gap junctions can transmit signals between cells, including miRNAs, leading to the amplification of adjacent cell damage. No previous study has addressed gap junctions and miRNAs in sepsis because the internal mechanism of sepsis-induced intestinal injury is complex. Therefore, we studied the relationship between connexin43 (Cx43) and miR-181b and provided a research direction for further study of sepsis. METHODS: A mouse caecal ligation and puncture method was used to construct a mouse sepsis model. Firstly, damage to intestinal tissues at different time points was analysed. The levels of Cx43, miR-181b, Sirt1, and FOXO3a in intestinal tissues and the transcription and translation of the apoptosis-related genes Bim and puma, which are downstream of FOXO3a were analysed. Secondly, the effect of Cx43 levels on miR-181b and Sirt1/FOXO3a signalling pathway activity was explored by using the Cx43 inhibitor heptanol. Finally, luciferase assays were used to determine miR-181b binding to the predicted target sequence. RESULTS: The results show that during sepsis, intestinal injury becomes increasingly worse with time, and the expression of Cx43 and miR-181b increase. In addition, we found that heptanol could significantly reduce intestinal injury. This finding indicates that inhibiting Cx43 regulates the transfer of miR-181b between adjacent cells, thereby reducing the activity of the Sirt1/FOXO3a signalling pathway and reducing the degree of intestinal injury during sepsis. CONCLUSIONS: In sepsis, the enhancement of Cx43 gap junctions leads to an increase in miR-181b intercellular transfer, affects the downstream SIRT1/FOXO3a signalling pathway and causes cell and tissue damage.

Interactions between Macrophages and Biofilm during Staphylococcus aureus-Associated Implant Infection: Difficulties and Solutions.

Staphylococcus aureus (S. aureus) biofilm is the major cause of failure of implant infection treatment that results in heavy social and economic burden on individuals, families, and communities. Planktonic S. aureus attaches to medical implant surfaces where it proliferates and is wrapped by extracellular polymeric substances, forming a solid and complex biofilm. This provides a stable environment for bacterial growth, infection maintenance, and diffusion and protects the bacteria from antimicrobial agents and the immune system of the host. Macrophages are an important component of the innate immune system and resist pathogen invasion and infection through phagocytosis, antigen presentation, and cytokine secretion. The persistence, spread, or clearance of infection is determined by interplay between macrophages and S. aureus in the implant infection microenvironment. In this review, we discuss the interactions between S. aureus biofilm and macrophages, including the effects of biofilm-related bacteria on the macrophage immune response, roles of myeloid-derived suppressor cells during biofilm infection, regulation of immune cell metabolic patterns by the biofilm environment, and immune evasion strategies adopted by the biofilm against macrophages. Finally, we summarize the current methods that support macrophage-mediated removal of biofilms and emphasize the importance of considering multi-dimensions and factors related to implant-associated infection such as immunity, metabolism, the host, and the pathogen when developing new treatments.

Synthetic neutrophil extracellular traps dissect bactericidal contribution of NETs under regulation of α-1-antitrypsin.

Deciphering the complex interplay of neutrophil extracellular traps (NETs) with the surrounding environment is a challenge with notable clinical implications. To bridge the gap in knowledge, we report our findings on the antibacterial activity against Pseudomonas aeruginosa of synthetic NET-mimetic materials composed of nanofibrillated DNA-protein complexes. Our synthetic system makes component-by-component bottom-up analysis of NET protein effects possible. When the antimicrobial enzyme neutrophil elastase (NE) is incorporated into the bactericidal DNA-histone complexes, the resulting synthetic NET-like structure exhibits an unexpected reduction in antimicrobial activity. This critical immune function is rescued upon treatment with alpha-1-antitrypsin (AAT), a physiological tissue-protective protease inhibitor. This suggests a direct causal link between AAT inhibition of NE and preservation of histone-mediated antimicrobial activity. These results help better understand the complex and, at times, contradictory observations of in vivo antimicrobial effects of NETs and AAT by excluding neutrophil, cytokine, and chemoattractant contributions.

Single-cell transcriptome reveals Staphylococcus aureus modulating fibroblast differentiation in the bone-implant interface.

BACKGROUND: This study aimed to delineate the cell heterogeneity in the bone-implant interface and investigate the fibroblast responses to implant-associated S. aureus infection. METHODS: Single-cell RNA sequencing of human periprosthetic tissues from patients with periprosthetic joint infection (PJI, n = 3) and patients with aseptic loosening (AL, n = 2) was performed. Cell type identities and gene expression profiles were analyzed to depict the single-cell landscape in the periprosthetic environment. In addition, 11 publicly available human scRNA-seq datasets were downloaded from GSE datasets and integrated with the in-house sequencing data to identify disease-specific fibroblast subtypes. Furthermore, fibroblast pseudotime trajectory analysis and Single-cell regulatory network inference and clustering (SCENIC) analysis were combined to identify transcription regulators responsible for fibroblast differentiation. Immunofluorescence was performed on the sequenced samples to validate the protein expression of the differentially expressed transcription regulators. RESULTS: Eight major cell types were identified in the human bone-implant interface by analyzing 36,466 cells. Meta-analysis of fibroblasts scRNA-seq data found fibroblasts in the bone-implant interface express a high level of CTHRC1. We also found fibroblasts could differentiate into pro-inflammatory and matrix-producing phenotypes, each primarily presented in the PJI and AL groups, respectively. Furthermore, NPAS2 and TFEC which are activated in PJI samples were suggested to induce pro-inflammatory polarization in fibroblasts, whereas HMX1, SOX5, SOX9, ZIC1, ETS2, and FOXO1 are matrix-producing regulators. Meanwhile, we conducted a CMap analysis and identified forskolin as a potential regulator for fibroblast differentiation toward matrix-producing phenotypes. CONCLUSIONS: In this study, we discovered the existence of CTHRC1+ fibroblast in the bone-implant interface. Moreover, we revealed a bipolar mode of fibroblast differentiation and put forward the hypothesis that infection could modulate fibroblast toward a pro-inflammatory phenotype through NPAS2 and TFEC.

Intermuscular Fat, But Not Subcutaneous Fat, Correlated With Major Complications After Primary Total Hip Arthroplasty.

RATIONALE AND OBJECTIVES: To investigate the relationship between upper-thigh intermuscular fat, subcutaneous fat measured by CT and major complications after primary total hip arthroplasty (THA). MATERIALS AND METHODS: Between 2015 and 2021, consecutive patients who had primary THA and preoperative hip CT were retrospectively included. Upper-thigh muscle cross-sectional intermuscular fat, subcutaneous fat, and muscle area were measured on hip CT images. The major complications included dislocation, aseptic loosening, infection, and periprosthetic fracture. The effect of upper-thigh intermuscular fat, subcutaneous fat and muscle area on the outcome was analyzed using multivariable cox proportional hazards analysis. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 3028 patients were included and 71 (2.34%) of them had major complications. During a median of 25 months of follow-up, patients showed increased incidence of total major complications with increased intermuscular fat area (log-rank p = 0.012). The multivariable cox regression revealed that per SD increment in intermuscular fat area was associated with higher risk of total major complications (HR = 2.04, 95% CI = 1.71-2.43, p < 0.001), dislocation (HR = 1.96, 95% CI = 1.44-2.66, p < 0.001), aseptic loosening (HR = 2.02, 95% CI = 1.30-3.16, p = 0.002), infection (HR = 1.94, 95% CI = 1.24-3.05, p = 0.004), and periprosthetic fracture (HR = 2.26, 95% CI = 1.67-3.07, p < 0.001). CONCLUSION: Upper-thigh intermuscular fat, but not subcutaneous fat measured on CT associated with the risk of major complications after primary THA.

Scrutinizing particle size related bond strengthening in anatase TiO2.

A series of small, middle, and large anatase TiO2 particles were synthesized through the hydrolysis of titanium tetraisopropoxide (TTIP) to investigate the size-related chemical bond length and strength variation. Unit cell volume contraction with decreasing particle size is identified from Rietveld refinement of high-resolution synchrotron powder X-ray diffraction (PXRD) patterns. More titanium vacancies are also found for smaller anatase particles. Contrary to the variation in unit cell volume, a larger Debye temperature ΘD(TiO2) derived from the linear and nonlinear fitting of atomic displacement parameters (Uiso(TiO2)) as a function of temperature is revealed for smaller anatase particles. The length of the Ti-O bond is also shorter for smaller anatase particles. Furthermore, optical phonon frequencies blue-shifting with the decrease in anatase particle size are determined by Raman spectroscopy. X-ray photoelectron spectroscopy (XPS) analysis rules out the presence of a large amount of Ti3+, while optical diffuse reflectance measurement eliminates the existence of a large number of oxygen vacancies in all particles. Combining the analysis results of PXRD, thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR), more structural and surface hydroxyls (-OH) appear to exist in smaller anatase particles. It is the structural and surface -OH that are responsible for the size-related chemical bond length and strength variation in the as-synthesized anatase particles.

A General Map of Transcriptional Expression of Virulence, Metabolism, and Biofilm Formation Adaptive Changes of Staphylococcus aureus When Exposed to Different Antimicrobials.

Biofilm formation of Staphylococcus aureus is the major cause of implant-associated infections (IAIs). Antimicrobial treatment is one of the most effective therapeutic options for S. aureus infections. However, it can also lead to adaptive transcriptomic changes due to extreme selective pressure, which may increase the risk of antimicrobial resistance. To study the transcriptional changes in S. aureus upon exposure to antimicrobial agents, we obtained expression profiles of S. aureus treated with six antimicrobials (flucloxacillin, vancomycin, ciprofloxacin, clindamycin, erythromycin, and linezolid, n = 6 for each group). We also included an untreated control group (n = 8) downloaded from the Gene Expression Omnibus (GEO) database (GSE70043, GSE56100) for integrated bioinformatic analyses. We identified 82 (44 up, 38 down) and 53 (17 up, 36 down) differentially expressed genes (DEGs) in logarithmic and stationary phases, respectively. When exposed to different antimicrobial agents, we found that manganese import system genes and immune response gene sbi (immunoglobulin G-binding protein Sbi) were upregulated in S. aureus at all stages. During the logarithmic phase, we observed adaptive transcriptomic changes in S. aureus mainly in the stability of protein synthesis, adhesion, and biofilm formation. In the stationary phase, we observed a downregulation in genes related to amino biosynthesis, ATP synthesis, and DNA replication. We verified these results by qPCR. Importantly, these results could help our understanding of the molecular mechanisms underlying the proliferation and antimicrobial resistance of S. aureus.

The Temporal Impact of Prosthesis Implantation and Semi-Quantitative Criteria on the Diagnostic Efficacy of Triple-Phase Bone Scanning for Periprosthetic Joint Infection.

OBJECTIVE: To evaluate the diagnostic efficacy of triple-phase bone scanning and the temporal impact of prosthesis implantation on the diagnostic efficacy of triple-phase bone scanning for periprosthetic joint infection (PJI). METHODS: Patients who were admitted to our hospital for joint pain and dysfunction after total joint arthroplasty between 2014 and 2020 were retrospectively included. Triple-phase bone scanning was performed, and the blood pool images were evaluated to obtain the semi-quantitative criteria. The patients were then grouped into six groups according to the time interval from index primary arthroplasty to triple-phase bone scanning. We examined whether there were significant differences in sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy between the groups. RESULTS: Overall, 66 patients who underwent total hip arthroplasty (THA) and 74 patients who underwent total knee arthroplasty (TKA) were analyzed. No significant differences were observed between visual analysis and semi-quantitative measurement in terms of sensitivity, specificity, PPV, NPV, and accuracy. For patients with a time interval from prosthesis implantation to bone scanning of >1 year, visual analysis had a higher PPV (100%) in patients who underwent THA and the use of semi-quantitative criteria had a higher NPV (85.7%) in patients who underwent TKA. CONCLUSION: The semi-quantitative criteria showed no advantages in the diagnosis of PJI. In addition, triple-phase bone scanning demonstrated good clinical diagnostic efficacy when the time interval from prosthesis implantation to bone scanning was >1 year.

The intestinal microbiota influences the microenvironment of metastatic colon cancer by targeting miRNAs.

This study aimed to investigate the molecular mechanisms through which the intestinal microbiota and microRNAs (miRNAs) participate in colon cancer metastasis. Intestinal flora data, and the GSE29621 (messenger RNA/long non-coding RNA [mRNA/lncRNA]) and GSE29622 (miRNA) datasets, were downloaded from The Cancer Gene Atlas and Gene Expression Omnibus databases, respectively. Immune-related cells in M1 vs. M0 samples were analyzed using the Wilcoxon test. Furthermore, an lncRNA-miRNA-mRNA (competing endogenous RNA [ceRNA]) network was constructed, and survival analysis of RNAs in the network was performed. A total of 16 miRNA-genus co-expression pairs containing eight microbial genera and 15 miRNAs were screened; notably, Porphyromonas and Bifidobacterium spp. were found to be associated with most miRNAs, and has-miR-3943 was targeted by most microbial genera. Furthermore, five immune cell types, including activated natural killer cells, M1 macrophages, resting mast cells, activated mast cells and neutrophils, were differentially accumulated between the M1 and M0 groups. Enrichment analysis suggested that mRNAs related to colon cancer metastasis were mainly involved in pathways related to bacterial and immune responses. Survival analysis revealed that TMEM176A and PALM3 in the ceRNA network were significantly associated with the prognosis of patients with colon cancer. In conclusion, this study revealed a potential mechanism by which the intestinal microbiota influences the colon cancer microenvironment by targeting miRNAs.