In the modern era, the expanding demand for implants has transformed the healthcare system by restoring and enhancing the function of various biological structures, thereby increasing the patients’ quality of life. These include urinary catheters, dental, orthopedic, cardiovascular implants, and sutures designed to perform various functions. However, these devices are more prone to microbial attack, contributing to biofilm formation mainly caused by multidrug-resistant ESKAPE pathogens, thereby increasing the risk of implant-associated infections and implant failure. This review summarizes the diverse array of implants available on the market and their associated infections caused by biofilm-producing pathogens, with a particular emphasis on the ESKAPE pathogen. Specific keywords were used to conduct a literature review using Google Scholar, Web of Science, PubMed, and Scopus databases. The data were then screened and integrated to explore the underlying principles of biofilm formation, its consequences, diagnostic approaches, and therapeutic studies. Currently, various methods are employed to diagnose these infections, including culture-based methods (tissue swab, culture, sonication) and non-culture methods (Dithiothreitol, XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide), Resazurin, BioTimer assays, and PCR). However, these studies indicate an increased difficulty in detecting infections caused by ESKAPE pathogens due to biofilm formation, highlighting the need for developing novel strategies. The recent advancements in the development of antimicrobial coatings, implant surface modifications, phage therapy, nanoparticles, antimicrobial peptides, and quorum-sensing inhibitors have shown promise in controlling these infections. Thus, these findings underscore the importance of research on innovative approaches and the development of infection-resistant implants, thereby reducing the clinical burden and improving patient outcomes.

Objective To investigate the role of the iron-sulfur cluster assembly factor SFU1 in the virulence-related traits of Candida albicans , particularly its function within the cariogenic cross-kingdom biofilm formed with Streptococcus mutans . Methods The SFU1 deletion and complemented strains were constructed. Their effects on growth, acid production, morphogenesis, metabolic activity, ROS accumulation, and biofilm formation of C. albicans were evaluated. The roles of SFU1 in the development, architecture, and spatial distribution of the C. albicans-S. mutans dual-species biofilm were further analyzed. The cariogenic metabolite profile and matrix synthesis were assessed by measuring lactic acid production, lactate dehydrogenase activity, extracellular polysaccharide content, and expression levels of related genes. Results The SFU1 deletion strain exhibited inhibited hyphal formation, reduced metabolic activity, elevated intracellular ROS levels, impaired biofilm formation, and downregulated expression of hyphal and adhesion-related genes ( ALS3, EFG1, UME6 ). In the cross-kingdom biofilm, the sfu1/sfu1 mutant failed to form hyphal networks, resulting in loose biofilm architecture, reduced biomass, and poor integration of S. mutans . Furthermore, the dual-species biofilm showed significantly decreased lactic acid and EPS production. Co-cultured S. mutans exhibited downregulated expression of EPS synthesis genes ( gtfB/C ) and upregulated expression of EPS degradation genes ( dexA/B ). Conclusion SFU1 modulates hyphal development, redox homeostasis, and biofilm formation in C. albicans , thereby profoundly affecting its pathogenic synergy with S. mutans . SFU1 deletion leads to disrupted architecture and attenuated cariogenic virulence of the dual-species biofilm. This study reveals the potential value of targeting fundamental metabolic pathways in C. albicans to interfere with the cariogenicity of cross-kingdom biofilms, and provides a novel perspective for the prevention and therapy of dental caries.

Background Psittacosis pneumonia, which is caused by Chlamydia psittaci, is a systemic inflammatory disease that often results in injury to multiple organs. Although liver and heart involvement are recognized, the incidence, risk factors, and predictors for acute kidney complications are not well known. Methods Our retrospective cohort study included 123 patients, comprising 47 individuals diagnosed with psittacosis pneumonia and 76 individuals with typical community-acquired pneumonia (CAP). These patients were admitted to Nanjing First Hospital, affiliated with Nanjing Medical University, between June 2019 and July 2024. The study conducted an analysis of clinical profiles, laboratory markers, and patient outcomes. The predictive efficacy of the Blood Urea Nitrogen to Albumin Ratio (BAR) and Lactate Dehydrogenase (LDH) in forecasting acute kidney injury (AKI) was assessed through the application of receiver operating characteristic (ROC) curve analysis. Results In comparison to typical CAP, psittacosis pneumonia is characterized by markedly elevated systemic inflammation, as evidenced by increased levels of procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6 (IL-6). Additionally, it presents with more severe lymphocytopenia, hypoalbuminemia, and extensive multi-organ damage, with a pronounced impact on hepatic and myocardial tissues. The incidence of AKI was significantly greater in the psittacosis group compared to the control group (34.0% versus 12.1%, P= 0.003). In the psittacosis cohort, AKI demonstrated an independent association with increased levels of LDH ( P = 0.01) and the BAR ( P < 0.001), whereas no such association was observed with traditional inflammatory markers. The BAR (AUC = 0.88) and LDH (AUC = 0.79) demonstrated effective predictive capabilities for AKI, with their combined application enhancing sensitivity to 85.71% and specificity to 87.50%. The implementation of targeted therapy using omadacycline resulted in prompt clinical and biochemical improvements across all patients. Conclusion Psittacosis pneumonia constitutes a distinct systemic immuno-inflammatory syndrome that presents a significant risk for AKI. The composite biomarker BAR and the cellular injury marker LDH demonstrate superior predictive capabilities for AKI compared to traditional inflammatory indices, thereby providing accessible tools for early risk stratification. These findings emphasize the necessity of recognizing psittacosis as a unique clinical entity and advocate for vigilant monitoring of renal function in affected patients.

Background To develop a new non-invasive screening method for sepsis by detecting urine samples. Methods A prospective study was conducted to collect urine samples from a cohort of 22 individuals diagnosed with sepsis and admitted to the Intensive Care Unit (ICU) of a university-affiliated teaching hospital in China. Utilizing proteomic and bioinformatics analyses, we sought to identify potential biomarkers indicative of sepsis. These biomarkers were subsequently validated using serum and urine samples from 31 patients with septic shock, 83 patients with sepsis, and 50 healthy controls. Receiver operating characteristic (ROC) curves were employed to determine the optimal cutoff values for these biomarkers. Based on the diagnostic thresholds derived from ROC analysis, colloidal gold test strips were developed and applied to screen a cohort of 92 ICU patients. The diagnostic accuracy of these test strips was rigorously assessed by comparing their results with those from immunofluorescence assays. Results Data-independent acquisition (DIA) proteomics analysis of urine samples identified 2,846 proteins, with stringent filtration criteria (fold change > 2 or < 0.5, P-value < 0.05) yielding 178 differentially expressed proteins (DEPs). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed significant enrichment of DEPs in pathways associated with “cell adhesion molecules,” “lysosomes,” and metabolic processes. The Boruta algorithm, integrating Random Forest and Support Vector Machine (SVM) analysis, identified urinary thrombomodulin (TM) as a key candidate molecule. Immunofluorescence analysis for validation trial showed rising trend in blood TM levels across disease severities: 7.55 (6.58-8.72) TU/mL in healthy controls, 10.08 (8.00-14.15) TU/mL in general sepsis, and 12.30 (7.54-18.68) TU/mL in septic shock. Conversely, urinary TM levels decreased: 23.65 (18.08-31.06) TU/mL, 17.70 (13.80-28.80) TU/mL, and 5.84 (4.00-11.59) TU/mL, respectively. At a urinary TM threshold of 15.46 TU/mL, the ROC AUC for sepsis diagnosis is 0.72, with 57% sensitivity and 88% specificity (P<0.05), showing no significant difference comparable to blood TM (P>0.05). For septic shock diagnosis and 28-day mortality prediction, a urinary TM threshold of 11.85 TU/mL yields an ROC AUC of 0.92, with 93% sensitivity and 81% specificity, outperforming blood TM (P<0.05). A urinary TM colloidal gold test strip, which turns red at TM levels above 15.46 TU/mL, was developed and validated on urine samples from 43 sepsis and 49 non-sepsis patients, achieving 86.1% sensitivity, 77.6% specificity and an overall accuracy of 81.5% for sepsis diagnosis. The Kappa test validated the concordance of the colloidal gold strip test with Sepsis 3.0 diagnostic criteria, while the McNemar test indicated no significant difference in sepsis diagnosis efficacy between the strip test and chemiluminescent immunofluorescence (p=0.228). Conclusions The utilization of urine test strips for the detection of TM offers a precise, convenient, and practical method for the screening of sepsis.

Background The carbapenem antibiotic meropenem is often used to treat life-threatening infections caused by Pseudomonas aeruginosa . Previous studies have shown that the susceptibility of P. aeruginosa to carbapenems is differentially regulated by the RNA chaperone Hfq, depending on the availability of preferred or less preferred carbon sources, a mechanism known as carbon catabolite repression (CCR). In this regulation, Hfq plays a CCR-conditioned repressive role on outer membrane porins that act as entry ports for carbapenems. In this study, we investigated whether meropenem response is modulated by the second messenger c-di-GMP, which is known to regulate several bacterial functions. Methods We used P. aeruginosa strains with high or low c-di-GMP levels and their Hfq-deficient derivatives to assess the role of c-di-GMP in modulating meropenem susceptibility and tolerance. Results We show that low intracellular c−di−GMP levels increase meropenem resistance and tolerance at sub−inhibitory concentrations, whereas high c−di−GMP diminishes both traits. Importantly, c−di−GMP status shapes the entire response trajectory, from exponential growth to the stationary phase. Furthermore, we show that c-di-GMP modulates meropenem response through mechanism(s) independent of Hfq-mediated porin repression and exerts a dominant effect over CCR-driven regulation. Conclusion This study supports the notion that P. aeruginosa meropenem susceptibility and tolerance are modulated by intracellular c-di-GMP concentrations, with low c-di-GMP levels promoting higher fitness. Our findings indicate that c-di-GMP exerts its regulatory effect through mechanisms distinct from Hfq-mediated porin control, underscoring the existence of parallel regulatory pathways that shape antibiotic response.

Objective The increasing antimicrobial resistance in non-typhoidal Salmonella (NTS) poses a growing challenge to clinical therapy. This study reports, for the first time, a carbapenem-resistant Salmonella enterica serovar Derby isolate. Although serovar Derby accounts for a relatively small proportion of clinical NTS infections, elucidating the mechanism, origin, and dissemination potential of its carbapenem resistance is crucial for enhancing surveillance and prevention strategies against resistant NTS. Methods Antimicrobial susceptibility testing was performed using commercial broth microdilution panels with the Beckman Coulter WalkAway 96 PLUS system. Whole-genome sequencing (WGS) and S1-pulsed-field gel electrophoresis (PFGE) were employed to characterize the chromosomes and plasmids of isolates. Conjugation assays were conducted to evaluate plasmid mobility. Additionally, the NCBI Genome and Pathogens databases were used to identify carbapenemase-producing Salmonella strains. Results A patient with aplastic anemia was admitted with abdominal pain and received successive treatments. During periods of recurrent fever, carbapenem-resistant S. Derby (CS_CRSA) and Escherichia coli (CS_CREco) were isolated from rectal swabs. WGS revealed that both strains carried a nearly identical IncFII plasmid (80,195/80,198 bp) harboring bla NDM-1 and qnrS1 genes. This plasmid contained a complete conjugation module, and could be transferred from CS_CRSA and CS_CREco to the recipient at efficiencies of (4.50 ± 1.29)×10 −2 and (3.17 ± 0.74)×10 −1 . Comparative analysis showed its high similarity to a resistance plasmid of Salmonella enterica serovar Typhimurium isolated from Zhejiang, China. As of June 25, 2025, 35 fully assembled Salmonella enterica strains carrying carbapenemase genes were identified, predominantly S. Typhimurium and its variants. Phylogenetic analysis indicated that most carbapenemase-producing Salmonella (CPSA) strains were scattered, while clonal dissemination was observed in some serotypes. Conclusion This study reports a clinical isolate of carbapenem-resistant S. Derby, likely resulting from horizontal transfer of a bla NDM-1 - carrying plasmid, which indicates that carbapenem resistance is extending to less common and low virulence serovars of Salmonella . The emergence of such strains poses a challenge to patient care, especially for immunocompromised populations suffering from invasive infections. Additionally, clonal dissemination of CPSA in certain serotypes warrants heightened vigilance and preventive measures.

Introduction Preterm infants exhibit heightened vulnerability to morbidity and mortality due to their underdeveloped immune systems and immature gastrointestinal tract. The gut microbiota plays a pivotal role in neonatal health, yet its establishment is influenced by multiple factors, including prematurity, antibiotic exposure, and feeding modalities. This study aimed to examine the interactions among gut bacteriophages, bacterial communities, and clinical variables in preterm infants to identify potential microbial biomarkers associated with health outcomes. Methods We employed metagenomic shotgun sequencing and co-occurrence network analysis to characterize the virome and bacterial communities in 12 preterm neonates at 14 and 28 days post-birth. This approach enabled the identification of dynamic microbial colonization patterns and key bacterial species and bacteriophages associated with clinical parameters. Results Staphylococcus epidermidis exhibited a significant decline over time, whereas Enterococcus faecalis and its associated bacteriophages showed progressive enrichment, becoming predominant by day 28. In contrast, the relative abundances of Clostridioides difficile and Klebsiella pneumoniae remained statistically stable between the two time points (14 vs. 28 days). Discussion These findings suggest that microbial changes during the first month of life may reflect a combination of host developmental processes and external influences, such as antibiotic exposure or delivery mode. The observed microbial signatures provide preliminary insights into early gut microbiota and virome development in preterm infants. However, their functional relevance and long-term stability require confirmation in larger, well-powered longitudinal studies with denser temporal sampling. The enrichment of Enterococcus faecalis may indicate its opportunistic colonization potential in the preterm gut and warrants further investigation regarding its role in gut homeostasis and immune system maturation.

Introduction Antibiotic resistance poses a critical and escalating global health crisis, leading to higher morbidity and mortality associated with infectious diseases. This problem is significantly exacerbated by intracellular bacterial pathogens, which are often shielded from conventional antibiotics and foster the emergence of persister populations. Recently, host-directed therapy (HDT) has been emerging as a promising strategy that aims to modulate host cellular processes or immune responses to enhance bacterial clearance. Nonetheless, the inherent complexity of host biology makes identifying appropriate and safe modulators challenging, unpredictable, and highly complicated. Methods Here, we present a cell-based high-throughput screen (HTS), coupled with an intracellular-induced reporter that was used to screen a library of nearly 37,000 small molecules with potentially pharmacological activity for compounds that inhibit host cell infection by intracellular pathogens. Results and discussion This multistage, screening protocol resulted in the identification of eight non-cytotoxic compounds that efficiently inhibited the intracellular growth of the Gram-negative bacterium Salmonella Typhimurium in human epithelial cells by ~2.5- to 6-fold, without inhibiting Salmonella growth in culture. Five of these eight molecules were also effective in controlling the intracellular replication of Salmonella in primary mouse macrophages by 1.5- to 38-fold. Strikingly, seven hits also inhibited the intracellular growth of the Gram-positive bacterial pathogen Listeria monocytogenes in epithelial cells by 1.5- to 10-fold. The structure–activity relationship approach successfully identified chemical analogs of one hit with enhanced biological activity as infection inhibitors. Overall, we describe a robust HTS platform that can be adapted for screening of compound libraries against other pathogens, and suggest that the identified compounds are potential candidates for downstream development of novel drugs against intracellular bacterial infections.

Background Anisakid nematodes, particularly the third-stage larvae (L3) of Hysterothylacium thalassini , pose a significant zoonotic risk associated with the consumption of fish. Ingestion of infected fish can trigger oxidative stress, inflammatory responses, and tissue damage in mammalian hosts. The growing incidence of anisakid infections necessitates the exploration of natural therapeutic agents with antioxidant and immunomodulatory properties. Terfezia claveryi , a desert truffle widely consumed in Saudi Arabia, is recognized for its rich phytochemical composition and potential bioactivity, making it a promising candidate for mitigating oxidative damage caused by parasites. Aim This study aimed to evaluate the therapeutic efficacy and antioxidant potential of Terfezia claveryi extract (TCE) against oxidative stress and splenic pathology induced by H. thalassini L3 infection in experimental mice. Methods A methanol–water extract of T. claveryi was prepared and analyzed for its phytochemical constituents using Fourier Transform Infrared (FT-IR) spectroscopy and colorimetric assays. Male C57BL/6 mice were divided into control and infected groups, with infection induced using fresh, thermally processed, or frozen L3 larvae. TCE was administered orally at a dose of 250 mg/kg. Antioxidant status in spleen tissues was evaluated through enzymatic assays for catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione (GSH), while oxidative stress markers—malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), and nitric oxide (NO)—were quantified in spleen samples. Histopathological examination of spleen tissues was performed, and inducible nitric oxide synthase (iNOS) expression was analyzed by qPCR and ELISA. Results Phytochemical screening of TCE revealed high phenolic content (46.72 ± 2.43 µg/ml), alongside measurable levels of flavonoids and tannins, confirming its strong antioxidant capacity. Infection with H. thalassini larvae caused pronounced splenic degeneration, congestion, and capsule thinning, accompanied by decreased antioxidant enzyme activities and GSH levels, and elevated oxidative markers (MDA, H 2 O 2 , NO). TCE treatment significantly restored antioxidant enzyme activities, reduced oxidative stress biomarkers, and improved splenic histoarchitecture. Moreover, iNOS gene and protein expression were markedly downregulated following TCE administration, indicating anti-inflammatory modulation. Conclusion T. claveryi extract exhibits potent antioxidant and immunomodulatory effects that mitigate oxidative damage and inflammatory stress induced by H. thalassini infection in mice. Although the extract does not target the parasite burden directly, its ability to restore oxidant–antioxidant balance and modulate host immune responses suggests a valuable supportive or adjunctive role in reducing infection-associated tissue injury and immunopathology. These findings indicate that desert truffle–derived bioactive compounds may serve as natural complementary agents to limit oxidative and inflammatory complications associated with anisakid infections and warrant further investigation in combination with antiparasitic therapies.

Objective Diabetic foot ulcers (DFUs) represent a serious diabetic complication requiring effective therapeutic interventions. This systematic review and meta-analysis evaluates the clinical outcomes and safety profile of antibiotic-loaded bone cement (ALBC), an innovative localized drug delivery approach, for managing DFU patients. Methods From their inception through October 2025, a comprehensive literature search was conducted across multiple databases including PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM Database. Our analysis focused exclusively on randomized clinical trials that compared ALBC therapy with standard treatment protocols in diabetic foot cases. The primary endpoints assessed were wound healing time and clinical effective rate. Secondary outcome measures encompassed length of hospitalization, surgical intervention frequency, visual analog scale (VAS) for pain assessment, and limb preservation rates. Statistical analysis was performed using R statistical software with random-effects modeling to account for potential heterogeneity. Results 22 RCTs involving 1,295 patients were included. All studies were conducted in China. Pooled analysis demonstrated that ALBC significantly shortened wound healing time (Mean Difference [MD] = -7.10 days, 95% CI: -12.88 to -1.32, p = 0.016, I² = 96%) and improved the clinical effective rate (Odds Ratio [OR] = 4.05, 95% CI: 2.70 to 6.07, p < 0.001, I² = 9.9%) compared to control. Furthermore, ALBC reduced the number of surgeries. The standardized mean difference (SMD) was -1.88, with a 95% CI from -3.29 to -0.47. It also reduced hospital stay, with a mean difference (MD) of -8.56 days and a 95% CI from -12.33 to -4.79. The VAS pain score was reduced, with an SMD of -1.29 and a 95% CI from -1.89 to -0.69. Additionally, the amputation rate was reduced, with an odds ratio (OR) of 0.19 and a 95% CI from 0.07 to 0.50. Subgroup and sensitivity analyses generally supported the robustness of these findings. No significant publication bias was detected. Conclusion Antibiotic-loaded bone cement (ALBC) therapy demonstrates significant efficacy and safety in managing diabetic foot ulcers, promoting rapid tissue regeneration while minimizing adverse effects. This intervention correlates with enhanced wound closure rates, diminished pain perception, decreased surgical intervention frequency, reduced hospitalization duration, and lower extremity amputation incidence. Current evidence substantiates the clinical implementation of ALBC therapy; however, additional rigorously designed investigations are warranted to strengthen the external validity of these findings across diverse patient populations.