Divergent Flowering Time Responses to Increasing Temperatures Are Associated With Transcriptome Plasticity and Epigenetic Modification Differences at FLC Promoter Region of Arabidopsis thaliana.

Understanding the genetic, and transcriptomic changes that drive the phenotypic plasticity of fitness traits is a central question in evolutionary biology. In this study, we utilised 152 natural Swedish Arabidopsis thaliana accessions with re-sequenced genomes, transcriptomes and methylomes and measured flowering times (FTs) under two temperature conditions (10°C and 16°C) to address this question. We revealed that the northern accessions exhibited advanced flowering in response to decreased temperature, whereas the southern accessions delayed their flowering, indicating a divergent flowering response. This contrast in flowering responses was associated with the isothermality of their native ranges, which potentially enables the northern accessions to complete their life cycle more rapidly in years with shorter growth seasons. At the transcriptome level, we observed extensive rewiring of gene co-expression networks, with the expression of 25 core genes being associated with the mean FT and its plastic variation. Notably, variations in FLC expression sensitivity between northern and southern accessions were found to be associated with the divergence FT response. Further analysis suggests that FLC expression sensitivity is associated with differences in CG, CHG and CHH methylation at the promoter region. Overall, our study revealed the association between transcriptome plasticity and flowering time plasticity among different accessions, providing evidence for its relevance in ecological adaptation. These findings offer deeper insights into the genetics of rapid responses to environmental changes and ecological adaptation.

Eliminating the effect of pH: Dual-matrix modulation adsorbent enables efficient lithium extraction from concentrated seawater.

Lithium ion sieve adsorbents frequently extract liquid lithium resources due to their adsorption effect and cost advantages. However, the adsorption effect is significantly influenced by the ambient pH. The pH effects on the adsorption process can be categorized into two main areas: the competition adsorption of impurity ions and the difference in surface zeta potential. A dual-matrix modulation adsorbent was prepared, comprising a carrier matrix modified with zwitterionic quaternary ammonium bases and an adsorption matrix modified with carboxylation. The zwitterionic quaternary ammonium base groups were employed to mitigate the competitive adsorption of impurity ions by acid-base neutralization. Furthermore, the negative charge of carboxyl groups was employed to diminish the discrepancy in surface zeta potential. The adsorption effect of the ion sieve adsorbent under natural conditions appeared to be significantly enhanced by the dual-matrix modulation, with the saturated adsorption capacity (28 mg/g) and adsorption selectivity (α(Li+/Mg2+)=24.23) being 6.3 and 7.8 times higher than that of the manganese-based adsorbent (HMO) under the same conditions, respectively. Moreover, the adsorption effect was found to be consistent with HMO under alkaline conditions. The results demonstrate that by optimizing the adsorption conditions of the adsorbent, the detrimental impact of pH on the adsorption process of lithium ion sieves can be eliminated.

NBCR-ac4C: A Deep Learning Framework Based on Multivariate BERT for Human mRNA N4-Acetylcytidine Sites Prediction.

N4-acetylcytidine (ac4C) plays a crucial role in regulating cellular biological processes, particularly in gene expression regulation and disease development. However, experiments to identify ac4C in a wet lab are time-consuming and costly, and the learning-based methods struggle to capture the underlying semantic knowledge and relations within sequences. To address this, we propose a deep learning approach called NBCR-ac4C based on pretrained models. Specifically, we employ Nucleotide Transformer and DNABERT2 to construct contextual embedding of nucleotide sequences, which effectively mine and express context relations between different features in the sequence. Convolutional neural network (CNN) and ResNet18 are then applied to further extract shallow and deep knowledge from context embedding. Depending on extensive experiments for the prediction of ac4C sites in nucleotide sequences, we observe that NBCR-ac4C outperforms general learning-based models. It achieves the highest accuracy (ACC) of 83.51% and an Area Under the Receiver Operating Characteristic Curve (AUROC) of 89.58% on an independent test set. Moreover, the proposed model, compared to the current state-of-the-art (SOTA) model LSA-ac4C, demonstrates higher ACC and AUROC by 0.81-3.7% and 0.05-1.58%, respectively. The data set and code are available on https://github.com/2103374200/NBCR to facilitate further discussion on NBCR-ac4C.

Mediating role of accelerated aging in the association between depression and mortality risk: findings from NHANES.

OBJECTIVE: To investigate the association between depression, accelerated biological aging, and mortality risk, and to assess whether accelerated aging mediates the relationship between major depression and mortality risk. METHODS: A prospective cohort of 12,761 participants aged 20 years or older from the 2005-2010 cycle of the National Health and Nutrition Examination Survey (NHANES) was analyzed. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores of ≥ 10 indicating major depression. Accelerated biological aging was measured using phenotypic age acceleration (PhenoAgeAccel). Multivariable linear regression models and subgroup analyses were used to examine the association between depression and accelerated aging, while weighted multivariable Cox proportional hazards regression models and subgroup analyses assessed the impact of major depression on mortality risk. Mediation analysis was performed to assess whether PhenoAgeAccel mediated the relationship between major depression and mortality outcomes. RESULTS: Among the 12,761 adults, the weighted mean age was 46.6 years, with 48.8% being male, and 6.9% experiencing major depression. The results showed a positive association between major depression and PhenoAgeAccel (ß: 0.61, 95% CI: 0.06-1.16). Over a median follow-up duration of 11.3 years (interquartile range: 9.9-13.1), major depression was associated with increased all-cause mortality (HR: 1.35, 95% CI: 1.13-1.62) and cardiovascular mortality (HR: 1.73, 95% CI: 1.18-2.54). However, the relationship with cancer mortality was not statistically significant after full adjustment for confounding factors. The mediation analysis further revealed that PhenoAgeAccel accounted for 10.32% and 5.12% of the associations between major depression and all-cause mortality, and cardiovascular mortality, respectively. CONCLUSION: Depression is associated with accelerated aging and contributes to increased all-cause and cardiovascular mortality. Accelerated aging partially mediates the association between major depression and mortality risk. Our findings highlight the urgent need to incorporate mental health care into public health strategies to delay population aging and reduce mortality risk.

Enhanced Benzene Adsorption in Chloro-Functionalized Metal-Organic Frameworks.

The functionalization of metal-organic frameworks (MOFs) to enhance the adsorption of benzene at trace levels remains a significant challenge. Here, we report the exceptional adsorption of trace benzene in a series of zirconium-based MOFs functionalized with chloro groups. Notably, MFM-68-Cl2, constructed from an anthracene linker incorporating chloro groups, exhibits a remarkable benzene uptake of 4.62 mmol g-1 at 298 K and 0.12 mbar, superior to benchmark materials. In situ synchrotron X-ray diffraction, Fourier transform infrared microspectroscopy, and inelastic neutron scattering, coupled with density functional theory modeling, reveal the mechanism of binding of benzene in these materials. Overall, the excellent adsorption performance is promoted by an unprecedented cooperation between chloro-groups, the optimized pore size, aromatic functionality, and the flexibility of the linkers in response to benzene uptake in MFM-68-Cl2. This study represents the first example of enhanced adsorption of trace benzene promoted by -CH···Cl and Cl···π interactions in porous materials.

[Retracted] Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose­derived stem cells into fibroblasts.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical images shown in Fig. 2B and C on p. 896 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published before this paper was received at International Journal of Molecular Medicine (several of which have been retracted). Moreover, the flow-cytometric data shown in Fig. 2A appeared to be potentially anomalous. In view of the fact that the abovementioned data had already apparently been published prior to the submission of this paper to International Journal of Molecular Medicine, the Editor has decided that the article should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 890-900, 2019; DOI: 10.3892/ijmm.2018.4006].

Potential causal and temporal relationship between plasma triglyceride levels and circulating leukocyte.

BACKGROUND: Circulating triglyceride (TG) and leukocytes, the main components of the vascular system, may impact each other and co-fuel atherosclerosis. While the causal relationship between plasma TG levels and leukocyte counts remains unclear. METHODS: Bidirectional mendelian randomisation (MR) analysis was conducted to investigate the potential causal relationship between TG levels and the counts of leukocytes and their subtypes. A cross-lagged panel model (CLPM) using a longitudinal healthy screening data (13,389 adults with an follow-up of 4 years) was fitted to examine the temporal relationship between them. RESULTS: Genetically predicted plasma TG levels were positively associated with total leukocyte counts (TLC) [ß(se)=0.195(0.01)], lymphocyte counts (LC) [ß(se)=0.196(0.019)], and neutrophill counts (NC) [ß(se)=0.086(0.01)], which remained significant after adjusting for several confounders. Inversely, the genetically predicted TLC [ß(se)=0.033(0.008)], LC [ß(se)=0.053(0.008)], and NC [ß(se)=0.034(0.008)] were positively associated with plasma TG levels. However, when all three of them were put into the MR model adjusted for each other, only LC was significantly associated with TG levels. There was no association between genetically predicted TG levels and monocyte counts (MC), basophil counts, and eosinophill counts. The results of CLPM showed that the temporal effect of elevated TLC, MC, LC, and NC on plasma TG levels were stronger than the inverse effect. CONCLUSION: Our findings suggesting a causal associations of plasma TG levels with TLC, LC, and NC. In turn, LC was positively associated with plasma TG levels. Additionally, elevated circulating LC may precede high plasma TG levels.

Effect of mitochondrial translocator protein TSPO on LPS-induced cardiac dysfunction.

INTRODUCTION: Sepsis-induced cardiac dysfunction is one of the most serious complications of sepsis. The mitochondrial translocator protein (TSPO), a mitochondrial outer membrane protein, is widely used as a diagnostic marker of inflammation-related diseases and can also lead to the release of inflammatory components. However, whether TSPO has a therapeutic effect on sepsis-induced cardiac dysfunction is unclear. OBJECTIVES: The aim of this study is to investigate the involvement of TSPO in the pathogenesis of sepsis-induced cardiac dysfunction and elucidate its underlying mechanism, as well as develop therapeutic strategies targeting TSPO for the prevention and treatment of sepsis-induced cardiac dysfunction. METHODS: The sepsis-induced cardiac dysfunction model was established by intraperitoneal injection of lipopolysaccharide (LPS)in C57BL/6 mice (LPS-induced cardiac dysfunction, LICD). TSPO knockout mice were constructed,and the effects of TSPO was detected by survival rate, echocardiography, HE staining, mitochondrial electron microscopy, TUNEL staining. TSPO-binding proteins were identified by co-immunoprecipitation and mass spectrometry. The mechanisms underlying between TSPO and voltage-dependent anion channel (VDAC) was studied through western blot and immunofluorescence. Proteolysis-Targeting Chimeras (PROTAC) technology was used to construct TSPO-PROTAC molecules that can degrade TSPO. RESULTS: Our present study found that LPS increased cardiac TSPO expression. Knockout of TSPO in C57BL/6 mice with LICD attenuated the cardiac pathology, mitochondrial dysfunction, and apoptosis of cardiomyocytes and significantly improved cardiac function and survival rate. Co-immunoprecipitation and mass spectrometry identified VDAC as a TSPO binding protein.Down-regulation of TSPO reduced PKA-mediated VDAC phosphorylation and VDAC oligomerization, ameliorated mitochondrial function, and reduced cardiomyocyte apoptosis. The study has clinical translational potential, because administration of TSPO-PROTAC to degrade TSPO improved cardiac function in mice with LICD. CONCLUSION: This study elucidated the effect of TSPO in LICD, providing a new therapeutic strategy to down-regulate TSPO by administration of TSPO-PROTAC for the prevention and treatment of LICD.

Integrated genomic, transcriptomic, and metabolomic analyses of Ilex hylonoma provide insights into the triterpenoid saponin biosynthesis.

Ilex is known for its rich content of secondary metabolites, particularly triterpenoid saponins. These compounds hold significant value in natural remedies and herbal medicine. However, the molecular mechanisms responsible for triterpenoid biosynthesis in plants of this genus remain largely unexplored. In this study, we successfully generated the first chromosome-scale genome of Ilex hylonoma. The assembly, comprising 20 anchored chromosomes, has an N50 contig size of 2.13 Mb and a scaffold size of 33.68 Mb. Comparative genome analyses with two other congeners with available chromosome-level genomes suggested that an end-to-end chromosome fusion event likely contributed to the reduction in chromosome number from n = 20 to n = 19 within this genus. By integrating transcriptomic and metabolomic data, we identified the gene expression patterns and metabolite profiles of I. hylonoma across three commonly utilized medicinal tissues. We subsequently pinpointed candidate genes involved in the regulation of triterpenoid saponin biosynthesis, including CYP450 genes, UGT genes, and associated transcription factors. Furthermore, yeast heterologous expression analysis revealed that ihyl08363 catalyzed the conversion of ß-amyrin into oleanolic acid, while ihyl04303 catalyzed the C-2α hydroxylation of oleanolic acid to produce maslinic acid. This integrated analysis provides valuable insights into the biosynthesis of important triterpenoid saponins in medicinal Ilex plants.

Efficient and robust reverse genetics system for bovine rotavirus generation and its application for antiviral screening.

Unveiling the molecular mechanisms underlying rotavirus replication and pathogenesis has been hampered by the lack of a reverse genetics (RG) system in the past. Since 2017, multiple plasmid-based RG systems for simian, human, and murine-Like rotaviruses have been established. However, none of the described methods have supported the recovery of bovine rotaviruses (BRVs). Here, we established an optimized plasmid-based RG system for BRV culture-adapted strain (BRV G10P [15] BLR) and clinical isolates (BRV G6P[1] C73, G10P[11] HM26) based on a BHK-T7 cell clone stably expressing T7 polymerase. Furthermore, using this optimized RG system, we successfully rescued the reporter virus BRV rC73/Zs, rHM26/Zs and rBLR/Zs, harboring a genetically modified 1.8-kb segment 7 encoding full-length nonstructural protein 3 (NSP3) fused to ZsGreen, a 232-amino acid green fluorescent protein. Analysis of the stability of genomic insertions showed that the rC73/Zs and rBLR/Zs replicated efficiently and were genetically stable in seven rounds of serial passaging, while rHM26/Zs can be stabilized only up to the third generation, indicating that the BRV segment composition may influence the viral fitness. In addition, we adopted the recombinant reporter viruses for high-throughput screening application and discovered 12 candidates out of 1440 compounds with potential antiviral activities against rotavirus. In summary, this improved RG system of BRVs represents an important tool with great potential for understanding the molecular biology of BRV and facilitates the development of novel therapeutics and vaccines for BRV.

Synthesis and Mechanism of a Green Scale and Corrosion Inhibitor.

A new green water treatment agent, a poly(aspartic acid)-modified polymer (PASP/5-AVA), was synthesized using polysuccinimide and 5-aminovaleric acid (5-AVA) in a hybrid system. The structure was characterized, and the scale and corrosion inhibition performance were carried out with standard static scale inhibition and electrochemical methods, respectively. The mechanism was explored using XRD, XPS, SEM, and quantum chemistry calculations. The results indicated that PASP/5-AVA exhibited better scale and corrosion inhibition performance than PASP and maintained efficacy and thermal stability of the scale inhibition effect for a long time. Mechanistic studies indicated that PASP/5-AVA interferes with the normal generation of CaCO3 and CaSO4 scales through lattice distortion and dispersion, respectively; the combined effect of an alkaline environment and terminal electron-withdrawing -COOH groups can induce the stable C- ionic state formation in -CH2- of the extended side chain, thus enhancing its chelating ability for Ca2+ ions. At the same time, the extension of the side chain length also enhances the adsorption ability of the agent on the metal surface, forming a thick film and delaying the corrosion of the metal surface. This study provides the necessary theoretical reference for the design of green scale and corrosion agents.

The mitochondrial stress signaling tunes immunity from a view of systemic tumor microenvironment and ecosystem.

Mitochondria play important roles in cell fate, calcium signaling, mitophagy, and the signaling through reactive oxygen species (ROS). Recently, mitochondria are considered as a signaling organelle in the cell and communicate with other organelles to constitute the mitochondrial information processing system (MIPS) that transduce input-to-output biological information. The success in immunotherapy, a concept of systemic therapy, has been proved to be dependent on paracrine interactions within the tumor microenvironment (TME) and distant organs including microbiota and immune components. We will adopt a broader view from the concept of TME to tumor micro- and macroenvironment (TM 2 E) or tumor-organ ecosystem (TOE). In this review, we will discuss the role of mitochondrial signaling by mitochondrial ROS, calcium flux, metabolites, mtDNA, vesicle transportation, and mitochondria-derived peptide in the TME and TOE, in particular immune regulation and effective cancer immunotherapy.

Prediction of lymphovascular invasion of gastric cancer based on contrast-enhanced computed tomography radiomics.

Background: Lymphovascular invasion (LVI) is a significant risk factor for lymph node metastasis in gastric cancer (GC) and is closely related to the prognosis and recurrence of GC. This study aimed to establish clinical models, radiomics models and combination models for the diagnosis of GC vascular invasion. Methods: This study enrolled 146 patients with GC proved by pathology and who underwent radical resection of GC. The patients were assigned to the training and validation cohorts. A total of 1,702 radiomic features were extracted from contrast-enhanced computed tomography images of GC. Logistic regression analyses were performed to establish a clinical model, a radiomics model and a combined model. The performance of the predictive models was measured by the receiver operating characteristic (ROC) curve. Results: In the training cohort, the age of LVI negative (-) patients and LVI positive (+) patients were 62.41 ± 8.41 and 63.76 ± 10.08 years, respectively, and there were more male (n = 63) than female (n = 19) patients in the LVI (+) group. Diameter and differentiation were the independent risk factors for determining LVI (-) and (+). A combined model was found to be relatively highly discriminative based on the area under the ROC curve for both the training (0.853, 95% CI: 0.784-0.920, sensitivity: 0.650 and specificity: 0.907) and the validation cohorts (0.742, 95% CI: 0.559-0.925, sensitivity: 0.736 and specificity: 0.700). Conclusions: The combined model had the highest diagnostic effectiveness, and the nomogram established by this model had good performance. It can provide a reliable prediction method for individual treatment of LVI in GC before surgery.

Deep learning-based image analysis predicts PD-L1 status from 18F-FDG PET/CT images in non-small-cell lung cancer.

Background: There is still a lack of clinically validated biomarkers to screen lung cancer patients suitable for programmed dead cell-1 (PD-1)/programmed dead cell receptor-1 (PD-L1) immunotherapy. Detection of PD-L1 expression is invasively operated, and some PD-L1-negative patients can also benefit from immunotherapy; thus, the joint modeling of both deep learning images and clinical features was used to improve the prediction performance of PD-L1 expression in non-small cell lung cancer (NSCLC). Methods: Retrospective collection of 101 patients diagnosed with pathology in our hospital who underwent 18F FDG PET/CT scans, with lung cancer tissue Tumor Propulsion Score (TPS) ≥1% as a positive expression. Lesions were extracted after preprocessing PET/CT images, and using deep learning 3D DenseNet121 to learn lesions in PET, CT, and PET/CT images, 1,024 fully connected features were extracted; clinical features (age, gender, smoking/no smoking history, lesion diameter, lesion volume, maximum standard uptake value of lesions [SUVmax], mean standard uptake value of lesions [SUVmean], total lesion glycolysis [TLG]) were combined for joint modeling based on the structured data Category Embedding Model. Results: Area under a receiver operating characteristic (ROC) curve (AUC) and accuracy of predicting PD-L1 positive for PET, CT, and PET/CT test groups were 0.814 ± 0.0152, 0.7212 ± 0.0861, and 0.90 ± 0.0605, 0.806 ± 0.023, 0.70 ± 0.074, and 0.950 ± 0.0250, respectively. After joint clinical feature modeling, the AUC and accuracy of predicting PD-L1 positive for PET/CT were 0.96 ± 0.00905 and 0.950 ± 0.0250, respectively. Conclusion: This study combines the features of 18F-FDG PET/CT images with clinical features using deep learning to predict the expression of PD-L1 in NSCLC, suggesting that 18F-FDG PET/CT images can be conducted as biomarkers for PD-L1 expression.

Association Between Systolic Blood Pressure and in-Hospital Mortality Among Congestive Heart Failure Patients with Chronic Obstructive Pulmonary Disease in the Intensive Care Unit: A Retrospective Cohort Study.

Background: There has been a growing body of research focusing on patients with Congestive Heart Failure (CHF) and chronic obstructive pulmonary disease (COPD) admitted to the intensive care unit (ICU). However, the optimal blood pressure (BP) level for such patients remains insufficiently explored. This study aimed to investigate the associations between systolic blood pressure (SBP) and in-hospital mortality among ICU patients with both CHF and COPD. Methods: This retrospective cohort study enrolled 6309 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. SBP was examined as both a continuous and categorical variable, with the primary outcome being in-hospital mortality. The investigation involved multivariable logistic regression, restricted cubic spline regression, and subgroup analysis to determine the relationship between SBP and mortality. Results: The cohort consisted of 6309 patients with concurrent CHF and COPD (3246 females and 3063 males), with an average age of 73.0 ± 12.5 years. The multivariate analysis revealed an inverse association between SBP and in-hospital mortality, both as a continuous variable (odds ratio = 0.99 [95% CI, 0.99~1]) and as a categorical variable (divided into quintiles). Restricted cubic spline analysis demonstrated an L-shaped relationship between SBP and mortality risk (P nonlinearity < 0.001), with an inflection point at 99.479 mmHg. Stratified analyses further supported the robustness of this correlation. Conclusion: The relationship between SBP and in-hospital mortality in patients with both CHF and COPD follows an L-shaped pattern, with an inflection point at approximately 99.479 mmHg.

SOX9 promotes hypoxic pulmonary hypertension through stabilization of DPP4 in pulmonary artery smooth muscle cells.

Pulmonary hypertension (PH) is a progressive cardiopulmonary disorder characterized by pulmonary vascular remodeling (PVR), primarily due to the excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This study aimed to investigate the role and molecular mechanism of SOX9 in hypoxic PH in rats. The findings revealed that SOX9 was upregulated in the pulmonary arteries and PASMCs of hypoxia-exposed rats. SOX9 knockdown inhibited hypoxia-induced proliferation and migration of PASMCs, reduced PVR, and subsequently alleviated hypoxia-induced PH in rats, suggesting that SOX9 plays a critical role in PH. Further investigation demonstrated that SOX9 interacted with DPP4, preventing its ubiquitin degradation in hypoxia-exposed PASMCs. DPP4 knockdown inhibited hypoxia-induced PASMC proliferation and migration, and administration of the DPP4 inhibitor sitagliptin (5 mg/kg) significantly reduced PVR and alleviated hypoxia-induced PH in rats, indicating that SOX9 contributes to PH by stabilizing DPP4. The results also showed that hypoxia induced YAP1 expression and dephosphorylation, leading to YAP1 nuclear localization. YAP1 knockdown promoted the degradation of HIF-1α in hypoxia-exposed PASMCs and inhibited hypoxia-induced proliferation and migration of PASMCs. Additionally, HIF-1α, as a transcription factor, promoted SOX9 expression by binding to the SOX9 promoter in hypoxia-exposed PASMCs. In conclusion, hypoxia promotes the proliferation and migration of PASMCs through the regulation of the YAP1/HIF-1α/SOX9/DPP4 signaling pathway, leading to PH in rats. These findings suggest that SOX9 may serve as a potential prognostic marker and therapeutic target for PH.

3D-printed porous titanium rods equipped with vancomycin-loaded hydrogels and polycaprolactone membranes for intelligent antibacterial drug release.

Implant-related infections pose significant challenges to orthopedic surgeries due to the high risk of severe complications. The widespread use of bioactive prostheses in joint replacements, featuring roughened surfaces and tight integration with the bone marrow cavity, has facilitated bacterial proliferation and complicated treatment. Developing antibacterial coatings for orthopedic implants has been a key research focus in recent years to address this critical issue. Researchers have designed coatings using various materials and antibacterial strategies. In this study, we fabricated 3D-printed porous titanium rods, incorporated vancomycin-loaded mPEG750-b-PCL2500 gel, and coated them with a PCL layer. We then evaluated the antibacterial efficacy through both in vitro and in vivo experiments. Our coating passively inhibits bacterial biofilm formation and actively controls antibiotic release in response to bacterial growth, providing a practical solution for proactive and sustained infection control. This study utilized 3D printing technology to produce porous titanium rod implants simulating bioactive joint prostheses. The porous structure of the titanium rods was used to load a thermoresponsive gel, mPEG750-b-PCL2500 (PEG: polyethylene glycol; PCL: polycaprolactone), serving as a novel drug delivery system carrying vancomycin for controlled antibiotic release. The assembly was then covered with a PCL membrane that inhibits bacterial biofilm formation early in infection and degrades when exposed to lipase solutions, mimicking enzymatic activity during bacterial infections. This setup provides infection-responsive protection and promotes drug release. We investigated the coating's controlled release, antibacterial capability, and biocompatibility through in vitro experiments. We established a Staphylococcus aureus infection model in rabbits, implanting titanium rods in the femoral medullary cavity. We evaluated the efficacy and safety of the composite coating in preventing implant-related infections using imaging, hematology, and pathology. In vitro experiments demonstrated that the PCL membrane stably protects encapsulated vancomycin during PBS immersion. The PCL membrane rapidly degraded at a lipase concentration of 0.2 mg/mL. The mPEG750-b-PCL2500 gel ensured stable and sustained vancomycin release, inhibiting bacterial growth. We investigated the antibacterial effect of the 3D-printed titanium material, coated with PCL and loaded with mPEG750-b-PCL2500 hydrogel, using a rabbit Staphylococcus aureus infection model. Imaging, hematology, and histopathology confirmed that our composite antibacterial coating exhibited excellent antibacterial effects and infection prevention, with good safety in trials. Our results indicate that the composite antibacterial coating effectively protects vancomycin in the hydrogel from premature release in the absence of bacterial infection. The outer PCL membrane inhibits bacterial growth and prevents biofilm formation. Upon contact with bacterial lipase, the PCL membrane rapidly degrades, releasing vancomycin for antibacterial action. The mPEG750-b-PCL2500 gel provides stable and sustained vancomycin release, prolonging its antibacterial effects. Our composite antibacterial coating demonstrates promising potential for clinical application.

The future of interleukin gene therapy in head and neck cancers.

INTRODUCTION: Head and neck cancer (HNC), primarily head and neck squamous cell carcinomas, originates from the squamous epithelium in areas like the oral cavity, lip, larynx, and oropharynx. With high morbidity impacting critical functions, combined treatments like surgery, radiation, and chemotherapy often fall short in advanced stages, highlighting the need for innovative therapies. AREAS COVERED: This review critically evaluates interleukin (IL) gene therapy for treating HNC. The discussion extends to key ILs in HNC, various gene therapy techniques and delivery methods. We particularly focus on the application of IL-2, IL-12, and IL-24 gene therapies, examining their mechanisms and outcomes in preclinical studies and clinical trials. The final sections address IL gene therapy challenges in HNC, exploring solutions and critically assessing future therapeutic directions. EXPERT OPINION: Despite advancements in genomic and immunotherapy, significant challenges in HNC treatment persist, primarily due to the immunosuppressive nature of the tumor microenvironment and the adverse effects of current therapies. The therapeutic efficacy of IL gene therapy hinges on overcoming these hurdles through refined delivery methods that ensure targeted, tumor-specific gene expression. Future strategies should focus on refining gene delivery methods and combining IL gene therapy with other treatments to optimize efficacy and minimize toxicity.