Stimuli-responsive materials in oral diseases: a review.

OBJECTIVES: Oral diseases, such as dental caries, periodontitis, and oral cancers, are highly prevalent worldwide. Many oral diseases are typically associated with bacterial infections or the proliferation of malignant cells, and they are usually located superficially. MATERIALS AND METHODS: Articles were retrieved from PubMed/Medline, Web of Science. All studies focusing on stimuli-responsive materials in oral diseases were included and carefully evaluated. RESULTS: Stimulus-responsive materials are innovative materials that selectively undergo structural changes and trigger drug release based on shifts at the molecular level, such as changes in pH, electric field, magnetic field, or light in the surrounding environment. These changes lead to alterations in the properties of the materials at the macro- or microscopic level. Consequently, stimuli-responsive materials are particularly suitable for treating superficial site diseases and have found extensive applications in antibacterial and anticancer therapies. These characteristics make them convenient and effective for addressing oral diseases. CONCLUSIONS: This review aimed to summarize the classification, mechanism of action, and application of stimuli-responsive materials in the treatment of oral diseases, point out the existing limitations, and speculate the prospects for clinical applications. CLINICAL RELEVANCE: Our findings may provide useful information of stimuli-responsive materials in oral diseases for dental clinicians.

Zinc-Ion Anchor Induced Highly Reversible Zn Anodes for High Performance Zn-Ion Batteries.

Unstable Zn interface with serious detrimental parasitic side-reactions and uncontrollable Zn dendrites severely plagues the practical application of aqueous zinc-ion batteries. The interface stability was closely related to the electrolyte configuration and Zn2+ depositional behavior. In this work, a unique Zn-ion anchoring strategy is originally proposed to manipulate the coordination structure of solvated Zn-ions and guide the Zn-ion depositional behavior. Specifically, the amphoteric charged ion additives (denoted as DM), which act as zinc-ion anchors, can tightly absorb on the Zn surface to guide the uniform zinc-ion distribution by using its positively charged -NR4 + groups. While the negatively charged -SO3 - groups of DM on the other hand, reduces the active water molecules within solvation sheaths of Zn-ions. Benefiting from the special synergistic effect, Zn metal exhibits highly ordered and compact (002) Zn deposition and negligible side-reactions. As a result, the advanced Zn||Zn symmetric cell delivers extraordinarily 7000 hours long lifespan (0.25 mA cm-2, 0.25 mAh cm-2). Additionally, based on this strategy, the NH4V4O10||Zn pouch-cell with low negative/positive capacity ratio (N/P ratio=2.98) maintains 80.4 % capacity retention for 180 cycles. A more practical 4 cm*4 cm sized pouch-cell could be steadily cycled in a high output capacity of 37.0 mAh over 50 cycles.

Intrinsically Decoupled Coordination Chemistries Enable Quasi-Eutectic Electrolytes with Fast Kinetics toward Enhanced Zinc-Ion Capacitors.

Eutectic electrolytes show potential beyond conventional low-concentration electrolytes (LCEs) in zinc (Zn)-ion capacitors (ZICs) yet suffer from high viscosity and sluggish kinetics. Herein, we originally propose a universal theory of intrinsically decoupling to address these issues, producing a novel electrolyte termed "quasi-eutectic" electrolyte (quasi-EE). Joint experimental and theoretical analyses confirm its unique solution coordination structure doped with near-LCE domains. This enables the quasi-EE well inherit the advanced properties at deep-eutectic states while provide facilitated kinetics as well as lower energy barriers via a vehicle/hopping-hybridized charge transfer mechanism. Consequently, a homogeneous electroplating pattern with much enhanced Sand's time is achieved on the Zn surface, followed by a twofold prolonged service-life with drastically reduced concentration polarization. More encouragingly, the quasi-EE also delivers increased capacitance output in ZICs, which is elevated by 12.4 %-144.6 % compared to that before decoupling. Furthermore, the pouch cell with a cathodic mass loading of 36.6 mg cm-2 maintains competitive cycling performances over 600 cycles, far exceeding other Zn-based counterparts. This work offers fresh insights into eutectic decoupling and beyond.

Correlation between Ki-67 or Profilin-1 Expression Levels, Clinicopathological Characteristics and Postoperative Prognosis in Patients with Bladder Cancer.

BACKGROUND: Bladder cancer is the most common malignancy of the urinary system, and the search for new and reliable biomarkers has important clinical significance for the personalized treatment of bladder cancer. This study aims to explore the correlation between nuclear proliferation antigen (Ki-67) or Profilin-1 (PFN1) levels, clinicopathological characteristics, and postoperative prognosis in patients with bladder cancer. METHODS: Patients with bladder cancer who underwent transurethral resection of bladder cancer tumor in The Fourth Affiliated Hospital of Soochow University, hospital from January 2019 to January 2021 were selected as the study group (n = 60), and patients with benign lesions of bladder cancer during the same period were selected as the control group (n = 60). The expression of Ki-67 and PFN1 in tumor and bladder tissues of the two groups was analyzed. Ki-67 recorded the patient's pathological parameters and calculated the patient's postoperative prognosis. The correlation between Ki-67 and PFN1 expression levels, pathological parameters, and postoperative prognosis was analyzed. RESULTS: The positive expression rates of Ki-67 and PFN1 in the study group were 63.33% and 73.33%, respectively, which were significantly higher than the positive expression rates in the control group (χ2 = 14.803, 17.757, p < 0.001). The positive expression rates of Ki-67 and PFN1 were related to histological grade, clinical stage, infiltration, and lymph node metastasis, and the differences were statistically significant (p < 0.05). Bladder cancer patients with non muscle-invasive bladder cancer (NMIBC), high-grade histological grade, Ta~T1 clinical stage, invasive, and lymph node metastasis have a higher Ki-67 positive expression rate than bladder cancer patients with muscle-invasive bladder cancer (MIBC), low-grade histological grade, T2~T4, non-invasive, and no lymph node metastasis. The high expression level of Ki-67 has little relationship with gender, age, tumor diameter, and vascular invasion (p > 0.05). The survival time and three-year survival rate of the Ki-67 positive expression group were significantly lower than those of the Ki-67 negative expression group (p < 0.05). The survival time and three-year survival rate of the PFN1 positive expression group were significantly lower than those of the PFN1 negative expression group (p < 0.05). CONCLUSION: The positive expression rates of Ki-67 and PFN1 in bladder tumor tissue are significantly higher than those in bladder tissue, and pathological pattern, histological grade, clinical stage, infiltration, and lymph node metastasis are related to the positive expression rates of Ki-67 and PFN1, and different genders, ages, tumors diameter and vascular invasion are not related to the positive expression rates of Ki-67 and PFN1. The survival time and three-year survival rates of bladder cancer patients with Ki-67 positive and PFN1 positive expression are shorter.

Association between exposure to a mixture of organochlorine pesticides and hyperuricemia in U.S. adults: A comparison of four statistical models.

The association between the exposure of organochlorine pesticides (OCPs) and serum uric acid (UA) levels remained uncertain. In this study, to investigate the combined effects of OCP mixtures on hyperuricemia, we analyzed serum OCPs and UA levels in adults from the National Health and Nutrition Examination Survey (2005-2016). Four statistical models including weighted logistic regression, weighted quantile sum (WQS), quantile g-computation (QGC), and bayesian kernel machine regression (BKMR) were used to assess the relationship between mixed chemical exposures and hyperuricemia. Subgroup analyses were conducted to explore potential modifiers. Among 6,529 participants, the prevalence of hyperuricemia was 21.15%. Logistic regression revealed a significant association between both hexachlorobenzene (HCB) and trans-nonachlor and hyperuricemia in the fifth quintile (OR: 1.54, 95% CI: 1.08-2.19; OR: 1.58, 95% CI: 1.05-2.39, respectively), utilizing the first quintile as a reference. WQS and QGC analyses showed significant overall effects of OCPs on hyperuricemia, with an OR of 1.25 (95% CI: 1.09-1.44) and 1.20 (95% CI: 1.06-1.37), respectively. BKMR indicated a positive trend between mixed OCPs and hyperuricemia, with HCB having the largest weight in all three mixture analyses. Subgroup analyses revealed that females, individuals aged 50 years and above, and those with a low income were more vulnerable to mixed OCP exposure. These results highlight the urgent need to protect vulnerable populations from OCPs and to properly evaluate the health effects of multiple exposures on hyperuricemia using mutual validation approaches.

MG53/TRIM72: multi-organ repair protein and beyond.

MG53, a member of the tripartite motif protein family, possesses multiple functionalities due to its classic membrane repair function, anti-inflammatory ability, and E3 ubiquitin ligase properties. Initially recognized for its crucial role in membrane repair, the therapeutic potential of MG53 has been extensively explored in various diseases including muscle injury, myocardial damage, acute lung injury, and acute kidney injury. However, further research has revealed that the E3 ubiquitin ligase characteristics of MG53 also contribute to the pathogenesis of certain conditions such as diabetic cardiomyopathy, insulin resistance, and metabolic syndrome. Moreover, recent studies have highlighted the anti-tumor effects of MG53 in different types of cancer, such as small cell lung cancer, liver cancer, and colorectal cancer; these effects are closely associated with their E3 ubiquitin ligase activities. In summary, MG53 is a multifunctional protein that participates in important physiological and pathological processes of multiple organs and is a promising therapeutic target for various human diseases. MG53 plays a multi-organ protective role due to its membrane repair function and its exertion of anti-tumor effects due to its E3 ubiquitin ligase properties. In addition, the controversial aspect of MG53's E3 ubiquitin ligase properties potentially causing insulin resistance and metabolic syndrome necessitates further cross-validation for clarity.

Mean ADC values and arterial phase hyperintensity discriminate small (≤ 3 cm) well-differentiated hepatocellular carcinoma from dysplastic nodule.

BACKGROUND/AIM: This research endeavor sought to distinguish small (≤ 3 cm) well-differentiated hepatocellular carcinoma (WD-HCC) from dysplastic nodules (DN) by employing traditional imaging features and mean apparent diffusion coefficient (mADC) values derived from diffusion-weighted imaging (DWI). MATERIALS AND METHODS: In this retrospective analysis, we assessed a cohort of ninety patients with confirmed dysplastic nodules (DNs) (n = 71) or well-differentiated hepatocellular carcinoma (WD-HCC) (n = 41) who had undergone dynamic contrast-enhanced magnetic resonance imaging between March 2018 and June 2021. Multivariable logistic regression analyses were executed to pinpoint characteristics that can effectively differentiate histologic grades. A region-of-interest (ROI) encompassing all lesion voxels was delineated on each slice containing the mass in the ADC map. Subsequently, the whole-lesion mean ADC (mADC) were computed from these delineations. A receiver operating characteristic (ROC) curve was generated to assess the discriminatory efficacy of the mADC values in distinguishing between WD-HCC and DN. RESULTS: Among the histopathological types from benign to malignant, mADC showed a significant decrease (P < 0.001). The mADCs were effective in distinguishing WD-HCC from DN [AUC, 0.903 (95% CI 0.849-0.958)]. The best cutoffs for the Youden index were 0.0012 mm2/s for mADC, with moderate sensitivity (70.7%) and high specificity (94.4%). MRI features including hyperintensity at arterial phase (odds ratio, 21.2; P = 0.009), mADC < 0.0012 mm2/s (odds ratio, 52.2; P < 0.001) were independent predictors for WD-HCC at multivariable analysis. The AUC value of hyperintensity at arterial phase was 0.857 (95% CI 0.786-0.928). The composite diagnostic criterion of arterial hyperintensity + mADC < 0.0012 mm2/s showed good performance [AUC, 0.926 (95% CI 0.878-0.975)], displaying increased sensitivity compared to individual assessments involving arterial hyperintensity (P = 0.013), mADC < 0.0012 mm2/s (P = 0.004), or LR-5 (P < 0.001), with similar specificity compared to LR-5 (P = 0.193). CONCLUSION: DN and WD-HCC displayed contrasting diffusion characteristics, attainable to distinguish with satisfactory accuracy. The utilization of arterial phase hyperintensity and mADC < 0.0012 on MRI facilitated the differentiation of WD-HCC from DN.

MRI spectrum of avascular necrosis of femoral head in patients treated for COVID-19.

BACKGROUND AND PURPOSE: This prospective observational study aimed to investigate the occurrence of avascular necrosis (AVN) of the femoral head in COVID-19 patients through MRI scans. The study examined the patterns of AVN in 110 individuals who had undergone conventional COVID-19 therapy and reported hip discomfort. This study highlights the importance of considering AVN as a potential complication of COVID-19 therapy, particularly in younger patients who experience hip discomfort. METHODS: Individuals who had corticosteroid treatment for COVID-19 and experienced hip discomfort during 6 months between January 2022 and August 2022 were included in this study, and an MRI scan was done to observe changes in the hip joint. RESULTS: The results were classified using the Ficat and Arlet classification system. The analysis revealed that AVN was not present in 91.81% of cases. However, Stage I AVN was detected in 4.54% of cases, Stage II AVN in 2.72% of cases, and Stage III AVN in 1.1% of cases. No cases of Stage IV AVN were observed. CONCLUSIONS: The study concludes that AVN occurred in 6% of individuals who underwent conventional therapy for COVID-19 and experienced hip discomfort. In these settings (post COVID-19), normal MRI results were more typical, and mild AVN (Stage I) was a frequent finding in MRI scans that were positive.

Identification of prognostic risk score of disulfidptosis-related genes and molecular subtypes in glioma.

Background: Programmed cell death is closely related to glioma. As a novel kind of cell death, the mechanism of disulfidptosis in glioma remains unclear. Therefore, it is of great importance to study the role of disulfidptosis-related genes (DRGs) in glioma. Methods: We first investigated the genetic and transcriptional alterations of 15 DRGs. Two consensus cluster analyses were used to evaluate the association between DRGs and glioma subtypes. In addition, we constructed prognostic DRG risk scores to predict overall survival (OS) in glioma patients. Furthermore, we developed a nomogram to enhance the clinical utility of the DRG risk score. Finally, the expression levels of DRGs were verified by immunohistochemistry (IHC) staining. Results: Most DRGs (14/15) were dysregulated in gliomas. The 15 DRGs were rarely mutated in gliomas, and only 50 of 987 samples (5.07 %) showed gene mutations. However, most of them had copy number variation (CNV) deletions or amplifications. Two distinct molecular subtypes were identified by cluster analysis, and DRG alterations were found to be related to the clinical characteristics, prognosis, and tumor immune microenvironment (TIME). The DRG risk score model based on 12 genes was developed and showed good performance in predicting OS. The nomogram confirmed that the risk score had a particularly strong influence on the prognosis of glioma. Furthermore, we discovered that low DRG scores, low tumor mutation burden, and immunosuppression were features of patients with better prognoses. Conclusion: The DRG risk model can be used for the evaluation of clinical characteristics, prognosis prediction, and TIME estimation of glioma patients. These DRGs may be potential therapeutic targets in glioma.

The long-term effectiveness and mechanism of oncolytic virotherapy combined with anti-PD-L1 antibody in colorectal cancer patient.

Colorectal cancer (CRC) is known to be resistant to immunotherapy. In our phase-I clinical trial, one patient achieved a 313-day prolonged response during the combined treatment of oncolytic virotherapy and immunotherapy. To gain a deeper understanding of the potential molecular mechanisms, we performed a comprehensive multi-omics analysis on this patient and three non-responders. Our investigation unveiled that, initially, the tumor microenvironment (TME) of this responder presented minimal infiltration of T cells and natural killer cells, along with a relatively higher presence of macrophages compared to non-responders. Remarkably, during treatment, there was a progressive increase in CD4+ T cells, CD8+ T cells, and B cells in the responder's tumor tissue. This was accompanied by a significant upregulation of transcription factors associated with T-cell activation and cytotoxicity, including GATA3, EOMES, and RUNX3. Furthermore, dynamic monitoring of peripheral blood samples from the responder revealed a rapid decrease in circulating tumor DNA (ctDNA), suggesting its potential as an early blood biomarker of treatment efficacy. Collectively, our findings demonstrate the effectiveness of combined oncolytic virotherapy and immunotherapy in certain CRC patients and provide molecular evidence that virotherapy can potentially transform a "cold" TME into a "hot" one, thereby improving sensitivity to immunotherapy.

Modulation of Dendritic Cell Function via Nanoparticle-Induced Cytosolic Calcium Changes.

Calcium nanoparticles have been investigated for applications, such as drug and gene delivery. Additionally, Ca2+ serves as a crucial second messenger in the activation of immune cells. However, few studies have systematically studied the effects of calcium nanoparticles on the calcium levels and functions within immune cells. In this study, we explore the potential of calcium nanoparticles as a vehicle to deliver calcium into the cytosol of dendritic cells (DCs) and influence their functions. We synthesized calcium hydroxide nanoparticles, coated them with a layer of silica to prevent rapid degradation, and further conjugated them with anti-CD205 antibodies to achieve targeted delivery to DCs. Our results indicate that these nanoparticles can efficiently enter DCs and release calcium ions in a controlled manner. This elevation in cytosolic calcium activates both the NFAT and NF-κB pathways, in turn promoting the expression of costimulatory molecules, antigen-presenting molecules, and pro-inflammatory cytokines. In mouse tumor models, the calcium nanoparticles enhanced the antitumor immune response and augmented the efficacy of both radiotherapy and chemotherapy without introducing additional toxicity. Our study introduces a safe nanoparticle immunomodulator with potential widespread applications in cancer therapy.

A new simplified risk assessment model enhances postoperative prophylaxis of venous thromboembolism in Chinese adult patients with inguinal hernia (CHAT-3): A prospective, multicenter, randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) significantly affects the prognosis of surgical patients with inguinal hernia. The complex Caprini score, commonly used for postoperative VTE risk assessment, poses practical challenges for surgeons in clinical settings. METHODS: The CHAT-3 trial, a prospective, multicenter, randomized controlled trial, compared a simple three-factor model to assess VTE risk against routine practices in post-inguinal hernia surgery (IHS) patients. The patients were randomly assigned (1:1) to the intervention or control arm. The intervention group used the three-factor model to identify patients at moderate or high risk of VTE for subsequent prophylaxis according to clinical guidelines. Both groups were followed for four weeks, with randomization implemented using computer-generated sequences. The primary outcome measured was the rate of VTE prophylaxis. Secondary outcomes included time spent on VTE risk assessment (surgeon self-reported), postoperative D-dimer trends, perioperative VTE occurrence, bleeding events, and the net clinical benefit. RESULTS: Of the 1,109 participants, 508 in the experimental group and 601 in the control group completed follow-up. The three-factor model showed higher VTE prophylaxis rates in all patients (pharmacologic prophylaxis: 26.2% vs. 6.00%, P<0.001) and particularly in those at high risk (pharmacologic prophylaxis: 57.3% vs. 9.50%, P<0.001). The experimental group significantly reduced VTE risk assessment time compared to the Caprini score (1.39±0.55 min vs. 5.73±1.35 min, P<0.001). The experimental group had lower D-dimer levels (0.26±0.73 mg/L vs. 0.35±0.55 mg/L, P=0.028). In the experimental group, the patients did not experience an increased risk of VTE (0% vs. 1.66%, P=0.268) and bleeding (1.18% vs. 0.67%, P=0.558) compared to the controls. There was no significant difference in net clinical benefit, which combined VTE and bleeding events, between the experimental and control groups (1.18% vs. 0.83%, P=0.559). CONCLUSION: Applying the simple three-factor model in perioperative VTE management could quickly identify the patient with a high risk of VTE and improve the prophylaxis rate of perioperative VTE. TRIAL REGISTRATION: XXX. TRIAL REGISTRATION: ChiCTR2000033769.