Curcumin analogue AC17-loaded dissolvable microneedles activate FOXO3 and enhance localized drug delivery for oral squamous cell carcinoma treatment.

Curcumin, a polyphenol extracted from turmeric, is a potential alternative for the treatment of oral squamous cell carcinoma (OSCC) due to its remarkable anticancer activity and low systemic toxicity. To further enhance the anticancer activity and bioavailability of curcumin, we synthesized a curcumin analogue, AC17, by modifying the benzene ring and methylene group of curcumin. A soluble hyaluronic acid microneedle patch (AC17@HAMN) was developed to ensure accurate and safe delivery of AC17 to tumor tissues. The inhibitory effect of AC17 on OSCC cells was stronger than that of curcumin and some common analogues. Transcriptome sequencing showed that the target genes of AC17 were mainly concentrated in apoptosis, cell cycle and cell senescence pathways. Among them, AC17 induces cell cycle arrest and inhibits cell proliferation mainly by activating FOXO3 signaling. With good penetration and dissolution properties, microneedles can deliver AC17 directly to the tumor site and show good anti-tumor effect. Moreover, AC17@HAMN showed good biosafety. In summary, AC17@HAMN offers high efficiency, minimal invasiveness, and few adverse reactions. This microneedle patch holds great promise for potential clinical applications, especially for the treatment of OSCC.

Temporal and spatial evolution of different heavy metal fractions and correlation with environmental factors after prolonged acid mine drainage irrigation: A column experiment.

Acid mine drainage (AMD) has global significance due to its low pH and elevated heavy metal content, which have received widespread attention. After AMD irrigation in mining areas, heavy metals are distributed among soil layers, but the influencing factors and mechanisms remain unclear. AMD contamination of surrounding soil is primarily attributed to surface runoff and irrigation and causes significant environmental degradation. A laboratory soil column experiment was conducted to investigate the temporal and spatial distribution of the heavy metals Cd and Cu, as well as the impact of key environmental factors on the migration and transformation of these heavy metals following long-term soil pollution by AMD. After AMD addition, the soil exhibited a significant increase in acidity, accompanied by notable alterations in various environmental parameters, including soil pH, Eh, Fe(II) content, and iron oxide content. Over time, Cd and Cu in the soil mainly existed in the exchangeable and carbonate-bound fractions. In spatial terms, exchangeable Cu increased with increasing depth. Pearson correlation analysis indicated significant negative correlations between pH and Cu, Cd, and Eh in pore water, as well as negative correlations between pH and the exchangeable fraction of Cd (F1), carbonate-bound fraction of Cd (F2), and exchangeable fraction of Cu (F1) in the solid phase. Additionally, a positive correlation was observed between pH and the residual fraction of Cu (F5). Furthermore, the soil total Cd content exhibited a positive correlation with pyrophosphate-Fe (Fep) and dithionite-Fe (Fed), while CdF1, CdF2, total Cu, and CuF1 displayed positive correlations with Fep. Our findings indicate that the presence of AMD in soil leads to alterations in the chemical fractions of Cd and Cu, resulting in enhanced bioavailability. These results offer valuable insights for developing effective remediation strategies for soils near mining sites.

Effects of Fe(II) bio-oxidation rate and alkali control on schwertmannite microstructure and adsorption of oxyanions: Characteristics, performance and mechanism.

Schwertmannite has attracted increasing interest for its excellent sorption of oxyanions such as AsO43-, CrO42-, and Sb(OH)6-. Controlling biomineralization by adjusting the Fe(II) oxidation rate and implementing alkali control can enhance the yield and adsorption performance of schwertmannite. However, the adsorption improvement mechanism is still unclear. The morphology, crystallinity, specific surface area (SSA) and oxyanion adsorption of schwertmannite synthesized with alkali control of solution pH and different Fe(II) oxidation rates were analyzed in this study. The differences in the adsorption mechanisms of As(V), Cr(VI) and Sb(V) on schwertmannite obtained under different synthesis conditions were also studied. Reducing the Fe(II) oxidation rate or maintaining the solution pH through alkali control significantly increased the SSA of schwertmannite and the proportion of outer-sphere sulfate. Alkali-controlled schwertmannite (Sch-C) exhibited superior As(V) and Sb(V) adsorption performance and slightly greater Cr(VI) adsorption than non-alkali-controlled schwertmannite. The As(V) and Sb(V) adsorption capacities of Sch-C greatly improved because the ultra-high SSA increased the surface hydroxyl content and reduced the passivation effect of amorphous precipitates on the mineral surface, allowing continuous sulfate exchange at inner mineral sites. An increased surface hydroxyl content had little effect on Cr(VI) adsorption, but an increased proportion of outer-sphere sulfate caused a slight increase in Cr(VI) adsorption. Sb(V) has a stronger hydroxyl exchange ability than As(V), but due to its octahedral structure, it exchanges only with outer-sphere sulfate on schwertmannite and hardly exchanges with inner-sphere sulfate.

Turning harmful Mn2+ to treasure: In-situ formed ε-MnO2 for removing heavy metals from acid mine drainage.

Acid mine drainage (AMD) contains high concentrations of heavy metals, causing serious environmental pollution. Current neutralization techniques fail to recover and utilize valuable heavy metals, and generate large quantities of hazardous sludge. Manganese (Mn) is generally present at high levels in AMD. Therefore, this paper proposed a technology to recover Mn from AMD, by adding KMnO4 to converting Mn into ε-MnO2. Ultra-Violet C (UVC) was used to photolyze the residual KMnO4. The study then evaluated the processes and mechanisms involved in the technology. The photolysis of KMnO4 in strong acidic conditions was determined, and new mechanisms were proposed. MnO2 produced by the photolysis process was formed through the reaction between Mn(III) and KMnO4. In the absence of KMnO4, Mn(III) underwent further photolysis and was reduced to Mn2+. The maximum adsorption capacities of in-situ formed ε-MnO2 for Pb2+, Cd2+, and Fe3+ were 449.80, 122.05, and 779.88 mg/g, respectively. Higher Mn-OH levels and MnO2 regeneration were crucial in improving adsorption performance. Proton exchange and inner-circle complexation were the main pathways for Pb2+ and Cd2+ adsorption by in-situ formed ε-MnO2. A phase transformation occurred when a substantial amount of Fe3+ was adsorbed, leading to the gradual transformation to MnFe binary oxides. When applying in-situ formed ε-MnO2 technology for actual AMD treatment, 98.62 % of Mn in AMD was recovered within 24 h in the presence of ε-MnO2 for possible further reuse in industries, with a final recovery of 0.76 kg/m3. Further, this technique removed other heavy metals and reduced the sludge volume by 20.99 % when used as a pre-treatment step for neutralization. These results demonstrated the broad potential of this treatment technology.

Prediction model of gleason score upgrading after radical prostatectomy based on a bayesian network.

OBJECTIVE: To explore the clinical value of the Gleason score upgrading (GSU) prediction model after radical prostatectomy (RP) based on a Bayesian network. METHODS: The data of 356 patients who underwent prostate biopsy and RP in our hospital from January 2018 to May 2021 were retrospectively analysed. Fourteen risk factors, including age, body mass index (BMI), total prostate-specific antigen (tPSA), prostate volume, total prostate-specific antigen density (PSAD), the number and proportion of positive biopsy cores, PI-RADS score, clinical stage and postoperative pathological characteristics, were included in the analysis. Data were used to establish a prediction model for Gleason score elevation based on the tree augmented naive (TAN) Bayesian algorithm. Moreover, the Bayesia Lab validation function was used to calculate the importance of polymorphic Birnbaum according to the results of the posterior analysis and to obtain the importance of each risk factor. RESULTS: In the overall cohort, 110 patients (30.89%) had GSU. Based on all of the risk factors that were included in this study, the AUC of the model was 81.06%, and the accuracy was 76.64%. The importance ranking results showed that lymphatic metastasis, the number of positive biopsy cores, ISUP stage and PI-RADS score were the top four influencing factors for GSU after RP. CONCLUSIONS: The prediction model of GSU after RP based on a Bayesian network has high accuracy and can more accurately evaluate the Gleason score of prostate biopsy specimens and guide treatment decisions.

Effects of synthesis temperature on ε-MnO2 microstructures and performance: Selective adsorption of heavy metals and the mechanism onto (100) facet compared with (001).

The heavy-metal adsorbent ε-MnO2 was produced through a simple, one-step oxidation-reduction reaction at three different synthesis temperatures (25 °C, 50 °C and 75 °C) and their morphology and chemical-physical properties were compared. Of the three materials, MnO2-25 had the largest specific surface area and the highest surface hydroxyl concentration. Its optimal performance was demonstrated by batch adsorption experiments with Pb2+, Cd2+ and Cu2+. Of the three metals, Pb2+ was adsorbed best (339.15 mg/g), followed by Cd2+ (107.50 mg/g) and Cu2+ (86.30 mg/g). When all three metals were present, Pb2+ was still absorbed best but now more Cu2+ was adsorbed than Cd2+. In order to explore the mechanism for the inconsistent adsorption order of Cd2+ and Cu2+ in single and competitive adsorption, we combined experimental data with density functional theory (DFT) calculations to elucidate the distinct adsorption nature of MnO2-25 towards these three metals. This revealed that the adsorption affinity of the (100) facet was superior to (001), and since the surface complexes were also more stable on (100), this facet was most likely determining the adsorption order for the single metals. When the metals were present in combination, Pb2+ preferentially occupied the active adsorption sites of (100), forcing Cu2+ to be adsorbed on the (001) facet where Cd2+ was only poorly bound. Thus, the adsorption behavior was affected by MnO2-25 surface chemistry at a molecular scale. This study provides an in-depth understanding of the adsorption mechanisms of the heavy metals on this adsorbent and offers theoretical guidance for production of adsorbent with improved removal efficiency.

In-situ Electrospinning for Intestinal Hemostasis.

INTRODUCTION: During routine surgery, rapid hemostasis, especially the rapid hemostasis of internal organs, is very important. The emergence of in-situ electrospinning technology has fundamentally solved this problem. It exhibits a high speed of hemostasis, and no bleeding occurs after surgery. Thus, it is of great significance. The use of sutures in some human organs, such as the intestines and bladder, is inadequate because fluid leakage occurs due to the presence of pinholes. METHODS: Three types of large intestine wounds with an opening of about 1 cm were investigated. They were untreated, treated by needle and threaded, and treated by hand-held electrospinning, respectively. RESULTS: The results show that hand-held electrospinning technique effectively prevented the exudation of fluids in the intestinal tract. The average diameter of the nanofibrous membrane was about 0.5 µm with hole of several micrometers. It can be elongated 90% without breakage. The hand-held electrospinning device could be used with nitrile gloves, preventing the risk of infection caused by exposed hands. DISCUSSION: This work can provide a reference for future animal experiments and clinical experiments. However, safety should be investigated before application.

The Stability and Survival Rate of Dental Implants After Preparation of the Site by Piezosurgery vs Conventional Drilling: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to assess the stability and survival rate of dental implants inserted with different site preparation techniques-piezoelectric inserts versus traditional rotary instruments. MATERIALS AND METHODS: Correlative research was located by searching articles in PubMed, EMBASE, and the Cochrane Library. This was accomplished independently by two different reviewers and supplemented by a manual search. Only prospective studies evaluating piezoelectric vs conventional implant site preparation in dental implantation were included in this review. A meta-analysis was performed on the stability and survival rate of implants. RESULTS: One thousand fifty-five articles were identified following the search strategy, of which five studies were finally included in this meta-analysis. With regard to the survival rate of implants, there was no statistically significant difference between piezoelectric and conventional implant site preparation (RR = 0.98, 95% CI: 0.94, 1.03; I2 = 0%, P = .86). On the other side, the piezoelectric group had better stability in the eighth week (MD = 4.24, 95% CI: 1.36, 7.12; I2 = 0%, P = .80) and 12th week (MD = 3.33, 95% CI: 0.59, 6.08; I2 = 0%, P = .87) compared with the conventional group. CONCLUSION: Within the limitations of this study, it suggests that the survival rate of implants may not be influenced by the site preparation techniques (piezoelectric vs conventional), but the piezoelectric group may achieve better stability than the conventional group.

Dietary nitrate protects skin flap against ischemia injury in rats via enhancing blood perfusion.

Insufficient blood supply is associated with high levels of necrosis in reconstructive surgery. Restoring blood flow to undersupplied ischemic tissue is the most important impact factor determining skin flap viability. Dietary nitrate, a significant source of nitric oxide, has multiple physiological functions, including regulator of blood flow, angiogenesis, and vasodilatation. However, the effects of dietary nitrate on ischemic skin flap remain unknown. The present study evaluated whether dietary nitrate supplementation altered blood flow of ischemic skin flap in rats. Our results showed that nitrate treatment significantly enhanced ischemic tissue survival. Mechanistically, nitrate therapy significantly increased serum nitrate and nitrite levels, blood perfusion, and angiogenesis. In addition, the circulating levels of Inflammatory mediators were decreased by nitrate supplementation. In conclusion, we demonstrated that dietary nitrate supplementation protected ischemic skin flap by enhancing ischemia-induced revascularization.

[Use of "gelatamp" colloidal silver gelatin sponge to prevent dry socket after extracting mandibular impacted teeth].

PURPOSE: To study the clinical effect of "gelatamp" colloidal silver gelatin sponge on preventing dry socket after extracting the mandibular impacted teeth. METHODS: 1350 teeth extracted from 976 patients who needed to extract the mandibular impacted teeth were divided into group A, group B and group C randomly. "Gelatamp" colloidal silver gelatin sponge was implanted into alveolar socket after teeth extraction in group A, with absorbable gelatin sponge was implanted into alveolar socket in group B and nothing was implanted into alveolar socket in group C. The incidence of dry socket was observed, the data was analyzed using SPSS10.0 software package. RESULTS: The incidence of dry socket was 0.44% in group A, 2% in group B and 4.44% in group C. There was significant difference in the incidence of dry socket between group A and group C(P<0.01). There was also significant difference between group B and group C(P<0.05) and between group A and group B(P<0.05). CONCLUSIONS: The results demonstrate that "gelatamp" colloidal silver gelatin sponge can prevent the occurrence of dry socket after teeth extraction, which is of wide clinical use.

[The mutations of the D-loop hypervariable region II and hypervariable region III of mitochondrial DNA in oral squamous cell carcinoma].

OBJECTIVE: To investigate the frequency of mitochondrial DNA (mtDNA) D-loop hypervariable region II (HVR II) and hypervariable region III (HVR III) mutations in oral squamous cell carcinoma (OSCC) and their correlation to provide the new targets for the prevention and treatment of OSCC. METHODS: The D-loop HVR II and HVR III regions of mtDNA in seven cases with OSCC tissues, matched with paracancerous tissues and normal mucosa tissues from the same case, were amplified by polymerase chain raction (PCR), then were detected by direct sequencing to find the mutantsites after the comparison of all sequencing results with the mtDNA Cambridge sequence in the GenBank database. RESULTS: 82 (56 species) nucleotide changes, with 51(26 species) nucleotide polymorphism, were found after the comparison of all sequencing results with the mtDNA Cambridge sequence in the GenBank database. 31(30 species) mutations, with 21 located within the HVR II and HVR III regions, were found in 3 tumor tissue samples, their paracancerous and normal mucosa tissue were found more polymorphic changes but no mutation. The mtDNA D-loop HVR II and HVR III regions mutation rate was 42.9% (3/7) in OSCC. CONCLUSION: The mtDNA D-loop HVR II and HVR III regions were highly polymorphic and mutable regions in OSCC. It suggested that the D-loop HVR II and HVR III regions of mtDNA might play a significant role in the tumorigenesis of OSCC. It may become new targets for the gene therapy of OSCC by regulating the above indexes.