Dual-loaded nano pesticide system based on industrial grade scaleable carrier materials with combinatory efficacy and improved safety.

Repeated and widespread use of single chemical pesticides raises concerns about efficiency and safety, developing multi-component synergistic pesticides provides a new route for efficient control of diseases. Most commercial compound formulations are open systems with non-adjustable released rates, resulting in a high frequency of applications. Meanwhile, although nano pesticide delivery systems constructed with different carrier materials have been extensively studied, realizing their actual scale-up production still has important practical significance due to the large-scale field application. In this study, a boscalid and pyraclostrobin dual-loaded nano pesticide system (BPDN) was constructed with industrial-grade carrier materials to facilitate the realization of large-scale production. The optimal industrial-scale preparation mechanism of BPDN was studied with surfactants as key factors. When agricultural emulsifier No.600 and polycarboxylate are used as the ratio of 1:2 in the preparation process, the BPDN has a spherical structure with an average size of 270 nm and exhibits superior physical stability. Compared with commercial formulation, BPDN maintains rate-stabilized release up to 5 times longer, exhibits better dispersion and spreading performance on foliar, has more than 20% higher deposition amounts, and reduces loss. A single application of BPDN could efficiently control tomato gray mold during the growing period of tomatoes due to extended duration and combinatory effectiveness, reducing two application times and labor costs. Toxicology tests on various objects systematically demonstrated that BPDN has improved safety for HepG2 cells, and nontarget organism earthworms. This research provides insight into creating safe, efficient, and environmentally friendly pesticide production to reduce manual operation times and labor costs. Accompanied by production strategies that can be easily scaled up industrially, this contributes to the efficient use of resources for sustainable agriculture.

Efficacy of Iminoctadine Trialbesilate and Trifloxystrobin in Inhibiting and Controlling Pear Powdery Mildew (Phyllactinia pyri) in Hebei Province, China.

Pear powdery mildew (PPM), caused by Phyllactinia pyri, is one of the most serious diseases affecting production in the Hebei pear-growing region of China. Iminoctadine trialbesilate and trifloxystrobin are known to have broad-spectrum activity against a wide range of plant pathogens, including P. pyri. A total of 105 P. pyri strains were isolated from 11 cities in Hebei Province from 2017 to 2019. Iminoctadine trialbesilate and trifloxystrobin significantly inhibited P. pyri growth. Microscopic observation showed that P. pyri mycelia had different degrees of desiccation and that the conidial cell contents had been released. The sensitivities of 60 P. pyri strains to iminoctadine trialbesilate and trifloxystrobin were determined in vitro, and the average EC50 values were 0.5773 ± 0.0014 and 1.2038 ± 0.0010 µg/ml, respectively. The average EC50 values for 85 and 75% of the strains with continuous single peak frequency distributions were 0.4534 ± 0.0012 and 0.8124 ± 0.0039 µg/ml, respectively. These data could be used as the baseline sensitivities of P. pyri to these two fungicides. The maximum difference multiples of the sensitivities of P. pyri strains from the different cities to iminoctadine trialbesilate and trifloxystrobin were 13.5- and 17.2-fold, respectively. Cluster analysis showed that there was no significant correlation between P. pyri sensitivity and geographical origin. The field efficacies in controlling PPM were higher than 85%. These findings can improve how we monitor iminoctadine trialbesilate and trifloxystrobin resistance and improve application efficiency.

CO2 Footprint of Thermal Versus Photothermal CO2 Catalysis.

Transformation of CO2 into value-added products via photothermal catalysis has become an increasingly popular route to help ameliorate the energy and environmental crisis derived from the continuing use of fossil fuels, as it can integrate light into well-established thermocatalysis processes. The question however remains whether negative CO2 emission could be achieved through photothermal catalytic reactions performed in facilities driven by electricity mainly derived from fossil energy. Herein, we propose universal equations that describe net CO2 emissions generated from operating thermocatalysis and photothermal reverse water-gas shift (RWGS) and Sabatier processes for batch and flow reactors. With these reactions as archetype model systems, the factors that will determine the final amount of effluent CO2 can be determined. The results of this study could provide useful guidelines for the future development of photothermal catalytic systems for CO2 reduction.

Differentiation of low- and high-grade pediatric gliomas with amide proton transfer imaging: added value beyond quantitative relaxation times.

OBJECTIVES: To evaluate whether amide proton transfer (APT) MRI can be used to characterize gliomas in pediatric patients and whether it provides added value beyond relaxation times. METHODS: In this prospective study, APT imaging and relaxation time mapping were performed in 203 pediatric patients suspected of gliomas from February 2018 to December 2019. The region of interest (ROI) in the tumor was automatically generated with artifact detection and ROI-shrinking algorithms. Several APT-related metrics (CESTR, CESTRnr, MTRRex, AREX, and APT#) and quantitative T1 and T2 were compared between low-grade and high-grade gliomas using the student's t-test or Mann-Whitney U-test. The performance of these parameters was assessed using the receiver operating characteristic (ROC) analysis. A stepwise multivariate logistic regression model was used to combine the imaging parameters. RESULTS: Forty-eight patients (mean age: 6 ± 4 years; 23 males and 25 females) were included in the final analysis. All the APT-related metrics except APT# had significantly (p < 0.05) higher values in the high-grade group than the low-grade group. Under different ROI-shrinking cutoffs, the quantitative T1 (p = 0.045-0.200) and T2 (p = 0.037-0.171) values of high-grade gliomas were typically lower than those of low-grade ones. The stepwise multivariate logistic regression revealed that CESTRnr and APT# were combined significant predictors of glioma grades (p < 0.05), with an area under the ROC curve (AUC) of 0.86 substantially larger than those of T1 (AUC = 0.69) and T2 (AUC = 0.68). CONCLUSIONS: APT imaging can be used to differentiate high-grade and low-grade gliomas in pediatric patients and provide added value beyond quantitative relaxation times. KEY POINTS: • Amide proton transfer (APT) MRI showed significantly (p < 0.05) higher values in pediatric patients with high-grade gliomas than those with low-grade ones. • The area under the curve was 0.86 for APT MRI to differentiate low-grade and high-grade gliomas in pediatric patients, which was substantially higher than that for quantitative T1 (0.69) and T2 (0.68). • APT MRI demonstrated added value beyond quantitative T1 and T2 mapping in characterizing pediatric gliomas.

Inhibitory effect of carboxylated nanodiamond on oral pathogenic bacteria Streptococcus mutans.

BACKGROUND: Nanodiamonds (NDs) have been demonstrated to have bactericidal activity on several microorganisms and can be used in various kinds of dental materials. NDs are potential candidates for antibacterial dental materials. However, the possible inhibitory effect of NDs on oral pathogenic bacteria is largely unknown. This study was performed to investigate the inhibitory effects of carboxylated nanodiamond (cND) on Streptococcus mutans. METHODS: Fourier transform infrared spectroscopy was used to confirm carboxyl groups on the surface of commercial cND. The inhibitory effect of serially diluted cND on S. mutans was evaluated by spectrophotometry and plating methods. Escherichia coli was treated as a positive control in spectrophotometry. Chlorhexidine was used as a positive control in plating methods. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to confirm the antibacterial activity of cND. RESULTS: The results showed that cND exhibited a significant inhibitory effect on S. mutans. For S. mutans, the minimum inhibitory concentration was 4 µg/ml and the minimum bactericidal concentration was 16 µg/ml. SEM and TEM results indicated that cND functioned as an antibacterial agent, likely due to its ability to disrupt the cell membrane of S. mutans. CONCLUSION: In conclusion, these findings demonstrated an inhibitory effect of cND on S. mutans and suggest its use as a potential antibacterial dental material.

Application of a surgical guide in the extraction of impacted mesiodentes: a randomized controlled trial.

OBJECTIVE: To explore and evaluate the application of a surgical guide in the extraction of impacted mesiodentes. MATERIALS AND METHODS: Patients with impacted mesiodentes approachable from the labial side of the maxilla were randomly divided into three groups. The surgical guide for group I was made using cone beam computed tomography (CBCT) and dental cast, whereas the surgical guide for group II was only made using CBCT data. Group I and group II were first evaluated to determine whether guide use could accurately locate the cementoenamel junction (CEJ) of the mesiodentes, and the impacted mesiodentes were extracted with the help of the surgical guide. Group III underwent an operation without a guide. For all patients, the preoperative design time, tooth searching time, operation time, complications, and costs were measured. RESULTS: The guides for group I and group II could locate the CEJ of the mesiodentes accurately, with good application effect during the operation. Group I and group II required additional preoperative design time compared with group III. However, the tooth searching time and operation time in groups I and II were significantly reduced compared with those in group III. Group I and group II showed no intraoperative complications, and two cases in group III showed imprecision during localization. The overall cost for group III was higher than that of group I or group II. But group I and group II required extra visits and costs. CONCLUSIONS: Despite some limitations, the surgical guide assisted with mesiodentes extraction and can improve the quality of the operation quality as well as reducing its economic burden, difficulty, and duration. Through proper design, we can create a high-quality surgical guide using only CBCT data. CLINICAL RELEVANCE: The surgical guide can be used as an important assistive tool in alveolar surgery.

Postoperative online follow-up improves the quality of life of patients who undergo extraction of impacted madibular third molars: a randomized controlled trial.

OBJECTIVE: To evaluate the effect of online follow-up on the quality of life of patients who undergo extraction of impacted mandibular third molars. MATERIALS AND METHODS: This study enrolled patients with impacted mandibular third molars who were treated at the Department of Oral and Maxillofacial Surgery of the Stomatological Hospital at Southern Medical University and divided them into test and control groups. The test group received an online follow-up on the first, third, and fifth days after tooth extraction, while the control group was not followed up with. Patients in both groups were reexamined on the postoperative seventh day, completing the postoperative symptom severity (PoSSe) scale to comprehensively and quantitatively evaluate their quality of life after tooth extraction. A visual analogue scale (VAS) was used to evaluate the degree of approval for an online follow-up after tooth extraction by 20 senior doctors (≥ 40 years old) and 20 young doctors (<4 0 years old). RESULTS: The PoSSe scale scores of the remaining options in the test group were significantly lower than those in the control group. The VAS score of senior doctors for online follow-up was significantly lower than that of young doctors. CONCLUSIONS: A postoperative online follow-up effectively improved the quality of life of patients who underwent extraction of impacted mandibular third molars. Compared with senior doctors, young doctors were more likely to approve an online follow-up after tooth extraction. CLINICAL RELEVANCE: Online medical care can be considered as an auxiliary tool to improve the effect of oral treatment.

CCL18-NIR1 promotes oral cancer cell growth and metastasis by activating the JAK2/STAT3 signaling pathway.

BACKGROUND: Chemokine (C-C motif) ligand 18 (CCL18) affects the malignant progression of varying cancers by activating chemokine receptors. Our previous work has shown that CCL18 promotes hyperplasia and invasiveness of oral cancer cells; however, the cognate receptors of CCL18 involved in the pathogenesis of oral squamous cell carcinoma (OSCC) have not yet been identified. This study aimed to investigate the molecular mechanisms which underlie promotive effects of CCL18 on OSCC progression by binding to functional receptors. METHODS: The expression of CCL18 receptor-NIR1 in OSCC was determined by conducting western blot, immunofluorescence, and immunocytochemistry assays. Chi square test was applied to analyze the relationship between expression levels of NIR1 and clinicopathological variables. Recombinant CCL18 (rCCL18), receptor siRNA and JAK specific inhibitor (AG490) were used in experiments investigating the effects of the CCL18-NIR1 axis on growth of cancer cells (i.e., proliferation, and metastasis), epithelial-mesenchymal transition (EMT) and the activation of the JAK2/STAT3 signaling pathway. RESULTS: NIR1 as functional receptor of CCL18 in OSCC, was found to be significantly upregulated in OSCC and positively related to the TNM stage of OSCC patients. rCCL18 induced the phenotypical alterations in oral cancer cells including cell growth, metastasis and EMT. The JAK2/STAT3 signaling pathway was confirmed to be a downstream pathway mediating the effects of CCL18 in OSCC. AG490 and knockdown of NIR1 could block the effects of rCCL18-induced OSCC. CONCLUSION: CCL18 can promote the progression of OSCC by binding NIR1, and the CCL18-NIR1 axis can activate JAK2/STAT3 signaling pathway. The identification of the mechanisms underlying CCL18-mediated promotion of OSCC progression could highlight potential therapeutic targets for treating oral cancer.

A feed-forward regulatory network lncPCAT1/miR-106a-5p/E2F5 regulates the osteogenic differentiation of periodontal ligament stem cells.

Periodontal ligament stem cells (PDLSCs) are characterized by multiple differentiation potential and potent self-renewal ability, yet much remains to be elucidated that what determines these properties. Long noncoding RNAs (lncRNAs) have been suggested to involve in multiple biological process under physiological and pathological conditions, including osteogenic differentiation. In the present study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified prostate cancer-associated ncRNA transcript-1 (lncPCAT1) was gradually increased in PDLSCs during consecutive osteogenic induction, and it could further positively regulate the osteogenic differentiation both in vitro and in vivo, whereas lncPCAT1 inhibition led to suppressed osteogenic differentiation. Thereafter, we inferred a predicted interaction between lncPCAT1 and miR-106a-5p and then confirmed the direct binding sites of miR-106a-5p on lncPCAT1. Although miR-106a-5p upregulation led to decreased osteogenic differentiation, lncPCAT1 overexpression could reverse its suppression, indicating that lncPCAT1 act as a competing endogenous RNA for miR-106a-5p. Moreover, lncPCAT1 could sponge miR-106a-5p to upregulate miR-106a-5p-targeted gene BMP2, which was a crucial gene involved in osteogenic differentiation. Interestingly, we found that E2F5, another target of miR-106a-5p, could bind to the promoter of lncPCAT1 and then form a feed-forward regulatory network targeting BMP2. In conclusion, our study provided a novel lncRNA-miRNA feed-forward regulatory network and a promising target to modulate the osteogenic differentiation of PDLSCs.

Combination of Suspension Array and Mycelial Growth Assay for Detecting Multiple-Fungicide Resistance in Botrytis cinerea in Hebei Province in China.

To provide a high-throughput, efficient, and accurate method to monitor multiple-fungicide resistance of Botrytis cinerea in the field, we used the suspension array, sequencing, and mycelial growth assay in our research. Discriminating-dose bioassays for detecting carbendazim, diethofencarb, boscalid, and iprodione resistance (CarR, DieR, BosR, and IprR, respectively) were used to analyze 257 isolates collected from Hebei Province in China during 2016 and 2017. High resistance frequencies to carbendazim (100%), diethofencarb (92.08%), and iprodione (86.59%) were detected. BosR isolates accounted for 11.67% of the total. In addition, 103 isolates were randomly selected for phenotype and genotype detection. The high-throughput suspension array was utilized to detect eight genotypes simultaneously, including BenA-E198, BenA-198A, SdhB-H272, SdhB-272Y, BcOS1-I365, BcOS1-365S, erg27-F412, and erg27-412S, which were associated with resistance toward carbendazim or diethofencarb, boscalid, iprodione, and fenhexamid (FenR), respectively. Most of the benzimidazole-resistant isolates (81.55%) possessed the E198V mutation in the BenA gene. Ninety-three isolates with dual resistance to carbendazim and diethofencarb showed the E198V/K mutation. All BosR isolates carried the H272R mutation in the SdhB gene. The I365S and Q369P+N373S (66.99%) mutations in the BcOS1 gene were more frequently observed. No mutation was detected in the erg27 gene in Hebei isolates. There were 13 resistance profile phenotypes. Phenotypes with triple resistance were the most common (83.50%), and CarRDieRBosSIprRFenS was the major type. CarR isolates that carried E198V/K/A were all highly resistant (HR) and only one F200Y mutant was moderately resistant (MR) to carbendazim. Isolates that possessed E198V/K were MR or HR to diethofencarb. BosR isolates that possessed H272R mutation were lowly resistant (LR). IprR isolates were all LR or MR. The distribution of half maximal effective concentrations of CarR isolates with E198V/K mutations and IprR isolates with Q369P+N373S mutations significantly increased from 2016 to 2017. Combined with our observations, a combination method of the high-throughput suspension array and the mycelial growth assay was suggested to accurately monitor multiple resistance of B. cinerea in the field.

TUC338 Overexpression Leads to Enhanced Proliferation and Reduced Apoptosis in Tongue Squamous Cell Carcinoma Cells In Vitro.

PURPOSE: Long noncoding RNAs are closely related to the development of tumors. In this study, we explored the contribution of the long noncoding RNA TUC338 to cellular processes in tongue squamous cell carcinoma (TSCC). MATERIALS AND METHODS: First, we detected TUC338 expression using quantitative reverse transcription-polymerase chain reaction in 25 patients. Then, we transfected a short hairpin RNA to silence TUC338 expression in the CAL-27 and SCC-9 cell lines. Tumor cell growth was determined by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and apoptosis and cell-cycle analyses were performed via flow cytometry. RESULTS: The results indicated that TUC338 was overexpressed in TSCCs (P < .05). In addition, silencing TUC338 in CAL-27 and SCC-9 cells inhibited cell growth and increased apoptosis significantly in vivo (P < .05). CONCLUSIONS: Long noncoding RNA TUC338 overexpression leads to enhanced proliferation and reduced apoptosis in TSCC.

A study on the inhibition of VEGF expression in salivary gland adenoid cystic carcinoma cells via iNOS gene RNAi in vitro.

In this study, we aimed to explore the effect of inducible nitric oxide synthase (iNOS) on vascular endothelial growth factor (VEGF) expression in salivary gland adenoid cystic carcinoma (SACC). Using RNAi, we transfected chemically synthesised iNOS siRNA into ACC-M cells (a highly metastatic adenoid cystic carcinoma cell line) and detected the change in the gene and protein expression levels of iNOS and VEGF by qRT-PCR and Western blotting. A transwell invasiveness assay was used to examine the changes in invasive ability of ACC-M cells. Cell growth was determined using a CCK-8 assay. Apoptosis and cell-cycle phases were detected by flow cytometry. We found that silencing iNOS down-regulated the expression of VEGF and then inhibited cell growth and invasiveness of SACC cells, while it increased apoptosis. Therefore, we concluded that iNOS can regulate VEGF expression and iNOS may be a therapeutic target.

Increased frequency of CD4+ CD25+ FOXP3+ cells correlates with the progression of 4-nitroquinoline1-oxide-induced rat tongue carcinogenesis.

OBJECTIVES: CD4+ CD25+ FoxP3+ T cells (Tregs) play an essential role in sustaining self-tolerance by negatively regulating immune responses. Increased frequencies of Tregs have been reported in a variety of human cancers. The aim of this study was to evaluate the prevalence of Tregs infiltration in the peripheral blood and regional lymph nodes during rat tongue carcinogenesis induced by 4-nitroquinoline-1-oxide (4NQO). MATERIALS AND METHODS: Forty-eight Sprague-Dawley rats were divided into the control (n = 16) and experimental groups (n = 32) to which 4NQO in drinking water was administered. Flow cytometry was used to analyze the prevalence of Tregs in lymphocytes of peripheral blood and regional lymph nodes during 4NQO-induced rat tongue carcinogenesis. CD4+ CD25+ FoxP3+ cells were expressed as a percentage of the total CD4+ cells. RESULTS: The frequency of Tregs in peripheral blood from squamous cell carcinoma rats was significantly higher than controls (3.82 ± 0.62 versus 1.40 ± 0.31 %, P < 0.001). The proportion of Tregs was sequentially increased from moderate dysplasia to severe dysplasia and SCC (1.94 ± 0.72, 2.29 ± 0.82, and 3.82 ± 0.62 %, respectively). The frequency of Tregs in regional lymph nodes from squamous cell carcinoma rats was also significantly higher than normal rat mucosa (14.67 ± 3.09 versus 5.53 ± 2.07 %, P < 0.001). The percentage of Tregs was gradually increased in moderate dysplasia, severe dysplasia, and SCC groups (8.93 ± 1.74, 10.15 ± 0.86, 14.67 ± 3.09 %, respectively) as compared to control group (5.53 ± 2.07 %). CONCLUSION AND CLINICAL RELEVANCE: Tregs in peripheral blood and lymph nodes were associated with disease progression during 4NQO-induced rat tongue carcinogenesis. This study indicated that the upregulation of Tregs might play important role during oral mucosa malignant transformation.

Potential susceptibility genes in patients with stage III and IV periodontitis: A whole-exome sequencing pilot study.

The aim of this study was to screen potential susceptibility genes using whole-exome sequencing (WES) in 15 Han Chinese patients with stage III or IV periodontitis and to evaluate the quantity and quality of genomic DNA extracted from saliva. DNA was extracted from saliva epithelial cells, quality-tested, and then subjected to WES and bioinformatics analyses. All variation loci were analyzed and interpreted following the American College of Medical Genetics and Genomics (ACMG) criteria. Candidate pathogenic variation loci were identified and verified using Sanger sequencing. Correlation and functional analyses of the candidate genes were used to identify potential susceptibility genes in patients with severe periodontitis. LFNG, LENG8, NPHS1, HFE, ILDR1, and DMXL2 genes were identified in over two cases each with shared mutations. Following these analyses, the DMXL2 gene was identified as being associated with stage III and IV periodontitis. These results suggest a potential pathophysiological risk mechanism for periodontitis, but need to be verified through larger clinical studies and mechanistic experiments to determine the pathogenicity of these gene mutations and their generalizability to a wider population of periodontitis patients. By screening candidate pathogenic variation loci using WES in 15 Han Chinese patients with stage III or IV periodontitis, our study could provide a pipeline and feasibility support for the identification of susceptibility genes in patients with stage III and IV periodontitis.

Novel ferroptosis signature for improving prediction of prognosis and indicating gene targets from single-cell level in oral squamous cell carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent kinds of cancers. Therefore, there is a pressing need to create a new risk scoring model to personalize the prognosis of OSCC patients and screen for patient-specific therapeutic agents and molecular targets. Methods: Firstly, A series of bioinformatics was performed to construct a novel ferroptosis-related prognostic model; Further, drug sensitivity analysis was used to screen for specific therapeutic agents for OSCC; Single-cell analysis was employed to investigate the enrichment of FRDEGs (ferroptosis-related differentially expressed genes) in the OSCC microenvironment; Finally, various experiments were conducted to screen and validate molecular therapeutic targets for OSCC. Results: In this study, we constructed a novel 10-FRDEGs risk scoring model. Base on the risk scoring model, we founded three potential chemotherapeutic agents for OSCC: 5Z)-7-Oxozeaenol, AT-7519, KIN001-266; In addition, FRDEGs were enriched in the epithelial cells of OSCC. Finally, we found that CA9 and CAV1 could regulate OSCC proliferation, migration and ferroptosis in vitro. Conclusion: A novel 10-FRDEGs risk scoring model can predict the prognosis of patients with OSCC.Further,5Z)-7-Oxozeaenol, AT-7519, KIN001-266 are potential chemotherapeutic agents for OSCC.Moreover, we identified CA9、CAV1 as potential molecular target for the treatment of OSCC.Our findings provide new directions for prognostic assessment and precise treatment of oral cell squamous carcinoma.

Combination of Bacillus tequilensis with difenoconazole to control pear black spot and the related synergistic mechanism.

Background: Pear black spot (PBS) is caused by Alternaria alternata and causes severe damage worldwide. It is particularly important to screen for synergistic fungicide combinations to address issues associated with the low efficacy of biocontrol agents, high dosage requirements and poor sustained effectiveness of chemical fungicides. Methods: In vitro and in vivo studies were performed to determine the efficacy of a treatment for this important disease. Additionally, transcriptomic and metabolomic analyses were performed to determine the main molecular and biochemical mechanisms involved in the interaction. Results: Bacillus tequilensis 2_2a has a significant synergistic effect with difenoconazole, causing hyphal entanglement and spore lysis and inhibiting the formation of PBS lesions in vitro. In the field, the control effect of the combination was greater than 95%. The pathways associated with the synergistic effect on the mycelia of A. alternata were divided into two main types: one included glycolysis, oxidative phosphorylation, and MAPK signal transduction, while the other included glycolysis, the TCA cycle, coenzyme A biosynthesis, sterol synthesis, and fatty acid degradation. Both types of pathways jointly affect the cell cycle. The main functions of the key genes and metabolites that have been verified as being affected are glucose synthesis and oxidative respiration, as well as citric acid synthesis, acetyl-CoA synthesis, and sterol synthesis. Both functions involve intracellular pyridine nucleotide metabolism and adenine nucleotide transformation. Conclusion: This study helps to reveal the synergistic mechanisms underlying the combined efficacy of biological and chemical agents, providing a scientific basis for field applications.

Effect of injectable calcium alginate-amelogenin hydrogel on macrophage polarization and promotion of jawbone osteogenesis.

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.

The antitumor effects of herbal medicine Triphala on oral cancer by inactivating PI3K/Akt signaling pathway: based on the network pharmacology, molecular docking, in vitro and in vivo experimental validation.

BACKGROUND: This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS: The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS: The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS: Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.

Comprehensive analysis of the expression of the IGF2BPs gene family in head and neck squamous cell carcinoma: Association with prognostic value and tumor immunity.

Background: Head and neck squamous cell carcinoma (HNSCC) represents a predominant type of cancer found in the head and neck region, characterized by a high incidence and unfavorable prognosis. The IGF2BPs gene family, which belongs to the RNA-binding protein class, has been critically implicated in several cancers, and its involvement in HNSCC necessitates further exploration. Objective: To explore the clinical significance and potential biological functions of the IGF2BPs gene family in HNSCC. Methods: A bioinformatic methodology was employed to examine the expression profile, diagnostic and prognostic significance, and biological mechanisms of the IGF2BPs gene family in HNSCC, with a particular emphasis on its involvement in the immune function of HNSCC. This was followed by in vitro investigations to unravel the biological roles of the IGF2BPs gene family in HNSCC. Results: This investigation has demonstrated that, in contrast with normal control tissue, HNSCC has a substantial elevation in the expression level of the IGF2BPs gene family. Patients with a high level of IGF2BPs gene family expression demonstrated higher prediction accuracy for HNSCC. Furthermore, patients with HNSCC and elevated IGF2BPs gene family expression levels exhibited poor survival outcomes. The IGF2BPs gene family displayed a significant association with a variety of immune infiltrating cells and immune genes in HNSCC. Studies conducted in vitro have confirmed that IGF2BP2 silencing suppressed the migration, proliferation, and invasion of HNSCC cells. Conclusions: It has been determined that the IGF2BPs gene family plays a crucial part in the onset and progression of HNSCC, and its association with tumor immunity has been established. The IGF2BPs gene family holds promising potential as a diagnostic and prognostic biomarker for HNSCC.