FAP Serves as a Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) poses significant challenges with poor survival rates and limited therapeutic strategies. Our study, using The Cancer Genome Atlas (TCGA) data, assesses cancer-associated fibroblast (CAF) gene signatures' clinical relevance. In our analysis across TCGA tumor types, differential gene expression analysis revealed that fibroblast activation protein (FAP) is upregulated in tumor tissues and associated with poorer survival rates in HNSCC. Furthermore, mechanistic studies employing gene-silencing techniques substantiated that FAP knockout led to a significant decrease in cellular proliferation, invasion, and migration in HNSCC cell lines. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we established that high FAP expression correlates with vital biological processes such as extracellular matrix organization, angiogenesis, and cellular motility. Importantly, FAP was found to regulate these processes by promoting the expression of key proteins involved in epithelial-mesenchymal transition-related pathways. Additionally, our analysis revealed a significant correlation between FAP expression and the expression profiles of immune checkpoint molecules, underscoring its potential role in immune modulation. Collectively, our findings illuminate FAP's pivotal role in HNSCC pathogenesis and its potential as a prognostic biomarker and therapeutic target. This research lays the groundwork for understanding the multifaceted roles and regulatory mechanisms of CAFs in HNSCC, thereby offering valuable perspectives for the development of targeted therapeutic strategies aimed at improving patient outcomes.

Abnormal Decrease of Macrophage ALKBH5 Expression Causes Abnormal Polarization and Inhibits Osteoblast Differentiation.

Peri-implant tissue inflammation is an inflammatory injury that occurs in the soft and hard tissues surrounding the implant and is the main cause of short- or long-term failure of implant prosthetic restorations, which is compounded by bone loss and bone destruction in the alveolar bone of diabetes patients with peri-implantitis. However, the mechanisms underlying the persistence of diabetic peri-implantitis, as well as the essential connections and key molecules that regulate its start and progression, remain unknown. In this study, we discovered that M1 macrophage polarization was abnormally enhanced in diabetic peri-implantitis and influenced the osteogenic differentiation of mesenchymal stem cells. RNA sequencing revealed that ALKBH5 expression was abnormally reduced in diabetic peri-implantitis. Further mechanism study showed that ALKBH5 and its mediated m6A can influence osteogenic differentiation, which in turn influences the persistence of diabetic peri-implantitis. Our findings present a new mechanism for the suppression of osteoblast development in diabetic peri-implantitis and a new treatment strategy to promote anabolism by inhibiting ALKBH5.

Prediction of inlet SO2 concentration of wet flue gas desulfurization (WFGD) by operation parameters of coal-fired boiler.

Circulating fluidized bed (CFB) boilers with wet flue gas desulfurization (WFGD) system is a popular technology for SO2 removal in the coal-fired thermal power plant. However, the long response time of continues emission monitoring system (CEMS) and the hardness of continuously monitoring the coal properties leads to the difficulties for controlling WFGD. It is important to build a model that is adaptable to the fluctuation of load and coal properties, which can obtain the SO2 concentration ahead CEMS, without relying on coal properties. In this paper, a prediction model of inlet SO2 concentration of WFGD considering the delay between the features and target based on long-short term memory (LSTM) network with auto regression feature is established. The SO2 concentration can be obtained 90 s earlier than CEMS. The model shows good adaptability to the fluctuation of SO2 concentration and coal properties. The root-mean-squared error (RMSE) and R squared (R2) of the model are 30.11 mg/m3 and 0.986, respectively. Meanwhile, a real-time prediction system is built on the 220 t/h unit. A field test for long-term operation has been conducted. The prediction system is able to continuously and accurately predict the inlet SO2 concentration of the WFGD, which can provide the operators with an accurate reference for the control of WFGD.

YTHDC1 Promotes Stemness Maintenance and Malignant Progression in Head and Neck Squamous Cell Carcinoma.

Background: YTH domain containing 1 (YTHDC1), an N6-methyladenosine (m6A) modification reading protein, plays a key role in regulating RNA translation and degradation. However, the role of YTHDC1 in head and neck squamous cell carcinoma (HNSCC) cancer stem cells remains largely unknown. This study is aimed at investigating the role of YTHDC1 in HNSCC and exploring its role in regulating cancer stem cells. Methods: RNA sequencing was used to detect differentially expressed genes (DEGs) between SCC9 spheres and SCC9 cells and to uncover molecular pathways and target molecules associated with CSCs. We detected YTHDC1 expression in The Cancer Genome Atlas (TCGA) database data and clinical samples. Subsequently, YTHDC1 gene suppression assays were performed in HNSCC cell lines to investigate the effect of YTHDC1 on tumor cell stemness maintenance, proliferation, and migration capacity. To further confirm the role of YTHDC1 in regulating cancer stem cells in HNSCC, we analyzed online HNSCC single-cell transcriptomic data to investigate YTHDC1 expression patterns at the single-cell level and the correlation of these levels with the expression of stem cell markers. Results: YTHDC1 expression levels were significantly upregulated in SCC9 spheres, and YTHDC1 was aberrantly expressed in HNSCC tumor tissues. The increased YTHDC1 expression was closely correlated with the clinical characteristics of HNSCC patients. YTHDC1 regulates the malignant phenotype of HNSCC in both in vivo and in vitro studies. Further single-cell transcriptomic data analysis revealed that YTHDC1 positively correlated with malignant epithelial cell stemness capacity at the single-cell level, and that YTHDC1 was involved in regulating stemness maintenance in HNSCC. Conclusions: These findings suggest that YTHDC1 may serve as a biomarker for stem maintenance and malignant progression in HNSCC, providing new insights into the treatment of cancer.

TAB2 Promotes the Biological Functions of Head and Neck Squamous Cell Carcinoma Cells via EMT and PI3K Pathway.

Background: Transforming growth factor ß 1-activated kinase 1 binding protein 2 (TAB2) mediates a variety of biological processes through activated nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB) signaling pathways. TAB2 has been reported to be upregulated in a variety of tumors. However, little is known about its potential role in oral squamous cell carcinoma (OSCC). Material and Methods. Patients' clinicopathological and transcription data were obtained from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry staining was used to determine TAB2 expression in OSCC tissues (IHC). The expression of TAB2 in OSCC cell lines was detected by western blotting. The CCK-8 test and flow cytometry assay were utilized to evaluate cell proliferation, apoptosis, and cell cycle in OSCC cell lines. Enrichment analysis and identification of predicted signaling pathways were performed by Gene Ontology and KEGG analysis. Finally, the expression of downstream signal molecules was performed using western blotting to validate the mechanism investigations. Results: TAB2 expression level was aberrantly upregulated in OSCC patients. TAB2 expression was shown to be inversely associated to prognosis. The phenotypic of OSCC cells was considerably impacted by TAB2. OSCC cells with deleted TAB2 exhibit decreased proliferation and increased apoptosis. Additionally, OSCC progression is aided by TAB2 overexpression. Further mechanism studies showed that TAB2 could regulate the progression of OSCC by mediating the upregulation of EMT and PI3K-AKT signaling pathways. Conclusion: This study sheds light on the carcinogenic role of TAB2 in OSCC and provides a potential therapeutic strategy.

Reallocation of cutaneous and global blood circulation during sauna bathing through a closed-loop model.

OBJECTIVE: Sauna bathing (SB) is an important strategy in cardiovascular protection, but there is no mathematical explanation for the reallocation of blood circulation during heat-induced superficial vasodilation. We sought to reveal such reallocation via a simulated hemodynamic model. METHODS: A closed-loop cardiovascular model with a series of electrical parameters was constructed. The body surface was divided into seven blocks and each block was modeled by a lumped resistance. These resistances were adjusted to increase skin blood flow (SBF), with the aim of reflecting heat-induced vasodilation during SB. Finally, the blood pressure was compared before and after SB, and the blood flow inside the aorta and visceral arteries were also analyzed. RESULTS: With increasing SBF in this model, the systolic, diastolic, and mean blood pressure in the arterial trunk decreased by 13-29, 18-36, and 19-37 mmHg, respectively. Despite the increase in the peak and mean blood flow in the arterial trunk, the diastolic blood flow reversal in the thoracic and abdominal aortas increased significantly. Nevertheless, the blood supply to the heart, liver, stomach, spleen, kidney, and intestine decreased by at least 25%. Moreover, the pulmonary blood flow increased significantly. CONCLUSION: Simulated heat-induced cutaneous vasodilation in this model lowers blood pressure, induces visceral ischemia, and promotes pulmonary circulation, suggesting that the present closed-loop model may be able to describe the effect of sauna bathing on blood circulation. However, the increase of retrograde flow in the aortas found in this model deserves further examination.

Clinical and hemodynamic insights into the use of internal iliac artery balloon occlusion as a prophylactic technique for treating postpartum hemorrhage.

Recently, the effectiveness of internal iliac artery balloon occlusion (IIABO) for treating postpartum hemorrhage caused by pernicious placenta previa (PPP) has been questioned. We conducted a retrospective analysis and hemodynamic simulation to assess the IIABO's effectiveness. The retrospective analysis involved 480 patients with PPP, among which 288 underwent IIABO treatment and the remaining 192 were used as controls. Blood loss and preoperative indicators were recorded, and multiple regression analysis was applied to test the effect of preoperative indicators on blood loss. Hemorrhage mechanisms were simulated using a numerical model. Results suggested that no significant difference in blood loss (1836 ± 1440 ml vs. 1784 ± 1647 ml, p = 0.22) was observed between the two groups. In addition, preoperative indicators, including age, weight, gestational age, gravidity, parity, blood type, anemia, or diabetes, were not associated with blood loss. In the simulation, after the intra-iliac artery was blocked, blood loss was caused by a reversed flow in the intrapelvic arteries, uterine veins, and uterine venules. The ratio of the time-averaged hemorrhage velocity (TAHV) in the balloon group to that in the control group was lower than that obtained in a clinical study (13.0% vs. 88.9%); in the presence of collateral circulation, blood loss occurred from collateral circulation and uterine venules after IIABO intervention, and the TAHV was 60%-90% that of the control group, which was closer to the clinical results (88.9%). These results suggest that IIABO cannot effectively treat postpartum hemorrhage because of the collateral circulation and reversed flow in the uterine venules.

The interaction between vacancy defects in gallium sulfide monolayer and a new vacancy defect model.

Vacancy defects are inevitable when synthesizing two-dimensional (2D) materials, and vacancy defects greatly affect the physical properties, such as magnetism and electronic properties. Currently, sufficient information is not available on whether and how the interaction of vacancy defects affects material properties and how to control these defects and their associated interaction for the development of new materials. In this study, the interaction between two adjacent vacancy defects of the gallium sulfide (GaS) monolayer is investigated using first-principles calculations based on density functional theory (DFT). The results indicate that the localized size of a Ga vacancy defect is the area within the S atoms second nearest to the neighboring vacancy defect. When the localized sizes of Ga vacancy defects intersect, a non-negligible interaction exists between the Ga vacancy defects. The interaction generally has been ignored by the traditional defect concentrations model but would affect the magnetic and electronic properties of the defective GaS monolayer. A vacancy defect cluster model (VDCM) is developed based on the system clustering method and then used to evaluate the interactions between vacancy defects. In order to check the reliability of the model, this research studies a defective MoS2 monolayer as an example and compares the band gap and density of states (DOS) calculated by using different vacancy defect models, including VDCM. The results indicate that VDCM has good accuracy relative to the traditional vacancy concentration model. This means that with the help of VDCM the properties of the defective system could be calculated more accurately considering some extent of nonuniform distribution of defects based on DFT.

Strain rate dependency of dislocation plasticity.

Dislocation glide is a general deformation mode, governing the strength of metals. Via discrete dislocation dynamics and molecular dynamics simulations, we investigate the strain rate and dislocation density dependence of the strength of bulk copper and aluminum single crystals. An analytical relationship between material strength, dislocation density, strain rate and dislocation mobility is proposed, which agrees well with current simulations and published experiments. Results show that material strength displays a decreasing regime (strain rate hardening) and then increasing regime (classical forest hardening) as the dislocation density increases. Accordingly, the strength displays universally, as the strain rate increases, a strain rate-independent regime followed by a strain rate hardening regime. All results are captured by a single scaling function, which relates the scaled strength to a coupling parameter between dislocation density and strain rate. Such coupling parameter also controls the localization of plasticity, fluctuations of dislocation flow and distribution of dislocation velocity.

KLF14 inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells by downregulating WNT3A.

KLF14 belongs to the Krüppel-like factor (KLF) family of transcription factors. The KLF family activate and/or repress transcription in a promoter- and cell-dependent manner by interacting with co-suppressors or co-activators. However, the function and mechanism of KLF14 in osteogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) is unknown. This study explores the impact and molecular mechanism of KLF14 in hMSC osteogenic differentiation in vitro. We found that KLF14 was highly expressed in hMSCs, and KLF14 expression gradually decreased after inducing osteogenic differentiation. Inhibiting KLF14 expression promoted osteogenic differentiation of hMSCs. We also found that KLF14 interacted with the WNT3A promoter. This interaction decreased expression of WNT3A and downstream osteogenesis-related target genes in the WNT signaling pathway, and resulted in cell cycle arrest. In conclusion, we describe a new mechanism for KLF14 in differentiation of hMSCs into osteoblasts and suggest a new target for clinical therapeutics related to human bone development.

Antitumorigenic Effect of Hsp90 Inhibitor SNX-2112 on Tongue Squamous Cell Carcinoma is Enhanced by Low-Intensity Ultrasound.

PURPOSE: The novel Hsp90 inhibitor SNX-2112 showed broad antitumor activity. However, it was still necessary to optimize the therapeutic dosage of SNX-2112 applied on tumors to obtain effective therapy with minimal dose to reduce toxicity. We investigated the role of low-intensity US in promoting antitumorigenic effect of low doses of SNX-2112 on tongue squamous cell carcinoma. METHODS: Cell viability was measured using CCK-8 assay or staining with Calcein AM/PI. Relative cumulative levels of SNX-2112 in cells were detected using high-performance liquid chromatography. The production of ROS was analyzed using fluorescence microscope and flow cytometer. Cellular apoptosis was detected using flow cytometer. The expression levels of proteins of the ERS-associated apoptosis signaling pathway were detected using Western blotting analysis. The efficacy and biosafety of SNX-2112 were also investigated in a mouse xenograft model. RESULTS: Low-intensity US combined with SNX-2112 exhibited significant antitumor effect, increased the absorption of SNX-2112 by cells even with a low dose, enhanced ROS generation and apoptosis. The combination regimen also inhibited the protein expression of Hsp90 and triggered apoptosis through endoplasmic reticulum stress (ERS) by enhancing PERK, CHOP and Bax protein levels, while downregulating the level of Bcl-2. Additionally, N-acetyl-L-cysteine (NAC), ROS scavenger, was able to reverse these results. Low-intensity US combined with SNX-2112 significantly inhibited tumor growth, prolonged survival of mice, decreased proliferation and promoted apoptosis with no visible damage or abnormalities in major organs in the mouse xenograft model with tongue squamous cell carcinoma. CONCLUSION: The antitumor effects of SNX-2112 were enhanced by low-intensity US. The most probable mechanism was that US sonoporation induced more SNX-2112 delivery to the cells and enhanced ROS production, triggering the ERS-associated apoptosis signaling pathway. Therefore, low-intensity US may increase the efficiency of conventional chemotherapy and reduce the dosage of SNX-2112 required and its side effects.

Acute and short-term efficacy of sauna treatment on cardiovascular function: A meta-analysis.

OBJECTIVE: The role of sauna bathing in cardiovascular function treatment has been increasingly explored, but insufficient attention has been paid to its efficacy. We performed a meta-analysis to provide more evidence for the efficacy of sauna treatment in cardiovascular nursing. METHODS: Sixteen peer-reviewed journal articles were screened to summarize the efficacy of the sauna on cardiovascular function. Both acute (0-30 min after the sauna) and short-term (2-4 weeks following the sauna treatment) efficacies were investigated. RESULTS: For pooled acute efficacy, body temperature and heart rate significantly (p<0.001) grew by 0.94℃ and 17.86 beats/min, respectively; reductions of 5.55 mmHg (p<0.001) and 6.50 mmHg (p<0.001) were also observed in systolic blood pressure and diastole blood pressure, respectively. For combined short-term efficacy, left ventricular ejection fraction (LVEF), 6-min walk distance, and flow-mediated dilation (p<0.001) increased by 3.27%, 48.11 m, and 1.71%, respectively; greater amelioration in LVEF was observed in participants with lower LVEF. The proportion of patients with New York Heart Association class III and IV decreased by 10.9% and 12.2%, respectively. Systolic blood pressure, diastolic blood pressure, brain natriuretic peptide concentration, left ventricular end-diastolic dimension, cardiothoracic ratio, and left atrial dimension reduced by 5.26 mmHg (p<0.001), 4.14 mmHg (p<0.001), 116.66 pg/mL (p<0.001), 2.79 mm (p<0.001), 2.628% (p<0.05), and 1.88 mm (p<0.05), respectively, while the concentration of norepinephrine in the plasma remained unchanged. CONCLUSION: Sauna treatment was found to play a positive role in improving cardiovascular function and physical activity levels, especially in patients with low cardiovascular function. These findings reveal that thermal intervention may be a promising means for cardiovascular nursing.

The preventive effect of Cuscutae Semen polysaccharide on bone loss in the ovariectomized rat model.

The seed of Cuscutae Semen has been used as a functional food to prevent osteoporosis and aging, and improve sexual function in Traditional Chinese Medicine. However, there is a little report on its beneficial effects on osteoporosis. The purpose of our study was to explore whether Cuscutae Semen polysaccharide (CSP) could prevent osteoporosis induced by estrogen deficiency in the ovariectomized rat model. The preventive effect of CSP was assessed using the ovariectomized (OVX) rat model by treatment with vehicle or CSP for 12 weeks. Serum indexes related to osteogenesis were measured using ELISA kits. The underlying mechanism of action of CSP was evaluated by qRT-PCR. The findings showed that CSP exerted bone protective effects via the increase of bone mass, BMD, IGF, TGF-ß, osteocalcin, and osteoprotegerin, and the decrease of TRAP and CTX levels in estrogen deficiency-induced osteoporosis, which is mediated by up-regulating the expression levels of Osterix, BMP-2, Runx2, and Smad5 and down-regulating the expression levels of TRAP, NFATc1, c-Fos, and cathepsin K. These findings suggested that CSP exhibited the preventive effects in the estrogen deficiency-induced osteoporosis via promoting bone formation and inhibiting bone resorption. Therefore, CSP may be developed as a promising agent for the prevention of estrogen deficiency-induced osteoporosis.

miR-182-5p Promotes Growth in Oral Squamous Cell Carcinoma by Inhibiting CAMK2N1.

BACKGROUND/AIMS: Emerging evidence suggests that the propagation of oral squamous cell carcinoma (OSCC) is influenced by the abnormal expression of microRNAs (miRNAs). This study aimed to characterize the involvement of miR-182-5p in OSCC by targeting the calcium/ calmodulin-dependent protein kinase II inhibitor CAMK2N1. METHODS: miR-182-5p expression was quantified in OSCC tissues and cell lines with reverse transcription polymerase chain reaction (RT-PCR). Cell colony formation, Cell Counting Kit-8 (CCK-8), Ki-67, and nude mouse xenograft assays were used to characterize the role of miR-182-5p in the proliferation of OSCC. A miR-182-5p target gene was identified with western blotting, RT-PCR, and luciferase activity assays. OSCC patient survival based on CAMK2N1 expression was also analyzed. RESULTS: miR-182-5p was up-regulated in in vitro cell lines and in vivo clinical OSCC samples. CCK-8, colony formation, and Ki-67 assays revealed that miR-182-5p promoted the growth and proliferation of OSCC cells. miR-182-5p directly targeted CAMK2N1, as evidenced by luciferase assays and target prediction algorithms. CAMK2N1 operated as a tumor suppressor gene in patients with OSCC. Down-regulating miR-182-5p expression in the CAL-27 cell line restored CAMK2N1-mediated OSCC cell proliferation. miR-182-5p expression inhibited the activation of AKT, ERK1/2, and NF-κB. Mice injected with CAL-27 cells transfected with miR-182-5p-inhibitor demonstrated a significant increase in tumor size and weight and increased CAMK2N1 mRNA and protein expression compared with the miR-negative control group. CONCLUSION: The miR-182-5p-CAMK2N1 pathway can be potentially targeted to regulate the proliferation of OSCC cells.

[Clinical application of lateral lag screw in fixing intracapsular sagittal condylar fracture].

OBJECTIVE: To introduce the clinical application and curative effect of lateral lag screw technique in fixing condylar intracapsular sagittal fractures. METHODS: Thirteen condyles with intracapsular sagittal fracture of 11 cases were fixed using lateral lag screw technique. Curative effects were observed by clinical and radiological follow-up for 6 approximately 30 months (mean 12 months) postoperatively. RESULTS: The favorable results were obtained in all cases. All patients were satisfied with the clinical results. slight malocclusion existed in 2 cases. Radiological abnormalities were seen in 3 cases by CT scanning, but without any obvious function disturbances. CONCLUSIONS: Lateral lag screw technique is a simple and effective treatment in fixing intracapsular sagittal condylar fractures.

[Application of distraction osteogenesis in severe maxillary hypoplasia secondary to cleft palate].

OBJECTIVE: To evaluate the effect of distraction osteogenesis in correction of severe undeveloped maxilla secondary to cleft palate and to evaluate the selection of distraction modality. METHODS: Distraction osteogenesis was performed upon 8 patients, 6 males and 2 females, aged 11 to 25 years, one with incomplete cleft palate, 4 with unilateral complete left palate, and 3 with bilateral complete cleft palate, all accompanied with severe maxillary hypoplasia. The 7 adult patients were treated by modified high-stepped Le Fort I osteotomy, the other patient, a child, was treated by Le Fort I osteotomy followed by rigid external distraction. X-ray films of skull in lateral, frontal, or panoramic positions, and X-ray film of temporomandibular joint in Schiller's position were taken pre- and postoperatively. In model surgery the accurate distraction distance was measured and the direction of distraction designed. Orthodontic therapy was started immediately after the distraction was completed and the distractor was removed after a period of 4 months' consolidation. RESULTS: The designed distraction was achieved in a11 8 patients. Except in one case with a bone defect 1 cm x 0.5 cm at the osteotomy line in the lateral wall of the right maxillary sinus, dense new bone was formed in the area of distraction in the other cases. The postoperative occlusal relationship was good and stable. No infection and other complication was found. During an average of 20 months' follow-up, the maxilla and occlusion were stable, and no relapse was found. The distance of forward distraction of the maxilla reached an average of l2 mm (5 approximately 15 mm). The SNA angle increased from 71 degree on average preoperatively to an average of 79 degree postoperatively. Both the facial appearance and occlusal relationship returned to normal in a11 the patients. CONCLUSION: Without need of bone grafting and with a stable effect and little influence on platatopharyngeal competence, distraction osteogenesis is an effective method of correcting maxillary hypoplasia secondary to cleft palate and is worthy of spreading.