Impact of preoperative [18F]FDG PET/CT vs. contrast-enhanced CT in the staging and survival of patients with clinical stage I and II non-small cell lung cancer: a 10-year follow-up study.

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.

Jujuboside A ameliorates cognitive deficiency in delirium through promoting hippocampal E4BP4 in mice.

OBJECTIVE: Delirium (acute brain syndrome) is a common and serious neuropsychiatric disorder characterized by an acute decline in cognitive function. However, there is no effective treatment clinically. Here we investigated the potential effect of jujuboside A (JuA, a natural triterpenoid saponin) on cognitive impairment in delirium. METHODS: Delirium models of mice were established by injecting lipopolysaccharide (LPS) plus midazolam and implementing a jet lag protocol. Novel object recognition test and Y maze test were used to evaluate the effects of JuA on delirium-associated cognitive impairment. The mRNA and protein levels of relevant clock factors and inflammatory factors were measured by qPCR and Western blotting. Hippocampal Iba1+ intensity was determined by immunofluorescence staining. KEY FINDINGS: JuA ameliorated delirium (particularly delirium-associated cognitive impairment) in mice, which was proved by the behavioural tests, including a preference for new objects, an increase of spontaneous alternation and improvement of locomotor activity. Furthermore, JuA inhibited the expression of ERK1/2, p-p65, TNFα and IL-1ß in hippocampus, and repressed microglial activation in delirious mice. This was attributed to the increased expression of E4BP4 (a negative regulator of ERK1/2 cascade and microglial activation). Moreover, loss of E4bp4 in mice abrogated the effects of JuA on delirium as well as on ERK1/2 cascade and microglial activation in the hippocampus of delirious mice. Additionally, JuA treatment increased the expression of E4BP4 and decreased the expression of p-p65, TNFα and IL-1ß in LPS-stimulated BV2 cells, supporting a protective effect of JuA on delirium. CONCLUSIONS: JuA protects against delirium-associated cognitive impairment through promoting hippocampal E4BP4 in mice. Our findings are of great significance to the drug development of JuA against delirium and related disorders.

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors.

In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.

[Ecological Risk and Migration Patterns of Heavy Metals in Soil and Crops in the Lead-Zinc Mining Area in Guizhou, China].

An accumulation of heavy metals in soil poses a risk to the ecological environment and human health. In this study, the concentrations of heavy metals in soil and crops were examined in a lead-zinc mining area in Guizhou Province, China. The distribution and sources of heavy metals were analyzed using GIS spatial mapping. The potential ecological risks of heavy metals were assessed using the potential ecological risk index (RI), and the human health risk assessment method recommended by the United States Environmental Protection Agency (USEPA) was used to quantify the health risk of residents exposed to heavy metals in the soil around lead-zinc mines. According to the results, the average of concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in the soil were 58, 7.9, 175, 64, 0.461, 65, 1539, and 2513 mg·kg-1, respectively, which were significantly higher than the background values in Guizhou Province. It was found that the As, Cd, Cu, Hg, Pb, and Zn concentrations were extremely irregular in the soil and that the concentrations decreased significantly with the distance to the smelters, which were greatly disturbed by human activities. Comprehensive evaluation of soil heavy metals using the potential ecological risk index revealed that the risks of soil heavy metals were pole-strength and strong levels, and Cd constituted the primary ecological risk factor. A total of 22% and 10% of the corn samples contained Pb and As above the heavy metal pollution thresholds in the national food safety standards. According to human health risk assessments, heavy metals in the soil present potential non-carcinogenic risks to adults or children, and pose a potential carcinogenic risk to children. Soil pH was an important controlling factor affecting the bioavailability, migration, and accumulation of Cd in soil-crop systems. This study provides data and theoretical support for the prevention and control of soil pollution in lead-zine mining areas.

Photo-crosslinked GelMA loaded with dental pulp stem cells and VEGF to repair critical-sized soft tissue defects in rats.

BACKGROUND: Tissue engineering of skin and mucosa is essential for the esthetic and functional reconstruction of individuals disfigured by trauma, resection surgery, or severe burns while overcoming the limited amount of autograft and donor site morbidity. PURPOSE: We aimed to determine whether a combination of Gelatin-methacryloyl (GelMA) hydrogel scaffold alone or loaded with either dental pulp stem cells (DPSCs) and/or vascular endothelial growth factor (VEGF) could improve skin wound healing in rats. MATERIALS AND METHODS: Four 10 mm full-thickness skin defects were created on the dorsum of 15 Sprague-Dawley rats. The wounds were treated with GelMA alone, GelMA+DPSCs, or GelMA+DPSCs+VEGF. Unprotected wounds were used as controls. Animals were euthanized at 1-, 2-, and 4 weeks post-surgery, and the healing wounds were harvested for clinical, histological, and RT-PCR analysis. RESULTS: No signs of clinical inflammation were observed among all groups. Few and sparse mononuclear inflammatory cells were observed in GelMA+DPSCs and GelMA+DPSCs+VEGF groups at 2 weeks, with complete epithelialization of the wounds. At 4 weeks, the epidermis in GelMA+DPSCs and GelMA+DPSCs+VEGF groups was indistinguishable from the empty defect and GelMA groups. The decrease in cellularity and increase in density of collagen fibers were observed over time in both GelMA+DPSCs and GelMA+DPSCs+VEGF groups but were more evident in the GelMA+DPSCs+VEGF group. The GelMA+DPSCs+VEGF group showed a higher expression of the KER 10 gene at all time points compared with the other groups. Expression of Col1 A1 and TGFß-1 were not statistically different over time neither among the groups. CONCLUSION: GelMA scaffolds loaded with DPSCs, and VEGF accelerated the re-epithelialization of skin wounds.

Sodium hydrosulfide alleviates aluminum toxicity in Brassica napus through maintaining H2S, ROS homeostasis and enhancing aluminum exclusion.

Hydrogen sulfide (H2S) is a gaseous mediator that plays versatile roles in plant growth and stress responses. However, the regulatory functions of H2S in plant responses to aluminum (Al) stress remain elusive. We observed that application of 20 µM of NaHS (H2S donor) or 0.2 mM of hypotaurine (HT, H2S scavenger) significantly mitigated the inhibition of rapeseed root growth caused by Al stress (150 µM). Exposure to Al for 6 h induced significant H2S accumulation and high levels were maintained thereafter, owing to the elevation of cysteine (83.73 %), L-cysteine desulfhydrase (LCD, 92.32 %), and cyanoalanine synthase (CAS, 11.23 %), and the inhibition of O-Acetyl-l-serine (thiol) lyase (OAS-TL, 15.13 %). Addition of HT significantly scavenged the prolonged H2S accumulation caused by Al stress. Exogenous NaHS maintained the H2S homeostasis through increasing OAS-TL activity (34.99 %) and inhibiting LCD activity (25.72 %), and cysteine level (39.53 %). Moreover, exogenous NaHS mitigated oxidative damage by enhancing antioxidant enzyme activity (SOD 26.27 %, POD 28.62 %, CAT 400.5 % and APX 92.68 %) and proline content (19.85 %). It also decreased root cell wall Al accumulation (20.52 %) by decreasing PME activity (24.64 %) and facilitating pectin methylation (16.74 %). Similar alleviative effects were observed when HT was added. These results suggest that H2S functions differential roles in Al stress response in rapeseed seedlings, depending on its local concentration and duration. Prolonged high H2S emissions might contribute to Al toxicity, while moderate exogenous H2S improves Al tolerance through controlling H2S and ROS accumulation and enhancing Al exclusion through replenishing antioxidant reservoirs and facilitating pectin methylation. It is therefore important that further study investigates how to orchestrate endogenous H2S levels and improve plant stress tolerance.

Heavy Metal Pollution and Source Contributions in Agricultural Soils Developed from Karst Landform in the Southwestern Region of China.

Heavy metal pollution of soil in agricultural areas is the most prominent environmental pollution problem in China, seriously affecting human health and food security. It has become one of the environmental problems to which all sectors of society attach great importance. Soil heavy metals in the weathering area of hazardous geological bodies in southwest China have naturally high background attributes. Therefore, ecological risk assessment and analysis of potential sources of soil heavy metals in southwest China is of great significance for soil health management, soil heavy metal pollution control and territorial spatial planning. In this study, we collected 787 soil samples (0-20 cm) in Xuanwei County in China and analyzed the concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb and Zn in soils. Igeo, RI, HI and CR were used to calculate the pollution levels, ecological risks and human health risks. Additionally, the PMF model and one-way ANOVA were used to identify the potential sources and discuss the factors affecting the enrichment of heavy metals. The results showed that the mean contents of the surface soils were 1.190 (Cd), 139.4 (Cr), 96.74 (Cu), 0.081 (Hg), 56.97 (Ni), 46.66 (Pb) and 130.1 (Zn) mg/kg. All heavy metals exceeded the background values of the A layer soil in Yunnan Province. The Igeo showed that Cd was the most hazardous element in the study area, followed by Cu, Cr, As, Ni and Pb. The RI showed that low ecological risks, moderate ecological risks, considerable ecological risks and strong ecological risks accounted for 3.81%, 55.27%, 37.74% and 3.18%, respectively, of the total samples, and Cd was the main dominant element. The HI values of the As element in children were greater than 1, indicating a non-carcinogenic risk, and other elements' risks were acceptable. The CR values of Cr and Ni were higher than their limits (1 × 10-4), and both had carcinogenic risks in children and adults, as did As in children. According to the PMF model, four heavy metals sources were identified: geological sources (32%), sources from mining activities (19.38%), atmospheric deposition sources (17.57%) and agricultural sources (31.05%). Thereinto, As and Pb were mainly derived from agricultural sources, Cd and Cr were mainly associated with geological sources, Cu was largely from mining activity sources, Hg was mainly from atmospheric deposition sources and Ni and Zn were mainly from geological sources, mining activities and agricultural activities. The parent material has a significant influence on the enrichment of heavy metals in the soil, and the heavy metals are significantly enriched in the carbonate parent material and quaternary parent material. Topography also plays a role in heavy metal accumulation; Cd, Cr, Cu, Ni and Zn gradually decreased with the increase in altitude, and As and Pb increased with the increase in altitude. Mn-oxide played a crucial part in the enrichment of Cu and Zn, while SOC, K2O and pH had little influence on the accumulation of heavy metals.

Tangeretin prevents cognitive deficit in delirium through activating RORα/γ-E4BP4 axis in mice.

Delirium is a common and serious neuropsychiatric syndrome characterized with acute cognitive and attentional deficits, however, the effective therapies are lacking. Here, using mouse models of delirium, we investigated the effects of tangeretin (TAN, a natural flavonoid) on cognitive impairment by assessing object preference with novel object recognition (NOR) test and spontaneous alternation with Y maze test. We found that TAN, as a RORα/γ agonist, prevented cognitive decline in delirious mice as evidenced by a normal novel object preference and increased spontaneous alternation. This was accompanied by decreased expression of ERK1/2, TNFα and IL-1ß as well as diminished microglial activation in delirious mice. The protective effect of TAN on delirium was mainly attributed to increased hippocampal E4BP4 expression (a known target of RORs and a regulator of cognition in delirium through modulating the ERK1/2 cascade and microglial activation) via activation of RORα/γ. In addition, TAN treatment modulated the expression of RORα/γ target genes (such as E4bp4 and Bmal1) and inhibited the expression of TNFα and IL-1ß in lipopolysaccharide (LPS)-stimulated cells, supporting a beneficial effect of TAN on delirium. In conclusion, TAN is identified as a RORα/γ agonist which promotes E4BP4 expression to prevent cognitive decline in delirious mice. Our findings may have implications for drug development of TAN for prevention and treatment of various diseases associated with cognitive deficiency.

The nuclear receptor REV-ERBα regulates CYP2E1 expression and acetaminophen hepatotoxicity.

CYP2E1 plays an important role in drug metabolism and drug-induced hepatotoxicity. Here, we aimed to investigate a potential role for the nuclear receptor REV-ERBα in regulation of CYP2E1 expression and acetaminophen (APAP)-induced hepatotoxicity, and to determine the underlying mechanisms.Regulatory effects of REV-ERBα on CYP2E1 expression were assessed in vivo (using Rev-erbα-/- mice) and in vitro (using AML12 and HepG2 cells). In vitro microsomal CYP2E1 activity was probed using its specific substrate p-nitrophenol. Pharmacokinetic and acute toxicity studies were performed with Rev-erbα-/- and wild-type mice after APAP administration.We found that Rev-erbα ablation led to decreases in hepatic CYP2E1 expression and activity in mice. In line with this, APAP-induced hepatotoxicity was attenuated in Rev-erbα-deficient mice. The attenuated toxicity was due to down-regulation of APAP metabolism mediated by CYP2E1, which was evidenced by a decrease in formation of the toxic intermediate metabolite NAPQI (i.e. reduced APAP-cysteine and APAP-N-acetylcysteine levels). Furthermore, positive regulation of CYP2E1 expression by REV-ERBα was confirmed in both AML12 and HepG2 cells. Based on luciferase reporter assays, it was found that REV-ERBα regulated Cyp2e1 transcription and expression through repression of DEC2.In conclusion, REV-ERBα positively regulates CYP2E1 expression in mice, thereby affecting APAP metabolism and hepatotoxicity.

SATB2: A versatile transcriptional regulator of craniofacial and skeleton development, neurogenesis and tumorigenesis, and its applications in regenerative medicine.

SATB2 (special AT-rich sequence-binding protein 2) is a member of the special AT-rich binding protein family. As a transcription regulator, SATB2 mainly integrates higher-order chromatin organization. SATB2 expression appears to be tissue- and stage-specific, and is governed by several cellular signaling molecules and mediators. Expressed in branchial arches and osteoblast-lineage cells, SATB2 plays a significant role in craniofacial pattern and skeleton development. In addition to regulating osteogenic differentiation, SATB2 also displays versatile functions in neural development and cancer progression. As an osteoinductive factor, SATB2 holds great promise in improving bone regeneration toward bone defect repair. In this review, we have summarized our current understanding of the physiological and pathological functions of SATB2 in craniofacial and skeleton development, neurogenesis, tumorigenesis and regenerative medicine.

[Factors Affecting the Translocation and Accumulation of Cadmium in a Soil-Crop System in a Typical Karst Area of Guangxi Province, China].

To understand the main factors influencing the translocation and accumulation of cadmium (Cd) in soil-crop systems in typical karst areas, 68 sets of paddy soil and rice grain samples were collected in Guangxi Province. These were used to analyze Cd concentrations and soil properties (pH, organic matter (OM) content, oxide content, and texture). Spearman's correlation coefficients and principal component analysis (PCA) were used to examine the effects of soil properties on Cd concentrations and identify the main influencing factors. The studied soils were highly enriched in iron oxide (TFe2O3), aluminum oxide (Al2O3), and manganese oxide (MnO) compared to background levels, with average concentrations of 20.2%, 19.0%, and 0.2%, respectively. However, the soils are relatively depleted in silica (SiO2), with an average concentration of 41.0%. The soils are strongly weathered and leached in study area, giving rise to rich occurrences of Fe-Mn nodules. The concentrations of TFe2O3 and MnO in the study soils were significantly correlated with soil Cd, rice seed Cd, and the Cd bioconcentration factor (BCF). The PCA analysis further showed that TFe2O3 and MnO in soils were the main factors affecting the migration and enrichment of Cd while soil pH, OM, and Al2O3 had less of an influence. Furthermore, SiO2 and soil texture indirectly affected the migration and enrichment of Cd. It is suggested that the Fe-Mn nodules effectively adsorb and immobilize Cd in the study area soils, acting as a heavy metal scavenger that reduced the biological accessibility of Cd.

BMP9-initiated osteogenic/odontogenic differentiation of mouse tooth germ mesenchymal cells (TGMCS) requires Wnt/ß-catenin signalling activity.

Teeth arise from the tooth germ through sequential and reciprocal interactions between immature epithelium and mesenchyme during development. However, the detailed mechanism underlying tooth development from tooth germ mesenchymal cells (TGMCs) remains to be fully understood. Here, we investigate the role of Wnt/ß-catenin signalling in BMP9-induced osteogenic/odontogenic differentiation of TGMCs. We first established the reversibly immortalized TGMCs (iTGMCs) derived from young mouse mandibular molar tooth germs using a retroviral vector expressing SV40 T antigen flanked with the FRT sites. We demonstrated that BMP9 effectively induced expression of osteogenic markers alkaline phosphatase, collagen A1 and osteocalcin in iTGMCs, as well as in vitro matrix mineralization, which could be remarkably blunted by knocking down ß-catenin expression. In vivo implantation assay revealed that while BMP9-stimulated iTGMCs induced robust formation of ectopic bone, knocking down ß-catenin expression in iTGMCs remarkably diminished BMP9-initiated osteogenic/odontogenic differentiation potential of these cells. Taken together, these discoveries strongly demonstrate that reversibly immortalized iTGMCs retained osteogenic/odontogenic ability upon BMP9 stimulation, but this process required the participation of canonical Wnt signalling both in vitro and in vivo. Therefore, BMP9 has a potential to be applied as an efficacious bio-factor in osteo/odontogenic regeneration and tooth engineering. Furthermore, the iTGMCs may serve as an important resource for translational studies in tooth tissue engineering.

Comparison of Donor Site Morbidity Between Anterolateral Thigh and Radial Forearm Free Flaps for Head and Neck Reconstruction: A Systematic Review and Meta-Analysis.

ABSTRACT: This meta-analysis aimed to provide an up-to-date comparison of donor site morbidity (DSM) between patients who underwent head and neck reconstruction with Anterolateral thigh (ALT) and radial forearm free (RFF) flaps. We searched the PubMed, Web of Science, EMBASE, and Cochrane Library databases to identify studies that compared DSM between ALT and RFF patients. Study quality was assessed using the Newcastle-Ottawa Scale. The pooled odds ratio (OR) of each DSM between ALT and RFF patients was estimated using a random- or fixed-effect model depending on the degree of interstudy heterogeneity. Sensitivity and subgroup analyses were performed if substantial heterogeneity was detected. Eighteen cohort studies with 1,018 patients (535 ALT and 483 RFF patients) were included. Compared with RFF, ALT were associated with lower risks of wound dehiscence (OR = 0.2, 95%CI: 0.10-0.42, P < 0.01), strength impairment (OR = 0.18, 95%CI: 0.07-0.47, P < 0.01), and movement impairment (OR = 0.19, 95%CI:0.07-0.49, P < 0.01). A subgroup analysis showed that ALT were associated with a lower risk of donor site numbness among patients undergoing tongue reconstruction (OR = 0.05, 95%CI: 0.01-0.25, P < 0.01), but not among all patients undergoing head and neck reconstruction. The pooled ORs of other DSMs demonstrated no significant difference between ALT and RFF patients. ALT are superior to RFF for head and neck reconstruction in terms of donor site wound dehiscence, strength impairment, movement impairment, and for tongue reconstruction specifically in terms of donor site numbness. No significant differences in the incidence of donor site hematoma/seroma, infection, or dissatisfaction with donor site appearance were identified between ALT and RFF patients.

Independent risk factors associated with higher mortality rates and recurrence of brain abscesses from head and neck sources.

OBJECTIVE: The aim of this study was to identify the features and independent risk factors associated with recurrence and mortality in patients with brain abscesses of head and neck origin. STUDY DESIGN: We designed a retrospective study of patients diagnosed with a brain abscess at the Massachusetts General Hospital between 1980 and 2017. Inclusion criteria were complete medical records, including medical and surgical history; and radiographic and microbiologic data. Multinomial logistic regression and Gray's test were used to evaluate the independent variables associated with recurrence and mortality. RESULTS: Eighty-eight cases met the inclusion criteria. Of these, 48 patients (54.5%) were men (mean age 50.5 ± 18.8 years). Significant association between etiology and cultured organisms was found only in cases of neurosurgical intervention with staphylococcal or streptococcal isolates (P < .05). Seizure activity was the only significant predictor of recurrence. Predictors of mortality included advanced age (P = .005); staphylococcal infection (P = .029); low monocyte count (P = .004); hyponatremia (P = .002); elevated blood urea nitrogen (P = .000); elevated creatinine (P = .002); hyperglycemia (P = .023); and status at discharge (P = .000). CONCLUSIONS: Independent risk factors, such as low monocyte count, hyponatremia, renal dysfunction, and hyperglycemia, were found to be associated with higher mortality rates in patients with brain abscesses of head and neck origin. These abnormalities should be promptly recognized and aggressively treated.

SNHG12/miR-326/E2F1 feedback loop facilitates the progression of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a kind of common malignant tumor worldwide. An increasing number of researches have validated that long non-coding RNAs (lncRNAs) are closely associated with the occurrence and development of multiple diseases, including cancers. However, the role of lncRNA SNHG12 in OSCC was largely unknown. In present study, qRT-PCR manifested the upregulation of SNHG12 expression in OSCC tissues and cells. Suppression of SNHG12 inhibited cell proliferation, migration, invasion, and EMT process in OSCC. Additionally, SNHG12 depletion also attenuated OSCC tumor growth in vivo. Thereafter, E2F1 was found to be a transcription factor of SNHG12 to stimulate its expression. More interestingly, SNHG12 deficiency reduced E2F1 expression in turn. MiR-326 was found to be shared between SNHG12 and E2F1. Besides, SNHG12 augmented E2F1 in OSCC through miR-326 sequestration. Finally, rescue assays demonstrated that overexpressed E2F1 restored the inhibitory effect resulted from SNHG12 silence, indicating that SNHG12 promoted the progression of OSCC by E2F1-dependent way. This research unveiled that SNHG12/miR-326/E2F1 feedback loop facilitated OSCC progression, which shed new light on therapeutic methods in OSCC.

Sublingual Gland Tumors Worldwide: A Descriptive Retrospective Study of 839 Cases.

PURPOSE: Sublingual gland tumors are rare. We sought to define the general features of sublingual gland tumors for clinical reference. In addition, we evaluated whether it would be safe to speculate that ∼90% sublingual gland tumors will be malignant and that ∼90% of those malignant tumors will be adenoid cystic carcinoma. MATERIALS AND METHODS: In the present study, we have reported data from a pleomorphic adenoma case of the sublingual gland and a case series of sublingual gland tumors. Global data of sublingual gland tumors were retrieved. The cases pathologically identified as either benign or malignant tumors of the sublingual gland were included. The demographic, pathologic, and treatment features were analyzed. RESULTS: Data from 1 recent case of pleomorphic adenoma of the sublingual gland and a 21-case series of sublingual gland tumors were retrieved. A total of 839 cases of sublingual gland tumors were analyzed in the present study. The most commonly encountered age group was 40 to 59 years (47.6%). Of the 367 patients with gender specified, 178 were men (48.5%) and 189 were women (51.5%). Malignant tumors predominated (n = 722 cases; 86.1% of 839). Most malignant tumors were adenoid cystic carcinoma (n = 376), just greater than one half (52.1%) of all malignant tumors. Surgery was the only reported treatment method for the benign tumors. The most common treatment methods for the 164 explicit malignant tumors were surgery plus radiotherapy for 82 patients (50%), followed by surgery alone for 70 patients (42.7%). CONCLUSIONS: To date and to the best of our knowledge, the present study is the most comprehensive study on the demographic, pathologic, and treatment features of global sublingual gland tumors. These findings have shown that ∼90% of sublingual gland tumors will be malignant. However, the assumption that ∼90% malignant sublingual gland tumors will be adenoid cystic carcinoma is incorrect, which could be a new critical clinical reference.

Physiological and molecular mechanism of cadmium (Cd) tolerance at initial growth stage in rapeseed (Brassica napus L.).

Cadmium (Cd) contaminated soil has threatened plant growth and human health. Rapeseed (Brassica napus L.), an ideal plant for phytoremediation, is an important source of edible vegetable oil, vegetable, animal fodder, green manure and biodiesel. For safe utilization of Cd polluted soil, physiological, biochemical, and molecular techniques have been used to understand mechanisms of Cd tolerance in B. napus. However, most of these researches have concentrated on vegetative and adult stages, just a few reports focus on the initial growth stage. Here, the partitioning of cadmium, gene expression level and activity of enzymatic antioxidants of H18 (tolerant genotype) and P9 (sensitive genotype) were investigated under 0 and 30 mg/L Cd stress at seedling establishment stage. Results shown that the radicle length of H18 and P9 under Cd stress were decreased by 30.33 (0.01 < P < 0.05) and 88.89% (P < 0.01) respectively. Cd concentration at cotyledon not radicle and hypocotyl in P9 was significantly higher than that in H18. The expression level of BnaHMA4c, which plays a key role in root-to-shoot translocation of Cd, was extremely higher in P9 than in H18 under both normal and Cd stress conditions. We also found that SOD, CAT and POD were more active in responding to Cd stress after 48 h, and the activity of SOD and CAT in H18 were higher than that in P9 at all observed time points. In conclusion, high activity of enzymatic antioxidants at initial Cd stress stage is the main detoxification mechanism in Cd-tolerant rapeseed, while the higher Cd transfer coefficient, driven by higher expression level of BnaHMA4c is the main mechanism for surviving radicle from initial Cd toxicity in Cd-sensitive rapeseed.

Bone Morphogenetic Protein-9-Stimulated Adipocyte-Derived Mesenchymal Progenitors Entrapped in a Thermoresponsive Nanocomposite Scaffold Facilitate Cranial Defect Repair.

Due to availability and ease of harvest, adipose tissue is a favorable source of progenitor cells in regenerative medicine, but has yet to be optimized for osteogenic differentiation. The purpose of this study was to test cranial bone healing in a surgical defect model utilizing bone morphogenetic protein-9 (BMP-9) transduced immortalized murine adipocyte (iMAD) progenitor cells in a citrate-based, phase-changing, poly(polyethylene glycol citrate-co-N-isopropylacrylamide) (PPCN)-gelatin scaffold. Mesenchymal progenitor iMAD cells were transduced with adenovirus expressing either BMP-9 or green fluorescent protein control. Twelve mice underwent craniectomy to achieve a critical-sized cranial defect. The iMAD cells were mixed with the PPCN-gelatin scaffold and injected into the defects. MicroCT imaging was performed in 2-week intervals for 12 weeks to track defect healing. Histologic analysis was performed on skull sections harvested after the final imaging at 12 weeks to assess quality and maturity of newly formed bone. Both the BMP-9 group and control group had similar initial defect sizes (P = 0.21). At each time point, the BMP-9 group demonstrated smaller defect size, higher percentage defect healed, and larger percentage defect change over time. At the end of the 12-week period, the BMP-9 group demonstrated mean defect closure of 27.39%, while the control group showed only a 9.89% defect closure (P < 0.05). The BMP-9-transduced iMADs combined with a PPCN-gelatin scaffold promote in vivo osteogenesis and exhibited significantly greater osteogenesis compared to control. Adipose-derived iMADs are a promising source of mesenchymal stem cells for further studies in regenerative medicine, specifically bone engineering with the aim of potential craniofacial applications.

Dentinogenesis and Tooth-Alveolar Bone Complex Defects in BMP9/GDF2 Knockout Mice.

Tooth development is regulated by sequential and reciprocal epithelium-mesenchymal interactions and their related molecular signaling pathways, such as bone morphogenetic proteins (BMPs). Among the 14 types of BMPs, BMP9 (also known as growth differentiation factor 2) is one of the most potent BMPs to induce osteogenic differentiation of mesenchymal stem cells. The purpose of this study was to examine potential roles of BMP9 signaling in tooth development. First, we detected the expression pattern of BMP9 in tooth germ during postnatal tooth development, and we found that BMP9 was widely expressed in odontoblasts, ameloblasts, dental pulp cells, and osteoblasts in alveolar bones. Then, we established a BMP9-KO mouse model. Gross morphological examination revealed that the tooth cusps of BMP9-KO mice were significantly abraded with shorter roots. Micro-computed tomography and three-dimensional reconstruction analysis indicated that the first molars of the BMP9-KO mice exhibited a reduced thickness dentin, enlarged pulp canals, and shortened roots, resembling the phenotypes of the common hereditary dental disease dentinogenesis imperfecta. Further, the alveolar bone of the BMP9-KO mutants was found to be shorter and had a decreased mineral density and trabecular thickness and bone volume fraction compared with that of the wild-type control. Mechanistically, we demonstrated that both dentin sialophosphoprotein and dentin matrix protein 1 were induced in dental stem cells by BMP9, whereas their expression was reduced when BMP9 was silenced. Further studies are required to determine whether loss of or decreased BMP9 expression is clinically associated with dentinogenesis imperfecta. Collectively, our results strongly suggest that BMP9 may play an important role in regulating dentinogenesis and tooth development. Further research is recommended into the therapeutic uses of BMP9 to regenerate traumatized and diseased tissues and for the bioengineering of replacement teeth.

Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps.

Surgical flaps are frequently affected by ischemia/reperfusion (I/R) injury. Calcium-sensing receptor (CaSR) and stromal cell-derived factor-1α (SDF-1α) are closely associated with myocardial I/R injury. This study was performed to evaluate the feasibility of applying SDF-1α to counteract CaSR activation-mediated I/R injury in ischemic free flaps. Free flaps that underwent ischemia for 3 h were equally randomized into five groups: CaCl2, NPS2143 + CaCl2, SDF-1α + CaCl2, AMD3100 + SDF-1α + CaCl2, and normal saline. The free flaps were harvested to evaluate flap necrosis and neovascularization after 2 h or 7 d of reperfusion. p-CaSR/CaSR was extensively expressed in vascular endothelial cells of free flaps after I/R injury, and activation of the SDF-1α/CXCR4 axis and NPS2143 could reduce the expression of cleaved caspase-3, caspase-9, FAS, Cyt-c, and Bax and increase Bcl-2 expression; the opposite was true after CaSR activation. Interestingly, initiation of the SDF-1α/CXCR4 axis might abrogate CaSR activation-induced I/R injury through enhancement of microvessel density. In conclusion, CaSR might become a novel therapeutic target of free flaps affected by I/R injury. Activation of the SDF-1α/CXCR4 axis and NPS2143 could counteract CaSR activation-mediated I/R injury and promote free flap survival through inhibition of caspase-3/caspase-9-related cell apoptosis and enhancement of neovascularization.