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Abstract Background Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity. Case presentation This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and β-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital. Conclusions OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.

Abstract Background An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. Methods The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. Results Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon’s head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. Conclusion Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.

Abstract The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. “PRI-E” consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means “the best Education”. This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.

Targeting metabolic reprogramming may be an effective strategy to enhance cancer treatment efficacy. Glutamine serves as a vital nutrient for cancer cells. Inhibiting glutamine metabolism has shown promise in preventing tumor growth both in vivo and in vitro through various mechanisms. Therefore, this review collates recent scientific literature concerning the correlation between glutamine metabolism and cancer treatment. Novel treatment modalities based on amino acid transporters, metabolites, and glutaminase are discussed. Moreover, we demonstrate the relationship between glutamine metabolism and tumor proliferation, drug resistance, and the tumor immune microenvironment, offering new perspectives for the clinical treatment of head and neck squamous cell carcinoma, particularly for combined therapies. Identifying innovative approaches for enhancing the efficacy of glutamine-based metabolic therapy is crucial to improving HNSCC treatment.

As proactivity becomes vital for organizational success, retaining proactive employees becomes increasingly important, making the relationship between a proactive personality and turnover intention a key research topic. While existing studies have largely depicted turnover as a consequence of dissatisfaction and have identified negative indirect relationships, this study seeks to challenge that perspective by proposing that, in today’s boundaryless career environment, people also engage in voluntary turnover for career advancement. Using a self-regulation career management model, we propose that proactive employees set ambitious career goals influenced by career aspirations, leading them to seek external opportunities and thus exhibit higher turnover intention. However, when organizations implement career management practices, this relationship weakens as proactive employees perceive opportunities to achieve their goals within their current organizations. We tested these hypotheses with a sample of 342 respondents using the SPSS macro PROCESS. The findings support our propositions, revealing a positive indirect effect through career aspirations, which diminishes when perceived organizational career management is strong.

Although several proteasome subunits have been shown to bind ubiquitin (Ub) chains, many ubiquitylated substrates also associate with 26S proteasomes via "shuttling factors." Unlike the well-studied yeast shuttling factors Rad23 and Dsk2, vertebrate homologs Ddi2 and Ddi1 lack a Ub-associated domain; therefore, it is unclear how they bind Ub. Here, we show that deletion of Ddi2 leads to the accumulation of Ub conjugates with K11/K48 branched chains. We found using affinity copurifications that Ddi2 binds Ub conjugates through its Ub-like domain, which is also required for Ddi2 binding to proteasomes. Furthermore, in cell extracts, adding Ub conjugates increased the amount of Ddi2 associated with proteasomes, and adding Ddi2 increased the binding of Ub conjugates to purified proteasomes. In addition, Ddi2 also contains a retroviral protease domain with undefined cellular roles. We show that blocking the endoprotease activity of Ddi2 either genetically or with the HIV protease inhibitor nelfinavir increased its binding to Ub conjugates but decreased its binding to proteasomes and reduced subsequent protein degradation by proteasomes leading to further accumulation of Ub conjugates. Finally, nelfinavir treatment required Ddi2 to induce the unfolded protein response. Thus, Ddi2 appears to function as a shuttling factor in endoplasmic reticulum-associated protein degradation and delivers K11/K48-ubiquitylated proteins to the proteasome. We conclude that the protease activity of Ddi2 influences this shuttling factor activity, promotes protein turnover, and helps prevent endoplasmic reticulum stress, which may explain nelfinavir's ability to enhance cell killing by proteasome inhibitors. [ABSTRACT FROM AUTHOR]

Automatic road extraction from satellite images is a popular research hotspot topic in the field of remote sensing. However, the complexity of road features and structures hinders their precise extraction. Road features have different saliency due to the occlusion of other objects and diverse road types. Road structures are scattered across various locations and affected by geographical conditions, population distribution, and transportation demands. These issues render current methods based on convolutional neural networks prone to fragmented and incomplete road extraction results. To address these issues, a Road Extraction Network with Dual-View Information Perception Based on GCN (RDPGNet) is proposed, where the GCN-based dual-view perceptron (GDVP) uses the superior information interaction capability of the GCN to explore road information under a dual view. In the GDVP, we first design the road feature saliency graph reasoning module (RFSG) and road structure homogeneous space graph reasoning module (RSHS) based on the features and structures. The RFSG obtains the similarity of road feature information in different regions as a similarity matrix to participate in the graph reasoning process, ensuring that equal treatment is given to regions with varying saliency levels. The RSHS projects the road structure onto a corresponding homogeneous space while aggregating and interacting with information through graph convolution, thereby enhancing the network’s perception of roads in diverse locations. Second, because multi-view information usually shares a potential common representation, a multi-view information fusion and alignment strategy (MVFA) is designed to comprehensively model road information. Experimental results obtained from two public datasets indicate that RDPGNet outperforms other state-of-the-art networks.

Predators are dependent on the capture of prey to meet their energetic and nutritive requirements, which brings the risk of predation to prey. The predation risk is divided into consumptive and non-consumptive effects. Non-consumptive effects may manifest through altered growth and ontogenetic trajectories in prey species, a dynamic modulated by olfactory or other sensory cues from predators. Bactrocera dorsalis Hendel represents a major invasive threat to global horticulture. While earlier research was primarily centered on the consumptive interactions between B. dorsalis and its natural enemies, the potential consequences of non-consumptive interactions on the development of B. dorsalis have been overlooked. In this study, we investigated the impact of predation risk effects, induced by both visual exposure to the predatory mantis Hierodula patellifera Serville and its associated odor, on the life history traits of B. dorsalis. Female B. dorsalis demonstrated a reduced developmental time in the presence of a caged predator (H. patellifera) or predator odors, but showed significantly increased fecundity. Conversely, males displayed no significant change in developmental time. Additionally, neither the female nor male body weight at death was significantly influenced by the predation risk from the caged predator or predator odors. This study investigated the effects of predation risk on the development and reproduction of B. dorsalis, emphasizing the potential importance of odor risk in biological and pest control.

Outbreaks of the oriental fruit fly, Bactrocera dorsalis (Hendel), present significant challenges to global fruit production, necessitating effective control measures that minimize environmental risks and pesticide resistance. This study aimed to develop and evaluate the effectiveness of four distinct push–pull control strategies for managing B. dorsalis outbreaks in a Nephelium lappaceum orchard. These strategies involved the inclusion of low-concentration abamectin, spraying repellent with a drone or manually, using methyl eugenol (ME) or food bait and employing either two types of attractants and repellents or a single type. The findings indicated that incorporating the low-concentration abamectin into the push–pull system, utilizing ME as an attractant instead of food lures and manually applying abamectin and attractants were all effective in reducing the B. dorsalis population size and minimizing fruit damage. While increasing the diversity of repellents and attractants enhanced the long-term effectiveness of the system, it did not result in a significant decrease in B. dorsalis population size or fruit damage rate compared to using a single repellent or attractant. In conclusion, the push–pull strategy emerged as a viable method for managing B. dorsalis outbreaks, offering potential benefits in reducing environmental risks and pesticide resistance. However, the study underscored the importance of the context-specific construction of push–pull strategies to optimize their effectiveness in orchard settings.

Since the outbreak of COVID-19, mask-wearing has become a widespread phenomenon. Even after the pandemic, people continue to maintain the habit of wearing masks in their daily lives. While existing research has explored how mask-wearing can influence wearers’ behavior in everyday life, its effects in the workplace have received less attention. Drawing on self-perception theory, this study examined the positive effect of mask-wearing in the workplace on wearers’ voice behavior via psychological safety. An online experiment (N = 291) using a within-subject manipulation of wearing masks supported our hypotheses. This study uncovered the positive psychological and behavioral consequences of mask-wearing beyond its benefits in people’s health conditions and everyday life.

Purpose: Although it is widely accepted that procrastination is counterproductive, active procrastination may be considered a constructive coping strategy in situations where work-related stress is high. Drawing upon the conservation of resource theory and the ego depletion theory, the article suggests that active procrastination can be influenced by perceived stress, mediated by ego depletion, and potentially moderated by the Big Five personality traits. Design/methodology/approach: Using hierarchical regression analysis, Hayes Process Macros, and the general path analytic framework, our hypotheses were investigated. The sample was made up of 651 Chinese civil servants. Findings/results: According to the results, ego depletion fully mediated the positive connection between perceived stress and active procrastination. Furthermore, extroversion, conscientiousness, and openness negatively moderate the link between perceived stress and ego depletion as well as mediating effect. While neuroticism exhibited a positive moderating effect. Practical implications: The findings can serve as references for civil servants and public organisations to address stress and create a more relaxed work environment. Recognising active procrastination as a potential coping strategy can help to reframe the perception of procrastination and guide organisations in supporting their employees’ wellbeing. Originality/value: This study extends comprehension of active procrastination in stressful situations and highlights the potential positive coping consequences of stress attributes. By exploring the mechanisms involved, the study sheds light on how perceived stress can influence active procrastination, with ego depletion serving as a mediating factor, which helps to explain how individuals may experience reduced self-control and subsequently engage in active procrastination as a coping strategy.

Summary: Objective: Spinal cord injury is a common occurrence during spinal surgery. In this study, we proposed a zoning laminectomy, which could reduce the incidence of nerve injury. We also discussed the safety and clinical efficacy of the zoning laminectomy for thoracic ossification of the ligamentum flavum (TOLF). Methods: Forty-five patients with TOLF who underwent zoning laminectomy from October 2016 to February 2020 were included in the retrospective analysis. The Japan Orthopedic Association (JOA) score was used to evaluate clinical outcomes. Meanwhile, the occurrence of complications was recorded. Results: All 45 patients underwent the operation successfully, and the mean follow-up period was 25.3 months, the mean operation time was 160.2 min, the average blood loss was 474.2 ml, and the average hospital time was 8.0 days. At the final evaluation, the JOA score was significantly higher than the preoperative JOA score (P

Proteasome inhibitors, such as bortezomib (BTZ), are highly effective and widely used treatments for multiple myeloma. One proposed reason for myeloma cells' exceptional sensitivity to proteasome inhibition is that they produce and continually degrade unusually large amounts of abnormal immunoglobulins. We, therefore, hypothesized that, heat shock may also be especially toxic to myeloma cells by causing protein unfolding, increasing further the substrate load on proteasomes, and, thus, putting further stress on their capacity for protein homeostasis. After a shift from 37 to 43 °C, all four myeloma lines studied underwent extensive apoptosis in 4 h, unlike 13 nonmyeloma cell lines, even though the myeloma cells induced heatshock proteins and increased protein degradation similar to other cells. Furthermore, two myeloma lines resistant to proteasome inhibitors were also more resistant to 43 °C. Shifting myeloma cells to 43, 41, or 39 °C (which was not cytotoxic) dramatically increased their killing by proteasome inhibitors and inhibitors of ubiquitination or p97/VCP. Combining increased temperature with BTZ increased the accumulation of misfolded proteins and substrate load on the 26S proteasome. The apoptosis seen at 43 °C and at 39 °C with BTZ was mediated by caspase-9 and was linked to an accumulation of the proapoptotic Bcl-2-family member Noxa. Thus, myeloma cells are exceptionally sensitive to increased temperatures, which greatly increase substrate load on the ubiquitin-proteasome system and eventually activate the intrinsic apoptotic pathway. Consequently, for myeloma, mild hyperthermia may be a beneficial approach to enhance the therapeutic efficacy of proteasome inhibitors. [ABSTRACT FROM AUTHOR]

BackgroundPrior research on the digital divide has documented substantial racial inequality in using web-based health resources. The recent COVID-19 pandemic led to accelerated mass digitization, raising alarms that underprivileged racial minority groups are left further behind. However, it is unclear to what extent the use of health information and communications technology by underprivileged racial minority groups is affected. ObjectiveWe have considered the COVID-19 disruption as a rare exogenous shock and estimated the impact of the accelerated digitization on the quantity and variety of patient portal use. In this study, we aimed to answer the following 2 key research questions. Did patients alter their use of health information and communications technology owing to COVID-19–induced digital acceleration? Does the effect differ across racial lines? MethodsWe used a longitudinal patient portal use data set gathered from a large urban academic medical center to explore the effect of accelerated digitization on the racial digital gap in health care. We limited the sample period of our study to 2 same periods (March 11 to August 30) in 2019 and 2020. Our final sample consisted of 25,612 patients belonging to 1 of the 3 racial groups: Black or African American (n=5157, 20.13%), Hispanic (n=253, 0.99%), and White (n=20,202, 78.88%) patients. We estimated the panel data regression using 3 different models: pooled ordinary least squares (OLS), random effect (RE), and fixed effect (FE). ResultsOur study yielded 4 findings. First, we confirmed that the racial digital divide remains a significant issue for telehealth; underprivileged racial minority group patients had lower patient portal use than White patients before the pandemic (Minority: OLS, β=−.158; P

Drawing upon the conservation of resource theory, we offer a framework for understanding the mechanism underlying the effect of public employees’ overqualification on their cognitive and behavioral outcomes, through both positive and negative paths. We propose that perceived overqualification elicits two subjective cognitions, namely, perceived control and psychological entitlement, which further lead to public employees’ behaviors through approach (organizational citizenship behavior) and avoidance (workplace deviance behavior) tendencies. A total of 421 public employees participated in the three-stage time-lag investigation. The findings indicated that public employees’ perceived overqualification is positively related to perceived control, and perceived control is positively related to organizational citizenship behavior. Perceived control completely mediates the relationship between perceived overqualification and organizational citizenship behavior. Perceived overqualification is positively related to psychological entitlement, and psychological entitlement is positively related to workplace deviance behavior. Psychological entitlement completely mediates the relationship between perceived overqualification and workplace deviance behavior. This study constructed a double-edged sword model of perceived overqualification based on the public sector, discussing the influence of public employees’ perceived overqualification on their workplace behaviors from the perspective of resource assessment and self-evaluation, and providing theoretical guidance for the practice of human resource management within the public sector.

Abstract Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.

Protein ubiquitination and SUMOylation are required for the maintenance of cellular protein homeostasis, and both increase in proteotoxic conditions (e.g. heat shock or proteasome inhibition). However, we found that when ubiquitination was blocked in several human cell lines by inhibiting the ubiquitin-activating enzyme with TAK243, there was an unexpected, large accumulation of proteins modified by SUMO2/3 chains or SUMO1, but not by several other ubiquitin-like proteins. This buildup of SUMOylated proteins was evident within 3-4 h. It required the small ubiquitin-like modifier (SUMO)-conjugating enzyme, UBC9, and the promyelocytic leukemia protein (PML) and thus was not due to nonspecific SUMO conjugation by ubiquitination enzymes. The SUMOylated proteins accumulated predominantly bound to chromatin and were localized to PML nuclear bodies. Because blocking protein synthesis with cycloheximide prevented the buildup of SUMOylated proteins, they appeared to be newly-synthesized proteins. The proteins SUMOylated after inhibition of ubiquitination were purified and analyzed by MS. In HeLa and U2OS cells, there was a cycloheximide-sensitive increase in a similar set of SUMOylated proteins (including transcription factors and proteins involved in DNA damage repair). Surprisingly, the inhibition of ubiquitination also caused a cycloheximide-sensitive decrease in a distinct set of SUMOylated proteins (including proteins for chromosome modification and mRNA splicing). More than 80% of the SUMOylated proteins whose levels rose or fell upon inhibiting ubiquitination inhibition underwent similar cycloheximidesensitive increases or decreases upon proteasome inhibition. Thus, when nuclear substrates of the ubiquitin-proteasome pathway are not efficiently degraded, many become SUMOmodified and accumulate in PML bodies. [ABSTRACT FROM AUTHOR]

We present a method to infer spatially and spatiotemporally correlated emissions of greenhouse gases from atmospheric measurements and a chemical transport model. The method allows fast computation of spatial emissions using a hierarchical Bayesian framework as an alternative to Markov chain Monte Carlo algorithms. The spatial emissions follow a Gaussian process with a Matérn correlation structure which can be represented by a Gaussian Markov random field through a stochastic partial differential equation approach. The inference is based on an integrated nested Laplacian approximation (INLA) for hierarchical models with Gaussian latent fields. Combining an autoregressive temporal correlation and the Matérn field provides a full spatiotemporal correlation structure. We first demonstrate the method on a synthetic data example and follow this using a well-studied test case of inferring UK methane emissions from tall tower measurements of atmospheric mole fraction. Results from these two test cases show that this method can accurately estimate regional greenhouse gas emissions, accounting for spatiotemporal uncertainties that have traditionally been neglected in atmospheric inverse modelling. [ABSTRACT FROM AUTHOR]

Abstract Background Epigenetic reprogramming is involved in multiple steps of human cancer evolution and is mediated by a variety of chromatin-modifying enzymes. Specifically, the histone lysine methyltransferase KMT2D is among the most frequently mutated genes in oral squamous cell carcinoma (OSCC). However, the mechanisms by which KMT2D affects the development of OSCC remain unclear. Results In the present study, we found that the expression of KMT2D was elevated in OSCC compared to paracancerous specimens and was correlated with a more advanced tumor grade. More importantly, knockdown of KMT2D impaired their reconstitution in patient-derived organoids and decreased the expression of CD133 and β-catenin in OSCC cells. In in vitro and in vivo models, knockdown of KMT2D reduced the colony formation, migration and invasion abilities of OSCC cells and delayed tumor growth. Mechanistically, the dual-luciferase reporter and co-immunoprecipitation assays in two individual OSCC cell lines indicated that KMT2D may cooperate with MEF2A to promote the transcription activity of CTNNB1, thereby enhancing WNT signaling. Conclusion The upregulation of KMT2D contributes to stem-like properties in OSCC cells by sustaining the MEF2A-mediated transcriptional activity of CTNNB1.

With the continuous increase in the capacity of the pumped storage generator motor, the overheating of the rotor area is becoming increasingly severe, which has a significant effect on the safe and reliable operation of the machine. The heat dissipation of the machine rotor by fully air-cooled is one of the key technologies to develop the new generation of pumped storage generator motors. In this paper, the electromagnetic field and fluid–thermal coupled field of a pumped storage generator motor are analyzed. The 2D transient time-step finite element model of the electromagnetic field of a pumped storage generator motor is established, and the eddy current loss of damping bars of the rotor is calculated by the finite element method. The additional loss of the rotor pole surface is calculated by analytical method. The mathematical and geometric models of the 3D fluid–thermal coupled field of the pumped storage generator motor are established and calculated. The complex fluid velocity distribution and the temperature distribution at different positions of the rotor under fully air-cooled fanless cooling conditions are investigated in detail. The calculated temperature of field winding is compared with the measured value, and the result shows that the calculated result coincident well with the test data. This research provides the technical reference for the development and temperature rise calculation for large pumped storage generator motors.

Proteasome inhibitors are used as research tools and to treat multiple myeloma, and proteasome activity is diminished in several neurodegenerative diseases. We therefore studied how cells compensate for proteasome inhibition. In 4 h, proteasome inhibitor treatment caused dramatic and selective induction of GAB ARA PL1 (but not other autophagy genes) and p62, which binds ubiquitinated proteins and GAB ARA PL1 on autophagosomes. Knockdown of p62 or GAB ARA PL1 reduced cell survival upon proteasome inhibition. p62 induction requires the transcription factor nuclear factor (erythroid-derived 2)-like 1 (Nrf1), which simultaneously induces proteasome genes. After 20-h exposure to proteasome inhibitors, cells activated autophagy and expression of most autophagy genes by an Nrf1-independent mechanism. Although p62 facilitates the association of ubiquitinated proteins with autophagosomes, its knockdown in neuroblastoma cells blocked the buildup of ubiquitin conjugates in perinuclear aggresomes and of sumoylated proteins in nuclear inclusions but did not reduce the degradation of ubiquitinated proteins. Thus, upon proteasome inhibition, cells rapidly induce p62 expression, which enhances survival primarily by sequestering ubiquitinated proteins in inclusions. [ABSTRACT FROM AUTHOR]

Abstract Background Studies suggest Porphyromonas gingivalis (Pg) increased the incidence of oral squamous cell carcinoma (OSCC). However, fimA genotypes distribution of Pg, the origination of Pg in tissue, and its prognostic value are inconclusive. We aimed to investigate the frequency of fimA genotypes in OSCC patients, study the association between Pg and OSCC, and explore the prognostic value of Pg. Methods The abundance of Pg in saliva from the OSCC group and the OSCC-free group was analysed by qPCR. The presence of Pg was explored in OSCC tissue and para-cancerous tissue by in situ hybridization. The frequency of fimA genotypes in saliva and OSCC tissue was determined by PCR, then PCR products were sequenced and compared. Clinical data were extracted, and patients followed up for a median period of 23 months. Clinicopathological variables were compared with the abundance of Pg using Pearson Chi-square test or Fisher’s exact test. The disease-free survival (DFS) rate was calculated by Kaplan–Meier method with log-rank tests. Results Comparing the OSCC-free group, 95 patients with OSCC showed a high abundance of Pg in saliva (P = 0.033), and OSCC tissue showed strong in situ expression of Pg compared with paired normal tissue. Patients with OSCC showed a dominant distribution of Pg with genotype I + Ib (21.1%), II (31.6%), and IV (21.1%). FimA genotypes detected in saliva were in accordance with those in OSCC tissue, there was, moreover, a significant similarity in amplified Pg fragments. Of the 94 responsive OSCC patients, the recurrence rate was 26.6% (25/94). Overabundance of Pg in saliva showed advanced pathologic staging (P = 0.008), longer disease-free time (P = 0.029) and lower recurrence rate (P = 0.033). The overabundance of Pg in saliva was associated with improved disease-free survival (P = 0.049). Conclusions This study indicated that Pg might involve in the pathogenesis of OSCC, Pg carrying fimA I, Ib, II, and IV were prevalent genotypes in patients with OSCC, the provenance of Pg in OSCC tissue might be from the salivary microbial reservoir, and the abundance of Pg in saliva might consider as a favorable potential prognostic indicator in OSCC.

A novel formal (4 + 1) annulation between N-(o-chloromethyl)aryl amides and 3-chlorooxindoles through in situ generated aza-ortho-QMs with 3-chlorooxindoles is reported for the synthesis of a series of 2,3′-spirobi (indolin)-2′-ones in high yields. Under structured illumination microscopy, compound 3a is found to change the mitochondrial morphology and induce mitophagy pathway, which might then trigger mitophagy in cancer cells.

Angiogenesis is essential for the development of tumors. Studies have shown that carcinoma-associated fibroblasts (CAFs) are involved in regulating tumor angiogenesis, but the mechanism remains unclear. Recently, long noncoding RNAs (lncRNAs) have been proved to play an important role in the angiogenesis of various tumors. However, there is currently no research involving the regulation of CAFs on the angiogenesis of oral squamous cell carcinoma (OSCC) mediated by lncRNAs. By analyzing microarray data, we identified that the expression of lncRNA FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) in OSCC patients is downregulated, compared to that in normal tissues. Quantitative polymerase chain reaction (qPCR) results demonstrated that FENDRR expression is lower in CAFs compared to normal fibroblasts (NFs) of OSCC patients. KEGG pathway analysis revealed that some genes differentially expressed between CAFs and NFs of HNSCC patients are enriched to the PI3K/AKT pathway. Further experiments confirmed that the downregulation of FENDRR can activate the PI3K/AKT pathway in NFs and enhances the expression of matrix metalloproteinase 9 (MMP9). The overexpression of FENDRR had the opposite effect. Besides, we co-cultured human umbilical vein endothelial cells (HUVECs) with CAFs, and the tube-forming ability of HUVECs co-cultured with CAFs overexpressing FENDRR decreased significantly. However, activation of the AKT pathway of CAFs overexpressing FENDRR can weaken the inhibitory effect of FENDRR on angiogenesis. In summary, our experiments are focused on the influence of lncRNAs in CAFs on OSCC angiogenesis for the first time and prove that FENDRR mediates CAFs’ regulation of OSCC angiogenesis through the PI3K/AKT pathway.

It has long been suggested that emotion, especially threatening emotion, facilitates early visual perception to promote adaptive responses to potential threats in the environment. Here, we tested whether and how fearful emotion affects the basic visual ability of visual acuity. An adapted Posner’s spatial cueing task was employed, with fearful and neutral faces as cues and a Vernier discrimination task as the probe. The time course of the emotional attention effect was examined by varying the stimulus onset asynchrony (SOA) of the cue and probe. Two independent experiments (Experiments 1 and 3) consistently demonstrated that the brief presentation of a fearful face increased visual acuity at its location. The facilitation of perceptual sensitivity was detected at an SOA around 300 ms when the face cues were presented for both 250 ms (Experiment 1) and 150 ms (Experiment 3). This effect cannot be explained by physical differences between the fearful and neutral faces because no improvement was found when the faces were presented inverted (Experiment 2). In the last experiment (Experiment 4), the face cues were flashed very briefly (17 ms), and we did not find any improvement induced by the fearful face. Overall, we provide evidence that emotion interacts with attention to affect basic visual functions.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide. Metastasis is the main cause of the death of OSCC patients. Long noncoding RNAs (lncRNAs), one of the key factors affecting OSCC metastasis, are a subtype of RNA with a length of more than 200 nucleotides that has little or no coding potential. In recent years, the important role played by lncRNAs in biological processes, such as chromatin modification, transcription regulation, RNA stability regulation, and mRNA translation, has been gradually revealed. More and more studies have shown that lncRNAs can regulate the metastasis of various tumors including OSCC at epigenetic, transcriptional, and post-transcriptional levels. In this review, we mainly discussed the role and possible mechanisms of lncRNAs in OSCC metastasis. Most lncRNAs act as oncogenes and only a few lncRNAs have been shown to inhibit OSCC metastasis. Besides, we briefly introduced the research status of cancer-associated fibroblasts-related lncRNAs in OSCC metastasis. Finally, we discussed the research prospects of lncRNAs-mediated crosstalk between OSCC cells and the tumor microenvironment in OSCC metastasis, especially the potential research value of exosomes and lymphangiogenesis. In general, lncRNAs are expected to be used for screening, treatment, and prognosis monitoring of OSCC metastasis, but more work is still required to better understand the biological function of lncRNAs.

Abstract Background Cancer-associated fibroblasts (CAFs) have been widely reported to promote tumor angiogenesis. However, the underlying mechanisms of the proangiogenic switch of CAFs remain poorly understood. This study aims to clarify the mechanisms underlying the proangiogenic switch of CAFs. Methods NIH/3T3 cells were treated with B16 and B16F10-derived exosomes. Then the CAFs markers and proangiogenic factors were detected by RT-PCR and Western blot. CCK-8 assay, transwell migration assay, tube formation assay, and in vivo Matrigel plug assay were conducted to determine the proangiogenic capability of CAFs. Western blot and AG490 were used to investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the proangiogenic switch of CAFs. Bioinformatics analysis, luciferase reporter assay, microRNA mimic and inhibitor, and xenograft models were used to investigate the role of mmu-miR-155-5p (miR-155) in the proangiogenic switch of CAFs. Results In this study, we show that melanoma cell-secreted exosomes can induce reprogramming of fibroblasts into CAFs and that exosomal miR-155 can trigger the proangiogenic switch of CAFs. Mechanistically exosomal miR-155 can be delivered into fibroblasts and promote the expression of proangiogenic factors, including vascular endothelial growth factor A (VEGFa), fibroblast growth factor 2 (FGF2), and matrix metalloproteinase 9 (MMP9), by directly targeting suppressor of cytokine signaling 1 (SOCS1). Downregulation of SOCS1 activates JAK2/STAT3 signaling pathway and elevates the expression levels of VEGFa, FGF2, and MMP9 in fibroblasts. Treatment with exosomes containing overexpressed miR-155 can promote angiogenesis, and the reduction of miR-155 in melanoma cell-secreted exosomes alleviates angiogenesis in vitro and in vivo. Conclusions These results demonstrate that by promoting the expression of proangiogenic factors in recipient fibroblasts via SOCS1/JAK2/STAT3 signaling pathway, melanoma cell-secreted exosomal miR-155 can induce the proangiogenic switch of CAFs. Although tumor angiogenesis is modulated by various factors, exosomal miR-155 may be a potential target for controlling melanoma angiogenesis and used to set up novel strategies to treat melanoma.

Proper assembly of the 26 S proteasome is required to efficiently degrade polyubiquitinated proteins. Many proteasome subunits contain the proteasome-COP9-initiation factor (PCI) domain, thus raising the possibility that the PCI domain may play a role in mediating proteasome assembly. We have previously characterized the PCI protein Yin6, a fission yeast ortholog of the mammalian Int6 that has been implicated in breast oncogenesis, and demonstrated that it binds and regulates the assembly of the proteasome. In this study, we isolated another PCI proteasome subunit, Rpn7, as a high copy suppressor that rescued the proteasome defects in yin6 null cells. To better define the function of the PCI domain, we aligned protein sequences to identify a conserved leucine residue that is present in nearly all known PCI domains. Replacing it with aspartate in yeast Rpn7, Yin6, and Rpn5 inactivated these proteins, and mutant human Int6 mislocalized in HeLa cells. Rpn7 and Rpn5 bind Rpn9 with high affinity, but their mutant versions do not. Our data suggest that this leucine may interact with several hydrophobic amino acid residues to influence the spatial arrangement either within the N-terminal tandem α-helical repeats or between these repeats and the more C-terminal winged helix subdomain. Disruption of such an arrangement in the PCI domain may substantially inactivate many PCI proteins and block their binding to other proteins. [ABSTRACT FROM AUTHOR]

Background: The novel antidepressant drug agomelatine has been observed to cause adverse effect of hepatotoxicity in clinical applications. This study was designed to explore protective agents and investigated the underlying mechanism on L02 cells. Method: L02 cells were treated with agomelatine and oxymatrine (OMT) and cell apoptosis were analyzed through flow cytometric analysis, CCK-8 assay and TUNEL assay. In a separate experiment, the expressions of ER stress-related proteins were determined by western blot. In addition, MG132, chloroquine (CQ) and bafilomycinA1(BafA1) were used to investigate the potential pathway participating in CHOP degradation. Results: OMT significantly rescued agomelatine-induced hepatocyte apoptosis. Agomelatine treatment resulted in accumulation of CHOP protein in L02 cells, and this phenomenon could be significantly reduced by OMT, whereas abolished by MG132 treatment. Conclusion: We have demonstrated for the first time that OMT ameliorates the hepatocyte toxicity induced by agomelatine through decreasing CHOP on protein level. The underlying mechanism was proved to involve the molecular events that OMT promotes CHOP degradation via proteasome pathway. Overall, these results suggest that using OMT in combination with agomelatine may provide a safety strategy for clinical depression treatment.