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With the social and economic development and technological progress, higher education has entered the stage of popularization. In the new period and situation, our higher education institutions are facing many challenges. How to improve teaching quality? How to cultivate innovative talents? How to adapt to the requirements of high-quality talents in the era of knowledge economy and other issues, all of which require colleges and universities to change their traditional concepts, establish modern university concepts and improve their core competitiveness. And to achieve this goal, we must strengthen the school management, especially the construction of college teachers. This paper puts forward specific measures to improve the professionalism of teachers in our colleges and universities from five aspects: Updating the concept of education and attaching importance to teachers' professional development. Create an atmosphere of respect for teachers and stimulate their creative energy. Improve institutional mechanisms to protect teachers' legitimate rights and interests. Broaden training channels to promote teachers' lifelong learning. Establish a scientific evaluation system to stimulate teachers' self-reflection.

Ternary transition metal sulfides have attracted much attention due to their superior electrochemical properties. Nevertheless, it is difficult to commercialize sulfides due to their intrinsic properties such as dull reaction kinetics and an insufficient number of active sites. Herein, a self-supporting porous NiCoMnS sulfide (NiCoMnS/NF) arrayed on nickel foam (NF) with 3D honeycomb-like structure was designed and prepared via a hydrothermal and post-sulfidation process. It was found that the 3D hierarchically network architecture, constructed by nanosheets with abundant cavities, endowed NiCoMnS/NF with a high specific area and rich ion/electron-transport channels, which facilitated ion/electron transfer and Faradaic reaction kinetic. The optimal NiCoMnS/NF exhibited a markedly improved electrochemical performance due to the merits of complementary multi-composition and unique 3D network structure with multi-level "superhighways". Furthermore, the NiCoMnS//AC device fabricated with NiCoMnS/NF cathode and activated carbon (AC) anode delivered an excellent specific charge and exceptional energy density. This work offers a reference for designing the structure of electrode materials.

Although personalized recommendation system is widely applied on various platforms and commercial websites, fewer studies have examined the impact of personalized recommendations on digital satisfaction and the experience of users from their perspective. Will the attitude toward personalized recommendations affect digital satisfaction? Why do some people hold a negative attitude towards personalized recommendations? This study uses the quantitative research methods of questionnaires to collect data with a sample size of 1002. The result shows that there is a positive correlation between the attitude toward personalized recommendations and digital satisfaction. Approximately 25.4% of participants reported that they do not prefer personalized recommendations who are senior people having a low sense of media literacy and online experience with lower information overload. This article adopts information overload theory and user involvement theory to explain the correlation between personalized recommendation and digital satisfaction involving the discussion of its advantages and disadvantages, attempting to call attention to the neglected Generation X.

Irritable bowel syndrome (IBS) was found in 11% of the general population worldwide. The current pharmacologic management of IBS was unsatisfactory, and it was accompanied by a number of adverse events. Melatonin was found to play an important role in gastrointestinal smooth muscle motility. Dysregulation of endogenous melatonin secretion has been found in IBS patients. Exogenous melatonin supplement has become one alternative treatment for IBS, but the evidence is inconclusive. The current meta-analysis sought to determine the efficacy of exogenous melatonin supplement in improving IBS severity in IBS patients.We included randomized controlled trials (RCTs) that investigated the efficacy of exogenous melatonin supplement in ameliorating IBS severity in IBS patients. This meta-analysis was conducted using a random effects model. The primary target outcomes were changes in IBS severity associated with melatonin or placebo.This meta-analysis of 4 RCTs and 115 participants revealed that exogenous melatonin supplement was associated with significantly better improvement in overall IBS severity than placebo (k = 4, Hedges' g = 0.746, 95% confidence intervals = 0.401-1.091, p 0.001). The subgroup without concurrent medication had the same result (p 0.001). In addition, exogenous melatonin supplement was also associated with significantly better improvement in IBS pain severity (p 0.001) and quality of life (p = 0.007) than placebo, but not in abdominal distension (p = 0.111) or sleep quality (p = 0.142). Finally, melatonin was associated with similar safety profiles with placebo.This meta-analysis provides evidence for the use of exogenous melatonin in IBS patients to ameliorate overall IBS severity, IBS pain severity, and quality of life.PROSPERO CRD42021269451.

Aims Trastuzumab, the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (ERBB2/HER2), is currently used as a first-line treatment for HER2 (+) tumours. However, trastuzumab increases the risk of cardiac complications without affecting myocardial structure, suggesting a distinct mechanism of cardiotoxicity. Methods and results We used medium from trastuzumab-treated human umbilical vein endothelial cells (HUVECs) to treat CCC-HEH-2 cells, the human embryonic cardiac tissue-derived cell lines, and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to assess the crosstalk between vascular endothelial cells (VECs) and cardiomyocytes. Protein mass spectrometry analysis was used to identify the key factors from VECs that regulate the function of cardiomyocytes. We applied RNA-sequencing to clarify the mechanism, by which PTX3 causes cardiac dysfunction. We used an anti-human/rat HER2 (neu) monoclonal antibody to generate a rat model that was used to evaluate the effects of trastuzumab on cardiac structure and function and the rescue effects of lapatinib on trastuzumab-induced cardiac side effects. Medium from trastuzumab-treated HUVECs apparently impaired the contractility of CCC-HEH-2 cells and iPSC-CMs. PTX3 from VECs caused defective cardiomyocyte contractility and cardiac dysfunction in mice, phenocopying trastuzumab treatment. PTX3 affected calcium homoeostasis in cardiomyocytes, which led to defective contractile properties. EGFR/STAT3 signalling in VECs contributed to the increased expression and release of PTX3. Notably, lapatinib, a dual inhibitor of EGFR/HER2, could rescue the cardiac complications caused by trastuzumab by blocking the release of PTX3. Conclusion We identified a distinct mode of cardiotoxicity, wherein the activation of EGFR/STAT3 signalling by trastuzumab in VECs promotes PTX3 excretion, which contributes to the impaired contractility of cardiomyocytes by inhibiting cellular calcium signalling. We confirmed that lapatinib could be a feasible preventive agent against trastuzumab-induced cardiac complications and provided the rationale for the combined application of lapatinib and trastuzumab in cancer therapy.

A dual-emission ratiometric fluorescent sensor Cu NCs–Al@ZIF-90 was synthesized for ATP detection. The fluorescence emission of Cu NCs and 2-ICA induced by ATP addition was changed reversely and independently.

Chondrolaryngoplasty is a classical facial feminization surgery for transgender women. In recent years, however, an increasing number of patients assigned female at birth are seeking chondrolaryngoplasty for esthetic purposes. Traditional chondrolaryngoplasty can no longer cope with problems of the growing group whose leading cause of laryngeal prominence differs from the transgender population.A modified technique is designed as a supplement to the classical procedure. After the cartilage reduction process, paired platysma flaps are raised and advanced successively, resulting in an overlapped area over the thyroid notch, to further camouflage the thyroid prominence. To evaluate the efficiency of the new technique, a retrospective survey of 34 patients (5 men and 29 women) who underwent the surgery from 2016 to 2021 was performed, via a 5-point Likert scale including 7 questions. Physician assessment was also accomplished to provide an extra estimation. Complications were followed up and analyzed to evaluate the safety of modified surgery as well.Although only half of the patients graded prominence changes more than "moderately changed," as many as 75.0% of them still expressed "completely satisfied" or "satisfied very much" with the outcome. Similarly, physician assessment indicated a satisfactory result in appearance improvement. No severe and irreversible complications occurred after surgery, but lasting scar-related issues were reported by 4 patients and should be paid more attention to.Generally speaking, the new technique is both safe, efficient, and satisfying for most patients, especially ones assigned females at birth with esthetic demand.

An increasing number of studies have evaluated the association between ultra-processed foods (UPF) consumption and metabolic disorders. However, the association between UPF intake and non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, we analysed data from 6545 participants who were recruited in National Health and Nutrition Examination Surveys 2011–2018. UPF were defined in light of the NOVA food classification system and divided into quartiles based on its proportion of total weight intake. Complex logistic regression models were used to assess the association between UPF and NAFLD. Mediation analyses were conducted to reveal underlying mediators. We found that NAFLD patients consumed more UPF than controls (925·92 ± 18·08 v. 812·70 ± 14·32 g/d, P < 0·001). Dietary intake of UPF (% weight) was negatively related to the Healthy Eating Index-2015 score (Spearman r = −0·32, P < 0·001). In the multivariable model, the highest quartile compared with the lowest, the OR (95 % CI) were 1·83 (1·33, 2·53) for NAFLD (OR per 10 % increment: 1·15; 95 % CI: 1·09, 1·22; P for trend < 0·001) and 1·52 (1·12, 2·07) for insulin resistance (OR per 10 % increment: 1·11; 95 % CI: 1·05, 1·18; P for trend = 0·002). Mediation analyses revealed that poor diet quality, high saturated fat and refined grain intake partly mediated the association between UPF and NAFLD. In conclusion, high UPF intake was associated with an increased risk of NAFLD in US adults. Further prospective studies are needed to verify these findings.

Gastric varices (GV) represent a common and severe complication in patients with portal hypertension, commonly seen in patients with cirrhosis and severe pancreatic disease. Endoscopic ultrasonography is a safe and efficacious approach that can perform real-time ultrasonic scanning and intervention for the gastrointestinal submucosa, portal vein and its tributaries, and collateral circulations during direct endoscopic observation. Recently, various studies have been published about endoscopic ultrasound (EUS)-guided management of GV, mainly including diagnosis, treatment, and prognostic analysis. This article reviews published articles and guidelines to present the development process and current management of EUS-guided GV procedures.

Lasers represent a promising method for implant decontamination, but evidence on implant surface changes and subsequent biofilm formation is limited. This study aimed to assess the effect of erbium-doped yttrium aluminum garnet (Er:YAG) laser treatment on zirconia and titanium discs, and the differences in biofilm formation as a result of surface alterations.A two-stage (in vitro and in vivo) experiment utilizing Er:YAG laser on titanium and zirconia discs was performed. In vitro, surface alterations, roughness, and elemental-material weight differences following laser treatment were assessed using scanning electron microscopy and atomic force microscopy. In vivo, four participants wore custom-made intra-oral stents, embedded with laser-treated and untreated titanium and zirconia discs overnight. Biofilm-coated discs were stained using nucleic acid fluorescence dye and visualized using multiphoton confocal laser scanning microscopy. Biofilm 3D structure, biomass, thickness, and live-to-dead bacteria ratio were assessed.Both titanium and zirconia discs treated with Er:YAG laser resulted in visual surface alterations, but showed no significant change in average surface roughness (titanium P = 0.53, zirconia P = 0.34) or elemental-material-weight (titanium, P = 0.98), (zirconia, P = 0.96). No significant differences in biofilm biomass, average thickness, and live-to-dead bacteria ratio of laser-treated titanium and zirconia discs were identified compared to untreated groups (titanium P 0.05, zirconia P 0.05). Generally, zirconia discs presented with a lower live-to-dead bacteria ratio compared to titanium discs, regardless of laser treatment.Er:YAG laser treatment of titanium and zirconia implant surfaces does not significantly affect surface roughness, elemental material weight, or early biofilm formation in the oral cavity.

Avian influenza virus (AIV)is easy to cause diseases in birds and humans.It causes great economic losses to the poultry farms and leads to public health problems. Using vaccines is the main approach to control the prevalence of AIV. In our previously published article, a recombinant Lactobacillus plantarum (L. plantarum) expressing the NP-M2 peptide ofH9N2 AIV was generated, and its protective effect was evaluated in a chicken model. In this study, the protective effect was estimated in mice model. Humoral and cellular immune response parameters were measured using flow cytometry adding to body weight loss, survival rate, virus load, and histopathological changes in the lung. The obtained results elucidated that, the recombinant L. plantarum can promote the activation of dendritic cells (DC), proliferation of T and B cells adding to eliciting protective secretory IgA (sIgA) and humeral IgG level in mice model. Accordingly, it could be used as a patent vaccine to control the AIV infection.

The incidence of moderate to severe pain after total knee arthroplasty (TKA) ranges from 30-60% [1]. In the context of enhanced recovery after surgery, multimodal analgesia with peripheral nerve block as the core has become the main method of postoperative analgesia after TKA, and good analgesia is conducive to the early recovery of patients. Genicular nerve block (GNB) provides good analgesia anterior to the knee, while infiltration between the popliteal artery and capsule of the knee (iPACK) block provides good analgesia posterior to the knee [2]. We report a case of genicular nerve block combined with iPACK block for postoperative analgesia after total knee arthroplasty.

Sepsis represents a syndrome of systemic inflammatory response, which is mostly a result of infection with various pathogenic microorganisms, characterized by an uncontrolled infection response of the organism leading to life-threatening organ dysfunction. Long noncoding RNA (lncRNA), as competing endogenous RNA, can affect the binding of microRNA (miRNA) to mRNA, thus influencing the development of sepsis. In this study, based on transcriptome data from GEO database, we screened differentially expressed lncRNAs and constructed lncRNA-miRNA-mRNA network. And pathway IL-17RA-1/miR-7847-3p/protein kinase C gamma (PRKCG) coexpression network was successfully sorted out. The effect of this network on LPS-induced sepsis model in THP-1 cells was also verified by CCK-8, scratch, ELISA, Western blot, and qRT-PCR assays. Corresponding binding sites of miR-7847-3p to IL-17RA-1 and miR-7847-3p to PRKCG were verified using dual luciferase gene reporter assays, respectively. Compared with control, si-IL-17RA-1 significantly inhibited the cell viability and migration ability of THP-1, and levels of proinflammatory factors IL-6, IL-1β, and TNF-α secreted were markedly decreased, and the expression of IL-17RA-1, PRKCG, p-MEKK1, and p-JNK were markedly reduced. In addition, IL-17RA-1 could target binding to miR-7847-3p and inhibit its expression, and miR-7847-3p could also bind to PRKCG. Our experiments demonstrate that IL17-RA-1 attenuates the sepsis response through the miR-7847-3p/MAPK pathway, and this competing endogenous RNA (ceRNA) network may be a potential approach to predict and combat sepsis.

To investigate the epidemiological features in children after the coronavirus disease 2019 (COVID-19) pandemic.This study collected throat swabs and serum samples from hospitalized pediatric patients of Renmin Hospital of Wuhan University, Wuhan, Hubei province, China before and after the COVID-19 pandemic. Respiratory infected pathogens [adenovirus (ADV), influenza virus A/B (Flu A/B), parainfluenza virus 1/2/3 (PIV1/2/3), respiratory syncytial virus (RSV), Mycoplasma pneumoniae (MP), and Chlamydia pneumoniae (CP)] were detected. The pathogens, age, and gender were used to analyze the epidemiological features in children after the COVID-19 pandemic.The pathogen detection rate was significantly higher in females than in males (P0.05), and the infection of PIV1 and MP was mainly manifested. After the COVID-19 pandemic, PIV1, PIV3, RSV, and MP had statistically different detection rates among the age groups (P0.05), and was mainly detected in patients aged 0-6 years, 0-3 years, 0-3 years, and 1-6 years, respectively. When comparing before the COVID-19 pandemic, the total detection rate of common respiratory pathogens was lower (P0.05). Except for the increase in the detection rate of PIV1 and CP, the infection rate of other pathogens had almost decreased.The prevention and control measures for the COVID-19 pandemic effectively changed the epidemiological features of common respiratory tract infectious diseases in pediatric children.

Aiming at the problems of low accuracy, poor real-time performance and large cumulative error in traditional depth camera visual synchronization positioning and map construction algorithms, this paper proposes an improved visual SLAM algorithm for mobile robots based on depth camera. According to the realization process of robot vision, a feature point extraction algorithm based on feature extraction and image segmentation watershed algorithm is proposed in the front-end process, which improves the real-time performance of the algorithm. Then the RE-RANSAC algorithm is used to eliminate the mismatched feature points to improve the matching accuracy, and then the accumulated error is eliminated through closed loop detection, and finally the process of robot mapping is completed. After simulation experiments, the feasibility of the improved algorithm is proved, and the robot’s mapping and trajectory estimation are completed. &nbsp

Due to advancements in scientific research and technological innovation, as well as the proliferation of the Internet of things, the Internet, and big data, the general public has gradually become aware of a new type of intelligent nursing system model known as the smart nursing system. The smart nursing system is a sensing system and information platform for the elderly in their homes, communities, and institutions for elderly care. Based on this, it provides timely, efficient, and cost-effective elderly care services in real time. These services utilize the Internet of things and the Internet as well. Through the monitoring of video data, we are able to differentiate the visual motions of these elderly individuals and determine whether they are in a normal life state or a fall state. This has the potential to better meet the diverse and multifaceted needs of senior citizens, enhance the quality of life of senior citizens in their final years, and provide senior citizens with greater humanistic care and spiritual solace. Our team has developed an intelligent nursing system based on the visual action recognition algorithm, also known as the deep learning (DL) algorithm. As a result of our simulation tests, we discovered that the algorithm can accurately identify the living situations of elderly individuals at home.

Previous studies show that astragaloside IV (ASIV) has anti-renal fibrosis effects. However, its mechanism remains elusive. In this study, we investigated the anti-fibrosis mechanisms of ASIV on chronic kidney disease (CKD) in vivo and in vitro. A CKD model was induced in rats with adenine (200 mg/kg/d, i.g.), and an in vitro renal fibrosis model was induced in human kidney-2 (HK-2) cells treated with TGF-β1. We revealed that ASIV significantly alleviated renal fibrosis by suppressing the expressions of epithelial–mesenchymal transition (EMT)-related proteins, including fibronectin, vimentin, and alpha-smooth muscle actin (α-SMA), and G2/M arrest-related proteins, including phosphorylated p53 (p-p53), p21, phosphorylated histone H3 (p-H3), and Ki67 in both of the in vivo and in vitro models. Transcriptomic analysis and subsequent validation showed that ASIV rescued ALDH2 expression and inhibited AKT/mTOR-mediated autophagy. Furthermore, in ALDH2-knockdown HK-2 cells, ASIV failed to inhibit AKT/mTOR-mediated autophagy and could not blunt EMT and G2/M arrest. In addition, we further demonstrated that rapamycin, an autophagy inducer, reversed the treatment of ASIV by promoting autophagy in TGF-β1-treated HK-2 cells. A dual-luciferase report assay indicated that ASIV enhanced the transcriptional activity of the ALDH2 promoter. In addition, a further molecular docking analysis showed the potential interaction of ALDH2 and ASIV. Collectively, our data indicate that ALDH2-mediated autophagy may be a novel target in treating renal fibrosis in CKD models, and ASIV may be an effective targeted drug for ALDH2, which illuminate a new insight into the treatment of renal fibrosis and provide new evidence of pharmacology to elucidate the anti-fibrosis mechanism of ASIV in treating renal fibrosis.

Contrast-enhanced ultrasound (CEUS) is a promising imaging modality in predicting the efficacy of neoadjuvant chemotherapy for pancreatic cancer, a tumor with high mortality. In this study, we proposed a deep-learning-based strategy for analyzing CEUS videos to predict the prognosis of pancreatic cancer neoadjuvant chemotherapy. Pre-trained convolutional neural network (CNN) models were used for binary classification of the chemotherapy as effective or ineffective, with CEUS videos collected before chemotherapy as the model input, and with the efficacy after chemotherapy as the reference standard. We proposed two deep learning models. The first CNN model used videos of ultrasound (US) and CEUS (US+CEUS), while the second CNN model only used videos of selected regions of interest (ROIs) within CEUS (CEUS-ROI). A total of 38 patients with strict restriction of clinical factors were enrolled, with 76 original CEUS videos collected. After data augmentation, 760 and 720 videos were included for the two CNN models, respectively. Seventy-six-fold and 72-fold cross-validations were performed to validate the classification performance of the two CNN models. The areas under the curve were 0.892 and 0.908 for the two models. The accuracy, recall, precision and F1 score were 0.829, 0.759, 0.786, and 0.772 for the first model. Those were 0.864, 0.930, 0.866, and 0.897 for the second model. A total of 38.2% and 40.3% of the original videos could be clearly distinguished by the deep learning models when the naked eye made an inaccurate classification. This study is the first to demonstrate the feasibility and potential of deep learning models based on pre-chemotherapy CEUS videos in predicting the efficacy of neoadjuvant chemotherapy for pancreas cancer.

Dental caries is one of the most common chronic diseases worldwide. Streptococcus mutans and Candida albicans are two major pathogens associated with dental caries. Several recent studies revealed that Lactobacillus plantarum inhibits S. mutans and C. albicans in biofilms and in a rodent model of dental caries. The aim of this study was to investigate the dose-dependent effect of L. plantarum against S. mutans and C. albicans in a planktonic model that simulated a high-caries-risk clinical condition. Mono-, dual-, and multi-species models were utilized, with five doses of L. plantarum (ranging from 1.0 × 104 to 1.0 × 108 CFU/mL). Real-time PCR was used to assess the expression of the virulence genes of C. albicans and S. mutans and the genes of L. plantarum. Student’s t-tests and one-way ANOVA, followed by post hoc tests, were employed to compare the cell viability and gene expression among groups. A dose-dependent inhibition on C. albicans and S. mutans was observed with increased dosages of L. plantarum. L. plantarum at 108 CFU/mL demonstrated the highest antibacterial and antifungal inhibitory effect in the dual- and multi-species models. Specifically, at 20 h, the growth of C. albicans and S. mutans was suppressed by 1.5 and 5 logs, respectively (p < 0.05). The antifungal and antibacterial effects were attenuated in lower doses of L. plantarum (104–107 CFU/mL). The expression of C. albicansHWP1 and ECE 1 genes and S. mutanslacC and lacG genes were significantly downregulated with an added 108 CFU/mL of L. plantarum (p < 0.05). The addition of 108 CFU/mL L. plantarum further inhibited the hyphae or pseudohyphae formation of C. albicans. In summary, L. plantarum demonstrated dose-dependent antifungal and antibacterial effects against C. albicans and S. mutans. L. plantarum emerged as a promising candidate for the creation of novel antimicrobial probiotic products targeting dental caries prevention. Further research is warranted to identify the functional metabolites produced by L. plantarum at different dosages when interacting with C. albicans and S. mutans.

This study aimed to evaluate the impact of Nystatin oral rinse on salivary and supragingival microbiota in adults with oral candidiasis and identify predictive factors related to individuals’ responses to Nystatin. The trial involved twenty participants who used 600,000 International Units/application of Nystatin oral rinse for seven days, four times a day, and were followed up at one week and three months after the rinse. The salivary and plaque microbiome of the participants were assessed via 16S rDNA amplicon sequencing. Overall, salivary and plaque microbiomes remained stable. However, among the participants (53 percent) who responded to Nystatin rinse (defined as free of oral Candida albicans post treatment), Veillonella emerged as a core genus alongside Streptococcus and Actinomyces in supragingival plaque at the 3-month follow-up. Furthermore, statistical models were fit to identify predictive factors of Nystatin rinse success (elimination of C. albicans) or failure (remaining C. albicans). The results revealed that an increased level of salivary Interferon (IFN)-γ-inducible protein (IP-10), also known as C-X-C motif chemokine ligand 10 (CXCL10), was an indicator of a failure of responding to Nystatin rinse. Future clinical trials are warranted to comprehensively assess the impact of antifungal treatment on the oral flora.

Aiming at the problems of traditional equipment fault diagnosis, such as poor real-time performance, low efficiency and strong subjectivity, a method of industrial equipment sub-health status monitoring based on big data technology was proposed. Firstly, the characteristic engineering of vibration signals is formed by preprocessing vibration signals collected by sensors located near the bearing shaft. Then, the deep residual shrinkage network DRSN was used to build the classification model. By tuning the model parameters, the optimal sub-health status identification model of industrial equipment was obtained. Finally, the accuracy, robustness and generalization of the model were verified. Experimental results show that this method has better generalization performance and can significantly improve the accuracy of industrial equipment fault diagnosis, which has important theoretical value and practical significance to solve the sub-health problems of industrial equipment.

Purpose: Increased activity of STAT3 is associated with progression of head and neck squamous cell carcinoma (HNSCC). Upstream activators of STAT3, such as JAKs, represent potential targets for therapy of solid tumors, including HNSCC. In this study, we investigated the anticancer effects of ruxolitinib, a clinical JAK1/2 inhibitor, in HNSCC preclinical models, including patient-derived xenografts (PDX) from patients treated on a window-of-opportunity trial. Experimental Design: HNSCC cell lines were treated with ruxolitinib, and the impact on activated STAT3 levels, cell growth, and colony formation was assessed. PDXs were generated from patients with HNSCC who received a brief course of neoadjuvant ruxolitinib on a clinical trial. The impact of ruxolitinib on tumor growth and STAT3 activation was assessed. Results: Ruxolitinib inhibited STAT3 activation, cellular growth, and colony formation of HNSCC cell lines. Ruxolitinib treatment of mice bearing an HNSCC cell line–derived xenograft significantly inhibited tumor growth compared with vehicle-treated controls. The response of HNSCC PDXs derived from patients on the clinical trial mirrored the responses seen in the neoadjuvant setting. Baseline active STAT3 (pSTAT3) and total STAT3 levels were lower, and ruxolitinib inhibited STAT3 activation in a PDX from a patient whose disease was stable on ruxolitinib, compared with a PDX from a patient whose disease progressed on ruxolitinib and where ruxolitinib treatment had minimal impact on STAT3 activation. Conclusions: Ruxolitinib exhibits antitumor effects in HNSCC preclinical models. Baseline pSTAT3 or total STAT3 levels in the tumor may serve as predictive biomarkers to identify patients most likely to respond to ruxolitinib.

Fragile X syndrome (FXS) is a leading form of inherited intellectual disability and single-gene cause of autism spectrum disorder (ASD) and is characterized by core deficits in cognitive flexibility, sensory sensitivity, emotion, and social interactions. Motor deficits are a shared feature of FXS and autism. The cerebellum has emerged as one of the target brain areas affected by neurodevelopmental diseases. Alterations in the cerebellar structure, circuits, and function may be the key drivers of impaired fine and gross motor skills in FXS and fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we briefly examined recent findings in FXS and present a discussion on the literature supporting motor skill deficits in FXS. Subsequently, we focused on neuropathological alterations in the cerebellum in FXS and FXTAS. We highlight studies that have directly examined the function of fragile X mental retardation protein and related epigenetic variations in the cerebellum. Overall, we obtained considerable supporting evidence for the hypothesis that cerebellar dysfunction is evident in FXS and FXTAS; however, compared with studies on other ASD models, studies on motor skills related to fragile X disorders are particularly rare and inconclusive. Hence, future research should address FXS-related motor and behavioral trajectories and examine the underlying mechanisms at both the cell and circuit levels.