EuRBPDB: a comprehensive resource for annotation, functional and oncological investigation of eukaryotic RNA binding proteins (RBPs).

RNA binding proteins (RBPs) are a large protein family that plays important roles at almost all levels of gene regulation through interacting with RNAs, and contributes to numerous biological processes. However, the complete list of eukaryotic RBPs including human is still unavailable. Here, we systematically identified RBPs in 162 eukaryotic species based on both computational analysis of RNA binding domains (RBDs) and large-scale RNA binding proteomic data, and established a comprehensive eukaryotic RBP database, EuRBPDB (http://EuRBPDB.syshospital.org). We identified a total of 311 571 RBPs with RBDs (corresponding to 6368 ortholog groups) and 3,651 non-canonical RBPs without known RBDs. EuRBPDB provides detailed annotations for each RBP, including basic information and functional annotation. Moreover, we systematically investigated RBPs in the context of cancer biology based on published literatures, PPI-network and large-scale omics data. To facilitate the exploration of the clinical relevance of RBPs, we additionally designed a cancer web interface to systematically and interactively display the biological features of RBPs in various types of cancers. EuRBPDB has a user-friendly web interface with browse and search functions, as well as data downloading function. We expect that EuRBPDB will be a widely-used resource and platform for both the communities of RNA biology and cancer biology.

Tea Polyphenols Attenuates Inflammation via Reducing Lipopolysaccharides Level and Inhibiting TLR4/NF-κB Pathway in Obese Mice.

Obesity is a worldwide epidemic and increases the risk of metabolic syndrome through chronic inflammation. Tea polyphenols (TP), the major functional component of tea, has shown preventive effects on obesity and obesity-related disease, but the underlying mechanism is complicated and remains obscure. The present study was aimed to elucidate the anti-inflammation effect of TP in high-fat-diet (HFD)-induced obese mice. Results showed that TP reduced obesity-induced inflammation and systemic lipopolysaccharides (LPS) level. The decrease of LPS level in circulation was followed by the downregulation of LPS specific receptor, toll-like receptor 4 (TLR4), and its co-receptor cluster of differentiation 14 (CD14) and adaptor protein differentiation factor 88 (MyD88) in hepatic and adipose tissues. That further inhibited the activation of nuclear factor κB (NF-κB). The serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß) and interleukin-6 (IL-6) were significantly decreased by TP in HFD-fed mice. TP also maintained the intestinal barrier integrity by increasing intestinal tight junction proteins and reversed gut dysbiosis in obese mice. These results suggested that TP attenuated obesity-induced inflammation by reducing systemic LPS level and inhibiting LPS-activated TLR4/NF-κB pathway.

Comparison of postoperative cytokine and hormone between endoscopically assisted and open parotid tumor resection.

OBJECTIVE: Endoscopically assisted extracapsular dissection through a single incision along the cephaloauricular furrow has been adapted as a method of access for operating on benign parotid gland tumors. However, no study has compared the immune and stress responses after surgery between the endoscopic procedure and conventional open surgery. METHODS: Through a randomized method, 50 patients with benign parotid gland tumors were assigned to undergo either endoscopically assisted extracapsular dissection or open parotidectomy. The postoperative inflammatory changes and hormonal response in the patients were analyzed at serum level during the preoperative period and at 12, 24, and 72 hr after either surgery. RESULTS: Twenty-three patients received an endoscopic procedure, while 27 underwent open surgery. The size of the incision, amount of intraoperative bleeding, volume of drainage, postoperative pain score, and satisfaction with appearance were all improved in the endoscopic procedure group. Additionally, the serum levels of C-reactive protein, interleukin (IL)-6, IL-10, and cortisol were significantly lower in the endoscopy group in comparison with those in the open surgery group. CONCLUSION: Endoscopically assisted extracapsular dissection on patients with benign parotid gland tumors is associated with lower inflammatory changes and hormone responses than open surgery, thereby reducing perioperative pathophysiological disturbance and enhancing recovery after surgery.

Effect of thread depth and thread pitch on the primary stability of miniscrews receiving a torque load : A finite element analysis.

PURPOSE: We have been developing a new type of miniscrew to specifically withstand orthodontic torque load. This study aimed to investigate the effect of thread depth and thread pitch on the primary stability of these miniscrews if stressed with torque load. METHODS: Finite element analysis (FEA) was used to evaluate the primary stability of the miniscrews. For thread depth analysis, the thread depth was set to 0.1-0.4 mm to construct 7 models. For thread pitch analysis, the thread pitch was set to 0.4-1.0 mm to construct another 7 models. A torque load of 6 Nmm was applied to the miniscrew, and the other parameters were kept constant for the analyses. Maximum equivalent stress (Max EQV) of cortical bone and maximum displacement of the miniscrews (Max DM) were the indicators for primary stability of the miniscrew in the 14 models. RESULTS: In the thread depth analysis, Max DM increased as the miniscrew thread depth increased, while Max EQV was smallest in model 3 (thread depth = 0.2, Max EQV = 8.91 MPa). In the pitch analysis, with an increase of the thread pitch, Max DM generally exhibited a trend to increase, while Max EQV of cortical bone showed a general trend to decrease. CONCLUSION: Considering the data of Max DM and Max EQV, the most appropriate thread depth and thread pitch of the miniscrews in our model was 0.2 and 0.7 mm, respectively. This knowledge may effectively improve the primary stability of newly developed miniscrews.

Optimization Analysis of Two-Factor Continuous Variable between Thread Depth and Pitch of Microimplant under Toque Force.

Microimplant, an anchorage device, is widely applied in clinical orthodontic treatment. Since tooth torque is required to be controlled during orthodontic tooth movement, a novel microimplant needs to be developed to apply better torque force during orthodontic. In this study, the optimal value ranges of thread depth and pitch under toque force were studied for choosing microimplant with relevant value ranges in clinical design from biomechanical perspective. Finite element analysis (FEA) and optimization design technology were used for accessing the optimal value ranges of thread depth and pitch under toque force. Thread depth (D) (0.1 mm to 0.4 mm) and pitch (P) (0.4 mm to 1 mm) were used as continuous variables, with the other parameters as constant, and the optimal value ranges were obtained by analyzing the tangent slope and sensitivity of the response curve. When a torque force of 6 Nmm was applied on the microimplant, the maximum equivalent stress (Max EQV) of cortical bone and maximum displacements (Max DM) of microimplant were analysis indexes. When 0.55 mm ≤ P ≤ 1 mm, the Max EQV of cortical bone was relatively smaller with less variation range. When 0.1 mm ≤ D ≤ 0.35 mm, the Max DM of microimplant was relatively smaller with less variation range. So in conclusion, the initial stability of microimplants with pitch 0.55 mm ≤ P ≤ 1 mm and thread depth 0.1 mm ≤ D ≤ 0.35 mm was better with the torque force applied.

Bibliometric Analysis of Chimeric Antigen Receptor-Based Immunotherapy in Cancers From 2001 to 2021.

Background: Chimeric antigen receptor (CAR)-based immunotherapy has shown great potential for the treatment of both hematopoietic malignancies and solid tumors. Nevertheless, multiple obstacles still block the development of CAR-based immunotherapy in the clinical setting. In this study, we aimed to summarize the research landscape and highlight the front lines and trends of this field. Methods: Literature published from 2001 to 2021 was searched in the Web of Science Core Collection database. Full records and cited references of all the documents were extracted and screened. Bibliometric analysis and visualization were conducted using CiteSpace, Microsoft Excel 2019, VOSviewer and R software. Results: A total of 5981 articles and reviews were included. The publication and citation results exhibited increasing trends in the last 20 years. Frontiers in Immunology and Blood were the most productive and most co-cited journals, respectively. The United States was the country with the most productive organizations and publications in the comprehensive worldwide cooperation network, followed by China and Germany. June, C.H. published the most papers with the most citations, while Maude, S.L. ranked first among the co-cited authors. The hotspots in CAR-based therapy research were multiple myeloma, safety and toxicity, solid tumors, CAR-engineered immune cells beyond T cells, and gene editing. Conclusion: CAR-based immunotherapy is a promising treatment for cancer patients, and there is an emerging movement toward using advanced gene modification technologies to overcome therapeutic challenges, especially in solid tumors, and to generate safer and more effective universal CAR-engineered cell products.

A Novel Prognostic Model for Oral Squamous Cell Carcinoma: The Functions and Prognostic Values of RNA-Binding Proteins.

PURPOSE: The biological roles and clinical significance of RNA-binding proteins (RBPs) in oral squamous cell carcinoma (OSCC) are not fully understood. We investigated the prognostic value of RBPs in OSCC using several bioinformatic strategies. MATERIALS AND METHODS: OSCC data were obtained from a public online database, the Limma R package was used to identify differentially expressed RBPs, and functional enrichment analysis was performed to elucidate the biological functions of the above RBPs in OSCC. We performed protein-protein interaction (PPI) network and Cox regression analyses to extract prognosis-related hub RBPs. Next, we established and validated a prognostic model based on the hub RBPs using Cox regression and risk score analyses. RESULTS: We found that the differentially expressed RBPs were closely related to the defense response to viruses and multiple RNA processes. We identified 10 prognosis-related hub RBPs (ZC3H12D, OAS2, INTS10, ACO1, PCBP4, RNASE3, PTGES3L-AARSD1, RNASE13, DDX4, and PCF11) and effectively predicted the overall survival of OSCC patients. The area under the receiver operating characteristic (ROC) curve (AUC) of the risk score model was 0.781, suggesting that our model exhibited excellent prognostic performance. Finally, we built a nomogram integrating the 10 RBPs. The internal validation cohort results showed a reliable predictive capability of the nomogram for OSCC. CONCLUSION: We established a novel 10-RBP-based model for OSCC that could enable precise individual treatment and follow-up management strategies in the future.

Tieguanyin Oolong Tea Extracts Alleviate Behavioral Abnormalities by Modulating Neuroinflammation in APP/PS1 Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative disease; tea components have important neuroprotective effects. This article explores the effects and mechanisms of Qingxiang Tiguanyin (Tgy-Q), Nongxiang Tieguanyin (Tgy-N), and Chenxiang Tieguanyin (Tgy-C) extracts on APP/PS1 AD model mice. Morris water maze and new object recognition experiments show that Tieguanyin extracts can effectively enhance the cognitive ability of APP/PS1 mice. H&E staining, Nissl staining, and immunohistochemical staining show that Tieguanyin extracts make nerve cell boundaries and nucleoli become clearer, relieve nucleus pyknosis, and effectively reduce Aß1-40 and Aß1-42 in the hippocampus and cortex. They also restore the morphology of microglia and astrocytes. In addition, Tieguanyin extracts can balance the oxidative stress level in the brain of APP/PS1 mice by improving the antioxidant capacity. Western blot results show that Tieguanyin extracts can reduce the expression of NF-κB p65, TNF-α, IL-1ß, IL-6, COX-2, and iNOS in mouse brain, which demonstrates that Tieguanyin extracts improves cognitive ability by alleviating inflammation. This article demonstrates for the first time that Tieguanyin extracts can inhibit the excessive activation of the NF-κB p65 signaling pathway and improve the antioxidant capacity in the cerebral cortex and hippocampus, to improve the cognitive ability of APP/PS1 mice. Our results shed light into the beneficial of Tieguanyin tea extracts on preventing and alleviating AD diseases.

Thread shape affects the stress distribution of torque force on miniscrews: a finite element analysis.

This study aimed to investigate the effect of miniscrews thread shape on the stress distribution receiving a torque load. Seven thread shapes (S,V1,V2,B1,B2,R1,R2) models were constructed and a 6 Nmm-torque load was applied. The order of maximum equivalent stress (EQV) value was V1 > V2 > B1 > R1 > R2 > B2 > S. The order of maximum displacement of miniscrew (Max DM) value was S > B2 > R1 = V1 > B1 > V2 > R2. Model R2 may be the most appropriate thread shape affording a torque force.

Liquid nitrogen cryotherapy of lip mucosa hemangiomas under inhalation general anesthesia with sevoflurane in early infancy.

Mucous membrane hemangiomas of the lip are common benign vascular tumors of infancy. This clinical study evaluated the efficacy and safety of liquid nitrogen cryotherapy of mucous membrane hemangiomas of the lip in early infancy. It was a retrospective review of 127 pediatric patients with hemangiomas involving the lips who underwent liquid nitrogen cryotherapy under inhalation general anesthesia with sevoflurane. Forty-one males and 86 females were treated. The overall median age at diagnosis of the mucous membrane hemangiomas was 3.6 months (range, 7 days to 18 months). The oral mucous membrane hemangioma involved the vermilion of the lower lip in 78 cases (61.4%), the vermilion of the upper lip in 40 cases (31.5%), and both vermilions in 9 cases (7.1%). No complications because of anesthesia occurred. The mean follow-up was 10 months, with a range of 8 to 14 months; 94 lesions (74.0%) were completely involuted, 22 lesions (17.3%) were mostly involuted, 11 lesions (8.7%) were partially involuted, and no lesion showed a small amount of involution. Liquid nitrogen cryotherapy is an effective, simple, and safe treatment for mucous membrane hemangiomas of the lip in early infancy.

Knockdown of SNHG8 repressed the growth, migration, and invasion of colorectal cancer cells by directly sponging with miR-663.

Aberrant expression of SNHG8 has been observed in some types of cancers. However, whether SNHG8 was aberrantly expressed in colorectal cancer and whether it could exert any function on the development of colorectal cancer remains largely elusive. In this study, we first investigated the expression pattern and biological function of SNHG8 in colorectal cancer. The expression level of SNHG8 was investigated in colorectal cancer tissues as well as in colorectal cancer cell lines by real-time PCR. Next, CCK8 assays were performed to evaluate the effects of SNHG8 on the proliferation of colorectal cancer cells and transwell assays were employed to evaluate migration and invasion. Bioinformatics were used for predicting the sponging miRNAs that interact with SNHG8. A dual luciferase reporter assay was adopted for the verification of interaction between SNHG8 and miRNA. Our data showed that SNHG8 was significantly up-regulated in colorectal cancer tissues and cell lines. In addition, knockdown of SNHG8 significantly inhibited the growth, migration, and invasion of colorectal cancer cells. It was predicted that miR-663 might interact with SNHG8 and the direct sponging was verified by dual luciferase reporter assay. Moreover, rescue experiments revealed that SNHG8 played a tumor promoting role by regulating miR-663. In the present study, we revealed that SNHG8 was up-regulated in colorectal cancer and promoted the proliferation, migration, and invasion of colorectal cancer by sponging miR-663, which helps to further reveal the underlying developmental mechanism of action and provides a potential therapeutic molecule for colorectal cancer therapy in the future.

Analysis on the stress of the bone surrounding mini-implant with different diameters and lengths under torque.

The purpose of this study is to compare the stress of the bone around the mini-implant under the two kinds of force: the composite force which contains torque and traditional single force. There were 96 finite element models formed by the combination of mini-implant and bone, with diameters of 1.2 mm, 1.6 mm, 2.0 mm and corresponding length being 6 mm, 8 mm, 10 mm, 12 mm, respectively. Each size corresponded to 8 models. Group SF (each size n=4) was loaded with 200 g single force, while Group CF (each size n=4) was loaded with composite force which contained 6N mm torque and 200 g single force. The maximum equivalent stress (Max EQS) of the bone surrounding mini implant with different loading directions was calculated, and the relationship of force direction, diameter and length was also evaluated. The Max EQS of Group CF was higher than that of Group SF. The effect of force direction on the stress was related to the diameter of mini implant, but had nothing to do with its length. The Max EQS of the cortical bone around mini implant in Group CF was higher (P<0.05) than that in Group SF. In contrast, there was no significant difference (P>0.05) between Group SF and Group CF in terms of bone stress when the diameter of mini implant was 1.6 mm or 2.0 mm. In our study, it is demonstrated that the diameter of mini-implant is better to be larger than 1.2 mm when a mini-implant is used in a torque control of tooth. The impact of this feature in the clinical setting needs to be verified.

Finite Element Analysis of Bone Stress around Micro-Implants of Different Diameters and Lengths with Application of a Single or Composite Torque Force.

BACKGROUND: Stress on the bone surrounding dental micro-implants affects implant success. PURPOSE: To compare the stress on the bone surrounding a micro-implant after application of a single force (SF) of 200 g or a composite force (CF) of 200 g and 6 N.mm torque. MATERIALS AND METHODS: Finite element models were developed for micro-implant diameters of 1.2, 1.6, and 2.0 mm, and lengths of 6, 8, 10, and 12 mm and either a SF or CF was applied. The maximum equivalent stress (Max EQS) of the bone surrounding the micro-implant was determined, and the relationships among type of force, diameter, and length were evaluated. RESULTS: The Max EQS of the CF exceeded that of the SF (P< 0.05). The effect of force on stress was related to implant diameter, but not to implant length. The larger CF led to greater instability of the micro-implant and the effect was most pronounced at an implant diameter of 1.2 mm. The use of implant diameters of 1.6 mm and 2.0 mm produced no significant difference in implant stability when either a CF or SF was applied. CONCLUSION: When considering the use of an implant to perform three-dimensional control on the teeth, the implant diameter chosen should be > 1.2 mm.

[Selection of optimal length and diameter of mini implant in two different forces: a three-dimensional finite element analysis].

OBJECTIVE: To investigate the effect of different length and diameters on the stability of mini implant and to select optimal length and diameter using continuous variation of parameters. METHODS: To perform 3-dimensional finite element analysis, finite element models of a maxilla, and mini implants with length of 6-12 mm and diameters of 1.2-2.0 mm were generated. Load of two different forces were applied to the head of mini implant. One type was horizontal force (HF), the other was composite force (CF). The maximum equivalent stress (Max EQV) in maxilla and the maximum displacement (Max DM) of mini implant were evaluated. RESULTS: The Max EQV in maxilla and Max DM of mini implant decreased as length and diameter increased. When length was more than 9 mm, the evaluation indexes were small and had a less change. Datas indicated that diameter played a more important role in reducing target, and was a more effective parameter in reducing Max EQV when CF was loaded. CONCLUSION: From biomechanical point of view, the choice of the length should not be more than 9 mm. When CF is loaded using the mini implant, diameter exceeding 1.2 mm are optimal design for mini implant.

Angoline: a selective IL-6/STAT3 signaling pathway inhibitor isolated from Zanthoxylum nitidum.

STAT3 signaling pathway is an important target for human cancer therapy. Thus, the identification of small-molecules that target STAT3 signaling will be of great interests in the development of anticancer agents. The aim of this study was to identify novel inhibitors of STAT3 pathway from the roots of Zanthoxylum nitidum (Roxb.) DC. The bioassay-guided fractionation of MeOH extract of Z. nitidum using a STAT3-responsive gene reporter assay led to the isolation of angoline (1) as a potent and selective inhibitor of the STAT3 signaling pathway (IC50=11.56 µM). Angoline inhibited STAT3 phosphorylation and its target gene expression and consequently induced growth inhibition of human cancer cells with constitutively activated STAT3 (IC50=3.14-4.72 µM). This work provided a novel lead for the development of anti-cancer agents targeting the STAT3 signaling pathway.

[Influence of the diameter and length of the mini-implant on the primary stability after loading with composite forces].

OBJECTIVE: To investigate the influence of the diameter and length of the mini-implant on the primary stability after loading with composite forces (CF) which contained torque and horizontal forces (HF). METHODS: Ninety-six finite element models were established by the combination of mini-implant and bone, diameters (1.2 mm, 1.6 mm, 2.0 mm) and length (6 mm, 8 mm, 10 mm, 12 mm). There were 12 sizes, each size corresponded with 8 models. Group HF (each size n = 4) was loaded with 1.96 N horizontal force and Group CF (each size n = 4) was loaded with composite force which contained 6 N·mm torque and 1.96 N horizontal force. The maximum displacement of mini-implant with different force directions, implant diameters and lengths were evaluated. RESULTS: The effect of force direction on the displacement related to diameter of mini-implant. The maximum displacement under load with HF respectively was changed with the changing of diameter[1.2 mm: (7.71 ± 0.49) µm; 1.6 mm: (3.94 ± 0.31) µm; 2.0 mm: (2.32 ± 0.43) µm], which were smaller than the maximum displacement of Group CF [1.2 mm: (9.22 ± 0.63) µm; 1.6 mm: (4.62 ± 0.52) µm; 2.0 mm: (2.69 ± 0.49) µm] (P < 0.05). When diameter was 1.2 mm, the difference of the maximum displacement [(1.61 ± 0.22) µm] between Group HF and CF was more obvious than that when the diameter was 1.6 mm or 2.0 mm [(0.64 ± 0.12), (0.49 ± 0.06) µm] (P < 0.05). CONCLUSIONS: The composite force had unfavorable effect on the primary stability of the mini-implant. The diameter of the mini-implant had better be larger than 1.2 mm when the composite forces were applied.

Anesthetic efficacy of inferior alveolar nerve block plus buccal infiltration or periodontal ligament injections with articaine in patients with irreversible pulpitis in the mandibular first molar.

OBJECTIVE: We compared the anesthetic efficacy of inferior alveolar nerve block (IANB) plus buccal infiltration (BI) and IANB plus periodontal ligament (PDL) articaine injections in patients with irreversible pulpitis in the mandibular first molar. STUDY DESIGN: Fifty-seven volunteers, patients with irreversible pulpitis in the mandibular first molar admitted to the Department of Stomatology, Second Affiliated Hospital, Sun Yat-Sen University, randomly received conventional IANB, containing 1.7 mL 4% articaine/HCl with 1:100,000 epinephrine, plus either BI or PDL injections containing 0.4 mL articaine/HCl with 1:100,000 epinephrine. The patients recorded the pain of the injections and endodontic access on a Heft-Parker visual analog scale (VAS). RESULTS: According to the VAS scores, all patients experienced no or mild pain with BI and PDL injections after the application of IANB. Anesthetic success occurred in 81.48% for IANB plus BI (IANB/BI) compared with 83.33% for IANB plus PDL injection (IANB/PDL injection). None of the observed differences between the 2 groups was significant (P > .05). CONCLUSION: Both injection combinations resulted in high anesthetic success in patients with irreversible pulpitis in the mandibular first molar.