Retinoic acid receptor-related orphan receptor alpha and synthetic RORα agonist against invasion and metastasis in tongue squamous cell carcinoma.

Retinoic acid receptor-related orphan receptor alpha (RORα), an essential tumor suppressor in a range of human malignancies, is classified as a member of the orphan nuclear receptor family. The most prevalent form of oral cancer, tongue squamous cell carcinoma (TSCC) is characterized by its severe malignancy and unfavorable prognosis. However, the extent to which its tumorigenesis mechanisms are associated with RORα expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORα is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORα was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORα in TSCC, we activated the expression of RORα in human TSCC cell line (SCC9 cells) by transfecting RORα cDNA and using the selective RORα agonist SR1078. The results show that RORα can significantly inhibit the invasion, migration, proliferation, and adhesion of TSCC cells and induce cell apoptosis. In addition, xenograft models confirmed the conclusion that stable activation or treatment with SR1078 to increase RORα content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORα in the progression of TSCC. In addition, the preliminary application results of SR1078 in TSCC show that SR1078 is expected to be a potential therapeutic medication for TSCC. These findings provide innovative perspectives on the development of potential biomarkers and agents for TSCC therapy. The objective is to introduce novel strategy and alternatives for the prevention and treatment of TSCC.

Comparison of progestin-primed ovarian stimulation regimen and antagonist regimen in women aged 35 years or older with diminished ovarian reserve: A propensity score-matched study.

OBJECTIVE: Diminished ovarian reserve (DOR) has been a major challenge in infertility treatment. The present study aimed to compare the efficacy of progestin-primed ovarian stimulation (PPOS) regimen and antagonist regimen in infertile patients aged 35 years or older with DOR. METHODS: A retrospective study of 289 in vitro fertilization (IVF) cycles from April 2016 to June 2022 was performed. Propensity score matching (PSM) was used to balance the baseline characteristics between the two groups at a ratio of 1:1. RESULTS: After matching, there were 87 cycles in the PPOS group and 87 cycles in the antagonist group. The primary outcome measures included the incidence of premature LH surge, the number of retrieved oocytes, and the number of mature oocytes, which were comparable between the two groups (all P values >0.05). There were no significant differences in laboratory indicators and final clinical outcomes between the two groups (all P values >0.05). CONCLUSIONS: For DOR patients aged 35 years or older, the number of retrieved oocytes and the number of mature oocytes were comparable between the PPOS and antagonist groups. Moreover, the two regimens showed no difference in the inhibition of premature LH surge.

Assessment of the osteogenic effect after maxillary sinus floor elevation and simultaneous implantation with or without bone grafts by analyzing trabecular bone parameters: a retrospective study

Abstract Objective: The aim of this population-based retrospective study was to compare the osteogenic effect of newly formed bone after maxillary sinus floor elevation (MSFE) and simultaneous implantation with or without bone grafts by quantitatively analyzing trabecular bone parameters. Methodology: A total of 100 patients with missing posterior maxillary teeth who required MSFE and implantation were included in this study. Patients were divided into two groups: the non-graft group (n=50) and the graft group (n=50). Radiographic parameters were measured using cone beam computed tomography (CBCT), and the quality of newly formed bone was analyzed by assessing trabecular bone parameters using CTAn (CTAnalyzer, SkyScan, Antwerp, Belgium) software. Results: In the selected regions of interest, the non-graft group showed greater bone volume/total volume (BV/TV), bone surface/total volume (BS/TV), trabecular number (Tb. N), and trabecular thickness (Tb. Th) than the graft group (p<0.001). The non-graft group showed lower trabecular separation (Tb. Sp) than the graft group (p<0.001). The incidence of perforation and bleeding was higher in the graft group than in the non-graft group (p<0.001), but infection did not significantly differ between groups (p>0.05). Compared to the graft group, the non-graft group showed lower postoperative bone height, gained bone height and apical bone height (p<0.001). Conclusion: MSFE with and without bone grafts can significantly improve bone formation. In MSFE, the use of bone grafts hinders the formation of good quality bone, whereas the absence of bone grafts can generate good bone quality and limited bone mass.

Designing nanohesives for rapid, universal, and robust hydrogel adhesion.

Nanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering.

In vivo recording of suprachiasmatic nucleus dynamics reveals a dominant role of arginine vasopressin neurons in circadian pacesetting.

The central circadian clock of the suprachiasmatic nucleus (SCN) is a network consisting of various types of neurons and glial cells. Individual cells have the autonomous molecular machinery of a cellular clock, but their intrinsic periods vary considerably. Here, we show that arginine vasopressin (AVP) neurons set the ensemble period of the SCN network in vivo to control the circadian behavior rhythm. Artificial lengthening of cellular periods by deleting casein kinase 1 delta (CK1δ) in the whole SCN lengthened the free-running period of behavior rhythm to an extent similar to CK1δ deletion specific to AVP neurons. However, in SCN slices, PER2::LUC reporter rhythms of these mice only partially and transiently recapitulated the period lengthening, showing a dissociation between the SCN shell and core with a period instability in the shell. In contrast, in vivo calcium rhythms of both AVP and vasoactive intestinal peptide (VIP) neurons in the SCN of freely moving mice demonstrated stably lengthened periods similar to the behavioral rhythm upon AVP neuron-specific CK1δ deletion, without changing the phase relationships between each other. Furthermore, optogenetic activation of AVP neurons acutely induced calcium increase in VIP neurons in vivo. These results indicate that AVP neurons regulate other SCN neurons, such as VIP neurons, in vivo and thus act as a primary determinant of the SCN ensemble period.

Mapping Multi-factor-mediated Chromatin Interactions to Assess Dysregulation of Lung Cancer-related Genes.

Studies on the lung cancer genome are indispensable for developing a cure for lung cancer. Whole-genome resequencing, genome-wide association studies, and transcriptome sequencing have greatly improved our understanding of the cancer genome. However, dysregulation of long-range chromatin interactions in lung cancer remains poorly described. To better understand the three-dimensional (3D) genomic interaction features of the lung cancer genome, we used the A549 cell line as a model system and generated high-resolution chromatin interactions associated with RNA polymerase II (RNAPII), CCCTC-binding factor (CTCF), enhancer of zeste homolog 2 (EZH2), and histone 3 lysine 27 trimethylation (H3K27me3) using long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET). Analysis showed that EZH2/H3K27me3-mediated interactions further repressed target genes, either through loops or domains, and their distributions along the genome were distinct from and complementary to those associated with RNAPII. Cancer-related genes were highly enriched with chromatin interactions, and chromatin interactions specific to the A549 cell line were associated with oncogenes and tumor suppressor genes, such as additional repressive interactions on FOXO4 and promoter-promoter interactions between NF1 and RNF135. Knockout of an anchor associated with chromatin interactions reversed the dysregulation of cancer-related genes, suggesting that chromatin interactions are essential for proper expression of lung cancer-related genes. These findings demonstrate the 3D landscape and gene regulatory relationships of the lung cancer genome.

Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer.

Rheumatoid arthritis (RA) is a chronic, heterogeneous autoimmune disease. Its high disability rate has a serious impact on society and individuals, but there is still a lack of effective and reliable diagnostic markers and therapeutic targets for RA. In this study, we integrated RA patient information from three GEO databases for differential gene expression analysis. Additionally, we also obtained pan-cancer-related genes from the TCGA and GTEx databases. For RA-related differential genes, we performed functional enrichment analysis and constructed a weighted gene co-expression network (WGCNA). Then, we obtained 490 key genes by intersecting the significant module genes selected by WGCNA and the differential genes. After using the RanddomForest, SVM-REF, and LASSO three algorithms to analyze these key genes and take the intersection, based on the four core genes (BTN3A2, CYFIP2, ST8SIA1, and TYMS) that we found, we constructed an RA diagnosis. The nomogram model showed good reliability and validity after evaluation, and the ROC curves of the four genes showed that these four genes played an important role in the pathogenesis of RA. After further gene correlation analysis, immune infiltration analysis, and mouse gene expression validation, we finally selected CYFIP2 as the cut-in gene for pan-cancer analysis. The results of the pan-cancer analysis showed that CYFIP2 was closely related to the prognosis of patients with various tumors, the degree of immune cell infiltration, as well as TMB, MSI, and other indicators, suggesting that this gene may be a potential intervention target for human diseases including RA and tumors.

Multiplexable intrinsic Fabry-Perot interferometric fiber sensors for multipoint hydrogen gas monitoring.

This Letter presents an approach to produce multiplexable optical fiber chemical sensor using an intrinsic Fabry-Perot interferometer (IFPI) array via the femtosecond laser direct writing technique. Using the hydrogen-sensitive palladium (Pd) alloy as a functional sensory material, Pd alloy coated IFPI devices can reproducibly and reversibly measure hydrogen concentrations with a detection limit of 0.25% at room temperature. Seven IFPI sensors were fabricated in one fiber and performed simultaneous temperature and hydrogen measurements at seven different locations. This Letter demonstrates a simple yet effective approach to fabricate multiplexable fiber optical chemical sensors for use in harsh environments.

Porcine deltacoronavirus nucleocapsid protein antagonizes IFN-ß production by impairing dsRNA and PACT binding to RIG-I.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus that causes watery diarrhea, vomiting and mortality in newborn piglets. Previous studies have suggested that PDCoV infection antagonizes RIG-I-like receptor (RLR)-mediated IFN-ß production to evade host innate immune defense, and PDCoV-encoded nonstructural protein nsp5 and accessory protein NS6 are associated with this process. However, whether the structural protein(s) of PDCoV also antagonize IFN-ß production remains unclear. In this study, we found that PDCoV nucleocapsid (N) protein, the most abundant viral structural protein, suppressed Sendai virus (SEV)-induced IFN-ß production and transcription factor IRF3 activation, but did not block IFN-ß production induced by overexpressing RIG-I/MDA5. Furthermore, study revealed that PDCoV N protein interacted with RIG-I and MDA5 in an in vitro overexpression system and evident interactions between N protein and RIG-I could be detected in the context of PDCoV infection, which interfered with the binding of dsRNA and protein activator of protein kinase R (PACT) to RIG-I. Together, our results demonstrate that PDCoV N protein is an IFN antagonist and utilizes diverse strategies to attenuate RIG-I recognition and activation.

miRNA-21 promotes osteogenesis via the PTEN/PI3K/Akt/HIF-1α pathway and enhances bone regeneration in critical size defects.

BACKGROUND: Functional reconstruction of maxillofacial bone defects is a considerable clinical challenge. Many studies have emphasized the osteogenic and angiopoietic abilities of stem cells for tissue regeneration. We previously showed that microRNA-21 (miRNA-21) can promote angiogenesis in human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs). In the present study, the role of miRNA-21 in osteogenic differentiation of bone marrow-derived stem cells (BMSCs) was investigated. METHODS: Western blotting and qPCR were performed to investigate the influences of miRNA-21 on osteogenic differentiation of BMSCs. The effects of miRNA-21 on PTEN/PI3K/Akt/HIF-1α pathway were also assessed using western blotting. To further evaluate the roles of miRNA-21 in osteogenesis in vivo, we conducted animal experiments in rat and canine. New bone formation was assessed using micro-CT and histological methods. RESULTS: In the present study, we found that miRNA-21 promotes the migration and osteogenic differentiation of bone marrow-derived stem cells (BMSCs) in vitro. Using gain- and loss-of-function studies, we found that miRNA-21 promoted the osteogenic ability of BMSCs by increasing P-Akt and HIF-1α activation. Finally, we verified the essential role of miRNA-21 in osteogenesis by implanting a miRNA-21-modified BMSCs/ß-tricalcium phosphate (ß-TCP) composite into critical size defects. Radiography, micro-CT, and histology revealed significantly greater volume of new bone formation in the miRNA-21 group than in the control group. CONCLUSION: In conclusion, our study demonstrated an essential role of miRNA-21 in promoting maxillofacial bone regeneration via the PTEN/PI3K/Akt/HIF-1α pathway.

Prevalence and correlates of suicidal ideation among college students: A mental health survey in Jilin Province, China.

BACKGROUND: The prevention of suicidal ideation plays a key role in reducing suicide rates. This study aimed to determine the prevalence of suicidal ideation among college students in Jilin Province, China, and to analyse the risk factors associated with suicidal ideation. METHODS: A total of 6284 valid data collection sheets were collected using the stratified cluster sampling method. The data collected were divided into four sections, namely, socio-demographic information, family and social interactions, daily habits, and mental health self-rating scales. RESULTS: The prevalence of suicidal ideation in the past 12 months was 9.2%. A multivariate logistic regression analysis showed that being a senior (OR = 1.769, 95%CI:1.225-2.555), general family relationships (OR = 1.641, 95%CI:1.172-2.298), frequent parental quarrels (OR = 1.398, 95%CI:1.027-1.902)/parental separation (OR = 2.497, 95%CI:1.414-4.408), the level of satisfaction with motherly love (OR = 2.261, 95%CI:1.454-3.515), having only one or two friend(s) (OR = 1.530, 95%CI:1.038-2.254), frequent excursions to bars/ karaoke halls/ song and dance halls (OR = 1.673, 95%CI:1.257-2.229) or billiard halls with friends (OR = 1.865, 95%CI:1.270-2.740), smoking (OR = 2.175, 95%CI:1.603-2.951), moderate sleep quality (OR = 1.636, 95%CI:1.115-2.402), and depressive symptoms (OR = 2.078, 95%CI: 1.710-2.525) were risk factors for suicidal ideation. Family factors had the most influence on suicidal ideation, whereas depression symptoms were identified to be a mediating factor between family, social interactions, or daily habits and suicidal ideation, and it only exerted direct effects. LIMITATIONS: This cross-sectional study cannot provide causal interpretations. CONCLUSION: Our findings showed the prevalence of suicidal ideation among college students in Jilin province. Among all the risk factors associated with suicidal ideation, family factors should be the main concern in the prevention of suicidal ideation, and interventions that target depression symptoms are key to reducing suicidal ideation.

Altered fractionation radiotherapy with or without chemotherapy in the treatment of head and neck cancer: a network meta-analysis.

OBJECTIVES: A Bayesian network meta-analysis (NMA) was conducted in patients with head and neck cancers (HNCs) to estimate the efficacy and safety of treatment with conventional fractionation radiotherapy (CF), conventional fractionation chemoradiotherapy (CF_CRT), hyperfractionated radiotherapy (HF), hyperfractionated chemoradiotherapy (HF_CRT), accelerated fractionation radiotherapy, accelerated fractionation chemoradiotherapy, accelerated hyperfractionated radiotherapy (HART) or accelerated hyperfractionated chemoradiotherapy (HACRT) to identify superior treatments to aid in clinical decisions. METHODS: PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for potentially eligible randomized controlled trials up to December 2016. Overall survival (OS), disease-free survival (DFS) and locoregional control (LRC) were considered efficacy outcomes, whereas acute toxicity and late toxicity on skin and mucosa were considered safety outcomes. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment in each index. RESULTS: Data from 72 trials with 21,868 participants were included in the analysis. Concerning OS, all treatments were associated with a significant advantage compared to CF alone, with HR effect sizes ranging from 0.64 to 0.83, and HACRT was significantly more effective than all the other treatments. The network comparisons of both HACRT vs HART and HF_CRT vs HF demonstrated a higher OS benefit, with an HR of 0.78 (95% credible interval [CrI]: 0.64-0.95) and 0.78 (95% CrI: 0.61-0.99), respectively. The results of SUCRA indicated that HACRT had the best ranking for OS and LRC, HF_CRT for DFS, HART for acute and late skin toxicity, CF_CRT for acute mucosal toxicity and HF_CRT for late mucosal toxicity. CONCLUSION: The NMA results support the notion that HACRT is the preferable treatment modality for HNCs because it has better rankings in all three efficacy indexes, although it does present a high risk of acute mucosal toxicity.

Functional reconstruction of critical-sized load-bearing bone defects using a Sclerostin-targeting miR-210-3p-based construct to enhance osteogenic activity.

A considerable amount of research has focused on improving regenerative therapy strategies for repairing defects in load-bearing bones. The enhancement of tissue regeneration with microRNAs (miRNAs) is being developed because miRNAs can simultaneously regulate multiple signaling pathways in an endogenous manner. In this study, we developed a miR-210-based bone repair strategy. We identified a miRNA (miR-210-3p) that can simultaneously up-regulate the expression of multiple key osteogenic genes in vitro. This process resulted in enhanced bone formation in a subcutaneous mouse model with a miR-210-3p/poly-l-lactic acid (PLLA)/bone marrow-derived stem cell (BMSC) construct. Furthermore, we constructed a model of critical-sized load-bearing bone defects and implanted a miR-210-3p/ß-tricalcium phosphate (ß-TCP)/bone mesenchymal stem cell (BMSC) construct into the defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. We also identified a new mechanism by which miR-210-3p regulates Sclerostin protein levels. This miRNA-based strategy may yield novel therapeutic methods for the treatment of regenerative defects in vital load-bearing bones by utilizing miRNA therapy for tissue engineering. STATEMENT OF SIGNIFICANCE: The destroyed maxillofacial bone reconstruction is still a real challenge for maxillofacial surgeon, due to that functional bone reconstruction involved load-bearing. Base on the above problem, this paper developed a novel miR-210-3p/ß-tricalcium phosphate (TCP)/bone marrow-derived stem cell (BMSC) construct (miR-210-3p/ß-TCP/BMSCs), which lead to functional reconstruction of critical-size mandible bone defect. We found that the load-bearing defect was almost fully repaired using the miR-210-3p construct. In addition, we also found the mechanism of how the delivered microRNA activated the signaling pathways of endogenous stem cells, leading to the defect regeneration. This miRNA-based strategy can be used to regenerate defects in vital load-bearing bones, thus addressing a critical challenge in regenerative medicine by utilizing miRNA therapy for tissue engineering.

Radiation resistant fiber Bragg grating in random air-line fibers for sensing applications in nuclear reactor cores.

This paper reports the testing results of radiation resistant fiber Bragg grating (FBG) in random air-line (RAL) fibers in comparison with FBGs in other radiation-hardened fibers. FBGs in RAL fibers were fabricated by 80 fs ultrafast laser pulse using a phase mask approach. The fiber Bragg gratings tests were carried out in the core region of a 6 MW MIT research reactor (MITR) at a steady temperature above 600°C and an average fast neutron (>1 MeV) flux >1.2 × 1014 n/cm2/s. Fifty five-day tests of FBG sensors showed less than 5 dB reduction in FBG peak strength after over 1 × 1020 n/cm2 of accumulated fast neutron dose. The radiation-induced compaction of FBG sensors produced less than 5.5 nm FBG wavelength shift toward shorter wavelength. To test temporal responses of FBG sensors, a number of reactor anomaly events were artificially created to abruptly change reactor power, temperature, and neutron flux over short periods of time. The thermal sensitivity and temporal responses of FBGs were determined at different accumulated doses of neutron flux. Results presented in this paper reveal that temperature-stable Type-II FBGs fabricated in radiation-hardened fibers can survive harsh in-pile conditions. Despite large parameter drift induced by strong nuclear radiation, further engineering and innovation on both optical fibers and fiber devices could lead to useful fiber sensors for various in-pile measurements to improve safety and efficiency of existing and next generation nuclear reactors.

The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-ß antagonizing mechanism: attenuation of PACT-mediated RIG-I/ MDA5 activation.

Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-ß production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N-PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-ß production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.

Accelerated or hyperfractionated radiotherapy for esophageal carcinoma: a meta-analysis of randomized controlled trials.

OBJECTIVE: The goal of this study was to evaluate the efficacy and safety of modified (accelerated and/or hyperfractionated) radiotherapy in the treatment of esophageal carcinoma, compared with conventional radiotherapy. METHODS: Studies published in the PubMed, Cochrane Library, EMBASE, CBM, VIP, CNKI and Wanfang databases in the most recent two decades were searched for use in this meta-analysis. Only randomized controlled trials were included. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were performed using RevMan 5.3 software. The assessment of publication bias and sensitivity analyses was conducted using Stata 13.0 software. RESULTS: Twenty trials with a total of 1,742 Chinese patients who met the inclusion criteria were included. The pooled results showed that modified radiotherapy improved the response rate compared with conventional schedules (OR =3.90, 95% confidence interval [CI]: 2.47-6.16, P<0.001). Favorable results were observed for the 1-year (OR =2.58, 95% CI: 2.05-3.26, P<0.001), 3-year (OR =2.30, 95% CI: 1.83-2.89, P<0.001) and 5-year (OR =2.36, 95% CI: 1.74-3.21, P<0.001) overall survival and for the 1-year (OR =2.46, 95% CI: 1.72-3.51, P<0.001), 3-year (OR =2.08, 95% CI: 1.49-2.90, P<0.001) and 5-year (OR =2.15, 95% CI: 1.38-3.34, P<0.001) overall local control rate in the modified fractionation radiotherapy group. However, the altered radiotherapy increased the risk of acute radiation esophagitis (OR =1.70, 95% CI: 1.27-2.28, P<0.001) and acute radiation tracheitis (OR =1.47, 95% CI: 1.09-1.99, P=0.01). No significant differences in the risk of esophageal perforation (OR =1.30, 95% CI: 0.51-3.32, P=0.58) or esophagorrhagia (OR =0.88, 95% CI: 0.41-1.88, P=0.74) were found between the two groups. CONCLUSION: Chinese patients with squamous cell esophagus carcinomas gained a significant benefit in terms of the response rate, survival and local control rates from the modified fractionation radiotherapy, but also had an increased risk of acute radiation reactions. Otherwise, there was no observed statistically significant difference in terms of early adverse reactions.