Bergaptol inhibits glioma cell proliferation and induces apoptosis via STAT3/Bcl-2 pathway.

Glioblastoma (GBM) is the most common primary malignant brain tumour and lacks therapeutic options with significant effects. The aberrant activation of STAT3 is a critical factor in glioma progression via activating multiple signalling pathways that promote glioma. Among them, the antiapoptotic gene Bcl-2 could be upregulated by p-STAT3, which is an important reason for the continuous proliferation of glioma. We previously reported that bergaptol, a natural furanocoumarin widely found in citrus products, exerts antineuroinflammatory effects by inhibiting the overactivation of STAT3. Here, we aimed to evaluate whether bergaptol could promote glioma apoptosis by inhibiting the STAT3/Bcl-2 pathway. This study found that bergaptol inhibited the proliferation and migration of GBM cell lines (U87 and A172) and promoted apoptosis in vitro. We also found that bergaptol significantly inhibited the STAT3/Bcl-2 pathway in GBM cells. U87 cells were implanted intracranially into nude mice to establish a glioma model, and glioma-bearing mice were treated with bergaptol (40 mg/kg). Bergaptol treatment significantly inhibited glioma growth and prolonged the glioma-bearing mice's survival time. In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.

Εfficacy and safety of vortioxetine (Lu AA21004) in the treatment of adult patients with major depressive disorder: A systematic review and a meta­analysis of randomized controlled trials.

Vortioxetine is a novel drug for the treatment of major depressive disorder (MDD). It has been reported that vortioxetine exhibits positive effect on the acute stage of MDD, while it can effectively prevent the recurrence of MDD during the maintenance period. Currently, the results of systematic reviews on vortioxetine are insufficient since several efficacy measures, such as the 24-Items Hamilton Rating Scale for Depression (HADRS-24) total score and other safety factors have not been evaluated. Therefore, the present study aimed to evaluate the efficacy and safety of different doses of vortioxetine on the treatment of adult patients with MDD via assessing more efficacy and safety indicators. The clinical, double-blind, parallel and randomized controlled trials (RCTs) on the effect of vortioxetine on MDD were retrieved from PubMed\Medline, EBSCO, Embase, Cochrane Library, OVID, Web of Science and clinical trial registration websites from database inception to November 2022. A total of two investigators independently screened the included references and independently evaluated their quality. The meta-analysis was performed using Revman 5.0 software. The present systematic review was registered in PROSPERO (registration no. CRD42018106343). In the present study 11 RCTs were included, with a total of 4,908 adult patients with MDD. More specifically, 1,158 patients were included in the 5-mg vortioxetine group, 736 in the 10-mg group, 298 in the 15-mg group, 864 in the 20-mg group and 1,852 in the placebo group. All 11 studies were randomized, double-blinded and parallel control trials, and all publications were evaluated as high quality. The meta-analysis results showed that patients in the 5-, 10- and 20-mg vortioxetine groups exhibited significantly higher Montgomery-Asberg Depression Rating Scale (MADRS) response (≥50%) and remission (≤10%) rates compared with the placebo group (P<0.05). The pooled analysis also revealed a statistically significant change in the total score of HADRS-24, MADRS, Sheehan Disability Scale (SDS), Clinical Global Impression Scale-Improvement (CGI-I) and HADRS-24 response rate in the 10- and 20-mg vortioxetine groups compared with the placebo group (P<0.05). However, no statistically significant changes in the total score of HADRS-24, MADRS, SDS, CGI-I and HADRS-24 response rate were obtained in the 5-mg group compared with the placebo group (P>0.05). Furthermore, the most common adverse events were nausea, hyperhidrosis, insomnia and vomiting, the incidence of which was increased with higher doses of vortioxetine. Overall, the results suggested that vortioxetine administration at doses of 5-20 mg was significantly effective and safe compared with placebo in the treatment of MDD. However, 5 mg vortioxetine displayed no difference in the HADRS-24, MADRS, SDS and CGI-I total scores, and HADRS-24 response rate. Furthermore, patient treatment with increasing vortioxetine doses was associated with good tolerance and high safety. Nevertheless, more multi-center, high-quality and long-term RCTs are still needed to support the aforementioned findings.

Analysis of low-carbon technology innovation efficiency and its influencing factors based on triple helix theory: Evidence from new energy enterprises in China.

Background and aim: Low-carbon technology innovation(L-CTI) is an essential way to realize the socio-economic transition to a low-carbon model. However, relatively few studies have been conducted on the calculation of low-carbon technology innovation efficiency(L-CTIE) and the identification of factors influencing it. The study intends to assess the L-CTIE of new energy enterprises(L-CTI-NEEs) and to analyze its influencing factors, so as to further improve the L-CTIE capability. Methods: Using the panel data of new energy enterprises(NEEs) in 2010-2020, DEA(BCC)-Malmquist-Tobit method is constructed to static and dynamic evaluate the L-CTIE of new energy enterprises(L-CTIE-NEEs), and analyze its influencing factors with triple helix theory. Results: During the study period, the L-CTIE among NEEs was quite different, and the Malmquist index change trend had phased characteristics. From the perspective of factors influencing innovation efficiency, technology integration capacity of enterprises, support intensity of government and cooperation scale of government-enterprises-universities & research institutions play a crucial part in promoting the EEFCH, PECH and SECH of L-CTIE-NEEs, while resource conversion capacity of universities & research institutions only promotes PECH. Conclusion: According to the research results, a triple helix model of L-CTI-NEEs is constructed to enhance its L-CTIE level.

MAX transcriptionally enhances PD-L1 to inhibit CD8+ T cell-mediated killing of lung adenocarcinoma cells.

Immune checkpoint blockade (ICB) therapies, such as monoclonal antibodies against the PD-1/PD-L1 immune checkpoint pathway, have been a major breakthrough in the treatment of lung cancer especially lung adenocarcinoma (LUAD), but their effectiveness is limited. High expression of PD-L1 in tumor cells is one of the key reasons evading immune surveillance, yet the mechanisms that regulate PD-L1 expression are not fully understood. By analyzing the chromatin immunoprecipitation sequencing data of MYC-associated X-factor (MAX) based on lung cancer cell lines, we found that the transcriptional regulator MAX is able to bind to the promoter region of the PD-L1 gene. Further, we performed several molecular biology experiments to determine that MAX promotes PD-L1 transcription in LUAD cells, which in turn assists LUAD cells to evade killing by CD8+ T cells, an effect that can be reversed by anti-PD-L1 antibody. In LUAD, the expression of MAX is positively correlated with PD-L1 and the infiltration of CD8+ T cells. Importantly, we further identified that high expression of the MAX/PD-L1 axis is associated with poor overall survival and fist progression of patients with LUAD. Thus, this study sheds light on the mechanism by which MAX inhibits CD8+ T cell-mediated killing of LUAD cells by activating PD-L1 transcription, and MAX may serve as a potential combinatorial target for ICB therapies that block the PD-1/PD-L1 pathway in LUAD.

JUND facilitates proliferation and angiogenesis of esophageal squamous cell carcinoma cell via MAPRE2 up-regulation.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a globally aggressive malignant tumor. This study aimed to investigate the mechanism of JUND in ESCC development via MAPRE2. METHODS: ESCC cells (KYSE-450 and ECA109) were transfected with small interfering RNA (si)-JUND, si-MAPRE2, si-JUND, or pcDNA3.1-MAPRE2. JUND and MAPRE2 expression in ESCC cells was detected with quantitative real-time polymerase chain reaction and western blot. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were used to determine ESCC cell proliferation. Dual-luciferase reporter gene and chromatin immunoprecipitation assays were performed to assess binding between JUND and MAPRE2. Human umbilical vein endothelial cells (HUVECs) were co-cultured with ESCC cell supernatants. Angiogenesis was assessed with an in vitro angiogenesis assay. Western blot was conducted to evaluate the expression of angiogenic proteins [vascular endothelial growth factor A (VEGFA), matrix metallopeptidase 9 (MMP-9), and angiopoietin-2 (ang2)]. RESULTS: The levels of expression of JUND and MAPRE2 were high in ESCC cells. Mechanistically, JUND bound to MAPRE2 promoter and increased MAPRE2 transcription. Downregulation of JUND or MAPRE2 inhibited KYSE-450 and ECA109 cell proliferation and reduced the levels of expression of VEGFA, MMP-9, and ang2 and tube formation in HUVECs co-cultured with ESCC cell supernatants. MAPRE2 upregulation counteracted the inhibitory effects of JUND silencing on cell proliferative and angiogenic capabilities in ESCC. CONCLUSIONS: JUND promoted MAPRE2 transcription, thereby facilitating cell proliferative and angiogenic abilities in ESCC.

Cordyceps militaris Modulates Intestinal Barrier Function and Gut Microbiota in a Pig Model.

This study investigated the effects of Cordyceps militaris (CM) on intestinal barrier function and gut microbiota in a pig model. A total of 160 pigs were randomly allocated to either a control group (fed the basal diet) or a CM group (fed the basal diet supplemented with 300 mg/kg CM). CM improved intestinal morphology and increased the numbers of goblet cells and intraepithelial lymphocytes. CM also elevated the expression of zona occluden-1, claudin-1, mucin-2 and secretory immunoglobulin A. Furthermore, the mucosal levels of pro-inflammatory cytokines were downregulated while the levels of anti-inflammatory cytokines were upregulated in the CM group. Mechanistically, CM downregulated the expression of key proteins of the TLR4/MyD88/NF-κB signaling pathway. Moreover, CM altered the colonic microbial composition and increased the concentrations of acetate and butyrate. In conclusion, CM can modulate the intestinal barrier function and gut microbiota, which may provide a new strategy for improving intestinal health.

LINC00205 Promotes Tumor Malignancy of Lung Adenocarcinoma Through Sponging miR-185-5p.

The emerging role of long noncoding RNAs (lncRNAs) in cancer, especially in lung adenocarcinoma (LUAD), is attracting increasingly more attention as a potential therapeutic target. However, whether lncRNA LINC00205 regulates the malignancy of LUAD has not been characterized. In this study, we discovered that LINC00205 was markedly upregulated in LUAD tissues and cell lines and correlated with poor prognosis of patients with LUAD. Our data showed that LINC00205 promoted the migration and proliferation of LUAD cells in vitro and tumor growth in vivo. Notably, the tumor suppressor miR-185-5p was found to be a direct target of LINC00205. In addition, miR-185-5p diminished the promotion of cell proliferation and migration mediated by LINC00205, whereas miR-185-5p inhibition had the opposite effect. In summary, our results show that LINC00205 contributes to LUAD malignancy by sponging miR-185-5p, which provides new insight into LUAD progression.

CircAGFG1 acts as a sponge of miR-4306 to stimulate esophageal cancer progression by modulating MAPRE2 expression.

OBJECTIVE: This work aims to determine the role of circular RNA (circRNA) AGFG1 and related molecular mechanism in esophageal squamous cell carcinoma (ESCC) cells. METHODS: CircAGFG1 expression in ESCC cell lines was probed with qRT-PCR. ESCC cells were transfected/cotransfected with si-circAGFG1, pcDNA3.1-circAGFG1, si-Microtubule Associated Protein RP/EB Family Member 2 (MAPRE2), pcDNA3.1-circAGFG1 + miR-4306 mimic or pcDNA3.1-circAGFG1 + si-MAPRE2. The interactions between circAGFG1 and miR-4306 as well as miR-4306 and MAPRE2 were confirmed by dual-luciferase reporter assay. Cell proliferation, migration and invasion were detected by CCK-8, cell scratch and Transwell assays, respectively. Relative RNA expression levels of circAGFG1, miR-4306 and MAPRE2 in ESCC cells were measured by qRT-PCR. The protein level of MAPRE2 in ESCC cells was monitored by Western blot. RESULTS: CircAGFG1 was observably upregulated in ESCC cell lines. Besides, circAGFG1 silencing hindered ESCC cell development in vitro, and these effects were enhanced by miR-4306 overexpression or MAPRE2 silencing. Mechanistic analysis evidenced that circAGFG1 might act as a competitive endogenous RNA of miR-4306 to relieve the repressive effect of miR-4306 on its target MAPRE2. CONCLUSION: CircAGFG1 facilitates ESCC progression via the miR-4306/MAPRE2 axis, and it may act as a possible biomarker for therapy and diagnosis in ESCC treatment.

Effect of heparinization on promoting angiogenesis of decellularized kidney scaffolds.

Native decellularized extracellular matrix provides an adequate platform for tissues and organs and promotes the development of organogenesis and tissue remodeling. However, thrombosis poses a great challenge that hinders the transplantation for a substantial organ in vivo. Therefore, anticoagulation and re-reendothelialization of organ biological scaffolds are the primary concerns to be addressed before orthotopic transplantation. Herein, a heparinized decellularized kidney scaffold (HEP-DKSs) was prepared using end-point attachment technology, followed by binding the vascular endothelial growth factor (VEGF) to greatly improve the hemocompatibility and angiogenesis of DKSs. Based on the anticoagulant, co-culture of human umbilical vein endothelial cells, and subcapsular transplantation of kidney experiments, HEP-VEGF-DKSs are shown to reduce platelet adhesion, which is crucial for subsequent vascularization and slow release of heparin and VEGF, suggesting its ability of improve neovascularization. Taken together, these data indicated an optimal anticoagulation function of HEP-VEGF-DKSs and the potential of vascularization for regeneration of whole decellularized kidney.

ATG7-mediated autophagy involves in miR-138-5p regulated self-renewal and invasion of lung cancer stem-like cells derived from A549 cells.

Activation and proliferation of cancer stem cells exert an important role in the invasion, metastasis, and recurrence of malignant tumors, including lung cancer. Therefore, exploring molecular targets related to self-renewal and mobility of lung cancer stem cells has important clinical significance. In our present study, we aimed to explore the effects of miR-138-5p on lung cancer stem-like cells and associated regulatory mechanism. In our present study, enhanced self-renewal capacity and elevated expression of cancer stem cells markers CD133, CD44, aldehyde dehydrogenase 1 of lung cancer stem-like cells derived from A549 cells were firstly verified. Then, obviously enhanced autophagy was found in lung cancer stem-like cells compared with parental cells A549. Besides, we found that enhanced autophagy induced by rapamycin promoted self-renewal and cell mobility of lung cancer stem-like cells and suppression of autophagy by 3-methyladenine exerted just opposite effects. In addition, miR-138-5p was found to be downregulated in lung cancer stem-like cells compared with that in parental cell A549. At the same time, overexpression of miR-138-5p by transfected with miR-138-5p mimic was found to effectively suppress self-renewal and invasion of lung cancer stem-like cells. Further study revealed that ATG7 was a target of miR-138-5p and overexpressed miR-138-5p suppressed ATG7-mediated autophagy. In addition, specific small interference RNA-ATG7 strengthened the inhibiting effect of miR-138-5p mimic on self-renewal and invasion of lung cancer stem-like cells. Taken together, we found that autophagy helped to maintain self-renewal and invasion ability of lung cancer stem-like cells and overexpressed miR-138-5p exerted anti-tumor effects by blocking the self-renewal and invasion of lung cancer stem-like cells through suppressing ATG7-mediated autophagy.

Theoretical model of pediatric orbital trapdoor fractures and provisional personalized 3D printing-assisted surgical solution.

Pediatric orbital trapdoor fractures are common in children and adolescents and usually require emergency surgical intervention. Herein, a personalized 3D printing-assisted approach to surgical treatment is proposed, serving to accurately and effectively repair pediatric orbital trapdoor fractures. We first investigated stress distribution in external force-induced orbital blowout fractures via numerical simulation, determining that maximum stresses on inferior and medial walls exceed those on superior and lateral walls and thus confer higher probability of fracture. We also examined 36 pediatric patients treated for orbital trapdoor fractures between 2014 and 2019 to verify our theoretical construct. Using 3D printing technique, we then created orbital models based on computed tomography (CT) studies of these patients. Absorbable implants were tailor-made, replicating those of 3D-printed models during surgical repairs of fractured orbital bones. As follow-up, we compared CT images and clinical parameters (extraocular movements, diplopia, enophthalmos) before and 12 months after operative procedures. There were only two patients with diplopia and six with enophthalmos >2 mm at 12 months, attesting to the efficacy of our novel 3D printing-assisted strategy.

Tartronic acid promotes de novo lipogenesis and inhibits CPT-1ß by upregulating acetyl-CoA and malonyl-CoA.

As a dicarboxylic acid with the structural formula HOOCCH (OH) COOH, tartronic acid is considered as an inhibitor of the transformation of carbohydrates into fat under fat-deficient diet conditions. However, the effect of tartronic acid on lipogenesis under high-fat diet conditions has yet to be established. In this work, we investigated the regulatory role of tartronic acid in lipogenesis in 3T3-L1 adipocytes and C57BL/6J mice. The results confirmed that tartronic acid promoted weight gain (without affecting food intake) and induced adipocyte hypertrophy in epididymal white adipose tissue and lipid accumulation in the livers of high-fat diet-induced obese mice. In vitro, tartronic acid promoted 3T3-L1 adipocyte differentiation by increasing the protein expression of FABP-4, PPARγ and SREBP-1. Moreover, the contents of both acetyl-CoA and malonyl-CoA were significantly upregulated by treatment with tartronic acid, while the protein expression of CPT-1ß were inhibited. In summary, we proved that tartronic acid promotes lipogenesis by serving as substrates for fatty acid synthesis and inhibiting CPT-1ß, providing a new perspective for the study of tartronic acid.

Robust phase shift keying modulation method for spin torque nano-oscillator.

The spin torque nano-oscillator (STNO) is a very promising candidate for next generation telecommunication systems due to its small size ~100 nm and high output frequency range. However, it still suffers low output power, usually smaller than µW, and very high phase noise. Also, the modulation method for the STNO should be further developed. The frequency modulation and amplitude modulation method for STNO can be easily applied because of the non-linear nature of STNO, yet it is very rare to see the proposal of a phase modulation method. In this work, we propose a robust phase shift keying modulation method for STNO. Its feasibility is demonstrated with both theoretical and numerical analysis, and its robustness is investigated under room temperature thermal noise. It is shown that our proposed phase modulation method can tune the phase arbitrarily, while the modulation speed can be as fast as 10 ns at room temperature. Comparing with the other phase modulation method, our approach has advantages of larger phase tuning range and stronger robustness against thermal noise.

miRNA-344b-1-3p modulates the autophagy of NR8383 cells during Aspergillus fumigatus infection via TLR2.

Autophagy serves a pivotal role in host defense during fungal infections, and the contribution by toll-like receptor 2 (TLR2) has been well demonstrated. It has been reported that microRNA-344a-1-3p (miR-344a-1-3p) can directly target TLR2. However, the expression of TLR2 significantly decreases during Aspergillus fumigatus infection. Therefore, the specific role of miR-344a-1-3p in the host defense against A. fumigatus infection remains to be elucidated. In the present study, A. fumigatus infection increased the expression of TLR2 and induced autophagy, which was indicated by increasing expression levels of autophagy-related protein 5 (ATG5), Beclin-1, light chain 3 (LC3)-1 and LC3-II, as measured by western blot analysis, and an increased number of GFP-LC3 puncta, as measured by fluorescence. Following transfection with miR-344a-1-3p mimics and/or TLR2, miR-344b-1-3p significantly inhibited the expression of TLR2, Beclin-1, ATG5, LC3-I and LC3-II, whereas the overexpression of TLR2 significantly attenuated the inhibitory effect on autophagy by miR-344b-1-3p. Collectively, these findings demonstrate that A. fumigatus can be controlled by the induction of autophagy following de-repression of the expression of TLR2, mediated by miR-344a-1-3p.

The influence of the stiffness of GelMA substrate on the outgrowth of PC12 cells.

Recent studies have shown the importance of cell-substrate interaction on neurone outgrowth, where the Young's modulus of the matrix plays a crucial role on the neurite length, migration, proliferation, and morphology of neurones. In the present study, PC12 cells were selected as the representative neurone to be cultured on hydrogel substrates with different stiffness to explore the effect of substrate stiffness on the neurone outgrowth. By adjusting the concentration of gelatin methacryloyl (GelMA), the hydrogel substrates with the variation of stiffnesses (indicated by Young's modulus) from approximately 3-180 KPa were prepared. It is found that the stiffness of GelMA substrates influences neuronal outgrowth, including cell viability, adhesion, spreading, and average neurite length. Our results show a critical range of substrate's Young's modulus that support PC12 outgrowth, and modulate the cell characteristics and morphology. The present study provides an insight into the relationship between the stiffness of GelMA hydrogel substrates and PC12 cell outgrowth, and helps the design and optimization of tissue engineering scaffolds for nerve regeneration.

Macrophage-Derived miRNA-Containing Exosomes Induce Peritendinous Fibrosis after Tendon Injury through the miR-21-5p/Smad7 Pathway.

Following tendon injury, the development of fibrotic healing response impairs tendon function and restricts tendon motion. Peritendinous tissue fibrosis poses a major clinical problem in hand surgery. Communication between macrophages and tendon cells has a critical role in regulating the tendon-healing process. Yet, the mechanisms employed by macrophages to control peritendinous fibrosis are not fully understood. Here we analyze the role of macrophages in tendon adhesion in mice by pharmacologically depleting them. Such macrophage-depleted mice have less peritendinous fibrosis formation around the injured tendon compared with wild-type littermates. Macrophage-depleted mice restart fibrotic tendon healing by treatment with bone marrow macrophage-derived exosomes. We show that bone marrow macrophages secrete exosomal miR-21-5p that directly targets Smad7, leading to the activation of fibrogenesis in tendon cells. These results demonstrate that intercellular crosstalk between bone marrow macrophages and tendon cells is mediated by macrophage-derived miR-21-5p-containing exosomes that control the fibrotic healing response, providing potential targets for the prevention and treatment of tendon adhesion.

An experimental study on the flocculating settling of unclassified tailings.

Unclassified tailings are the main backfilling aggregates in mines and their settling is the first step in the utilization of tailings; thus, it is very important to determine their settling behavior. The aim of this study was to understand the flocculating settling behavior of unclassified tailings with different factors. The combination of property detection, laboratory experiments and industrial tests were used to assess the flocculating settling behavior of unclassified tailings; the orthogonal experimental design and the control variate method were used for an experimental design. The results show that the flocculating settling velocity of unclassified tailings decreases with the increase of slurry concentration and that this settling velocity increases first and then decreases with the increase of flocculant unit consumption. The underflow concentration is positively correlated with the slurry concentration and negatively correlated with the flocculant unit consumption and flocculant concentration. Slower feed velocity could produce higher concentration underflow but lower clarity overflow water. The greater the mud height, the higher the underflow concentration and the suspended solids concentration in the overflow water. The underflow concentration has a maximum at the rake speed of 0.3 r/min, and the rake speed has little effect on the suspended solids concentration in the overflow water. By analyzing the settling velocity, the underflow concentration, the suspended solids concentration in the overflow water and the solid flux, the following parameters of the flocculating settling experiments were determined: the flocculant type is APAM with a molecular weight of 12 million, the flocculant unit consumption is 30 g/t, the slurry concentration is 6 vol.%, the flocculant concentration is 0.1 wt.%, the rake speed is 0.3 r/min, and the feed velocity is 0.4 L/min (its solid flux is 0.523 t/(m2·h)). The industrial tests were carried out based on the laboratory settling data, and the appropriate selection parameters of the industrial tests were estimated.

Interpenetrating polymer network hydrogels composed of chitosan and photocrosslinkable gelatin with enhanced mechanical properties for tissue engineering.

Gelatin and chitosan (CS) are widely used natural biomaterials for tissue engineering scaffolds, but the poor mechanical properties of pure gelatin or CS hydrogels become a big obstacle that limits their use as scaffolds, especially in load-bearing tissues. This study provided a novel mechanism of forming interpenetrating network (IPN) of gelatin methacryloyl (GelMA) and CS hydrogels by covalent bonds and hydrophobic interactions through photocrosslinking and basification, respectively. By characterization of the compressive and tensile moduli, ultimate tensile stress and strain, it was found that semi-IPN and IPN structure can greatly enhance the mechanical properties of GelMA-CS hydrogels compared to the single network CS or GelMA. Moreover, the increase of either GelMA or CS concentration can strengthen the hydrogel network. Then, the swelling, enzymatic degradation, and morphology of GelMA-CS hydrogels were also systematically investigated. The excellent biocompatibility of GelMA-CS hydrogels was demonstrated by large spreading area of bone mesenchymal stem cells on hydrogel surfaces when CS concentration was <2% (w/v). According to this study, the multiple requirements of properties can be fulfilled by carefully selecting the GelMA and CS compositions for IPN hydrogels.

Role of Computed Tomography Scan in Dental Trauma: A Cross-Sectional Study.

BACKGROUND: Dental trauma is caused by fracture(s) in the vertical plane and the horizontal plane of roots. The objective of this study is to perform multiple diagnostic modalities for the diagnosis of horizontal root fracture(s) of the tooth. METHODS: A total of 250 patients with dental complaints were subjected to intraoral radiography, multidetector helical computed tomography (MDHCT), and limited cone beam computed tomography (LCBCT). The suspected tooth was extracted, visually inspected, and subjected to microcomputed tomography (micro-CT). Images were observed in the lightbox, and a fracture was considered if it had been directly visualized as radiolucent line traversing tooth root. Wilcoxon test/Tukey post hoc test was performed at 99% of confidence level. RESULTS: With respect to visual inspection, for LCBCT, intraoral radiography, MDHCT, and micro-CT, sensitivities were 0.988, 0.972, 0.967, and 0.979; accuracies were 0.956, 0.785, 0.905, and 0.888; false-positive values were 5, 21, 12, and 11; and false-negative values were 3, 24, 3, and 11, respectively. The area of the image visible at one time was in the order of treatment without radiography < intraoral radiography < MDHCT < micro-CT < LCBCT. CONCLUSION: The LCBCT had the highest sensitivity and accuracy for diagnosis of horizontal tooth root fracture(s). LEVEL OF EVIDENCE: I. TRIAL REGISTRY: researchregistry3647, dated December 31, 2016 (www.researchregistry.com).

MiR-344b-1-3p targets TLR2 and negatively regulates TLR2 signaling pathway.

OBJECTIVES: COPD is an abnormal inflammatory response characterized by decreased expression of TLR2 in patients, which is suggested to induce invasive pulmonary aspergillosis (IPA). MicroRNAs (miRNAs) have been shown to play important roles in the pathogenesis of human respiratory system disorders. Therefore, the aim of this study was to identify the miRNAs involved in the regulation of TLR2 signaling in COPD. MATERIALS AND METHODS: miRNA microarray analysis was performed to screen for the dysregulated miRNAs in alveolar macrophages (AMs) isolated from COPD rats. The interaction between these miRNAs and TLR2 gene was predicted using miRBase and validated using dual luciferase assay. Based on the analysis, a novel miR-344b-1-3p was identified as a novel modulator of TLR2 gene. Then, the mechanism through which miR-344b-1-3p regulated TLR2 expression was explored using cigarette smoke extract (CSE)-pretreated NR8383 cells. Moreover, by subjecting CSE-pretreated NR8383 cells to Pam3CSK4, the effect of miR-344b-1-3p on NF-κB activity and other important mediators of COPD, including IRAK-1, ERK, TNF-α, IL-1ß, and MIP-2, was also assessed. RESULTS: COPD rat model was successfully induced by smoke inhalation. Among the 11 upregulated miRNAs in AMs from COPD rats, miR-344b-1-3p was predicted to be a novel miRNA targeting TLR2 gene. In the CSE pretreated NR8383 cells exposed to Pam3CSK4, miR-344b-1-3p inhibition increased the expression levels of TLR2, TNF-α, and IL-1ß and decreased the expression levels of MIP-2. In addition, the phosphorylation of IRAK-1, IκBα, and IRK was augmented by miR-344b-1-3p inhibition. CONCLUSION: Findings outlined in this study suggest that miR-344b-1-3p was an effective modulator of TLR2 gene, which can be employed as a promising therapeutic and preventive target of IPA in COPD patients.