Management for children and adolescents with overweight and obesity: a recommendations mapping.

BACKGROUND: Childhood obesity is a global public health issue, and the status of clinical practice guidelines (CPGs) as instruction manuals for the management of childhood obesity remains unclear. This study aims to identify and apprise the methodological and reporting quality of CPGs focused on childhood obesity and provide an overview of key recommendations. METHODS: Databases and websites reporting guidelines were searched from January, 2018 to September, 2023. The methodological quality was graded using the AGREE II, and RIGHT was used to assess the reporting completeness. RESULTS: Among the six included CPGs, two were rated as high quality and considered "Recommended" and three were reported no less than 80%. CPGs included 184 recommendations cover diagnosis, assessment and management of complications, interventions and prevention. The diagnostic criteria for children with obesity over 2 years of age are based on normative BMI percentiles, depending on sex and age. CPGs recommended the delivery of multi-component behavior-changed interventions included controlling diet and increasing physical activity. Pharmacological interventions and bariatric surgery are considered as complementary therapies. CONCLUSION: CPGs for childhood obesity should emphasize the impact of psychological factors and consider the provision of interventions from multiple settings, and could consider the role of complementary alternative therapies. IMPACT: Six guidelines have been published in the past 5 years focusing children obesity. Recommendations covered diagnosis, multiple intervention and prevention. Guidelines should focus on the role of complementary alternative therapies. Guidelines should emphasize the impact of psychological factors. Guidelines should consider the provision of interventions from multiple settings.

Metal- and light-free decarboxylative direct C-H alkylation of heteroarenes at room temperature.

This study reports a metal- and light-free decarboxylative C-H alkylation of heteroarenes at room temperature. The reaction generates various primary, secondary, and tertiary alkyl radicals and functionalizes seven different privileged scaffolds widely present in bioactive molecules. During this process, one equivalent of hypervalent iodine(III) carboxylates (HICs) plays dual roles as an alkyl radical precursor and an oxidant.

Safety and efficacy of mitapivat, an oral pyruvate kinase activator, in adults with non-transfusion dependent α-thalassaemia or ß-thalassaemia: an open-label, multicentre, phase 2 study.

BACKGROUND: Patients with non-transfusion-dependent thalassaemia (NTDT), although they do not require regular blood transfusions for survival, can still accrue a heavy burden of comorbidities. No approved disease-modifying therapies exist for these patients. We aimed to investigate the safety and efficacy of mitapivat (Agios Pharmaceuticals, Cambridge, MA, USA), a pyruvate kinase activator, in adults with non-transfusion-dependent (NTD) α-thalassaemia or NTD ß-thalassaemia. METHODS: In this open-label, multicentre, phase 2 study, patients were recruited from four academic clinical study sites in Oakland, CA, and Boston, MA, USA; Toronto, ON, Canada; and London, UK. Patients were eligible if they were aged 18 years or older, with NTDT (including ß-thalassaemia with or without α-globin gene mutations, haemoglobin E ß-thalassaemia, or α-thalassaemia), and a baseline haemoglobin concentration of 10·0 g/dL or lower. During a 24-week core period, mitapivat was administered orally at 50 mg twice daily for the first 6 weeks followed by an escalation to 100 mg twice daily for 18 weeks thereafter. The primary endpoint was haemoglobin response (a ≥1·0 g/dL increase in haemoglobin concentration from baseline at one or more assessments between weeks 4 and 12). Efficacy and safety were assessed in the full analysis set (ie, all patients who received at least one dose of study drug). This study is registered with ClinicalTrials.gov, NCT03692052, and is closed to accrual. FINDINGS: Between Dec 28, 2018, and Feb 6, 2020, 27 patients were screened, of whom 20 were enrolled (15 [75%] with ß-thalassaemia and five [25%] with α-thalassaemia) and received mitapivat. The median age of patients was 44 years (IQR 35-56), 15 (75%) of 20 patients were female, five (25%) were male, and ten (50%) identified as Asian. 16 (80% [90% CI 60-93]) of 20 patients had a haemoglobin response (p<0·0001), five (100%) of five with α-thalassaemia and 11 (73%) of 15 with ß-thalassaemia. 17 (85%) patients had a treatment-emergent adverse event, and 13 had a treatment-emergent event that was considered to be treatment related. One serious treatment-emergent adverse event occurred (grade 3 renal impairment), which was considered unrelated to study drug, resulting in discontinuation of treatment. The most commonly reported treatment-emergent adverse events were initial insomnia (ten [50%] patients), dizziness (six [30%]), and headache (five [25%]). No patients died during the 24-week core period. INTERPRETATION: These efficacy and safety results support the continued investigation of mitapivat for the treatment of both α-thalassaemia and ß-thalassaemia. FUNDING: Agios Pharmaceuticals.

Carrier Transport Regulation of Pixel Graphene Transparent Electrodes for Active-Matrix Organic Light-Emitting Diode Display.

Integrating a graphene transparent electrode (TE) matrix with driving circuits is essential for the practical use of graphene in optoelectronics such as active-matrix organic light-emitting diode (OLED) display, however it is disabled by the transport of carriers between graphene pixels after deposition of a semiconductor functional layer caused by the atomic thickness of graphene. Here, the carrier transport regulation of a graphene TE matrix by using an insulating polyethyleneimine (PEIE) layer is reported. The PEIE forms an ultrathin uniform film (≤10 nm) to fill the gap of the graphene matrix, blocking horizontal electron transport between graphene pixels. Meanwhile, it can reduce the work function of graphene, improving the vertical electron injection through electron tunneling. This enables the fabrication of inverted OLED pixels with record high current and power efficiencies of 90.7 cd A-1 and 89.1 lm W-1 , respectively. By integrating these inverted OLED pixels with a carbon nanotube-based thin-film transistor (CNT-TFT)-driven circuit, an inch-size flexible active-matrix OLED display is demonstrated, in which all OLED pixels are independently controlled by CNT-TFTs. This research paves a way for the application of graphene-like atomically thin TE pixels in flexible optoelectronics such as displays, smart wearables, and free-form surface lighting.

Combined BSA-Seq and RNA-Seq Reveal Genes Associated with the Visual Stay-Green of Maize (Zea mays L.).

Maize has become one of the most widely grown grains in the world, and the stay-green mutant allows these plants to maintain their green leaves and photosynthetic potential for longer following anthesis than in non-mutated plants. As a result, stay-green plants have a higher production rate than non-stay-green varieties due to their prolonged grain-filling period. In this study, the candidate genes related to the visual stay-green at the maturation stage of maize were investigated. The F2 population was derived from the T01 (stay-green) and the Xin3 (non-stay-green) cross. Two bulked segregant analysis pools were constructed. According to the method of combining ED (Euclidean distance), Ridit (relative to an identified distribution unit), SmoothG, and SNP algorithms, a region containing 778 genes on chromosome 9 was recognized as the candidate region associated with the visual stay-green in maize. A total of eight modules were identified using WGCNA (weighted correlation network analysis), of which green, brown, pink, and salmon modules were significantly correlated with visual stay-green. BSA, combined with the annotation function, discovered 7 potential candidate genes, while WGCNA discovered 11 stay-green potential candidate genes. The candidate range was further reduced due through association analysis of BSA-seq and RNA-seq. We identified Zm00001eb378880, Zm00001eb383680, and Zm00001eb384100 to be the most likely candidate genes. Our results provide valuable insights into this new germplasm resource with reference to increasing the yield for maize.

Fermi-Level Depinning in Metal/Ge Junctions by Inserting a Carbon Nanotube Layer.

Germanium (Ge)-based devices are recognized as one of the most promising next-generation technologies for extending Moore's law. However, one of the critical issues is Fermi-level pinning (FLP) at the metal/n-Ge interface, and the resulting large contact resistance seriously degrades their performance. The insertion of a thin layer is one main technique for FLP modulation; however, the contact resistance is still limited by the remaining barrier height and the resistance induced by the insertion layer. In addition, the proposed depinning mechanisms are also controversial. Here, the authors report a wafer-scale carbon nanotube (CNT) insertion method to alleviate FLP. The inserted conductive film reduces the effective Schottky barrier height without inducing a large resistance, leading to ohmic contact and the smallest contact resistance between a metal and a lightly doped n-Ge. These devices also indicate that the metal-induced gap states mechanism is responsible for the pinning. Based on the proposed technology, a wafer-scale planar diode array is fabricated at room temperature without using the traditional ion-implantation and annealing technology, achieving an on-to-off current ratio of 4.59 × 104 . This work provides a new way of FLP modulation that helps to improve device performance with new materials.

Drug response hysteresis in the concentration-QTc analysis of early clinical trials.

According to the International Conference on Harmonisation E14 Q&As R3, concentration-QTc analysis can serve as an alternative to the by-time-point analysis or intersection-union test as the primary basis for decisions to classify the QTc risk of a drug. In a recent scientific white paper on concentration-QTc analysis, a pre-specified linear mixed effect model was suggested to study a QTc prolongation effect. The model assumes a direct time-concordant relationship (direct effect) between QTc interval and drug-concentrations. In the case of lagged drug QTc effects, also called 'hysteresis', a linear direct effect model may yield a biased QTc estimate. In this work, we estimate the bias of QTc effects via simulations when hysteresis is not accounted for in the linear mixed effect model analysis. Simulations are performed to compare different methods of identifying hysteresis when two physiologically plausible QT drug mechanisms are considered. The focus of this paper is to provide hysteresis identification methods and assess the influence of hysteresis in estimating the QT prolongation for most commonly observed QT-Concentration profiles.

[Prognosis and Related Factors of Patients with Pathological Complete Response after Neoadjuvant Therapy for Gastric Cancer].

Objective To investigate the related factors of pathological complete response(pCR)of patients with gastric cancer treated by neoadjuvant therapy and resection,and to analyze the risk factors of prognosis. Methods The clinical and pathological data of 490 patients with gastric cancer who received neoadjuvant therapy followed by radical gastrectomy from January to December in 2008 were retrospectively analyzed.Univariate and multivariate analyses were performed to identify the risk factors affecting pCR and prognosis. Results Among the 490 patients,41 achieved pCR,and the overall pCR rate was 8.3%(41/490).The pCR rate was 16.0% in the neoadjuvant chemoradiation group and 6.4% in the neoadjuvant chemotherapy group.The results of multivariate analysis showed that neoadjuvant chemoradiation(OR=4.401,95% CI=2.023-9.574,P<0.001)and preoperative therapeutic response as partial response(OR=40.492,95% CI=5.366-305.572,P<0.001)were independent predictors of pCR after neoadjuvant therapy.Multivariate analysis of prognosis showed that poorly differentiated tumor(HR=1.809,95% CI=1.104-2.964,P=0.019),gastric cardia-fundus-body tumor(HR=2.025,95% CI=1.497-2.739,P<0.001),≤15 intraoperative dissected lymph nodes(HR=1.482,95% CI=1.059-2.073,P=0.022),and postoperative complications(HR=1.625,95% CI=1.156-2.285,P=0.005)were independent risk factors for prognosis,while pCR(HR=0.153,95% CI=0.048-0.484,P=0.001)and postoperative adjuvant chemotherapy(HR=0.589,95% CI=0.421-0.823,P<0.001)were independent protective factors of prognosis. Conclusions Patients who achieved pCR after neoadjuvant therapy for locally advanced gastric cancer might have promising long-term survival,and pCR is an independent predictor for overall survival.Compared with chemotherapy alone,preoperative chemoradiotherapy can significantly improve the pCR rate of patients with locally advanced gastric cancer.

Epileptic Seizure after Use of Moxifloxacin in Man with Legionella longbeachae Pneumonia.

Legionellosis caused by Legionella longbeachae is diagnosed mainly by PCR. We report a case of L. longbeachae infection in mainland China, which was diagnosed by metagenomic next-generation sequencing, in a man who developed an epileptic seizure after using moxifloxacin. Metagenomic next-generation sequencing may be a useful tool to detect Legionella spp.

A first-in-human, phase 1, dose-escalation study of ABBV-176, an antibody-drug conjugate targeting the prolactin receptor, in patients with advanced solid tumors.

ABBV-176 is an antibody-drug conjugate composed of the humanized antibody h16f (PR-1594804) conjugated to a highly potent, cytotoxic cross-linking pyrrolobenzodiazepine dimer (PBD; SGD-1882) targeting the prolactin receptor (PRLR), which is overexpressed in several solid tumor types. This phase 1, dose-escalation study (NCT03145909) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-176 in patients with advanced solid tumors likely to exhibit elevated levels of PRLR. Patients received ABBV-176 once every 3 weeks. Dose escalation was by an exposure-adjusted, continual reassessment method. Dose-limiting toxicities (DLTs) were assessed from the first day of dosing until the next dose of ABBV-176 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Nineteen patients received ABBV-176 at doses from 2.7-109.35 µg/kg. Patients enrolled had colorectal cancer (n = 11), breast cancer (n = 6), or adrenocortical carcinoma (n = 2). DLTs occurred in 4 patients and included thrombocytopenia (n = 2; both at 99.9-µg/kg dose level), neutropenia (n = 2; 78.3-µg/kg and 99.9-µg/kg dose levels), and pancytopenia (n = 1; 109.35-µg/kg dose level). The most common treatment-emergent adverse events related to ABBV-176 were thrombocytopenia, neutropenia, increased aspartate aminotransferase, nausea, fatigue, and pleural effusions. Effusions and edema were common, and timing of onset suggested possible cumulative ABBV-176 toxicity. Tumor expression of PRLR varied among patients enrolled and analyzed. No patient had an objective response. MTD was not formally determined, as identification of a tolerable dose was confounded by late-onset toxicities. ABBV-176 was associated with significant toxicity in this phase 1, dose-escalation study. Although cytopenias were often dose limiting, effusions and edema were also common and had late onset that suggested cumulative toxicity. No responses were observed, although data were available from a small number of patients with variable tumor PRLR expression. This study was terminated after the dosing of 19 patients.

Geraniin inhibits proliferation and induces apoptosis through inhibition of phosphatidylinositol 3-kinase/Akt pathway in human colorectal cancer in vitro and in vivo.

Geraniin, a polyphenolic component isolated from Phyllanthus amarus, has been reported to possess diverse biological activities, including antitumor, antiinflammatory, antihyperglycemic, antihypertensive, and antioxidant. However, the role and underlying mechanisms of geraniin in colorectal cancer still remain unclear. In the present study, we found that geraniin notably inhibited cell proliferation and clonogenic formation of colorectal cancer cell SW480 and HT-29 in a dose-dependent manner by Cell Counting Kit 8, EdU, and colony formation assays, respectively. Additionally, geraniin remarkably induced apoptosis of SW480 and HT-29 cells in a dose-dependent way by Hoechst 33342 staining, flow cytometric analysis, and TdT-mediated dUTP nick-end labeling assays and increased the expressions of Bax, caspase-3, and caspase-9, while decreased the level of Bcl-2. Besides, wound healing, transwell migration, and invasion assays demonstrated that geraniin obviously inhibited the migration and invasion of SW480 and HT-29 cells. Moreover, it also inhibited the levels of phospho (p)-phosphatidylinositol 3-kinase and p-Akt. Furthermore, in-vivo animal study revealed that geraniin had the significant inhibitory effects on tumor growth and promoted cancer cell apoptosis remarkably, which further confirmed the antitumor effect of geraniin. Taken together, the present study exhibited the positive role of geraniin in inhibiting proliferation and inducing apoptosis through suppression of phosphatidylinositol 3-kinase/Akt pathway in colorectal cancer cells in vitro and in vivo, which might provide new insights in searching for new drug candidates of anticolorectal cancer.

Advanced Lithium Metal-Carbon Nanotube Composite Anode for High-Performance Lithium-Oxygen Batteries.

The low Coulombic efficiency and hazardous dendrite growth hinder the adoption of lithium anode in high-energy density batteries. Herein, we report a lithium metal-carbon nanotube (Li-CNT) composite as an alternative to the long-term untamed lithium electrode to address the critical issues associated with the lithium anode in Li-O2 batteries, where the lithium metal is impregnated in a porous carbon nanotube microsphere matrix (CNTm) and surface-passivated with a self-assembled monolayer of octadecylphosphonic acid as a tailor-designed solid electrolyte interphase (SEI). The high specific surface area of the Li-CNT composite reduces the local current density and thus suppresses the lithium dendrite formation upon cycling. Moreover, the tailor-designed SEI effectively separates the Li-CNT composite from the electrolyte solution and prevents the latter's further decomposition. When the Li-CNT composite anode is coupled with another CNTm-based O2 cathode, the reversibility and cycle life of the resultant Li-O2 batteries are drastically elevated.

The Smad2/3/4 complex binds miR-139 promoter to modulate TGFß-induced proliferation and activation of human Tenon's capsule fibroblasts through the Wnt pathway.

The activation and proliferation of human Tenon's fibroblasts (HTFs) play a vital role in the fibrosis in the pathology of the scar formation after the glaucoma filtration surgery. Transforming growth factor ß1 (TGFß1)/Smads signaling has been reported to promote fibrosis. In our previous study, we revealed that TGFß1-induced orbital fibroblast activation and proliferation through Wnt/ß-catenin signaling. As microRNA (miR)-139 could target several factors in Wnt signaling to modulate fibrosis, here, the effect and mechanism of miR-139 in HTF activation and proliferation were investigated. miR-139 overexpression significantly reversed the TGFß1-induced increase in collagen I and α-smooth muscle actin contents and proliferation in HTFs. CTNNB1 and CTNND1 were direct downstream of miR-139 and can significantly restore the suppressive effect of miR-139 on the activation and proliferation in HTFs under TGFß1 stimulation. Smad2/3/4 complex inhibits the transcription activity of miR-139, most possibly by Smad4 binding to the miR-139 promoter. Taken together, we demonstrated a new mechanism of HTF activation and proliferation from the perspective of miRNA regulation, which may provide new strategies for improving the fibrosis after the glaucoma filtration surgery.

[The Effects of PKCι on Anti-tumor Activity of Cytokine-induced Killer Cells Against Pancreatic Cancer Cells and the Possible Underlying Mechanisms].

OBJECTIVE: To study the impact of atypical protein kinase Cι (PKCι) isoform PKC on the pancreatic cancer cells towards the tumoricidal effect of cytokine-induced killer (CIK) cells and explore its mechanisms. METHODS: CIK cells were prepared by inducing mononuclear cells isolated from the peripheral blood of healthy people with interleukin-2 (IL-2), interferon (IFN) and CD3 mAb and subsequently co-cultured with pancreatic epithelial cell HPDE6-C7, pancreatic cancer cells MiaPaCa and PANC-1 with or without PKC inhibitor named sodium thiomalate (ATM). All cells were divided into control group, ATM group, co-culture group with CIK and co-culture group with CIK+ATM. Cell count was used to detect the growth of each group from 1 to 8 d. Flow cytometry was used to detect the death rate of the cell lines after 48 h cell culture in each group. The small hairpin RNA (shRNA) was used for PKCι knockdown and the recombinant plasmid transfection was for PKCι overexpression in pancreatic cancer cells. Western blot and real-time fluorescent quantitative PCR (qRT-PCR) were utilized to determine the expression of PKCι protein and the impact on gene expression of transforming growth factor-ß (TGF-ß), a downstream effector modulated by PKC. Different mass concentrations of TGF-ß (1, 10, 20 ng/mL) were added into the co-culture of MiaPaCa and PANC-1 with CIK. The cell death rate was detected by flow cytometry 48 h later, so as to explore the possible mechanisms of the impact of PKCι on the tumoricidal effects of CIK cells. RESULTS: ATM and CIK were shown to suppress the growth and induce apoptosis or death of pancreatic cancer cells, meanwhile, ATM can enhance the tumoricidal effect of CIK on pancreatic cancer cells. Moreover, we found that PKCι knockdown in pancreatic cancer cells can down-regulate the gene expression of TGF-ß. In return, PKCι overexpression in pancreatic cancer cells can increase the gene expression of TGF-ß. The death rate of cancer cells with 10, 20 ng/mL TGF-ß was lower compared with the control group (P < 0.05). CONCLUSIONS: PKCι knockdown in pancreatic cancer cells can not only inhibit the growth of pancreatic cancer cells, but also enhance the tumoricidal effects of CIK on cancer cells. The possible mechanism of PKCι is to affect the immune escape of tumor cells by regulating the expression of TGF-ß.

Clinical evaluation of P-glycoprotein inhibition by venetoclax: a drug interaction study with digoxin.

1. Venetoclax is a novel, small molecule B-cell lymphoma-2 (BCL-2) inhibitor that has demonstrated clinical efficacy in a variety of haematological malignancies. Since venetoclax is an inhibitor of P glycoprotein (P-gp) transporter, a study was conducted in healthy, female volunteers to evaluate the effect of venetoclax on the pharmacokinetics of digoxin, a P-gp probe substrate. 2. Volunteers received a single oral dose of digoxin (0.5 mg) with or without a single oral dose of venetoclax (100  mg). Serial blood samples were obtained for pharmacokinetic assessments of digoxin and venetoclax and serial urine samples were obtained for measurement of digoxin concentrations. Safety was assessed throughout the study. 3. Coadministration of digoxin and venetoclax increased digoxin maximum observed plasma concentration (Cmax) by 35% and area under the plasma-concentration time curve (AUC0-∞) by 9%. Digoxin half-life, renal clearance and the fraction excreted unchanged in urine remained relatively similar. The results of this study indicate that venetoclax can increase the concentrations of P-gp substrates. Narrow therapeutic index P-gp substrates should be administered six hours prior to venetoclax to minimise the potential interaction.

[The Influence of New Medium with RGD on Cell Growth,Cell Fusion and Expression of Exogenous Gene].

OBJECTIVE: To investigate the influence of a new culture medium added with RGD on cell growth,cell fusion and expression of exogenous gene. METHODS: A new medium was prepared by adding different concentrations of RGD to ordinary culture medium. The optimum concentration of RGD was determined by observation of the growth of human pancreatic epithelial cell line HPDE6-C7. After determining the optimum concentration of RGD,different concentrations of cells HPDE6-C7 (5×104,105,5×105 mL－1) were inoculated in the two mediums. The morphology,adherence,growth and density of the cells were observed by inverted microscope; The ratio of clone formation and the positive rate of cloning were compared between the two cultures after fusion; The fluorescence intensity after the transfection of plasmid with green fluorescent protein (GFP) and the protein expression after transfection of plasmid with KRAS were observed to campare the expression of exogenous genes between the new medium with ordinary medium. RESULTS: Firstly,the optimal concentration of RGD was 10 ng/mL. Compared with the normal medium,the cultured cells with RGD had better morphology,adhesion and faster proliferation. In addition,both of the number and positive rate of clones formed in the new medium were significantly higher than that in the ordinary medium (P<0.05);The fluorescence intensity after transfection of exogenous gene GFP in the new medium was significantly higher than that in normal medium (P<0.05); Expression level of exogenous gene KRAS of the new medium was also significantly higher than that in normal medium. CONCLUSION: The new culture medium has highlighted advantages in cell growth,cell fusion and expression of exogenous genes. RGD peptide has widely prospect and potential value in the cell culture.

A case of herbicide-induced acute fibrinous and organizing pneumonia?

BACKGROUND: To improve the understanding of acute fibrinous and organizing pneumonia (AFOP), we present one case of AFOP proven by percutaneous lung biopsy along with clinical features, chest imaging and pathology. CASE PRESENTATION: A 50-year-old man was admitted to our department after he was given empiric therapy for community-acquired pneumonia (CAP). The clinical symptoms of the patient were dry cough, chills, night sweats and high fevers. Chest computed tomography (CT) scan showed a high-density shadow in the right lung lobe, similar to lobular pneumonia. The patient was preliminarily diagnosed with community-acquired pneumonia; however, antibacterial treatment was ineffective. To confirm the diagnosis, we performed bronchoscopy and percutaneous lung biopsy; pathology was consistent with AFOP. After he was treated with glucocorticoids, the patient's symptoms were relieved, and the shadow seen on imaging dissipated during the follow-up period. CONCLUSIONS: AFOP is a rare histopathological diagnosis that can be easily misdiagnosed. Clinicians need to consider the possibility of AFOP in the case of invalid antibacterial therapy.

Epigenetic downregulated ITGBL1 promotes non-small cell lung cancer cell invasion through Wnt/PCP signaling.

Integrin, beta-like 1 (ITGBL1), is a ß-integrin-related extracellular matrix protein which contains ten EGF-like repeats domain. Surprisingly, we screen Oncomine Database and found that ITGBL1 is more commonly downregulated in non-small cell lung cancer (NSCLC) tissues, and the result reminds us to explore its significance in NSCLC. Thus, we retrieved DRUGSURV Database and found that downregulated ITGBL1 predicts a poor prognosis of patients. These results provided us the clues that ITGBL1 might be a tumor suppressor in NSCLC. However, the biological functions of ITGBL1 have not been reported to date. In the current study, we surprisingly found that knockdown of ITGBL1 in NSCLC cell lines could promote cancer cell migration and invasion. Furthermore, recombinant ITGBL1 protein-treated cancer cell could inhibit cell migration and invasion. These results suggested that ITGBL1 plays a suppressive role in NSCLC progression. We further found that the downregulation of ITGBL1 might result from highly expressed miR-576-5p in NSCLC tissues, and the activity of Wnt/PCP signaling was enhanced when the level of ITGBL1 was inhibited. In conclusion, our results suggest that ITGBL1 is a novel tumor suppressor in NSCLC progression.

Broadband tunable microwave photonic phase shifter with low RF power variation in a high-Q AlN microring.

An all-optically tunable microwave photonic phase shifter is demonstrated based on an epitaxial aluminum nitride (AlN) microring with an intrinsic quality factor of 3.2×106. The microring adopts a pedestal structure, which allows overcoupling with 700 nm gap size and facilitates the fabrication process. A phase shift for broadband signals from 4 to 25 GHz is demonstrated by employing the thermo-optic effect and the separate carrier tuning technique. A phase tuning range of 0°-332° is recorded with a 3 dB radio frequency (RF) power variation and 48 mW optical power consumption. In addition, AlN exhibits intrinsic second-order optical nonlinearity. Thus, our work presents a novel platform with a low propagation loss and the capability of electro-optic modulation for applications in integrated microwave photonics.

MiRNA-21 promotes fibrosis in orbital fibroblasts from thyroid-associated ophthalmopathy.

PURPOSE: This study aimed to determine the role of miR-21 in orbital fibroblasts obtained from donors with thyroid-associated ophthalmopathy (TAO) and to elucidate the regulation of fibrosis by miR-21 in the pathological process of TAO. METHODS: The expression of miR-21 was investigated in orbital tissues from 26 donors with TAO and 10 donors without TAO. Human orbital fibroblasts were cultivated from TAO donors, and the role of miR-21 in orbital fibroblast proliferation, apoptosis, and differentiation was analyzed. Moreover, the effect of transforming growth factor-beta1 (TGF-ß1) on miR-21 expression was also analyzed. In addition, the regulation of miR-21 in TGF-ß1-induced collagen production was determined. RESULTS: The expression of miR-21 in orbital fibroblasts from TAO was higher than in donors without TAO. Additional experiments demonstrated that miR-21 enhanced proliferation, decreased apoptosis, and promoted differentiation in TAO orbital fibroblasts. Moreover, this study also showed that TGF-ß1 induced miR-21 expression in a time- and dose-dependent manner and miR-21 promoted collagen I mRNA expression and total collagen production induced by TGF-ß1. Additionally, miR-21 activated the TGF-ß1/Smad signaling pathway by enhancing Smad3 phosphorylation. CONCLUSIONS: The present study shows that miR-21 regulates cell proliferation, apoptosis, and differentiation in orbital fibroblasts from TAO, and acts as a mediator in TGF-ß1-induced collagen production. These data predict a close association between miR-21 and orbital muscle fibrosis, and provide a novel therapeutic target for TAO.