Process Mass Intensity (PMI): A Holistic Analysis of Current Peptide Manufacturing Processes Informs Sustainability in Peptide Synthesis.

Small molecule therapeutics represent the majority of the FDA-approved drugs. Yet, many attractive targets are poorly tractable by small molecules, generating a need for new therapeutic modalities. Due to their biocompatibility profile and structural versatility, peptide-based therapeutics are a possible solution. Additionally, in the past two decades, advances in peptide design, delivery, formulation, and devices have occurred, making therapeutic peptides an attractive modality. However, peptide manufacturing is often limited to solid-phase peptide synthesis (SPPS), liquid phase peptide synthesis (LPPS), and to a lesser extent hybrid SPPS/LPPS, with SPPS emerging as a predominant platform technology for peptide synthesis. SPPS involves the use of excess solvents and reagents which negatively impact the environment, thus highlighting the need for newer technologies to reduce the environmental footprint. Herein, fourteen American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) member companies with peptide-based therapeutics in their portfolio have compiled Process Mass Intensity (PMI) metrics to help inform the sustainability efforts in peptide synthesis. This includes PMI assessment on 40 synthetic peptide processes at various development stages in pharma, classified according to the development phase. This is the most comprehensive assessment of synthetic peptide environmental metrics to date. The synthetic peptide manufacturing process was divided into stages (synthesis, purification, isolation) to determine their respective PMI. On average, solid-phase peptide synthesis (SPPS) (PMI ≈ 13,000) does not compare favorably with other modalities such as small molecules (PMI median 168-308) and biopharmaceuticals (PMI ≈ 8300). Thus, the high PMI for peptide synthesis warrants more environmentally friendly processes in peptide manufacturing.

Magnetic-field-controlled positioning of magnetic domain wall in tie-shaped asymmetric nanowire and its application for magnetic field detection.

With topological spin texture, magnetic domain walls have soliton-like dynamic behaviors in magnetic nanowires, which can be used in information transmission and storage technology. Therefore, precisely controlling the dynamic behavior of the magnetic domain wall and its pinning behavior is one of the important technical challenges in realizing domain-wall-based spintronic devices. In this work, a geometrically defect-free scheme for domain wall pinning/depinning is proposed using micromagnetic simulations based on a tie-shaped asymmetric nanowire, which can precisely control the position of the magnetic domain wall in an external magnetic field. The results show that the domain wall in tie-shaped nanowires exhibits excellent linear response and ultrafast time response to external magnetic fields, which endow them with potential applications for high-frequency weak-magnetic-field detection. We further propose a scheme for constructing a magnetic-field sensor using the tie-structured nanowire, and we study its feasibility.

Critical examination of the characterization techniques, and the evidence, for the existence of extra-long amylopectin chains.

It has been suggested that amylopectin can contain small but significant amounts of extra-long chains (ELCs), which could affect functional properties, and also would have implications for the mechanism of starch biosynthesis. However, current evidence for the existence of ELCs is ambiguous. The amylose/amylopectin separation and the characterization techniques used for the investigation of ELCs are reviewed, problems in those techniques are examined, and studies of ELCs of amylopectin are discussed. A model for the biosynthesis of amylopectin chains in terms of conventional biosynthesis enzymes, which provides an excellent fit to a large amount of experimental data, is used to provide a rigorous definition of ELCs. In addition, current investigations of ELCs, involving separation, is hindered by the lack of a method to quantitatively separate all the amylopectin from starch without any traces of residual amylose (which would have long chains). Unambiguous evidence for the existence of ELCs can be obtained using two-dimensional (2D) characterization, these dimensions being the degree of polymerization of a chain and the size of the whole molecule. Available 2D data indicate that there are no ELCs present in currently detectable quantities in native rice starches. However, concluding this more rigorously requires improvements in the resolution of current 2D methods.

Thoracic Endovascular Aortic Repair of Highly Tapered Type B Aortic Dissection with Proximal Tapered Stent Grafts and Distal Restrictive Stent Grafts.

BACKGROUND: This study evaluated aortic remodeling in highly tapered type B aortic dissection (TBAD) patients who underwent thoracic endovascular aortic repair (TEVAR) with a proximal tapered stent graft plus a distal restrictive stent graft to maximize thoracic coverage while avoiding distal excessive oversizing. METHODS: Thirty-four patients presenting with highly tapered TABD were randomized to restricted TEVAR (r-TEVAR) and standard TEVAR groups. Highly tapered TBAD was defined as the maximal diameter of the true lumen at proximal and distal thoracic aorta landing zone tapers greater than 8 mm or taper ratio greater than 20%. Patients in the r-TEVAR group underwent proximal tapered stent grafts plus distal restrictive stent grafts, to match the taper ratio of the descending thoracic aorta (DTA) and extend the length of stent coverage. Patients in the standard TEVAR group underwent proximal tapered stent grafts implantation without distal restrictive stent grafts. Aortic remodeling was estimated by computed tomography angiography (CTA) during the follow-up. RESULTS: In total, 16 patients underwent r-TEVAR, and 18 patients underwent standard TEVAR. The taper ratio of the stent graft matched the DTA in the r-TEVAR group (24.7 ± 3.4% vs. 27.3 ± 4.2%, P = 0.068), but did not match that in the standard TEVAR group (13.5 ± 3.3% vs. 30.5 ± 9.6%, P < 0.001). The length of stent graft coverage in the r-TEVAR group was longer than that in the standard TEVAR group (220.4 ± 21.1 mm vs. 175.3 ± 17.8 mm, P < 0.001). Compared with the standard TEVAR group, the r-TEVAR group had better complete remodeling of the DTA at 6 months (40% vs. 5.6%, P = 0.03), 12 months (60% vs. 16.7%, P = 0.027), and 24 months (78.6% vs. 41.2%, P = 0.036) after the operation. There was no difference in the cumulative survival rate between the r-TEVAR and standard TEVAR groups (P = 0.166). CONCLUSIONS: The r-TEVAR with overlapping proximal tapered stent grafts and distal restrictive stent grafts can match the taper of highly tapered TABD, extend the length of stent graft coverage, and lead to better remodeling of the DTA than standard TEVAR.

Prevalence, awareness and control of type 2 diabetes mellitus and risk factors in Chinese elderly population.

BACKGROUND: Type 2 diabetes mellitus is an expanding global public health issue, especially in developing countries. This study aimed to investigate the prevalence, awareness and control rate of type 2 diabetes mellitus, and assess its risk factors in elderly Chinese individuals. METHODS: The health screening data of 376,702 individuals aged ≥ 65 years in Wuhan, China, were collected to analyse the prevalence, awareness, and control rates of diabetes. Indices, including fasting plasma glucose and other biochemical indicators, were measured for all participants using standard methods at the central laboratory. Multilevel logistic regression analysis was performed to assess the key determinants of the prevalence, awareness, and control rates of diabetes. RESULTS: The prevalence, awareness, and control rates of diabetes in the Chinese individuals aged ≥ 65 years were 18.80%, 77.14%, and 41.33%, respectively. There were statistically significant differences in the prevalence, awareness, and control rates by gender. Factors associated with diabetes prevalence were age, body mass index (BMI), and central obesity; while those associated with awareness and control were gender, education level, marital status, physical activity, alcohol consumption, BMI, and central obesity. CONCLUSIONS: Diabetes is an important public health problem in the elderly in China. The awareness and control rates have improved, but overall remained poor. Therefore, effective measures to raise awareness and control the rates of diabetes should be undertaken to circumvent the growing disease burden in elderly Chinese people.

CDK1/2/5 inhibition overcomes IFNG-mediated adaptive immune resistance in pancreatic cancer.

OBJECTIVE: Adaptive immune resistance mediated by the cytokine interferon gamma (IFNG) still constitutes a major problem in cancer immunotherapy. We develop strategies for overcoming IFNG-mediated adaptive immune resistance in pancreatic ductal adenocarcinoma cancer (PDAC). DESIGN: We screened 429 kinase inhibitors for blocking IFNG-induced immune checkpoint (indoleamine 2,3-dioxygenase 1 (IDO1) and CD274) expression in a human PDAC cell line. We evaluated the ability of the cyclin-dependent kinase (CDK) inhibitor dinaciclib to block IFNG-induced IDO1 and CD274 expression in 24 human and mouse cancer cell lines as well as in primary cancer cells from patients with PDAC or ovarian carcinoma. We tested the effects of dinaciclib on IFNG-induced signal transducer and activator of transcription 1 activation and immunological cell death, and investigated the potential utility of dinaciclib in combination with IFNG for pancreatic cancer therapy in vivo, and compared gene expression levels between human cancer tissues with patient survival times using the Cancer Genome Atlas datasets. RESULTS: Pharmacological (using dinaciclib) or genetic (using shRNA or siRNA) inactivation of CDK1/2/5 not only blocks JUN-dependent immune checkpoint expression, but also triggers histone-dependent immunogenic cell death in immortalised or primary cancer cells in response to IFNG. This dual mechanism turns an immunologically 'cold' tumour microenvironment into a 'hot' one, dramatically improving overall survival rates in mouse pancreatic tumour models (subcutaneous, orthotopic and transgenic models). The abnormal expression of CDK1/2/5 and IDO1 was associated with poor patient survival in several cancer types, including PDAC. CONCLUSION: CDK1/2/5 kinase activity is essential for IFNG-mediated cancer immunoevasion. CDK1/2/5 inhibition by dinaciclib provides a novel strategy to overcome IFNG-triggered acquired resistance in pancreatic tumour immunity.

Combined Detection of Plasma Tumor Necrosis Factor-α Converting Enzyme and Notch1 is Valuable in Screening Endoleak After Endovascular Abdominal Aortic Aneurysms Repair.

OBJECTIVES: Endoleaks may be present in up to 25% of patients after endovascular abdominal aortic aneurysm repair (EVAR) and there is no clear consensus on valuable biomarkers to determine endoleak presence. The aim of this study was to examine the potential value of plasma tumor necrosis factor-α converting enzyme (TACE) and Notch1 concentrations in determining endoleak presence after EVAR. METHODS: A total of 110 patients with abdominal aortic aneurysm who underwent EVAR were enrolled in our study, and plasma TACE and Notch1 concentrations were measured prior to and 6 months after EVAR. Logistic regression was performed to assess the association of postoperative plasma TACE and Notch1 concentrations with endoleak after adjusting for potential confounders. The ability of plasma TACE and Notch1 concentrations to determine endoleak presence was assessed using receiver operating characteristic curves and area under the curve (AUC). RESULTS: Twenty-four patients developed endoleaks 6 months after EVAR. Both postoperative plasma TACE and Notch1 concentrations were higher in patients with endoleak than in those without endoleak (2376.4 ± 28.1 pg/ml vs. 2094.1 ± 27.3 pg/ml, P < 0.01; 218.6 ± 1.9 pg/ml vs. 195.0 ± 2.1 pg/ml, P < 0.01, respectively). The AUCs from receiver operating characteristic curve analysis of plasma TACE and Notch1 concentrations in determining endoleak presence were 0.844 (95% CI 0.771 to 0.918, P < 0.01) and 0.860 (95% CI 0.791 to 0.930, P < 0.01), respectively. Combining the detection of plasma Notch1 and TACE concentrations could improve the accuracy in determining endoleak presence (AUC 0.930, 95% CI 0.883 to 0.978, P < 0.01). The predicted probability cutoff of 0.22 yielded a sensitivity of 95.8% and a specificity of 82.6% for endoleak presence. CONCLUSIONS: Plasma TACE and Notch1 levels can discriminate patients with and without endoleak 6 months after EVAR, and have a potential role in screening patients requiring computed tomography angiography.

Development of Recombinase Polymerase Amplification Combined with Lateral Flow Detection Assay for Rapid and Visual Detection of Ralstonia solanacearum in Tobacco.

Bacterial wilt caused by Ralstonia solanacearum is a serious soilborne disease that results in severe losses to tobacco (Nicotiana tabacum) production in China. In this study, a novel RPA-LFD assay for the rapid visual detection of R. solanacearum was established using recombinase polymerase amplification (RPA) and lateral-flow dipstick (LFD). The RPA-LFD assay was performed at 37°C in 30 min without complex equipment. Targeting the sequence of the RipTALI-9 gene, we designed RPA primers (Rs-rpa-F/R) and an LF probe (Rs-LF-probe) that showed high specificity to R. solanacearum. The sensitivity of RPA-LFD assay to R. solanacearum was the same as that in conventional PCR at 1 pg genomic DNA, 103 CFU/g artificially inoculated tobacco stems, and 104 CFU/g artificially inoculated soil. The RPA-LFD assay could also detect R. solanacearum from plant and soil samples collected from naturally infested tobacco fields. These results suggest that the RPA-LFD assay developed in this study is a rapid, accurate molecular diagnostic tool with high sensitivity for the detection of R. solanacearum.

Cathepsin B is a mediator of organelle-specific initiation of ferroptosis.

Ferroptosis is a type of non-apoptotic regulated cell death that involves excessive iron accumulation and subsequent lipid peroxidation. Although the antioxidant mechanisms of ferroptosis have been extensively studied recently, little is known about the interactions between the different organelles that control ferroptosis. Here, we show that the translocation of lysosomal cysteine protease cathepsin B (CTSB) into the nucleus is an important molecular event that mediates organelle-specific initiation of ferroptosis in human pancreatic cancer cells. Iron-dependent lysosomal membrane permeability triggers the release of CTSB from the lysosome to nucleus during ferroptosis. Mechanistically, nuclear CTSB accumulation causes DNA damage and subsequent activation of the stimulator of interferon response CGAMP interactor 1 (STING1/STING)-dependent DNA sensor pathway, which ultimately leads to autophagy-dependent ferroptosis. Consequently, the genetic inhibition of CTSB-dependent STING1 activation by RNAi prevents ferroptosis in cell culture and animal models. These new findings not only enhance our understanding of the mechanism by which organelles specifically trigger ferroptosis, but also may provide a potential way to enhance the anticancer activity of ferroptosis therapy.

Inhibition of carnitine palmitoyl transferase 1A-induced fatty acid oxidation suppresses cell progression in gastric cancer.

BACKGROUND: Gastric cancer (GC) has a high rate of metastasis which thereason leading to death. Carnitine palmitoyl transferase 1a (CPT1A) has been reported to play a critical obstacle to various types of cancer progression, which is an attractive focus in anti-cancer therapy. However, the underlying molecular mechanisms of CPT1A involved in GC have not been clarified clear. METHODS: To determine the expression of CPT1A in human GC tissues and cells and illustrate whether it is correlated with the clinical pathologic characteristics and prognosis in GC patients. Its roles and potential mechanisms in regulating tumor growth and invasion were evaluated by CPT1A knockdown/overexpression of GC cells in vitro. RESULTS: Marked upregulation of CPT1A protein expression was observed in GC cells and tissues, which was associated with grade, pathological stage, lymph node metastasis and poor prognosis in patients with GC. CPT1A overexpression also promoted the proliferation, invasion, EMT process of GC cells. In addition, CPT1A upregulation activated GC cell fatty acid oxidation (FAO) via increasing NADP+/NADPH ratio, whereas inhibiting of FAO abolished the effects of CPT1A on GC cell proliferation and migration. CONCLUSION: Our results examine that CPT1A-mediated FAO activation increases GC cell proliferation and migration, supporting that CPT1A is a useful prognostic biomarker and an attractive focus for GC.

A novel circFMN2 promotes tumor proliferation in CRC by regulating the miR-1182/hTERT signaling pathways.

BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with colorectal cancer (CRC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for CRC from the aspect of circRNA-microRNA (miRNA)-mRNA interaction. METHODS: We investigated the expression of circRNAs in five paired CRC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between CRC tissues and non-cancerous matched tissues. We focused on hsa_circ_0005100, which is located on chromosome 1 and derived from FMN2, and thus we named it as circFMN2. The expression of circFMN2 was detected in 88 CRC tissues and cell lines by quantitative real-time PCR. Functional assays were performed to evaluate the effects of circFMN2 on proliferation in vitro, and on tumorigenesis in vivo. The relationship between circFMN2 and miR-1182 was confirmed by luciferase reporter assay. RESULTS: circFMN2 was found to be significantly up-regulated in CRC tissues and cell lines. Moreover, knockdown of circFMN2 significantly inhibited cell proliferation and migration in vitro. Bioinformatics analysis predicted that there is a circFMN2/miR-1182/hTERT axis in CRC progression. Dual-luciferase reporter system validated the direct interaction of circFMN2, miR-1182, hTERT. Western blot verified that inhibition of circFMN2 decreased hTERT expression. Importantly, we demonstrated that circFMN2 was up-regulated in serum exosomes from CRC patients. CONCLUSION: In conclusion, circFMN2 is a central component linking circRNAs to progression of CRC via an miR-1182/hTERT axis.

Predisposing Factors for Migration of the Iliac Limb and Reintervention after Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: Migration of the iliac limb after endovascular abdominal aortic aneurysm repair (EVAR) can result in type 1b and 3 endoleaks, which are relatively common causes of reintervention after EVAR. The aim of the present study was to investigate the factors influencing migration of the iliac limb and methods of treatment. METHODS: From April 2012 to September 2017, 4 patients experienced migration of the iliac limb, requiring additional iliac stent graft implantation intraoperatively or at follow-up at our institute. Patient 1 was a 74-year-old man in whom preoperative computed tomography angiography (CTA) revealed a large aneurysm. The patient underwent EVAR with a bifurcated stent graft, and the left iliac stent graft migrated into the aneurysm sac. Patient 2 was a 53-year-old man in whom CTA revealed a large abdominal aortic aneurysm (AAA) involving the bilateral common iliac artery (CIA), with occlusion of the left hypogastric artery. An iliac stent graft was deployed to the right CIA to preserve the hypogastric artery. CTA, at 5 years of follow-up, showed migration of the right iliac limb and impending rupture. Patient 3 was a 61-year-old man with a ruptured AAA, and CTA revealed a large AAA and dilated CIA. The patient underwent EVAR with a bifurcated stent graft. Three years after EVAR, CTA showed that the right iliac limb migrated and kinked, with rupture of the stent graft. Patient 4 was an 80-year-old man with a ruptured AAA and aortocaval fistula. CTA revealed a large aneurysm involving the bilateral CIA. The patient underwent urgent EVAR with a bifurcated stent graft, and a cuff was deployed to seal the landing zone of the left CIA to preserve the hypogastric artery. Type 3 endoleak occurred because of the migration and detachment of the left iliac limb. All 4 patients underwent additional iliac stent graft implantation to connect or reline the iliac limb. RESULTS: The mean diameter of the aneurysms was 85.3 ± 18.9 mm, and 2 patients were diagnosed with ruptured AAAs. The mean diameter, length, and proportional engagement rate of the CIA that experienced migration of the iliac limb were 25.50 ± 11.1 mm, 32.8 ± 6.6 mm, and 72.75% ± 17.88%, respectively. Oversizing of the iliac stent graft was 10-20% in 2 patients and was less than 10% in the other 2 patients. The migrated iliac limbs were bell-bottom stent grafts. All patients underwent additional iliac stent graft implantation successfully, and there were no deaths or complications perioperatively. The patients were followed up from 7 months to 3 years and remained in good condition. CONCLUSIONS: Migration of the iliac limb after EVAR was influenced by a complex combination of several factors including a large aneurysm (>60 mm in diameter), dilated or aneurysmal CIA (>18 mm in diameter), short length of fixation (<70%), lower degree of iliac limb oversizing (<10-20%), and bell-bottom of the iliac limb. Patients with these factors require more vigorous surveillance after EVAR. The implantation of an additional stent graft is effective and is the most common reintervention procedure.

Highly Water-Soluble Methotrexate-Polyethyleneglycol-Rhodamine Prodrug Micelle for High Tumor Inhibition Activity.

Highly water-soluble prodrug micelle (50-fold compared with free MTX) of methotrexate-polyethyleneglycol-rhodamine (MTX-PEG-rhodamine) and MTX-mPEG was synthesized by the esterification reaction. The stability of the prodrug micelles was evaluated in phosphate buffer saline (PBS) with 10% fetal bovine serum (FBS). The tumor volume of the saline, MTX, and MTX-PEG-rhodamine groups was increased 3.7-fold, 2.8-fold, and 1.8-fold, respectively, compared with the initial tumor volume. TUNEL and drug distribution results further confirmed that the micelle of MTX-PEG-rhodamine possessed fewer side effects on the normal tissue compared with MTX. The prodrug micelle showed four advantages: retention of the drug activity site, higher water solubility of methotrexate (MTX), ease of preparation and application, and preferential accumulation in tumor tissues. These advantages of MTX-mPEG make it a promising drug delivery system (DDS) for clinical use.

Procaine is a specific DNA methylation inhibitor with anti-tumor effect for human gastric cancer.

DNA hypermethylation and the silencing of tumor suppressor genes caused by DNA hypermethylation is considered as a molecular hallmark of many kinds of cancers. Procaine, a local anesthetic, has been shown as a potential DNA methylation inhibitor in some types of cancers. However, the influence of procaine on DNA methylation regulation as well as the biological function in gastric cancer is still unknown. We report here that procaine represses the DNA-methylation level and promotes the proliferation arrest and apoptosis of gastric cancer cells. Global DNA methylation measurement demonstrates that procaine significantly reduces the global DNA methylation level. Analyses of the DNMTs expression and activity show procaine represses the activity, but not the expression, of DNMT1/DNMT3A. Further evidence on specific genes shows that procaine reduces the DNA methylation level in the promoter regions of CDKN2A and RARß genes through abrogating the binding of DNMT1/DNMT3A toward these regions. This repression would not be reversed by the overexpression of DNMT1/DNMT3A. Moreover, RT-qPCR and luciferase report assays demonstrate that procaine leads to the upregulation of CDKN2A and RARß due to the activation of the promoter of these genes. In the end, we test the function of procaine toward gastric cancer cells and find that procaine has the growth inhibitory and apoptosis inducement effect toward gastric cancer cells. Collectively, our data not only uncovers the regulation mechanisms of procaine to DNA methylation but also suggests an anti-tumor potential of procaine specific to the gastric carcinoma and provides a new therapeutic strategy for gastric carcinoma.

The Effect of LncRNA H19/miR-194-5p Axis on the Epithelial-Mesenchymal Transition of Colorectal Adenocarcinoma.

BACKGROUND/AIMS: Since the combined actions of lncRNAs and miRNAs have been considered to be involved in the occurrence and development of various neoplasms, the main purpose of this study was to discover whether and how lncRNA H19 and miR-194 influenced the epithelial-mesenchymal transition (EMT) process of colorectal adenocarcinoma (CRA). METHODS: Totally 214 pairs of CRA and adjacent normal tissues were collected, and 5 human CRA cell lines (i.e. HCT116, HT-29, RKO SW280 and Lovo) were purchased. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was adopted to quantify the H19 and miR-194-5p expressions in cells and tissues. The expressions of FoxM1, E-cadherin, vimentin, N-cadherin were determined using western blot. On the side, si-H19, si-NC, miR-194-5p mimic, miR-194-5p inhibitor and negative control (NC) were transfected into CRA cell lines. Meanwhile, the invasive, migratory and proliferative conditions of the cells were assessed through transwell, wound healing and colony-forming experiments, with final verification of the relationship between H19 and miR-194-5p employing dual-luciferase reporter gene assay. RESULTS: Highly-expressed H19, lowly-expressed miR-194-5p, low-grade differentiation and lymph node metastasis appeared as the independent predictors of unfavorable prognosis in CRA patients' (all P< 0.05). It indicated that FoxM1 expression displayed positive correlations with H19 expression, yet negative associations with miR-194-5p expression within CRA tissues (P< 0.05). In addition, transfection of H19-siRNA and miR-145-5p mimic triggered a conspicuous increase in E-cadherin expression, as well as an evidently down-regulation in vimentin and N-cadherin expressions within HT29 and RKO cells (P< 0.05). On the other hand, the invasive and migratory capacities of CRA cells were significantly hindered (P< 0.05). Moreover, the luciferase reporter gene assay confirmed that H19 modified miR-194-5p expression through directly targeting at it (P< 0.05). Ultimately, FoxM1 could reverse the role of miR-194-5p in inhibiting invasion, migration and EMT of CRA cells (P< 0.05). CONCLUSION: LncRNA H19/miR-194/FoxM1 axis could serve as a profound target for the diagnosis and treatment of CRA.

Active synchronization and modulation of fiber lasers with a graphene electro-optic modulator.

We report the synchronization of two actively Q-switched fiber lasers operating at 1.5 µm and 2 µm with a shared broadband graphene electro-optic modulator. Two graphene monolayer sheets separated with a high-kHfO2 dielectric layer are configured to enable broadband light modulation. The graphene electro-optic modulator is shared by two optical fiber laser cavities (i.e., an erbium-doped fiber laser cavity and a thulium/holmium-codoped fiber laser cavity) to actively Q-switch the two lasers, resulting in stable synchronized pulses at 1.5 µm and 2 µm with a repetition rate ranging from 46 kHz to 56 kHz.

Visually Detecting the Variation of miR-301a Expression Using Gold Nanoparticle Beacon.

It is well known that microRNA-301a plays an important role in many diseases, as well as is overexpressed in human colon cancer and affects the process of tumorigenesis. Determination of the miR-301a expression provides insight into the mechanism of tumor progression. In this study, we designed a special hairpin deoxyribonucleic acid (DNA) for miR-301a to functionalize gold nanoparticles, which served as a beacon for detecting miR-301a expression. A-quenching efficiency up to 90% was achieved. The beacon we designed in this study can monitor the precise variation of miR-301a expression in vivo. The strategy reported in this study is a promising approach for the measurement of miRNA in living cells. Moreover, it has a great potential in the study of drug screening and discovery.

Associations of physical activity and fruit and vegetable intake with well-being and depressive symptoms among obese schoolchildren in Wuhan, China: a cross-sectional study.

BACKGROUND: The prevalence of childhood obesity is increasing and psychological disorder is a common comorbidity of obesity. We investigated the associations of physical activity (PA) and fruit and vegetable (FV) intake with well-being and depressive symptoms among obese schoolchildren. METHODS: Participants included 188 obese children aged 9.8 ± 0.7 years living in Wuhan, China. Self-administered questionnaires were used to collect the children's PA and FV intake information. PA was considered to be high if the child participated in sport and/or vigorous free play at least 3 days per week with 60 min per day, while sufficient FV intake was defined as consuming FV 5 times per day. Children's well-being and depressive symptoms were assessed by standard questionnaires. Multiple logistic regression was performed to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of the relationships of PA and FV intake with well-being and depressive symptoms. RESULTS: High PA and sufficient FV intake were independently associated with significantly decreased risks for depressive symptoms (for PA, OR: 0.39, 95% CI: 0.16-0.92; for FV, OR: 0.21, 95% CI: 0.08-0.55) and poor well-being (for PA, OR: 0.35, 95% CI: 0.16-0.74), respectively. Furthermore, interactive inverse associations were observed between combined high PA and sufficient FV intake with poor well-being and depressive symptoms. Compared to their counterparts, children with high PA and sufficient FV intake had significantly reduced risk for poor well-being (OR: 0.16, 95%CI: 0.05-0.55) and depressive symptoms (OR: 0.12, 95% CI: 0.03-0.48). CONCLUSIONS: High PA and sufficient FV intake are inversely associated with the risks of poor well-being and depressive symptoms among obese Chinese schoolchildren.

TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis.

Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. Methotrexate (MTX) is one of the earliest cytotoxic drugs and serves as an anti-metabolite and anti-folate chemotherapy for various types of cancer. However, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the efficacy of MTX therapies in clinics. Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years. More and more evidences have shown that lncRNAs play regulatory roles in various biological activities and disease progression including drug resistance in cancer cells. Here, we observed lncRNA TUG1 was associated to the MTX resistant in colorectal cancer cells. Firstly, quantitative analysis indicated that TUG1 was significantly increased in tumors which were resistant to MTX treatment. TUG1 knockdown re-sensitized the MTX resistance in colorectal cancer cells, which were MTX-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis.