Iron-Catalyzed Synthesis of Peroxylpyrrolo[2,1-a]isoquinolines through Oxidative Dearomatization.

A mild late-stage modification of pyrrolo[2,1-a]isoquinolines was established through iron-catalyzed oxidative dearomatization and peroxidation. Peroxylated pyrroloisoquinolines have been prepared readily with hydroperoxide in low to good yields (up to 72%) at room temperature. Interestingly, the treatment of fully aromatized pyrrolo[1,2-a]quinolines under the current reaction system resulted in the formation of ring-opening products.

Abnormalities of the Amygdala in schizophrenia: a real world study.

BACKGROUND: Amygdala plays an important role in schizophrenia (SC), but its mechanisms are still unclear. Therefore, we investigated the relationship between the resting-state magnetic resonance imaging (rsMRI) signals of the amygdala and cognitive functions, providing references for future research in this area. METHODS: We collected 40 drug-naïve SC patients and 33 healthy controls (HC) from the Third People's Hospital of Foshan. We used rsMRI and the automatic segmentation tool to extract the structural volume and local neural activity values of the amygdala and conducted Pearson correlation analysis with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Finally, we compared the clinical data, as well as the volume and functional changes of the amygdala in SC patients before and after treatment. RESULTS: Compared with HC, SC had widespread cognitive impairments, significant abnormalities in left amygdala function, while the reduction in volume of SC was not significant. Further Pearson correlation analysis with Bonferroni correction showed that only Immediate memory (learning) was significantly negatively correlated with fractional amplitude of low-frequency fluctuation (FALFF, r = -0.343, p = 0.001, p' = 0.014 (Bonferroni correction)). When compared and analyzed the data difference of SC before and after treatment, we found that immediate memory and delayed memory of SC showed varying degrees of recovery after treatment (tlearning = -2.641, plearning = 0.011; tstory memory = -3.349, pstory memory = 0.001; tlist recall = -2.071, plist recall = 0.043; tstory recall = -2.424, pstory recall = 0.018). But the brain structure and function did not recover. CONCLUSION: There was significant dysfunction in the amygdala in SC, and after conventional treatment, the function of the amygdala did not improve with the improvement of clinical symptoms and cognitive function.

Remdesivir Treatment in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19): A Comparative Analysis of In-hospital All-cause Mortality in a Large Multicenter Observational Cohort.

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized patients with coronavirus disease 2019 (COVID-19) in randomized trials, but data from clinical practice are limited. METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between August and November 2020 and treated with RDV within 2 days of hospitalization vs those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges [NSO], low-flow oxygen [LFO], high-flow oxygen/noninvasive ventilation [HFO/NIV], and invasive mechanical ventilation/extracorporeal membrane oxygenation [IMV/ECMO]) and 2-month admission window and excluded if discharged within 3 days of admission (to exclude anticipated discharges/transfers within 72 hours, consistent with the Adaptive COVID-19 Treatment Trial [ACTT-1] study). Cox proportional hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV, and IMV/ECMO. RESULTS: A total of 28855 RDV patients were matched to 16687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14 and 28 days, respectively, compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14 days (hazard ratio [95% confidence interval]: 0.76 [0.70-0.83]) and 28 days (0.89 [0.82-0.96]). This mortality benefit was also seen for NSO, LFO, and IMV/ECMO at 14 days (NSO: 0.69 [0.57-0.83], LFO: 0.68 [0.80-0.77], IMV/ECMO: 0.70 [0.58-0.84]) and 28 days (NSO: 0.80 [0.68-0.94], LFO: 0.77 [0.68-0.86], IMV/ECMO: 0.81 [0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14 days (0.81 [0.70-0.93]) but no statistical significance at 28 days. CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among patients with COVID-19. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

Liquid Metal pH Morphology Sensor Used for Biological Microenvironment Detection.

pH is one of the important parameters of a biological microenvironment, which is closely related to cell growth, development, vitality, division, and differentiation. Monitoring the pH of a microenvironment is helpful to monitor the cell metabolism as well as to understand the cellular life cycle. The sensitivity of liquid metals (LMs) to hydrogen ions has aroused our interest. Here, we propose a novel but facile pH sensor using liquid gallium (LM for short) droplet morphological change as the readout. The pH sensing characteristics of the LM droplet were examined, especially the shape response. LM can form solid native oxide skin rapidly in oxygenated solution, and the oxide layer will be removed in acidic or alkaline solutions, which will cause a great change in surface tension. The phenomenon is the change of LM morphology from macroscopic observation. We explored the electrochemical characteristics of LM at different pH values, explained the mechanism of surface change, and calibrated the relationship curve between LM morphology and pH and the interference of impurity ions on the sensor. Finally, we proposed a detection algorithm for the LM pH morphology sensor and tried to automatically detect pH with a mobile app, which was applied to the pH detection of cell culture solution. We believe that the response characteristics of LM to hydrogen ions have great potential in microenvironment detection.

Research Progress on the SERPINE1 Protein and Chronic Inflammatory Diseases of the Upper Respiratory Tract: A Literature Review.

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases.

Presence or absence of choroidal hyper-transmission by SD-OCT imaging distinguishes inflammatory from neovascular lesions in myopic eyes.

PURPOSE: To compare the characteristics of choroidal transmission in punctate inner choroidopathy (PIC) with or without choroidal neovascularization (CNV) and myopic CNV (mCNV) using spectral domain optical coherence tomography (SD-OCT). METHODS: This retrospective observational case series includes 22 consecutive myopic patients (22 eyes) recruited from April 2016 until April 2018 who complained of acute blurring of vision and showed evidence of hyper-reflective material on SD-OCT imaging. Each patient underwent a comprehensive eye examination and imaging with fundus fluorescein angiography (FFA), SD-OCT, and SD-OCT angiography (SD-OCTA). Based on the results of SD-OCTA imaging and the color fundus imaging, the patients were divided into 2 groups: a group with myopic choroidal neovascularization (mCNV group, n = 10 eyes) and a group with PIC and no evidence of CNV at baseline (PIC group, n = 12 eyes). Four eyes diagnosed with PIC developed secondary PIC-CNV during follow-up. The characteristics of choroidal transmission in these eyes using SD-OCT imaging were compared. RESULTS: At baseline, none of the PIC lesions showed any evidence of blood flow within the lesions on OCTA imaging. However, all of the eyes with mCNV showed flow signals within the subretinal neovascularization on SD-OCTA and subretinal or intra-retinal fluid on SD-OCT imaging. These eyes with mCNV showed subretinal hyper-reflectivity associated with choroidal hypo-transmission accompanied by retinal pigment epithelium (RPE) and ellipsoid zone (EZ) disruption. In eyes with PIC inflammatory lesions, disruption of both the RPE and EZ were observed in 33% of the inflammatory lesions, and disruption of the EZ alone was observed in 67% of the lesions at the baseline. They all showed a hyper-reflective subretinal lesion located above RPE. Three cases (25%) showed evidence of choroidal hyper-transmission at the baseline, while the remaining had normal transmission within the first month after onset. Hyper-transmission then developed in all the lesions as the disease progressed. Four cases of PIC (33%) developed PIC-related CNV that showed choroidal hypo-transmission along with hyper-transmission with disruption of the RPE and EZ. In cases with PIC-related CNV, evidences of neovascularization on SD-OCTA imaging were all detected afterwards. No intra-retinal fluid was detected before secondary CNV occurred. CONCLUSION: SD-OCT imaging can noninvasively differentiate and track the progression of inflammatory lesions and myopic CNV by using the presence of choroidal hyper-transmission as a sign of just an inflammatory lesion and the presence hypo-transmission as a sign of a secondary CNV, which provides a convenient strategy for diagnosis and treatment of these lesions.

CM-SHARE: Development, Integration, and Adoption of an Electronic Health Record-Linked Digital Health Solution to Support Care for Diabetes in Primary Care.

IN BRIEF Chronic conditions such as diabetes are largely managed by primary care providers (PCPs), with significant patient self-management. This article describes the development, pilot testing, and fine-tuning of a Web-based digital health solution to help PCPs manage patients with cardiometabolic diseases during routine office encounters. It shows that such products can be successfully integrated into primary care settings when they address important unmet needs and are developed with input from end-users.

SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy.

BACKGROUND: Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)-induced pathological cardiac hypertrophy. METHODS: Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation of aging-related cardiac hypertrophy. Cardiac hypertrophy was also induced by Ang II (1.3 mg/kg/d for 4 weeks) in male C57BL/6J Sirt2 knockout mice, cardiac-specific SIRT2 transgenic (SIRT2-Tg) mice, and their respective littermates (8 to ≈12 weeks old). Metformin (200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice. RESULTS: SIRT2 protein expression levels were downregulated in hypertrophic hearts from mice. Sirt2 knockout markedly exaggerated cardiac hypertrophy and fibrosis and decreased cardiac ejection fraction and fractional shortening in aged (24-month-old) mice and Ang II-infused mice. Conversely, cardiac-specific SIRT2 overexpression protected the hearts against Ang II-induced cardiac hypertrophy and fibrosis and rescued cardiac function. Mechanistically, SIRT2 maintained the activity of AMP-activated protein kinase (AMPK) in aged and Ang II-induced hypertrophic hearts in vivo as well as in cardiomyocytes in vitro. We identified the liver kinase B1 (LKB1), the major upstream kinase of AMPK, as the direct target of SIRT2. SIRT2 bound to LKB1 and deacetylated it at lysine 48, which promoted the phosphorylation of LKB1 and the subsequent activation of LKB1-AMPK signaling. Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function. CONCLUSIONS: SIRT2 promotes AMPK activation by deacetylating the kinase LKB1. Loss of SIRT2 reduces AMPK activation, promotes aging-related and Ang II-induced cardiac hypertrophy, and blunts metformin-mediated cardioprotective effects. These findings indicate that SIRT2 will be a potential target for therapeutic interventions in aging- and stress-induced cardiac hypertrophy.

Progress, Mechanisms and Applications of Liquid-Metal Catalyst Systems.

Among the significant growths of liquid metal (LM) research achieved over the past few years, the field of LM as catalysts offers promising opportunities for material scientists to exploit, and thus, burgeoning progress has been made. This article presents an overview of recent progress in developing LM catalysis, which spans from liquid-phase catalysts, photocatalysts, heterogeneous catalysts, and bimetallic catalysts, to catalysts based on liquid-metal/metal-oxide (LM/MO) frameworks. The different types, preparation methods, and typical applications of LM catalysts are classified and reviewed. Typical catalytic applications of LM systems discussed include the growth of graphene films/nanoribbons/carbon nanotube, photocatalytic degradation of CR or PFOA/splitting of H2 O/reduction of CO2 , and catalytic reactions like butane or acetylene dehydrogenation, methanol steam reforming, and reduction of potassium ferricyanide. The prospects, future trends, and challenges of LM catalysts are also mentioned.

Using the consolidated framework for implementation research to understand safety net health system efforts to increase colorectal cancer screening rates.

Guided by the Consolidated Framework for Implementation Research (CFIR), this study aimed to identify factors that influence implementation of evidence-based provider and client-oriented strategies to promote colorectal cancer (CRC) screening in safety net health systems. Site visits and key informant interviews (n=33) were conducted with project leaders and staff in five health systems funded by an American Cancer Society grants program. Within- and cross-site analyses identified CFIR constructs that influenced implementation of provider and client-oriented strategies to promote CRC screening through colonoscopies and fecal immunochemical tests. Of the five CFIR domains, constructs within four CFIR domains (inner setting, outer setting, individual characteristics and process domains) were particularly salient in discussions of implementation while constructs within one CFIR domain (characteristics of the intervention) were not. This study provides a detailed description of how facilitating and inhibiting factors influenced the implementation of evidence-based practices related to CRC screening within safety net health systems. These findings can inform future efforts to promote evidence-based strategies to increase CRC screening rates in safety net health systems.

Process evaluation of health fairs promoting cancer screenings.

BACKGROUND: Low income and uninsured individuals often have lower adherence to cancer screening for breast, cervical and colorectal cancer. Health fairs are a common community outreach strategy used to provide cancer-related health education and services. METHODS: This study was a process evaluation of seven health fairs focused on cancer screening across the U.S. We conducted key-informant interviews with the fair coordinator and conducted baseline and follow-up surveys with fair participants to describe characteristics of participants as well as their experiences. We collected baseline data with participants at the health fairs and telephone follow-up surveys 6 months following the fair. RESULTS: Attendance across the seven health fairs ranged from 41 to 212 participants. Most fairs provided group or individual education, print materials and cancer screening during the event. Overall, participants rated health fairs as very good and participants reported that the staff was knowledgeable and that they liked the materials distributed. After the fairs, about 60% of participants, who were reached at follow-up, had read the materials provided and had conversations with others about cancer screening, and 41% talked to their doctors about screening. Based on findings from evaluation including participant data and coordinator interviews, we describe 6 areas in planning for health fairs that may increase their effectiveness. These include: 1) use of a theoretical framework for health promotion to guide educational content and activities provided, 2) considering the community characteristics, 3) choosing a relevant setting, 4) promotion of the event, 5) considerations of the types of services to deliver, and 6) evaluation of the health fair. CONCLUSIONS: The events reported varied in reach and the participants represented diverse races and lower income populations overall. Most health fairs offered education, print materials and onsite cancer screening. Participants reported general satisfaction with these events and were motivated through their participation to read educational materials or discuss screening with providers. Public health professionals can benefit from this process evaluation and recommendations for designing and evaluating health fairs.

Occurrence and impact of polychlorinated dibenzo-p-dioxins/dibenzofurans in the air and soil around a municipal solid waste incinerator.

To assess the influence of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) on the environment in the vicinity of municipal solid waste incinerators (MSWIs), we determined the levels of PCDD/Fs in air and soil samples collected around a MSWI, which is the largest in China. The International Toxicity Equivalency Quantity (I-TEQ) concentrations of PCDD/Fs in air samples were from 0.0300 to 1.03pgI-TEQ/m(3) (0.445-13.6pg/m(3)), with an average of 0.237pgI-TEQ/m(3), while in soil samples they ranged from 0.520 to 3.40pgI-TEQ/g (2.41-88.7pg/g) with an average of 1.49pgI-TEQ/g. The concentrations of PCDD/Fs in air and soil samples were comparable to other areas, and PeCDFs were the dominant contributors, which was different from stack gas homologue patterns. Multivariate statistical analysis showed that PCDD/Fs emission from the MSWI did not directly affect the profiles of PCDD/Fs in air and soils, so that vehicles and unidentified emission sources should be considered. The daily inhalation levels of PCDD/Fs for children (0.0110 to 0.392pgI-TEQ/(kg·day) and adults (0.00600 to 0.221pgI-TEQ/(kg·day) near the MSWI were lower than the tolerable daily intake of 1.00 to 4.00pg WHO-TEQ/(kg·day), but in winter the values were higher than in summer. These results can be used as basic data for assessing the risk of PCDD/Fs exposure in residents living around this MSWI, and more monitoring programs and studies should be carried out around MSWIs.

Patient Navigation in a Colorectal Cancer Screening Program.

CONTEXT: Colorectal cancer (CRC) is the second leading cause of cancer death among cancers affecting both men and women in the United States. The Centers for Disease Control and Prevention's Colorectal Cancer Control Program (CRCCP) supports both direct clinical screening services (screening provision) and activities to promote screening at the population level (screening promotion). OBJECTIVE: The purpose of this study was to characterize patient navigation (PN) programs for screening provision and promotion for the first 1 to 2 years of program funding. PARTICIPANTS: We conducted a cross-sectional survey of the 29 CRCCP grantees (25 states and 4 tribal organizations) and 14 in-depth interviews to assess program implementation. MAIN OUTCOME MEASURES: The survey and interview guide collected information on CRC screening provision and promotion activities and PN, including the structure of the PN program, characteristics of the navigators, funding mechanism, and navigators' activities. RESULTS: Twenty-four of 28 CRCCP grantees of the survey used PN for screening provision whereas 18 grantees used navigation for screening promotion. Navigators were often trained in nursing or public health. Navigation activities were similar for both screening provision and promotion, and common tasks included assessing and responding to patient barriers to screening, providing patient education, and scheduling appointments. For screening provision, activities centered on making reminder calls, educating patients on bowel preparation for colonoscopies, and tracking patients for completion of the tests. Navigation may influence screening quality by improving patients' bowel preparation for colonoscopies. CONCLUSIONS: Our study provides insights into PN across a federally funded CRC program. Results suggest that PN activities may be instrumental in recruiting people into cancer screening and ensuring completed screening and follow-up.

Semaphorin 3A blocks the formation of pathologic choroidal neovascularization induced by transforming growth factor beta.

OBJECTIVE: Choroidal neovascularization (CNV) is a major cause of vision loss in retinal diseases such as age-related macular degeneration (AMD). Previously, we demonstrated that semaphorin3A (Sema3A), which is a chemorepellent guidance molecule, inhibited the formation of retina neovascularization. In the present study, we investigated the antiangiogenic effects of Sema3A on transforming growth factor beta (TGF-ß) in vitro and in vivo. METHODS: Enzyme-linked immunosorbent assays (ELISAs) were used to measure the TGF-ß levels in the vitreous humor of patients with AMD and controls. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study, and a laser-induced CNV mouse model was prepared for the in vivo study. The HUVECs were incubated with TGF-ß and Sema3A. The proliferation, migration, apoptosis, and tube formation of the cells were then measured using BrdU, Transwell, flow cytometry, and Matrigel assays, respectively, and the SMAD2/3 signaling pathways were analyzed using western blot analysis. The C57BL/6J mouse retina was exposed to a laser to induce choroidal neovascularization (CNV), and Sema3A was injected intravitreously. After 14 days, fundus fluorescein angiography was performed to evaluate the leakage area of the CNV. The vascular endothelial growth factor (VEGF) and TGF-ß concentrations in the retina-choroid complex were measured with ELISA. Components of the p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase-1/2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), and SMAD2/3 signaling pathways in the Sema3A-treated groups were analyzed using western blotting. RESULTS: In this study, we first verified that the vitreous TGF-ß level was higher in patients with neovascular AMD than in the controls. We also showed that Sema3A inhibited TGF-ß-induced HUVEC proliferation, migration, and tube formation and inhibited the downstream SMAD2/3 signaling pathway. Sema3A also induced TGF-ß-stimulated HUVEC apoptosis and inhibited the response of TGF-ß in vitro. In vivo, the TGF-ß level was increased in the CNV mouse model. Sema3A not only inhibited laser-induced CNV formation but also inhibited the uptake of VEGF and TGF-ß. In the western blot analysis, Sema3A was shown to inhibit the phosphorylation of p38 MAPK, ERK1/2, and JNK and to inhibit the SMAD2/3 signaling pathway after Sema3A treatment in CNV mice. CONCLUSIONS: Sema3A can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation.

A systematic review of special events to promote breast, cervical and colorectal cancer screening in the United States.

BACKGROUND: Special events are common community-based strategies for health promotion. This paper presents findings from a systematic literature review on the impact of special events to promote breast, cervical or colorectal cancer education and screening. METHODS: Articles in English that focused on special events involving breast, cervical, and/or colorectal cancer conducted in the U.S. and published between January 1990 and December 2011 were identified from seven databases: Ovid, Web of Science, CINAHL, PsycINFO, Sociological Abstract, Cochrane Libraries, and EconLit. Study inclusion and data extraction were independently validated by two researchers. RESULTS: Of the 20 articles selected for screening out of 1,409, ten articles on special events reported outcome data. Five types of special events were found: health fairs, parties, cultural events, special days, and plays. Many focused on breast cancer only, or in combination with other cancers. Reach ranged from 50-1732 participants. All special events used at least one evidence-based strategy suggested by the Community Guide to Preventive Services, such as small media, one-on-one education, and reducing structural barriers. For cancer screening as an outcome of the events, mammography screening rates ranged from 4.8% to 88%, Pap testing was 3.9%, and clinical breast exams ranged from 9.1% to 100%. For colorectal screening, FOBT ranged from 29.4% to 76%, and sigmoidoscopy was 100% at one event. Outcome measures included intentions to get screened, scheduled appointments, uptake of clinical exams, and participation in cancer screening. CONCLUSIONS: Special events found in the review varied and used evidence-based strategies. Screening data suggest that some special events can lead to increases in cancer screening, especially if they provide onsite screening services. However, there is insufficient evidence to demonstrate that special events are effective in increasing cancer screening. The heterogeneity of populations served, event activities, outcome variables assessed, and the reliance on self-report to measure screening limit conclusions. This study highlights the need for further research to determine the effectiveness of special events to increase cancer screening.

Improving accuracy and efficiency of the machined PEEK denture based on NSGA-II integrated GABP neural network.

OBJECTIVES: The polymer polyetheretherketone (PEEK) is gradually being used in dental restorations because of its excellent mechanical properties, chemical resistance, fatigue resistance, thermal stability, radiation translucency and good biocompatibility. To process PEEK dentures with lower surface roughness as quickly as possible, the non-dominated sorting genetic algorithm-II (NSGA-II) integrated genetic algorithm back propagation (GABP) neural network was proposed, which can adjust the combination of process parameters for milling PEEK dentures. METHODS: The PEEK machining was conducted using a four-axis dental milling machine at different process parameters. The surface roughness of PEEK dentures was characterized using surface roughness profiler and scanning electron microscopy (SEM). The optimum machining performance of milling PEEK dentures was investigated using a multi-objective optimization model named as NSGA-II integrated GABP neural network algorithm. The surface roughness (Ra) and material removal rate (MRR) were used as optimization objectives. RESULTS: The multi-objective optimization model effectively improved surface roughness and machining efficiency for milling PEEK dentures. The validation experiments showed that the surface roughness of all PEEK dentures was less than 0.2µm, which was within the range of surface roughness set in this paper. The GABP surface roughness prediction model had an average error of 6 %. For the same surface roughness value, the optimized milling parameters all had a greater material removal rate. SIGNIFICANCE: The research results can improve current PEEK denture CAD/CAM technology by providing appropriate milling parameters using NSGA-II integrated GABP algorithm.

Electrochemical aptasensor based on DNA-templated copper nanoparticles and RecJf exonuclease-assisted target recycling for lipopolysaccharide detection.

An electrochemical aptasensor for detecting lipopolysaccharides (LPS) was fabricated based on DNA-templated copper nanoparticles (DNA-CuNPs) and RecJf exonuclease-assisted target recycling. The DNA-CuNPs were synthesized on a double-stranded DNA template generated through the hybridization of the LPS aptamer and its complementary chain (cDNA). In the absence of LPS, the CuNPs were synthesized on DNA double-strands, and a strong readout corresponding to the CuNPs was achieved at 0.10 V (vs. SCE). In the presence of LPS, the fabricated aptamer could detach from the DNA double-strand to form a complex with LPS, disrupting the template for the synthesis of CuNPs on the electrode. Meanwhile, RecJf exonuclease could hydrolyze the cDNA together with this single-stranded aptamer, releasing the LPS for the next round of aptamer binding, thereby enabling target recycling amplification. As a result, the electrochemical signal decreased and could be used to indicate the LPS content. The fabricated electrochemical aptasensor exhibited an extensive dynamic working range of 0.01 pg mL-1 to 100 ng mL-1, and its detection limit was 6.8 fg mL-1. The aptasensor also exhibited high selectivity and excellent reproducibility. Moreover, the proposed aptasensor could be used in practical applications for the detection of LPS in human serum samples.

3D Printing of TPU-Liquid Metal Composite Inks for the Preparation of Flexible Sensing Electronics.

Direct 3D printing of liquid metal is difficult to form and easy to destroy. In this paper, we developed a 3D printed composite material consisting of a thermoplastic polyurethane (TPU) matrix and liquid metal (LM) dispersed droplets, and introduced the method for realizing 3D printed devices with this composite material: First, the LM is added to 10~50wt %TPU at 190~200 °C through ultrasonic blending to prepare blended ink. After solid cooling, the LM-TPU composite fiber with a diameter of 600 µm was prepared by Wellzoom desktop extruder at 190 °C at an extrusion speed of 400 mm/min. It has excellent elasticity, with a tensile limit of 0.637 N/m2, and the TPU could evenly wrap LM droplets. Finally, the LM-TPU fiber is 3D printed at 240 °C by using a 3D printer, and 2D/3D flexible electronic devices with heating and conductive functions could be prepared. The microcircuit has good electrical conductivity; after adding voltage, the circuit has heat release; it could be used as heating equipment to keep warm and used in various flexible wearable electronic products.

SIRT1 mediates the protective function of Nkx2.5 during stress in cardiomyocytes.

Nkx2.5 plays protective roles in cardiac homeostasis and survival in the postnatal hearts. However, the underlying molecular mechanisms that mediate the protective functions of Nkx2.5 remain unknown. Here, we showed that Nkx2.5 was downregulated in response to various stresses and was required for protection against the stress-induced apoptosis of cardiomyocytes. SIRT1, a member of the sirtuin family of proteins, was found to be a direct transcriptional target of Nkx2.5 and was required for the Nkx2.5-mediated protection of cardiomyocytes from doxorubicin (DOX)-induced apoptosis. Moreover, using chromatin immunoprecipitation assays, we found that Nkx2.5 was able to bind to the SIRT1 promoter and that this binding was significantly decreased in DOX-treated mouse hearts. Furthermore, the cardiac-specific overexpression of SIRT1 decreased the DOX-induced apoptosis of cardiomyocytes in SIRT1 transgenic mouse hearts compared with the hearts of their wild-type littermates. These findings demonstrate that SIRT1 acts as a direct transcriptional target of Nkx2.5 that maintains cardiomyocyte homeostasis and survival.