8 research outputs found

    DataSheet1_Design and synthesis of ERα agonists: Effectively reduce lipid accumulation.docx

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    In recent years, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing worldwide. Hepatic lipid deposition is a major feature of NAFLD, and insulin resistance is one of the most important causes of lipid deposition. Insulin resistance results in the disruption of lipid metabolism homeostasis characterized by increased lipogenesis and decreased lipolysis. Estrogen receptor α (ERα) has been widely reported to be closely related to lipid metabolism. Activating ERa may be a promising strategy to improve lipid metabolism. Here, we used computer-aided drug design technology to discover a highly active compound, YRL-03, which can effectively reduce lipid accumulation. Cellular experimental results showed that YRL-03 could effectively reduce lipid accumulation by targeting ERα, thereby achieving alleviation of insulin resistance. We believe this study provides meaningful guidance for future molecular development of drugs to prevent and treat NAFLD.</p

    MiRNA and mRNA-Controlled Double-Cascaded Amplifying Circuit Nanosensor for Accurate Discrimination of Breast Cancers in Living Cells, Animals, and Organoids

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    Metastasis is the leading cause of death in patients with breast cancer. Detecting high-risk breast cancer, including micrometastasis, at an early stage is vital for customizing the right and efficient therapies. In this study, we propose an enzyme-free isothermal cascade amplification-based DNA logic circuit in situ biomineralization nanosensor, HDNAzyme@ZIF-8, for simultaneous imaging of multidimensional biomarkers in live cells. Taking miR-21 and Ki-67 mRNA as the dual detection targets achieved sensitive logic operations and molecular recognition through the cascade hybridization chain reaction and DNAzyme. The HDNAzyme@ZIF-8 nanosensor has the ability to accurately differentiate breast cancer cells and their subtypes by comparing their relative fluorescence intensities. Of note, our nanosensor can also achieve visualization within breast cancer organoids, faithfully recapitulating the functional characteristics of parental tumor. Overall, the combination of these techniques offers a universal strategy for detecting cancers with high sensitivity and holds vast potential in clinical cancer diagnosis

    DataSheet1_Efficacy and safety of levosimendan in patients with sepsis: a systematic review and network meta-analysis.docx

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    Objective: We conducted a systematic review to assess the advantages and disadvantages of levosimendan in patients with sepsis compared with placebo, milrinone, and dobutamine and to explore the clinical efficacy of different concentrations of levosimendan.Methods: PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang data, VIP, and CBM databases were searched using such keywords as simendan, levosimendan, and sepsis. The search time was from the establishment of the database to July 2023. Two researchers were responsible for literature screening and data collection respectively. After the risk of bias in the included studies was evaluated, network meta-analysis was performed using R software gemtc and rjags package.Results: Thirty-two randomized controlled trials (RCTs) were included in the network meta-analysis. Meta-analysis results showed that while levosimendan significantly improved CI levels at either 0.1 µg/kg/min (mean difference [MD] [95%CrI] = 0.41 [−0.43, 1.4]) or 0.2 µg/kg/min (MD [95%CrI] =0.54 [0.12, 0.99]). Levosimendan, at either 0.075 µg/kg/min (MD [95% CrI] =0.033 [−0.75, 0.82]) or 0.2 µg/kg/min (MD [95% CrI] = −0.014 [−0.26, 0.23]), had no significant advantage in improving Lac levels. Levosimendan, at either 0.1 µg/kg/min (RR [95% CrI] = 0.99 [0.73, 1.3]) or 0.2 µg/kg/min (RR [95% CrI] = 1.0 [0.88, 1.2]), did not have a significant advantage in reducing mortality.Conclusion: The existing evidence suggests that levosimendan can significantly improve CI and lactate levels in patients with sepsis, and levosimendan at 0.1 µg/kg/min might be the optimal dose. Unfortunately, all interventions in this study failed to reduce the 28-day mortality.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441220.</p

    DataSheet2_Efficacy and safety of levosimendan in patients with sepsis: a systematic review and network meta-analysis.docx

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    Objective: We conducted a systematic review to assess the advantages and disadvantages of levosimendan in patients with sepsis compared with placebo, milrinone, and dobutamine and to explore the clinical efficacy of different concentrations of levosimendan.Methods: PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wanfang data, VIP, and CBM databases were searched using such keywords as simendan, levosimendan, and sepsis. The search time was from the establishment of the database to July 2023. Two researchers were responsible for literature screening and data collection respectively. After the risk of bias in the included studies was evaluated, network meta-analysis was performed using R software gemtc and rjags package.Results: Thirty-two randomized controlled trials (RCTs) were included in the network meta-analysis. Meta-analysis results showed that while levosimendan significantly improved CI levels at either 0.1 µg/kg/min (mean difference [MD] [95%CrI] = 0.41 [−0.43, 1.4]) or 0.2 µg/kg/min (MD [95%CrI] =0.54 [0.12, 0.99]). Levosimendan, at either 0.075 µg/kg/min (MD [95% CrI] =0.033 [−0.75, 0.82]) or 0.2 µg/kg/min (MD [95% CrI] = −0.014 [−0.26, 0.23]), had no significant advantage in improving Lac levels. Levosimendan, at either 0.1 µg/kg/min (RR [95% CrI] = 0.99 [0.73, 1.3]) or 0.2 µg/kg/min (RR [95% CrI] = 1.0 [0.88, 1.2]), did not have a significant advantage in reducing mortality.Conclusion: The existing evidence suggests that levosimendan can significantly improve CI and lactate levels in patients with sepsis, and levosimendan at 0.1 µg/kg/min might be the optimal dose. Unfortunately, all interventions in this study failed to reduce the 28-day mortality.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023441220.</p

    Presentation_1_Psychometric Properties of the Chinese Version of the Brief Borderline Symptom List in Undergraduate Students and Clinical Patients.pdf

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    <p>The brief version of the Borderline Symptom List (BSL-23) is a self-rated scale developed from the initial 95-item version of Borderline Symptom List (BSL-95). The current study aimed to evaluate the psychometric properties of the Chinese version of the BSL-23. A total of 570 undergraduate students and 323 clinical patients completed the BSL-23, the borderline subscale of the Personality Diagnostic Questionnaire (PDQ-4+), the Center for Epidemiologic Studies Depression Scale (CES-D), the Barratt Impulsiveness Scale, 11th version (BIS-11), the Childhood Trauma Questionnaire (CTQ) and the Attachment Style Questionnaire (ASQ). A Confirmatory Factor Analysis (CFA) was conducted to test the one-factor structure of the BSL-23. Cronbach’s alpha, Omega coefficient, Split-Half coefficient, Mean Inter-Item Correlation (M<sub>IC</sub>) and test-retest reliability were also measured. The correlations between the BSL-23 and other psychological variables were used to assess criterion-related validity and convergent validity. Participants who scored ≥ 5 on the borderline subscale of the PDQ-4+ were placed into the borderline personality disorder (BPD) screening-positive group, while the others were placed into the screening-negative group. Independent sample t-tests were performed to examine the differences in BSL-23 scores between the BPD screening-positive group and the BPD screening-negative group. The CFA results supported the one-factor structure of the BSL-23 in both samples. The internal consistency was high both in the undergraduate sample (Cronbach’s α = 0.93, Omega = 0.95, Split-Half coefficient = 0.89, M<sub>IC</sub> = 0.38) and the clinical sample (Cronbach’s α = 0.97, Omega = 0.97, Split-Half coefficient = 0.96, M<sub>IC</sub> = 0.56). The test-retest reliability within 2 weeks was 0.62. The BSL-23 displayed moderate to high correlations with the PDQ-4+-Borderline subscale, the CES-D, the BIS-11, the CTQ and the ASQ (r = 0.35 – 0.70). In addition, the BSL-23 discriminated between the BPD screening-positive and the BPD screening-negative participants, and also between the patient sample and undergraduate sample. In conclusion, the Chinese version of the BSL-23 has satisfactory psychometric properties to assess BPD symptoms.</p

    Effective Synergistic Effect of Dipeptide-Polyoxometalate-Graphene Oxide Ternary Hybrid Materials on Peroxidase-like Mimics with Enhanced Performance

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    Dipeptide-polyoxometalates (POMs)-graphene oxide (GO) ternary hybrid is an excellent peroxidase-like mimic, exhibiting enhanced peroxidase-like activity compared to POMs alone. The hybrid was readily prepared through a reprecipitation method involving electrostatic encapsulation of H<sub>3</sub>PW<sub>12</sub>O<sub>40</sub> (PW<sub>12</sub>) by cationic diphenylalanine (FF) peptide and coassembly of FF@PW<sub>12</sub> spheres with graphene oxide (GO). Using 3,3′,5,5′-tetramethylbenzidine (TMB) as the chromogenic substrate, the peroxidase-like activity of FF@PW<sub>12</sub> was evaluated in the heterogeneous phase, and it is 13 times higher than that of pristine PW<sub>12</sub> in the homogeneous phase. Furthermore, ternary hybrids of FF@PW<sub>12</sub>@GO containing 5 wt % GO could enhance the activity 1.7 times higher than that of FF@PW<sub>12</sub>. The noncovalent interactions of hydrogen bonding and ionic interaction between GO and POMs are speculated to result in the synergistic effect for the enhancement of peroxidase-like performance. The strong interactions between rGO and PW<sub>12</sub> are evaluated by a four-probe Hall measurement via the van der Pauw method, and rGO is significantly p-doped by the doping effect of PW<sub>12</sub> with lower LUMO energy than that of the energy level of rGO and also due to the electron reservoir feature of PW<sub>12</sub>. Cyclic voltammogram measurements also suggest that GO causes significant influence on the electronic structure of the reduced forms of the redox couples of PW<sub>12</sub>. The nature of the TMB catalytic reaction may originate from the generation of the hydroxyl radical (<sup>•</sup>OH) from the decomposition of H<sub>2</sub>O<sub>2</sub> by ternary hybrids and the formation of peroxo species of POM. Taking advantage of the UV–vis signals of TMB being correlated to the concentration of H<sub>2</sub>O<sub>2</sub>, FF@PW<sub>12</sub>@GO can be used to detect H<sub>2</sub>O<sub>2</sub> within the limit of detection of 0.11 μM, and the detection range is 1–75 μM. The present method indeed opens up a promising route in constructing heterogeneous peroxidase-like mimics through the use of POMs via the introduction of GO for building H<sub>2</sub>O<sub>2</sub> sensors

    In-Plane Mosaic Potential Growth of Large-Area 2D Layered Semiconductors MoS<sub>2</sub>–MoSe<sub>2</sub> Lateral Heterostructures and Photodetector Application

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    Considering the unique layered structure and novel optoelectronic properties of individual MoS<sub>2</sub> and MoSe<sub>2</sub>, as well as the quantum coherence or donor–acceptor coupling effects between these two components, rational design and artificial growth of in-plane mosaic MoS<sub>2</sub>/MoSe<sub>2</sub> lateral heterojunctions film on conventional amorphous SiO<sub>2</sub>/Si substrate are in high demand. In this article, large-area, uniform, high-quality mosaic MoS<sub>2</sub>/MoSe<sub>2</sub> lateral heterojunctions film was successfully grown on SiO<sub>2</sub>/Si substrate for the first time by chemical vapor deposition (CVD) technique. MoSe<sub>2</sub> film was grown along MoS<sub>2</sub> triangle edges and occupied the blanks of the substrate, finally leading to the formation of mosaic MoS<sub>2</sub>/MoSe<sub>2</sub> lateral heterojunctions film. The composition and microstructure of mosaic MoS<sub>2</sub>/MoSe<sub>2</sub> lateral heterojunctions film were characterized by various analytic techniques. Photodetectors based on mosaic MoS<sub>2</sub>/MoSe<sub>2</sub> lateral heterojunctions film, triangular MoS<sub>2</sub> monolayer, and multilayer MoSe<sub>2</sub> film are systematically investigated. The mosaic MoS<sub>2</sub>/MoSe<sub>2</sub> lateral heterojunctions film photodetector exhibited optimal photoresponse performance, giving rise to responsivity, detectivity, and external quantum efficiency (EQE) up to 1.3 A W<sup>–1</sup>, 2.6 × 10<sup>11</sup> Jones, and 263.1%, respectively, under the bias voltage of 5 V with 0.29 mW cm<sup>–2</sup> (610 nm), possibly due to the matched band alignment of MoS<sub>2</sub> and MoSe<sub>2</sub> and strong donor–acceptor delocalization effect between them. Taking into account the similar edge conditions of transition metal dichalcogenides (TMDCs), such a facile and reliable approach might open up a unique route for preparing other 2D mosaic lateral heterojunctions films in a manipulative manner. Furthermore, the mosaic lateral heterojunctions film like MoS<sub>2</sub>/MoSe<sub>2</sub> in the present work will be a promising candidate for optoelectronic fields

    2000W Blue laser directed energy deposition of AlSi7Mg: process parameters, molten pool characteristics, and appearance defects

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    Aluminium alloys are difficult to be manufactured by directed energy deposition (DED) with the widely used infrared laser because of the low absorptivity. A blue laser with a 450 nm wavelength has a significantly higher laser absorptivity in processing aluminium. Here, we developed a 2000 W blue laser directed energy deposition (BL-DED) system for additive manufacturing. In this system, a coaxial camera, a paraxial high-speed camera, and a paraxial infrared camera were simultaneously adopted to analyze the formation and evolution of molten pool characteristics. The relationships among the molten pool characteristics, depositing states, and appearance defects were built. We successfully printed the curved thin wall with good appearance quality by the manual in-situ control of appearance defects. This work demonstrated the advantages of the blue laser in DED of aluminium alloy, which could melt the powders under lower energy input conditions and result in a more stable deposition process.</p
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