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SR9009 is an activator of REV-ERBs with diverse biological activities, including improving exercise tolerance and controlling skeletal muscle mass. To optimise the carbamate motif of SR9009, analogues of SR9009 were synthesised and evaluated. All of them showed REV-ERB-α agonist activities. Among them, 5a, 5f, 5 g, 5m, and 5p showed potencies equivalent to or slightly higher than the potency of SR9009 in vitro. These data indicate that the halogenated benzyl group is an indispensable active group in these compounds. 5m, 5p and SR9009 improved exercise tolerance in normal mice in vivo. Additionally, in hyperlipidemic mice, 5m and 5p not only improved exercise tolerance but also lowered blood lipid levels. 5m and 5p displayed stronger hypoglycaemic activity than SR9009.
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Glicolipídeos , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares , Tiofenos , Animais , Camundongos , Tiofenos/farmacologia , Tiofenos/química , Tiofenos/síntese química , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/agonistas , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Glicolipídeos/farmacologia , Glicolipídeos/química , Glicolipídeos/síntese química , Relação Estrutura-Atividade , Masculino , Humanos , Estrutura Molecular , Camundongos Endogâmicos C57BL , Pirrolidinas/farmacologia , Pirrolidinas/química , Pirrolidinas/síntese química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Relação Dose-Resposta a Droga , Tolerância ao Exercício/efeitos dos fármacosRESUMO
The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA-dependent RNA polymerase (RdRp) has emerged as a potential target for broad-spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently-used structural substitution methods to design new nucleoside analogues is challenging. In this study, we explore the use of the "ring-opening" strategy to design new base mimics, thereby using these base mimics to design new nucleoside analogues with broad-spectrum antiviral activities. A total of 29 compounds were synthesized. Their activity against viral RdRp was initially screened using an influenza A virus RdRp high-throughput screening model. Then, the antiviral activity of 38a was verified against influenza virus strain A/PR/8/34 (H1N1), demonstrating a 50% inhibitory concentration (IC50) value of 9.95 µM, which was superior to that of ribavirin (the positive control, IC50 = 11.43 µM). Moreover, 38a also has inhibitory activity against coronavirus 229E with an IC50 of 30.82 µM. In addition, compounds 42 and 46f exhibit an 82% inhibition rate against vesicular stomatitis virus at a concentration of 20 µM and hardly induce cytotoxicity in host cells. This work demonstrates the feasibility of designing nucleoside analogues with "ring-opening" bases and suggests the "ring-opening" nucleosides may have greater polarity, and designing prodrugs is an important aspect of optimizing their antiviral activity. Future research should focus on enhancing the conformational restriction of open-loop bases to mimic Watson-Crick base pairing better and improve antiviral activity.
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Antivirais , Desenho de Fármacos , Nucleosídeos , RNA Polimerase Dependente de RNA , Antivirais/farmacologia , Antivirais/química , Antivirais/síntese química , Nucleosídeos/química , Nucleosídeos/farmacologia , RNA Polimerase Dependente de RNA/antagonistas & inibidores , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Humanos , Animais , Células Madin Darby de Rim Canino , Cães , Relação Estrutura-AtividadeRESUMO
Magnetic Functional Nanomaterials Co1-yZnyRExFe2-xO4 (RE (rare-earth) = La,Sm,Gd) were prepared using the sol-gel combustion method. XRD characterization confirms that the ferrite samples we synthesized are single-phase cubic structures. The variation in the average crystalline size and lattice parameter is related to RE ion doping. The Mössbauer spectra of CoRExFe2-xO4 are two sets of magnetic six-wire peaks that indicate the ferrimagnetic behavior of the sample. The calcination temperature greatly influences the absorption area of Mössbauer for CoFe2O4, indicating that the calcination temperature affects the iron ion content at the octahedral B and tetrahedral A sites. Additionally, scanning electron microscopy measurements of the substituted specimens reveal that the ferrite powders are nanoparticles. With an increase in RE ions, the coercivity increases, and the saturation magnetization changes obviously. The XRD characterization of Co0.7Zn0.3LaxFe2-xO4 shows that the main crystalline phase of the sample is the cubic spinel structure phase, and there are fewer secondary crystalline phases. The lattice parameter tends to decrease with the substitution of La3+ ions. The average grain size decreased significantly with the increase in La content. From ferrimagnetic state transition to relaxation behavior, the hyperfine magnetic field decreases in La concentration by room temperature Mössbauer spectra. With the substitution of La3+ ions, both the saturation magnetization and coercivity of the samples were reduced, and the coercivity of all samples was lower.
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CdxNi0.5-xCu0.2Zn0.3Fe2O4 (0 ≤ x ≤ 0.50) ferrite with a spinel structure was prepared using the sol-gel self-propagation method. The effects of Cd2+ doping on the structure, morphology, dielectric, and magnetic properties of Ni-Cu-Zn ferrite were examined using XRD, SEM, EDX, FTIR, MPMS, and dielectric tests. The cubic spinel structure was verified by XRD and FTIR analyses. The crystallite size and particle size information of the samples were obtained with XRD and SEM analysis. The sample particle size belonged to a class of nanoscale materials with a particle size range of 1-100 nm. The minor difference between the grain size and particle size indicated that the sample nanoparticles were composed of numerous microcrystals. The EDX spectra indicated that the samples contained all stoichiometric elements. MPMS was used to measure the hysteresis lines of the samples. According to the hysteresis line, the saturation magnetization intensity (Ms), coercivity (Hc), and magnetic moment (µB) of the sample increased and then decreased with the increase in cadmium concentration. The magnetization strength (Ms) is between 4-67 emu/g, and the coercivity (Hc) is between 9-46 Oe. The curves of the real part of the dielectric constant (ε'), the imaginary part of the dielectric constant (εâ³), and the loss factor (tanδ) with frequency were measured in the frequency range 100 Hz-100 kHz by means of an impedance analyzer. The complex modulus spectrum was analyzed to understand the dynamics of the conduction process.
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Perovskite is the largest mineral on earth and has a variety of excellent physical and chemical properties. La1-xRxFeO3 (R = Co, Al, Nd, Sm) were synthesized using the sol-gel method and analyzed by XRD, TG-DTA, and VSM. With the increase in the Co2+ doping content, the diffraction peak drifted in the direction of a larger angle. The grain size of La1-xRxFeO3(R = Co) is mainly concentrated between 50.7 and 133.5 nm. As the concentration of Co2+ increased, the magnetic loop area and magnetization increased. La1-xRxFeO3(R = Al) is an orthorhombic perovskite structure, the grain size decreased with the increase in Al3+ doping concentration, and the minimum crystallite is 17.9 nm. The magnetic loop area and magnetization increased with the increase in Al3+ ion concentration. The enclosed area of the M-H curve of the sample decreased, and the ferromagnetic order gradually weakened and tended to be antiferromagnetic, which may be due to the increase in sintering temperature, decrease in the iron oxide composition, and changes in the magnetic properties. Proper doping can improve the magnetization of La1-xRxFeO3(R = Nd), refine the particles, and obtain better magnetic performance. As the Nd3+ ion concentration increased, the magnetic properties of the samples increased. Ms of La0.85Co0.15FeO3 prepared by different calcination time increases with the increase in calcination time. As the Sm3+ ion concentration increased, the magnetic properties of the samples increased. Proper doping can improve the magnetization of La1-xRxFeO3(R = Sm), refine the particles, and generate better magnetic performance.
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Emerging photocatalytic technology promises to provide an effective solution to the global energy crisis and environmental pollution. Graphite carbon nitride (g-C3 N4 ) has gained extensive attention in the scientific community due to its excellent physical and chemical properties, attractive electronic band structure, and low cost. In this paper, research progress in design strategies for g-C3 N4 -based photocatalysts in the past five years is reviewed from the perspectives of nanostructure construction, element doping, and heterostructure construction. To clarify the relationship between application requirements and structural design, variations in the morphology, electronic energy band structure, light absorption capacity, as well as interfacial charge transfer caused by various modification strategies are discussed in detail. The recent applications of g-C3 N4 -based photocatalysts for pollutant degradation and bacterial disinfection are reviewed, as well as the antimicrobial activity and degradation mechanisms. Finally, current challenges and future development directions for the practical application of g-C3 N4 -based photocatalysts are tentatively discussed.
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Desinfecção , Poluentes Ambientais , Bactérias , CatáliseRESUMO
Foodborne contaminants are closely related to anthropologic activities and represent an important food safety hazard. The study of metabolic transformation and toxic side effects of foodborne contaminants in the body is important for their safety assessment. Liver microsomes contain a variety of enzymes related to substance metabolism and biotransformation. An in vitro model simulating liver metabolic transformation is associated with a significant advantage in the study of the metabolic transformation mechanisms of contaminants. This review summarizes the recent progress in the application of liver microsomes in metabolic transformation and toxicity evaluation of various foodborne pollutants based on metabolic kinetics, molecular docking and enzyme inhibition studies. The purpose of this review is to distinguish the existing studies involving liver microsomes and provide strategies for their application in the future. Finally, the prospects and challenges of the liver microsomal model are discussed.
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Zearalenone (ZEN), one of the most contaminated Fusarium toxins worldwide, is very common in contaminating wheat, corn oil and other foods. People are more vulnerable to ZEN exposure with more daily caloric intake, yet little is known about the combined effect of different dietary patterns with mycotoxins. This study aimed to compare the effects of long-term ZEN exposure on the overall biochemical landscape of the "gut-blood-liver axis" under normal diet and high-fat diet (HFD) using a combined multi-omics approach. The results indicated that ZEN exposure, possibly via the phenylalanine metabolic pathway, led to dysbiosis of mouse flora, suppression of short-chain fatty acids (SCFAS) metabolism, systemic inflammatory responses, and disturbances in serum and liver metabolism, which were exacerbated in synergy with HFD and ultimately led to a more severe state of lipid metabolism in the liver. We further found that ZEN exposure attenuated the indole-3-propionic acid (IPA) metabolic pathway, enhanced 2-hydroxybutyric acid metabolism in serum, and attenuated ß-alanine metabolism in liver which was positively correlated with the abundance of Prevotellaceae UCG-004, Prevotellaceae UCG-001, and Prevotellaceae NK3B31 groups. The results highlighted the damaging effects of ZEN on the gut-blood-liver axis under different dietary patterns, which might serve as a reference for future studies exploring the combined effects of fungal toxins and multiple dietary patterns.
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Micotoxinas , Tricotecenos , Zearalenona , Animais , Dieta , Humanos , Fígado , Camundongos , Micotoxinas/metabolismo , Zearalenona/toxicidadeRESUMO
We disclose that the carbonates of 4-hydroxy-2-cyclopentenones can form π-allylpalladium-based 1,2-carbodipoles, which isomerize to interesting η2 -Pd0 -cyclopentadienone complexes. Compared with the labile parent cyclopentadienone, the HOMO energy of the related η2 -complex was significantly raised via the back-bonding of Pd0 as a π-Lewis base, rendering the uncoordinated C=C bond an electron-richer dienophile in inverse-electron-demand aza-Diels-Alder-type reactions with diverse 1-azadienes. The vinylogous (aza)Morita-Baylis-Hillman or cross Rauhut-Currier addition to (imine)carbonyls or activated alkenes, respectively, was also realized to afford chiral [4+2] or [2+2] cycloadducts, respectively, after trapping the re-generated π-allylpalladium species. New C1 -symmetric ligands from simple chiral sources were developed, exhibiting high stereoselectivity even with racemic substrates via an unusual dynamic kinetic resolution process. Besides, tropone could be similarly activated by a Pd0 complex.
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1-naphthol (1-NAP) is the main metabolite of pesticide carbaryl and naphthalene, and is also a genotoxic and carcinogenic intermediate in the synthesis of organic compound, dyes, pigment and pharmaceutical industry. In this work, two novel haptens were designed and synthesized for developing a competitive indirect enzyme-linked immunosorbent assay (ciELISA) method for 1-NAP in urine samples. The assay showed a limit of detection of 2.21 ng/mL and working range from 4.02 ng/mL to 31.25 ng/mL for 1-NAP in optimized working buffer. The matrix effect of samples was eliminated via 15-fold dilution of optimized working buffer. Good average recoveries (102.4%-123.4%) with a coefficient of variation from 11.7% to 14.7% was obtained for spiked urine samples. Subsequent instrument verification test showed good correlation between the results of ciELISA and high-performance liquid chromatography. The developed ciELISA is a high-throughput tool to monitor 1-NAP in urine, which can provide technical support for the establishment of biological exposure level for the exposure to carbaryl, naphthalene and other related pollutants.
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Anticorpos Monoclonais/química , Ensaio de Imunoadsorção Enzimática/métodos , Haptenos/química , Naftóis/urina , Resíduos de Praguicidas/urina , Anticorpos Monoclonais/imunologia , Carbaril/metabolismo , Exposição Ambiental/análise , Limite de Detecção , Naftalenos/metabolismo , Naftóis/imunologia , Resíduos de Praguicidas/imunologia , Resíduos de Praguicidas/metabolismoRESUMO
Rapid, accurate, and safe screening of foodborne pathogenic bacteria is essential to effectively control and prevent outbreaks of foodborne illness. Fluorescent sensors constructed from carbon dots (CDs) and nanomaterial-based quenchers have provided an innovative method for screening of pathogenic bacteria. Herein, an ultrasensitive magnetic fluorescence aptasensor was designed for separation and detection of Staphylococcus aureus (S. aureus). Multicolor fluorescent CDs with a long fluorescent lifetime (6.73 ns) and high fluorescence stability were synthesized using a facile hydrothermal approach and modified cDNA as a highly sensitive fluorescent probe. CD fluorescence was quenched by Fe3O4 + aptamer via fluorescence resonance energy transfer (FRET). Under optimal conditions, the FRET-based aptasensor can detect S. aureus accompanied by a wide linear range of 50-107 CFU·mL-1 and a detection limit of 8 CFU·mL-1. Compared with other standard methods, this method was faster and more convenient, and the entire test was finished within 30 min. The capability of the aptasensor was simultaneously investigated on food samples. Additionally, the developed CDs exhibited excellent biocompatibility and were thus applied as fluorescent probes for bioimaging both in vitro and in vivo. This new platform provided an excellent application of the CDs for detecting and bioimaging pathogenic bacteria.
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Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Pontos Quânticos/química , Staphylococcus aureus/isolamento & purificação , Animais , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/toxicidade , Carbono/química , Carbono/toxicidade , DNA/química , DNA/toxicidade , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes/toxicidade , Contaminação de Alimentos/análise , Sucos de Frutas e Vegetais/microbiologia , Células Hep G2 , Humanos , Limite de Detecção , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidade , Camundongos Nus , Leite/microbiologia , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Fenilenodiaminas/química , Fenilenodiaminas/toxicidade , Pontos Quânticos/toxicidade , Staphylococcus aureus/químicaRESUMO
An ON-OFF-ON dual-function fluorescent nanoprobe is described for the trace detection of ferric ions and inositol hexaphosphate (IP6) in living cells. It is based on the use of yellow-fluorescent nitrogen-doped carbon dots (YN-CDs). Highly fluorescent YN-CDs were synthesized by a hydrothermal process. They have an absolute quantum yield of 2.15% and excitation/emission peaks at 420/575 nm. Fluorescence is quenched by Fe3+via photo-induced electron transfer. The quenchometric assay has a 34 nM detection limit for Fe(iii). On addition of IP6 which has a high affinity for Fe3+ due to the formation of Fe-O-P bonds, fluorescence becomes gradually restored. The resulting ON-OFF-ON assays for Fe(iii) and IP6 are reliable and sensitive. IP6 can be detected at concentrations as low as 2 nM. The nanoprobe was then applied to the determination of Fe3+ and IP6 in living cells in a food matrix. Furthermore, YN-CDs exhibited excellent biocompatibility. Hence, the probe can be applied as a fluorescent ink for bioimaging, both in vitro (cancer cells and bacteria) and in vivo (nematodes and mice).
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Ferro/análise , Ácido Fítico/análise , Pontos Quânticos/química , Animais , Apium/química , Carbono/química , Grão Comestível/química , Escherichia coli , Fluorescência , Análise de Alimentos , Frutas/química , Células Hep G2 , Humanos , Limite de Detecção , Camundongos Nus , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Nematoides , Espectrometria de Fluorescência/métodosRESUMO
An atom-economic and highly efficient vinylogous umpolung strategy is developed for deconjugated carbonyl compounds, which generate electron-deficient π-allylpalladium complexes with Pd(OAc)2 under ligand-free conditions. In cooperation with a chiral-phosphonium-based phase-transfer catalyst, the asymmetric direct oxidative allylic alkylations of 3-substituted oxindoles are furnished under O2 atmosphere. The γ- or even remote ϵ-regioselective alkylation products, with substantial substituents, are delivered with excellent enantioselectivity, and can be further used to access diverse chiral spirocyclic architectures effectively. The Mukaiyama dienol silyl ether can be utilized similarly, indicating that the current active π-allylpalladium species results from tautomerization of the PdII -dienolate intermediate.
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Magnetic resonance imaging (MRI) machines have horizontal or upright static magnetic field (SMF) of 0.1-3 T (Tesla) at sites of patients and operators, but the biological effects of these SMFs still remain elusive. We examined 12 different cell lines, including 5 human solid tumor cell lines, 2 human leukemia cell lines and 4 human non-cancer cell lines, as well as the Chinese hamster ovary cell line. Permanent magnets were used to provide 0.2-1 T SMFs with different magnetic field directions. We found that an upward magnetic field of 0.2-1 T could effectively reduce the cell numbers of all human solid tumor cell lines we tested, but a downward magnetic field mostly had no statistically significant effect. However, the leukemia cells in suspension, which do not have shape-induced anisotropy, were inhibited by both upward and downward magnetic fields. In contrast, the cell numbers of most non-cancer cells were not affected by magnetic fields of all directions. Moreover, the upward magnetic field inhibited GIST-T1 tumor growth in nude mice by 19.3% (p < 0.05) while the downward magnetic field did not produce significant effect. In conclusion, although still lack of mechanistical insights, our results show that different magnetic field directions produce divergent effects on cancer cell numbers as well as tumor growth in mice. This not only verified the safety of SMF exposure related to current MRI machines but also revealed the possible antitumor potential of magnetic field with an upward direction.
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Proliferação de Células , Campos Magnéticos , Animais , Contagem de Células , Linhagem Celular , Cricetinae , HumanosRESUMO
The biodegradable microcapsules based on chitosan for a controlled delivery of clove oil were prepared by the single coagulation process. The effect of chitosan concentration, core to shell ratio, types of emulsifier, flocculating agent and hardening agent on the microcapsule diameter and the particle size distribution of microcapsule were investigated. The optimized conditions for the preparation of microcapsules with well-defined structure and narrow dispersibility were under that (1) the concentration of chitosan was 1.0 wt%, (2) clove oil to chitosan ratio was 75:25, (3) OP-10 and 10 wt% sodium sulfate were used as emulsifier and flocculating agent respectively, and (4) the concentration hardening agent glyoxal was 1 wt% based on the weight of chitosan. The uniform spherical structures with smooth surfaces with a particle size distribution of 1-15 µm were evidenced by SEM images of microcapsules. Core-shell, hetero-structures were confirmed by optical micrograph. The chemical component of the microcapsules was determined by FTIR. Thermal analysis showed the microcapsules were thermally stable below 150 degrees C. It was found that the pH value and temperature play important roles on the release rate of clove oil from the microcapsules. The release volume of clove oil from microcapsules at pH = 7, and pH = 10 were smaller than that at pH = 2. And the release volume of Clove oil from microcapsules at 60 degrees C was smaller than that at 20 degrees C and 40 degrees C, which showed a sustained and prolonged release.
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Cápsulas/química , Óleo de Cravo/química , Quitosana/química , Óleo de Cravo/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Floculação , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe pulmonary disease in humans and represents the second example of a highly pathogenic coronavirus (CoV) following severe acute respiratory syndrome coronavirus (SARS-CoV). Genomic studies revealed that two viral proteases, papain-like protease (PLpro) and 3C-like protease (3CLpro), process the polyproteins encoded by the MERS-CoV genomic RNA. We previously reported that SARS-CoV PLpro acts as both deubiquitinase (DUB) and IFN antagonist, but the function of the MERS-CoV PLpro was poorly understood. In this study, we characterized MERS-CoV PLpro, which is a protease and can recognize and process the cleavage sites (CS) of nsp1-2, nsp2-3 and nsp3-4. The LXGG consensus cleavage sites in the N terminus of pp1a/1ab, which is generally essential for CoV PLpro-mediated processing, were also characterized in MERS-CoV. MERS-CoV PLpro, like human SARS-CoV PLpro and NL63-CoV PLP2, is a viral deubiquitinating enzyme. It acts on both K48- and K63-linked ubiquitination and ISG15-linked ISGylation. We confirmed that MERS-CoV PLpro acts as an IFN antagonist through blocking the phosphorylation and nuclear translocation of IFN regulatory factor 3 (IRF3). These findings indicate that MERS-CoV PLpro acts as a viral DUB and suppresses production of IFN-ß by an interfering IRF3-mediated signalling pathway, in addition to recognizing and processing the CS at the N terminus of replicase polyprotein to release the non-structural proteins. The characterization of proteolytic processing, DUB and IFN antagonist activities of MERS-CoV PLpro would reveal the interactions between MERS-CoV and its host, and be applicable to develop strategies targeting PLpro for the effective control of MERS-CoV infection.
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Infecções por Coronaviridae/metabolismo , Coronaviridae/enzimologia , Interferon beta/antagonistas & inibidores , Papaína/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Proteínas Virais/metabolismo , Sequência de Aminoácidos , Domínio Catalítico , Coronaviridae/química , Coronaviridae/genética , Infecções por Coronaviridae/virologia , Humanos , Fator Regulador 3 de Interferon/metabolismo , Interferon beta/metabolismo , Dados de Sequência Molecular , Papaína/química , Papaína/genética , Fosforilação , Poliproteínas/genética , Poliproteínas/metabolismo , Processamento de Proteína Pós-Traducional , Proteólise , Alinhamento de Sequência , Ubiquitina , Proteases Específicas de Ubiquitina/química , Proteases Específicas de Ubiquitina/genética , Proteínas Virais/química , Proteínas Virais/genéticaRESUMO
The Latent Dirichlet Allocation (LDA) model is used to extract the text themes of newspaper news and construct the Chinese Economic Policy Uncertainty (EPU) Index. On this basis, based on the relevant data of Chinese A-share listed companies from 2008 to 2020, this paper empirically analyzes the impact of EPU on peer effects of firms R&D investment, and finds that EPU will aggravate the peer effects of firms R&D investment. Furthermore, the moderating effect of manager's motivation to maintain reputation on the process of EPU influencing the peer effects of firms R&D investment was tested, and the mechanism of EPU influencing the peer effects of firms R&D investment through financial frictions was verified.
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Investimentos em Saúde , Aprendizado de Máquina , Incerteza , Modelos Estatísticos , Humanos , China , Pesquisa/economiaRESUMO
Objective: In this study, we aimed to evaluate the current status of the quality of life (QOL) of pediatric patients and plasma glucose concentration regulation in children with type 1 diabetes (T1DM) in the Ningxia Hui autonomous region. Methods: The study involved children with T1DM admitted to the General Hospital of Ningxia Medical University between October 2011 and October 2021. The children and their parents completed general information and quality of life (QOL) questionnaires. The regulation of plasma glucose concentration was assessed based on HbA1c levels, and plasma glucose and QOL-influencing components were investigated. Results: Among the 136 pediatric patients diagnosed with T1DM, the mean glycated hemoglobin (HbA1c) level was recorded at 8.7% (7.2%, 10.5%). A breakdown of the patient cohort revealed that 44 patients (32.4%) demonstrated good regulation of plasma glucose, 33 patients (24.3%) exhibited acceptable glycemic control, and 59 patients (43.3%) displayed poor regulation of plasma glucose. The control of plasma glucose in pediatric patients diagnosed with T1DM was affected by the duration of the disease, the patient's age, the frequency of daily plasma glucose measurements, the use of CGM, diabetic ketoacidosis (DKA), and the education level of the mother. The control of plasma glucose, dietary management, DKA, the ability to learn, and health education are interfering factors of quality of life in children diagnosed with T1DM. Effective control of plasma glucose may ensure the QOL in children with T1DM, and DKA was the risk factor for QOL. Conclusion: In Ningxia, the regulation of plasma glucose in pediatric and adolescent patients with T1DM remains suboptimal, leading to poor QOL. There is a pressing need to enhance glucose regulation and QOL through comprehensive strategies, which include reinforced dietary management, rigorous monitoring of plasma glucose levels, and heightened health education levels.
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Shaping ceramic materials into sophisticated architecture with 3D hierarchical structure is desirable in multiapplication yet remains challenge due to their brittle and stiff nature. Herein, a new method to achieve ceramic architectures with unsupported and large-spanning structure by shaping vat photopolymerization 3D printed hydrogel preceramic skeleton with unique flexible and deformable character is proposed. Specifically, the present photopolymerizable hydrogel preceramic achieves one stone, two birds: the photosensitive polymer matrix coupled with ceramic nanoparticles for the first shaping by vat photopolymerization 3D printing and the secondary plasticity of the 3D printed ceramic body through flexible shape deformation of hydrogel networks. Inorganic binder aluminum dihydrogen phosphate serves as hydrogel dispersion medium to achieve ultralow shrinkage photopolymerization ceramic. Compared with conventional polymer-derived photocuring ceramics, the linear shrinkage of lamina structure is solely 2%, and which of cubic ceramic structure is just 13.3%. More importantly, one 3D printed preceramic is conducted to reshape repeatedly myriad constructions, realizing reusability of intrinsic brittle ceramic, improving manufacturing fault tolerance rate. Finally, a variety of paradigms for ceramic structure applications are proposed toward stereo circuit, biomedicine, and catalytic applications, breaking the limitation of intrinsic brittleness of ceramic in high-precision manufacturing of complex ceramic devices.
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Enhancing the selectivity of alpha2-adrenoceptor (α2A-AR) agonists remains an unresolved issue. Herein, we reported the design of an α2A-AR agonist using the conformation constraint method, beginning with medetomidine. The structure-activity relationship indicated that the 8-substituent of chromane derivatives exerted the most pronounced effect on α2A-AR agonistic activity. Compounds A9 and B9 were identified as the most promising, exhibiting EC50 values of 0.78 and 0.23 nM, respectively. Their selectivity indexes surpassed dexmedetomidine (DMED) by 10-80 fold. In vivo studies demonstrated that both A9 and B9 dose-dependently increased the loss of righting reflex in mice, with ED50 values of 1.54 and 0.138 mg/kg, respectively. Binding mode calculations and mutation studies suggested the indispensability of the hydrogen bond between ASP1283.32 and α2A-AR agonist. In particular, A9 and B9 showed no dual reverse pharmacological effect, a characteristic exhibited by DMED in α2A-AR activation.