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The discovery and utilization of main-group element catalysts that behave similarly to transition metal (TM) complexes have become increasingly active areas of investigation in recent years. Here, we report a series of Lewis acidic bismuth(III) complexes that allow for the catalytic allylic C(sp3)-H functionalization of olefins via an organometallic complexation-assisted deprotonation mechanism to generate products containing new C-C bonds. This heretofore unexplored mode of main-group reactivity was applied to the regioselective functionalization of 1,4-dienes and allylbenzene substrates. Experimental and computational mechanistic studies support the key steps of the proposed catalytic cycle, including the intermediacy of elusive Bi-olefin complexes and allylbismuth species.
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BACKGROUND: Posterior cortical atrophy (PCA) is a rare condition characterized by early-onset and progressive visual impairment. Individuals with PCA have relatively early-onset and progressive dementia, posing certain needs for early detection. Hence, this study aimed to investigate the association of alterations in outer retinal and choroidal structure and microvasculature with PCA neuroimaging and clinical features and the possible effects of apolipoprotein E(APOE) ε4 allele on outer retinal and choroidal alterations in participants with PCA, to detect potential ocular biomarkers for PCA screening. METHODS: This cross-sectional study included PCA and age- and sex-matched healthy control participants from June 2022 to December 2023. All participants with PCA completed a comprehensive neurological evaluation. All participants were recorded baseline information and underwent an ophthalmic evaluation. Quantitative analyses were performed using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). Adaptive optics scanning laser ophthalmoscopy (AO-SLO) was performed in some patients. In participants with PCA, the influence of APOE ε4 on outer retinal and choroidal alterations and the correlation of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA were investigated. RESULTS: A total of 28 participants (53 eyes) with PCA and 56 healthy control participants (112 eyes) were included in the current study. Compared with healthy control participants, participants with PCA had significantly reduced outer retinal thickness (ORT) (p < 0.001), choriocapillaris vessel density (VD) (p = 0.007), choroidal vascular index (CVI) (p = 0.005) and choroidal vascular volume (CVV) (p = 0.003). In participants with PCA, APOE ε4 carriers showed thinner ORT (p = 0.009), and increased choriocapillaris VD (p = 0.004) and CVI (p = 0.004). The PCA neuroimaging features were positively associated with the ORT, CVI and CVV. Furthermore, differential correlations were observed of PCA clinical features with the CRT, CVV and CVI. CONCLUSIONS: Our findings highlighted the association of outer retinal and choroidal alterations with PCA neuroimaging and clinical features in participants with PCA. Noninvasive SS-OCT and SS-OCTA can provide potential biomarkers for the diagnosis and management of PCA, improving awareness of PCA syndrome among ophthalmologists, neurologists, and primary care providers.
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Corioide , Neuroimagem , Tomografia de Coerência Óptica , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos , Corioide/diagnóstico por imagem , Corioide/patologia , Idoso , Neuroimagem/métodos , Atrofia/patologia , Retina/diagnóstico por imagem , Retina/patologia , Apolipoproteína E4/genéticaRESUMO
OBJECTIVE: To explore if oral insulin could delay onset of stage 3 type 1 diabetes (T1D) among patients with stage 1/2 who carry HLA DR4-DQ8 and/or have elevated levels of IA-2 autoantibodies (IA-2As). RESEARCH AND METHODS: Next-generation targeted sequencing technology was used to genotype eight HLA class II genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, and DPB1) in 546 participants in the TrialNet oral insulin preventative trial (TN07). Baseline levels of autoantibodies against insulin (IAA), GAD65 (GADA), and IA-2A were determined prior to treatment assignment. Available clinical and demographic covariables from TN07 were used in this post hoc analysis with the Cox regression model to quantify the preventive efficacy of oral insulin. RESULTS: Oral insulin reduced the frequency of T1D onset among participants with elevated IA-2A levels (HR 0.62; P = 0.012) but had no preventive effect among those with low IA-2A levels (HR 1.03; P = 0.91). High IA-2A levels were positively associated with the HLA DR4-DQ8 haplotype (OR 1.63; P = 6.37 × 10-6) and negatively associated with the HLA DR7-containing DRB1*07:01-DRB4*01:01-DQA1*02:01-DQB1*02:02 extended haplotype (OR 0.49; P = 0.037). Among DR4-DQ8 carriers, oral insulin delayed the progression toward stage 3 T1D onset (HR 0.59; P = 0.027), especially if participants also had high IA-2A level (HR 0.50; P = 0.028). CONCLUSIONS: These results suggest the presence of a T1D endotype characterized by HLA DR4-DQ8 and/or elevated IA-2A levels; for those patients with stage 1/2 disease with such an endotype, oral insulin delays the clinical T1D onset.
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Development of low-cost, efficient, and stable electrocatalysts for oxygen evolution reaction (OER) is the key issue for a large-scale hydrogen production. Recently, in-situ corrosion of stainless steel seems to be a feasible technique to obtain an efficient OER electrode, while a wide variety of corrosive agents often lead to significant difference in catalytic performance. Herein, we synthesized Ni-Fe based nanomaterials with OER activity through a facile one-step hydrothermal etching method of stainless steel mesh, and investigated the influence of three halogen oxyacid salts (KClO3, KBrO3, KIO3) on water oxidation performance. It was found that the reduction product of oxyacid salts has the pitting effect on the stainless steel, which plays an important role in regulating the morphology and composition of the nanomaterials. The KBrO3-derived electrode shows optimal OER performance, giving the small overpotential of 228 and 270 mV at 10 and 100 mA cm-2 respectively, a low Tafel slope of 36.2 mV dec-1, as well as durable stability in the long-time electrolysis. This work builds an internal relationship between the corrosive agents and the OER performance of the as-prepared electrodes, providing promising strategies and research foundations for further improving the OER performance and optimizing the structure of stainless steel electrodes.
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Electrolytes endowed with high oxidation/reduction interfacial stability, fast Li-ion desolvation process and decent ionic conductivity over wide temperature region are known critical for low temperature and fast-charging performance of energy-dense batteries, yet these characteristics are rarely satisfied simultaneously. Here, we report anchored weakly-solvated electrolytes (AWSEs), that are designed by extending the chain length of polyoxymethylene ether electrolyte solvent, can achieve the above merits at moderate salt concentrations. The -O-CH2-O- segment in solvent enables the weak four-membered ring Li+ coordination structure and the increased number of segments can anchor the solvent by Li+ without largely sacrificing the ionic dissociation ability. Therefore, the single salt/single solvent AWSEs enable solvent co-intercalation-free behavior towards graphite (Gr) anode and high oxidation stability towards high-nickel cathode (LiNi0.8Co0.1Mn0.1O2-NCM811), as well as the formation of inorganic rich electrode/electrolyte interphase on both of them due to the anion-rich solvation shells. The capacity retention of Gr||NCM811 Ah-class pouch cell can reach 70.85 % for 1000 cycles at room-temperature and 75.86 % for 400 cycles at -20 °C. This work points out a promising path toward the molecular design of electrolyte solvents for high-energy/power battery systems that are adaptive for extreme conditions.
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BACKGROUND: A new classification system for acetabular fractures has been proposed in recent years, which is called the 3-column classification. However, this system does not provide information regarding quadrilateral plate fractures. To address this issue, we utilized three-dimensional (3D) fracture line mapping and heat map to analyze the link between the 3-column classification and quadrilateral plate fractures. METHODS: We collected CT scan data from 177 patients who had been diagnosed with acetabular fractures. Additionally, we utilized a CT scan of a healthy adult to generate a standard acetabular model. We utilized the collected CT data of the fracture to create a 3D model and subsequently reduced it. We then matched each acetabular fracture model with the standard acetabular model and mapped all of the fracture lines to the standard model. 3D fracture lines and heat maps were created by overlapping all fracture lines. Fracture characteristics were then summarized using these maps. RESULTS: This study analyzed a total of 221 acetabular fractures. The most frequently observed fracture type, based on the three-column classification, was A1.2, which corresponds to fractures of the anterior column. In contrast, the least common type of fracture was A4, which represents fractures of the central wall. It was noted that quadrilateral plate fractures were frequently observed in fractures classified as type B and C according to the three-column classification. CONCLUSIONS: Among the three-column classification, the QLP fractures are commonly observed in type B and C. It is important to carefully identify these fractures during the diagnostic process. Therefore, based on the three-column classification, we have amalgamated quadrilateral plate fractures and formulated a classification program for acetabular fractures.
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Acetábulo , Fraturas Ósseas , Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Humanos , Acetábulo/lesões , Acetábulo/diagnóstico por imagem , Feminino , Masculino , Adulto , Fraturas Ósseas/classificação , Fraturas Ósseas/diagnóstico por imagem , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Idoso , Adulto Jovem , Idoso de 80 Anos ou mais , AdolescenteRESUMO
In the field of digital humanities, color research aims to discover explanations for painting history and color usage habits. However, researchers analyzing color relationships is challenging and time-consuming, as it requires color extraction and a detailed review of many painting images for reference and comparison of color relationships. In our work, we propose ColorNetVis, an interactive color network analysis tool that enables researchers to explore color relationships through color networks. The core of ColorNetVis is a bipartite network model that establishes a bipartite relationship between colors and Chinese painting within a scope based on color difference measurement. It constructs a one-mode color network through projection algorithms and similarity calculation methods to discover the relationship between colors. We propose a coordinated set of views to demonstrate the combination of determined color networks with painting types and real-world attributes. We use color space view, color attribute distribution view, and single color query components to assist researchers in conducting detailed color analysis and validation. Through case studies, researcher reviews, and user studies, we demonstrate that ColorNetVis can effectively help researchers discover knowledge of color relationships and potential color research directions.
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Glycosylation is a valuable tool for modulating protein solubility; however, the lack of reliable research strategies has impeded efficient progress in understanding and applying this modification. This study aimed to bridge this gap by investigating the solubility of a model glycoprotein molecule, the carbohydrate-binding module (CBM), through a two-stage process. In the first stage, an approach involving chemical synthesis, comparative analysis, and molecular dynamics simulations of a library of glycoforms was employed to elucidate the effect of different glycosylation patterns on solubility and the key factors responsible for the effect. In the second stage, a predictive mathematical formula, innovatively harnessing machine learning algorithms, was derived to relate solubility to the identified key factors and accurately predict the solubility of the newly designed glycoforms. Demonstrating feasibility and effectiveness, this two-stage approach offers a valuable strategy for advancing glycosylation research, especially for the discovery of glycoforms with increased solubility.
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Aprendizado de Máquina , Simulação de Dinâmica Molecular , Solubilidade , Glicosilação , Glicoproteínas/químicaRESUMO
Obtaining suitable adsorbents for selective separation of SO2 from flue gas still remains an important issue. A stable Zr(IV)-MOF (Zr-PTBA) can be conveniently synthesized through the self-assembly of a tetracarboxylic acid ligand (H4L = 4,4',4'',4'''-(1,4-phenylenebis(azanetriyl))tetrabenzoic acid) and ZrCl4 in the presence of trace water. It exhibits a three-dimensional porous structure. The BET surface area is 1112.72 m2/g and the average pore size distribution focus on 5.9, 8.0 and 9.3 Å. Interestingly, Zr-PTBA shows selective adsorption of SO2. The maximum uptake reaches 223.21 cm3/g at ambient condition. While it exhibits lower adsorption uptake of CO2 (30.50 cm3/g) and hardly adsorbs O2 (2.57 cm3/g) and N2 (1.31 cm3/g). Higher IAST selectivities of SO2/CO2 (21.9), SO2/N2 (912.7), SO2/O2 (2269.9) and SO2/CH4 (85.0) have been obtained, which reveal its' excellent gas separation performance. Breakthrough experiment further confirms its application for flue gas deep desulfurization both in dry and humid conditions. Furthermore, the gas adsorption results and mechanisms have also been studied by theoretical calculations.
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In recent years, anterior tibiofibular ligament-distal fascicle transfers for anterior talofibular ligament augmentation repair have proposed. However, a comprehensive biomechanical study on the anterior tibiofibular ligament-distal fascicle transfer is still lacking. We are established four distinct groups, namely the normal, the anterior talofibular ligament rupture, the anterior talofibular ligament repair, and the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer. We assessed the anterior drawer test and varus stress test of the ankle in each group. Moreover, we employed the model to simulate and compute the total displacement and von-Mises stress of the talus cartilage at varying gait phases, including foot strike, tibia vertical, and toe-off phases. The results of the anterior drawer test and varus stress test revealed that the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group exhibited greater closeness to the normal group. Regarding von-Mises stress in cartilage, the three gait instants had higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Nevertheless, regarding total displacement, the toe-off phases exhibited higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Using ATiFL-DF transfer to augment ATFL repair is a potential feasible procedure. However, this procedure could potentially compromise the anterior tibiofibular ligament's contribution to the dynamic stability of the ankle. Therefore, we recommend conducting further in-depth research to ensure the suitability and success of this technique in a clinical environment.
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Articulação do Tornozelo , Análise de Elementos Finitos , Instabilidade Articular , Ligamentos Laterais do Tornozelo , Humanos , Ligamentos Laterais do Tornozelo/cirurgia , Instabilidade Articular/cirurgia , Instabilidade Articular/fisiopatologia , Articulação do Tornozelo/cirurgia , Articulação do Tornozelo/fisiopatologia , Fenômenos Biomecânicos , Adulto , Masculino , Doença CrônicaRESUMO
BACKGROUND: Achilles tendon rupture (ATR) is a significant injury that can require surgery and can have the risk of re-rupture even after successful treatment. Consequently, to minimize this risk, it is important to have a thorough understanding of the rehabilitation protocol and the impact of different rehabilitation approaches on preventing re-rupture. MATERIALS AND METHODS: Two independent team members searched several databases (PubMed, EMBASE, Web of Science, Cochrane Library, and CINAHL) to identify randomized controlled trials (RCTs) on operative treatment of ATR. We included articles that covered open or minimally invasive surgery for ATR, with a detailed rehabilitation protocol and reports of re-rupture. The study protocol has been registered at PROSPERO and has been reported in the line with PRISMA Guidelines, Supplemental Digital Content 1, http://links.lww.com/JS9/C85 , Supplemental Digital Content 2, http://links.lww.com/JS9/C86 and assessed using AMSTAR Tool, Supplemental Digital Content 3, http://links.lww.com/JS9/C87 . RESULTS: A total of 43 RCTs were eligible for the meta-analysis, encompassing a combined cohort of 2553 patients. Overall, the postoperative incidence of ATR patients developing re-rupture was 3.15% (95% CI: 2.26-4.17; I2 =44.48%). Early immobilization group patients who had ATR had a 4.07% (95% CI: 1.76-7.27; I2 =51.20%) postoperative incidence of re-rupture; Early immobilization + active range of motion (AROM) group had an incidence of 5.95% (95% CI: 2.91-9.99; I2 =0.00%); Early immobilization + weight-bearing group had an incidence of 3.49% (95% CI: 1.96-5.43; I2 =20.06%); Early weight-bearing + AROM group had an incidence of 3.61% (95% CI: 1.00-7.73; I2 =64.60%); Accelerated rehabilitation (immobilization) group had an incidence of 2.18% (95% CI: 1.11-3.59; I2 =21.56%); Accelerated rehabilitation (non-immobilization) group had a rate of 1.36% (95% CI: 0.12-3.90; I2 =0.00%). Additionally, patients in the immediate AROM group had a postoperative re-rupture incidence of 3.92% (95% CI: 1.76-6.89; I2 =33.24%); Non-immediate AROM group had an incidence of 2.45% (95% CI: 1.25-4.03; I2 =22.09%). CONCLUSIONS: This meta-analysis suggests the use of accelerated rehabilitation intervention in early postoperative rehabilitation of the Achilles tendon. However, for early ankle joint mobilization, it is recommended to apply after one to two weeks of immobilization.
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Tendão do Calcâneo , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismos dos Tendões , Humanos , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Ruptura/cirurgia , Traumatismos dos Tendões/cirurgia , Traumatismos dos Tendões/reabilitação , Incidência , Deambulação Precoce/estatística & dados numéricosRESUMO
OBJECTIVE: The talus is an important component in the ankle, and its treatment after injury is crucial. However, complications and adverse events due to incomplete traditional classifications may still occur, and these classifications fail to analyze the patterns and distribution of fractures from a three-dimensional perspective. Therefore, in this study, we aimed to analyze the location and distribution of fracture lines in different types of talus fractures using three-dimensional (3D) and heat mapping techniques. Additionally, we aimed to determine the surface area of the talus that can be utilized for different approaches of internal fixation, aiding in the planning of surgical procedures. METHODS: We retrospectively analyzed data from CT scans from 126 patients diagnosed with talus fractures at our two hospitals. We extracted the CT data of a healthy adult and created a standard talus model. We performed 3D reconstruction using patients' CT images and superimposed the fracture model onto the standard model for drawing fracture lines. Subsequently, we converted the fracture lines into a heat map for visualization. Additionally, we measured 20 specimens to determine the boundary for various ligaments attached to the talus. We determined the surface area of the talus available for different surgical approaches by integrating the boundary data with previously reported data on area of exposure. RESULTS: Without considering the displacement distance of the fracture, fracture types were classified as follows, by combining Hawkins and Sneppen classifications: talar neck, 41.3%; posterior talar tubercle, 22.2%; body for the talus and comminuted, 17.5%; lateral talar tubercle, 11.9%; and talar head, 7.1%. We established fracture line and heat maps using this classification. Additionally, we demonstrated the available area for anteromedial, anterolateral, posteromedial, posterolateral, and medial malleolus osteotomy and Chaput osteotomy approaches. CONCLUSION: Fracture line and heat map analyses can aid surgeons in planning a single or combined surgical approach for the reduction and internal fixation of talus fractures. Demonstrating the different surgical approaches can help surgeons choose the most effective technique for individual cases.
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Fixação Interna de Fraturas , Fraturas Ósseas , Imageamento Tridimensional , Tálus , Tomografia Computadorizada por Raios X , Humanos , Tálus/lesões , Tálus/cirurgia , Tálus/diagnóstico por imagem , Estudos Retrospectivos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/classificação , Idoso , Adulto Jovem , Adolescente , Fraturas do Tornozelo/cirurgia , Fraturas do Tornozelo/diagnóstico por imagemRESUMO
OBJECTIVE: To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed. Together with available clinical covariables, we applied the Cox regression model to assess HLAII immunogenic associations with the disease progression. RESULTS: First, the current investigation updated the previously reported genetic associations of DQA1*03:01-DQB1*03:02 (hazard ratio [HR] = 1.25, P = 3.50*10-3) and DQA1*03:03-DQB1*03:01 (HR = 0.56, P = 1.16*10-3), and also uncovered a risk association with DQA1*05:01-DQB1*02:01 (HR = 1.19, P = 0.041). Second, after adjusting for DQ, DPA1*02:01-DPB1*11:01 and DPA1*01:03-DPB1*03:01 were found to have opposite associations with progression (HR = 1.98 and 0.70, P = 0.021 and 6.16*10-3, respectively). Third, DRB1*03:01-DRB3*01:01 and DRB1*03:01-DRB3*02:02, sharing the DRB1*03:01, had opposite associations (HR = 0.73 and 1.44, P = 0.04 and 0.019, respectively), indicating a role of DRB3. Meanwhile, DRB1*12:01-DRB3*02:02 and DRB1*01:03 alone were found to associate with progression (HR = 2.6 and 2.32, P = 0.018 and 0.039, respectively). Fourth, through enumerating all heterodimers, it was found that both DQ and DP could exhibit associations with disease progression. CONCLUSIONS: These results suggest that HLAII polymorphisms influence progression from islet autoimmunity to T1D among at-risk subjects with islet autoantibodies.
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Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/prevenção & controle , Soroconversão , Genótipo , Haplótipos , Progressão da Doença , Cadeias HLA-DRB1/genética , Cadeias beta de HLA-DQ/genética , Alelos , Frequência do GeneRESUMO
Background: The transfer of the anterior tibiofibular ligament distal fascicle (ATiFL-DF) for the augmentation repair of the anterior talofibular ligament (ATFL) shows potential as a surgical technique. However, evidences on the benefits and disadvantages of this method in relation to ankle joint function are lacking. Purpose: This study aimed to provide comprehensive experimental data to validate the feasibility of ATiFL-DF transfer augmentation repair of the ATFL. Methods: This study included 50 embalmed ankle specimens to measure various morphological features, such as length, width, thickness, and angle, for evaluating similarities between the ATiFL-DF and ATFL. Furthermore, 24 fresh-frozen ankle specimens were examined for biomechanical testing of the ATiFL-DF transfer augmented repair of the ATFL. Finally, 12 pairs of ATiFL-DF and ATFL tissues from fresh-frozen ankle specimens were treated with gold chloride staining to analyze mechanoreceptor densities. Results: Anatomical studies found that the lengths and thicknesses of the ATFL and ATiFL-DF are similar. Biomechanical outcomes showed that performing ATiFL-DF transfer for ATFL repair can improve the stability of the talus and ankle joints. This is evident from the results of the anterior drawer, axial load, and ultimate failure load tests. However, performing ATiFL-DF transfer may compromise the stability of the distal tibiofibular joint, based on the Cotton and axial load tests at an external rotation of 5°. Analysis of the histological findings revealed that mechanoreceptor densities for four types of mechanoreceptors were comparable between the ATiFL-DF and ATFL groups. Conclusion: ATiFL-DF transfer is a viable method for augmenting ATFL repair. This technique helps to improve the stability of the talus and ankle joints while compensating for proprioception loss. Although ATiFL-DF transfer augmented repair of the ATFL may negatively affect the stability of the distal tibiofibular joint, this procedure can enhance the stability of the talus and ankle joints.
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8:2 polyfluoroalkyl phosphate diester (8:2 diPAP) has been shown to accumulate in the liver, but whether it induces hepatotoxicity and lipid metabolism disorders remains largely unknown. In this study, zebrafish embryos were exposed to 8:2 diPAP for 7 d. Hepatocellular hypertrophy and karyolysis were noted after exposure to 0.5 ng/L 8:2 diPAP, suggesting suppressed liver development. Compared to the water control, 8:2 diPAP led to significantly higher triglyceride and total cholesterol levels, but markedly lower levels of low-density lipoprotein, implying disturbed lipid homeostasis. The levels of two peroxisome proliferator activated receptor (PPAR) subtypes (pparα and pparγ) involved in hepatotoxicity and lipid metabolism were significantly upregulated by 8:2 diPAP, consistent with their overexpression as determined by immunohistochemistry. In silico results showed that 8:2 diPAP formed hydrogen bonds with PPARα and PPARγ. Among seven machine learning models, Adaptive Boosting performed the best in predicting the binding affinities of PPARα and PPARγ on the test set. The predicted binding affinity of 8:2 diPAP to PPARα (7.12) was higher than that to PPARγ (6.97) by Adaptive Boosting, which matched well with the experimental results. Our results revealed PPAR - mediated adverse effects of 8:2 diPAP on the liver and lipid metabolism of zebrafish larvae.
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Doença Hepática Induzida por Substâncias e Drogas , Fluorocarbonos , Transtornos do Metabolismo dos Lipídeos , Animais , Peixe-Zebra , Fosfatos , Metabolismo dos Lipídeos , PPAR alfa , PPAR gamaRESUMO
PARP1 is one of six enzymes required for the highly error-prone DNA repair pathway microhomology-mediated end joining (MMEJ) and needs to be inhibited when over-expressed. In order to study the PARP1 inhibitory effect of fused tetracyclic or pentacyclic dihydrodiazepinoindolone derivatives (FTPDDs) by quantitative structure-activity relationship technique, six models were established by four kinds of methods, heuristic method, gene expression programming, random forester, and support vector regression with single, double, and triple kernel function respectively. The single, double, and triple kernel functions were RBF kernel function, the integration of RBF and polynomial kernel functions, and the integration of RBF, polynomial, and linear kernel functions respectively. The problem of multi-parameter optimization introduced in the support vector regression model was solved by the particle swarm optimization algorithm. Among the models, the model established by support vector regression with triple kernel function, in which the optimal R 2 and RMSE of training set and test set were 0.9353, 0.9348 and 0.0157, 0.0288, and R2 cv of training set and test set were 0.9090 and 0.8971, shows the strongest prediction ability and robustness. The method of support vector regression with triple kernel function is a great promotion in the field of quantitative structure-activity relationship, which will contribute a lot to designing and screening new drug molecules. The information contained in the model can provide important factors that guide drug design. Based on these factors, six new FTPDDs have been designed. Using molecular docking experiments to determine the properties of new derivatives, the new drug was ultimately successfully designed.
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Adenocarcinoma , Encefalite , Masculino , Humanos , Autoimunidade , Dopamina , Próstata , Adenocarcinoma/complicaçõesRESUMO
The design of surface ligands is crucial for ligand-protected gold nanoparticles (AuNPs). Herein, following the principle of green synthesis, environmentally friendly gold nanoparticles (AuNPs@His@CC, AuHC) were fabricated based on dual ligands of histidine and carboxylated chitosan. AuHC showed the advantages of low toxicity, good photoluminescent stability and ideal biocompatibility. Compared with single histidine-coated gold nanoclusters (AuNCs@His, AuH), AuHC presented enhanced fluorescence attributed to the addition of chitosan. The blue-emitting AuHC has a unique response to Fe3+ with detection limits as low as 9.51 nM. Interestingly, the quenched fluorescence of AuHC-Fe3+ system could be restored through the introduction of PPi with a detection limit of 10.6 µM. So an "on-off-on" fluorescence sensing platform was achieved. Apart from good optical properties and sensing, the designed AuHC demonstrated outstanding photothermal conversion efficiency (27.8 %), which made it ideal material for thermal ablation of tumor. To be specific, after laser irradiation (660 nm, 0.78 W cm-2, 10 min) of AuHC, the survival rate of HeLa cells as a tumor cell model decreased to 12.7 %, indicating that AuHC has a significant tumor inhibition effect in vitro. Besides, AuHC also could be a befitting candidate for overcoming drug-resistant tumor cells such as MCF-7/ADR cells. Notably, AuHC can markedly ablate solid tumors in 4T1 tumor-bearing mice after laser irradiation (660 nm, 0.78 W cm-2, 10 min). Hence this work provides insight into the design of multifunctional AuNPs platform for simultaneously integrating the ion sensing and photothermal therapy of cancer.
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Quitosana , Nanopartículas Metálicas , Humanos , Animais , Camundongos , Terapia Fototérmica , Ouro , Fluorescência , Células HeLa , HistidinaRESUMO
Layered oxides represent a prominent class of cathodes employed in lithium-ion batteries. The structural degradation of layered cathodes causes capacity decay during cycling, which is generally induced by anisotropic lattice strain in the bulk of cathode particle and oxygen release at the surface. However, particularly in lithium-rich layered oxides (LLOs) that undergo intense oxygen redox reactions, the challenge of simultaneously addressing bulk and surface issues through a singular modification technique remains arduous. Here a thin (1-nm) and coherent spinel-like phase is constructed on the surface of LLOs particle to suppress bulk strain and surface O2 release by just adjusting the amount of lithium source during synthesis. The spinel-like phase hinders the surface O2 release by accommodating O2 inside the surface layer, while the trapped O2 in the bulk impedes strain evolution by ≈70% at high voltages compared with unmodified LLOs. Consequently, the enhanced structural stability leads to an improved capacity retention of 97.6% and a high Coulombic efficiency of ≈99.5% after 100 cycles at 0.1°C. These findings provide profound mechanistic insights into the functioning of surface structure and offer guidance for synthesizing high-capacity cathodes with superior cyclability.
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Background: Florbetapir positron emission tomography (AV45 PET) is a widely employed modality for detecting cerebral amyloid-ß (Aß) deposition. However, in clinical settings, patients with cognitive impairment are frequently unable to sustain adequate stillness during the scanning procedure. Therefore, we aimed to investigate the effects of a short acquisition time on the image quality and Aß detectability of AV45 PET. Methods: In this cross-sectional study, 29 patients with Alzheimer's disease (AD) and 13 healthy participants underwent 15-minute AV45 PET/magnetic resonance imaging scanning. The PET data were subsequently reconstructed into 15-, 10-, 8-, 6-, 4-, 2-, and 1-minute duration groups (G15, G10, G8, G6, G4, G2, and G1). Subjective PET image quality was scored based on a 5-point Likert scale (poor-excellent: 1-5), and objective image quality was evaluated by the signal-to-noise ratio (SNR) of the 1 cm3 region of interest (ROI) inside the cerebellum. Aß detectability was assessed by the calculation of regional standardized uptake value ratio (SUVR) values in all groups. The Kruskal-Wallis rank sum test and paired t-test were performed to compare the subjective scores, SNR, and SUVR values. The visual inspection was also performed by 2 nuclear physicians to give a binary diagnosis to each case. Results: The subjective scores were decreased in the groups with shortened scanning time relative to the G15 group (4.67±0.48, all P<0.05). Notably, a good image quality score was also given to the G10 group (4.40±0.63), and sufficient image quality could be achieved with the G8 (3.86±0.68) and G6 (3.14±0.52) groups. The SNR values were decreased by 10.33%, 17.74%, and 23.26% in the G10, G8, and G6 group, respectively (all P<0.05). Compared with the G15 group (1.48±0.16), the composite SUVR values were increased in the G10 (1.50±0.16), G8 (1.50±0.17), and G6 groups (1.51±0.18, all P<0.05). By visual inspection, the diagnoses of each case in the G10, G8, and G6 group were identical with those in the G15 group. Conclusions: The acquisition time of AV45 PET is required to reach at least 6 minutes to achieve acceptable image quality and maintained Aß detectability.