We report the control of guest release profiles by dialing-in desirable interactions between guest molecules and pores in metal–organic frameworks (MOFs). The interactions can be derived by the rate ...constants that were quantitatively correlated with the type of functional group and its proportion in the porous structure; thus the release of guest molecules can be predicted and programmed. Specifically, three probe molecules (ibuprofen, rhodamine B, and doxorubicin) were studied in a series of robust and mesoporous MOFs with multiple functional groups MIL-101(Fe)-(NH2) x , MIL-101(Fe)-(C4H4) x , and MIL-101(Fe)-(C4H4) x (NH2)1–x . The release rate can be adjusted by 32-fold rhodamine from MIL-101(Fe)-(NH2) x , and the time of release peak can be shifted by up to 12 days over a 40-day release period doxorubicin from MIL-101(Fe)-(C4H4) x (NH2)1–x , which was not obtained in the physical mixture of the single component MOF counterparts nor in other porous materials. The corelease of two pro-drug molecules (ibuprofen and doxorubicin) was also achieved.
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IJS, KILJ, NUK, PNG, UL, UM
Covalent organic frameworks (COFs) with amine linkage in both three and two dimensions, COF-300-AR and COF-366-M-AR, were synthesized by direct reduction of their corresponding COFs with imine ...linkage, COF-300 and COF-366-M, respectively. The quantitative reduction was confirmed by Fourier transform infrared and cross-polarization magic angle spinning NMR (both 13C and 15N) spectroscopy. These amine COFs were highly crystalline and exhibited excellent chemical stability in strong acids and bases. The abundant amino groups in the COF-300-AR backbone facilitated the electrochemical reduction of CO2 on silver electrodes in a concerted manner and led to selective generation of CO. Specifically, CO conversion efficiency was raised from 13% to 53% at −0.70 V and from 43% to 80% at −0.85 V (versus a reversible hydrogen electrode) in comparison with that of a bare silver electrode. The porosity of COFs favored molecular diffusion to the electrode surface, and the amine functional groups close to the electrode surface promoted CO2 conversion efficiency by forming carbamate intermediates.
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•Synthesis of amine-linked COFs in both 2D and 3D forms•Stability in both strong acid and base•Construction of molecularly defined interface•Electrochemical reduction of CO2 with high efficiency and selectivity
By extending covalent bonds to two-dimensional (2D) and three-dimensional (3D) frameworks, the emergence of covalent organic frameworks (COFs) represents a new and exciting branch in porous and crystalline materials. Currently, the discovery of new linkages and improvement of chemical stability are the two most pressing challenges for the development of COFs. We report the synthesis of an amine-linked COFs in both 2D and 3D forms. These COFs exhibited excellent stability in strong acid and base. Furthermore, by depositing COF-300-AR on a flat silver electrode, we were able to construct a molecularly defined interface for electrochemical reduction of CO2 to CO with high efficiency and selectivity. Spectroscopic studies revealed that the concerted behavior between COFs and the silver electrode at their interface was responsible for the promoted performance. This molecularly defined interface approach improves the selectivity of the electrochemical reaction without sacrificing the overall efficiency.
Amine-linked covalent organic frameworks (COFs) were synthesized by the reduction of parent imine-linked COFs by crystal-to-crystal transformation. The excellent chemical stability of these COFs in combination with the presence of a large amount of amine functional groups led to a robust and molecularly defined interface at the silver metal surface as an electrode for the electrochemical reduction of CO2. The concerted operation of COF and the metal surface resulted in high conversion efficiency and excellent selectivity against the reduction of water.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Non-alcoholic fatty liver disease and its related complications are becoming one of the most important health problems globally. The liver functions as both a metabolic and an immune organ. The ...crosstalk between hepatocytes and intrahepatic immune cells plays a key role in coordinating a dual function of the liver in terms of the protection of the host from antigenic overload as a result of receiving nutrients and gut microbiota antigenic stimulation via facilitating immunologic tolerance. B cells are the most abundant lymphocytes in the liver. The crucial role of intrahepatic B cells in energy metabolism under different immune conditions is now emerging in the literature. The accumulating evidence has demonstrated that the antibodies and cytokines produced by B cells in the microenvironment play key and distinct roles in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Herein, we have aimed to consolidate and update the current knowledge about the pathophysiological roles of B cells as well as the underlying mechanisms in energy metabolism. Understanding how B cells can exacerbate and suppress liver damage by exploiting the antibodies and cytokines they produce will be of great importance for designing B-cell targeting therapies to treat various liver diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Cross allocation-based consensus mechanism is introduced.•An optimal model-based judgment penalty for non-cooperative DMs is proposed.•The uniqueness of consensus allocation and judgment adjustment ...can be ensured.•Comparison analysis and experimental simulation are done.
Consensus adjustment is crucial in group decision making (GDM), aiming to reduce discrepancies in decision makers’ (DMs’) judgments for final decision results. The consensus adjustments made by DMs are interactive rather than independent. However, few studies investigate the consensus adjustment problem from the perspective of interactions among DMs. This study first constructs a model to determine the total minimum consensus adjustment under the requirements of consensus threshold and individual-collective judgment bias. Then, a consensus adjustment approach based on cross-allocation scheme is proposed to address the inconsistency between individual and collective minimum adjustments, which concerns all DMs’ individual favorable allocation results under the total minimum consensus adjustment. The cross-allocation scheme ensures unanimous support for the same allocation result among all rational DMs, thereby eliminating the discrepancies among them. Subsequently, the optimization model-based minimum consensus judgment penalty is formulated to handle the non-cooperative behaviors of DMs. Furthermore, we show how to determine the unique consensus adjustment result for the non-cooperative DMs using the cross-allocation scheme. Therefore, our study contributes by developing a new GDM method that conducts consensus adjustment allocation by considering interactions among DMs. Finally, a case study is employed to demonstrate the specific application of the new method and discuss its efficiency. Meanwhile, comparison analysis and simulation experiments are provided.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Combination therapy with pegylated interferon (PEG‐IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the ...patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add‐on PEG‐IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real‐world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)‐negative NAs‐treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add‐on PEG‐IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south‐central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml 2.405 and >1.0 log10 IU/ml 7.370); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
•LPS was injected intraperitoneally into rats at PND14.•Expression of LRP3 inflammasome proteins elevated in LPS-treated adolescent.•The aberrant expression occurred in neurons and ...microglia.•LPS-treated rats exhibited anxiety-like behavior.
Neonatal inflammation may affect brain development and lead to cognitive and emotional deficits at adolescence and adulthood. The nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) is the core component of NLRP3 inflammasome, which may involve in neuroinflammation. We explored if early-life exposure to the bacterial endotoxin lipopolysaccharide (LPS) could promote the expression of proteins related to NLRP3 inflammasome, including NLRP3, the apoptosis-associated speck-like protein (ASC) and cysteiny aspartate-specific protease (Caspase-1) in the forebrain, and behavioral alteration in adolescent rats.
Two-week old Sprague Dawley rats were divided into naïve control, vehicle (phosphate buffered saline, PBS) control and LPS (100μg/kg, i.p.) treatment groups. Anxiety and depression-like behaviors were examined around 1month age, with the expression of NLRP3, ASC and Caspase-1 in the prefrontal cortex (PFC) and hippocampus analyzed by means of immunohistochemistry and western blot.
LPS-treated rats exhibited anxiety but not depressive-like behavior as indicated by results of open field, elevated plus maze, dark-light box, sucrose preference and forced swimming tests. Increased immunolabeling of NLRP3, ASC and Caspase-1 in neurons and/or microglia occurred in the PFC and hippocampus in LPS-treated adolescents relative to controls, with immunoblot shown elevated levels of these proteins.
Early-life inflammatory stress promotes the expression of NLRP3 inflammasome proteins in the brain and the occurrence of anxiety-like behavior in adolescent rats.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This report summarizes the clinical characteristics of intractable anemia as part of the clinical presentation of Hirschsprung's disease (HD) and aims to strengthen clinicians' ability to recognize ...early signs of HD.
An 11-year-old boy with a 6-year history of intractable anemia, low hemoglobin level (55 g/L), poor response to oral iron supplementation and blood transfusion, and difficulty with defecation was diagnosed with HD. A 19-month-old boy with a 3-month history of intractable anemia, low hemoglobin level (64 g/L), poor response to oral iron supplementation and blood transfusion, delayed meconium passage, and history of intestinal obstruction was also diagnosed with HD. Both patients underwent surgery, after which anemia was corrected effectively in both cases. Two more cases of intractable anemia as the chief complaint and diagnoses of HD over different durations since the onset of anemia (ranging from 1.7 years to 21 years) were identified in a literature search. Both patients underwent surgery, after which anemia was corrected.
Intractable anemia as part of the clinical presentation of HD is extremely rare. Detailed inquiries of medical histories and physical examinations are key to early diagnoses and preventing misdiagnoses. Anemia in HD patients may primarily be caused by impaired iron absorption due to HD.
Understanding of the RNA editing process has been broadened considerably by the next generation sequencing technology; however, several issues regarding this regulatory step remain unresolved--the ...strategies to accurately delineate the editome, the mechanism by which its profile is maintained, and its evolutionary and functional relevance. Here we report an accurate and quantitative profile of the RNA editome for rhesus macaque, a close relative of human. By combining genome and transcriptome sequencing of multiple tissues from the same animal, we identified 31,250 editing sites, of which 99.8% are A-to-G transitions. We verified 96.6% of editing sites in coding regions and 97.5% of randomly selected sites in non-coding regions, as well as the corresponding levels of editing by multiple independent means, demonstrating the feasibility of our experimental paradigm. Several lines of evidence supported the notion that the adenosine deamination is associated with the macaque editome--A-to-G editing sites were flanked by sequences with the attributes of ADAR substrates, and both the sequence context and the expression profile of ADARs are relevant factors in determining the quantitative variance of RNA editing across different sites and tissue types. In support of the functional relevance of some of these editing sites, substitution valley of decreased divergence was detected around the editing site, suggesting the evolutionary constraint in maintaining some of these editing substrates with their double-stranded structure. These findings thus complement the "continuous probing" model that postulates tinkering-based origination of a small proportion of functional editing sites. In conclusion, the macaque editome reported here highlights RNA editing as a widespread functional regulation in primate evolution, and provides an informative framework for further understanding RNA editing in human.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fluorescent protein (FP)-based genetically encoded indicators are valuable tools for reporting signaling activities with high spatial-temporal resolution in living cells and animal models. Thereinto, ...single circularly permuted FP-based intensity sensors (cpFP sensors or cpFP-based sensors, unless otherwise specified) are of particular interest due to their unprecedented high sensitivity and fast kinetics. In this review, we summarized the recent progress with cpFP sensors, focusing on the practical considerations in sensor development and usage, and categorization of cpFP sensors. We also discuss future directions in improvement of existing sensors, development of new sensors, and functional super-resolution imaging with cpFP sensors.
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Near-infrared probes including dyes, nanoparticles and proteins have been particularly useful for in vivo imaging because of their ability to penetrate tissue deeper with minimal ...scattering and autofluorescence, opening the door to study cell biology in physiological conditions.
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Taking the advantage of reduced scattering and low autofluorescence background, the NIR fluorescence probes, such as fluorescence proteins, organic molecules and nanoparticles, not only hold the promise of in vivo imaging of biological processes in physiology and pathology with high signal-to-noise ratio, but also for clinical diagnosis. In this review, we provide an overview of the recent progress on NIR probes, focusing on fundamental mechanisms of NIR dyes and nanoparticles, and protein engineering strategies for NIR proteins.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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