Electronic coupling is important in determining charge-transfer rates and dynamics. Coupling strength is sensitive to both intermolecular, e.g., orientation or distance, and intramolecular degrees of ...freedom. Hence, it is challenging to build an accurate machine learning model to predict electronic coupling of molecular pairs, especially for those derived from the amorphous phase, for which intermolecular configurations are much more diverse than those derived from crystals. In this work, we devise a new prediction algorithm that employs two consecutive KRR models. The first model predicts molecular orbitals (MOs) from structural variation for each fragment, and coupling is further predicted by using the overlap integral included in a second model. With our two-step procedure, we achieved mean absolute errors of 0.27 meV for an ethylene dimer and 1.99 meV for a naphthalene pair, much improved accuracy amounting to 14-fold and 3-fold error reductions, respectively. In addition, MOs from the first model can also be the starting point to obtain other quantum chemical properties from atomistic structures. This approach is also compatible with a MO predictor with sufficient accuracy.
Given the importance and beneficial characteristics of decorated azetidines in medicinal chemistry, efficient strategies for their synthesis are highly sought after. Herein, we report a facile ...synthesis of the elusive all-carbon quaternary-center-bearing azetidines. By adopting a well-orchestrated polar-radical relay strategy, ring strain release of bench-stable benzoylated 1-azabicyclo1.1.0butane (ABB) can be harnessed for nickel-catalyzed Suzuki Csp2–Csp3 cross-coupling with commercially available boronic acids in broad scope (>50 examples), excellent functional group tolerance, and gram-scale utility. Preliminary mechanistic studies provided insights into the underlying mechanism, wherein the ring opening of ABB with a catalytic quantity of bromide accounts for the conversion of ABB into a redox-active azetidine, which subsequently engages in the cross-coupling reaction through a radical pathway. The synergistic bromide and nickel catalysis could intriguingly be derived from a single nickel source (NiBr2). Application of the method to modify natural products, biologically relevant molecules, and pharmaceuticals has been successfully achieved as well as the synthesis of melanocortin-1 receptor (MC-1R) agonist and vesicular acetylcholine transporter (VAChT) inhibitor analogues through bioisosteric replacements of piperidine with azetidine moieties, highlighting the potential of the method in drug optimization studies. Aside from the synthesis of azetidines, we demonstrate the ancillary utility of our nickel catalytic system toward the restricted Suzuki cross-coupling of tertiary alkyl bromides with aryl boronic acids to construct all-carbon quaternary centers.
Introduction and hypothesis
Interstitial cystitis/bladder pain syndrome (IC/BPS) and irritable bowel syndrome (IBS) often occur concomitantly without an obvious reason. It is important to determine ...the relationship between these related diseases. We aimed to determine whether IBS increase the risk of IC/BPS.
Methods
We identified newly diagnosed IBS patients between 2002 and 2013 from a nationwide database as the IBS cohort. Subjects diagnosed with IC/BPS before IBS were excluded. Cox’s regression analysis with a hazard ratio (HR) of IC/BPS between IBS and the non-IBS cohort was applied to unmatched and matched (16 confounders of propensity scores) models. The time from diagnosis of IBS to IC/BPS was also calculated.
Results
In the unmatched group, which included 100,124 IBS (55% female) and 874,048 non-IBS patients, the IC/BPS adjusted HR was 1.292 (95% confidence interval CI, 1.131–1.476;
p
< 0.0001) in the IBS cohort compared with the non-IBS cohort. In the matched group, there were 85,359 patients in each cohort, and the IC/BPS HR was 1.599 (95% CI, 1.344–1.903;
p
< 0.0001). The average numbers of years until the development of IC/BPS in the IBS cohort and non-IBS cohort were 4.60 ± 2.58 (
n
= 253) and 5.99 ± 3.49 (
n
= 295) years, respectively.
Conclusions
IBS was shown to increase the risk of IC/BPS in this 12-year cohort study. The time from the diagnosis of IBS to IC/BPS was 5.35 ± 3.18 years. A common pathophysiology of IBS and IC/BPS is possible. Clinicians should be mindful of the association and promote collaborative care of these two elusive diseases.
Recurrent obscure gastrointestinal bleeding (OGIB) in patients with chronic kidney disease is a challenge often faced by physicians, given the need for repeated hospitalizations, multiple extensive ...examinations, limited treatment options, and high medical costs. The purpose of this study was to identify the clinical characteristics of uremic patients undergoing deep enteroscopy for OGIB and analyze the risk factors for rebleeding in these patients after undergoing single-balloon enteroscopy (SBE).
Out of 765 patients with OGIB who underwent 1004 procedures of SBE in four teaching hospitals, 78 uremic patients with OGIB were enrolled. Clinical characteristics and endoscopic findings were collected, and multiple variables were analyzed to determine the risk of rebleeding after SBE.
The diagnostic yield was 75.6%, and the rebleeding rate was 29.5% in the enrolled uremic patients. The most common etiology was angiodysplasia (74.6%) and the most common site was the jejunum (50.8%). The endoscopic intervention rate was 62.8% and most patients were treated with argon plasma coagulation (75.6%). Among the eight patients with valvular heart disease (VHD), four (50%) had severe aortic stenosis, and the remaining had non-aortic stenosis-VHD. VHD (p < 0.05) and angiodysplasia (p < 0.05) were both associated with a higher rebleeding rate.
VHD may be an independent risk factor associated with rebleeding after SBE in uremic patients with OGIB. Moreover, uremic patients with angiodysplasia-related bleeding appear to have a higher rebleeding rate than those with alternative causes of bleeding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Regulatory B cells (Bregs) are a B cell subset that plays a suppressive role in immune responses. The CD19
CD1d
CD5
Bregs that can execute regulatory functions via secreting IL-10 are defined as B10 ...cells. Bregs suppress autoimmune and inflammatory diseases, whereas they exacerbate infectious diseases caused by bacteria, viruses, or parasites. Notably, the molecular mechanisms regulating the development and functions of Bregs are still largely unknown. Furthermore, the biological impact of Bregs in fungal infection has not yet been demonstrated. Here, we compared the gene expression profiles of IL-10-producing and -non-producing mouse splenic B cells stimulated with lipopolysaccharide (LPS) or anti-CD40 antibody. Blimp-1, a transcription factor known to be critical for plasma cell differentiation, was found to be enriched in the IL-10-producing B cells. The frequency of Blimp-1
B10 cells was increased in LPS-treated mice and in isolated B10 cells that were stimulated with LPS. Surprisingly, B cell-specific Blimp-1 knockout (Cko) mice, generated by CD19 promoter driven Cre recombinase-dependent deletion of
(gene encoding Blimp-1), showed higher frequencies of B10 cells both in the steady state and following injection with LPS, as compared with control littermates. However, B10 cells lacking Blimp-1 failed to efficiently suppress the proliferation of naïve CD4
T cells primed with anti-CD3 and anti-CD28 antibodies. B10 cells can be stimulated for further differentiation into plasmablasts, and a subset of plasmablasts express IL-10. We found that B10 cells from Cko mice failed to generate both IL-10-non-producing and IL-10-producing plasmablasts. Mechanistically, we found that Blimp-1 can directly suppress
, whereas, in the presence of activated STAT3, Blimp-1 works together with activated STAT3 to upregulate
. Moreover, we also found that B10 cells improve the clearance of
infection but worsen the infection mortality. Notably, a lack of Blimp-1 in B10 cells did not change these effects of adoptively transferred B10 cells on fungal infections. Together, our data show that Blimp-1 regulates the generation, differentiation, and IL-10 production of Bregs.
We aimed to investigate the effect of a mental health website intervention on perceived stress, depression, sleep quality, and social support in women with recurrent miscarriage (RM). Performing a ...randomized controlled trial, the participants in the experimental group (n = 31) received a 12-week mental health website intervention; the participants in the control group (n = 31) received RM standard medical care only. The paired t-tests results for the mean posttest scores for depression (p = .023) and perceived stress (p = .041) in the experimental group showed a significant decrease, but did not in the control group.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Terminally differentiated B cell, the plasma cell, is the sole cell type capable of producing antibodies in our body. Over the past 30 years, the identification of many key molecules controlling B ...cell activation and differentiation has elucidated the molecular pathways for generating antibody-producing plasma cells. Several types of regulation modulating the functions of the important key molecules in B cell activation and differentiation add other layers of complexity in shaping B cell responses following antigen exposure in the absence or presence of T cell help. Further understanding of the mechanisms contributing to the proper activation and differentiation of B cells into antibody-secreting plasma cells may enable us to develop new strategies for managing antibody humoral responses during health and disease. Herein, we reviewed the effect of different types of regulation, including transcriptional regulation, post-transcriptional regulation and epigenetic regulation, on B cell activation, and on mounting memory B cell and antibody responses. We also discussed the link between the dysregulation of the abovementioned regulatory mechanisms and B cell-related disorders.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Mineral trioxide aggregate (MTA) is the most frequently used repair material in endodontics, but the long setting time and reduced mechanical strength in acidic environments are major shortcomings. ...In this study, a novel sol-gel-derived calcium silicate cement (sCSC) was developed using an initial Ca/Si molar ratio of 3, with the most effective mixing orders of reactants and optimal HNO
catalyst volumes. A Fourier transform infrared spectrometer, scanning electron microscope with energy-dispersive X-ray spectroscopy, and X-ray powder diffractometer were used for material characterization. The setting time, compressive strength, and microhardness of sCSC after hydration in neutral and pH 5 environments were compared with that of MTA. Results showed that sCSC demonstrated porous microstructures with a setting time of ~30 min, and the major components of sCSC were tricalcium silicate, dicalcium silicate, and calcium oxide. The optimal formula of sCSC was sn200, which exhibited significantly higher compressive strength and microhardness than MTA, irrespective of neutral or pH 5 environments. In addition, both sn200 and MTA demonstrated good biocompatibility because cell viability was similar to that of the control. These findings suggest that sn200 merits further clinical study for potential application in endodontic repair of perforations.
The purpose of this work is to explore the international humanitarian relief organizations in Taiwan, and find the most crucial performance indicators of humanitarian logistics, according to the ...experience and opinion of those large NGOs in Taiwan. The research gathered detailed information on situations from literature and collected the data by questionnaire. Based on the information gathered from questionnaires, quantitative weight was calculated through the participation of experts by using AHP in this research. According to the humanitarian relief organizations' experiences and opinion in this research, the most critical performance indicators in humanitarian relief logistics is responsiveness, and the following is agility, reliability, cost, and dialog with authorities. Although the AHP method has been applied in many research of performance indicators chosen, there is no research using AHP to prioritize the performance indicators in the humanitarian logistics field, especially in Taiwan. Future research could include the smaller or reputable organizations in Taiwan to get more comprehensive opinions. Besides, the chosen indicators could be utilized in the actual case of humanitarian rescue action.
Herein we report ketones as feedstock materials in radical cross-coupling reactions under Ni/photoredox dual catalysis. In this approach, simple condensation first converts ketones into prearomatic ...intermediates that then act as activated radical sources for cross-coupling with aryl halides. Our strategy enables the direct benzylation/benzoylation of (hetero)arenes under mild reaction conditions with high functional group tolerance.
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