Allergic asthma is a highly prevalent airway inflammatory disease, which involves the interaction between the immune system, environmental and genetic factors. Co-relation between allergic asthma and ...gut microbiota upon the change of diet have been widely reported, implicating that oral intake of alternative medicines possess a potential in the management of allergic asthma. Previous clinical, in vivo, and in vitro studies have shown that the Pentaherbs formula (PHF) comprising five traditional Chinese herbal medicines Lonicerae Flos, Menthae Herba, Phellodendri Cortex, Moutan Cortex, and Atractylodis Rhizoma possesses an anti-allergic and anti-inflammatory potential through suppressing various immune effector cells. In the present study, to further investigate the anti-inflammatory activities of PHF in allergic asthma, intragastrical administration of PHF was found to reduce airway hyperresponsiveness, airway wall remodeling and goblet cells hyperplasia in an ovalbumin (OVA)-induced allergic asthma mice model. PHF also significantly suppressed pulmonary eosinophilia and asthma-related cytokines IL-4 and IL-33 in bronchoalveolar lavage (BAL) fluid. In addition, PHF modulated the splenic regulatory T cells population, up-regulated regulatory interleukin (IL)-10 in serum, altered the microbial community structure and the short chain fatty acids content in the gut of the asthmatic mice. This study sheds light on the anti-inflammatory activities of PHF on allergic asthma. It also provides novel in vivo evidence that herbal medicines can ameliorate symptoms of allergic diseases may potentially prevent the development of subsequent atopic disorder such as allergic asthma through the influence of the gut microbiota.
Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the ...syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than GdDOTA
. These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy.
OBJECTIVE We examined the associations of clinical profiles in type 2 diabetic patients who developed severe hypoglycemia and their clinical outcomes, including death and all-site cancer. RESEARCH ...DESIGN AND METHODS A consecutive cohort of 8,767 type 2 diabetic patients with and without severe hypoglycemia in the 12 months before enrollment were recruited between 1995 and 2007, with follow-up until 2009. Severe hypoglycemia was defined by ICD-9 codes as hospitalizations resulting from hypoglycemia. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% CIs of clinical factors collected at enrollment for severe hypoglycemia. RESULTS In this cohort, mean age was 57.4 (SD 13.2) years and median disease duration of diabetes was 5 (interquartile range IQR 1-11) years. During a median follow-up of 6.71 (IQR 3.47-10.38) years, 235 patients had severe hypoglycemia (incidence 3.96 95% CI 3.45-4.46 per 1,000 patient-years). At enrollment, patients with and without severe hypoglycemia had similar cancer rates. During follow-up, patients with severe hypoglycemia had a higher incidence of all-site cancer (13.4 vs. 6.4%, P < 0.0001) and mortality (32.8 vs. 11.2%, P < 0.0001) than those without severe hypoglycemia. After adjusting for confounders, old age, low BMI, high glycated hemoglobin, low triglyceride (TG), low LDL cholesterol (LDL-C), albuminuria, and chronic kidney disease were independent predictors for severe hypoglycemia. CONCLUSIONS In type 2 diabetes, severe hypoglycemia is associated with advanced age, renal dysfunction, poor glycemic control, and cancer subphenotypes (low BMI, low LDL-C, and low TG).
Purpose
To quantify the defocus characteristics in the near‐work environment at home and investigate the relationship with subsequent myopia progression.
Methods
Fifty subjects (aged 7–12 years) were ...recruited and followed for 1 year. The home near‐work environment (writing desk) was measured at a baseline home‐visit using the Kinect‐for‐Windows to capture a 3‐dimensional image. The depth values of the image were then converted into scene defocus with respect to the subject’s viewpoint. The defocus characteristics were quantified as the dioptric volume (the total amount of net defocus, or DV) and standard deviation of the defocus values (SDD). Information on home size, time spent outdoors, and in front of a desk were also obtained. Univariate correlation, and multivariate regression were used to assess the association between myopia progression, defocus characteristics, and other co‐variates.
Results
The baseline spherical equivalent refraction (M) and refraction change over 1 year (∆M) were − 1.51 ± 2.02 D and − 0.56 ± 0.45 D respectively. DV was not significantly correlated with ∆M (Spearman’s ρ = −0.25, p = 0.08), while SDD was negatively correlated to ∆M (Spearman’s ρ = −0.42, p = 0.003). Although SDD was not a significant predictor in multivariate analysis, the regional DV at 15°–20° eccentricity was significant (p = 0.001). Home size (F2,50 = 7.01, p = 0.002) and time spent outdoors (Independent t = −2.13, p = 0.04) were also associated with ∆M, but not time spent in front of desk (Independent t = 0.78, p = 0.44).
Conclusion
The defocus profile in the home environment within the para‐central field of view is associated with childhood refractive error development.
Obesity is a risk factor that promotes progressive kidney disease. Studies have shown that an adipocytokine imbalance contributes to impaired renal function in humans and animals, but the underlying ...interplay between adipocytokines and renal injury remains to be elucidated. We aimed to investigate the mechanisms linking obesity to chronic kidney disease. We assessed renal function in high-fat (HF) diet-fed and normal diet-fed rats, and the effects of preadipocyte- and adipocyte-conditioned medium on cultured podocytes. HF diet-fed and normal diet-fed Sprague Dawley rats were used to analyze the changes in plasma BUN, creatinine, urine protein and renal histology. Additionally, podocytes were incubated with preadipocyte- or adipocyte-conditioned medium to investigate the effects on podocyte morphology and protein expression. In the HF diet group, 24 h urinary protein excretion (357.5 ± 64.2 mg/day vs 115.9 ± 12.4 mg/day, P < 0.05) and the urine protein/creatinine ratio were significantly higher (1.76 ± 0.22 vs 1.09 ± 0.15, P < 0.05), increased kidney weight (3.54 ± 0.04 g vs 3.38 ± 0.04 g, P < 0.05) and the glomerular volume and podocyte effacement increased by electron microscopy. Increased renal expression of desmin and decreased renal expression of CD2AP and nephrin were also seen in the HF diet group (P < 0.05). Furthermore, we found that adipocyte-conditioned medium-treated podocytes showed increased desmin expression and decreased CD2AP and nephrin expression compared with that in preadipocyte-conditioned medium-treated controls (P < 0.05). These findings show that adipocyte-derived factor(s) can modulate renal function. Adipocyte-derived factors play an important role in obesity-related podocytopathy.
We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island DNA hypermethylation and transcriptional silencing in colorectal cancer. By screening cell lines and ...validating tumor-specific hypermethylation in a panel of primary human colorectal cancer samples, we estimate that nearly 5% or more of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find larger numbers of genes hypermethylated in individual tumors, and a higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and to facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Designing efficient catalyst for the oxygen evolution reaction (OER) is of importance for energy conversion devices. The anionic redox allows formation of O-O bonds and offers higher OER ...activity than the conventional metal sites. Here, we successfully prepare LiNiO
2
with a dominant 3
d
8
L
configuration (
L
is a hole at O 2
p
) under high oxygen pressure, and achieve a double ligand holes 3
d
8
L
2
under OER since one electron removal occurs at O 2
p
orbitals for Ni
III
oxides. LiNiO
2
exhibits super-efficient OER activity among LiMO
2
,
R
MO
3
(M = transition metal,
R
= rare earth) and other unary 3d catalysts. Multiple in situ/operando spectroscopies reveal Ni
III
→Ni
IV
transition together with Li-removal during OER. Our theory indicates that Ni
IV
(3
d
8
L
2
) leads to direct O-O coupling between lattice oxygen and *O intermediates accelerating the OER activity. These findings highlight a new way to design the lattice oxygen redox with enough ligand holes created in OER process.
The catalytic hydrogenation of nitrophenols is widely utilized for both industrial synthesis and environmental protection, thus efficient and cost-effective catalysts are in urgent need. Still, the ...cost and scarcity of the materials still inhibit their application and the active sites are not well specified, especially in the complex catalysts. Herein, we developed an atomic Pd-doped nanoporous Ni/NiO (Pd1@np-Ni/NiO) catalyst via facial dealloying for efficient nitrophenol hydrogenation reaction under mild conditions. Pd1@np-Ni/NiO achieves an excellent specific activity (1301 min–1 mgPd –1, 35.2 times that of commercial Pd/C), nearly 100% selectivity, and continuous reproducibility. The catalytic performance is highly relevant to the Ni sites on the catalysts regarding the exposure sites and the intrinsic property. The metal/metal oxide interfacial structure could cooperatively accelerate the catalytic reaction kinetics. The atomic dopants could effectively modulate the electronic structure, facilitate the absorption of molecules, and reduce the energy barrier of catalytic hydrogenation reaction. Based on the efficient catalyst, the protype nitrophenol//NaBH4 battery is designed for efficient material conversion and power output, which is very attractive for green energy systems.
Metal oxides of the spinel family have shown great potential towards the oxygen evolution reaction (OER), but the fundamental OER mechanism of spinel oxides is still far from being completely ...understood, especially for the role of the metal ions. Owing to various coordinated sites of divalent/trivalent metals ions and surface conditions (morphology and defects), it is a great challenge to have a fair assessment of the electrocatalytic performance of spinel systems. Herein, we demonstrated a series of MFe
O
(M = Fe, Co, Ni, Zn) with a well-controlled morphology to achieve a comprehensive study of electrocatalytic activity toward OER. By utilizing several in situ analyses, we could conclude a universal rule that the activities for OER in the metal oxide systems were determined by the occurrence of a phase transformation, and this structural transformation could work well in both crystallographic sites (T
and O
sites). Additionally, the divalent metal ion significantly dominated the formation of oxyhydroxide through an epitaxial relationship, which depended on the atomic arrangement at the interface of spinel and metal oxyhydroxide, while trivalent metal ions remained unchanged as a host lattice. The metal oxyhydroxide was formed during a redox reaction rather than being formed during OER. The occurrence of the redox reaction seems to accompany a remarkable increase in resistance and capacitance might result from the structural transformation from spinel to metal oxyhydroxide. We believe that the approaching strategies and information obtained in the present study can offer a guide to designing a promising electrocatalytic system towards the oxygen evolution reaction and other fields.
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