A Ti-incorporated metal organic framework structure (MOF) MIL-125, and its amine-functionalized form, NH2-MIL-125, were directly synthesized via a solvothermal route aided by microwave heating, and ...their adsorption (H2O, CO2), separation (isoprene/2-methyl butane) and catalytic properties (olefin cycloaddition, oxidative desulfurization) were investigated. Display omitted
► Titanium-incorporated materials MIL-125 and NH2-MIL-125 were synthesized. ► NH2-MIL-125 was also prepared via microwave heating. ► CO2, N2, and H2O adsorption properties were measured at different temperatures. ► Redox and acid/base catalytic properties were investigated. ► Liquid phase separation of C5 olefin/paraffin was conducted.
A Ti-incorporated metal organic framework structure, MIL-125, and its amine-functionalized form, NH2-MIL-125, were synthesized via a solvothermal route aided by microwave heating. The samples were characterized by XRD, SEM, TGA, EA, UV–vis spectroscopy, and N2 adsorption–desorption measurements. MIL-125 was unstable in aqueous solution, but NH2-MIL-125 was stable both in water and in heptane; its hydrophilic property was further confirmed by water vapor adsorption. NH2-MIL-125 showed moderate CO2 adsorption capacity (136mgg−1) but excellent selectivity over N2 (>27:1) at 298K with a low heat of adsorption surpassing the performance of MIL-125. Four consecutive CO2 adsorption–desorption cycles over NH2-MIL-125 showed completely reversible adsorbent regeneration at 298K under a helium flow for a total duration of 550min. Catalytic properties of the materials were evaluated by cycloaddition of epichlorohydrin and oxidative desulfurization of dibenzothiophene. Finally, batch mode liquid-phase competitive separation of isoprene from 2-methyl butane was conducted, revealing high selectivity of isoprene against 2-methyl butane (ca. 7.8 and 9.7) over MIL-125 and NH2-MIL-125, respectively.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Lactobacillus plantarum DK119 (DK119) isolated from the fermented Korean cabbage food was used as a probiotic to determine its antiviral effects on influenza virus. DK119 intranasal or oral ...administration conferred 100% protection against subsequent lethal infection with influenza A viruses, prevented significant weight loss, and lowered lung viral loads in a mouse model. The antiviral protective efficacy was observed in a dose and route dependent manner of DK119 administration. Mice that were treated with DK119 showed high levels of cytokines IL-12 and IFN-γ in bronchoalveolar lavage fluids, and a low degree of inflammation upon infection with influenza virus. Depletion of alveolar macrophage cells in lungs and bronchoalveolar lavages completely abrogated the DK119-mediated protection. Modulating host innate immunity of dendritic and macrophage cells, and cytokine production pattern appeared to be possible mechanisms by which DK119 exhibited antiviral effects on influenza virus infection. These results indicate that DK119 can be developed as a beneficial antiviral probiotic microorganism.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Podocyte injury inevitably results in leakage of proteins from the glomerular filter and is vital in the pathogenesis of diabetic nephropathy (DN). The underlying mechanisms of podocyte injury ...facilitate finding of new therapeutic targets for DN treatment and prevention. Tangeretin is an O-polymethoxylated flavone present in citrus peels with anti-inflammatory and antioxidant properties. This study investigated the renoprotective effects of tangeretin on epithelial-to-mesenchymal transition-mediated podocyte injury and fibrosis through oxidative stress and hypoxia caused by hyperglycemia. Mouse podocytes were incubated in media containing 33 mM glucose in the absence and presence of 1-20 μM tangeretin for up to 6 days. The in vivo animal model employed db/db mice orally administrated with 10 mg/kg tangeretin for 8 weeks. Non-toxic tangeretin inhibited glucose-induced expression of the mesenchymal markers of N-cadherin and α-smooth muscle actin in podocytes. However, the reduced induction of the epithelial markers of E-cadherin and P-cadherin was restored by tangeretin in diabetic podocytes. Further, tangeretin enhanced the expression of the podocyte slit diaphragm proteins of nephrin and podocin down-regulated by glucose stimulation. The transmission electron microscopic images revealed that foot process effacement and loss of podocytes occurred in diabetic mouse glomeruli. However, oral administration of 10 mg/kg tangeretin reduced urine albumin excretion and improved foot process effacement of diabetic podocytes through inhibiting loss of slit junction and adherenes junction proteins. Glucose enhanced ROS production and HIF-1α induction in podocytes, leading to induction of oxidative stress and hypoxia. Similarly, in diabetic glomeruli reactive oxygen species (ROS) production and HIF-1α induction were observed. Furthermore, hypoxia-evoking cobalt chloride induced epithelial-to-mesenchymal transition (EMT) process and loss of slit diaphragm proteins and junction proteins in podocytes, which was inhibited by treating submicromolar tangeretin. Collectively, these results demonstrate that tangeretin inhibited podocyte injury and fibrosis through blocking podocyte EMT caused by glucose-induced oxidative stress and hypoxia.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and cerebral small vessel disease (CSVD) burden, especially according to the NAFLD severity. A total of 1,260 ...participants were included. The CSVD burden was assessed with white matter hyperintensities (WMH), lacunes, and microbleeds (MBs) on brain MRI. An ultrasound diagnosis of fatty liver was made based on standard criteria, and the Fibrosis-4 (FIB-4) index was used to classify participants with NAFLD with having a high-intermediate (FIB-4 ≥1.45) or low (FIB-4 < 1.45) probability of advanced fibrosis. A multivariable logistic regression analysis was used to assess the association between NAFLD and the presence of moderate to severe WMH, lacunes, and MBs. NAFLD had a significant association only with moderate to severe WMH (OR: 1.64, 95% CI: 1.10-2.42), even after controlling for cardiometabolic risk factors. A linear trend test showed a significant association between the severity of NAFLD fibrosis and the presence of moderate to severe WMH (p for trend <0.001). Our findings suggest that NAFLD, especially NAFLD with fibrosis, has a significant association with the presence of moderate to severe WMH in cognitively normal individuals, and NAFLD severity predicted more frequent moderate to severe WMH.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
To characterize the course of Alzheimer's disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging ...from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The incidence and mortality rates of colorectal cancer (CRC) has been reported to be strongly associated to sex/gender difference. CRC shows sexual dimorphism, and sex hormones have been shown to ...affect the tumor immune microenvironment. This study aimed to investigate location-dependent sex differences in tumorigenic molecular characteristics in patients with colorectal tumors, including adenoma and CRC.
A total of 231 participants, including 138 patients with CRC, 55 patients with colorectal adenoma, and 38 healthy controls, were recruited between 2015 and 2021 at Seoul National University Bundang Hospital. All patients underwent colonoscopy and acquired tumor lesion samples were further analyzed for programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) expression, deficient mismatch repair (dMMR), and microsatellite instability (MSI) status. This study was registered with ClinicalTrial.gov, number NCT05638542.
The average of combined positive score (CPS) was higher in serrated lesions and polyps (lesions/polyps) compared to conventional adenomas (5.73 and 1.41, respectively, P < 0.001). No significant correlation was found between sex and PD-L1 expression within the groups, regardless of histopathological diagnosis. In multivariate analysis where each sex was further stratified by tumor location due to their interaction in CRC, PD-L1 expression was inversely correlated with males having proximal CRC with a CPS cutoff of 1 (Odds ratio (OR) 0.28, P = 0.034). Females with proximal CRC showed a significant association with dMMR/MSI-high (OR 14.93, P = 0.032) and high EGFR expression (OR 4.17, P = 0.017).
Sex and tumor location influenced molecular features such as PD-L1, MMR/MSI status and EGFR expression in CRC, suggesting a possible underlying mechanism of sex-specific colorectal carcinogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
17β-estradiol (E2) is known to have a protective effect in colorectal cancer (CRC); thus, E2 may be effective for cancer immunotherapy in CRC. The aim of this study is to evaluate the effect of ...combination therapy with E2 and anti-programmed cell death receptor-1 ligand (PD-L1) antibodies, and the effects of sex and estrogen on colon tumor growth, PD-L1 expression, and tumor-associated cell populations in an MC38 colon tumor model. Male mice showed increased MC38 colon tumor growth and PD-L1 expression in tumor sections as well as higher proportion of cancer-associated fibroblasts (CD45−CD31−CD140a+), PD-L1-expressing tumor cells (CD45−CD274+) and tumor-associated macrophages (TAMs) (CD11b+F4/80+CD274+) compared to female mice. E2 treatment prior to MC38 injection significantly reduced these phenomena in male mice. Furthermore, co-treatment with E2 and anti-PD-L1 antibodies significantly inhibited MC38 tumor growth and reduced PD-L1-expressing cells in male mice compared to treatment with either E2 or anti-PD-L1 antibodies alone. Combination treatment with E2 and anti-PD-L1 decreased TAM population (CD11b+F4/80+) in the tumor mass while increasing M1 TMAs (CD11b+F4/80+CD86+). These results suggest that estrogen inhibits MC38 tumor growth by downregulating PD-L1 expression and regulating tumor-associated cell populations. Furthermore, estrogen boosted the effect of anti-PD-L1 antibody in the MC38 tumor model.
•17β-estradiol is known to have a protective effect in colon cancer development.•Sex differences exist in MC38 tumor growth, PD-L1 expression, and cell populations.•17β-estradiol treatment before MC38 injection reduced high cell types in males.•Synergistic effect of 17β-estradiol on anti-tumorigenic effect of anti-PD-L1.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Transition metals, such as iron (Fe)- or cobalt (Co)-based nanomaterials, are promising electrocatalysts for oxygen reduction reactions (ORR) in fuel cells due to their high theoretical activity and ...low cost. However, a major challenge to using these metals in place of precious metal catalysts for ORR is their low efficiency and poor stability, thus new concepts and strategies should be needed to address this issue. Here, we report a hybrid aciniform nanostructures of Fe nanofragments embedded in thin nitrogen (N)-doped graphene (Fe@N-G) layers via a heat treatment of graphene oxide-wrapped iron oxide (Fe
2
O
3
) microparticles with melamine. The heat treatment leads to transformation of Fe
2
O
3
microparticles to nanosized zero-valent Fe fragments and formation of core-shell structures of Fe nanofragments and N-doped graphene layers. Thin N-doped graphene layers massively promote electron transfer from the encapsulated metals to the graphene surface, which efficiently optimizes the electronic structure of the graphene surface and thereby triggers ORR activity at the graphene surface. With the synergistic effect arising from the N-doped graphene and Fe nanoparticles with porous aciniform nanostructures, the Fe@N-G hybrid catalyst exhibits high catalytic activity, which was evidenced by high E
1/2
of 0.82 V, onset potential of 0.93 V, and limiting current density of 4.8 mA cm
−2
indicating 4-electron ORR, and even exceeds the catalytic stability of the commercial Pt catalyst.
Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, ...prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex‐common cells omitted sex description more often compared to sex‐specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.
Cell sex is an important biological variable due to variations in sex chromosome gene expression and developmental biology events. This review underlines inadequate reporting of cell sex origin in vitro studies published in high‐impact oncology journals in 2020. Considering growing evidence of sex‐specific disparities in cancer biology and treatment, our results highlight the importance of disclosing cell sex in preclinical and clinical studies. This practice is essential for a better understanding and the successful application of biomedical research discoveries (Created with BioRender.com).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Gut microbiota and blood neutrophil-to-lymphocyte ratio (NLR) are associated with systemic inflammation; however, data on the association between gut microbiota and NLR are lacking. We investigated ...the association between gut microbiota and NLR. A total of 1,309 subjects who had available data on NLR and 16 S rRNA sequencing of gut microbiota were included in this study. They were grouped according to NLR quartile (Q) as follows: lower Q (n = 328, <25% of NLR range), middle 2Q (n = 653, ≥25% to <75%) and upper Q (n = 328, ≥75%). The diversity and composition of the human gut microbiota in the groups were calculated. The phylogenetic diversity of gut microbiota in the lower group was significantly higher than in the middle 2Q group (P = 0.040). The beta-diversity was significantly different among the three groups (P = 0.043), between the lower and middle 2Q groups (P = 0.029), and between the lower and upper groups (P = 0.026). Bacteroides eggerthii showed a positive correlation with NLR (q = 0.015). The diversity and composition of the gut microbiome were different between the NLR groups. Particularly, patients with a lower NLR had a greater diversity of gut microbiota.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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