PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis

Chang Rok Kim, Taichi Noda, Hyunkyung Kim, Gibeom Kim, Seongwan Park, Yongwoo Na, Seiya Oura, Keisuke Shimada, Injin Bang, Jun-Yeong Ahn, Yong Ryoul Kim, Se Kyu Oh, Hee-Jung Choi, Jong-Seo Kim, Inkyung Jung, Ho Lee, Yuki Okada, Masahito Ikawa, Sung Hee Baek, PHF7 Modulates BRDT Stability and Histone-to-Protamine Exchange during Spermiogenesis, Cell Reports, Volume 32, Issue 4, 2020, 107950, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2020.107950

The influence of contralateral circulation on computational fluid dynamics of intracranial arteries: simulated versus measured flow velocities

Abstract Background This study aimed to retrospectively evaluate the influence of contralateral anterior circulation on computational fluid dynamics (CFD) of intracranial arteries, by comparing the CFD values of flow velocities in unilateral anterior circulation with the measured values from phase-contrast magnetic resonance angiography (PC-MRA). Methods We analyzed 21 unilateral anterior circulation models without proximal stenosis from 15 patients who performed both time-of-flight MRA (TOF-MRA) and PC-MRA. CFD was performed with the inflow boundary condition of a pulsatile flow of the internal carotid artery (ICA) obtained from PC-MRA. The outflow boundary condition was given as atmospheric pressure. Simulated flow velocities of the middle cerebral artery (MCA) and anterior cerebral artery (ACA) from CFD were compared with the measured values from PC-MRA. Results The velocities of MCA were shown to be more accurately simulated on CFD than those of ACA (Spearman correlation coefficient 0.773 and 0.282, respectively). In four models with severe stenosis or occlusion of the contralateral ICA, the CFD values of ACA velocities were significantly lower (< 50%) than those measured with PC-MRA. ACA velocities were relatively accurately simulated in the models including similar diameters of both ACAs. Conclusion It may be necessary to consider the flow condition of the contralateral anterior circulation in CFD of intracranial arteries, especially in the ACA. Relevance statement Incorporating the flow conditions of the contralateral circulation is of clinical importance for an accurate prediction of a rupture risk in Acom aneurysms as the bidirectional flow and accurate velocity of both ACAs can significantly impact the CFD results. Key points • CFD simulations using unilateral vascular models were relatively accurate for MCA. • Contralateral ICA steno-occlusion resulted in an underestimation of CFD velocity in ACA. • Contralateral flow may need to be considered in CFD simulations of ACA. Graphical Abstrac

MODIS ????????? ??????????????? ????????? ???????????? ????????? ???????????? ?????? ?????? ?????? ??????

Korean fir (Abies koreana Wilson) is one of the most important environmental indicator tree species for assessing climate change impacts on coniferous forests in the Korean Peninsula. However, due to the nature of alpine and subalpine regions, it is difficult to conduct regular field surveys of Korean fir, which is mainly distributed in regions with altitudes greater than 1,000 m. Therefore, this study analyzed the vegetation change trend of Korean fir using regularly observed remote sensing data. Specifically, normalized difference vegetation index (NDVI) from Moderate Resolution Imaging Spectroradiometer (MODIS), land surface temperature (LST), and precipitation data from Global Precipitation Measurement (GPM) Integrated Multi-satellitE Retrievalsfor GPM from September 2003 to 2020 for Hallasan and Jirisan were used to analyze vegetation changes and their association with environmental variables. We identified a decrease in NDVI in 2020 compared to 2003 for both sites. Based on the NDVI difference maps, areas for healthy vegetation and high mortality of Korean fir were selected. Long-term NDVI time-series analysis demonstrated that both Hallasan and Jirisan had a decrease in NDVI at the high mortality areas (Hallasan: -0.46, Jirisan: -0.43). Furthermore, when analyzing the long-term fluctuations of Korean fir vegetation through the Hodrick-Prescott filter-applied NDVI, LST, and precipitation, the NDVI difference between the Korean fir healthy vegetation and high mortality sitesincreased with the increasing LST and decreasing precipitation in Hallasan. Thissuggests that the increase in LST and the decrease in precipitation contribute to the decline of Korean fir in Hallasan. In contrast, Jirisan confirmed a long-term trend of declining NDVI in the areas of Korean fir mortality but did not find a significant correlation between the changes in NDVI and environmental variables (LST and precipitation). Further analyses of environmental factors, such as soil moisture, insolation, and wind that have been identified to be related to Korean fir habitats in previous studies should be conducted. This study demonstrated the feasibility of using satellite data for long-term monitoring of Korean fir ecosystems and investigating their changes in conjunction with environmental conditions. Thisstudy provided the potential forsatellite-based monitoring to improve our understanding of the ecology of Korean fir

A solution-based route to compositionally complex metal oxide structures using high-entropy layered double hydroxides

Although complex metal oxides with tailored compositions are increasingly in demand for applications in advanced technologies, their preparation by solution-based routes, which are typically low cost and easy to scale up, is challenging. Here, we report high-entropy layered double hydroxides (HE-LDHs) having complex compositions as precursors for complex metal oxides. Furthermore, we reveal that the ionic radii are the key factors determining the incorporation of the metal cations into the hydroxide layers, which can contain up to 10 different kinds of metal cations simultaneously having a metal cation ratio inherited from the reaction solution. Furthermore, spinel-based complex oxides can be prepared by heat treating the HE-LDHs in air, and their metal cation ratios are maintained over expansive heat-treatment temperatures (up to 1,200??C). Therefore, the results reveal that complex oxides with tailored compositions can be prepared using solution-based approaches, enabling the large-scale fabrication of oxides with precisely controlled physicochemical properties for various applications

Could Natural Products Help in the Control of Obesity? Current Insights and Future Perspectives

Obesity is a global issue faced by many individuals worldwide. However, no drug has a pronounced effect with few side effects. Green tea, a well-known natural product, shows preventive effects against obesity by decreasing lipogenesis and increasing fat oxidation and antioxidant capacity. In contrast, other natural products are known to contribute to obesity. Relevant articles published on the therapeutic effect of natural products on obesity were retrieved from PubMed, Web of Science, and Scopus. The search was conducted by entering keywords such as “obesity”, “natural product”, and “clinical trial”. The natural products were classified as single compounds, foods, teas, fruits, herbal medicines—single extract, herbal medicines—decoction, and herbal medicines—external preparation. Then, the mechanisms of these medicines were organized into lipid metabolism, anti-inflammation, antioxidation, appetite loss, and thermogenesis. This review aimed to assess the efficacy and mechanisms of effective natural products in managing obesity. Several clinical studies reported that natural products showed antiobesity effects, including Coffea arabica (coffee), Camellia sinensis (green tea), Caulerpa racemosa (green algae), Allium sativum (garlic), combined Ephedra intermedia Schrenk, Thea sinensis L., and Atractylodes lancea DC extract (known as Gambisan), Ephedra sinica Stapf, Angelica Gigantis Radix, Atractylodis Rhizoma Alba, Coicis semen, Cinnamomi cortex, Paeoniae radix alba, and Glycyrrhiza uralensis (known as Euiiyin-tang formula). Further studies are expected to refine the pharmacological effects of natural products for clinical use

Prognostic implications of soluble programmed death-ligand 1 and its dynamics during chemotherapy in unresectable pancreatic cancer

In pancreatic cancer, acquiring a sufficient amount of tumor tissue is an obstacle. The soluble form of PD-L1 (sPD-L1) may have immunosuppressive activity. Here, we evaluated the prognostic implications of sPD-L1 in unresectable pancreatic cancer. We prospectively enrolled 60 patients treated with first-line FOLFIRINOX chemotherapy. We collected blood samples at diagnosis, first response assessment and disease progression. Serum sPD-L1 levels were measured using enzyme-linked immunosorbent assays. The median sPD-L1 level was 1.7 ng/mL (range, 0.4-5.7 ng/mL). Patients with low sPD-L1 level (<4.6 ng/mL) at diagnosis showed better overall survival (OS) than those with high sPD-L1 level (P= 0.015). Multivariate analysis identified sPD-L1 and the neutrophil-to-lymphocyte ratio as independent prognostic factors for OS. During chemotherapy, more patients achieved complete response (CR)/partia I response (PR) as their best response when sPD-L1 was decreased at the first response assessment (P = 0.038). In the patients who achieved CR/PR as their best response, sPD-L1 was significantly higher at the time of disease progression than at the first response assessment (P = 0.025). In conclusion, the sPD-L1 level at diagnosis exhibits a prognostic value in pancreatic cancer. Furthermore, sPD-L1 dynamics correlate with disease course and could be used to understand various changes in the tumor microenvironment during chemotherapy

The prognostic role of soluble TGF-beta and its dynamics in unresectable pancreatic cancer treated with chemotherapy

Objectives Transforming growth factor-beta (TGF-beta) is a multifunctional regulatory factor. Here we measured serum soluble TGF-beta (sTGF-beta) levels and evaluated its dynamics and prognostic capabilities during chemotherapy in unresectable pancreatic cancer patients. Methods We prospectively enrolled 60 patients treated with FOLFIRINOX as the first-line palliative chemotherapy. We collected blood samples at the time of diagnosis, first response assessment, and disease progression and measured serum sTGF-beta using an enzyme-linked immunosorbent assay. Results The patients' median overall survival (OS) and progression-free survival (PFS) were 10.3 (95% confidence interval [CI], 8.5-12.1) and 6.5 (95% CI, 4.9-8.1) months, respectively. Patients with low sTGF-beta at diagnosis (<31.2 ng/mL) had better OS and PFS than patients with high sTGF-beta, respectively, (OS, 13.7 vs 9.2 months; hazard ratio [HR], 2.602; P = .004; PFS, 9.0 vs 5.8 months; HR, 2.010; P = .034). At the time of disease progression, sTGF-beta was increased compared with that of diagnosis (mean, 26.4 vs 23.9 ng/mL). In particular, sTGF-beta was significantly increased at disease progression in patients with a partial response (mean, 25.7 vs 31.0 ng/mL; P = .049). Conclusions Pretreatment sTGF-beta levels can serve as a prognostic indicator in unresectable pancreatic cancer patients treated with FOLFIRINOX chemotherapy. Likewise, the dynamics of sTGF-beta during chemotherapy have prognostic value.

AMPK–SKP2–CARM1 signalling cascade in transcriptional regulation of autophagy

Autophagy is a highly conserved self-digestion process, which is essential for maintaining homeostasis and viability in response to nutrient starvation. Although the components of autophagy in the cytoplasm have been well studied, the molecular basis for the transcriptional and epigenetic regulation of autophagy is poorly understood. Here we identify co-activator-associated arginine methyltransferase 1 (CARM1) as a crucial component of autophagy in mammals. Notably, CARM1 stability is regulated by the SKP2-containing SCF (SKP1-cullin1-F-box protein) E3 ubiquitin ligase in the nucleus, but not in the cytoplasm, under nutrient-rich conditions. Furthermore, we show that nutrient starvation results in AMP-activated protein kinase (AMPK)-dependent phosphorylation of FOXO3a in the nucleus, which in turn transcriptionally represses SKP2. This repression leads to increased levels of CARM1 protein and subsequent increases in histone H3 Arg17 dimethylation. Genome-wide analyses reveal that CARM1 exerts transcriptional co-activator function on autophagy-related and lysosomal genes through transcription factor EB (TFEB). Our findings demonstrate that CARM1-dependent histone arginine methylation is a crucial nuclear event in autophagy, and identify a new signalling axis of AMPK-SKP2-CARM1 in the regulation of autophagy induction after nutrient starvation

More accurate prediction of metastatic pancreatic cancer patients' survival with prognostic model using both host immunity and tumor metabolic activity

Introduction Neutrophil to lymphocyte ratio (NLR) and standard uptake value (SUV) by F-18-FDG PET represent host immunity and tumor metabolic activity, respectively. We investigated NLR and maximum SUV (SUVmax) as prognostic markers in metastatic pancreatic cancer (MPC) patients who receive palliative chemotherapy. Methods We reviewed 396 MPC patients receiving palliative chemotherapy. NLR was obtained before and after the first cycle of chemotherapy. In 118 patients with PET prior to chemotherapy, SUVmax was collected. Cut-off values were determined by ROC curve. Results In multivariate analysis of all patients, NLR and change in NLR after the first cycle of chemotherapy (Delta NLR) were independent prognostic factors for overall survival (OS). We scored the risk considering NLR and Delta NLR and identified 4 risk groups with different prognosis (risk score 0 vs 1 vs 2 vs 3: OS 9.7 vs 7.9 vs 5.7 vs 2.6 months, HR 1 vs 1.329 vs 2.137 vs 7.915, respectively; P<0.001). In PET cohort, NLR and SUVmax were independently prognostic for OS. Prognostication model using both NLR and SUVmax could define 4 risk groups with different OS (risk score 0 vs 1 vs 2 vs 3: OS 11.8 vs 9.8 vs 7.2 vs 4.6 months, HR 1 vs 1.536 vs 2.958 vs 5.336, respectively; P<0.001). Conclusions NLR and SUVmax as simple parameters of host immunity and metabolic activity of tumor cell, respectively, are independent prognostic factors for OS in MPC patients undergoing palliative chemotherapy

Skeletal muscle depletion predicts survival of patients with advanced biliary tract cancer undergoing palliative chemotherapy

Background: No prior study has investigated the dynamics of body weight with body muscle mass as a prognostic factor in advanced biliary tract cancer (BTC) patients undergoing palliative chemotherapy. We investigated whether low skeletal muscle mass affects survival in patients with BTC, with a co-analysis of body weight loss and body mass index (BMI). Results: By multivariate analysis, low skeletal muscle mass at diagnosis and decreased SMI during chemotherapy (p = 0.008 and p < 0.001, respectively) were poor prognostic factors for overall survival (OS). Subgroup analysis revealed that low skeletal muscle mass patients who were overweight or obese (BMI = 25 kg/ m(2)) showed worse OS (p < 0.001). Additionally, patients with both decreased BMI and SMI during chemotherapy had worse OS (p < 0.001). Furthermore, patients with decreased SMI had shorter survival regardless of change in BMI. However, for patients with SMI maintained during chemotherapy, decreased BMI had no effect on survival (p = 0.576). Materials and Methods: We consecutively enrolled 524 patients with advanced BTC who received palliative chemotherapy between 2003 and 2013. Total muscle cross-sectional area (cm(2)) at the L3 level assessed by computed tomography was analyzed. We defined low skeletal muscle mass as a skeletal muscle index (SMI) < 48.5 cm(2)/m(2) (men) and < 39.5 cm(2)/m(2) (women) using ROC curves. Conclusions: Low skeletal muscle mass, obesity and muscle depletion during palliative chemotherapy are meaningful prognostic factors in advanced BTC. Considering muscle depletion with weight change could help to more accurately predict prognoses of patients with BTC