Miracle-dz/UniFAR-FTUs huggingface dataset:
The Strengthening and Toughening of Biodegradable Poly (Lactic Acid) Using the SiO2-PBA Core–Shell Nanoparticle

The balance of strengthening and toughening of poly (lactic acid) (PLA) has been an intractable challenge of PLA nanocomposite development for many years. In this paper, core–shell nanoparticles consisting of a silica rigid core and poly (butyl acrylate) (PBA) flexible shell were incorporated to achieve the simultaneous enhancement of the strength and toughness of PLA. The effect of core–shell nanoparticles on the tensile, flexural and Charpy impact properties of PLA nanocomposite were experimentally investigated. Scanning electron microscopy (SEM) and small-angle X-ray scattering (SAXS) measurements were performed to investigate the toughening mechanisms of nanocomposites. The experimental results showed that the addition of core–shell nanoparticles can improve the stiffness and strength of PLA. Meanwhile, its elongation at break, tensile toughness and impact resistance were enhanced simultaneously. These observations can be attributed to the cavitation of the flexible shell in core–shell nanoparticles and the resultant shear yielding of the matrix. In addition, a three-dimensional finite element model was also proposed to illustrate the damage processes of core–shell nanoparticle-reinforced polymer composites. It was found that, compared with the experimental performance, the proposed micromechanical model is favorable to illustrate the mechanical behavior of nanocomposites.
Non-Alcoholic Fatty Liver Disease Is Associated with Higher Metabolic Expenditure in Overweight and Obese Subjects: A Case-Control Study

Non-alcoholic fatty liver disease (NAFLD) is a common condition in Western countries. However, their metabolic characteristics are poorly known even though they could be important. Therefore, the objective of this study was to measure resting metabolic parameters in overweight/obese adults with hepatic steatosis compared to controls, matched for age, sex, and obesity level. Hepatic steatosis was diagnosed with liver ultrasound. Energy metabolism was measured with indirect calorimetry: energy expenditure (REE), predicted REE, the ratio between REE and the predicted REE, and the respiratory quotient (RQ) were reported. We measured some anthropometric, body composition, and bio-humoral parameters; 301 participants with NAFLD were matched for age, sex, and obesity level with 301 participants without NAFLD. People with NAFLD showed significantly higher REE (1523 ± 238 vs. 1464 ± 212 kcal, p = 0.005), REE/REE predicted ratio (98.2 ± 9.4 vs. 95.7 ± 8.1, p = 0.002), and RQ (0.88 ± 0.08 vs. 0.85 ± 0.07, p = 0.03). Moreover, the NAFLD group had significantly higher inflammatory and insulin-resistance parameters compared to controls. In conclusion, NAFLD is associated with a significantly higher metabolic expenditure, as measured with indirect calorimetry, compared to a similar cohort of individuals without this condition. Higher inflammatory levels in patients with NAFLD can probably explain our findings, even if other research is needed on this issue.
Substrate‐specificity of cytochrome P450‐mediated detoxification as an evolutionary strategy for specialization on furanocoumarin‐containing hostplants: CYP6AE89 in parsnip webworms

The parsnip webworm, Depressaria pastinacella, is restricted to two hostplant genera containing six structurally diverse furanocoumarins. Of these, imperatorin is detoxified by a specialized cytochrome P450, CYP6AB3. A previous whole‐larva transcriptome analysis confirmed the presence of nine transcripts that belong to the CYP6AE subfamily. Here, by examining midgut‐specific gene expression patterns we determined that CYP6AE89 transcripts were highly expressed and furanocoumarin‐inducible. Computer docking and energy‐minimization of a CYP6AE89 model with all six furanocoumarins showed that 5‐methoxylated bergapten and 8‐methoxylated xanthotoxin had the smallest distances from the heme to the proton‐donor residue in the catalytic I‐helix, and that the 5,8‐dimethoxylated isopimpinellin and bergapten had the smallest energy‐minimized distance from the heme oxygen to the furan ring double bond. To evaluate this prediction, we expressed the CYP6AE89 protein in an Escherichia coli system, and used it to detect high catalytic activity against the two mono‐methoxylated linear furanocoumarins – bergapten and xanthotoxin – and weak activity against isopimpinellin. Thus, CYP6AE89, like CYP6AB3, is probably specialized for detoxifying only a subset of hostplant furanocoumarins. A maximum‐likelihood tree built with six representative lepidopterans with manually annotated cytochrome P450s shows that CYP6AE89 may have evolved much faster than the other CYP6AE proteins, possibly indicative of host selection pressure.
Hydrophilic titanium surface-induced macrophage modulation promotes pro-osteogenic signalling.

OBJECTIVES As biomaterial-induced modulation of mediators of the immune response may be a potential therapeutic approach to enhance wound healing events, the aim of this study was to delineate the effects of titanium surface modification on macrophage phenotype and function. MATERIAL AND METHODS Rodent bone marrow derived macrophages were polarised into M1 and M2 phenotypes and cultured on micro-rough (SLA) and hydrophilic modified SLA (modSLA) titanium discs. Macrophage phenotype and cytokine secretion were subsequently assessed by immunostaining and ELISA, respectively. Osteoblast gene expression in response to culture in the M1 and M2 macrophage conditioned media was also evaluated over 7 days by RT-PCR. RESULTS M1-macrophage culture on the modSLA surface promoted an M2-like phenotype as demonstrated by marked CD163 protein expression, Arg1 gene expression and the secretion of cytokines that significantly up-regulated in osteoblasts the expression of genes associated with the TGFß/BMP signalling pathway and osteogenesis. In comparison, M2-macrophage culture on SLA surface promoted an inflammatory phenotype and cytokine profile that was not conducive for osteogenic gene expression. CONCLUSIONS Macrophages are able to alter or switch their phenotype according to the signals received from the biomaterial surface. A hydrophilic micro-rough titanium surface topography elicits a macrophage phenotype associated with reduced inflammation. This article is protected by copyright. All rights reserved.
Knockdown of PAK1 Inhibits the Proliferation and Invasion of Non–Small Cell Lung Cancer Cells Through the ERK Pathway

The p21-activated kinase (PAK) family of serine/threonine kinases plays a pivotal role in various human tumors, as supported by our previous report on the overexpressed PAK isoforms in non–small cell lung cancer (NSCLC). To better understand the role of PAKs in tumorigenesis, the authors examined PAK1 expression patterns and its significance in NSCLC. It was demonstrated by immunohistochemical staining that PAK1 was increased and localized in the cytoplasm in 151 of 207 cases. High levels of PAK1 expression correlated with a histologic type of tumor (squamous cell carcinoma), tumor node metastasis stage, and lymph nodal status. We also examined the biological role of PAK1 in lung cancer cell lines transfected with PAK1-small interfering RNA. Decreased expression of PAK1 inhibited lung cancer cell proliferation and invasion, which is the major cause of lung cancer malignancy. Downregulated expression of PAK1 hampered rapidly accelerated fibrosarcoma/mitogen-activated extracellular signal-regulated kinase/extracellular signal-regulated kinase pathway activity but did not affect Wnt/β-catenin signaling. Our findings suggest that PAK1 is an important oncogene in NSCLC, as decreased expression of PAK1 inhibited the proliferation and invasion of NSCLC cells by blocking the ERK pathway. These results provide evidence for using PAK1 inhibition as potential anticancer therapy.
Overexpression of miR-223 inhibits foam cell formation by inducing autophagy in vascular smooth muscle cells.

BACKGROUND Vascular smooth muscle cells (VSMCs) play an important role in foam cell formation, a hallmark of atherosclerosis obliterans (ASO). We recently demonstrated that miR-223 is significantly upregulated both in atherosclerotic arteries and in the serum sample of ASO patients. However, it is still unknown if miR-223 is implicated in the foam cell formation of VSMCs. The current study aimed to investigate the role of miR-223 in the foam cell formation of VSMCs. METHODS Artery and serum samples were collected from ASO patients. Human VSMCs were isolated from the normal arteries of healthy donors. For miR-223 overexpression, miR-223 mimic was transfected into VSMCs using Lipofectamine 2000. Foam cell formation was evaluated by lipid accumulation using Oil Red O staining. Luciferase assay was adopted to confirm the target gene of miRNA. RESULTS miR-223 was significantly upregulated in both the arteries and serum samples from ASO patients. miR-223 overexpression significantly inhibited the foam cell formation and decreased total intracellular cholesterol levels in VSMCs. miR-223 overexpression induced autophagy of VSMCs. Blocking autophagy by 3-methyladenine or autophagy-related 7 (Atg7) siRNAs attenuated the inhibitory effect of miR-223 overexpression on foam cell formation. Luciferase assay showed that IGF-1R is a direct target of miR-223. miR-223 overexpression reduced protein levels of IGF-1R expression and the phosphorylated form of PI3K and Akt proteins. CONCLUSIONS miR-223 overexpression inhibited foam cell formation in VSMCs, at least partially, via inducing autophagy. The IGF-1R/PI3K/Akt signaling pathway may be also involved in this mechanism.
People With COPD Who Respond to Ground-Based Walking Training Are Characterized by Lower Pre-training Exercise Capacity and Better Lung Function and Have Greater Progression in Walking Training Distance

Purpose: To investigate the characteristics that distinguish responders from nonresponders to ground-based walking training (GBWT) in people with chronic obstructive pulmonary disease (COPD). Methods: An analysis was undertaken of data collected during a trial of GBWT in people with COPD. Responders to GBWT were defined in 2 ways: (1) improved time on the endurance shuttle walk test of ≥190 sec (criterion A); or (2) improved ability to walk, perceived by the participant to be at least “moderate” (criterion B). Differences in participant characteristics, pre-training exercise capacity, health-related quality of life, and the improvement in the distance walked during the training program were examined between responders and nonresponders. Results: Of the 95 participants randomized to GBWT (age 69 ± 8 yr, forced expiratory volume in 1 sec [FEV1] % predicted = 43% ± 15%), data were available for analysis on 78 and 73 patients by criterion A and criterion B, respectively. According to criterion A, 32 (41%) participants were responders. The odds of being a responder increased with increasing FEV1 % predicted (OR = 1.2; 95% CI, 1.0-1.5, for every 5% increase) and increased with decreasing pre-training incremental shuttle walk distance (OR = 1.4; 95% CI, 1.0-1.8, for every 50-m decrement). According to criterion B, 42 (58%) participants were responders. There were no differences in characteristics or pre-training measures between the responders and nonresponders. For both criteria, responders demonstrated greater change in the distance walked during the training program (P < .05). Conclusion: Responders to GBWT had lower pre-training exercise capacity, had better lung function, and demonstrated greater change in the distance walked during the training program.
Efficacy and safety of 25 and 50 μg desmopressin orally disintegrating tablets in Japanese patients with nocturia due to nocturnal polyuria: Results from two phase 3 studies of a multicenter randomized double‐blind placebo‐controlled parallel‐group development program

This study assessed the efficacy and safety of desmopressin orally disintegrating tablets (ODTs) in Japanese males (50 and 25 μg) and females (25 μg) with nocturia due to nocturnal polyuria (NP). Two Phase 3 randomized double‐blind placebo‐controlled studies of 342 males and 190 females with nocturia due to NP were conducted. The primary endpoint was change from baseline in mean number of nocturnal voids. In addition, time to first awakening to void, nocturnal urine volume, NP index (NPI), and quality of life were assessed during a 12‐week treatment period. In males, 50 and 25 μg desmopressin ODTs significantly reduced the number of nocturnal voids by −1.21 (P < .0001) and − 0.96 (P = .0143), respectively, and significantly prolonged the time to first awakening to void by 117.60 minutes (P < .0001) and 93.37 minute (P = .0009), respectively, with no safety concerns. In females, 25 μg desmopressin ODT significantly prolonged the time to first awakening to void by 116.11 minutes (P = .0257), with no safety concerns. The reduction in the number of nocturnal voids (−1.11) was not significantly different compared with placebo (P = .0975). Desmopressin ODTs (50 and 25 μg) were an effective and well‐tolerated treatment for nocturia due to NP in Japanese males, and desmopressin ODT 50 μg is an appropriate dose in these patients. For patients who are likely to experience hyponatremia, such as elderly males, starting with 25 μg desmopressin ODT should be considered.
How Substitutional Point Defects in Two-Dimensional WS2 Induce Charge Localization, Spin-Orbit Splitting, and Strain.

Control of impurity concentrations in semiconducting materials is essential to device technology. Because of their intrinsic confinement, the properties of two-dimensional semiconductors such as transition metal dichalcogenides (TMDs) are more sensitive to defects than traditional bulk materials. The technological adoption of TMDs is dependent on the mitigation of deleterious defects and guided incorporation of functional foreign atoms. The first step towards impurity control is the identification of defects and assessment of their electronic properties. Here, we present a comprehensive study of point defects in monolayer tungsten disulfide (WS2) grown by chemical vapor deposition (CVD) using scanning tunneling microscopy/spectroscopy, CO-tip noncontact atomic force microscopy, Kelvin probe force spectroscopy, density functional theory, and tight-binding calculations. We observe four different substitutional defects: chromium (Cr_W) and molybdenum (Mo_W) at a tungsten site, oxygen at sulfur sites in both bottom and top layers (O_S top/bottom), as well as two negatively charged defects (CD type I and CD type II). Their electronic fingerprints unambiguously corroborate the defect assignment and reveal the presence or absence of in-gap defect states. Cr_W forms three deep unoccupied defect states, two of which arise from spin-orbit splitting. The formation of such localized trap states for Cr_W differs from the Mo_W case and can be explained by their different d shell energetics and local strain, which we directly measured. Utilizing a tight-binding model the electronic spectrum of the isolectronic substitutions O_S and Cr_W are mimicked in the limit of a zero hopping term and infinite onsite energy at a S and W site, respectively. The abundant CDs are negatively charged, which leads to a significant band bending around the defect and a local increase of the contact potential difference. In addition, CD-rich domains larger than 100 nm are observed causing a work function increase of 1.1 V. While most defects are electronically isolated, we also observed hybrid states formed between Cr_W dimers. The important role of charge localization, spin-orbit coupling, and strain for the formation of deep defect states observed at substitutional defects in WS2 as reported here will guide future efforts of targeted defect engineering and doping of TMDs.
Altitude and fungal diversity influence the structure of Antarctic cryptoendolithic Bacteria communities.

Endolithic growth within rocks is a critical adaptation of microbes living in harsh environments where exposure to extreme temperature, radiation, and desiccation limits the predominant life-forms, such as in the ice-free regions of Continental Antarctica. The microbial diversity of the endolithic communities in these areas has been sparsely examined. In this work, diversity and composition of bacterial assemblages in the cryptoendolithic lichen-dominated communities of Victoria Land (Continental Antarctica) were explored using a high-throughput metabarcoding approach, targeting the V4 region of 16S rDNA. Rocks were collected in 12 different localities (from 14 different sites), along a gradient ranging from 1,000 to 3,300 m a.s. l. and at a sea distance ranging from 29 to 96 km. The results indicate Actinobacteria and Proteobacteria are the dominant taxa in all samples and defined a 'core' group of bacterial taxa across all sites. The structure of bacteria communities is correlated with the fungal counterpart and among the environmental parameters considered, altitude was found to influence bacterial biodiversity, while distance from sea had no evident influence. This article is protected by copyright. All rights reserved.
Isoliquiritigenin‐induced vasodilation by activating large‐conductance Ca2+‐activated K+ channels in mouse mesenteric arteries

Isoliquiritigenin (ISL) is a flavonoid substance with a chalcone structure, which exerts anti‐tumour, anti‐oxidation and anti‐inflammatory activity. The large‐conductance calcium‐activated potassium channel (BKCa) is an important potassium channel with negative feedback regulation on the vascular smooth muscle cells (VSMCs) membrane. The activation of BKCa channel causes the hyperpolarization of VSMCs. It plays an important role in relaxation of blood vessels. Previous studies have shown that ISL causes the relaxation of the aorta and the basilar artery of the rat. However, there have not been studies on regulation of ISL in mesenteric arteries. To examine whether ISL causes the relaxation of the mesenteric artery of mice, we recorded vasodilation of mouse mesenteric arterial rings with a myograph. After contraction of arterial rings with phenylephrine, we added ISL to the arterial rings and measured its relaxation effect. To further examine which channel was involved in this relaxation effect, we tested the effects of ISL on endothelium‐dependent and endothelium‐independent vasodilation. Then we used BKCa channel blockers tetraethylammonium and iberiotoxin, to detect whether the BKCa channel is involved in ISL‐induced vasodilation. Mesenteric arterial smooth muscle cells were isolated by enzyme digestion. Bis‐(1, 3‐dibutylbarbituric acid) trimethine oxonol staining was used to measure membrane potential of mesenteric arterial smooth muscle cells. We identified a vasodilation effect caused by ISL on mouse mesenteric arterial rings pre‐contracted by phenylephrine in a concentration‐dependent manner, with an EC50 of 13.71 ± 1.1 μmol/L. The vasodilation effect of ISL is endothelium‐independent. K+ channel inhibitors tetraethylammonium and iberiotoxin reduced the vasodilation induced by ISL which suggested the involvement of BKCa channel.
A positive feedback loop comprising LHW-TMO5 and local auxin biosynthesis regulates initial vascular development in Arabidopsis roots.

The phytohormone auxin governs various developmental processes in plants including vascular formation. Auxin transport and biosynthesis are important factors in determining auxin distribution in tissues. While the role of auxin transport in vein pattern formation is widely recognized, that of auxin biosynthesis in vascular development is poorly understood. Heterodimer complexes comprising two basic helix-loop-helix protein families, LONESOME HIGHWAY (LHW) and TARGET OF MONOPTEROS5 (TMO5)/TMO5-LIKE1 (T5L1), are master transcriptional regulators of the initial process of vascular development. The LHW-TMO5/T5L1 dimers regulate vascular initial cell production, vascular cell proliferation, and xylem fate determination in the embryo and root apical meristem (RAM). In this study, we investigated the function of local auxin biosynthesis in initial vascular development in RAM. Results showed that LHW-T5L1 upregulated the expression of YUCCA4 (YUC4), a key auxin biosynthesis gene. The expression of YUC4 was essential for promoting xylem differentiation and vascular cell proliferation in RAM. Conversely, auxin biosynthesis was required for maintaining the expression levels of LHW, TMO5/T5L1, and their targets. Our results suggest that local auxin biosynthesis forms a positive feedback loop for fine-tuning the level of LHW-TMO5/T5L1, which is necessary for initiating vascular development.
Small but Steady Steps in Stroke Medicine in Japan

December 14, 1702, was an unforgettable day for many Japanese, when 47 samurais from Ako Domain launched a raid on their foe's residence in the snowy night of Edo (the former name of Tokyo) and avenged their deceased master, who was illogically forced to commit suicide by self‐disembowelment on a sword, after waiting and planning for a year and a half persevering through all sorts of hardships. They have been repeatedly praised by Bunraku (puppet play) and Kabuki plays, novels, and movies. On the same day 316 years later (December 14, 2018), a Stroke and Cardiovascular Disease Control Act was proclaimed by the Japanese government to vanquish these national maladies.1 Eight basic policies on stroke and cardiovascular diseases are listed in the new law: (1) promotion of education to the general population and prevention by national and local governments; (2) development of a system for transportation using an ambulance and others and acceptance of emergent patients; (3) development of medical institutes where specialized medical care for stroke and cardiovascular diseases can be offered; (4) maintenance and improvement of participation in social activities and other quality of life for patients with subsequent complications; (5) development of a system for collaboration among agencies involved in health, medical care, and welfare, such as hospital ambulance services, social welfare services, and others; (6) human resource development for health, medical support, and welfare; (7) development of a system for collection and provision of information; and (8) promotion of research. The Japan Stroke Association, a stroke support organization, and other organizations prepared the draft for the basic law on stroke in 2009 and appealed to the government for its enactment but without success. The bill was then expanded to include cardiovascular disease in general and was then finally approved. The Japan Stroke Society, an academic organization, has joined with the Japanese Circulation Society for the 5‐year strategy for stroke and cardiovascular diseases (Stop CVD Project) since 2016 in anticipation of the basic law. Although stroke has long been called the Japanese national disease, the government was relatively slow to act to take measures for stroke care compared with cancer care. The new Act is a steady step forward for tomorrow's stroke medicine in Japan.