The catalytic transfer hydrogenation (CTH) reaction is considered as a potential route for upgrading bio-based carbonyls to their corresponding alcohols. Herein, a series of Zr-based metal−organic ...frameworks (Zr-MOFs) containing various types of metal node to ligand coordinations were synthesized and tested for CTH of furfural (FUR) to furfuryl alcohol (FOL). It was found that metal node coordination plays a more important role than porosity in Zr-MOFs. MOF-808 (synthesized using a scaled-up approach to achieve a higher batch yield), with the lowest metal node to ligand coordination (coordination number 6), was found to be the most active catalyst among the various tested Zr-MOFs. Furthermore, M-MOF-808, modified by simple methanol activation (M), outperformed the pristine MOF-808 in CTH of FUR to FOL even at 30 °C in the presence of 2-propanol (IPA) as the hydrogen source. The simple modification of the metal node in the Zr-MOF changed the acid–base properties of the MOF-808 surface through the development of coordinatively unsaturated sites (CUS), hydroxyl and methoxy groups in the framework of the Zr-MOF, which probably help to facilitate the adsorption of FUR and IPA onto the metal node surfaces of the catalyst. To evaluate the versatility of methanol activation in CTH, further substrates, including other types of biomass and representative carbonyl compounds over M-MOF-808, were tested. To demonstrate heterogeneous catalysis, the catalyst was recycled for five consecutive cycles, with little loss after the first cycle, and was fully characterized to observe any changes in its structure. Mechanistic insights were provided by isotopically labeled 2-propanol-d 8 experiments, indicating FUR reduction through transfer hydrogenation. Finally, the reaction mechanism for CTH of FUR to FOL was proposed in detail using density functional theory (DFT) calculations over metal node modified model systems of a 6-connected Zr-MOF.
A "masked face", that is, decreased facial expression is considered as one of the cardinal symptoms among individuals with Parkinson's disease (PD). Both spontaneous and voluntary mimicry toward ...others' emotional expressions is essential for both social communication and emotional sharing with others. Despite many studies showing impairments in facial movements in PD in general, it is still unclear whether voluntary, spontaneous, or both types of mimicry are affected and how the impairments affect the patients' quality of life. We investigated to verify whether impairments in facial movements happen for spontaneous as well as for voluntary expressions by quantitatively comparing muscle activations using surface electromyography. Dynamic facial expressions of Neutral, Anger, Joy, and Sad were presented during recordings in corrugator and zygomatic areas. In the spontaneous condition, participants were instructed to simply watch clips, whereas in the voluntary condition they were instructed to actively mimic the stimuli. We found that PD patients showed decreased mimicry in both spontaneous and voluntary conditions compared to a matched control group, although movement patterns in each emotion were similar in the two groups. Moreover, whereas the decrease in mimicry correlated with the decrease not in a health-related quality of life index (PDQ), it did so in a more subjective measurement of general quality of life index (SWB). The correlation between facial mimicry and subjective well-being index suggests that the 'masked face' symptom deteriorates patients' quality of life in a complex way affecting social and psychological aspects, which in turn may be linked to the increased depression risk among individuals with PD.
Angiogenesis is a multistep process that requires coordinated migration, proliferation, and junction formation of vascular endothelial cells (ECs) to form new vessel branches in response to growth ...stimuli. Major intracellular signaling pathways that regulate angiogenesis have been well elucidated, but key transcriptional regulators that mediate these signaling pathways and control EC behaviors are only beginning to be understood. Here, we show that YAP/TAZ, a transcriptional coactivator that acts as an end effector of Hippo signaling, is critical for sprouting angiogenesis and vascular barrier formation and maturation. In mice, endothelial-specific deletion of Yap/Taz led to blunted-end, aneurysm-like tip ECs with fewer and dysmorphic filopodia at the vascular front, a hyper-pruned vascular network, reduced and disarranged distributions of tight and adherens junction proteins, disrupted barrier integrity, subsequent hemorrhage in growing retina and brain vessels, and reduced pathological choroidal neovascularization. Mechanistically, YAP/TAZ activates actin cytoskeleton remodeling, an important component of filopodia formation and junction assembly. Moreover, YAP/TAZ coordinates EC proliferation and metabolic activity by upregulating MYC signaling. Overall, these results show that YAP/TAZ plays multifaceted roles for EC behaviors, proliferation, junction assembly, and metabolism in sprouting angiogenesis and barrier formation and maturation and could be a potential therapeutic target for treating neovascular diseases.
Endoplasmic reticulum (ER) stress is involved in non-alcoholic fatty liver disease (NAFLD), but the relationship between oxidative stress, another well-known risk factor of NAFLD, and ER stress has ...yet to be elucidated. In this study, we treated mice with tunicamycin (TM) (2 mg/kg body weight) for 48 h to induce ER stress in the liver and examined the metabolic pathway that synthesizes the endogenous antioxidant, glutathione (GSH). Tunicamycin (TM) treatment significantly increased mRNA levels of CHOP and GRP78, and induced lipid accumulation in the liver. Lipid peroxidation in the liver tissue also increased from TM treatment (CON vs. TM; 3.0 ± 1.8 vs. 11.1 ± 0.8 nmol MDA/g liver,
< 0.001), which reflects an imbalance between the generation of reactive substances and antioxidant capacity. To examine the involvement of GSH synthetic pathway, we determined the metabolomic changes of sulfur amino acids in the liver. TM significantly decreased hepatic S-adenosylmethionine concentration in the methionine cycle. The levels of cysteine in the liver were increased, while taurine concentration was maintained and GSH levels profoundly decreased (CON vs. TM; 8.7 ± 1.5 vs. 5.4 ± 0.9 µmol GSH/g liver,
< 0.001). These results suggest that abnormal cysteine metabolism by TM treatment resulted in a decrease in GSH, followed by an increase in oxidative stress in the liver. In HepG2 cells, decreased GSH levels were examined by TM treatment in a dose dependent manner. Furthermore, pretreatment with TM in HepG2 cells potentiated oxidative cell death, by exacerbating the effects of tert-butyl hydroperoxide. In conclusion, TM-induced ER stress was accompanied by oxidative stress by reducing the GSH synthesis, which made the liver more susceptible to oxidative stress.
Mutations that inactivate negative translation regulators cause autism spectrum disorders (ASD), which predominantly affect males and exhibit social interaction and communication deficits and ...repetitive behaviors. However, the cells that cause ASD through elevated protein synthesis resulting from these mutations remain unknown. Here we employ conditional overexpression of translation initiation factor eIF4E to increase protein synthesis in specific brain cells. We show that exaggerated translation in microglia, but not neurons or astrocytes, leads to autism-like behaviors in male mice. Although microglial eIF4E overexpression elevates translation in both sexes, it only increases microglial density and size in males, accompanied by microglial shift from homeostatic to a functional state with enhanced phagocytic capacity but reduced motility and synapse engulfment. Consequently, cortical neurons in the mice have higher synapse density, neuroligins, and excitation-to-inhibition ratio compared to control mice. We propose that functional perturbation of male microglia is an important cause for sex-biased ASD.
A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 macrophages. The ...target compounds 1a–m have first been assessed for cytotoxicity against RAW 264.7 macrophages to determine their non-cytotoxic concentration(s) for anti-inflammatory testing to make sure that the inhibition of PGE2 and NO production would not be caused by cytotoxicity. It was found that compounds 1f and 1m were the most potent PGE2 inhibitors with IC50 values of 7.1 and 1.1 μM, respectively. In addition, these compounds also showed inhibitory effects of 11.6% and 37.19% on LPS-induced NO production, respectively. The western blots analysis of COX-2 and iNOS showed that the PGE2 and NO inhibitory effect of compound 1m are attributed to inhibition of COX-2 and iNOS protein expression through inactivation of p38.
The lack of adequate and detailed epidemiological data of Parkinson's disease (PD), especially in Asia, is a barrier to future disease burdens and the prospect of effective public health plans. This ...study aimed to investigate temporal trends in the incidence and prevalence of PD in South Korea from 2010 to 2015, based on uniform diagnostic criteria.
This study examined all PD patients registered in a South Korean national registry database of more than 50 million individuals. We analyzed the incidence and prevalence of PD according to age, gender, and region.
The annual incidence of PD was between 22.4-27.8 cases per 100,000 individuals. During the 6-year study period, there were 73,726 new PD patients, 42.3% of whom were men. The standardized incidence of PD increased over time in men but remained constant in women until 2013 but began to increase in 2014. The female-to-male ratio in the incidence of PD was 1.4:1 while the female-to-male ratio in the prevalence of PD was 1.6:1. The age- and gender-standardized prevalence of PD increased from 115.9 cases per 100,000 individuals in 2010 to 139.8 cases per 100,000 individuals in 2015. From 2014, the incidence and prevalence of PD peaked in individuals aged between 80 and 89 years in both men and women. Regional analysis also showed an increased prevalence of PD in all regions of Korea.
The incidence and prevalence of PD in Korea were higher in women and increased gradually from 2010 to 2015. The findings may contribute to epidemiological studies of PD in Asia, and may provide clues on risk factors for PD.
Archaea are one of the least-studied members of the gut-dwelling autochthonous microbiota. Few studies have reported the dominance of methanogens in the archaeal microbiome (archaeome) of the human ...gut, although limited information regarding the diversity and abundance of other archaeal phylotypes is available.
We surveyed the archaeome of faecal samples collected from 897 East Asian subjects living in South Korea. In total, 42.47% faecal samples were positive for archaeal colonisation; these were subsequently subjected to archaeal 16S rRNA gene deep sequencing and real-time quantitative polymerase chain reaction-based abundance estimation. The mean archaeal relative abundance was 10.24 ± 4.58% of the total bacterial and archaeal abundance. We observed extensive colonisation of haloarchaea (95.54%) in the archaea-positive faecal samples, with 9.63% mean relative abundance in archaeal communities. Haloarchaea were relatively more abundant than methanogens in some samples. The presence of haloarchaea was also verified by fluorescence in situ hybridisation analysis. Owing to large inter-individual variations, we categorised the human gut archaeome into four archaeal enterotypes.
The study demonstrated that the human gut archaeome is indigenous, responsive, and functional, expanding our understanding of the archaeal signature in the gut of human individuals. Video Abstract.
As autophony can be accompanied by several conditions, it is important to find co-morbidities. This paper reports a patient with Kennedy's disease (spinobulbar muscular atrophy, an X-linked, ...hereditary, lower motor neuron disease) having autophony as the first symptom.
A 62-year-old male presented to the otorhinolaryngology department with autophony that began 2 years previously and worsened after losing weight 3 months prior to presentation. Otoscopic examination demonstrated inward and outward movement of the tympanic membrane, synchronised with respiration. Although he had no other symptoms, facial twitching was found on physical examination. In the neurology department, lower motor neuron disease, with subtle weakness of the tongue, face and upper limbs, and gynaecomastia, were confirmed. He was diagnosed with Kennedy's disease based on genetic analysis.
Autophonia was presumed to be attributed to bulbofacial muscle weakness due to Kennedy's disease, and worsened by recent weight loss. Patients with autophony require a thorough history-taking and complete physical examination to assess the nasopharynx and the integrity of lower cranial function.
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