Metal-support interaction is of great significance for catalysis as it can induce charge transfer between metal and support, tame electronic structure of supported metals, impact adsorption energy of ...reaction intermediates, and eventually change the catalytic performance. Here, we report the metal size-dependent charge transfer reversal, that is, electrons transfer from platinum single atoms to sulfur-doped carbons and the carbon supports conversely donate electrons to Pt when their size is expanded to ~1.5 nm cluster. The electron-enriched Pt nanoclusters are far more active than electron-deficient Pt single atoms for catalyzing hydrogen evolution reaction, exhibiting only 11 mV overpotential at 10 mA cm
and a high mass activity of 26.1 A mg
at 20 mV, which is 38 times greater than that of commercial Pt/C. Our work manifests that the manipulation of metal size-dependent charge transfer between metal and support opens new avenues for developing high-active catalysts.
Highlights • Depression and frailty are two common and pervasive conditions in older age. • We conducted the first meta-analysis exploring the relationship between these constructs. • In ...cross-sectional studies, participants with frailty had fourfold increased odds of depression. • People with depression were at approximately fourfold increased odds of having frailty. • Pooled data from longitudinal studies confirmed the heighted risk of comorbidity.
We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer's disease (AD), vascular dementia ...(VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27
, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787-0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576-0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556-0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620-1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818-0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383-1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449-0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475-1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD.
Abstract
Background
The Coronavirus disease 2019 (COVID-19) pandemic has placed a great burden on Taiwan’s health care system. It has also had a great impact on other public health issues, including ...cancer screening. Delayed cancer screening was also noticed in the U.S. during the pandemic, which may have led to both delayed diagnosis and poor prognosis. In Taiwan, population-based cancer screening for breast cancer, oral cancer, colon cancer and cervical cancer has been executed and ongoing for years.
Method
In this study we have analyzed the change in screening numbers for cancer during the period of the 2019 to 2021 COVID-19 outbreak in Taiwan.
Results
Through our results we found that total cancer screening numbers decreased from 307,547 to 103,289 (a 66% decrease) from the years 2020 to 2021. Specifically, a 63%, 79%, 65% and 71% decrease in screening cases was seen for colon cancer, oral cancer, cervical cancer and breast cancer, respectively, during that period. A similar condition was noticed when comparing 2019 to 2021 when the disclosed total cancer screening numbers decreased by 70% (2019–2021); 65%, 83%, 70% and 76% in colon cancer, oral cancer, cervical cancer and breast cancer, respectively. Among these various cancer screenings, oral cancer screening showed the greatest reduction rate (a drop of 83% compared to 2019 and 79% compared to 2020). We also compared the reduction rates taken from different regions in Taiwan. It was in Taipei, where most COVID-19 cases were noted, that the greatest reduction rate of cancer screening numbers occurred (a drop of76% compared to 2019 and 74% compared to 2020). A proportional decrease of screening cases was also noticed in all areas when confirmed COVID-19 cases rose.
Conclusions
Screening for cancers dropped significantly due to the pandemic and its effect on long-term health needs to be evaluated. Additionally, efforts should be taken to address these cancer screening number deficits which have taken place during the COVID-19 pandemic.
Day care service (DCS) provides various activities in a professional environment to meet the old people with functional limitations. However, relatively little is known about the effects of DCS on ...physical and mental functions. This was a retrospective study that we used a comprehensive geriatric assessment to evaluate the changes before and after DCS among participants in a hospital-affiliated geriatric day care center in Taiwan. The burden of the participants' families was also assessed. The 18 participants with a median age of 80.9 (interquartile range (IQR) 75.2-86.6 y/o) were enrolled and followed up for 6 months. Based on the clinical dementia rating (CDR), disease stage was very mild in 3 participants, mild in 10, moderate in 3, and severe in 2. The activities of daily living (ADL) scores of the participants improved significantly from 75 (IQR 60.0-80.0) at baseline to 77.5 (IQR 65.0-90.0) at the 6 month (p < 0.001), and mini-mental state examination (MMSE) scores from 15 (IQR 11.5-20.0) to 18 (IQR 15.8-24.0) (p = 0.026). There was a positive correlation of baseline mini-nutritional assessment-short form score and the 3-level version of the European Quality of Life-5 dimensions utility index with both ADL and MMSE scores at the 6-month follow-up. In addition, the family burden scale was reduced from 22 to 15 (p = 0.002). The physical and cognitive functions in old people with dementia who received DCS were maintained or partially improved, and their families' stress burden was alleviated.
Sarcopenia, a newly recognized geriatric syndrome, is characterized by age-related decline of skeletal muscle plus low muscle strength and/or physical performance. Previous studies have confirmed the ...association of sarcopenia and adverse health outcomes, such as falls, disability, hospital admission, long term care placement, poorer quality of life, and mortality, which denotes the importance of sarcopenia in the health care for older people. Despite the clinical significance of sarcopenia, the operational definition of sarcopenia and standardized intervention programs are still lacking. It is generally agreed by the different working groups for sarcopenia in the world that sarcopenia should be defined through a combined approach of muscle mass and muscle quality, however, selecting appropriate diagnostic cutoff values for all the measurements in Asian populations is challenging. Asia is a rapidly aging region with a huge population, so the impact of sarcopenia to this region is estimated to be huge as well. Asian Working Group for Sarcopenia (AWGS) aimed to promote sarcopenia research in Asia, and we collected the best available evidences of sarcopenia researches from Asian countries to establish the consensus for sarcopenia diagnosis. AWGS has agreed with the previous reports that sarcopenia should be described as low muscle mass plus low muscle strength and/or low physical performance, and we also recommend outcome indicators for further researches, as well as the conditions that sarcopenia should be assessed. In addition to sarcopenia screening for community-dwelling older people, AWGS recommends sarcopenia assessment in certain clinical conditions and healthcare settings to facilitate implementing sarcopenia in clinical practice. Moreover, we also recommend cutoff values for muscle mass measurements (7.0 kg/m(2) for men and 5.4 kg/m(2) for women by using dual X-ray absorptiometry, and 7.0 kg/m(2) for men and 5.7 kg/m(2) for women by using bioimpedance analysis), handgrip strength (<26 kg for men and <18 kg for women), and usual gait speed (<0.8 m/s). However, a number of challenges remained to be solved in the future. Asia is made up of a great number of ethnicities. The majority of currently available studies have been published from eastern Asia, therefore, more studies of sarcopenia in south, southeastern, and western Asia should be promoted. On the other hand, most Asian studies have been conducted in a cross-sectional design and few longitudinal studies have not necessarily collected the commonly used outcome indicators as other reports from Western countries. Nevertheless, the AWGS consensus report is believed to promote more Asian sarcopenia research, and most important of all, to focus on sarcopenia intervention studies and the implementation of sarcopenia in clinical practice to improve health care outcomes of older people in the communities and the healthcare settings in Asia.
Chronic kidney disease (CKD), low serum albumin, and anemia are known risk factors for cognitive decline in older people. We investigated the association between kidney function and cognitive ...impairment severity in oldest-old people with a diagnosis of Alzheimer's disease (AD).
A cross-sectional study of patients aged 80 years and older was conducted at a veterans' home in Taiwan between 2012 and 2016. Their estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Diseases (MDRD) equation. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR).
A total of 84 patients (age mean ± SD, 86.6 ± 3.9 years) had MMSE scores of 10.1 ± 6.7, and CDR scores of 1.6 ± 0.7. The average eGFR was 61.7 ± 21.5 mL/min/1.73m
. The mean hemoglobin concentration was 12.7 ± 1.7 g/dl, and the mean albumin concentration was 4.5 ± 4.8 g/dl. Multivariate regression analyses showed that scores of CDR were significantly correlated with eGFR after adjustment for potential confounders. The scores of MMSE were significantly correlated with serum albumin and hemoglobin after adjustment for potential confounders.
We found dementia severity was significantly associated with kidney function, serum albumin, and hemoglobin in the oldest-old with AD. We recommend that oldest-old people with a diagnosis of AD be evaluated to determine kidney function, as well as nutritional and hematological status. Further study is needed to establish whether prevention of CKD deterioration, and correction of malnutrition and anemia may help to slow cognitive decline in oldest-old people with dementia.
Colletotrichum gloeosporioides species complex (CGSC) is the major pathogen causing strawberry anthracnose in Taiwan. Benzimidazoles and strobilurins are common fungicides used to control strawberry ...anthracnose. A total of 108 CGSC isolates were collected from five major strawberry-producing areas in Taiwan. The half-maximal effective concentration (EC50) values of most CGSC isolates for benomyl (59 isolates), carbendazim (70 isolates), and thiabendazole (63 isolates) were higher than 500 µg a.i./mL. Strobilurin tests showed that the EC50 values of most CGSC isolates for azoxystrobin (66 isolates), kresoxim-methyl (42 isolates), and trifloxystrobin (56 isolates) were higher than 500 µg a.i./mL. However, most CGSC isolates were sensitive to pyraclostrobin at 100 µg a.i./mL. Fungicide tests indicated that CGSC isolates show multi-resistance to benzimidazoles and strobilurins. Benzimidazole-resistant isolates were associated with a point mutation in codon 198 of the β-tubulin gene, and strobilurin-resistant isolates did not correspond with mutation in the cyt b gene or alternative oxidase activity.
Our previous study found that 2-phenyl-4-quinolone (2-PQ) derivatives are antimitotic agents, and we adopted the drug design concept of scaffold hopping to replace the 2-aromatic ring of 2-PQs with a ...4-aromatic ring, representing 4-phenyl-2-quinolones (4-PQs). The 4-PQ compounds, whose structural backbones also mimic analogs of podophyllotoxin (PPT), maybe a new class of anticancer drugs with simplified PPT structures. In addition, 4-PQs are a new generation of anticancer lead compounds as apoptosis stimulators. On the other hand, previous studies showed that 4-arylcoumarin derivatives with 5-, 6-, and 7-methoxy substitutions displayed remarkable anticancer activities. Therefore, we further synthesized a series of 5-, 6-, and 7-methoxy-substituted 4-PQ derivatives (
-
) by Knorr quinoline cyclization, and examined their anticancer effectiveness. Among these 4-PQs, compound
demonstrated excellent antiproliferative activities against the COLO205 cell line (50% inhibitory concentration (IC
) = 0.32 μM) and H460 cell line (IC
= 0.89 μM). Furthermore, we utilized molecular docking studies to explain the possible anticancer mechanisms of these 4-PQs by the docking mode in the colchicine-binding pocket of the tubulin receptor. Consequently, we selected the candidate compounds
,
,
,
,
,
, and
to predict their absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. Pharmacokinetics (PKs) indicated that these 4-PQs displayed good drug-likeness and bioavailability, and had no cardiotoxic side effects or carcinogenicity, but we detected risks of drug-drug interactions and AMES toxicity (mutagenic). However, structural modifications of these 4-PQs could improve their PK properties and reduce their side effects, and their promising anticancer activities attracted our attention for further studies.
Natural phenolic products from herbal medicines and dietary plants constitute the main source of lead compounds for the development of the new drug. 4,4-Dimethylcurcumin (DMCU) is a synthetic ...curcumin derivative and exhibits anticancer activities against breast, colon, lung, and liver cancers. However, further development of DMCU is limited by unfavorable compound properties such as very low aqueous solubility and moderate stability. To increase its solubility, we installed either or both of the ethylene-carbonate-linked L-valine side chains to DMCU phenolic groups and produced targeted 1-trifluoroacetic acid (1-TFA) and 2-trifluoroacetic acid (2-TFA) derivatives. The terminus L-valine of ethylene-carbonate-linked side chain is known to be a L-type amino acid transporter 1 (LAT1) recognition element and therefore, these two derivatives were expected to readily enter into LAT1-expressing cancer cells. In practice, 1-TFA or 2-TFA were synthesized from DMCU in four steps with 34–48% overall yield. Based on the corresponding LC-MS analysis, water solubility of DMCU, 1-TFA, and 2-TFA at room temperature (25 ± 1 °C) were 0.018, 249.7, and 375.8 mg/mL, respectively, indicating >10,000-fold higher solubility of 1-TFA and 2-TFA than DMCU. Importantly, anti-proliferative assay demonstrated that 2-TFA is a potent anti-cancer agent against LAT1-expressing lung cancer cells NCI-H460, NCI-H358, and A549 cells due to its high intracellular uptake compared to DMCU and 1-TFA. In this study, we logically designed and synthesized the targeted compounds, established the LC-MS analytical methods for evaluations of drug solubility and intracellular uptake levels, and showed improved solubility and anti-cancer activities of 2-TFA. Our results provide a strategical direction for the future development of curcuminoid-like phenolic compounds.
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