Notes

Semiparametric investigation regarding multivariate screen depend data with nonlinear connections.
ERCC6 deficiency alleviated neuronal damage and apoptosis. Macrophage infiltration and inflammatory response were suppressed by si-ERCC6 treatment. Moreover, ERCC6 blockage ameliorated astrocyte and microglia activation and cell senescence in the damaged spinal cord. Excessive oxidative stress was significantly decreased by ERCC6 knockdown in SCI. Conclusion Collectively, ERCC6 exerts crucial functions in mediating physiological processes (apoptosis, inflammation, senescence, and oxidative stress), implying that ERCC6 might act as a prospective therapeutic target against SCI.The COVID-19 pandemic resulting from the spread of SARS-CoV-2 spurred devastating health and economic crises around the world. Neutralizing antibodies and licensed vaccines were developed to combat COVID-19, but progress was slow. In addition, variants of the receptor-binding domain (RBD) of the spike protein confer resistance of SARS-CoV-2 to neutralizing antibodies, nullifying the possibility of human immunity. Therefore, investigations into the RBD mutations that disrupt neutralization through convalescent antibodies are urgently required. In this study, we comprehensively and systematically investigated the binding stability of RBD variants targeting convalescent antibodies and revealed that the RBD residues F456, F490, L452, L455, and K417 are immune-escaping hotspots, and E484, F486, and N501 are destabilizing residues. Our study also explored the possible modes of actions of emerging SARS-CoV-2 variants. All results are consistent with experimental observations of attenuated antibody neutralization and clinically emerging SARS-CoV-2 variants. We identified possible immune-escaping hotspots that could further promote resistance to convalescent antibodies. The results provide valuable information for developing and designing novel monoclonal antibody drugs to combat emerging SARS-CoV-2 variants.Virtual screening is a cost- and time-effective alternative to traditional high-throughput screening in the drug discovery process. Both virtual screening approaches, structure-based molecular docking and ligand-based cheminformatics, suffer from computational cost, low accuracy, and/or reliance on prior knowledge of a ligand that binds to a given target. Here, we propose a neural network framework, NeuralDock, which accelerates the process of high-quality computational docking by a factor of 106, and does not require prior knowledge of a ligand that binds to a given target. By approximating both protein-small molecule conformational sampling and energy-based scoring, NeuralDock accurately predicts the binding energy, and affinity of a protein-small molecule pair, based on protein pocket 3D structure and small molecule topology. We use NeuralDock and 25 GPUs to dock 937 million molecules from the ZINC database against superoxide dismutase-1 in 21 h, which we validate with physical docking using MedusaDock. Due to its speed and accuracy, NeuralDock may be useful in brute-force virtual screening of massive chemical libraries and training of generative drug models.
The objective of this study was to describe the development process of the Korean Healthy Eating Index (KHEI) based on the Korea National Health and Nutrition Examination Survey (KNHANES).

The components of KHEI were selected based on Dietary Guidelines for Koreans, domestic and overseas dietary quality indices, and results of the analysis of association with chronic diseases. The standards for scoring of KHEI were selected based on the 2015 Dietary Reference Intakes for Koreans (KDRI). The KHEI scores of Korean adults were calculated using a 1-day 24-h recall data in the 2013-2015 KNHANES.

The KHEI included eight adequacy components evaluating the proper intake of recommended foods such as fruit, vegetable, and milk and three moderation components evaluating the consumption of food that limit intake such as sodium and saturated fatty acid. In addition, three balance components assessing the balance of energy intake were included. The KHEI score was defined to range from the minimum of 0 point to the maximum of 100 points. Among Korean adults, the total KHEI score was 63.2 out of 100. Gender and age differences were found in the average of total KHEI scores. Women showed higher score than men (61.7 in men and 64.7 in women, respectively). By age group, 20s and 30s showed the lowest scores with 57.4 and 61.1 respectively, and the scores increased with age by peaking at 67.8 in ages 60-69 and slowed down again in ages 70 or over.

The KHEI can be useful for establishing and assessing national nutritional policies and in epidemiological studies to assess the relationship between overall dietary quality and chronic diseases. KHEI will need to be continuously updated to reflect changes in dietary guidelines and the KDRI.
The KHEI can be useful for establishing and assessing national nutritional policies and in epidemiological studies to assess the relationship between overall dietary quality and chronic diseases. Selleckchem LLY-283 KHEI will need to be continuously updated to reflect changes in dietary guidelines and the KDRI.
While many obesity studies have pointed out the importance of meal regularity, few have conducted empirical analyses using data from food diaries. We examined the association between meal regularity (
, meal time regularity [MTR] and calorie intake regularity [CIR]) and weight loss.

We collected food diary data from 637 women who had participated in commercial weight loss programs for 28-168 days (4-24 weeks). This study defined "meal regularity" in terms of two concepts MTR and CIR. MTR refers to how regularly people eat their meals (
, at certain times each day), whereas CIR refers to how regularly people consume a certain amount of calories at each meal. We conducted multiple regression analyses.

MTR (model 1 β = -2,576.526,
< 0.001; model 2 β = -1511.447,
< 0.05; model 3 β = -1,721.428,
< 0.05) and CIR (model 1 β = -1,231.551,
< 0.01; model 2 β = -2,082.353,
< 0.001; model 3 β = -1,343.490,
< 0.01) turned out to be significant determinants of the amount of weight loss in breakfast, lunch, and dinner contexts. While meal regularity (
, MTR and CIR) was significantly associated with weight loss, daily calorie intake from meals was not significantly associated with the amount of weight loss (model 1 β = 0.13,
> 0.05; model 2 β = 0.11,
> 0.05; model 3 β = 0.14,
> 0.05). Subjects who consumed an equal amount of calories per meal throughout the day lost more weight than those who did not (model 4 β = -3,675.51,
< 0.001).

Eating each meal (
, breakfast, lunch, and dinner) at a certain time every day may increase weight loss success. Also, consuming the same amount of calories at each meal may help weight loss success.
Eating each meal (i.e., breakfast, lunch, and dinner) at a certain time every day may increase weight loss success. Also, consuming the same amount of calories at each meal may help weight loss success.
Patients with chronic kidney disease (CKD) have a high concentration of uremic toxins in their blood and often experience muscle atrophy. Indoxyl sulfate (IS) is a uremic toxin produced by tryptophan metabolism. Although an elevated IS level may induce muscle dysfunction, the effect of IS on physiological concentration has not been elucidated. Additionally, the effects of ursolic acid (UA) on muscle hypertrophy have been reported in healthy models; however, it is unclear whether UA ameliorates muscle dysfunction associated with chronic diseases, such as CKD. Thus, this study aimed to investigate whether UA can improve the IS-induced impairment of mitochondrial biogenesis.

C2C12 cells were incubated with or without IS (0.1 mM) and UA (1 or 2 µM) to elucidate the physiological effect of UA on CKD-related mitochondrial dysfunction and its related mechanisms using real-time reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay.

IS suppressed the expression of differentiation marker genes without decreasing cell viability. IS decreased the mitochondrial DNA copy number and ATP levels by downregulating the genes pertaining to mitochondrial biogenesis (
,
,
,
, and
), fusion (
and
), oxidative phosphorylation (
and
), and fatty acid oxidation (
,
,
and
). Furthermore, IS increased the intracellular mRNA and secretory protein levels of interleukin (IL)-6. Finally, UA ameliorated the IS-induced impairment in C2C12 cells.

Our results indicated that UA improves the IS-induced impairment of mitochondrial biogenesis by affecting differentiation, ATP levels, and IL-6 secretion in C2C12 cells. Therefore, UA could be a novel therapeutic agent for CKD-induced muscle dysfunction.
Our results indicated that UA improves the IS-induced impairment of mitochondrial biogenesis by affecting differentiation, ATP levels, and IL-6 secretion in C2C12 cells. Therefore, UA could be a novel therapeutic agent for CKD-induced muscle dysfunction.
Colorectal cancer (CRC) is the third most common cancer worldwide and has a high recurrence rate, which is associated with cancer stem cells (CSCs). β-carotene (BC) possesses antioxidant activity and several anticancer mechanisms. However, no investigation has examined its effect on colon cancer stemness.

CD133
CD44
HCT116 and CD133
CD44
HT-29 cells were isolated and analyzed their self-renewal capacity by clonogenic and sphere formation assays. Expressions of several CSCs markers and Wnt/β-catenin signaling were examined. In addition, CD133
CD44
HCT116 cells were subcutaneously injected in xenograft mice and analyzed the effect of BC on tumor formation, tumor volume, and CSCs markers in tumors.

BC inhibited self-renewal capacity and CSC markers, including
,
,
,
, Sox2, and β-catenin
. The effects of BC on CSC markers were confirmed in primary cells isolated from human CRC tumors. BC supplementation decreased the number and size of tumors and delayed the tumor-onset time in xenograft mice injected with CD133
CD44
HCT116 cells. The inhibitory effect of BC on CSC markers and the Wnt/β-catenin signaling pathway in tumors was confirmed
as well.

These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.
These results suggest that BC may be a potential therapeutic agent for colon cancer by targeting colon CSCs.
Alzheimer's disease (AD) is one of the most representative neurodegenerative disease mainly caused by the excessive production of amyloid beta (Aβ). Several studies on the antioxidant activity and protective effects of
(PT) against cerebral ischemia-induced neuronal damage have been reported. Based on this background, the present study investigated the protective effects of PT against cognitive impairment in AD.

We orally administered PT (50 and 100 mg/kg/day) for 14 days in an Aβ
-induced mouse model and conducted behavioral experiments to test cognitive ability. In addition, we evaluated the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and measured the production of lipid peroxide, nitric oxide (NO), and reactive oxygen species (ROS) in tissues.

PT treatment improved the space perceptive ability in the T-maze test, object cognitive ability in the novel object recognition test, and spatial learning/long-term memory in the Morris water-maze test. Moreover, the levels of AST and ALT were not significantly different among the groups, indicating that PT did not show liver toxicity.
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