Study on the Impact of Dietary Patterns on Cardiovascular Metabolic Comorbidities among Adults.

Background: The prevalence of cardiovascular metabolic comorbidities (CMM) among adults is relatively high, imposing a heavy burden on individuals, families, and society. Dietary patterns play a significant role in the occurrence and development of CMM. This study aimed to identify the combined types of CMM in adult populations and investigate the impact of dietary patterns on CMM. Methods: Participants in this study were from the sixth wave of the China Health and Nutrition Survey (CHNS). Dietary intake was assessed using a three-day 24-hour dietary recall method among 4,963 participants. Latent profile analysis was used to determine dietary pattern types. Two-step cluster analysis was performed to identify the combined types of CMM based on the participants' conditions of hyperuricemia, dyslipidemia, diabetes, renal dysfunction, hypertension, and stroke. Logistic regression analysis with robust standard errors was used to determine the impact of dietary patterns on CMM. Results: Participants were clustered into three dietary patterns (Pattern 1 to 3) and five CMM types (Class I to V). Class I combined six diseases, with a low proportion of diabetes. Class II also combined six diseases but with a high proportion of diabetes. Class III combined four diseases, with a high proportion of hypertension. Class IV combined three diseases, with the highest proportions of hyperuricemia, diabetes, and renal dysfunction. Class V combined two diseases, with high proportions of dyslipidemia and renal dysfunction. Patients with Class III CMM had a significantly higher average age than the other four classes (P ≤ 0.05). Compared to those with isolated dyslipidemia, individuals with a low-grain, high-fruit, milk, and egg (LCHFM) dietary pattern had a higher risk of developing dyslipidemia combined with renal dysfunction (Class V CMM) with an odds ratio of 2.001 (95% CI 1.011-3.960, P≤ 0.05). Conclusion: For individuals with isolated dyslipidemia, avoiding a low-grain, high-fruit, milk, and egg (LCHFM) dietary pattern may help reduce the risk of developing dyslipidemia combined with renal dysfunction (Class V CMM).

Involvement of oxidative stress-AMPK-Cx43-NLRP3 pathway in extracellular matrix remodeling of gastric smooth muscle cells in rats with diabetic gastroparesis.

This study aimed to investigate the changes in oxidative stress, adenosine monophosphate-activated protein kinase (AMPK), connexin43 (Cx43), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression, and extracellular matrix (ECM) in the gastric smooth muscle tissues of rats with diabetic gastroparesis (DGP) and high glucose-cultured gastric smooth muscle cells, determine the existence of oxidative stress-AMPK-Cx43-NLRP3 pathway under high glucose condition, and the involvement of this pathway in ECM remodeling in DGP rats. The results showed that with increasing duration of diabetes, oxidation stress levels gradually increased, the AMPK activity decreased first and then increased, NLRP3, CX43 expression, and membrane/cytoplasm ratio of Cx43 expression were increased in the gastric smooth muscle tissues of diabetic rats. Changes in ECM of gastric smooth muscle cells were observed in DGP rats. The DGP group showed higher collagen type I content, increased expression of Caspase-1, transforming growth factor-beta 3 (TGF-ß3), and matrix metalloproteinase-2 (MMP-2), decreased tissue inhibitor of metalloproteinase-1 (TIMP-1) expression, and higher interleukin-1 beta content when compared with the control group. For gastric smooth muscle cells cultured under higher glucose, the MMP-2 and TGF-ß3 expression was decreased, TGF-ß1 and TIMP-1 expression was increased, the interleukin-1 beta content was decreased in cells after inhibition of NLRP3 expression; the NLRP3 and Caspase-1 expression was decreased, and adenosine triphosphate content was lower after inhibition of Cx43; the expression of NLRP3, Caspase-1, P2X7, and the membrane/cytoplasm ratio of CX43 expression was decreased in cells after inhibition of AMPK and oxidative stress, the phospho-AMPK expression was also decreased after suppressing oxidative stress. Our findings suggest that high glucose induced the activation of the AMPK-Cx43-NLRP3 pathway through oxidative stress, and this pathway was involved in the ECM remodeling of gastric smooth muscles in DGP rats by regulating the biological functions of TGF-ß3, TGF-ß1, MMP-2, and TIMP-1.

Involvement of Rictor/mTORC2/Akt/GLUT4 pathway in the regulation of energy metabolism in the gastric smooth muscle of diabetic rats.

Diabetes mellitus can be accompanied by a variety of complications. The purpose of the present study was to characterize the Rictor/mTOR complex 2 (mTORC2)/Akt/glucose transporter 4 (GLUT4) pathway and its effects on energy metabolism in the gastric smooth muscle of diabetic rats. Diabetes was induced in rats using streptozotocin and their phenotype was compared with untreated rats. The relationship between gastric motility and energy metabolism was analyzed by comparing the contraction and ATP metabolism of muscle strips. Western blotting was used to detect the expression of key proteins in the pathway. The diabetic rats demonstrated less frequent and less powerful gastric smooth muscle contractions. The concentrations of ADP, AMP, and ATP, and the energy charge in gastric smooth muscle changed in different periods of diabetes, and these changes were consistent with changes in mechanistic target of rapamycin (mTOR) protein content. The expression of the key intermediates in signal transduction in the Rictor/mTORC2/Akt/GLUT4 pathway also underwent significant changes. Rictor protein expression increased during the development of diabetes, but the activation of mTORC2 did not increase with the increase in Rictor expression. GLUT4 translocation is regulated by Akt and its expression change during the development of diabetes. These findings suggest that altered energy metabolism is present in gastric smooth muscle that is associated with changes in the Rictor/mTORC2/Akt/GLUT4 pathway. Rictor/mTORC2/Akt/GLUT4 pathway may be involved in the regulation of energy metabolism in the gastric smooth muscle of diabetic rats and the development of diabetic gastroparesis.

Quercetagitrin Inhibits Tau Accumulation and Reverses Neuroinflammation and Cognitive Deficits in P301S-Tau Transgenic Mice.

Intracellular tau accumulation is a hallmark pathology of Alzheimer's disease (AD) and other tauopathies. Tau protein, in the hyperphosphorylated form, is the component of paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) in AD. Blocking tau aggregation and/or phosphorylation is currently a promising strategy for AD treatment. Here, we elucidate that quercetagitrin, a natural compound derived from African marigold (Tagetes erecta), could inhibit tau aggregation and reduce tau phosphorylation at multiple disease-related sites in vitro. Moreover, the in vivo effect of quercetagitrin was assessed in P301S-tau transgenic via oral administration. The compound treatment restored the cognitive deficits and neuron loss in the mice. The formation of NFTs and tau phosphorylations in the hippocampus and cortex of the mice was also prevented by the compound. Moreover, quercetagitrin feeding displayed neuroinflammation protection through the inhibition of NF-κB activation in the mice. Together, our data reveal that quercetagitrin possesses the potential to further develop as a therapeutic medicine for AD and other tauopathies.

Observation of Robust and Long-Ranged Superperiodicity of Electronic Density Induced by Intervalley Scattering in Graphene/Transition Metal Dichalcogenide Heterostructures.

Two-dimensional (2D) h-BN and transition metal dichalcogenides (TMDs) are widely used as substrates of graphene because they are insulating, atomically flat, and without dangling bonds. Usually, it is believed that such insulating substrates will not affect the electronic properties of graphene, especially when the moiré pattern generated between them is quite small. Here, we present a systematic study of the electronic properties of graphene/TMD heterostructures with the period of the moiré pattern <1 nm, and our results reveal an unexpected sensitivity of electronic properties in graphene to the 2D insulating substrates. We demonstrate that there is a robust and long-ranged superperiodicity of electronic density in graphene, which arises from the scattering of electrons between the two valleys of graphene in the graphene/TMD heterostructures. By using scanning tunneling microscope and spectroscopy, three distinct atomic-scale patterns of the electronic density are directly imaged in every graphene/TMD heterostructure.

ULK1 Depletion Protects Mice from Diethylnitrosamine-Induced Hepatocarcinogenesis by Promoting Apoptosis and Inhibiting Autophagy.

Purpose: The uncoordinated-51 like kinase 1 (ULK1) is an important serine/threonine protein kinase involved in autophagy, especially for the initiation stage. Previous studies have shown that ULK1 could be used as a prognostic marker in predicting poor progression-free survival and a therapeutic target for hepatocellular carcinoma (HCC) when treated with sorafenib; however, its role during hepatocarcinogenesis remains to be elucidated. Methods: CCK8 and colony formation assay were used to detect cell growth ability. Western blotting was performed to determine expression level of protein. Data from public database were downloaded to analyze expression of ULK1 at mRNA level and predict survival time. RNA-seq was conducted to reveal disturbed gene profile orchestrated by ULK1 depletion. A diethylnitrosamine (DEN)-induced HCC mice model was used to uncover the role of ULK1 in hepatocarcinogenesis. Results: ULK1 was up-regulated in liver cancer tissues and cell lines, and knockdown of ULK1 promoted apoptosis and suppressed proliferation of liver cancer cells. In in vivo experiments, Ulk1 depletion attenuated starvation-induced autophagy in mice liver, reduced diethylnitrosamine (DEN)-induced hepatic tumor number and size, and prevented tumor progression. Further, RNA-seq analysis revealed a close relationship between Ulk1 and immunity with significant changes in gene sets enriched in the interleukin and interferon pathways. Conclusion: ULK1 deficiency prevented hepatocarcinogenesis and inhibited hepatic tumor growth, and might be a molecular target for the prevention and treatment of HCC.

Resonance Raman Studies on Heme Ligand Stretching Modes in Methionine80-Depleted Cytochrome c: Fe-His, Fe-O2, and O-O Stretching Modes.

The peroxidase activity of cytochrome (cyt) c increases when Met80 dissociates from the heme iron, which is related to the initial cyt c membrane permeation step of apoptosis. Met80-dissociated cyt c can form an oxygenated species. Herein, resonance Raman spectra of Met80-depleted horse cyt c (M80A cyt c) were analyzed to elucidate the heme ligand properties of Met80-dissociated cyt c. The Fe-His stretching (νFe-His) mode of ferrous M80A cyt c was observed at 236 cm-1, and this frequency decreased by 1.5 cm-1 for the 15N-labeled protein. The higher νFe-His frequency of M80A cyt c than of other His-ligated heme proteins indicates strong heme coordination and the imidazolate character of His18. Peaks attributed to the Fe-O2 stretching (νFe-O2) and O-O stretching (νO-O) modes of the oxygenated species of M80A cyt c were observed at 576 and 1148 cm-1, respectively, under an 16O2 atmosphere, whereas the frequencies decreased to 544 and 1077 cm-1, respectively, under an 18O2 atmosphere. The νFe-O2 mode of Hydrogenobacter thermophilus (HT) M59A cyt c552 was observed at 580 cm-1 under an 16O2 atmosphere, whereas the frequency decreased to 553 cm-1 under an 18O2 atmosphere, indicating that relatively high νFe-O2 frequencies are characteristic of c-type cyt proteins. By comparison of the simultaneously observed νFe-O2 and νO-O frequencies of oxygenated cyt c and other oxygenated His-ligated heme proteins, the frequencies tend to have a positive linear relationship; the νFe-O2 frequency increases when the νO-O frequency increases. The imidazolate character of the heme-coordinated His and strong Fe-O and O-O bonds are characteristic of cyt c and apparently related to the peroxidase activity when Met80 dissociates from the heme iron.

Hope and life satisfaction among Chinese shadow education tutors: The mediating roles of positive coping and perceived social support.

Previous studies of the relationship between hope and life satisfaction left the underlying mechanism of how hope predicts life satisfaction unexplored to scholars. This study thus investigates the two potential mediators in the relationship between hope and life satisfaction among a sample of Chinese shadow education institution (SEI) tutors who may be under immense professional development pressure from a cross-sectional approach. The main body of the study consists of an online survey in which 221 SEI tutors reported their hope, positive coping, perceived social support, and life satisfaction. The survey results were analyzed using mediation and moderation analysis via SPSS 23.0. The results indicated that positive coping improved the relationship between hope and life satisfaction, supporting the hypothesis regarding the serial mediating effect of positive coping and perceived social support. In other words, tutors with a high level of hope tend to adopt positive coping strategies, thus will receive more social support and improve life satisfaction. Our findings revealed the independent and accumulative mediating effects of positive coping and perceived social support on the relationship between hope and life satisfaction, and had implications for the psychological intervention of SEI tutors who are currently facing enormous industry pressure.

Gender-based differences in the relationships among proactive personality, perceived entrepreneurial support and entrepreneurial intention of Chinese private college students: A moderated mediation model.

Proactive personality is a key determinant of entrepreneurial intention. Few studies have explored the mediating and moderating mechanisms underlying this relationship. This study investigates the association between proactive personality and entrepreneurial intention and examines the mediating role of perceived entrepreneurial support and the moderating role of gender. Using a cross-sectional design, 1,515 senior students (women = 838, men = 677) from Chinese private colleges were recruited using random cluster sampling. They completed a battery of self-reported online questionnaires on proactive personality, perceived entrepreneurial support, and entrepreneurial intention. The results revealed that perceived entrepreneurial support mediates the association between proactive personality and entrepreneurial intention. Moderated mediation analysis indicated that the relationship between proactive personality and perceived entrepreneurial support and that between perceived entrepreneurial support and entrepreneurial intention are moderated by gender. Specifically, the positive association between proactive personality and entrepreneurial intention was stronger in male students, and the positive association between perceived entrepreneurial support and entrepreneurial intention was stronger in female students. This study contributes to the understanding of how proactive personality predicts entrepreneurial intention in Chinese private college students and bears implications for higher education institutions and policymakers that entrepreneurship promotion agenda should focus on improving perceived entrepreneurial support and considering the gender of students.

Visualizing Commognitive Responsibility Shift in Collaborative Problem-Solving During Computer-Supported One-to-One Math Tutoring.

The aim of this study is to use a commognitive responsibility framework to visualize responsibility shift in collaborative problem solving (CPS) during computer-supported one-to-one tutoring. Commognitive responsibility shift means that individuals' cognitive responsibility shift can be reflected by the discourse in communication. For our sample, we chose a 15-year-old Chinese boy and his mathematics teacher with 6 years of teaching experience, both of whom have experienced computer-supported learning and teaching mathematics, respectively. We collected four tutoring videos (each 60-90 min; in total, more than 330 min) online, and a 45-min interview video from the teacher. We found that the third type of commognitive responsibility shift in both the teacher's and student's CPS behavior online is not only teacher-student comparison but also alternating-led, which includes teacher-student-led (TS) and student-teacher-led (ST).

The Role of Perceived Social Support and Stress in the Relationship between Hope and Depression among Chinese Shadow Education Tutors: A Serial Mediation Model.

The association between hope and depression has been studied, leaving the underlying mechanism of how hope might predict depression unexplored. With a cross-sectional design, this study investigated two possible mediating factors in the relationship between hope and depression among Chinese shadow education tutors, who confront a high turnover rate and are at high risk for depression. Altogether, 221 tutors participated in the survey, and reported their dispositional hope, perceived social support (PSS), perceived stress (PS), and depression. Results indicated that both PSS and PS mediated the relationship between hope and depression. Results also supported the hypothesized serial mediating effect. In other words, hope as a positive disposition may promote PSS, which can mitigate PS. The reduced PS, in turn, alleviates depression. This finding not only shed light on the independent and accumulative mediating effects of PSS and PS, but also has implications for preventive interventions among Chinese shadow education tutors experiencing the enormous pressure of instability. This serial mediation model should be confirmed by further longitudinal study.

Insulin-like growth factor-1 inhibits apoptosis of rat gastric smooth muscle cells under high glucose condition via adenosine monophosphate-activated protein kinase (AMPK) pathway.

INTRODUCTION: Diabetic gastroparesis (DGP) is a common chronic complication of diabetes characterized by decreased gastric motility, and an effective number of gastric smooth muscle cells (GSMCs) ensures gastric motility. A previous study documented that apoptosis was present in gastric smooth muscles in rats with DGP and adenosine monophosphate-activated protein kinase (AMPK) was an important factor of apoptosis of rat GSMCs cultured under high glucose conditions. This study aimed to explore the effect of insulin-like growth factor-1 (IGF-1) on apoptosis of high glucose cultured rat GSMCs after silencing of AMPK and elucidate the underlying mechanism. MATERIAL AND METHODS: A total of 120 rats were divided into normal control (NC, n = 20), diabetic gastroparesis (DGP, n = 50) and DGP + IGF-1 (n = 50) groups. After establishing the rat model of DGP, rats in the DGP+IGF-1 group received an intraperitoneal injection of IGF-1 at a dose of 1.5 µg/kg/d for 10 weeks. The level of AMPK activity, liver kinase B1 (LKB1) activity, and calcium/calmodulin-dependent protein kinase b (CaMKKb) expression in rat gastric smooth muscle tissues was detected by Western blot analysis. Apoptosis in rat gastric smooth muscle tissues was detected by TUNEL assay. We also cultured rat GSMCs in vitro under high glucose (HG) condition (35 mM), incubated cells with IGF-1, and silenced AMPK with siRNA. The cells were divided into HG, HG + IGF-1, HG + siRNA, and HG + siRNA + IGF-1 groups. The apoptosis rates of rat GSMCs after silencing AMPK were detected by TUNEL assay and flow cytometry, and apoptosis-related protein expression in rat GSMCs was detected by Western blot. RESULTS: IGF-1 decreased LKB1 activity, CaMKKb expression, AMPK activity, and inhibited apoptosis in rat gastric smooth muscle tissues. Compared with rat GSMCs cultured in vitro under HG conditions, apoptosis rates were reduced after treatment with IGF-1 and AMPK silencing (both p < 0.01). Apoptosis rates were higher in the HG + siRNA group compared with the HG + IGF-1 group (p < 0.05). IGF-1 down-regulated the expression of calcium/calmodulin-dependent kinase II (CaMKII) and p53, up-regulated the expression of p21, PLC-b3, PI3K p110 Ser1070, and the activities of Akt, p70S6K, mTORC1, and mTORC2. IGF-1 also up-regulated Bcl-2 expression and down-regulated the expression of BAX and Caspase-3. CONCLUSIONS: IGF-1 can inhibit the apoptosis of rat GSMCs under high glucose conditions, its mechanism may be related to the regulation of expression and activity of p53, PI3K, TSC-2, Akt, mTOR, 4E-BP1, p70S6K, p21, CaMKII, and PLC-b3 in rat GSMCs acting through AMPK pathway.

Deep Exemplar-Based Color Transfer for 3D Model.

Recoloring 3D models is a challenging task that often requires professional knowledge and tedious manual efforts. In this article, we present the first deep-learning framework for exemplar-based 3D model recolor, which can automatically transfer the colors from a reference image to the 3D model texture. Our framework consists of two modules to solve two major challenges in the 3D color transfer. First, we propose a new feed-forward Color Transfer Network to achieve high-quality semantic-level color transfer by finding dense semantic correspondences between images. Second, considering 3D model constraints such as UV mapping, we design a novel 3D Texture Optimization Module which can generate a seamless and coherent texture by combining color transferred results rendered in multiple views. Experiments show that our method performs robustly and generalizes well to various kinds of models.

The Influence of Transcranial Magnetoacoustic Stimulation Parameters on the Basal Ganglia-Thalamus Neural Network in Parkinson's Disease.

Objective: Parkinson's disease (PD) is a degenerative disease of the nervous system that frequently occurs in the aged. Transcranial magnetoacoustic stimulation (TMAS) is a neuronal adjustment method that combines sound fields and magnetic fields. It has the characteristics of high spatial resolution and noninvasive deep brain focusing. Methods: This paper constructed a simulation model of TMAS based on volunteer's skull computer tomography, phased controlled transducer and permanent magnet. It simulates a transcranial focused sound pressure field with the Westervelt equation and builds a basal ganglia and thalamus neural network model in the PD state based on the Hodgkin-Huxley model. Results: A biased sinusoidal pulsed ultrasonic TMAS induced current with 0.3 T static magnetic field induction and 0.2 W⋅cm-2 sound intensity can effectively modulate PD states with RI ≥ 0.633. The magnitude of magnetic induction strength was changed to 0.2 and 0.4 T. The induced current was the same when the sound intensity was 0.4 and 0.1 W⋅cm-2. And the sound pressure level is in the range of -1 dB (the induced current difference is less than or equal to 0.019 µA⋅cm-2). TMAS with a duty cycle of approximately 50% can effectively modulates the error firings in the PD neural network with a relay reliability not less than 0.633. Conclusion: TMAS can modulates the state of PD.

College Satisfaction, Sense of Achievement, Student Happiness and Sense of Belonging of Freshmen in Chinese Private Colleges: Mediation Effect of Emotion Regulation.

Sense of belonging constitutes a critical component of college students' retention and academic achievement, especially in disadvantaged higher education institutions such as private colleges in China. Using nationwide survey data (n = 3816) from Chinese private colleges, this study explores how college satisfaction, sense of achievement, and student happiness contribute to freshmen' sense of belonging. Structural equation modeling analyses have identified the significant positive associations between freshmen's emotion regulation and sense of belonging. In particular, emotion regulation plays a mediating role in the relations between college satisfaction, sense of achievement, student happiness, and the sense of belonging. Therefore, private colleges should design and implement orientation programs to improve freshmen's learning experience, especially college satisfaction and student happiness, to enhance their sense of belonging.

Dietary Bacillus subtilis supplementation alleviates alcohol-induced liver injury by maintaining intestinal integrity and gut microbiota homeostasis in mice.

Alcoholic liver disease (ALD) is a worldwide health problem with limited therapeutic options, which is associated with gut-derived endotoxins, particularly lipopolysaccharide (LPS) and intestinal microbiota dysbiosis. Recently, probiotics, synbiotics and other food additive interventions have been shown to be effective in decreasing or preventing the progression of ALD. Bacillus subtilis (B. subtilis) and its metabolic products are widely used as food additives to maintain intestinal health, but the protective effects of B. subtilis against alcohol-induced liver injury are poorly understood. In the present study a chronic alcohol-induced liver injury model was constructed based on the Lieber-DeCarli diet and it aimed to determine whether dietary B. subtilis supplementation may alleviate alcohol-induced liver injury. Results revealed that prophylactic B. subtilis supplementation partially restored gut microbiota homeostasis and relieved alcohol-induced intestinal barrier injury, which significantly decreased the translocation of bacterial endotoxins to the blood. In addition, the decreased serum LPS alleviated hepatic inflammation via the toll-like receptor 4 pathway, resulting in improved hepatic structure and function. These results demonstrated that dietary B. subtilis supplementation imparts novel hepatoprotective functions by improving intestinal permeability and homeostasis.

Aspartame and sucralose extend the lifespan and improve the health status of C. elegans.

Aspartame (ASP) and sucralose (SUC) are non-nutritive sweeteners which are widely consumed worldwide. They are considered safe for human consumption, but their effects on certain physiological aspects, such as the lifespan or health status, of the organism have not yet been studied in depth and only limited data are available in the literature. The objectives of this study were to evaluate the effects of ASP and SUC on the lifespan and health indexes using Caenorhabditis elegans (C. elegans) as a model system. Interestingly, it was shown that at the concentrations tested, ASP (0.03-3 mg mL-1) showed an increasing trend of the mean lifespan of C. elegans, with a significant increase of 27.6% compared to the control at 3 mg mL-1. Similarly, SUC (ranging from 0.03 to 10 mg mL-1) also significantly increased the mean lifespan by 20.3% and 22.3% at 0.03 and 0.3 mg mL-1, respectively. However, 10 mg mL-1 SUC had a negative effect on the lifespan, though it did not reach a statistically significant level. In addition, ASP and SUC decreased lipofuscin accumulation and transiently improved motility, indicating improved health status. Nonetheless, they had different effects on food intake and intestinal fat deposition (IFD) at different intervals of time. Taken together, our findings revealed that ASP and SUC can prolong the lifespan and improve the health status of C. elegans.

Isobavachalcone ameliorates cognitive deficits, and Aß and tau pathologies in triple-transgenic mice with Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects 50 million people worldwide. The current medicines have modest benefits in preventing or curing AD. Thus, it is urgent to discover drugs with the potential to change the progression of the disease. The primary clinical symptoms are memory loss and anxiety, while the critical pathological characteristics are Aß plaques and hyperphosphorylated tau tangles. In this study, isobavachalcone (ISO), isolated from Psoralea corylifolia, was administered to 3×Tg-AD mice. It has been shown that this compound could significantly improve anxiety, memory and recognition deficits in the AD mice, attenuate the accumulation of Aß oligomers, reduce the hyperphosphorylation of tau, and prevent the production of tau filaments. The metabolomic analysis implicates that the most probable pathways affected by ISO were bile secretion, tyrosine metabolism, and purine metabolism. In summary, ISO possesses the potential for further development as a drug candidate for AD.

Inhibitory Effects of Isobavachalcone on Tau Protein Aggregation, Tau Phosphorylation, and Oligomeric Tau-Induced Apoptosis.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases without any effective medicine treatments. The neurofibrillary tangles containing hyperphosphorylated tau protein are one important pathological characteristic. Thus, one practicable strategy for AD drug design is to discover compounds that could inhibit tau protein aggregation and/or phosphorylation. In this study, isobavachalcone, a natural plant-derived compound, has been shown to inhibit tau protein aggregation and disaggregate tau fibrils in vitro by directly interacting with tau protein at amino acids I278, V309, etc. It is able to reduce tau phosphorylation at four disease-related sites in vivo by regulating the critical kinase and protein phosphatase, GSK3ß and PP2A. The compound also exhibits protection against tau oligomers-induced apoptosis through the mitochondria and ER mediated apoptotic pathways. In summary, isobavachalcone is a promising candidate for further evaluation as a potential preventive and therapeutic medicine for AD.

Spermidine inhibits neurodegeneration and delays aging via the PINK1-PDR1-dependent mitophagy pathway in C. elegans.

Aging is the primary driver of various diseases, including common neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Currently there is no cure for AD and PD, and the development of novel drug candidates is demanding. Spermidine is a small anti-aging molecule with elimination of damaged mitochondria via the process of mitophagy identified as a molecular mechanism of action. Here, we show that spermidine inhibits memory loss in AD worms and improves behavioral performance, e.g., locomotor capacity, in a PD worm model, both via the PINK1-PDR1-dependent mitophagy pathway. Additionally, spermidine delays accelerated aging and improves healthspan in the DNA repair-deficient premature aging Werner syndrome (WS) worm model. While possible intertwined interactions between mitophagy/autophagy induction and DNA repair by spermidine are to be determined, our data support further translation of spermidine as a possible therapeutic intervention for such diseases.