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Despite the growing recognition of the impact of urban environments on social health, limited research explores the combined associations of multiple urban exposures, particularly in dense cities. This study examines the interplay between greenspace, air pollution, and social health as well as the underlying pathways and population heterogeneity in Hong Kong using cross-sectional survey data from 1,977 adults and residential environmental data. Social health includes social contacts, relations, and support. Greenspace used street-view greenness (SVG), park density, and the normalized difference vegetation index (NDVI). 100-m daily ground NO 2 and O 3 , indicative of air pollution, were derived using a spatiotemporal deep learning model. Mediators involved physical activity and negative emotions. Main analyses were performed in a 1000-m buffer with multivariate logistical regressions, stratification, interaction, and Partial Lease Square - Structural Equation Modelling (PLS-SEM). Multi-exposure models revealed positive associations between park density/SVG and social contacts, as well as between SVG and social relations, while O 3 was negatively associated with social relations/support. Significant moderators included age, birthplace, employment, and education. PLS-SEM indicated direct positive associations between SVG and social contacts/relations and significant indirect negative associations between NO 2 /O 3 and social health via negative emotions. This study adds to urban health research by exploring complex relationships between greenspace, air pollution, and social health, highlighting the role of the environment in fostering social restoration., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

A rational crystallization strategy is essential to obtain high-quality protein crystals, yet the established methods suffer from different limitations arising from the single regulation on either nucleation or supersaturation. Herein, a nucleation-supersaturation dual-driven crystallization (DDC) strategy that realizes synergistic regulation of heterogeneous nucleation sites and solution supersaturation based on dual surface and confinement effects for efficient protein crystallization is reported. This strategy relies on a p(PEGDA-co-DMAA) hydrogel template with pre-filled NaCl under designed concentrations. Once dropping hen egg white lysozyme (HEWL) protein solution on the hydrogel, the wrinkled surface provides numerous nucleation sites, while the internal structure regulates the solution supersaturation in the crystallization region through diffusion. Finally, DDC strategy can create high-quality HEWL crystals with large sizes (100-300 µm), well-defined morphologies (hexagon and tetragon), and a significantly accelerated nucleation time (9-12 times faster than that achieved using the conventional hanging drop method). It also performs well at wider protein concentrations (10-50 mg mL -1 ) and categories (e.g., achieving fast crystallization and large-size crystals of trypsin), therefore demonstrating clear advantages and great potential for efficiently fabricating protein crystals desirable for diverse applications., (© 2023 Wiley‐VCH GmbH.)

Due to their biocompatibility and adjustable chemical structure and morphology, hydrogels have great potential in many applications, and can be used to enhance protein crystal quality and crystallization efficiency, contributing to biomedicine manufacturing. Monodispersed PEGDA hydrogel microspheres (HMSs) were synthesized using a Lego-inspired microfluidic device. The generated droplets were then UV polymerized, partially hydrolyzed with 0.1 M NaOH solution to improve their absorption capacity, and soaked in a buffer solution containing 0, 0.5, 1, 2, and 4 M NaCl. Salt-loaded HMSs were used as the medium for the enhanced crystallization of hen egg white lysozyme from aqueous solutions. Different supersaturations were achieved in the protein solutions by releasing NaCl of different concentrations from HMSs, as confirmed by electrical conductivity measurements. HMSs with or without NaCl can both provide heterogeneous nucleation sites due to their nano-porous structure and wrinkled surface. The addition of NaCl-loaded HMSs to the protein solution can also increase or decrease the supersaturation in the whole solution or locally near the HMS, leading to controllable nucleation time and crystal size distribution dependent on the NaCl concentration loaded into HMSs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Behaviors of swimming rodents are not uniform, exhibiting large variations, which may underlie the individual differences in swimming exercise-induced benefits. The study aimed to monitor individualized swimming behavior and evaluate its biological significance. Methods: A swimming tank which can monitor individualized rodent swimming behavior during exercise was established. A total of 45 mice were subjected to swimming training for 1 month (1 h per day) and the swimming behaviors of each mouse were recorded. Results: The swimming behaviors of mice displayed considerable variations in aspects of distance, velocity, and area preference. For example, nearly one-third of mice preferred to swim in central area and most of the mice exhibited an even area distribution. Long-term exercise training improved cardiac systolic function and decreased blood pressure in mice, but hardly changed swimming behaviors. Analyses of the relationship between swimming behavior and cardiovascular adaptations to exercise training revealed that swimming behavior indicated the biological effects of swimming training. Specifically, mice which preferred swimming at the central zone or were trainable in behavior during 1-month training exhibited better outcomes in cardiac function and blood pressure post long-term exercise. Mechanistically, a centralized swimming behavior indicated a smaller stress during exercise, as evidenced by a milder activation of hypothalamic-pituitary-adrenal axis. Discussion: These results suggest that swimming behavior during training indicates individualized adaptations to long-term exercise, and highlight a biological significance of swimming behavior monitoring in animal studies., Competing Interests: Authors SH and XC were employed by Chengdu Techman Software Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yu, Liu, Li, He, Hu, Sun, Yan, Zhao, Cheng, Li, Gao, Liu and Zhang.)

Ethnopharmacological Relevance: Ulcerative colitis (UC) is an idiopathic intestinal disease characterized by chronic inflammation with unknown etiology. Kuijieling decoction is a traditional Chinese Medicine with unique therapeutic efficacy for UC., Aim of the Study: To validate the effects of Kuijieling decoction on vitamin A metabolism and retinoic acid (RA) production, along with evaluation of its immunomodulatory activity, and further clarify the upstream mechanisms underlying Treg/Th17 regulation that contribute to therapeutic effects against UC., Materials and Methods: Network pharmacology and molecular docking analyses were employed to predict the potential anti-UC targets of Kuijieling and associated pathways. A rat model of UC was generated by treatment with trinitrobenzene sulfonic acid (TNBS) to induce inflammation. T lymphocytes were induced to differentiate into Th17 via combined stimulation with the cytokines TGF-β1, IL-6 and IL-23. Expression levels of RA/RARα-related factors (RARα, CRABPII, Smad3, IL-6R and IL-23R) and Treg/Th17 cell-related factors (Foxp3, RORγt) were measured via western blot (WB), quantitative real-time PCR (RT-qPCR), and immunohistochemistry analyses. Components of the vitamin A metabolic pathway (vitamin A, retinol, retinoic acid) and Treg/Th17 cell-related cytokines (IL-10, IL-17, IL-21) were evaluated using ELISA. Flow cytometry was performed to determine the percentages of Treg and Th17 cells., Results: The action targets of Kuijieling were significantly associated with T cell activation, Th17 cell differentiation and the immune response. IL-2, IL-6, STAT3 and RARα displayed strong binding affinities with the main components of Kuijieling, suggesting an important role in its therapeutic efficacy. Kuijieling promoted vitamin A metabolism and RA/RARα signaling in UC rats and T lymphocytes. Moreover, Kuijieling effectively regulated the Treg/Th17 cell balance in UC rats and T lymphocytes and relieved inflammation. The protective effect of Kuijieling was weakened after inhibition of the RA/RARα signaling pathway., Conclusions: Kuijieling promotes vitamin A metabolism and RA synthesis, enhances interactions between RA, intracellular binding protein CRABPII and nuclear receptor RARα, and upregulates Smad3 and Foxp3, thus promoting Treg differentiation. Simultaneously, Kuijieling inhibited expression of IL-6R and IL-23R genes and production of RORγt, leading to suppression of Th17 differentiation, and ultimately, reduction of the Th17/Treg cell ratio., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dissecting and understanding the cancer ecosystem, especially that around the tumor margins, which have strong implications for tumor cell infiltration and invasion, are essential for exploring the mechanisms of tumor metastasis and developing effective new treatments. Using a novel tumor border scanning and digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we identified a 500 µm-wide zone centered around the tumor border in patients with liver cancer, referred to as "the invasive zone". We detected strong immunosuppression, metabolic reprogramming, and severely damaged hepatocytes in this zone. We also identified a subpopulation of damaged hepatocytes with increased expression of serum amyloid A1 and A2 (referred to collectively as SAAs) located close to the border on the paratumor side. Overexpression of CXCL6 in adjacent malignant cells could induce activation of the JAK-STAT3 pathway in nearby hepatocytes, which subsequently caused SAAs' overexpression in these hepatocytes. Furthermore, overexpression and secretion of SAAs by hepatocytes in the invasive zone could lead to the recruitment of macrophages and M2 polarization, further promoting local immunosuppression, potentially resulting in tumor progression. Clinical association analysis in additional five independent cohorts of patients with primary and secondary liver cancer (n = 423) showed that patients with overexpression of SAAs in the invasive zone had a worse prognosis. Further in vivo experiments using mouse liver tumor models in situ confirmed that the knockdown of genes encoding SAAs in hepatocytes decreased macrophage accumulation around the tumor border and delayed tumor growth. The identification and characterization of a novel invasive zone in human cancer patients not only add an important layer of understanding regarding the mechanisms of tumor invasion and metastasis, but may also pave the way for developing novel therapeutic strategies for advanced liver cancer and other solid tumors., (© 2023. The Author(s).)

Background: Emerging evidence suggests neighborhood greenness is associated with physical activity; however, the sitting-specific associations with multi-source greenness metrics remain unclear, especially in high-density cities., Objectives: This cross-sectional study examined: 1) the associations of street-view greenness (SVG) and traditional greenness metrics (i.e., Normalized Difference Vegetable Index (NDVI) and park density) with sitting time; 2) the potential moderating/mediating roles of objective/perceived air pollution and perceived roadside noise; and 3) how the associations vary by demographics and socioeconomic status., Methods: Interview survey data of 1977 adults in Hong Kong from 2014 and 2015 was linked to environmental data. Using an object-based image classification algorithm, SVG was derived from Google Street View images, capturing human-viewed street-level greenery. NDVI was derived from Landsat 8 satellite images using the normalized difference between the near-infrared and red bands. Park density was calculated by point density. In the main analyses including regressions, parallel mediation, interaction, and stratified models, the environmental metrics were measured within a 1000-m Euclidean buffer of residence., Results: SVG and park density were negatively associated with sitting time after adjusting for covariates including physical activity while NDVI was not significantly associated with sitting time, and results were robust with 800-1800 m Euclidean and 1400-1800 m network distance. Greenness-sitting associations were not moderated/mediated by perceived air pollution/roadside noise while SVG-sitting associations were moderated by objective NO 2 , O 3 , and PM 2.5 and mediated by O 3 . SVG-sitting associations differed by age, having under-school-aged children, birthplace, education, and occupation type while associations between traditional greenness metrics and prolonged sitting showed no significant population heterogeneity., Conclusions: SVG appears to be more accurate in estimating exposure than traditional metrics to reflect greenness-sitting associations, objective air pollution moderating and mediating roles, and population heterogeneity, which emphasizes the importance of street-level greenness planning for health promotion in terms of reducing sitting time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: Residential greenness was theoretically associated with health-related consumption behaviors concerning the socio-ecological model and restoration environment theory, but empirical studies were limited, especially in high-density cities. We examined the associations of residential greenness with unhealthy consumption behaviors (infrequent breakfast consumption, infrequent fruit consumption, infrequent vegetable consumption, alcohol drinking, binge drinking, cigarette smoking, moderate-to-heavy smoking, and heavy smoking) using street-view and conventional greenness metrics in high-density Hong Kong., Methods: This cross-sectional study employed survey data from 1,977 adults and residence-based objective environmental data in Hong Kong. Street-view greenness (SVG) was extracted from Google Street View images using an object-based image classification algorithm. Two conventional greenness metrics were used, including normalized difference vegetation index (NDVI) derived from Landsat 8 remote-sensing images and park density derived from a geographic information system database. In the main analyses, logistic regression analyses together with interaction and stratified models were performed with environmental metrics measured within a 1000-m buffer of residence., Results: A standard deviation higher SVG and NDVI were significantly associated with fewer odds of infrequent breakfast consumption (OR = 0.81, 95% CI 0.71-0.94 for SVG; OR = 0.83, 95% CI 0.73-0.95 for NDVI), infrequent fruit consumption (OR = 0.85, 95% CI 0.77-0.94 for SVG; OR = 0.85, 95% CI 0.77-0.94 for NDVI), and infrequent vegetable consumption (OR = 0.78, 95% CI 0.66-0.92 for SVG; OR = 0.81, 95% CI 0.69-0.94 for NDVI). The higher SVG was significantly associated with less binge drinking and the higher SVG at a 400-m buffer and a 600-m buffer were significantly associated with less heavy smoking. Park density was not significantly associated with any unhealthy consumption behaviors. Some of the above significant associations were moderated by moderate physical activity, mental and physical health, age, monthly income, and marital status., Conclusions: This study highlights the potential beneficial impact of residential greenness, especially in terms of street greenery, on healthier eating habits, less binge drinking, and less heavy smoking., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Hyperlipidemia results in endothelial dysfunction, which is intimately associated with disturbed mitochondrial homeostasis, and is a real risk factor for cardiovascular diseases (CVDs). Triphenylphosphonium (TPP+)-HT, constructed by linking a mitochondrial-targeting moiety TPP+ to hydroxytyrosol (HT), enters the cell and accumulates in mitochondria and is thus an important candidate drug for preventing hyperlipidemia-induced endothelial injury. In the present study, we found that TPP-HT has a better anti-inflammatory effect than HT. In vivo, TPP-HT significantly prevented hyperlipidemia-induced adverse changes in the serological lipid panel, as well as endothelial and mitochondrial dysfunction of the thoracic aorta. Similarly, in vitro, TPP-HT exhibited similar protective effects in palmitate (PA)-induced endothelial dysfunction, particularly enhanced expression of the mitochondrial ETC complex II, recovered FoxO1 expression in PA-injured human aorta endothelial cells (HAECs) and promoted FoxO1 nuclear translocation. We further demonstrated that FoxO1 plays a pivotal role in regulating ATP production in the presence of TPP-HT by using the siFoxO1 knockdown technique. Simultaneously, TPP-HT enhanced Nrf2 nuclear translocation, consistent with the in vivo findings of immunofluorescence, and the antioxidant effect of TPP-HT was almost entirely blocked by siNrf2. Concomitantly, TPP-HT’s anti-inflammatory effects in the current study were primarily mediated via the p38 MAPK/NF-κB signaling pathway in addition to the FoxO1 and Nrf2 pathways. In brief, our findings suggest that mitochondria-targeted TPP-HT prevents lipotoxicity induced endothelial dysfunction by enhancing mitochondrial function and redox balance by promoting FoxO1 and Nrf2 nuclear translocation.

Recent technological advances in multi-omics and bioinformatics provide an opportunity to develop precision health assessments, which require big data and relevant bioinformatic methods. Here we collect multi-omics data from 4,277 individuals. We calculate the correlations between pairwise features from cross-sectional data and then generate 11 biological functional modules (BFMs) in males and 12 BFMs in females using a community detection algorithm. Using the features in the BFM associated with cardiometabolic health, carotid plaques can be predicted accurately in an independent dataset. We developed a model by comparing individual data with the health baseline in BFMs to assess health status (BFM-ash). Then we apply the model to chronic patients and modify the BFM-ash model to assess the effects of consuming grape seed extract as a dietary supplement. Finally, anomalous BFMs are identified for each subject. Our BFMs and BFM-ash model have huge prospects for application in precision health assessment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pharmaceutical cocrystals have matured into an effective technique for tuning the physicochemical and mechanical properties of drugs in solid form simultaneously. Herein, in order to provide a novel cocrystal form of oral medicine metformin hydrochloride (MH), citric acid (CA) was selected as an efficient ligand after screening a variety of inorganic and organic acids. Thus, based on the principle of crystal engineering, we report a novel cocrystal: metformin hydrochloride - citric acid (MHCA) after the systematic screening, which was experimentally proved to be constituted with 1:1 stoichiometry. Compared with pure MH, MHCA has been proved higher solubility in water, methanol, and ethanol from 283.15 to 313.15 K. Through single-crystal X-ray diffraction (SC-XRD), the particular molecular structure of MHCA has been determined as the orthorhombic system and Pbca space group. Besides, the binding model of MH-CA was built for investigating the binding energy and stability between two components at 278, 298, and 318 K, which were found to be essential for the prediction and analysis of cocrystals. The contribution of different intermolecular interactions and the strength of molecular packing in the cocrystal also have been investigated by Hirshfeld surface analysis. It was found that the cocrystal structure was mainly stabilized by intermolecular hydrogen bonds existing as N-H···O between components, which indicated that the diffusion-combination trend of molecules enhanced the regular array of cocrystal. The results revealed that the molecules of MH and CA formed supramolecular cocrystals mainly induced by hydrogen bonds after passive contacts, such as co-crystallization or grind., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Metformin hydrochloride (MET-HCl) was applied as a model compound to investigate the nucleation behavior in four hydroxylic solvents based on the experimental and simulated methods. Over 320 induction time experiments were measured in four solvents, and the induction time increased in the order: water < methanol < ethanol < n-propanol. The metastable zone widths were determined with different cooling rates and saturation temperatures. According to classical nucleation theory, the nucleation kinetics and thermodynamic parameters (interfacial energy, critical nucleus size and Gibbs free energy) were estimated. The result indicates that the nucleation rate of MET-HCl in water was highest among four solvents. The density functional theory (DFT) calculation was applied to reveal the solvent-solute interaction in crystal nucleation, showing the binding energies increased in the order: water < methanol < ethanol < n-propanol. The simulation results combined with experimental data suggested that the stronger the interactions of solvent-solute molecules, the more difficult the nucleation becomes., (Copyright © 2022. Published by Elsevier B.V.)

Biological age (BA) has been proposed to evaluate the aging status instead of chronological age (CA). Our study shows evidence that there might be multiple "clocks" within the whole-body system: systemic aging drivers/clocks overlaid with organ/tissue-specific counterparts. We utilize multi-omics data, including clinical tests, immune repertoire, targeted metabolomic molecules, gut microbiomes, physical fitness examinations, and facial skin examinations, to estimate the BA of different organs (e.g., liver, kidney) and systems (immune and metabolic system). The aging rates of organs/systems are diverse. People's aging patterns are different. We also demonstrate several applications of organs/systems BA in two independent datasets. Mortality predictions are compared among organs' BA in the dataset of the United States National Health and Nutrition Examination Survey. Polygenic risk score of BAs constructed in the Chinese Longitudinal Healthy Longevity Survey cohort can predict the possibility of becoming centenarian., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Lenalidomide (LDM), widely used for the treatment of transfusion-dependent anaemia, has low oral bioavailability due to its poor aqueous solubility. Herein, we selected nicotinamide (NIC) as a coformer and synthesized a novel pharmaceutical cocrystal: lenalidomide-nicotinamide cocrystal (LNC) with a 1:1 stoichiometric ratio for enhancing the physicochemical properties of LDM, such as solubility and stability. For evaluating the ability to form cocrystal of LDM and NIC, a model of hydrogen-bond propensity (HBP) was utilized to calculate the hydrogen bond formation possibility for every hydrogen bond pair based on theexisting structuralinformation in the database. Afterward, solid-state grinding and liquid-assisted grinding methods were conducted to synthesize LNC, which were then characterized using powder X-ray diffraction, thermal and spectroscopic analysis. Besides, in the heating process, an interesting and anomalous phenomenon called thermal phase transition of the cocrystal was firstly observed and visualized by the hot stage microscope. Notably, the second thermal stage controlled by the vapor pressure of NIC was further determined experimentally and theoretically, which means that intermolecular hydrogen bonds gradually break when NIC occurs phase transition (from liquid to gas). Further, the physicochemical stability of cocrystal was proved reliable after being tested under accelerated stability conditions of 40 °C/75% RH for one month. Compared to lenalidomide and their physical mixture (molar ratio of 1:1), the dissolution and solubility of LNC have also been improved., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The polymorphism of apremilast has been investigated. Two polymorphs have been identified and characterized by differential scanning calorimeter, fourier transform infrared spectroscopy, and powder X-ray diffractometer. Solubilities of apremilast forms B and E in three binary solvents of methanol-water, acetonitrile-water, and acetonitrile-methanol have been measured using the static method at a temperature ranging from 288.15 K to 328.15 K under standard atmospheric pressure. Subsequently, the solubility data have been analyzed using the Wilson, NRTL, and UNIQUAC thermodynamic models, respectively. Furthermore, the Gibbs energy of solution and the radial distribution function have been calculated using the molecular simulation method to evaluate the dissolution mechanism. The Gibbs energy of solution reveals that the rank of solute-solvent interaction correlated well with solubility order in binary solvent mixtures, and the radial distribution function indicates that weakening of solvent-solvent interaction led to an increase in solubility., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We have proposed a new tumor sensitization and targeting (TST) framework, named in vivo computation, in our previous investigations. The problem of TST for an early and microscopic tumor is interpreted from the computational perspective with nanorobots being the "natural" computing agents, the high-risk tissue being the search space, the tumor targeted being the global optimal solution, and the tumor-triggered biological gradient field (BGF) providing the aided knowledge for fitness evaluation of nanorobots. This natural computation process can be seen as on-the-fly path planning for nanorobot swarms with an unknown target position, which is different from the traditional path planning methods. Our previous works are focusing on the TST for a solitary lesion, where we proposed the weak priority evolution strategy (WP-ES) to adapt to the actuating mode of the homogeneous magnetic field used in the state-of-the-art nanorobotic platforms, and some in vitro validations were performed. In this paper, we focus on the problem of TST for multifocal tumors, which can be seen as a multimodal optimization problem for the "natural" computation. To overcome this issue, we propose a sequential targeting strategy (Se-TS) to complete TST for the multiple lesions with the assistance of nanorobot swarms, which are maneuvered by the external actuating and tracking devices according to the WP-ES. The Se-TS is used to modify the BGF landscape after a tumor is detected by a nanorobot swarm with the gathered BGF information around the detected tumor. Next, another nanorobot swarm will be employed to find the second tumor according to the modified BGF landscape without being misguided to the previous one. In this way, all the tumor lesions will be detected one by one. In other words, the paths of nanorobots to find the targets can be generated successively with the sequential modification of the BGF landscape. To demonstrate the effectiveness of the proposed Se-TS, we perform comprehensive simulation studies by enhancing the WP-ES based swarm intelligence algorithms using this strategy considering the realistic in-body constraints. The performance is compared against that of the "brute-force" search, which corresponds to the traditional systemic tumor targeting, and also against that of the standard swarm intelligence algorithms from the algorithmic perspective. Furthermore, some in vitro experiments are performed by using Janus microparticles as magnetic nanorobots, a two-dimensional microchannel network as the human vasculature, and a magnetic nanorobotic control system as the external actuating and tracking system. Results from the in silico simulations and in vitro experiments verify the effectiveness of the proposed Se-TS for two representative BGF landscapes.

Aging is characterized by the loss of homeostasis and the general decline of physiological functions, accompanied by various degenerative diseases and increased rates of mortality. Aging targeting small molecule screens have been performed many times, however, few have focused on endogenous metabolic intermediates-metabolites. Here, using C. elegans lifespan assays, we conducted a worm metabolite screen and identified an eukaryotes conserved metabolite, myo-inositol (MI), to extend lifespan, increase mobility and reduce fat content. Genetic analysis of enzymes in MI metabolic pathway suggest that MI alleviates aging through its derivative PI(4,5)P 2 . MI and PI(4,5)P 2 are precursors of PI(3,4,5)P 3 , which is negatively related to longevity. The longevity effect of MI is dependent on the tumor suppressor gene, daf-18 (homologous to mouse Pten), independent of its classical pathway downstream genes, akt or daf-16. Furthermore, we found MI effects on aging and lifespan act through mitophagy regulator PTEN induced kinase-1 (pink-1) and mitophagy. MI's anti-aging effect is also conserved in mouse, indicating a conserved mechanism in mammals.

Not all individuals age at the same rate. Methods such as the 'methylation clock' are invasive, rely on expensive assays of tissue samples and infer the ageing rate by training on chronological age, which is used as a reference for prediction errors. Here, we develop models based on convoluted neural networks through training on non-invasive three-dimensional (3D) facial images of approximately 5,000 Han Chinese individuals that achieve an average difference between chronological or perceived age and predicted age of ±2.8 and 2.9 yr, respectively. We further profile blood transcriptomes from 280 individuals and infer the molecular regulators mediating the impact of lifestyle on the facial-ageing rate through a causal-inference model. These relationships have been deposited and visualized in the Human Blood Gene Expression-3D Facial Image (HuB-Fi) database. Overall, we find that humans age at different rates both in the blood and in the face, but do so coherently and with heterogeneity peaking at middle age. Our study provides an example of how artificial intelligence can be leveraged to determine the perceived age of humans as a marker of biological age, while no longer relying on prediction errors of chronological age, and to estimate the heterogeneity of ageing rates within a population.

Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations' non-tissue-specific "core transcriptome signatures" (CSs) of 8,476 genes generated from the TCGA database. We developed the core-signature drug-to-gene (csD2G) software to scan 3,546 drug treatment profiles against the reference signatures. csD2G significantly outperformed conventional cell line-based gene perturbation signatures and existing drug-repositioning methods in both coverage and specificity. We highlight this with 3 demonstrated applications: (1) repositioned category of psychiatric drugs to inhibit the TGF-β pathway; (2) antihypertensive calcium channel blockers predicted to activate AMPK and inhibit AKT pathways, and validated by clinical electronic medical records; and (3) 7 drugs predicted and validated to selectively target the AKT-FOXO and AMPK pathways and thus regulate worm lifespan., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

The RNA-binding protein LIN-28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin-28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN-28-regulated microRNA let-7 was required for these effects by targeting akt-1/2 and decreasing their protein levels. AKT-1/2 and the downstream DAF-16 transcription factor were both required for the lifespan and germline stem cell effects of lin-28. The pathway also mediated dietary restriction induced lifespan extension and reduction in germline stem cell number. Thus, the LIN-28/let-7/AKT/DAF-16 axis we delineated here is a program that plays an important role in balancing reproduction and somatic maintenance and their response to the environmental energy level-a central dogma of the 'evolutionary optimization' of resource allocation that modulates aging., (© 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

A new approach to measure the 3D profile of a texture object is proposed utilizing light field imaging, in which three key steps are required: a disparity map is first obtained by detecting the slopes in the epipolar plane image with the multilabel technique; the intrinsic parameters of the light field camera are then extracted by camera calibration; at last, the relationship between disparity values and real distances is built up by depth calibration. In the last step, a linear calibration method is proposed to achieve accurate results. Furthermore, the depth error is also investigated and compensated for by reusing the checkerboard pattern. The experimental results are in good agreement with the 3D models, and also indicate that the light field imaging is a promising 3D measurement technique.