Cancer-cell-secreted extracellular vesicles target p53 to impair mitochondrial function in muscle.

Skeletal muscle loss and weakness are associated with bad prognosis and poorer quality of life in cancer patients. Tumor-derived factors have been implicated in muscle dysregulation by inducing cachexia and apoptosis. Here, we show that extracellular vesicles secreted by breast cancer cells impair mitochondrial homeostasis and function in skeletal muscle, leading to decreased mitochondrial content and energy production and increased oxidative stress. Mechanistically, miR-122-5p in cancer-cell-secreted EVs is transferred to myocytes, where it targets the tumor suppressor TP53 to decrease the expression of TP53 target genes involved in mitochondrial regulation, including Tfam, Pgc-1α, Sco2, and 16S rRNA. Restoration of Tp53 in muscle abolishes mitochondrial myopathology in mice carrying breast tumors and partially rescues their impaired running capacity without significantly affecting muscle mass. We conclude that extracellular vesicles from breast cancer cells mediate skeletal muscle mitochondrial dysfunction in cancer and may contribute to muscle weakness in some cancer patients.

Cholesterol inhibits human voltage-gated proton channel hHv1.

Although human sperm is morphologically mature in the epididymis, it cannot fertilize eggs before capacitation. Cholesterol efflux from the sperm plasma membrane is a key molecular event essential for cytoplasmic alkalinization and hyperactivation, but the underlying mechanism remains unclear. The human voltage-gated proton (hHv1) channel functions as an acid extruder to regulate intracellular pHs of many cell types, including sperm. Aside from voltage and pH, Hv channels are also regulated by distinct ligands, such as Zn2+ and albumin. In the present work, we identified cholesterol as an inhibitory ligand of the hHv1 channel and further investigated the underlying mechanism using the single-molecule fluorescence resonance energy transfer (smFRET) approach. Our results indicated that cholesterol inhibits the hHv1 channel by stabilizing the voltage-sensing S4 segment at resting conformations, a similar mechanism also utilized by Zn2+. Our results suggested that the S4 segment is the central gating machinery in the hHv1 channel, on which voltage and distinct ligands are converged to regulate channel function. Identification of membrane cholesterol as an inhibitory ligand provides a mechanism by which the hHv1 channel regulates fertilization by linking the cholesterol efflux with cytoplasmic alkalinization, a change that triggers calcium influx through the CatSper channel. These events finally lead to hyperactivation, a remarkable change in the mobility pattern indicating fertilization competence of human sperm.

Voltage sensor dynamics of a bacterial voltage-gated sodium channel NavAb reveal three conformational states.

High-resolution structures of voltage-gated sodium channels (Nav) were first obtained from a prokaryotic ortholog NavAb, which provided important mechanistic insights into Na+ selectivity and voltage gating. Unlike eukaryotic Navs, the NavAb channel is formed by four identical subunits, but its ion selectivity and pharmacological profiles are very similar to eukaryotic Navs. Recently, the structures of the NavAb voltage sensor at resting and activated states were obtained by cryo-EM, but its intermediate states and transition dynamics remain unclear. In the present work, we used liposome flux assays to show that purified NavAb proteins were functional to conduct both H+ and Na+ and were blocked by the local anesthetic lidocaine. Additionally, we examined the real-time conformational dynamics of the NavAb voltage sensor using single-molecule FRET. Our single-molecule FRET measurements on the tandem NavAb channel labeled with Cy3/5 FRET fluorophore pair revealed spontaneous transitions of the NavAb S4 segment among three conformational states, which fitted well with the kinetic model developed for the S4 segment of the human voltage-gated proton channel hHv1. Interestingly, even under strong activating voltage, the NavAb S4 segment seems to adopt a conformational distribution similar to that of the hHv1 S4 segment at a deep resting state. The conformational behaviors of the NavAb voltage sensor under different voltages need to be further examined to understand the mechanisms of voltage sensing and gating in the canonical voltage-gated ion channel superfamily.

Arachidonic acid reverses cholesterol and zinc inhibition of human voltage-gated proton channels.

Unlike other members of the voltage-gated ion channel superfamily, voltage-gated proton (Hv) channels are solely composed of voltage sensor domains without separate ion-conducting pores. Due to their unique dependence on both voltage and transmembrane pH gradients, Hv channels normally open to mediate proton efflux. Multiple cellular ligands were also found to regulate the function of Hv channels, including Zn2+, cholesterol, polyunsaturated arachidonic acid, and albumin. Our previous work showed that Zn2+ and cholesterol inhibit the human voltage-gated proton channel (hHv1) by stabilizing its S4 segment at resting state conformations. Released from phospholipids by phospholipase A2 in cells upon infection or injury, arachidonic acid regulates the function of many ion channels, including hHv1. In the present work, we examined the effects of arachidonic acid on purified hHv1 channels using liposome flux assays and revealed underlying structural mechanisms using single-molecule FRET. Our data indicated that arachidonic acid strongly activates hHv1 channels by promoting transitions of the S4 segment toward opening or "preopening" conformations. Moreover, we found that arachidonic acid even activates hHv1 channels inhibited by Zn2+ and cholesterol, providing a biophysical mechanism to activate hHv1 channels in nonexcitable cells upon infection or injury.

Multidimensional Widefield Infrared-Encoded Spontaneous Emission Microscopy: Distinguishing Chromophores by Ultrashort Infrared Pulses.

Photoluminescence (PL) imaging has broad applications in visualizing biological activities, detecting chemical species, and characterizing materials. However, the chemical information encoded in the PL images is often limited by the overlapping emission spectra of chromophores. Here, we report a PL microscopy based on the nonlinear interactions between mid-infrared and visible excitations on matters, which we termed MultiDimensional Widefield Infrared-encoded Spontaneous Emission (MD-WISE) microscopy. MD-WISE microscopy can distinguish chromophores that possess nearly identical emission spectra via conditions in a multidimensional space formed by three independent variables: the temporal delay between the infrared and the visible pulses (t), the wavelength of visible pulses (λvis), and the frequencies of the infrared pulses (ωIR). This method is enabled by two mechanisms: (1) modulating the optical absorption cross sections of molecular dyes by exciting specific vibrational functional groups and (2) reducing the PL quantum yield of semiconductor nanocrystals, which was achieved through strong field ionization of excitons. Importantly, MD-WISE microscopy operates under widefield imaging conditions with a field of view of tens of microns, other than the confocal configuration adopted by most nonlinear optical microscopies, which require focusing the optical beams tightly. By demonstrating the capacity of registering multidimensional information into PL images, MD-WISE microscopy has the potential of expanding the number of species and processes that can be simultaneously tracked in high-speed widefield imaging applications.

Age-atypical brain functional networks in autism spectrum disorder: a normative modeling approach.

BACKGROUND: Despite extensive research into the neural basis of autism spectrum disorder (ASD), the presence of substantial biological and clinical heterogeneity among diagnosed individuals remains a major barrier. Commonly used case‒control designs assume homogeneity among subjects, which limits their ability to identify biological heterogeneity, while normative modeling pinpoints deviations from typical functional network development at individual level. METHODS: Using a world-wide multi-site database known as Autism Brain Imaging Data Exchange, we analyzed individuals with ASD and typically developed (TD) controls (total n = 1218) aged 5-40 years, generating individualized whole-brain network functional connectivity (FC) maps of age-related atypicality in ASD. We then used local polynomial regression to estimate a networkwise normative model of development and explored correlations between ASD symptoms and brain networks. RESULTS: We identified a subset exhibiting highly atypical individual-level FC, exceeding 2 standard deviation from the normative value. We also identified clinically relevant networks (mainly default mode network) at cohort level, since the outlier rates decreased with age in TD participants, but increased in those with autism. Moreover, deviations were linked to severity of repetitive behaviors and social communication symptoms. CONCLUSIONS: Individuals with ASD exhibit distinct, highly individualized trajectories of brain functional network development. In addition, distinct developmental trajectories were observed among ASD and TD individuals, suggesting that it may be challenging to identify true differences in network characteristics by comparing young children with ASD to their TD peers. This study enhances understanding of the biological heterogeneity of the disorder and can inform precision medicine.

Extracellular vesicles in cancer therapy.

Extracellular vesicles (EVs), including a variety of membrane-enclosed nanosized particles carrying cell-derived cargo, mediate a major type of intercellular communication in physiological and pathological processes. Both cancer and non-cancer cells secrete EVs, which can travel to and influence various types of cells at the primary tumor site as well as in distant organs. Tumor-derived EVs contribute to cancer cell plasticity and resistance to therapy, adaptation of tumor microenvironment, local and systemic vascular remodeling, immunomodulation, and establishment of pre-metastatic niches. Therefore, targeting the production, uptake, and function of tumor-derived EVs has emerged as a new strategy for stand-alone or combinational therapy of cancer. On the other hand, as EV cargo partially reflects the genetic makeup and phenotypic properties of the secreting cell, EV-based biomarkers that can be detected in biofluids are being developed for cancer diagnosis and for predicting and monitoring tumor response to therapy. Meanwhile, EVs from presumably safe sources are being developed as delivery vehicles for anticancer therapeutic agents and as anticancer vaccines. Numerous reviews have discussed the biogenesis and characteristics of EVs and their functions in cancer. Here, I highlight recent advancements in translation of EV research outcome towards improved care of cancer, including developments of non-invasive EV-based biomarkers and therapeutic agents targeting tumor-derived EVs as well as engineering of therapeutic EVs.

Cancer-secreted miRNAs regulate amino-acid-induced mTORC1 signaling and fibroblast protein synthesis.

Metabolic reprogramming of non-cancer cells residing in a tumor microenvironment, as a result of the adaptations to cancer-derived metabolic and non-metabolic factors, is an emerging aspect of cancer-host interaction. We show that in normal and cancer-associated fibroblasts, breast cancer-secreted extracellular vesicles suppress mTOR signaling upon amino acid stimulation to globally reduce mRNA translation. This is through delivery of cancer-derived miR-105 and miR-204, which target RAGC, a component of Rag GTPases that regulate mTORC1 signaling. Following amino acid starvation and subsequent re-feeding, 13 C-arginine labeling of de novo synthesized proteins shows selective translation of proteins that cluster to specific cellular functional pathways. The repertoire of these newly synthesized proteins is altered in fibroblasts treated with cancer-derived extracellular vesicles, in addition to the overall suppressed protein synthesis. In human breast tumors, RAGC protein levels are inversely correlated with miR-105 in the stroma. Our results suggest that through educating fibroblasts to reduce and re-prioritize mRNA translation, cancer cells rewire the metabolic fluxes of amino acid pool and dynamically regulate stroma-produced proteins during periodic nutrient fluctuations.

A Mathematical Model of the Disruption of Glucose Homeostasis in Cancer Patients.

In this paper, we investigate the disruption of the glucose homeostasis at the whole-body level by the presence of cancer disease. Of particular interest are the potentially different responses of patients with or without hyperglycemia (including diabetes mellitus) to the cancer challenge, and how tumor growth, in turn, responds to hyperglycemia and its medical management. We propose a mathematical model that describes the competition between cancer cells and glucose-dependent healthy cells for a shared glucose resource. We also include the metabolic reprogramming of healthy cells by cancer-cell-initiated mechanism to reflect the interplay between the two cell populations. We parametrize this model and carry out numerical simulations of various scenarios, with growth of tumor mass and loss of healthy body mass as endpoints. We report sets of cancer characteristics that show plausible disease histories. We investigate parameters that change cancer cells' aggressiveness, and we exhibit differing responses in diabetic and non-diabetic, in the absence or presence of glycemic control. Our model predictions are in line with observations of weight loss in cancer patients and the increased growth (or earlier onset) of tumor in diabetic individuals. The model will also aid future studies on countermeasures such as the reduction of circulating glucose in cancer patients.

Multi-laboratory validation study of a real-time PCR method for detection of Salmonella in baby spinach.

The FDA Bacteriological Analytical Manual (BAM) Salmonella culture method takes at least 3 days for a presumptive positive result. The FDA developed a quantitative PCR (qPCR) method to detect Salmonella from 24-h preenriched cultures, using ABI 7500 PCR system. The qPCR method has been evaluated as a rapid screening method for a broad range of foods by single laboratory validation (SLV) studies. The present multi-laboratory validation (MLV) study was aimed to measure the reproducibility of this qPCR method and compare its performance with the culture method. Sixteen laboratories participated in two rounds of MLV study to analyze twenty-four blind-coded baby spinach test portions each. The first round yielded ∼84% and ∼82% positive rates across laboratories for the qPCR and culture methods, respectively, which were both outside the fractional range (25%-75%) required for fractionally inoculated test portions by the FDA's Microbiological Method Validation Guidelines. The second round yielded ∼68% and ∼67% positive rates. The relative level of detection (RLOD) for the second-round study was 0.969, suggesting that qPCR and culture methods had similar sensitivity (p > 0.05). The study demonstrated that the qPCR yields reproducible results and is sufficiently sensitive and specific for the detection of Salmonella in food.

Clinical Efficacy of Different Doses of Canagliflozin Combined with Metformin in the Treatment of Type 2 Diabetes: Meta-Analysis.

Background: With social development, an aging population, and the increasing trend of obesity, type 2 diabetes (T2DM) has become one of the major problems affecting human health across the globe. Methods: Information on controlled trials was retrieved from four databases to obtain the effects of different doses of canagliflozin combined with metformin for treating T2DM. After a rigorous evaluation of the quality of the literature, data analysis was performed using RevMan 5.3 software. Results: We included 8 studies in this meta-analysis. The least square (LS) means of HbA1c and FPG in the test group were statistically lower than the control group. Our analysis revealed that the adverse reactions were not significantly different between the experimental and control groups (OR: 1.03; 95% Cl: 0.94, 1.12; P = .555). Also, we found that the urinary tract infection of the experimental group was not statistically different from the control group (OR: 0.94; 95% Cl: 0.71, 1.24; P = .648). Moreover, we identified that the blood pressure and blood lipids of the experimental group did not statistically differ from the control group. Conclusion: The meta-analysis demonstrates that high doses of canagliflozin combined with metformin may be potentially effective in patients with T2DM, as evidenced by LS means of HbA1c and FPG, and the above conclusions need to be verified by more high-quality studies.

Exploring Oxidoreductases from Extremophiles for Biosynthesis in a Non-Aqueous System.

Organic solvent tolerant oxidoreductases are significant for both scientific research and biomanufacturing. However, it is really challenging to obtain oxidoreductases due to the shortages of natural resources and the difficulty to obtained it via protein modification. This review summarizes the recent advances in gene mining and structure-functional study of oxidoreductases from extremophiles for non-aqueous reaction systems. First, new strategies combining genome mining with bioinformatics provide new insights to the discovery and identification of novel extreme oxidoreductases. Second, analysis from the perspectives of amino acid interaction networks explain the organic solvent tolerant mechanism, which regulate the discrete structure-functional properties of extreme oxidoreductases. Third, further study by conservation and co-evolution analysis of extreme oxidoreductases provides new perspectives and strategies for designing robust enzymes for an organic media reaction system. Furthermore, the challenges and opportunities in designing biocatalysis non-aqueous systems are highlighted.

Dual mechanisms of posttranscriptional regulation of Tet2 by Let-7 microRNA in macrophages.

Tet methylcytosine dioxygenase 2 (Tet2) is an epigenetic regulator that removes methyl groups from deoxycytosine residues in DNA. Tet2-deficient murine macrophages show increased lipopolysaccharide (LPS)-induced and spontaneous inflammation at least partially because Tet2 acts to restrain interleukin (IL)-1ß and IL-6 expression in induced cells. MicroRNAs have emerged as critical regulatory noncoding RNAs that tune immune cell responses to physiological perturbations and play roles in pathological conditions in macrophages. To determine if a microRNA played any role in Tet2 activity, we examined the interrelationship of Tet2 action and the let-7 microRNA family, utilizing several let-7 microRNA engineered murine models. We first showed that Tet2, but not Tet3, is a direct target of the let-7a-1/let-7d/let-7f-1 (let-7adf) microRNAs in macrophages. We found that overexpression or deletion of the let-7adf gene cluster causes altered IL-6 induction both in tissue culture cells induced by LPS treatment in vitro as well as in a Salmonella infection mouse model in vivo. Mechanistically, let-7adf promotes IL-6 by directly repressing Tet2 levels and indirectly by enhancing a Tet2 suppressor, the key TCA cycle metabolite, succinate. We found that Let-7adf promotes succinate accumulation by regulating the Lin28a/Sdha axis. We thereby identify two pathways of let-7 control of Tet2 and, in turn, of the key inflammatory cytokine, IL-6, thus characterizing a regulatory pathway in which a microRNA acts as a feedback inhibitor of inflammatory processes.

Effect of liver cirrhosis on erectile function in rats: A study combining bioinformatics analysis and experimental research.

To explore the mechanism through which liver cirrhosis (LC) causes erectile dysfunction (ED). Bioinformatic analysis was used to predict the potential signalling pathways in LC-induced ED, and N-nitrosodiethylamine was used to establish a rat model of LC. H&E staining, Western blotting and RT-qPCR were used to detect pathological tissue damage and changes in mRNA and protein expression levels. In addition, the expression levels of sex hormones such as estradiol (E2), prolactin (PRL) and testosterone (T) were measured. The hypoxia-inducible factor (HIF) pathway was an important pathway in our bioinformatics prediction. Pathological damages were detected in the liver and penile tissues of the model rats. Compared with the normal group's serum hormone levels, E2 and PRL were increased in LC rats, while T was decreased (p < 0.01). The mRNA and protein expression results from penis tissues showed that endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were both downregulated, and HIF-1α was upregulated in the model group compared to the normal group (p < 0.01). These data suggest that LC hinders erectile function and causes histopathological changes in the penis by affecting the expression of HIF-1α, eNOS, iNOS, E2, PRL and T.

Effects of Exogenous L-Asparagine on Poplar Biomass Partitioning and Root Morphology.

L-Asparagine (Asn) has been regarded as one of the most economical molecules for nitrogen (N) storage and transport in plants due to its relatively high N-to-carbon (C) ratio (2:4) and stability. Although its internal function has been addressed, the biological role of exogenous Asn in plants remains elusive. In this study, different concentrations (0.5, 1, 2, or 5 mM) of Asn were added to the N-deficient hydroponic solution for poplar 'Nanlin895'. Morphometric analyses showed that poplar height, biomass, and photosynthesis activities were significantly promoted by Asn treatment compared with the N-free control. Moreover, the amino acid content, total N and C content, and nitrate and ammonia content were dramatically altered by Asn treatment. Moreover, exogenous Asn elicited root growth inhibition, accompanied by complex changes in the transcriptional pattern of genes and activities of enzymes associated with N and C metabolism. Combined with the plant phenotype and the physiological and biochemical indexes, our data suggest that poplar is competent to take up and utilize exogenous Asn dose-dependently. It provides valuable information and insight on how different forms of N and concentrations of Asn influence poplar root and shoot growth and function, and roles of Asn engaged in protein homeostasis regulation.

Transcriptome Analysis Reveals Critical Genes and Pathways in Carbon Metabolism and Ribosome Biogenesis in Poplar Fertilized with Glutamine.

Exogenous Gln as a single N source has been shown to exert similar roles to the inorganic N in poplar 'Nanlin895' in terms of growth performance, yet the underlying molecular mechanism remains unclear. Herein, transcriptome analyses of both shoots (L) and roots (R) of poplar 'Nanlin895' fertilized with Gln (G) or the inorganic N (control, C) were performed. Compared with the control, 3109 differentially expressed genes (DEGs) and 5071 DEGs were detected in the GL and GR libraries, respectively. In the shoots, Gln treatment resulted in downregulation of a large number of ribosomal genes but significant induction of many starch and sucrose metabolism genes, demonstrating that poplars tend to distribute more energy to sugar metabolism rather than ribosome biosynthesis when fertilized with Gln-N. By contrast, in the roots, most of the DEGs were annotated to carbon metabolism, glycolysis/gluconeogenesis and phenylpropanoid biosynthesis, suggesting that apart from N metabolism, exogenous Gln has an important role in regulating the redistribution of carbon resources and secondary metabolites. Therefore, it can be proposed that the promotion impact of Gln on poplar growth and photosynthesis may result from the improvement of both carbon and N allocation, accompanied by an efficient energy switch for growth and stress responses.

Electrochemical Enzyme Sensor Based on the Two-Dimensional Metal-Organic Layers Supported Horseradish Peroxidase.

Metal-organic frames (MOFs) have recently been used to support redox enzymes for highly sensitive and selective chemical sensors for small biomolecules such as oxygen (O2), hydrogen peroxide (H2O2), etc. However, most MOFs are insulative and their three-dimensional (3D) porous structures hinder the electron transfer pathway between the current collector and the redox enzyme molecules. In order to facilitate electron transfer, here we adopt two-dimensional (2D) metal-organic layers (MOLs) to support the HRP molecules in the detection of H2O2. The correlation between the current response and the H2O2 concentration presents a linear range from 7.5 µM to 1500 µM with a detection limit of 0.87 µM (S/N = 3). The sensitivity, reproducibility, and stability of the enzyme sensor are promoted due to the facilitated electron transfer.

Potassium channel selectivity filter dynamics revealed by single-molecule FRET.

Potassium (K) channels exhibit exquisite selectivity for conduction of K+ ions over other cations, particularly Na+. High-resolution structures reveal an archetypal selectivity filter (SF) conformation in which dehydrated K+ ions, but not Na+ ions, are perfectly coordinated. Using single-molecule FRET (smFRET), we show that the SF-forming loop (SF-loop) in KirBac1.1 transitions between constrained and dilated conformations as a function of ion concentration. The constrained conformation, essential for selective K+ permeability, is stabilized by K+ but not Na+ ions. Mutations that render channels nonselective result in dilated and dynamically unstable conformations, independent of the permeant ion. Further, while wild-type KirBac1.1 channels are K+ selective in physiological conditions, Na+ permeates in the absence of K+. Moreover, whereas K+ gradients preferentially support 86Rb+ fluxes, Na+ gradients preferentially support 22Na+ fluxes. This suggests differential ion selectivity in constrained versus dilated states, potentially providing a structural basis for this anomalous mole fraction effect.

Socioeconomic status, social capital, health risk behaviors, and health-related quality of life among Chinese older adults.

BACKGROUND: There is limited knowledge on the mediating role of different health risk behavior on the relationship between social capital, socioeconomic status (SES), and health-related quality of life (HRQoL) in Chinese older adults. We conducted this study to (a) investigate the condition of health risk behaviors of the Chinese elderly, and (b) assess the relationship between SES, social capital, health risk behaviors, and HRQoL. METHODS: A sample of 4868 adults aged 60 years and older were included in this study, from the China's Health-related Quality of Life Survey for Older Adults 2018. Participants' demographic characteristics, SES (education level, family income), health risk behaviors (smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder) were collected. Social capital and HRQoL were assessed by the 16-item Personal Social Capital Scale (PSCS-16) and WHOQOL-Old, respectively. Structural equation modeling (SEM) was applied to examine the associations between variables. RESULTS: The proportion of smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder were 32.1, 36.3, 62.5, 45.7, 31.8, and 45.5%, respectively. Significant differences were observed in education level, family income, and social capital between elderly individuals with and without each of the six health risk behavior (all p-values < 0.05). Elderly individuals who reported smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder had significantly lower HRQoL than those without these unhealthy behaviors (all p-values < 0.05). SEM analysis showed that SES and social capital positively associated with alcohol consumption. Social capital negatively associated with smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder. SES negatively associated with smoking, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder. Smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder correlated with poorer HRQoL. CONCLUSIONS: Chinese older adults demonstrated a high incidence of health risk behaviors, especially for physical inactivity (62.5%) and unhealthy dietary behavior (45.7%). Social capital and SES were correlated with the elderly's HRQoL, as well as with the health risk behaviors. Health risk behaviors played potential mediating role on the relationship between social capital, SES, and HRQoL in Chinese older adults.

Association between diet-related knowledge, attitudes, behaviors, and self-rated health in Chinese adult residents: a population-based study.

BACKGROUND: Diet-related knowledge, attitudes, and behaviors (KABs) are important for building healthier dietary patterns. We conducted this study to (a) investigate diet conditions of Chinese adult residents from the perspective of knowledge, attitudes, and behaviors, and (b) assess the association between diet-related KABs and self-rated health. METHODS: We analyzed the 2015 China Health and Nutrition Survey (CHNS) data. Individuals aged 18 years and older were included as study subjects (n = 12,814), assessing their diet-related knowledge, attitudes, behaviors, and self-rated health. Comparison of diet-related KABs in urban and rural residents was conducted using chi-square test. Ordinal logistic regression analysis was adopted to examine the association between diet-related KABs and self-rated health. RESULTS: The proportion of knowing about the Chinese Food Pagoda (CFP) or the Dietary Guidelines for Chinese Residents (DGCR) was 27.1%. 34.3% of the participants were assessed as having adequate dietary knowledge literacy. 24.3% reported a positive attitude towards healthy eating. 27.6 and 65.9% of the participants reported proactively looking for nutrition knowledge and preferring eating fruits & vegetables, respectively. Chi-square test indicated that rural people experienced poorer diet-related knowledge, attitudes, and behaviors than urban residents (all p-values < 0.01). Regression analysis revealed that participants who knew about CFP/DGCR (OR = 1.11, 95% CI = 1.08-1.15), had adequate dietary knowledge literacy (OR = 1.12, 95% CI = 1.10-1.15), held positive attitude towards healthy eating (OR = 1.14, 95% CI = 1.09-1.19), proactively looked for nutrition knowledge (OR = 1.11, 95% CI = 1.08-1.15), and preferred eating fruits & vegetables (OR = 1.09, 95% CI = 1.07-1.12) had significantly better self-rated health. CONCLUSIONS: Chinese adult residents experienced poor diet-related knowledge, attitudes, and behaviors. Rural people had significantly worse diet conditions than urban residents. Better diet-related knowledge, attitudes, and behaviors were associated with higher self-rated health in Chinese adult residents.