Associations of prediabetes and sleep duration, and inflammation as a mediator in the China Health and Retirement Longitudinal Study.

OBJECTIVE: The objective of this study was to examine the relationship between sleep duration and prediabetes, as well as to evaluate the influence of inflammation in mediating this association. METHODS: A total of 4632 participants from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study, comprising both baseline and 4-year follow-up data. The prospective relationship between sleep duration and the risk of prediabetes was examined using logistic regression models. We used multinomial logistic regression to evaluate the impact of prediabetes on sleep duration changes over follow-up, assessing the role of C-reactive protein in the association using mediation analysis. RESULTS: Participants with short sleep duration (<5 hours) had a higher risk of prediabetes (odds ratios=1.381 [95% CI: 1.028-1.857]) compared to those with normal sleep durations (7-8 hours). However, excessive sleep durations (≥9 hours) did not show a statistically significant association with prediabetes risk. Moreover, individuals at least 60years old who experienced short sleep durations exhibited a higher risk of prediabetes. Individuals with prediabetes were more likely to have shorter sleep duration than excessive sleep duration (relative risk ratios=1.280 [95% CI: 1.059-1.547]). The mediation analysis revealed a mediating effect of C-reactive protein on the association between prediabetes and reduced sleep duration. CONCLUSIONS: Short sleep duration was identified as a risk factor for the incidence of prediabetes. Conversely, prediabetes was found to contribute to shorter sleep duration rather than excessive sleep duration. Moreover, elevated levels of C-reactive protein may serve as a potential underlying mechanism that links prediabetes with shorter sleep.

Realizing multiferroics in α-Ga2S3via hole doping: a first-principles study.

Using first-principles calculations, we report the realization of multiferroics in an intrinsic ferroelectric α-Ga2S3 monolayer. Our results show that the presence of intrinsic gallium vacancies, which is the origin of native p-type conductivity, can simultaneously introduce a ferromagnetic ground state and a spontaneous out-of-plane polarization. However, the high switching barrier and thermodynamic irreversibility of the ferroelectric reversal path disable the maintenance of ferroelectricity, suggesting that the defect-free form should be a prerequisite for Ga2S3 to be multiferroic. Through applying strain, the behavior of spontaneous polarization of the pristine α-Ga2S3 monolayer can be effectively regulated, but the non-magnetic ground state does not change. Strikingly, via an appropriate concentration of hole doping, stable ferromagnetism with a high Curie temperature and robust ferroelectricity can be concurrently introduced in the α-Ga2S3 monolayer. Our work provides a feasible method for designing 2D multiferroics with great potential in future device applications.

Association between PM10 pollution and the hospitalization of chronic obstructive pulmonary disease with comorbidity: evidence in 17 cities of Henan, Central China.

Particulate matter (PM10) changes have been confirmed as one of the contributory factors affecting human health, the association between PM10 pollution and the hospitalization of chronic obstructive pulmonary disease (COPD) with comorbidity diseases was rarely reported. The same inpatient more than twice times admissions with COPD illness from January 1, 2016 to December 31, 2021 were identified from hospitals in the 17 cities of Henan, Central China. City-specific associations were firstly estimated using the case time series (CTS) model and then combined to obtain the regional average association. The multivariate meta-analytic model produces pooled estimates of the set of coefficients representing the PM10-COPD hospitalizations association across the 17 cities. Cause-specific hospitalization analyses were performed by COPD patients with different comorbidity combinations. A total of 34,348 elderly (age ≥ 65) subjects were analyzed and with a total of 35,122.35 person-years. These coefficients can be used to compute the linear exposure-response curve expressed as relative risk (RR) in per 10 µg/m3 increase in PM10 at lag03, which was 1.0091 (95% CI 1.0070-1.0112) for COPD with comorbidity, 1.0089 (95% CI 1.0067-1.0110) for COPD with circulatory system diseases, 1.0079 (95% CI 1.0052-1.0105) for COPD with respiratory system diseases, 1.0076 (95% CI 1.0032-1.0121) for COPD with endocrine system diseases, and 1.0087 (95% CI 1.0013-1.0162) for COPD with genitourinary system diseases, respectively. Some heterogeneity was found across cities, with estimates ranging from 1.0227 in the Puyang and Jiaozuo to 1.0053 in Henan Provance, China. The effect of higher PM10, on average, was higher in studies for northern cities, with a steeper raise in risk: per 10 µg/m3 increase in PM10, the RR from 1.0062 (95% CI 1.0030-1.0093) for the 10th percentile of latitude to 1.0124 (95% CI 1.0089-1.0160) for the 90th percentile. Our findings indicated that PM10 exposure may increase the risk of hospitalizations for COPD with comorbidity. Moreover, there might be a higher morbidity risk associated with PM10 in northern latitudes, indicating that stricter air quality standards could potentially reduce PM10-related morbidity among individuals with COPD. These findings have implications for the implementation of effective clean air interventions aligned with national climate policies.

Association of social isolation and cognitive performance: a longitudinal study using a four-wave nationwide survey.

BACKGROUND: This study aimed to examine the bidirectional relationship between social isolation and cognitive performance among Chinese middle-aged and older adults. METHODS: We used four waves of data from the China Health and Retirement Longitudinal Study. A latent growth model (LGM) was applied to examine the association between social isolation and cognitive performance across different characteristics. RESULTS: In the analysis, we ultimately included 9,367 participants after excluding respondents with missing key variables. Social isolation and cognitive performance showed significant differences across time. After adjusting for the confounders, there was a significant association between higher social isolation and poor cognitive performance (ß = -1.38, p < 0.001), and higher levels of social isolation resulted in a more pronounced decline in cognition over time (ß = 0.17, p < 0.001). Additionally, the path coefficient between the initial level of cognition at baseline and the slope of social isolation was - 0.07 (p < 0.001) and 0.01 (p = 0.021), respectively. For the correlation between slopes, our study found that females' cognition scores were more susceptible to social isolation (ß = - 2.78, p < 0.001). Similarly, regarding cognition scores, the influence of social isolation was greater among people with education below the primary level (ß = - 2.89, p = 0.002) or a greater number of chronic diseases (ß = - 2.56, p = 0.001). CONCLUSION: Our findings support the bidirectional association between social isolation and cognition. Specifically, higher baseline social isolation and its rate of increase over time contribute to an intensification of cognitive decline at follow-up. Besides, poorer cognitive performance predicted higher social isolation.

Trinitroaromatic Salts as High-Energy-Density Organic Cathode Materials for Li-Ion Batteries.

Even though organic molecules with designed structures can be assembled into high-capacity electrode materials, only limited functional groups such as -C═O and -C═N- could be designed as high-voltage cathode materials with enough high capacity. Here, we propose a common chemical raw material, trinitroaromatic salt, to have promising potential to develop organic cathode materials with high discharge voltage and capacity through a strong delocalization effect between -NO2 and aromatic ring. Our first-principles calculations show that electrochemical reactions of trinitroaromatic potassium salt C6H2(NO2)3OK are a 6-electron charge-transfer process, providing a high discharge capacity of 606 mAh g-1 and two voltage plateaus of 2.40 and 1.97 V. Electronic structure analysis indicates that the discharge process from C6H2(NO2)3OK to C6H2(NO2Li2)3OK stabilizes oxidized [C6]n+ to achieve a stable conjugated structure through electron delocalization from -NO2 to [C6]n+. The ordered layer structure C6H2(NO2)3OK can provide large spatial pore channels for Li-ion transport, achieving a high ion diffusion coefficient of 3.41 × 10-6 cm2 s-1.

Transition Metal-Modified Co4 Clusters Supported on Graphdiyne as an Effective Nitrogen Reduction Reaction Electrocatalyst.

Conversion of N2 into NH3 through the electrochemical nitrogen reduction reaction (NRR) under ambient conditions represents a novel green ammonia synthesis method. The main obstacle for NRR is lack of efficient, stable, and cost-effective catalysts. In this work, by using density functional theory calculations, 16 transition metal-modified Co4 clusters supported on graphdiyne (GDY) as potential NRR catalysts were systematically screened. Through the examinations of stability, N2 activation, selectivity, and activity, Ti-, V-, Cr-, Mn-, and Zr-Co3@GDY were identified as the promising candidates toward NRR. Further explorations on the NRR mechanisms and the Pourbaix diagrams suggest that Ti-Co3@GDY was the most promising candidate catalyst, as it has the lowest limiting potential and high stability under the working conditions. The high activities originate from the synergy effect, where the Co3 cluster acts as the electron donor and the heteroatom serves as the single active site throughout the NRR process. Our results offer a new perspective for advancing sustainable NH3 production.

Reaction mechanism and kinetics of Criegee intermediate and hydroperoxymethyl formate.

The reaction mechanism and kinetics of the simplest Criegee intermediate CH2OO reaction with hydroperoxymethyl formate (HPMF) was investigated at high-level quantum chemistry calculations. HPMF has two reactive functional groups, -C(O)OH and -OOH. The calculated results of thermodynamic data and rate constants indicated that the insertion reactions of CH2OO with -OOH group of HPMF were more favorable than the reactions of CH2OO with -C(O)OH group. The calculated overall rate constant was 2.33 × 10-13 cm3/(molecule⋅sec) at 298 K and the rate constants decreased as the temperature increased from 200 to 480 K. In addition, we also proved the polymerization reaction mechanism between CH2OO and -OOH of HPMF. This theoretical study interpreted the previous experimental results, and supplied the structures of the intermediate products that couldn't be detected during the experiment.

Atomic structure and electrical property of ionic liquids at the MoS2 electrode with varying interlayer spacing.

Understanding the structure and properties at the electrolyte-electrode interface is vital for the rational design of the supercapacitors or other electrochemical devices. In this work, we explored the influence of interlayer spacing of the MoS2 electrode on the interfacial structure and electrical properties of sodium-ionic liquids (ILs) electrolytes via performing the all-atom molecular dynamics simulations. From the number density, charge density, and electrical potential distribution near the surface, the Mo- and S-terminal edges possess positive and negative features when the interlayer spacing is less than 8.5 Å. Meanwhile, the strength of the first density layer of ILs increases with the increase of the interlayer spacing of MoS2 for both Mo- and S- terminal surfaces in the neutral or charging state. Furthermore, the coordination number of sodium ion at the electrode surface was analyzed, and it was shown that the S-terminal surface has a larger coordination number than that on the Mo-terminal surface. Interestingly, the coordination number of MoS2 with the interlayer spacing of 8.0 Å is the lowest in the ranges of 6.5~8.5 Å. The electrolyte's charge screening factor also reflects the opposite electrical state of Mo- and S-terminal surfaces and weakens with increasing the interlayer spacing and surface charge density. The obtained understanding of ILs at electrode interfaces with different layer spacings in this work will provide insight into the molecular mechanisms of ILs-based sodium supercapacitors or other electrochemical devices in critical chemical engineering processes.

Cyanidin-3-O-ß-glucoside inactivates NLRP3 inflammasome and alleviates alcoholic steatohepatitis via SirT1/NF-κB signaling pathway.

Alcoholic liver disease (ALD) is a major cause of liver disease worldwide. In patients with ALD, an increased level of hepatic inflammasome components was observed, together with an increased circulating pro-inflammatory cytokines. Cyanidin-3-O-ß-glucoside (Cy-3-G) is a bioactive compound belonging to the anthocyanin group, which widely exists in deep-colored fruits and vegetables. Consumption of Cy-3-G is associated with lower risks of non-alcoholic fatty liver disease (NAFLD), liver fibrosis, obesity, atherosclerosis, and inflammation. However, whether Cy-3-G has effects on inflammasome formation and activation thereby protects against alcohol-induced liver damage remain elusive. In this study, we identified that dietary provision of Cy-3-G remarkably attenuated liver damage caused by excess energy intake and alcohol consumption. Supplement with Cy-3-G mediated NAD+ homeostasis, which stimulated SirT1 activity, resulting in suppressed NF-κB acetylation. Interestingly, Cy-3-G treatment suppressed NF-κB acetylation when SirT1 action was blunted by selective antagonist, and subsequently suppressed NLRP3 inflammasome activation and proinflammatory cytokines release in hepatic cell lines. Our findings first demonstrate that Cy-3-G at a physiologically achievable dosage alleviates alcohol-induced hepatic inflammation via inactivation of NLRP3 inflammasome and deacetylation of NF-κB, suggesting a promising therapeutic approach to alleviate alcohol-induced liver damage.

Study on ozonolysis of asymmetric alkenes with matrix isolation and FT-IR spectroscopy.

O3 and alkenes are important reactants in the formation of SOA in the atmosphere. The intermediates and reaction mechanism of ozonation of alkene is an important topic in atmospheric chemistry. In this study, the low-temperature matrix isolation was used to capture the intermediates such as Primary ozonides (POZs), Criegee Intermediates (CIs), and Secondary ozonides (SOZs) generated from ozonation of 2-methyl-1-butene (2M1B) and 2-methyl-2-butene (2M2B). The results have been identified by the vacuum infrared spectroscopy and theoretical calculation. Our results show that during the ozonation of asymmetric alkenes, two kinds of CIs and more than two kinds of SOZs were generated due to the different decomposition modes of POZs. The infrared absorption peaks of (CH3)2COO and CH3CH2C(CH3)OO for O-O telescopic vibration was determined to be 889 cm-1 and 913 cm-1, respectively. Using the merged jet method, it was found that a large amount of HCHO was produced during the ozonation of 2M1B, and glyoxal and methylglyoxal were produced in the ozonation of 2M2B. Our findings highlight the importance of asymmetric alkene ozonolysis reactions in producing CIs, further improving the understanding of the generation of CIs from ozonation of alkenes.

Spin transport properties of 1,4,5,8-naphthalenetetracarboxylic dianhydride based molecular devices.

Using density functional theory combined with the nonequilibrium Green's function method, spin-dependent transport properties of molecular devices consisting of the 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTCDA) molecule anchored via C and O linkages to zigzag graphene nanoribbon (ZGNR) electrodes were systematically investigated. Calculation results showed that the two connection modes display a good spin transport performance in both parallel (P) and anti-parallel (AP) configurations. Particularly, oxygen connection significantly improves the spin filtration effect. These observations were validated by analyzing spin-resolved transmission spectra, band structures and spatial distribution of molecular orbitals within the bias window. Further comparison of the results of different models indicated that the linkage plays a crucial role in improving the spin transport properties for the proposed NTCDA-ZGNR system, giving them potential applications in high-performance multifunctional spintronic devices.

First-principles study on screening doped TiO2(B) as an anode material with high conductivity and low lithium transport resistance for lithium-ion batteries.

As a promising anode material, TiO2(B) has attracted much attention in recent years due to its high power and capacity performances. First-principles calculations are performed here to reveal the electronic properties and the transport of lithium (Li) in the bulk TiO2(B) with and without atomic doping. It is found that a 4-fold coordinated O atom has the lowest formation energy and the smallest bandgap and is the atom that most easily forms an O-vacancy (Ov). In this work, a series of p-type (N, P, As), n-type (F, Cl, Br), and isoelectronic (S, Se, Te) dopants in TiO2(B) are studied. For n-type dopants, the substitution of the F atom has no significant effect on the electronic structure, which results in the lowest formation energy. This result demonstrates that the F atom can provide high intrinsic stability. Analysis of the insertion process of Li in doped TiO2(B) shows that N-doping is the most competitive choice because it not only introduces a lower bandgap of TiO2(B) but it also has the highest binding energy with Li. The advantage of N-doping is derived from the self-compensation effect. Also, three possible transport paths of Li in TiO2(B) were studied via the CI-NEB method. The results show that the energy barrier of all diffusion paths of F doping is lower than that of pure TiO2(B), where path 2 along the b-axis channel has the lowest energy (0.32 eV). This study is expected to shed some light on the electronic structures of TiO2(B) and the transport properties of Li in it.

Defective Graphene on the Transition-Metal Surface: Formation of Efficient Bifunctional Catalysts for Oxygen Evolution/Reduction Reactions in Alkaline Media.

Supported single-atom catalysts (SACs) have attracted enormous attention because of their high selectivity, activity, and efficiency, compared to conventional nanoparticles and metal bulk catalysts. However, all of these unique merits rely on the stability of the SAC, as reported by many investigators. To avoid aggregation of single-metal atoms and maintain the high performance of the SAC, various substrates have been tried to support them, particularly on graphene nanosheets. A spontaneous interface phenomenon between graphene and the Co (and Ni) substrate discovered in this work is that the holes in the graphene layer can stimulate metal atoms to pop up from a metal substrate and fill the double vacancy in graphene (DV-G) and stabilize on the graphene surface. The unique structure of the lifted metal atom is expected to be useful for the bifunctional SAC for electrocatalytic oxygen evolution reactions (OERs) and oxygen reduction reactions (ORRs). Our first-principles calculations indicate that the DV-G on the Co(0001) surface can serve as an excellent bifunctional OER/ORR catalyst in alkaline media with extremely low overpotentials of 0.39 V for OER and only 0.36 V for ORR processes, which are even lower than those for previously reported bifunctional catalysts. We believe that the catalytic activity stems from the interface coupling effect between the DV-G and metal substrate, as well as the charge redistribution in the graphitic sheet.

Nicotinamide riboside protects against liver fibrosis induced by CCl4 via regulating the acetylation of Smads signaling pathway.

AIMS: Increasing nicotinamide adenine dinucleotide (NAD+) by Nicotinamide riboside (NR) provides protective benefits in multiple disorders. However, the role of NR on liver fibrosis is unclear. We performed in vivo and in vitro experiments to test the hepatic protective effects of NR against liver fibrosis and the underlying mechanisms. MATERIALS AND METHODS: Mice were injected with CCl4 to establish liver fibrosis model. NR was given by gavage to explore the hepatic protection of NR. LX-2 cells were given a TGF-ß stimulation ±â€¯NR, the activation of LX-2 cells and the acetylation of Smads were analyzed. To further confirm the role of Sirt1 on the protective pathway of NR, we knockdown Sirt1 in LX-2 cells. KEY FINDINGS: We found NR could prevent liver fibrosis and reverse the existing liver fibrosis. NR inhibited the activation of LX-2 cells induced by TGF-ß, activated Sirt1 and deacetylated Smad2/3. Sirt1 knockdown diminished the inhibiting effect of NR on LX-2 cells activation, and increased expressions of acetylated Smads. In conclusion, NR could prevent liver fibrosis via suppressing activation of hepatic stellate cells (HSCs). This protective effect was mediated by regulating the acetylation of Smads signaling pathway. SIGNIFICANCE: NR protected mice against liver fibrosis induced by CCl4. NR suppressed activation of hepatic stellate cells induced by TGF-ß. NR protects liver fibrosis via increasing the activity of Sirt1 and decreasing the expression of P300, resulting in the deacetylation of Smads in stellate cells.

Correction to: A DFT study on the mechanism of the organocatalytic synthesis of a benzoxazine-substituted indolizine derivative.

The original version of this article unfortunately contained a mistake. The presentation of Diagram 2, Fig. 2 and Fig. 3 were incorrect.

Dipole controlled Schottky barrier in the blue-phosphorene-phase of GeSe based van der Waals heterostructures.

Controlling the interface structure is of utmost importance to regulating the nanoscale Schottky barrier height (SBH). Herein, by using first-principles calculations, the electronic properties of the graphene (G) based blue-phosphorene-phase of GeSe van der Waals (vdW) heterostructures, including M/G and X/G interfaces (M = Ge; X = Se), are systematically investigated. When the layer spacing exceeds the vdW gap, n-type Schottky contacts are formed for both MX/G and XM/G heterojunctions. With the layer spacing decreasing to equilibrium distances, due to different charge transfer across the interface, MX/G and XM/G heterojunctions display n- and p-type Schottky contacts, respectively. Further decreasing the layer distance makes both heterojunctions transit into p-type ones. The layer-spacing-dependent SBHs can be rationalized by the increased charge transfer across the interface and the resulting interfacial dipole enhancement. Enlightened by the finding of dipole-controlled SBHs, using MX as building blocks, two different stacking patterns, i.e., nMX-MX-G and nXM-XM-G (n = 1 and 2), are designed to further modulate the SBH. Interestingly, due to the presence of the intrinsic dipole of MX, it is found that the magnitude and orientation of the interfacial dipole can be artificially engineered. With n increasing from 0 to 2, nMX-MX-G with an X/G interface changes from the n-type Schottky contact to Ohmic contact. The Fermi level meets the conduction band and G shows a p-type doping feature finally. Likewise, transition from p-type Schottky contact to Ohmic contact is observed for the nXM-XM-G with M/G interface, accompanied by the Fermi level touching the valence band and the feature of n-type doping for G. The role of nMX stacking seems like the role of applying an external electric field (E-field): applying positive E-field is equivalent to the increase of dipole moment while negative E-field corresponds to the offset of dipole moment. In brief, the SBHs of GeSe/G contact are found to be tunable which originates from the intrinsic dipole of MX. The predictable SBHs for these kinds of charming built-in dipole systems are expected to be highly desirable in electronic devices.

Association of Circulating Adipsin, Visfatin, and Adiponectin with Nonalcoholic Fatty Liver Disease in Adults: A Case-Control Study.

BACKGROUND/AIMS: Some adipokines, such as adiponectin and leptin, have been reported to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), while the association of adipsin and visfatin with NAFLD still remains unclear. This study aimed to examine the association of circulating adipsin, visfatin, and adiponectin with NAFLD in Chinese adults. METHODS: We recruited a total of 211 eligible subjects, including 100 NAFLD cases and 111 age and sex frequency-matched controls. Circulating adipsin, visfatin, and adiponection concentrations were measured by enzymatic immunoassay. Unconditional logistic regression was conducted to assess the associations between quartiles of adipokines and NAFLD. RESULTS: Compared with the controls, NAFLD cases had higher levels of adipsin and lower levels of visfatin and adiponectin. By multivariate logistic analysis, adjusting for potential confounders, circulating adipsin levels were found to be positively associated with NAFLD risk, and circulating levels of visfatin and adiponectin were inversely associated with the risk of NAFLD (all p-trend < 0.05). The ORs were 3.76 (95% CI 1.27-11.08) for adipsin, 0.30 (95% CI 0.10-0.91) for visfatin, and 0.30 (95% CI 0.10-0.88) for adiponectin comparing subjects in the highest quartile with those in the lowest. After stratified by obesity status, the association of higher adipsin with increased risk of NAFLD was only observed in nonobese group. Additionally, the inverse association between adiponectin and NAFLD was found in both groups. CONCLUSIONS: These results indicated that increased circulating levels of adipsin and decreased circulating levels of visfatin and adiponectin were independently associated with the increased risk of NAFLD.

Cyanidin-3-O-ß-glucoside regulates the activation and the secretion of adipokines from brown adipose tissue and alleviates diet induced fatty liver.

AIM: Cyanidin-3-O-ß-glucoside (Cy-3-G) the most abundant monomer of anthocyanins has multiple protective effects on many diseases. To date, whether Cy-3-G could regulate the function of brown adipose tissue (BAT) is still unclear and whether this regulation could influence the secretion of adipokines from BAT to prevent non-alcoholic fatty liver disease (NAFLD) indirectly remains to be explored. In this study we investigated the effect of Cy-3-G on BAT and the potential role of Cy-3-G to prevent fatty liver through regulating the secretion of BAT. METHODS: Male C57BL/6 J mice were fed with a high fat high cholesterol (HFC) diet with or without 200 mg/kg B.W Cy-3-G for 8 weeks. In in vitro experiments, the differentiated brown adipocytes (BAC) and C3H10T1/2 clone8 cells were treated with 0.2 mM palmitate with or without Cy-3-G for 72 or 96 h. Then the culture media of C3H10T1/2 clone8 cells were collected for measuring the adipokines secretion by immunoblot assay and were applied to culture HepG2 cells or LO2 cells for 24 h. Lipid accumulation in HepG2 cells or LO2 cells were evaluated by oil red O staining. RESULTS: Here we found that Cy-3-G regulated the activation of BAT and the expression of adipokines in BAT which were disrupted by HFC diet and alleviated diet induced fatty liver in mice. In in vitro experiments, Cy-3-G inhibited the release of adipokines including extracellular nicotinamide phosphoribosyltransferase (eNAMPT) and fibroblast growth factor 21 (FGF21) from differentiated C3H10T1/2 clone8 cells induced by palmitate, which was accompanied by a reduction of lipid accumulation in HepG2 cells and LO2 cells cultured by the corresponding collected media of C3H10T1/2 clone8 cells. CONCLUSIONS: These results indicate that Cy-3-G can regulate the thermogenic and secretory functions of BAT. Furthermore, our data suggest that the protective effect of Cy-3-G on hepatic lipid accumulation is probably via regulating the secretion of adipokines from BAT.

Blood-based novel biomarkers for nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease has become a social health challenge of global concern. The term nonalcoholic steatohepatitis (NASH) is a more severe condition than simple steatosis and distinguishing NASH from nonalcoholic fatty liver disease is particularly important. Liver biopsy remains a gold standard in diagnosing NASH. Meanwhile, radiological techniques such as ultrasonography and MRI are also applied widely. However, the invasive and expensive examination is not suitable for screening, and there is a great need for reliable and appropriate biomarkers to screen patients for NASH. Based on the current studies of blood-based novel biomarkers, we attempt to summarize the latest findings on biomarkers for NASH, including blood biomarkers encompassing proteins, lipids and miRNAs; the correlation between extracellular vesicles and NASH; and treatment strategies for NASH.

Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway.

BACKGROUND: Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor which is present in foods such as milk and beer. It was reported that NR can prevent obesity, increase longevity, and promote liver regeneration. However, whether NR can prevent ethanol-induced liver injuries is not known. This study aimed to explore the effect of NR on ethanol induced liver injuries and the underlying mechanisms. METHODS: We fed C57BL/6 J mice with Lieber-DeCarli ethanol liquid diet with or without 400 mg/kg·bw NR for 16 days. Liver injuries and SirT1-PGC-1α-mitochondrial function were analyzed. In in vitro experiments, HepG2 cells (CYP2E1 over-expressing cells) were incubated with ethanol ±â€¯0.5 mmol/L NR. Lipid accumulation and mitochondrial function were compared. SirT1 knockdown in HepG2 cells were further applied to confirm the role of SirT1 in the protection of NR on lipid accumulation. RESULTS: We found that ethanol significantly decreased the expression and activity of hepatic SirT1 and induced abnormal expression of enzymes of lipid metabolism in mice. Both in vivo and in vitro experiments showed that NR activated SirT1 through increasing NAD+ levels, decreased oxidative stress, increased deacetylation of PGC-1α and mitochondrial function. In SirT1 knockdown HepG2 cells, NR lost its ability in enhancing mitochondrial function, and its protection against lipid accumulation induced by ethanol. CONCLUSIONS: NR can protect against ethanol induced liver injuries via replenishing NAD+, reducing oxidative stress, and activating SirT1-PGC-1α-mitochondrial biosynthesis. Our data indicate that SirT1 plays an important role in the protection of NR against lipid accumulation and mitochondrial dysfunctions induced by ethanol.