Reversible Dual Fluorescence-Lifetime Imaging of Mitochondrial GSH and Microviscosity: Real-Time Evaluation of Ferroptosis Status.

Ferroptosis, as a new form of regulated cell death, is implicated in various physiological and pathological processes. Developing a single probe for an independent analysis of multiple analytes related to ferroptosis can provide more accurate information and simplify the detection procedures, but it faces great challenges. In this work, we develop a fluorescent probe for the simultaneous detection of GSH through ratiometric fluorescence response and microviscosity via a fluorescence lifetime model. Based on the reversible Michael addition reaction between GSH and unsaturated C═C bond, the probe responds reversibly to GSH with a ratiometric fluorescence variation and a fast response time (t1/2 = 4.7 s). At the same time, the probe is sensitive to environmental viscosity by changing its fluorescence lifetimes. The probe was applied to monitor the drug-induced ferroptosis process through both the classical Xc-/GSH/GPX4- and DHODH-mediated defense mechanisms. We hope that the probe will provide a useful molecular tool for the real-time live-cell imaging of GSH dynamics, which is benefit to unveiling related physiological and pathological processes.

LZP is required for hepatic triacylglycerol transportation through maintaining apolipoprotein B stability.

The conserved zona pellucida (ZP) domain is found in hundreds of extracellular proteins that are expressed in various organs and play a variety of roles as structural components, receptors and tumor suppressors. A liver-specific zona pellucida domain-containing protein (LZP), also named OIT3, has been shown to be mainly expressed in human and mouse hepatocytes; however, the physiological function of LZP in the liver remains unclear. Here, we show that Lzp deletion inhibited very low-density lipoprotein (VLDL) secretion, leading to hepatic TG accumulation and lower serum TG levels in mice. The apolipoprotein B (apoB) levels were significantly decreased in the liver, serum, and VLDL particles of LZP-deficient mice. In the presence of LZP, which is localized to the endoplasmic reticulum (ER) and Golgi apparatus, the ER-associated degradation (ERAD) of apoB was attenuated; in contrast, in the absence of LZP, apoB was ubiquitinated by AMFR, a known E3 ubiquitin ligase specific for apoB, and was subsequently degraded, leading to lower hepatic apoB levels and inhibited VLDL secretion. Interestingly, hepatic LZP levels were elevated in mice challenged with a high-fat diet and humans with simple hepatic steatosis, suggesting that LZP contributes to the physiological regulation of hepatic TG homeostasis. In general, our data establish an essential role for LZP in hepatic TG transportation and VLDL secretion by preventing the AMFR-mediated ubiquitination and degradation of apoB and therefore provide insight into the molecular function of LZP in hepatic lipid metabolism.

Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Discovery of an insulin-induced gene binding compound that ameliorates nonalcoholic steatohepatitis by inhibiting sterol regulatory element-binding protein-mediated lipogenesis.

BACKGROUND AND AIMS: NASH is associated with high levels of cholesterol and triglyceride (TG) in the liver; however, there is still no approved pharmacological therapy. Synthesis of cholesterol and TG is controlled by sterol regulatory element-binding protein (SREBP), which is found to be abnormally activated in NASH patients. We aim to discover small molecules for treating NASH by inhibiting the SREBP pathway. APPROACH AND RESULTS: Here, we identify a potent SREBP inhibitor, 25-hydroxylanosterol (25-HL). 25-HL binds to insulin-induced gene (INSIG) proteins, stimulates the interaction between INSIG and SCAP, and retains them in the endoplasmic reticulum, thereby suppressing SREBP activation and inhibiting lipogenesis. In NASH mouse models, 25-HL lowers levels of cholesterol and TG in serum and the liver, enhances energy expenditure to prevent obesity, and improves insulin sensitivity. 25-HL dramatically ameliorates hepatic steatosis, inflammation, ballooning, and fibrosis through down-regulating the expression of lipogenic genes. Furthermore, 25-HL exhibits both prophylactic and therapeutic efficacies of alleviating NASH and atherosclerosis in amylin liver NASH model diet-treated Ldlr-/- mice, and reduces the formation of cholesterol crystals and associated crown-like structures of Kupffer cells. Notably, 25-HL lowers lipid contents in serum and the liver to a greater extent than lovastatin or obeticholic acid. 25-HL shows a good safety and pharmacokinetics profile. CONCLUSIONS: This study provides the proof of concept that inhibiting SREBP activation by targeting INSIG to lower lipids could be a promising strategy for treating NASH. It suggests the translational potential of 25-HL in human NASH and demonstrates the critical role of SREBP-controlled lipogenesis in the progression of NASH by pharmacological inhibition.

Dual-band achromatic metalens-assisted grating couplers for wavelength demultiplexing.

The design of grating couplers (GCs) that can (de)multiplex and couple arbitrarily defined spatial light into photonic devices is crucial for miniaturized integrated chips. However, traditional GCs have a limited optical bandwidth due to their wavelength's dependency on the coupling angle. In this paper, we propose a device that addresses this limitation by combining a dual-broadband achromatic metalens (ML) with two focusing GCs. By controlling the frequency dispersion, the waveguide-mode-based ML achieves excellent dual-broadband achromatic convergence and separates broadband spatial light into opposing directions at normal incidence. The focused and separated light field matches the grating diffractive mode field and is then coupled into two waveguides by the GCs. This ML-assisted GCs device exhibits a good broadband property with -3 dB bandwidths of 80 nm at 1.31 µm (CE ∼ -6 dB) and 85 nm at 1.51 µm (CE ∼ -5 dB), which almost covers the entire designed working bands, representing an improvement over traditional spatial light-GC coupling. This device can be integrated into optical transceivers and dual-band photodetectors to enhance the bandwidth of wavelength (de)multiplexing.

miRNA-126a-3p participates in hippocampal memory via alzheimer's disease-related proteins.

Memory formation and consolidation necessitate gene expression and new protein synthesis. MicroRNAs (miRNAs), a family of small noncoding RNAs that inhibit target gene mRNA expression, are involved in new memory formation. In this study, elevated miR-126a-3p (miR-126) levels were found to contribute to the consolidation of contextual fear memory. Using different commonly mined algorithms and luciferase reporter assay, we found two Alzheimer's disease (AD)-related proteins, namely EFHD2 and BACE1, but not ADAM9, were the targets downregulated by miR-126 after CFC training. Moreover, we indicated that upregulated miR-126 could promote the formation of contextual fear memory by modulating its target EFHD2. Finally, we demonstrated that miR-126 overexpression in dentate gyrus of hippocampus could reduce Aß plaque area and neuroinflammation, as well as rescue the hippocampal memory deficits in APP/PS1 mice. This study adds to the growing body of evidence for the role of miRNAs in memory formation and demonstrates the implication of EFHD2 protein regulated by miR-126 in the adult brain.

Coexistence of circular dichroism and asymmetric transmission in Babinet-complementary metamaterials.

Chiral metamaterials with circular dichroism (CD) or asymmetric transmission (AT) draw enormous attention for their attractive applications in polarization transformers, circular polarizers, and biosensing. In this study, a feasible trilayer chiral metamaterials (TCM) is designed and investigated in theory and simulation. The proposed TCM is composed of a nanoslit layer and a Babinet-complementary nanorod layer separated by a nanoslit spacer. Owing to symmetry breaking by the tilted nanoslit in metal film, the TCM shows simultaneous CD and AT effects in the near-infrared region. The simulated electric charge distributions prove that the chirality arises from the excitation of asymmetric electric dipole resonant modes due to the coupling of adjacent unit cells. Moreover, CD and AT can be tuned by the tilted angle of the nanoslit and the thickness of the spacer, the fitting functions of which are consistent with the theoretical formulas based on transmittance matrix analysis. The proposed nanostructure offers a potential strategy for manipulating metamaterials with simultaneous CD and AT effects, allowing a multitude of exciting applications such as ultra-sensitive polarization transformer and biosensor.

[Randomized double-blind placebo-controlled trial of Jingfang Granules in treatment of common cold(wind-cold syndrome)].

Jingfang Granules have the effects of inducing sweating to releasing exterior, dispersing wind and dispelling dampness. Modern studies have demonstrated that it has antipyretic and antiviral activities. Therefore, this trial was conducted to evaluate the efficacy and safety of Jingfang Granules in the treatment of common cold(wind-cold syndrome). A total of 138 common cold(wind-cold syndrome) patients meeting the inclusion and exclusion criteria were randomly assigned into the experimental group(n=92) and the placebo group(n=46) at a ratio of 2∶1 and respectively received Jingfang Granules and Jingfang Granules simulation agent. The treatment lasted for 5 d, and the follow-up time was 8 d. Recovery time was employed as the main indicator of efficacy. The median reco-very time of the experimental group was 3.33 d, shorter than that 7.00 d of the placebo group. The efficacy of the experimental group was better than that of the placebo group(P<0.000 1). The major symptom severity score-time AUC of the experimental group was 489.90±206.95, which was smaller than that of the placebo group(763.50±339.53). The recovery rate and marked effective rate of the experimental group were higher than those of the placebo group, The above outcomes were statistically significant between the two groups(P<0.05). The disappearance time and rate of single symptoms including aversion to cold, nasal congestion, runny nose, cough, headache, pharyngeal itching/pain, white sputum, and somatalgia also had significant differences between the two groups(P<0.05), indicating that Jingfang Granules had good performance in alleviating the above symptoms. During the study period, one case of the experimental group had a slight increase in serum creatinine, which returned to the normal level after re-examination. The incidence of adverse reactions was 1.10%, and no serious adverse reaction was found. The two groups had no significant difference in the incidence of adverse reactions. In conclusion, Jingfang Granules can significantly shorten the course of common cold(wind-cold syndrome) and quickly alleviate the clinical symptoms, demonstrating good safety and clinical advantages.

Increasing the circular dichroism of the planar chiral nanostructure by inducing coupling between the coverage layer and the planar nanostructure.

Circular dichroism (CD) has been widely studied in recent decades because of its wide application in biomedical detection. Nanostructures with different heights (NDH) usually increase the transmission CD effect. To achieve such nanostructures, one needs to repeatedly perform the electron-beam lithography (EBL) method twice or more, layer-by-layer, which is a very complicated process. Here, we propose a method to prepare NDH by combining the EBL and oblique angle deposition (OAD) techniques. L-shaped planar silver nanostructures are prepared using EBL and normal electron beam deposition, and the OAD method is then used to partially cover one arm of the L-shaped nanostructure. Numerical simulations reveal that the height difference in the two arms of the L-shaped NDH (LSNDH) causes a difference in the polarization directions of the left- (LCP) and right-circularly polarized (RCP) incident light, thereby, generating CD effects. A 2D material is used to cover the LSNDH to further increase the charge polarization direction differences, which considerably increases the CD effect. These results are useful in simplifying and increasing the convenience of the preparation method of 3D chiral nanostructures. Furthermore, the proposed nanostructure may have potential application in biosensor, such as chiral enantiomer sensors.

Giant circular dichroism of chiral L-shaped nanostructure coupled with achiral nanorod: anomalous behavior of multipolar and dipolar resonant modes.

Chirality, which has long been known as an intrinsic property of living organisms, has caught the interest of researchers due to the rapid emergence of chiral metamaterials. The chiroptical response of noble metal nanostructures in visible and near-infrared regions has been widely investigated. Herein, we propose a bilayer Ag metastructure, in which a chiral L-shaped nanostructure at the bottom is coupled with an achiral nanorod acquiring different positions in the top layer with respect to the long and/or short arm of the chiral L-shaped nanostructure at the bottom layer. The metastructure generates a giant circular dichroism (CD) signal resulting from the strong coupling of the multipolar and dipolar resonant modes on the two layers, in the visible and near-infrared regions. With changing the position of the achiral nanorod, an unusual reversal of the CD spectra is observed, along with a fourfold increase in CD intensity in the short wavelength range due to the multipolar resonant modes. The position of the achiral nanorod is tailored by the azimuthal angle of the substrate during the fabrication of the metastructure using the oblique angle deposition method. This study provides insights into the variation of the coupling strength between a chiral L-shaped nanostructure and an achiral nanorod. The results can be useful in designing chiral-achiral composite nanoantennas for sensing devices.

Aerosol optical properties under different pollution levels in the Pearl River Delta (PRD) region of China.

To clarify the aerosol hygroscopic growth and optical properties of the Pearl River Delta (PRD) region, integrated observations were conducted in Heshan City of Guangdong Province from October 19 to November 17, 2014. The concentrations and chemical compositions of PM2.5, aerosol optical properties and meteorological parameters were measured. The mean value of PM2.5 increased from less than 35 (excellent) to 35-75 µg/m3 (good) and then to greater than 75 µg/m3 (pollution), corresponding to mean PM2.5 values of 24.9, 51.2, and 93.3 µg/m3, respectively. The aerosol scattering hygroscopic growth factor (f(RH = 80%)) values were 2.0, 2.12, and 2.18 for the excellent, good, and pollution levels, respectively. The atmospheric extinction coefficient (σext) and the absorption coefficient of aerosols (σap) increased, and the single scattering albedo (SSA) decreased from the excellent to the pollution levels. For different air mass sources, under excellent and good levels, the land air mass from northern Heshan had lower f(RH) and σsp values. In addition, the mixed aerosol from the sea and coastal cities had lower f(RH) and showed that the local sources of coastal cities have higher scattering characteristics in pollution periods.

Effect of potential HONO sources on peroxyacetyl nitrate (PAN) formation in eastern China in winter.

As an important secondary photochemical pollutant, peroxyacetyl nitrate (PAN) has been studied over decades, yet its simulations usually underestimate the corresponding observations, especially in polluted areas. Recent observations in north China found unusually high concentrations of PAN during wintertime heavy haze events, but the current model still cannot reproduce the observations, and researchers speculated that nitrous acid (HONO) played a key role in PAN formation. For the first time we systematically assessed the impact of potential HONO sources on PAN formation mechanisms in eastern China using the Weather Research and Forecasting/Chemistry (WRF-Chem) model in February of 2017. The results showed that the potential HONO sources significantly improved the PAN simulations, remarkably accelerated the ROx (sum of hydroxyl, hydroperoxyl, and organic peroxy radicals) cycles, and resulted in 80%-150% enhancements of PAN near the ground in the coastal areas of eastern China and 10%-50% enhancements in the areas around 35-40°N within 3 km during a heavy haze period. The direct precursors of PAN were aldehyde and methylglyoxal, and the primary precursors of PAN were alkenes with C > 3, xylenes, propene and toluene. The above results suggest that the potential HONO sources should be considered in regional and global chemical transport models when conducting PAN studies.

Gene therapy by lentivirus-mediated RNA interference targeting extracellular-regulated kinase alleviates neuropathic pain in vivo.

BACKGROUNDS: Neuropathic pain is an abnormal pain, which is related to the activation of extracellular-regulated kinase (ERK) signaling. This study was to investigate the effects of ERK knockdown via lentivirus-mediated RNA interference on allodynia in rats with chronic compression of the dorsal root ganglia (DRG) and to uncover the potential mechanisms. METHODS: The model of chronic compression of the dorsal root ganglia (CCD) was established in rats by surgery. Gene silence was induced by injecting rats with lentivirus expressing ERK short hairpin RNA (shRNA). Behavioral test was performed by calculating paw withdrawal mechanical threshold (PWMT) and thermal paw withdrawal latency (TPWL). RESULTS: We firstly generated lentivirus expressing ERK shRNA to downregulate ERK gene expression both in vitro and in vivo by using Western blot analysis and quantitative reverse transcription polymerase chain reaction. In CCD, ERK mRNA, and protein levels in DRG neurons were dramatically increased, accompanied with decreased PWMT and TPWL. Lentivirus-mediated RNA interference decreased ERK gene expression in DRG neurons and normalized the PWMT and TPWL in CCD rats, but not in rats infected with lentivirus expressing negative control shRNA. Further, calcium responses of DRG neurons to the hypotonic solution and 4α-phorbol 12,13-didecanoate were enhanced in CCD rats, which were suppressed by lentivirus-mediated ERK gene silence. Finally, the levels of transient receptor potential vanilloid 4 gene expressions in DRG neurons and L4 to L5 spinal cord isolated from CCD rats were dramatically upregulated, which were reversed by lentivirus-mediated ERK gene knockdown. CONCLUSION: Lentivirus-mediated RNA interference (RNAi) silencing targeting ERK might reverse CCD-induced neuropathic pain in rats through transient receptor potential vanilloid 4.

Chalcone derivatives bearing chromen or benzo[f]chromen moieties: Design, synthesis, and evaluations of anti-inflammatory, analgesic, selective COX-2 inhibitory activities.

Thirty-eight chalconederivatives bearing a chromen or benzo[f]chromen moiety were synthesized and evaluated for their anti-inflammatory and analgesic activities. Using an ear edema model, anti-inflammatory activities were observed for compounds 3a-3s (ear inflammation: 1.75-3.71 mg) and 4a-4s (ear inflammation: 1.71-4.94 mg). All compounds also displayed analgesic effects with inhibition values of 66.7-100% (3a-3s) and 96.2-100% (4a-4s). The 12 compounds that displayed excellent anti-inflammatory and analgesic effects were tested for their inhibitory activity against ovine COX-1 and COX-2. Six compounds bearing a chromen moiety were weak inhibitors of the COX-1 isozyme but showed moderate COX-2 isozyme inhibitory effects (IC50s from 0.37 µM to 0.83 µM) and COX-2 selectivity indexes (SI: 22.49-9.34). Those bearing a benzo[f]chromen moiety were more selective toward COX-2 than those bearing a chromen moiety with IC50s from 0.25 µM to 0.43 µM and COX-2 selectivity indexes from SI: 31.08 to 20.67.

A Bioinspired, Highly Transparent Surface with Dry-Style Antifogging, Antifrosting, Antifouling, and Moisture Self-Cleaning Properties.

Transparent coatings with antireflection, antifogging, antifrosting, antifouling, and moisture self-cleaning properties can dramatically improve the efficiency and convenience of optical elements and thus are highly desirable for practical applications. Here, it is demonstrated that a bionic nanocone surface (BNS) fabricated by a facile, low-cost process consisting of template-assisted prepolymer curing followed by surface modification can possess the multiple functions listed above. The polymer coating firmly adheres to a glass substrate due to bonding agents. After SiO2 nanoparticle deposition and low-surface-energy fluorosilane modification, the coating shows low microdroplet adhesion. As a result, the as-prepared BNS exhibits a high transmittance when exposed to fog and good clarity even when the temperature decreases to -20 °C in a humid environment. Dipping the BNS into exemplified graphite powder has almost no influence on the transparency, and the BNS can realize self-cleaning of moisture when the surface is covered with a thick layer of man-made contaminants.

Chiral response of a metasurface composed of nanoholes and tilted nanorods.

Circular dichroism (CD) of metasurfaces has been used in biological monitoring, analytical chemistry, and perfect polarization converters. In this work, a metasurface consisting of nanoholes and tilted nanorods is proposed to achieve the CD effect. Numerical calculations show that electrical current forms between the film and the tilted nanorods under circularly polarized light illumination, and CD effects originate from the coupling between the current oscillations at the film and those on the tilted nanorods. This electrical oscillation mode provides unique coupling mechanisms for the CD effect. In addition, CD is strongly dependent on the structural parameters, and the resonant modes can be tuned by modulating the currents on the film. These results are helpful for designing novel chiral optical structures and provide unique methods for circular polarizers.

Enhanced circular dichroism of tilted zigzag-shaped nanohole arrays.

Circular dichroism (CD) of nanostructures is in great demand for applications in biological molecules, photocurrent devices, and photocatalysis. Planar nanostructures can be prepared in a concise manner, and their CD effects have gained much research interest. In this study, tilted zigzag-shaped nanohole (TZSN) arrays are proposed, and the CD effect is studied by the finite element method. A strong resonance occurs in the gap by tuning the charge distributions between adjacent nanoholes. Meanwhile, the CD effect of TZSN arrays is strongly dependent on the structural parameters of TZSN. Results provide a novel method for tuning the CD effects of nanohole arrays on a film.

Insights into the phenomenon of an explosive growth and sharp decline in haze: A case study in Beijing.

A severe haze episode occurred in winter in the North China Plain (NCP), and the phenomenon of an explosive growth and sharp decline in PM2.5 (particulate matter with an aerodynamic diameter equal to or less than 2.5 µm) concentration was observed. To study the systematic causes for this phenomenon, comprehensive observations were conducted in Beijing from November 26 to December 2, 2015; during this period, meteorological parameters, LIDAR data, and the chemical compositions of aerosols were determined. The haze episode was characterized by rapidly varying PM2.5 concentration, and the highest PM2.5 concentration reached 667 µg/m3. During the haze episode, the NCP was dominated by a weak high-pressure system and continuously low PBL (planetary boundary layer) heights, which are unfavorable conditions for the diffusion of pollutants. The large increases in the concentrations of SNA (SO42-, NO3- and NH4+) during the haze implied that the formation of SNA was the largest contribution. Water vapor also played a vital role in the formation of haze by promoting the chemical transformation of secondary pollutants, which led to higher PM2.5 concentrations. The spatial distributions of PM2.5 in Beijing at different times and the backward trajectories of the air masses also indicated that pollutants from surrounding provinces in particular, contributed to the higher PM2.5 concentration.

Characteristics of one-year observation of VOCs, NOx, and O3 at an urban site in Wuhan, China.

A continuous online observation of ozone and its precursors (NOx, VOCs) was carried out in central urban Wuhan from September 2016 to August 2017. The concentration levels of ozone, NOx, VOCs and their variations in urban Wuhan were analyzed, as well as effects of VOCs on ozone photochemical generation and the main controlling factors for ozone production. During the observation period, the average concentrations of ozone and NOx in Wuhan was 22.63 and 30.14 ppbv, respectively, and the average concentration of VOCs was 32.61 ppbv (42.3% alkanes, 13.0% alkenes, 10.0% aromatics, 7.3% acetylene, 9.9% OVOCs, and 10.5% halohydrocarbons). Ozone concentration was higher in spring and summer as compared with autumn and winter, wheras VOCs and NOx concentratios were lower in spring and summer but higher in autumn and winter. Aromatics and alkenes, two of VOCs species, showed the highest contributions to ozone formation potential in Wuhan (35.7% alkenes, 35.4 aromatics, 17.5% alkanes, 8.6% OVOCs, 1.6% halogenated hydrocarbons, and 1.4% acetylene). Among all VOCs species, those with the highest contribution were ethylene, m-xylene, toluene, propylene and o-xylene. The contribution of these five compounds to the total ozone formation potential concentration was 43.90%. Ozone-controlling factors in Wuhan changed within one day; during the early morning hours (6:00-9:00), VOCs/NOx was low, and ozone generation followed a VOCs-limited regime. However, during the peak time of ozone concentration (12:00-16:00), the ratio of VOCs/NOx was relatively high, suggesting that ozone generation followed a NOx-limited regime.

SNMDA: A novel method for predicting microRNA-disease associations based on sparse neighbourhood.

miRNAs are a class of small noncoding RNAs that are associated with a variety of complex biological processes. Increasing studies have shown that miRNAs have close relationships with many human diseases. The prediction of the associations between miRNAs and diseases has thus become a hot topic. Although traditional experimental methods are reliable, they could only identify a limited number of associations as they are time-consuming and expensive. Consequently, great efforts have been made to effectively predict reliable disease-related miRNAs based on computational methods. In this study, we present a novel approach to predict the potential microRNA-disease associations based on sparse neighbourhood. Specifically, our method takes advantage of the sparsity of the miRNA-disease association network and integrates the sparse information into the current similarity matrices for both miRNAs and diseases. To demonstrate the utility of our method, we applied global LOOCV, local LOOCV and five-fold cross-validation to evaluate our method, respectively. The corresponding AUCs are 0.936, 0.882 and 0.934. Three types of case studies on five common diseases further confirm the performance of our method in predicting unknown miRNA-disease associations. Overall, results show that SNMDA can predict the potential associations between miRNAs and diseases effectively.