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The research focused on addressing various challenges in intelligent top caving theory, intelligent perception and recognition key technology, intelligent caving comprehensive decision-making technology, and remote caving intelligent control technology of fully mechanized top coal caving face. This is being done under the “13th Five-Year” national key research and development plan, specifically designed for the key technology and demonstration of intelligent fully mechanized top coal caving mining method with annual production of 10 million of tons in extra-thick coal seam. The research has resulted in the following outcomes: ① Comprehensive experiments were conducted to understand the interaction process of crushing and migrating of roof and top coal combination (RTCC) and the fragmentation distribution of RTCC under different roof conditions. A three-dimensional laser goaf space detection technology has been developed, and the arching phenomenon of top coal blocks on contact, at coal discharge process with multiple coal discharge ports, has been validated. In addition, the numerical simulation of multi-port intelligent coal caving in extra-thick coal seam is carried out with the constraints of mining and caving coordination, high recovery rate, and low gangue ratio, and the number of coal caving ports is determined. those provide a reliable theoretical basis for optimizing intelligent coal-caving processes. ②The research has explored the geological information and physical characteristics of coal and gangue in the working face, along with full-cycle sensing elements of the top coal caving process. This has led to the development of a comprehensive sensing technology system, including real time detection of top coal thickness, accurate identification of coal and gangue, and dynamic measurement of coal flow, providing crucial data information support for decision making of intelligent coal top caving technology. ③A multi-source information database has been established for the man-machine-environment interface, and a decision-making model has been developed for fully mechanized top caving in extra-thick coal seams. An intelligent coal top caving decision-making software based on the Q-learning algorithm has been created, utilizing artificial intelligence for coal and gangue identification, top coal thickness detection, and coal quantity monitoring. ④A high-precision inertial navigation monitoring and control technology for intelligent fully mechanized caving faces has been developed, enabling real-time positioning, attitude monitoring, and action control for the shearer, hydraulic support, and scraper conveyor. An intelligent mine-integrated communication scheduling system and a remote-integrated control platform for fully mechanized caving have also been established. Those allow for the successful implementation of intelligent coal caving in remote one-button start mode. ⑤Advanced technologies such as ground-penetrating radar for top coal thickness detection, vibration-audio-hyperspectral for coal-gangue identification, and laser three-dimensional scanning for real-time coal caving monitoring are utilized in the 8222 Working Face of Tashan Mine. Intelligent coal caving decision software is applied in fully mechanized caving operations, leading to a control of errors within 10.71% for top coal thickness detection, 9.32% for mixed gangue rate, and 7.8% for coal caving amount. On average, each coal caving cycle now saves about 30 minutes, leading to intelligent and efficient coal caving operations with an annual output of 15 million tons.

Fully mechanized top coal caving technology has become the mainstream way of high yield and high efficiency mining in extra thick coal seams in China. The accurate control of the top-coal drawing mechanical parts is of significance to realize the automation and intellectualization of top-coal caving mining. Mastering the spatial motion law of the coal caving mechanism is the premise of accurate control. The immediate shape of the hydraulic support coal caving mechanism is jointly controlled by the support height, support attitude, extension length of the plug plate, and the relative position of the rear scraper, which has an important impact on the coal caving opening and the coal-passing height of the support. This study establishes a 3–D numerical model of four- legs top-coal caving hydraulic support (No. ZF15000/27.5/42) by using the finite element software ABAQUS. Hinge and translator connectors are used to simulate the rotation behavior and expansion-contraction behavior for hinge point and plug plate, respectively. Taking the support height (H), tail beam swing angle (α), and the plug plate extension length (l) as control variables, the spatial motion law of the hinge point between shield beam and tail beam and the end of the plug plate are modeled. The critical security equation for evaluating collision between top-coal drawing mechanical parts and rear scraper is obtained by using Levenberg-Marquardt fitting iteration method. A database for describe the calibration relationship, which contains the end coordination of plug plate, the dimension of the top-coal drawing opening, and H, α, and l, is established. The sensor type and installation position for sensing and controlling the attitude of the top-coal drawing mechanism are recommended, the approach for calculating the tail beam angle based on travel sensor is derived. Through field verification of top-coal drawing opening width, it is concluded that the relative error between measured value and calculated value meets the requirements for accurate control of top-coal drawing mechanism. The approach for controlling the top-coal drawing opening dimension is proposed, which has been successfully applied in the field.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic interstitial lung disease. Intricate pathogenesis of pulmonary fibrosis and only two approved medications with side effects and high cost bring us the challenge of fully understanding this lethal disease and urgency to find more safe and low-cost therapeutic alternatives. Purpose: Demethyleneberberine (DMB) has been demonstrated to have various anti-inflammatory, antioxidant, antifibrosis and anti-cancer bioactivities. The objective of this study was to evaluate the effect of DMB on pulmonary fibrosis and investigate the mechanism. Methods: Bleomycin (BLM)-induced pulmonary fibrosis was established in mice to evaluate the antifibrotic effect of DMB in vivo. A549 and MRC5 cells were used to evaluate the effect of DMB on epithelial–mesenchymal transition (EMT) and fibroblast–myofibroblast transition (FMT) in vitro. High throughput sequencing, biotin–avidin system and site-directed mutagenesis were applied to explore the mechanism of DMB in alleviating pulmonary fibrosis. Results: DMB alleviated BLM-induced pulmonary fibrosis in vivo by improving the survival state of mice, significantly reducing pulmonary collagen deposition and oxidative stress and improving lung tissue morphology. Meanwhile, DMB was demonstrated to inhibit epithelial–mesenchymal transition (EMT) and fibroblast–myofibroblast transition (FMT) in vitro. High throughput sequencing analysis indicated that GREM1, a highly upregulated profibrotic mediator in IPF and BLM-induced pulmonary fibrosis, was significantly downregulated by DMB. Furthermore, USP11 was revealed to be involved in the deubiquitination of GREM1 in this study and DMB promoted the ubiquitination and degradation of GREM1 by inhibiting USP11. Remarkably, DMB was demonstrated to selectively bind to the Met776 residue of USP11, leading to disruption of USP11 deubiquitinating GREM1. In addition, DMB presented an equivalent antifibrotic effect at a lower dose compared with pirfenidone and showed no obvious toxicity or side effects. Conclusions: This study revealed that USP11/GREM1 could be a potential target for IPF management and identified that DMB could promote GREM1 degradation by inhibiting USP11, thereby alleviating pulmonary fibrosis.

The control method of deformation of large sections of soft rock formations in coal mines is a major problem in mining practice. Taking Wangzhuang Coal Mine in Shanxi Province, China, for example, the support method of large sections of soft rock formations was studied to control the deformation of the top and bottom plates and two gangs, and to obtain the damage of the surrounding rocks at different depths through drilling imaging. In addition, the displacement, plastic area and stress field distribution patterns of surrounding rocks are obtained by simulating in FLAC3D. Coupling support for broken, plastic and elastic zones is achieved using bolts, grout anchors, and long anchor cables. The bottom of the road is effectively controlled by floor grout and concrete reverse arches. The results show that under the combination of anchorage and grout, the fault depth and degree of the surrounding rocks are less than the original support method, which can effectively reduce the subsidon of the roof and the deformation of the two gangs. It is important to note that anchorage cable set support can effectively reduce shear fault areas in floor and two gang plastic areas, and reduce the weight of the pavement floor. This study provides a technical reference for the support of large sections of soft rock roadways in coal mines.

Objective This systematic review aimed to explore the potential association between dietary cholesterol intake and esophageal cancer risk. Methods A literature search was conducted using PubMed, Embase, and Web of Science databases from inception to March 2019 according to specific inclusion and exclusion criteria. Pooled estimates with odds ratio (ORs) and 95% confidence intervals (CIs) were obtained using random effects models. Results Nine articles of 12 independent studies were included in the final meta-analysis. Pooled analysis suggested that dietary cholesterol intake may increase the risk of esophageal cancer (summarized OR = 1.424, 95% CI = 1.191–1.704). Consistent results were found in American (summarized OR = 1.410, 95% CI = 1.130–1.758) and European populations (summarized OR = 1.556, 95% CI = 1.021–2.373). Subgroup analysis by disease type showed that dietary cholesterol intake had a significant association with the development of esophageal adenocarcinoma and esophageal squamous cell carcinoma. Conclusion Our findings indicated that dietary cholesterol intake could significantly increase the risk of developing esophageal cancer in both European and American populations. Further high-quality studies are necessary to confirm the effects of cholesterol intake.

When using the explicit dynamic relaxation approach (DRA) to model the quasi-static rock breakage, fragmentation, and flow problems, especially the top-coal caving question, introducing numerical damping into the solution equation is inevitable for reducing the vibration frequency and impact speed of mesh nodes, which is significantly affect the fidelity of the computation results. Although the DRA has been widely adopted to simulate top-coal caving, the reasonable value and calibration method of numerical damping are still open issues. In this study, the calibration process of reasonable numerical damping for modeling top-coal caving is investigated by comparing with the experimental results, in which several geometry parameters of the drawing funnel are selected as the calibration indexes. The result shows that the most reasonable numerical damping value is 0.07 for the numerical modeling of interval top-coal caving in extra-thick coal seams. Finally, the correlation between the numerical damping and the physical top-coal drawing process is discussed. The numerical damping indirectly reflects the fragmentation in multi scale of coal mass and friction interaction between coal particles during the caving process, which reduces the vibration intensity of the top-coal caving system and dissipates the kinetic energy.

In top-coal caving, the window control of hydraulic support is a key issue to the perfect economic benefit. The window is driven by the electro-hydraulic control system whose command is produced by the control model and the corresponding algorithm. However, the model of the window’s control is hard to establish, and the optimal policy of window action is impossible to calculate. This paper studies the issue theoretically and, based on the 3D simulation platform, proposes a deep reinforcement learning method to regulate the window action for top-coal caving. Then, the window control of top-coal caving is considered as the Markov decision process, for which the deep Q-network method of reinforcement learning is employed to regulate the window’s action effectively. In the deep Q-network, the reward of each step is set as the control criterion of the window action, and a four-layer fully connected neural network is used to approximate the optimal Q-value to get the optimal action of the window. The 3D simulation experiments validated the effectiveness of the proposed method that the reward of top-coal caving could increase to get a better economic benefit.

Rock bursts occur frequently in coal mines, and the mechanical properties of saturated coal specimens under coupled static-dynamic loading need to be studied in detail. Comparative tests of coal specimens having different water content under static and static-dynamic loading are conducted using the split Hopkinson pressure bar (SHPB) and RMT-150C test systems. The results demonstrate that the natural specimen strength is greater than that of seven-day (7D) saturated specimens under both uniaxial compression and triaxial static compression loading; however, the dynamic strength of 7D saturated specimens is lower than that of natural specimens under one-dimensional static-dynamic loading. The particle size of the 7D saturated specimens is relatively small under uniaxial static compression and one-dimensional static-dynamic loading, and the specimen particle sizes before and after static triaxial loading tests and three-dimensional static-dynamic loading tests do not exhibit an obvious difference.

Coal seam water injection (CSWI) is an effective technology that is widely used for preventing rock burst in coal mines. To deepen the understanding of the mechanism of CSWI to prevent rock burst, new equipment was designed to prepare forcedly saturated coal samples in this study and a series of mechanical experiments was conducted to investigate the mechanical properties, acoustic emission (AE), and energy dissipation characteristics of the coal samples in natural, naturally saturated, and forcedly saturated states. The experimental results show that the forced saturation treatment can significantly improve P-wave velocity and water content of coal samples, as water can penetrate more into micropores and fractures. The forced saturation method also significantly promotes the deformation capacity of the coal sample and reduces the strength by 83.37%. The main reason of the bearing capacity decrease for the forcedly saturated coal samples is plastic yielding rather than brittle crack propagation and slip. The derivative of the volumetric dissipation energy was proposed to evaluate the outburst proneness. The forced saturation method significantly reduces the risk of sudden release of energy and is more effective in preventing rock burst in coal seams than the natural saturation method.

When inducing cracks, soundless cracking agents (SCAs) do not generate vibration, harmful gas, dust, nor flying rock fragment, making them suitable for hard rock roof breaking, rock burst prevention, oil or gas reservoir stimulation, and building demolition. In this study, SCA-induced crack initiation and propagation in different stress conditions were modelled using a modified cohesive element method. A new traction-separation law for describing rock compressive shear strength was proposed. The crack length and direction in bidirectional isobaric and unequal stress fields were analyzed in detail. The crack initiation pressure and the incremental ratio of crack length to SCA expansion pressure were proposed as two indicators to evaluate the difficulty in rock breaking in deep underground. Results indicate that (1) the modified cohesive element method used in this study is feasible to model crack propagation in deep rocks; (2) the maximum expansion pressure of SCAs depends on rock elastic modulus and geostress field and should be measured under a condition similar to deep underground prior to SCA borehole spacing design; when using the SCAs with a maximum expansion pressure of 100 MPa in 600 m underground, the suggested borehole spacing is less than 220 mm; and (3) σ3 dominates the crack initiation pressure while the principal stress ratio σ3/σ1 and notch direction control the direction of crack propagation.

A particle element approach based on continuum-discontinuum element method (CDEM) is applied to optimize the automated top-coal drawing techniques in extra-thick coal seams. Numerical models with 100 drawing openings are created according to the field engineering geological conditions of Tongxin coal mine in China. An automated coal drawing control approach in numerical modelling based on time criterion is proposed. The rock mixed rate, top-coal recovery rate and the variance of the drawn top coal amount are counted and set as the statistical indicators to evaluate the top-coal drawing techniques. The traditional top-coal drawing criterion, “rocks appear, close the opening”, leads to low recovery of top coal and waste of coal resources in extra-thick coal seams, significantly weakening the transport stability and efficiency of the scraper conveyer. A three-round unequal time top-coal drawing technique is proposed for automated top-coal drawing. Three drawing openings, corresponding to the three top-coal drawing rounds respectively, are working at the same time; in each round, the top-coal drawing sequence is from the first drawing opening at one end of the working face to last drawing opening at another end; the drawing time of each round is not equal and increases with the round number. The numerical inversion approach of iteration steps can be used for real top-coal drawing time estimation and automated drawing process design to achieve a better top coal drawing effect, while the exact time for each drawing round still needs to be corrected by engineering practice.

The massive emission of low concentrations (≤0.5%) of methane (CH4) from ventilation roadways results in resource waste and environmental pollution. To mitigate these emissions, an enrichment tower for low-concentration methane is designed, and segregation and non-segregation experiments are conducted. The results reveal that stable concentrations of methane under segregation and non-segregation states in the enrichment tower gradually increase with height, with a maximum methane concentration of 0.64% and 0.54%, respectively. This shows that the methane enrichment effect in free diffusion conditions is more significant under the segregation state than under the non-segregation state. The stable concentration of methane in the middle and upper sections of the enrichment tower shows an increasing trend. However, the stable concentration of methane in the lower section of the enrichment tower has an increasing trend (less than 0.50%). According to the methane molecule Boltzmann distribution law, methane concentration enrichment decreases with height, and the conversion of the methane from the segregated to non-segregated is irreversible. Consequently, industrial applications of methane enrichment from buoyant forces are not feasible for low concentrations of methane.

In order to study the mechanism of the dual side roof cutting technology on the composite disaster of gas and coal spontaneous combustion in goaf, a model for the evolution of porosity and permeability in the dual side roof cutting working face was constructed. The location of the occurrence of the compound disaster of gas explosion and coal spontaneous combustion under the double-sided roof cutting mode was studied, and the sensitivity of the evolution pattern of the compound disaster area to the amount of air supply and gas gush was summarized. The results indicate that the top cutting pressure relief technology significantly reduces the permeability of porous media, and the sensitivity of the goaf on the intake side to airflow disturbances is significantly reduced. As the volume of air supply increases, the distance between the gas explosion risk area and the coal spontaneous combustion risk area gradually decreases, and the probability of composite disaster areas is 0. The increase of air supply and gas emission makes the gas concentration in the middle and deep goaf increase in an exponential function, and the width of the gas explosion risk area increases gradually. When the outflow reaches 40 m3 /min, there is no composite disaster zone, indicating that the rapid increase in outflow inhibits the occurrence of composite disasters. [ABSTRACT FROM AUTHOR]

Lighting conditions are an important factor affecting dry-cured products. This study investigated the effects of treatments with different light intensities (0 lx, 1000 lx, 25000 lx) and different light sources including red light, blue light, UV-light on oxidation leve and flavor change in dry-cured Wuchang fish. The results showed that dry-cured Wuchang fish exhibited an attractive brown-yellow color, the highest oxidation degree of myoglobin (Mb), the highest fat oxidation under the light conditions of 25000 lx light intensity and UV-light irradiation. This phenomenon was observed that the degree of Mb oxidation was increased, while the degree of fat oxidation was increased. At 25000 lx light intensity and UV-light irradiation, dry-cured Wuchang fish showed an ignificantly decreased fatty acid conten (especially oleic acid and linoleic acid), significantly increased characteristic volatile compound contents (22 for 25,000 lx light intensity and 27 for UV-light irradiation), which contributed to the improvement of quality stability of dry-cured Wuchang fish. Our findings provide theoretical support for the industrial application of exogenous light in dry-cured Wuchang fish.

Abstract Background Systemic sclerosis (SSc; also known as “scleroderma”) is an autoimmune disorder characterized by extensive fibrosis, vascular changes, and immunologic dysregulation. Baicalein (phenolic flavonoid derived from Scutellaria baicalensis Georgi) has been used to treat the pathological processes of various fibrotic and inflammatory diseases. In this study, we investigated the effect of baicalein on the major pathologic characteristics of SSc: fibrosis, B-cell abnormalities, and inflammation. Methods The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. SSc mice were produced by injecting bleomycin and treated with baicalein (25, 50, or 100 mg/kg). The antifibrotic features of baicalein and its mechanisms were investigated by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry. Results Baicalein (5–120 μM) significantly inhibited the accumulation of the extracellular matrix and fibroblast activation in transforming growth factor (TGF)-β1- and platelet derived growth factor (PDGF)-induced human dermal fibroblasts, as evidenced by abrogated deposition of total collagen, decreased secretion of soluble collagen, reduced collagen contraction capability and downregulation of various fibrogenesis molecules. In a bleomycin-induced model of dermal fibrosis in mice, baicalein (25–100 mg/kg) restored dermal architecture, ameliorated inflammatory infiltrates, and attenuated dermal thickness and collagen accumulation in a dose-dependent manner. According to flow cytometry, baicalein reduced the proportion of B cells (B220+ lymphocytes) and increased the proportion of memory B cells (B220+CD27+ lymphocytes) in the spleens of bleomycin-induced mice. Baicalein treatment potently attenuated serum levels of cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta) and autoantibodies (anti-scleroderma 70 (Scl-70), anti-polymyositis-scleroderma (PM-Scl), anti-centromeres, anti-double stranded DNA (dsDNA). In addition, baicalein treatment can significantly inhibit the activation of TGF-β1 signaling in dermal fibroblasts and bleomycin-induce mice of SSc, evidenced by reducing the expression of TGF-β1 and IL-11, as well as inhibiting both small mother against decapentaplegic homolog 3 (SMAD3) and extracellular signal-related kinase (ERK) activation. Conclusions These findings suggest that baicalein has therapeutic potential against SSc, exerting modulating B-cell abnormalities, anti-inflammatory effects, and antifibrosis.

This study investigated the effects of ultrasound treatment on the quality of salted Culter alburnus fish. The results showed that with the increasing ultrasound power, the structural degradation of muscle fibers was intensified, and the conformation of myofibrillar protein was significantly changed. The high-power ultrasound treatment group (300 W) had relatively higher thiobarbiturate reactive substance content (0.37 mg malondialdehyde eq/kg) and peroxidation value (0.63 mmol/kg). A total of 66 volatile compounds were identified with obvious differences among groups. The 200 W ultrasound group exhibited fewer fishy substances (Hexanal, 1-Pentene-3-ol, and 1-Octane-3-ol). Compared with control group, ultrasound groups (200, 300 W) contained more umami taste-related amino peptides such as γ-Glu-Met, γ-Glu-Ala, and Asn-pro. In the ultrasound treatment group, L-isoleucine and L-methionine, which may be used as flavor precursors, were significantly down-regulated, while carbohydrates and its metabolites were up-regulated. Amino acid, carbohydrate, and FA (fatty acyls) metabolism products in salted fish were enriched by ultrasound treatment, and those products might ultimately be related to the taste and flavor of salted fish.

Background:A. chinense frequently used in Miao medicine to treat rheumatic diseases. However, as a famous toxic herb, Alangium chinense and its representative components exhibit ineluctable neurotoxicity, thus creating significant challenges for clinical application. The combined application with compatible herbs in Jin-Gu-Lian formula attenuates such neurotoxicity according to the compatible principle of traditional Chinese medicines.Purpose: We aimed to investigate the detoxification of the compatible herbs in Jin-Gu-Lian formula on A. chinense-induced neurotoxicity and investigate its mechanism.Methods: Neurobehavioral and pathohistological analysis were used to determine the neurotoxicity in rats administered with A. chinense extract (AC), extract of compatible herbs in Jin-Gu-Lian formula (CH) and combination of AC with CH for 14 days. The mechanism underlying the reduction of toxicity by combination with CH was assessed by enzyme-linked immunosorbent assays, spectrophotometric assays, liquid chromatography tandem-mass spectrometry and real-time reverse transcription-quantitative polymerase chain reaction.Results: Compatible herbs attenuated the AC-induced neurotoxicity as evidenced by increased locomotor activity, enhanced grip strength, the decreased frequency of AC-induced morphological damage in neurons, as well as a reduction of neuron-specific enolase (NSE) and neurofilament light chain (NEFL) levels. The combination of AC and CH ameliorated AC-induced oxidative damage by modulating the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). AC treatment significantly reduced the levels of monoamine and acetylcholine neurotransmitters in the brains of rats, including acetylcholine (Ach), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine (NE), and serotonin (5-HT). Combined AC and CH treatment regulated the abnormal concentrations and metabolisms of neurotransmitters. Pharmacokinetic studies showed that the co-administration of AC and CH significantly decreased plasma exposure levels of two main components of AC, as evidenced by the reduction of maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC) compared to AC. In addition, the AC-induced downregulation in mRNA expression of cytochrome P450 enzymes was significantly reduced in response to combined AC and CH treatment.Conclusion: Compatible herbs in Jin-Gu-Lian formula alleviated the neurotoxicity induced by A. chinense by ameliorating oxidative damage, preventing abnormality of neurotransmitters and modulating pharmacokinetics.

The exfoliation of bulk two-dimensional metal–organic framework (MOF) into few-layered nanosheets has attracted much attention recently. In this work, an environmental-friendly route has been developed for layered-MOF (MAMS-1) delamination using deep eutectic solvent (DES), which is more sustainable and efficient alternative than conventional organic solvents for MOF nanosheet preparation. Under sonication condition, DES as solvents, the highest exfoliation rate of MAMS-1 is up to 70% with two host layers via poly(vinylpyrrolidone) (PVP) surfactant-assisted method. The presence of tert-butyl exteriors and the atomically thickness endow the MOF nanosheets stable suspension for at least one month. Due to the 2D structure and excellent stability, MAMS-1 nanosheet (MAMS-1-NS) was chosen as a good candidate to encapsulate Eu3+ cations. The obtained Eu3+@MAMS-1-NS acts as a multi-responsive luminescent sensor through fluorescence quenching, and can specifically recognize Fe3+ (LOD = 0.40 μM, KSV = 1.05 × 105 M−l), Hg2+ (LOD = 0.038 μM, KSV = 5.78 × 106 M−l), Cr2O72− (LOD = 0.33 μM, KSV = 1.55 × 105 M−l) and MnO4− (LOD = 0.088 μM, KSV = 4.49 × 105 M−l). Compared with bulk Eu3+@MAMS-1, the sensitivity of Eu3+@MAMS-1-NS is greatly improved owing to its ultrathin nanosheet morphology and highly accessible active sites on the surface.

BACKGROUND: Interferon-γ (IFN-γ) plays an important role in the proceedings of vitiligo through recruiting lymphocytes to the lesional skin. However, the potential effects of IFN-γ on skin melanocytes and the subsequent contribution to the vitiligo pathogenesis are still unclear. OBJECTIVE: To investigate the effects of IFN-γ on viability and cellular functions of melanocytes. METHODS: Primary human melanocytes were treated with IFN-γ. Cell viability, apoptosis, cell cycle melanin content and intracellular reactive oxygen species (ROS) level were measured. mRNA expression was examined by real-time PCR. The release of interleukin 6 (IL-6) and heat shock protein 70 (HSP-70) was monitored by ELISA. β-galactosidase staining was utilized to evaluate melanocyte senescence. RESULTS: Persistent IFN-γ treatment induced viability loss, apoptosis, cell cycle arrest and senescence in melanocytes. Melanocyte senescence was characterized as the changes in pigmentation and morphology, as well as the increase of β-galactosidase activity. Increase of p21Cip1/Waf1 protein was evident in melanocytes after IFN-γ treatment. IFN-γ induction of senescence was attenuated by siRNAs against p21, Janus kinase 2 (JAK2) or signal transducer and activator of transcription 1 (STAT1), but not by JAK1 siRNA nor by p53 inhibitor pifithrin-α. IFN-γ treatment increased the accumulation of intracellular ROS in melanocytes, while ROS scavenger N-acetyl cysteine (NAC) effectively inhibited IFN-γ induced p21 expression and melanocyte senescence. IL-6 and HSP-70 release was significantly induced by IFN-γ treatment, which was largely inhibited by NAC. The increase of IL-6 and HSP-70 release could also be observed in senescent melanocytes. CONCLUSION: IFN-γ can induce senescence in melanocytes and consequently enhance their immuno-competency, leading to a vitiligo-prone milieu.