Dysfunctions of gene transcription and translation inthe nociceptive pathways play the critical role in development and maintenance of chronic pain. Circular RNAs (circRNAs) are emerging as new players in regulation of gene expression, but whether and how circRNAs are involved in chronic pain remain elusive. We showed here that complete Freund's adjuvant-induced chronic inflammation pain significantly increased circRNA-Filip1l (filamin A interacting protein 1-like) expression in spinal neurons of mice. Blockage of this increase attenuated complete Freund's adjuvant-induced nociceptive behaviors, and overexpression of spinal circRNA-Filip1l in naive mice mimicked the nociceptive behaviors as evidenced by decreased thermal and mechanical nociceptive threshold. Furthermore, we found that mature circRNA-Filip1l expression was negatively regulated by miRNA-1224 via binding and splicing of precursor of circRNA-Filip1l (pre-circRNA-Filip1l) in the Argonaute-2 (Ago2)-dependent manner. Increase of spinal circRNA-Filip1l expression resulted from the decrease of miRNA-1224 expression under chronic inflammation pain state. miRNA-1224 knockdown or Ago2 overexpression induced nociceptive behaviors in naive mice, which was prevented by the knockdown of spinal circRNA-Filip1l. Finally, we demonstrated that a ubiquitin protein ligase E3 component n-recognin 5 (Ubr5), validated as a target of circRNA-Filip1l, plays a pivotal role in regulation of nociception by spinal circRNA-Filip1l. These data suggest that miRNA-1224-mediated and Ago2-dependent modulation of spinal circRNA-Filip1l expression regulates nociception via targeting Ubr5, revealing a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain. Significance StatementcircRNAs are emerging as new players in regulation of gene expression. Here, we found that the increase of circRNA-Filip1l mediated by miRNA-1224 in an Ago2-dependent way in the spinal cord is involved in regulation of nociception via targeting Ubr5. Our study reveals a novel epigenetic mechanism of interaction between miRNA and circRNA in chronic inflammation pain.

Relative mRNA level ** 0d 2h 1d 3d 7d Time after CFA injection Mettl14 0.0 0.5

BackgroundFacial skin is exposed to the environment, which marks it with obvious signs of aging. Based on multi-dimensional non-invasive evaluation data, female facial skin can be characterized in detail. However, there are few studies on the general aging rules of facial skin. Most skin aging studies divide the ages into 5–10-year intervals, so they have lacked dynamic matching with facial skin aging.AimTo explore facial skin aging rules, discuss the main parameters of facial skin aging, propose an unequal-distance aging division method based on the main skin parameters, and study the skin characteristics of Chinese women of different aging stages.MethodsWe comprehensively described the skin status as 24 non-invasive skin parameters belonging to five dimensions: skin wrinkles, texture, stain, color and barrier function. We performed polynomial fitting on the 21 skin parameters that were significantly correlated with age and derived the rules of aging in the different dimensions. Based on the wrinkle dimension, the facial skin aging process was divided into four stages, and the skin characteristics of the different stages were compared.ResultsSkin wrinkles increased, texture deteriorated, acne decreased, pigment spots increased, skin tone darkened, and sebum secretion decreased with age, according to the polynomial fitting. The aging stage was divided into an incubation period (18–30 years old), an aging occurrence period (31–42 years old), a rapid aging period (43–47 years old), and a stable aging period (48–60 years old), according to the wrinkles. Different aging stages had different skin characteristics.ConclusionThe incubation period is the critical period for the appearance of skin stains; the skin texture gradually deteriorates during the aging occurrence period; the rapid aging period is a critical period for the aging of skin parameters; skin status during the stable aging period is the worst.

Geographical, environmental and pollution conditions affect facial skin health, but their effects on skin appearance have not been elucidated. This study aimed to describe the skin barrier and skin tone characteristics of Chinese subjects according to lifestyle and environmental conditions using in vitro measurements. In total, 1092 women aged 22–42 years were recruited from 7 representative Chinese cities. Eight skin parameters (hydration, sebum, pH, transdermal water loss, individual type angle, melanin index, erythema index, yellowness) were measured using noninvasive instruments; individual lifestyle data were also collected. Data on four meteorological factors (air temperature, relative humidity, sunshine duration, wind speed) and seven air pollution indicators (air quality index, fine particulate matter, breathable particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone) were collected in each city from the China Meteorological Administration. Facial skin characteristics differed significantly between cities. Facial skin barrier characteristics and skin tones showed regional differences, with a better skin barrier associated with the western region, as indicated by high skin hydration and sebum secretion and a low pH value. According to the value of transdermal water loss, lighter and darker skin tones were found in the western and southern regions, respectively. Environmental conditions affected facial skin status. Air pollution induced facial skin issues, with fine particulate matter and nitrogen dioxide contributing the most. Individual lifestyles affected the facial skin barrier and skin tone.

Background The ITA° is the gold standard for skin tone classification. Different skin tones are often associated with different skin characteristics and issues. Different skin types are often associated with different skin characteristics and issues in China. Aims To study the population's skin color distribution and accompanying skin problems according to the ITA° classification standard. Methods A total of 1092 women aged 22–42 years were recruited in 7 cities in China. All biophysical parameter measurements (SM, CM, TWEL, pH, R2, GLOSS_DSCT, MEXA, ERYTH, ITA°; 9 indexes total) were quantified with noninvasive instruments. All volunteers provided consent before enrollment. Result The main skin color categories were light (II), very light (I), intermediate (III), and tan (IV). The results demonstrated that the characteristics of the facial skin based on the ITA° were significantly different among cities and age groups and were associated with different skin issues. Conclusions Lighter skin was associated with worse skin elasticity; intermediate skin was associated with worse skin hydration content and was most prone to being oily; and darker skin was associated with poor barrier function. Established principal component regression (PCR) indicated that pH, gloss GLOSS_DSC, MEXA, ERYTH, TEWL, and SM had significant effects on the ITA°.