Inhibition of NLRP3 Inflammasome Activation and Pyroptosis in Macrophages by Taraxasterol Is Associated With Its Regulation on mTOR Signaling.

Taraxasterol (TAS) is an active ingredient of Dandelion (Taraxacum mongolicum Hand. -Mazz.), a medicinal plant that has long been used in China for treatment of inflammatory disorders. But the underlying mechanism for its therapeutic effects on inflammatory disorders is not completely clear. Inflammasome activation is a critical step of innate immune response to infection and aseptic inflammation. Among the various types of inflammasome sensors that has been reported, NLR family pyrin domain containing 3 (NLRP3) is implicated in various inflammatory diseases and therefore has been most extensively studied. In this study, we aimed to explore whether TAS could influence NLPR3 inflammasome activation in macrophages. The results showed that TAS dose-dependently suppressed the activation of caspase-1 in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin treatment, resulting in reduced mature interleukin-1ß (IL-1ß) release and gasdermin D (GSDMD) cleavage. TAS greatly reduced ASC speck formation upon the stimulation of nigericin or extracellular ATP. Consistent with reduced cleavage of GSDMD, nigericin-induced pyroptosis was alleviated by TAS. Interestingly, TAS time-dependently suppressed the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 signaling induced by LPS priming. Like TAS, both INK-128 (inhibiting both mTORC1 and mTORC2) and rapamycin (inhibiting mTORC1 only) also inhibited NLRP3 inflammasome activation, though their effects on mTOR signaling were different. Moreover, TAS treatment alleviated mitochondrial damage by nigericin and improved mouse survival from bacterial infection, accompanied by reduced IL-1ß levels in vivo. Collectively, by inhibiting the NLRP3 inflammasome activation, TAS displayed anti-inflammatory effects likely through regulation of the mTOR signaling in macrophages, highlighting a potential action mechanism for the anti-inflammatory activity of Dandelion in treating inflammation-related disorders, which warrants further clinical investigation.

Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China.

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

Evidence from central Mexico supporting the Younger Dryas extraterrestrial impact hypothesis.

We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon-rich, lacustrine layer, containing nanodiamonds, microspherules, and other unusual materials that date to the early Younger Dryas and are interpreted to result from an extraterrestrial impact. These proxies were found in a 27-m-long core as part of an interdisciplinary effort to extract a paleoclimate record back through the previous interglacial. Our attention focused early on an anomalous, 10-cm-thick, carbon-rich layer at a depth of 2.8 m that dates to 12.9 ka and coincides with a suite of anomalous coeval environmental and biotic changes independently recognized in other regional lake sequences. Collectively, these changes have produced the most distinctive boundary layer in the late Quaternary record. This layer contains a diverse, abundant assemblage of impact-related markers, including nanodiamonds, carbon spherules, and magnetic spherules with rapid melting/quenching textures, all reaching synchronous peaks immediately beneath a layer containing the largest peak of charcoal in the core. Analyses by multiple methods demonstrate the presence of three allotropes of nanodiamond: n-diamond, i-carbon, and hexagonal nanodiamond (lonsdaleite), in order of estimated relative abundance. This nanodiamond-rich layer is consistent with the Younger Dryas boundary layer found at numerous sites across North America, Greenland, and Western Europe. We have examined multiple hypotheses to account for these observations and find the evidence cannot be explained by any known terrestrial mechanism. It is, however, consistent with the Younger Dryas boundary impact hypothesis postulating a major extraterrestrial impact involving multiple airburst(s) and and/or ground impact(s) at 12.9 ka.

[Efficacy and safety of 308 nm excimer laser for vitiligo].

OBJECTIVE: To assess the efficacy and safety of the 308 nm excimer laser for the treatment of vitiligo. METHODS: We treated 170 patients with stable vitiligo by using the 308 nm excimer laser. The lesions of vitiligo were treated one to two times per week for 10-30 times. Efficacies were evaluated every 7 days and 3 days after the treatments were completed. Patients were followed up for two months. RESULTS: The rates of "remarkably improved" and "cured" were 67.97% and 32.03% in faces, 54.55% and 27.27% in necks, 63.26% and 26.53% in trunks, 38.84% and 15.70% in limbs, and 0 and 0 in hands and feet. The areas of faces had a better response than those of necks, trunks, or limbs (P < 0.01), and the areas of trunks or limbs had better response than that of hands and feet (P < 0.01). CONCLUSION: The 308 nm excimer laser is safe and effective in treating stable vitiligo and the efficacy varies in different lesion sites.

Predicting lipase types by improved Chou's pseudo-amino acid composition.

By proposing a improved Chou's pseudo amino acid composition approach to extract the features of the sequences, a powerful predictor based on k-nearest neighbor was introduced to identify the types of lipases according to their sequences. To avoid redundancy and bias, demonstrations were performed on a dataset where none of the proteins has > or =25% sequence identity to any other. The overall success rate thus obtained by the 10-fold cross-validation test was over 90%, indicating that the improved Chou's pseudo amino acid composition might be a useful tool for extracting the features of protein sequences, or at lease can play a complementary role to many of the other existing approaches.

[Flashlamp-pumped pulsed dye laser (585 nm) in the treatment of port-wine stains--a retrospective study of 2317 Chinese patients].

OBJECTIVE: To evaluate the efficacy and safety of 585 nm flashlamp-pumped pulsed dye lasers (PDL) in the treatment of port-wine stains (PWS). METHODS: A retrospective review was performed in 2 317 patients with PWS who visited the Dermatology Laser Centre of PUMC Hospital and accepted treatment with 585 nm PDL. The correlation between the treatment efficacy and the treatment sessions, lesion types, and usage of other therapies were analyzed. The adverse effects were also observed. RESULTS: All the 2 317 patients with PWS received 1-13 consecutive treatments with PDL at 2-3-month intervals. The median number of treatment was 4.93 and the median energy density was 8.29 J/cm2. The response rate after 8 treatments sessions were 84%. The response rate in patients whose lesions are characterized as purple plaques with proliferation and treated with isotope, CO2, cryotherapy, and other treatments was significantly lower than the total response rate (P < 0.05). Superficial scar, hyperpigmentation, and hypopigmentation were found in 5.2%, 2.5%, and 4.0% of these patients, respectively. CONCLUSION: 585 nm PDL is effective and safe in treating PWS.

[Clinical efficacy of Q-switched Alexandrite laser for pigmentary skin diseases in 4656 patients].

OBJECTIVE: To evaluate the clinical efficacy and safety of Q-switched Alexandrite laser in the treatment of pigmentary skin, diseases ( PSDs). METHODS: Totally 4 656 patients with PSDs were treated with Q-switched Alexandrite laser. These PDSs included nevus of Ota, seborrheic keratosis, tattoo, naevus fusco-caeruleus zygomaticus, cafe-au-lait-spots, lentigo, naevus of Ito, and spilus naevus. The outcomes and adverse events after treatment were oberserved. RESULTS: The response rate was 92.31% and the cure rate was 55.39% for nevus of Ota after six times of treatment, and the cure rate was 100% after nine times of treatment. The response rate was 100% for freckles, seborrheic keratosis, and naevus fuscocaeruleus zygomaticus after four times of treatment. The response rate was more than 77.18% and the cure rate was more than 50% for tattoos after three times of treatment, including amateur tattoo, artificial eyebrow, eyelid lines, and traumatic tattoo. However, after four times of treatment, the response rate and the cure rate were only 50. 00% and 21.43% for cafe-au-lait spots, and 50.00% and 25.00% for spilus naevus, respectively. The response rate was 35.29% for lentigo and 25.00% for naevus of Ito/ spilus naevus after four times of treatment. CONCLUSION: Q-switched Alexandrite laser is effective in the treatment of nevus of Ota, seborrheic keratosis, tattoo, and naevus fusco-caeruleus zygomaticus, but has limited efficacy for cafe-au-lait-spots, lentigo, naevus of Ito, and spilus naevus.

[Effectiveness and safety of long-pulsed Alexandrite laser for hair removal in 1702 patients].

OBJECTIVE: To evaluate the effectiveness and safety of long-pulsed Alexandrite laser for hair removal. METHODS: Hair removal was performed in 1702 hirsute patients with long-pulsed Alexandrite laser. Among them 1603 patients received two or more operations. RESULTS: In patients who received 2, 3, 4, 5, and > or =6 operations, the effectiveness rates were 9.79%, 18.33%, 29.10%, 37.64%, and 82.68%, respectively. The number of operation correlated with the effectiveness, and > or =6 operations resulted in superior outcomes. Pigmentation occurred in 0.94% of the patients (16/1702). CONCLUSION: The long-pulsed Alexandrite laser system is effective and safe in removing hair.