Targeting pericentric non-consecutive motifs for heterochromatin initiation.

Pericentric heterochromatin is a critical component of chromosomes marked by histone H3 K9 (H3K9) methylation1-3. However, what recruits H3K9-specific histone methyltransferases to pericentric regions in vertebrates remains unclear4, as does why pericentric regions in different species share the same H3K9 methylation mark despite lacking highly conserved DNA sequences2,5. Here we show that zinc-finger proteins ZNF512 and ZNF512B specifically localize at pericentric regions through direct DNA binding. Notably, both ZNF512 and ZNF512B are sufficient to initiate de novo heterochromatin formation at ectopically targeted repetitive regions and pericentric regions, as they directly recruit SUV39H1 and SUV39H2 (SUV39H) to catalyse H3K9 methylation. SUV39H2 makes a greater contribution to H3K9 trimethylation, whereas SUV39H1 seems to contribute more to silencing, probably owing to its preferential association with HP1 proteins. ZNF512 and ZNF512B from different species can specifically target pericentric regions of other vertebrates, because the atypical long linker residues between the zinc-fingers of ZNF512 and ZNF512B offer flexibility in recognition of non-consecutively organized three-nucleotide triplets targeted by each zinc-finger. This study addresses two long-standing questions: how constitutive heterochromatin is initiated and how seemingly variable pericentric sequences are targeted by the same set of conserved machinery in vertebrates.

NLRP3 regulates CIITA/MHC II axis and interferon-γ-inducible chemokines in Malassezia globosa-infected keratinocytes.

CIITA, a member of NOD-like receptor (NLR) family, is the major MHC II trans-activator and mediator of Th1 immunity, but its function and interaction with NLRP3 have been little studied. We found activation of NLRP3 inflammasome, increased expression of CIITA, CBP, pSTAT1, STAT1, MHC II, IFN-γ and IFN-γ-inducible chemokines (CCL1 and CXCL8), and colocalisation of NLRP3 with CIITA in Malassezia folliculitis lesions, Malassezia globosa-infected HaCaT cells and mouse skin. CoIP with anti-CIITA or anti-NLRP3 antibody pulled down NLRP3 or both CIITA and ASC. NLRP3 silencing or knockout caused CIITA downexpression and their colocalisation disappearance in HaCaT cells and mouse skin of Nlrp3-/- mice, while CIITA knockdown had no effect on NLRP3, ASC, IL-1ß and IL-18 expression. NLRP3 inflammasome inhibitors and knockdown significantly suppressed IFN-γ, CCL1, CXCL8 and CXCL10 levels in M. globosa-infected HaCaT cells. CCL1 and CXCL8 expression was elevated in Malassezia folliculitis lesions and reduced in Nlrp3-/- mice. These results demonstrate that M. globosa can activate NLRP3 inflammasome, CIITA/MHC II signalling and IFN-γ-inducible chemokines in human keratinocytes and mouse skin. NLRP3 may regulate CIITA by their binding and trigger Th1 immunity by secreting CCL1 and CXCL8/IL-8, contributing to the pathogenesis of Malassezia-associated skin diseases.

Elevating Discharge Voltage of Li2CO3-routine Li-CO2 Battery over 2.9 V at an Ultra-wide Temperature Window.

The Li-CO2 batteries utilizing greenhouse gas CO2 possess advantages of high energy density and environmental friendliness. However, these batteries following Li2CO3-product route typically exhibit low work voltage (<2.5 V) and energy efficiency. Herein, we have demonstrated for the first time that cobalt phthalocyanine (CoPc) as homogeneous catalyst can elevate the work plateau towards 2.98 V, which is higher than its theoretical discharge voltage without changing the Li2CO3-product route. This unprecedented discharge voltage is illustrated by mass spectrum and electrochemical analyses that CoPc has powerful adsorption capability with CO2 (-7.484 kJ/mol) and forms discharge intermediate of C33H16CoN8O2. Besides high discharge capacity of 18724 mAh/g and robust cyclability over 1600 hours (1000 mAh/g cut-off) at a current density of 100 mA/g , the batteries show high temperature adaptability (-30~80 °C). Our work is paving a promising avenue for the progress of high-efficiency Li-CO2 batteries.

Characteristics and Outcomes of Electric Bicycle-Related Open-Globe Injuries in a Tertiary Hospital in North China.

BACKGROUND: The aim was to describe the characteristics and outcomes of patients treated for electric bicycle-related open-globe injuries (OGIs). METHODS: A retrospective chart review of all patients who presented with electric bicycle-related OGIs was performed at the Hebei Eye Hospital in North China between January 2012 and December 2018. Demographic data, injury type, presenting clinical examination findings, best-corrected visual acuity (BCVA), secondary ocular complications, necessary surgical procedures and long-term outcome data were recorded. RESULTS: Twenty-six patients with electric bicycle-related OGIs met the inclusion criteria and were enrolled in the study. Eighteen of the 26 patients (69.2%) were males. the average age of these patients was 44.0 years old. The injuries peaked in winter in the hour between 15:00 and 20:00. Among the patients, 23 (88.5%) were farm workers, 2 (7.7%) were industrial workers, 1 (3.8%) was student. The types of OGIs were 23 ruptures (88.5%), 3 penetrating injuries (11.5%). Data on zone of injuries included 1 zone I injuries (3.8%), 12 zone II injuries (46.2%), 13 zone III injuries (50.0%). Nine eyes (34.6%) had traumatic cataract, 24 eyes (92.3%) had vitreous hemorrhage, 20 eyes (79.9%) had retinal detachment, 19 eyes (73.1%) had choroidal detachment. Ten eyes (38.4%) had hand motion or worse vision at final follow-up. four eyes (15.4%) which had injuries involving all 3 zones resulted in enucleation or evisceration. With respect to BCVA, the initial BCVA was 2.7±0.3 and the final BCVA was 2.0±0.7, indicating that the patients' BCVA was significantly improved by surgery ( t =4.3, P <0.001). CONCLUSIONS: Electric bicycle-related OGIs may have severe consequences. Modern surgical techniques can increase the rate of globe salvage although final vision remains poor. Therefore, increased awareness, proposed policies and suggestions should focus on regulating the use of electric bicycles and reinforcing laws and regulations to improve safety and prevent injuries.

Ferredoxin reductase regulates proliferation, differentiation, cell cycle and lipogenesis but not apoptosis in SZ95 sebocytes.

Ferredoxin reductase (FDXR), a mitochondrial membrane-associated flavoprotein, is essential for electron transfer and modulates p53-dependent apoptosis in cancer cells.FDXR may be implicated in epidermal and sebocytic differentiation, but its explicit function in sebocytes remains to be elucidated. In the present study, immunohistochemistry revealed that FDXR expression was increased in sebaceous cells of acne lesions. FDXR, PPARγ, LXRα/ß, SREBP1 and Sox9 expression was incremental during sebocyte differentiation. FDXR overexpression induced by Ad-GFP-FDXR infection enhanced differentiation, reactive oxygen species (ROS), lipogenesis and PPARγ expression, and consequnently inhibited proliferation in SZ95 sebocytes. Flow cytometry showed that FDXR overexpression induced significant blockade of G2/M phase but had no effect on sub-G1 (apoptotic) sebocytes. Insulin-like growth factor-1 (IGF-1)-induced FDXR and PPARγ expression and lipogenesis were abolished by pretreatment with PI3K inhibitor LY294002. These results suggest that FDXR overexpression might promote differentiation and lipogenesis via ROS production and suppress proliferation via G2/S blockade in SZ95 sebocytes. IGF-1 could facilitate differentiation and lipogenesis through PI3K/Akt/FDXR pathway. FDXR could serve as a potential marker of advanced sebaceous differentiation, and its overexpression may be involved in the development of acne lesions.

Fisheye Image Detection of Trees Using Improved YOLOX for Tree Height Estimation.

Tree height is an essential indicator in forestry research. This indicator is difficult to measure directly, as well as wind disturbance adds to the measurement difficulty. Therefore, tree height measurement has always been an issue that experts and scholars strive to improve. We propose a tree height measurement method based on tree fisheye images to improve the accuracy of tree height measurements. Our aim is to extract tree height extreme points in fisheye images by proposing an improved lightweight target detection network YOLOX-tiny. We added CBAM attention mechanism, transfer learning, and data enhancement methods to improve the recall rate, F1 score, AP, and other indicators of YOLOX-tiny. This study improves the detection performance of YOLOX-tiny. The use of deep learning can improve measurement efficiency while ensuring measurement accuracy and stability. The results showed that the highest relative error of tree measurements was 4.06% and the average relative error was 1.62%. The analysis showed that the method performed better at all stages than in previous studies.

Penile annular and scrotal eczematoid syphilids with penile chancre redux.

We describe a 17-year-old man who developed penile annular and scrotal eczematoid syphilids with penile chancre redux. Dermoscopy showed linear-irregular and hairpin vessels with white scales in annular lesions. Histopathology displayed psoriasiform hyperplasia with perivascular lymphoplasmacytic dermal infiltrate. Rapid plasma reagin and Treponema pallidumparticle agglutination assays were positive. The lesions disappeared after intramuscular benzathine penicillin.

Immunophenotyping comparison of inflammatory cells between Malassezia folliculitis and pityriasis versicolor lesions.

Immunophenotyping of inflammatory dermal infiltrates in Malassezia folliculitis (MF) and pityriasis versicolor (PV) lesions is less reported. Immunohistochemistry was performed on 21 MF lesions, 10 PV lesions, and 10 control skin. CD3+, CD4+, CD8+, CD20+, CD68+, and CD117+ cells were increased in MF compared with PV and normal skin (P < 0.01-0.05), while CD3+, CD4+, and CD20+ cells were higher in PV than in normal skin (P < 0.05). Dermal CD1a+ cells were higher only in PV (P < 0.05). Although both cellular and humoral immune responses are involved in pathogenesis of MF and PV, their difference may contribute to clinicopathological discrepancy between two disorders. LAY SUMMARY: Malassezia folliculitis and pityriasis versicolor are common Malassezia-induced superficial mycoses. Their clinicopathological discrepancy may be due to the difference of cellular and humoral immune responses.

The efficient biomineralization and adsorption of cadmium (Cd2+) using secretory organo-biominerals (SOBs) produced by screened Alcaligenes faecalis K2.

Cadmium-contaminated wastewater has attracted increasing concerns due to its non-biodegradable properties and high toxicity. To explore eco-friendly and economically feasible strategies, the screened Alcaligenes faecalis K2 were employed for the biomineralization and recovery of Cd2+ from wastewater while producing considerable secretory organo-biominerals (SOBs) as bioadsorbents. At 75 mg/L Cd2+ exposure, 85.5% of Cd2+ was removed by K2, 43.0% of which was fixed in the granular SOBs. SOBs were convenient for separating from the solution. The adsorption capacity of granular sorbent made from SOBs was verified to be greater than 77.1 mg/g. Practically, 89.5% of 75 mg/L of Cd2+ could be stably removed while ereK2 continuously generated SOBs in a moving-bed biofilm reactor (MBBR). To sum up, the production of bioadsorbents can be achieved by K2, while removing Cd with live microorganisms, which was conducive to making full use of materials and improving Cd removal efficiency.

Cellular automaton modeling of peritectic transformation⋆.

A two-dimensional multiphase cellular automaton (CA) model is proposed for the prediction of growth kinetics and microstructural evolution during peritectic transformation of Fe-C alloys. The proposed model is validated by comparing the simulation results with the experimental measurements and analytical predictions for the growth kinetics of the [Formula: see text] -phase and the concentration distributions. The simulated time evolution of the [Formula: see text] -phase thickness and the concentration distribution in the [Formula: see text] -phase agree well with the experimental data, demonstrating the quantitative capabilities of the proposed model. The influences of the holding temperature and [Formula: see text] -phase thickness on the [Formula: see text] -phase growth behavior are analyzed based on the simulation results. The [Formula: see text] -phase growth velocity is found to decrease with increasing the [Formula: see text] -phase thickness and holding temperature. Simulations are also performed for the microstructural evolution during isothermal peritectic transformation of Fe-C alloys with the primary [Formula: see text] -phase being an equiaxed dendrite under different holding temperatures. It is found that the driving force for [Formula: see text] -phase growth increases with decreasing temperature.

Association between rainfall and readmissions of rheumatoid arthritis patients: a time-stratified case-crossover analysis.

It has been reported that local weather is associated with the symptoms of joint pain in patients with rheumatoid arthritis (RA), and many people believe their pain becomes worse when facing rainy days. However, limited studies explored the effects of weather on RA patients' healthcare-seeking behavior. Our study aimed to investigate the relationship between rainfall and readmission behavior of patients with RA in Hefei, China, based on hospitalization data from the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2012 to June 2016 and weather data from National Meteorological Information Center during the same study period. Using a time-stratified case-crossover study design and conditional logistic regression, we found a negative association between current day rainfall and readmission (unadjusted: OR = 0.82, p < 0.05; adjusted: OR = 0.83, p < 0.1), which is contrary to our common belief. In lagged models, we observed that rainfall was significantly and positively associated with readmissions at lag 6 days (unadjusted: OR = 1.12, p < 0.1; adjusted: OR = 1.17, p < 0.05) and lag 7 days (unadjusted: OR = 1.13, p < 0.05; adjusted: OR = 1.21, p < 0.01). Additionally, stratified analyses showed the unanticipated finding was only statistically significant for younger patients (< 65 years) and females. Our study adds new evidence that the association between the healthcare-seeking behavior of patients with RA and local rainfall may be different, compared with the positive relationship between symptoms of joint pain and rainfall.

The short-term effects of air pollutants on hospitalizations for respiratory disease in Hefei, China.

Previous studies have shown that ambient air pollution is associated with respiratory morbidity. However, the effects of air pollutants on health have rarely been studied in China. Our study aimed to estimate the short-term effects of particulate air pollutants on hospitalizations for three types of respiratory disease: pneumonia, chronic obstructive pulmonary disease (COPD), and asthma. We collected data on daily admissions for patients with each disease from the New Rural Cooperative Medical System (NRCMS) in Hefei, China. Daily records of air pollutants and meteorological data from January 2014 to March 2016 were also obtained. Distributed lag nonlinear models were employed in the analysis to evaluate the association between daily air pollutants and admissions. The highest effect of each pollutant on COPD hospital admission was observed with PM2.5 at lag 12 (RR = 1.068, 95% CI 1.017 to 1.121) and PM10 at lag 10 (RR = 1.031, 95% CI 1.002 to 1.060), for an increase of 10 µg/m3 in concentrations of the pollutants. The short-term effects of PM10 on asthma hospital admissions peaked at lag 12 (RR = 1.057, 95% CI 1.010 to 1.107). According to our stratified analysis, we found that the effects on COPD admission were more pronounced in the warm season than in the cold season, and the elderly (≥ 65 years) and females were more vulnerable to air pollution.

Bicanalicular Lacerations: Clinical Characteristics and Surgical Outcomes With a New Bicanalicular Silicone Stent.

BACKGROUND: Bicanalicular lacerations are relatively rare and more of a surgical challenge in clinical practice. The purpose of this study is to evaluate the clinical characteristics and surgical outcomes of bicanalicular lacerations with a new bicanalicular silicone stent at a tertiary eye care center. METHODS: All patients who underwent bicanalicular lacerations repair from January 2013 and December 2018 were retrospectively reviewed. Data collected for each patient included patient demographics, affected sides, cause of injuries, the timing of management, associated ocular injuries, the timing of stent removal, duration of follow-up and the outcomes of the surgical repair with a new bicanalicular silicone stent. RESULTS: Thirty-six patients with bicanalicular lacerations met the inclusion criteria and were enrolled in the study. The mean age of the patients was 43.8 years old (range: 2-73years). Of the 36 patients, 33 (91.7%) were males and 3 (8.3%) were females. The right eye was injured in 17 patients (47.2%). All patients underwent surgical intervention within 24 hours. The most common cause of bicanalicular lacerations was electric bicycles accidents (7 patients, 19.4%), and followed by motor vehicle accidents (6 patients, 16.7%), blunt objects (6 patients, 16.7%), fights (6 patients, 16.7%), falls (3 patients, 12%), dog bites (2 patients, 5.6%), hook injuries (2 patients, 5.6%), broken glass (2 patients, 5.6%), and sharp objects (2 patients, 5.6%). The most common associated ocular injuries were orbital fracture (61.1%), followed by lid lacerations and open globe injuries. The functional success rate was 86.1%. The average interval between the surgery and the stent removal was 13.8 weeks (range: 8-20 weeks). All the stents were removed successfully without any difficulty in the outpatient department. The follow-up after stent removal ranged from 2 to 12 months (mean: 5.1months). CONCLUSIONS: Bicanalicular lacerations involvement occured in 6.8% of all canalicular lacerations. The most common cause of bicanalicular lacerations was electric bicycles accidents and the most common associated ocular injuries was orbital fracture in North China. The new bicanalicular silicone stent achieved good functional success (86.1%) in the management of bicanalicular lacerations.

FoxO1 enhances differentiation and apoptosis in human primary keratinocytes.

Forkhead box-O1 (FoxO1) is a key nutrient- and growth factor-dependent regulator of metabolism, but its functional role in human primary keratinocytes (HPKs) is less known. To investigate the role of FoxO1 in HPKs and effect of insulin-like growth factor 1 (IGF-1) and isotretinoin on FoxO1 expression, HPKs were treated with 1.2 mmol/L calcium chloride, 1-20 ng/mL IGF-1 and 0.1-10 µmol/L isotretinoin. Recombinant adenovirus expressing FoxO1 or FKHR shRNA lentivirus transfection was introduced to upregulate or silence FoxO1 expression. Epidermal FoxO1 immunostaining was lower in acne lesion than in normal skin. FoxO1 overexpression induced involucrin expression, G2/M arrest and apoptosis but suppressed proliferation, while FoxO1 silencing decreased involucrin expression but increased proliferation, S phase and viable cells in HPKs. IGF-1 downregulated FoxO1 and involucrin but upregulated p-Akt expression in HPKs, which was blocked by pretreatment with LY294002. Isotretinoin enhanced FoxO1, p53 and p21 but inhibited p-FoxO1 and involucrin expression in HPKs. These results demonstrate that FoxO1 promotes differentiation and apoptosis in HPKs. IGF-1 may reduce keratinocyte differentiation through PI3K/Akt/FoxO1 pathway, while isotretinoin can reinforce FoxO1 expression. FoxO1 may be involved in acne pathogenesis and could serve as a potential therapeutic target.

Overexpression of Androgen, Oestrogen and Progesterone Receptors in Skin Lesions of Becker's Naevus.

Becker's naevus is androgen-dependent. The aim of this study was to investigate whether oestrogen and progesterone receptors are involved in this disorder. Immunohistochemistry showed that epidermal expression of androgen receptors, oestrogen receptors (α, ß) and progesterone receptors was higher in skin lesions of Becker's naevus than in perilesional and control skin. Androgen receptor overexpression was observed in pilosebaceous glands, while oestrogen and progesterone receptor overexpression was seen in hair follicles, but not in sebaceous glands in skin lesions compared with perilesional skin. Reverse tran-scription PCR and Western blot revealed that levels of androgen, oestrogen and progesterone receptors were generally upregulated in skin lesions compared with perilesional and control skin, and their expression was usually higher in perilesional than in control skin. These results suggest that simultaneous overexpression of androgen, oestrogen and progesterone receptors might be implicated in the pathogenesis of Becker's naevus.

Overexpression of NLRP3, NLRC4 and AIM2 inflammasomes and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in Malassezia folliculitis.

The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear. The objective of the study was to determine the expression of 4 canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion. Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1ß, TLR2, TLR4, Dectin-1, Dectin-2 and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects. Furthermore, NLRP1, NLRP3, NLRC4, AIM2, caspase-1 and IL-1ß mRNA was measured by quantitative real-time PCR (qRT-PCR) in 12 MF cases and 10 controls. Immunohistochemical analysis revealed that NLRP3, NLRC4, AIM2, Casp-1, IL-1ß, TLR2, TLR4, Dectin-1, Dectin-2 and NFκB expression was up-regulated in the epidermis and dermal inflammatory cells of MF lesion compared with control skin (P < .01-.05), but NLRP1 expression was not different between both groups (P > .05). qRT-PCR showed that levels of NLRP3, Casp-1 and IL-1ß mRNA were significantly increased (P < .01-.05), whereas those of NLRP1, NLRC4 and AIM2 mRNA were slightly augmented compared to control skin (P > .05). Our observation suggests that simultaneous activation of NLRP3, NLRC4 and AIM2 inflammasomes may play an important role in the pathogenesis of MF.

Estradiol inhibits Th17 cell differentiation through inhibition of RORγT transcription by recruiting the ERα/REA complex to estrogen response elements of the RORγT promoter.

The symptoms of vaginal candidiasis exacerbate in the second half of the menstrual cycle in premenopausal women when the serum estradiol level is elevated. Estradiol has been shown to inhibit Th17 differentiation and production of antifungal IL-17 cytokines. However, little is known about the mechanisms. In the present study, we used mouse splenocytes and found that estradiol inhibited Th17 differentiation through downregulation of Rorγt mRNA and protein expression. Estradiol activated estrogen receptor (ER)α to recruit repressor of estrogen receptor activity (REA) and form the ERα/REA complex. This complex bound to three estrogen response element (ERE) half-sites on the Rorγt promoter region to suppress Rorγt expression. Estradiol induced Rea mRNA and protein expression in mouse splenocytes. Using Rea small interfering RNA to knock down Rea expression enhanced Rorγt expression and Th17 differentiation. Alternatively, histone deacetylase 1 and 2 bound to the three ERE half-sites, independent of estradiol. Histone deacetylase inhibitor MS-275 dose- and time-dependently increased Rorγt expression and subsequently enhanced Th17 differentiation. In 15 healthy premenopausal women, high serum estradiol levels are correlated with low RORγT mRNA levels and high REA mRNA levels in the vaginal lavage. These results demonstrate that estradiol upregulates REA expression and recruits REA via ERα to the EREs on the RORγT promoter region, thus inhibiting RORγT expression and Th17 differentiation. This study suggests that the estradiol/ERα/REA axis may be a feasible target in the management of recurrent vaginal candidiasis.