Dampening of ISGylation of RIG-I by ADAP regulates type I interferon response of macrophages to RNA virus infection.

While macrophage is one of the major type I interferon (IFN-I) producers in multiple tissues during viral infections, it also serves as an important target cell for many RNA viruses. However, the regulatory mechanism for the IFN-I response of macrophages to respond to a viral challenge is not fully understood. Here we report ADAP, an immune adaptor protein, is indispensable for the induction of the IFN-I response of macrophages to RNA virus infections via an inhibition of the conjugation of ubiquitin-like ISG15 (ISGylation) to RIG-I. Loss of ADAP increases RNA virus replication in macrophages, accompanied with a decrease in LPS-induced IFN-ß and ISG15 mRNA expression and an impairment in the RNA virus-induced phosphorylation of IRF3 and TBK1. Moreover, using Adap-/- mice, we show ADAP deficiency strongly increases the susceptibility of macrophages to RNA-virus infection in vivo. Mechanically, ADAP selectively interacts and functionally cooperates with RIG-I but not MDA5 in the activation of IFN-ß transcription. Loss of ADAP results in an enhancement of ISGylation of RIG-I, whereas overexpression of ADAP exhibits the opposite effect in vitro, indicating ADAP is detrimental to the RNA virus-induced ISGylation of RIG-I. Together, our data demonstrate a novel antagonistic activity of ADAP in the cell-intrinsic control of RIG-I ISGylation, which is indispensable for initiating and sustaining the IFN-I response of macrophages to RNA virus infections and replication.

Impaired FXR-CPT1a signaling contributes to parenteral nutrition-induced villus atrophy in short-bowel syndrome.

Parenteral nutrition (PN)-induced villus atrophy is a major cause of intestinal failure (IF) for children suffering from short bowel syndrome (SBS), but the precise mechanism remains unclear. Herein, we report a pivotal role of farnesoid X receptor (FXR) signaling and fatty acid oxidation (FAO) in PN-induced villus atrophy. A total of 14 pediatric SBS patients receiving PN were enrolled in this study. Those patients with IF showed longer PN duration and significant intestinal villus atrophy, characterized by remarkably increased enterocyte apoptosis concomitant with impaired FXR signaling and decreased FAO genes including carnitine palmitoyltransferase 1a (CPT1a). Likewise, similar changes were found in an in vivo model of neonatal Bama piglets receiving 14-day PN, including villus atrophy and particularly disturbed FAO process responding to impaired FXR signaling. Finally, in order to consolidate the role of the FXR-CPT1a axis in modulating enterocyte apoptosis, patient-derived organoids (PDOs) were used as a mini-gut model in vitro. Consequently, pharmacological inhibition of FXR by tauro-ß-muricholic acid (T-ßMCA) evidently suppressed CPT1a expression leading to reduced mitochondrial FAO function and inducible apoptosis. In conclusion, impaired FXR/CPT1a axis and disturbed FAO may play a pivotal role in PN-induced villus atrophy, contributing to intestinal failure in SBS patients.

Langerhans cell histiocytosis in children with refractory diarrhoea and hypoalbuminaemia as the initial presentation: two case reports and a literature review.

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.

What are the barriers and facilitators to advance care planning with older people in long-term care facilities? A qualitative study.

AIM: To explore the views and preferences for advance care planning from the perspectives of residents, family members and healthcare professionals in long-term care facilities. DESIGN: A qualitative descriptive design. METHODS: We conducted semi-structured interviews with 12 residents of long-term care facilities, 10 family members and 14 healthcare professionals. Data were analysed using reflexive thematic analysis. The social ecological model was used to develop implementation recommendations. RESULTS: We constructed a conceptual model of barriers and facilitators to advance care planning in long-term care facilities, drawing upon four dominant themes from the qualitative analysis: (1) The absence of discourse on end-of-life care: a lack of cultural climate to talk about death, the unspoken agreement to avoid conversations about death, and poor awareness of palliative care may hinder advance care planning initiation; (2) Relational decision-making process is a dual factor affecting advance care planning engagement; (3) Low trust and 'unsafe' cultures: a lack of honest information sharing, risks of violating social expectations and damaging social relationships, and risks of legal consequences may hinder willingness to engage in advance care planning; (4) Meeting and respecting residents' psychosocial needs: these can be addressed by readiness assessment, initiating advance care planning in an informal and equal manner and involving social workers. CONCLUSION: Our findings show that residents' voices were not being heard. It is necessary to identify residents' spontaneous conversation triggers, articulate the value of advance care planning in light of the family's values and preferences, and respect residents' psychosocial needs to promote advance care planning in long-term care facilities. Advance care planning may alleviate the decision-making burden of offspring in nuclear families. IMPLICATIONS FOR CLINICAL PRACTICE: The evidence-based recommendations in this study will inform the implementation of context-specific advance care planning in Asia-Pacific regions. PATIENT AND PUBLIC CONTRIBUTION: Patients and caregivers contributed to the interview pilot and data collection.

Relationship between dry skin and pressure injury in older patients: A multicentre cross-sectional survey in China.

Dry skin and pressure injuries in older persons have become global health care problems. This was a multicentre, prospective cross-sectional study in 44 hospitals and 8 long term care institutions from 20 provinces, autonomous regions and municipalities in China and aimed to explore the relationship between the two skin problems in older patients. We mainly found 11 602 cases with dry skin and 1076 cases with pressure injuries in a total of 33 769 valid participants. The overall prevalence of dry skin and pressure injuries was 34.4% (95% confidence interval [CI] 33.9-34.9) and 3.1% (95% CI 2.9-3.3). Stage 2+ pressure injuries were the most (32.9%), followed by stage 1 (32.4%). The patients with dry skin had more pressure injuries than ones without dry skin (50.0% vs 33.9%). The patients with very severe and severe dry skin had more pressure injury risk (OR 2.22 and 1.90) and more stage 2+ pressure injury risk (OR 2.83 and 1.63). Other nine predictors associated with overall pressure injuries and stage 2+ pressure injuries. The area under receiver operating characteristic (ROC) curve of the predictive models of overall pressure injuries and stage 2+ pressure injuries were 0.89 (95% CI 0.88-0.90) and 0.91 (95% CI 0.90-0.92), respectively.

Clinical application of autophagy proteins as prognostic biomarkers in colorectal cancer: a meta-analysis.

Aim: To evaluate the prognostic value of autophagy proteins in colorectal cancer (CRC). Methods: Six potential autophagy proteins were analyzed (Beclin-1, LC3A, LC3B, ULK1, ATG10 and p62). Hazard ratios (HRs) and 95% CIs for overall survival (OS) of CRC patients were calculated. Results: A total of 20 studies were included. High expression of LC3B and p62 was associated with favorable OS (HR: 0.56, 95% CI: 0.40-0.80; HR: 0.76, 95% CI: 0.61-0.96), whereas high expression of Beclin-1 (HR: 1.47, 95% CI: 1.05-2.06) and ULK1 (HR: 1.92. 95% CI: 1.05-3.53) might predict worse OS in CRC patients. Conclusion: Beclin-1, LC3B and p62 might act as promising prognostic biomarkers for CRC. High LC3 and p62 expression can be reliable tools for metastasis prediction.

Efficacy of computerized cognitive training on improving cognitive functions of stroke patients: A systematic review and meta-analysis of randomized controlled trials.

AIM: To evaluate the effects of computerized cognitive training on the cognitive functions of stroke patients. BACKGROUND: With increased publications on computerized cognitive training, a meta-analysis is essential to determine the effects of computerized cognitive training among stroke patients. DESIGN: A systematic review and meta-analysis of randomized controlled studies. DATA SOURCES: Cochrane Library, Pubmed, EBSCO, Scopus, China National Knowledge Infrastructure, China Biology Medicine disc and Wanfang Database were explored to search for research studies from inception to January 2020. REVIEW METHODS: Six outcomes indicators were considered to determine the effects of computerized cognitive training. Two reviewers were selected to search and independently appraise the available articles from various databases. Meta-analysis was performed using the RevMan 5.3 software. RESULTS: A total of 622 patients with 17 studies were included. Computerized cognitive training significantly improves global cognition, working memory, attention and executive function of stroke patients. However, there was inadequate evidence to demonstrate any effects of computerized cognitive training on activities of daily living and depression. CONCLUSION: Computerized cognitive training improves the cognitive functions of stroke patients. However, further research studies are needed to confirm its efficacy in activities of daily living as well as on alleviating depression.

Long-term outcomes of various pediatric short bowel syndrome in China.

PURPOSE: The goal of this study was to analyze long-term outcome of various pediatric short bowel syndrome (SBS) at an intestinal rehabilitation center in China. METHODS: One hundred and fifty-seven children with SBS were enrolled in this study from October 1988 to July 2019. Their long-term follow-up outcome was analyzed according to the age of disease onset, parenteral nutrition (PN) duration, and anatomic types of short bowel, respectively. The clinical characteristics, which included demographics, the length of residual small bowel, PN duration, PN dependence, SBS-related complications such as IF-related liver disease (IFALD), catheter-related bloodstream infection (CRBI), and mortality were compared among the groups. RESULTS: The main etiology for SBS were intestinal atresia, NEC, and volvulus. Five of 157 patients did not wean off PN. The incidence of IFALD and CRBI was 24.2 and 22.3%, respectively. Sixteen cases died because of infection and liver failure and eight patients lost to follow-up. The survival rate of the 157 patients was 84.7%. PN duration was longer in the infants and children group (284 ± 457 d vs. 110 ± 64 d, P = 0.021; R = 0.264, P = 0.001) and more patients did not wean off PN than in the neonates group (11.6% vs. 0, P = 0.001; R = 0.295, P < 0.001). Patients with PN with a duration of longer than 90 days had more CRBIs (30.6%, P = 0.025; R = 0.236, P = 0.003). Additionally, the rate of CRBI was higher in patients with stoma (30.0%, P = 0.032). There was no difference in mortality among the groups. In five PN dependence patients, none was SBS onset in neonates. CONCLUSION: Pediatric patients with SBS could achieve favorable long-term survival and enteral autonomy. Different standards of SBS classification such as the age of disease onset, PN duration, and anatomic types of short bowel did not impact the overall mortality of pediatric SBS. Prolonged PN duration positively correlated with the age of disease onset and the incidence of CRBI. Patients with the complete continuity of intestinal tract suffered less from CRBI.

Micronutrient deficiencies in pediatric short bowel syndrome: a 10-year review from an intestinal rehabilitation center in China.

PURPOSE: Vitamins and trace elements are essential nutrients for growth and intestinal adaptation in children with short bowel syndrome (SBS). This study aimed to assess micronutrients' status during and after weaning off PN in pediatric SBS. METHODS: This retrospective study evaluated the follow-up of 31 children with SBS between Jan 2010 and Sep 2019. Clinical data were reviewed from the patients' electric medical record. Serum electrolytes, trace elements, vitamin B12, vitamin D, and folate concentrations were collected before and after enteral autonomy. RESULTS: Thirty-one SBS cases were reviewed (median onset age 11 days after birth, 51.6% boys, mean PN duration 4 months, and mean residual small intestine length 58.2 cm). Median duration of follow-up was 10 months (interquartile range [IQR]: 4, 19). The common micronutrient deficiencies were zinc (51.6%), copper (38.7%), vitamin D (32.3%), and phosphorus (25.8%) after the transition to EN. The proportion of patients deficient in vitamin D decreased dramatically from 93.5% to 32.3% (P < 0.001), and serum concentrations of vitamin D increased significantly (27.4 ± 12.3 vs. 60.3 ± 32.9 nmol/l, P = 0.03) after achieving full enteral feeding more than 1 month. Additionally, serum magnesium levels significantly increased (0.76 ± 0.17 vs. 0.88 ± 0.14 mmol/l, P = 0.03). Hemoglobin levels elevated significantly after weaning off PN (104.3 ± 10.7 vs. 117.8 ± 13.7 g/l, P = 0.03). CONCLUSIONS: Micronutrient deficiencies remain a common problem in pediatric SBS through intestinal rehabilitation. Therefore, we strongly recommend supplementation of more vitamin D and trace elements (zinc, copper, and phosphorus) under regular monitoring during long-term intestinal rehabilitation.

Time-dependence of NIHSS in predicting functional outcome of patients with acute ischemic stroke treated with intravenous thrombolysis.

OBJECTIVES: The National Institute of Health Stroke Scale (NIHSS) is a predictor for the prognosis of acute ischaemic stroke (AIS) and its prediction is time-dependent. We examined the performance of NIHSS at different timepoints in predicting functional outcome of patients with thrombolysed AIS. METHODS: This prospective study included 269 patients with AIS treated with recombinant tissue plasminogen activator (rt-PA). Unfavourable functional outcome was defined as modified Rankin Scale score 4-6 at 3 months after rt-PA treatment. Receiver operating characteristic curves were used to examine the predictive power of NIHSS score at admission and 2 hours/24 hours/7 days/10 days after rt-PA treatment. Youden's index was used to select the threshold of NIHSS score. Logistic regression was used to estimate the ORs of unfavourable functional outcome for patients with NIHSS score higher than the selected thresholds. RESULTS: The threshold of NIHSS score at admission was 12 (sensitivity: 0.51, specificity: 0.84) with an acceptable predictive power (area under curve [AUC] 0.74) for unfavourable functional outcome. The threshold changed to 5 at 24 hours after rt-PA treatment (sensitivity: 0.83, specificity: 0.65) and remained unchanged afterwards. The predictive power and sensitivity sequentially increased over time and peaked at 10 days after rt-PA treatment (AUC 0.92, sensitivity: 0.85, specificity: 0.80). NIHSS scores higher than the thresholds were associated with elevated risk of unfavourable functional outcome at all timepoints (all p<0.001). CONCLUSIONS: NIHSS is time-dependent in predicting AIS prognosis with increasing predictive power over time. Since patients whose NIHSS score ≥ 12 are likely to have unfavourable functional outcome with rt-PA treatment only, mechanical thrombectomy should be largely taken into consideration for these patients.

Skin injury prevalence and incidence in China: a multicentre investigation.

OBJECTIVE:: To quantify the prevalence and incidence of different skin injuries, pressure ulcers (PU), skin tears (ST) and incontinence-associated dermatitis (IAD) in China, and to identify their causes to aid prevention and control. METHOD:: A cross-sectional observational study was conducted across nine tertiary hospitals. Registered nurses were trained on a standard approach to injury assessment and examination. The study was carried out at the same time on the same day across the participating centres. Participating patients were examined for PU, ST or IAD. RESULTS:: A total of 13,176 inpatients were assessed and 233 PU were identified, of which 126 occurred in hospitals, 99 cases at home and eight cases within community hospitals. In addition, there were 141 skin tears and 97 IADs. CONCLUSION:: This study involved the largest number of hospitals, to date (in China). Therefore, the prevalence and rate of incidence of skin injury obtained in this study may represent a regional baseline in China.

In utero exposure to 25-hydroxyvitamin D and risk of childhood asthma, wheeze, and respiratory tract infections: A meta-analysis of birth cohort studies.

BACKGROUND: Studies of the associations between in utero 25-hydroxyvitamin D (25[OH]D) exposure and risk of childhood asthma, wheeze, and respiratory tract infections are inconsistent and inconclusive. OBJECTIVES: We sought to assess associations between 25(OH)D levels in cord blood or maternal venous blood and risk of offspring's asthma, wheeze, and respiratory tract infections. METHODS: Data were derived from PubMed, Embase, Google Scholar, references from relevant articles, and de novo results from published studies until December 2015. A random-effects meta-analysis was conducted among 16 birth cohort studies. RESULTS: Comparing the highest with the lowest category of 25(OH)D levels, the pooled odds ratios were 0.84 (95% CI, 0.70-1.01; P = .064) for asthma, 0.77 (95% CI, 0.58-1.03; P = .083) for wheeze, and 0.85 (95% CI, 0.66-1.09; P = .187) for respiratory tract infections. The observed inverse association for wheeze was more pronounced and became statistically significant in the studies that measured 25(OH)D levels in cord blood (0.43; 95% CI, 0.29-0.62; P < .001). CONCLUSIONS: Accumulated evidence generated from this meta-analysis suggests that increased in utero exposure to 25(OH)D is inversely associated with the risk of asthma and wheeze during childhood. These findings are in keeping with the results of 2 recently published randomized clinical trials of vitamin D supplementation during pregnancy.

A quality control circle process to improve implementation effect of prevention measures for high-risk patients.

The aim of the study was to analyse the influence of prevention measures on pressure injuries for high-risk patients and to establish the most appropriate methods of implementation. Nurses assessed patients using a checklist and factors influencing the prevention of a pressure injury determined by brain storming. A specific series of measures was drawn up and an estimate of risk of pressure injury determined using the Braden Scale, analysis of nursing documents, implementation of prevention measures for pressure sores and awareness of the system both before and after carrying out a quality control circle (QCC) process. The overall scores of implementation of prevention measures ranged from 74.86 ± 14.24 to 87.06 ± 17.04, a result that was statistically significant (P < 0.0025). The Braden Scale scores ranged from 8.53 ± 3.21 to 13.48 ± 3.57. The nursing document scores ranged from 7.67 ± 3.98 to 10.12 ± 1.63; prevention measure scores ranged from 11.48 ± 4.18 to 13.96 ± 3.92. Differences in all of the above results are statistically significant (P < 0.05). Implementation of a QCC can standardise and improve the prevention measures for patients who are vulnerable to pressure sores and is of practical importance to their prevention and control.

Educational campaign to increase knowledge of pressure ulcers.

BACKGROUND: A pressure ulcer (PU) steering group was set up in Zhongda Hospital in China to develop a campaign to increase knowledge of PUs, to improve management and reduce incidence. METHOD: Questionnaires were completed by 275 nurses to ascertain their knowledge of PUs. The initial questionnaire indicated that the nurses had insufficient knowledge of PUs. The steering group then ran a campaign focusing on standardising the management of PUs. The measurement of PU knowledge for all nurses was tested after 2 years of training. RESULTS: After 2 years, the nursing staff's knowledge of PUs had improved. Usage of the Braden scale had risen from (60.0±22.9) to (88.0±9.0) and showed a statistically significant difference (p<0.01). Moreover, the rate for patients reported as being at high risk of developing a PU had increased from 0.98% in 2012 to 1.24% in 2013, while the occurrence rate of PUs in the hospital had decreased from 0.09% in 2012 to 0.05% in 2013. CONCLUSION: The campaign significantly enhanced the knowledge of PUs and improved the ability of nursing staff to evaluate PU risks, resulting in a decrease in the occurrence of PUs.

Age- and gender-related dispersion of brain networks across the lifespan.

The effects of age and gender on large-scale resting-state networks (RSNs) reflecting within- and between-network connectivity in the healthy brain remain unclear. This study investigated how age and gender influence the brain network roles and topological properties underlying the ageing process. Ten RSNs were constructed based on 998 participants from the REST-meta-MDD cohort. Multivariate linear regression analysis was used to examine the independent and interactive influences of age and gender on large-scale RSNs and their topological properties. A support vector regression model integrating whole-brain network features was used to predict brain age across the lifespan and cognitive decline in an Alzheimer's disease spectrum (ADS) sample. Differential effects of age and gender on brain network roles were demonstrated across the lifespan. Specifically, cingulo-opercular, auditory, and visual (VIS) networks showed more incohesive features reflected by decreased intra-network connectivity with ageing. Further, females displayed distinctive brain network trajectory patterns in middle-early age, showing enhanced network connectivity within the fronto-parietal network (FPN) and salience network (SAN) and weakened network connectivity between the FPN-somatomotor, FPN-VIS, and SAN-VIS networks. Age - but not gender - induced widespread decrease in topological properties of brain networks. Importantly, these differential network features predicted brain age and cognitive impairment in the ADS sample. By showing that age and gender exert specific dispersion of dynamic network roles and trajectories across the lifespan, this study has expanded our understanding of age- and gender-related brain changes with ageing. Moreover, the findings may be useful for detecting early-stage dementia.

Research on highway rain monitoring based on rain monitoring coefficient.

The real-time and accurate monitoring of severe weather is the key to reducing traffic accidents on highways. Currently, rainy day monitoring based on video images focuses on removing the impact of rain. This article aims to build a monitoring model for rainy days and rainfall intensity to achieve precise monitoring of rainy days on highways. This paper introduces an algorithm that combines the frequency domain and spatial domain, thresholding, and morphology. It incorporates high-pass filtering, full-domain value segmentation, the OTSU method (the maximum inter-class difference method), mask processing, and morphological opening for denoising. The algorithm is designed to build the rain coefficient model Prain coefficient and determine the intensity of rainfall based on the value of Prain coefficient. To validate the model, data from sunny, cloudy, and rainy days in different sections and time periods of the Jinan Bypass G2001 line were used. The aim is to raise awareness about driving safety on highways. The main findings are: the rain coefficient model Prain coefficient can accurately identify cloudy and rainy days and assess the intensity of rainfall. This method is not only suitable for highways but also for ordinary road sections. The model's accuracy has been verified, and the algorithm in this study has the highest accuracy. This research is crucial for road traffic safety, particularly during bad weather such as rain.

Effect of Personality and Pain Catastrophizing on Postoperative Analgesia Following Cesarean Section: A Prospective Cohort Study.

Purpose: This study aimed to investigate the effects of different psychological personalities and pain catastrophizing levels on postoperative analgesia in patients undergoing cesarean section. Patients and Methods: Puerperas who underwent cesarean section at our hospital between January and August 2023 were recruited into the study and assessed using the Eysenck Personality Questionnaire-Revised Short Scale (EPQRSC) and Pain Catastrophizing Scale (PCS). Data on the numerical pain intensity at rest and during activity 24 h after surgery, number and dosage of analgesia pumps, and satisfaction with analgesia were recorded. According to the numerical pain score during activity 24 h post-operation, the patients were divided into the analgesia incomplete group (≥4) and control group (<4). Univariate analysis, Spearman correlation analysis, and binary logistic regression analysis were used to evaluate the influence of personality characteristics and PCS on postoperative analgesia. Results: A total of 778 women were included in the study. The incidence of inadequate analgesia was 89.8%. The satisfaction rate of analgesia was 66.8%. Univariate analysis showed that extraversion; neuroticism; PCS; numbers of previous cesarean delivery; ASA; analgesic satisfaction; and 24-h analgesia pump compressions and dosage were associated with postoperative analgesia after cesarean section (P<0.05). Using binary logistic regression analysis, the first cesarean section (odds ratio [OR]=0.056, 95% confidence interval [CI]=1.913-19.174), the number of 24-h analgesic pump compressions (OR=8.464, 95% CI=0.356-0.604), extraversion (OR=0.667, 95% CI=0.513-0.866), neuroticism (OR=1.427, 95% CI=1.104-1.844), and PCS (OR=7.718, 95% CI=0.657-0.783) were factors affecting postoperative analgesia. Conclusion: The incidence of inadequate analgesia after a cesarean section was high (89.8% on the first day after surgery). Formulating accurate analgesia programs for women undergoing cesarean section with extraversion, neuroticism personality characteristics, and pain catastrophizing behaviors is necessary for improving their postoperative analgesia effects and satisfaction and promoting postpartum comfort.

The Suppression Effects of Fat Mass and Obesity Associated Gene on the Hair Follicle-Derived Neural Crest Stem Cells Differentiating into Melanocyte by N6-Methyladenosine Modifying Microphthalmia-Associated Transcription Factor.

Background and Objectives: Melanocyte (MC), derived from neural crest stem cell (NCSC), are involved in the production of melanin. The mechanism by which NCSC differentiates to MC remains unclear. N6-methyladenosine (m6A) modification was applied to discuss the potential mechanism. Methods and Results: NCSCs were isolated from hair follicles of rats, and were obtained for differentiation. Cell viability, tyrosinase secretion and activity, and transcription factors were combined to evaluated the MC differentiation. RT-qPCR was applied to determine mRNA levels, and western blot were used for protein expression detection. Total m6A level was measured using methylated RNA immunoprecipitation (MeRIP) assay, and RNA immunoprecipitation was used to access the protein binding relationship. In current work, NCSCs were successfully differentiated into MCs. Fat mass and obesity associated gene (FTO) was aberrant downregulated in MCs, and elevated FTO suppressed the differentiation progress of NCSCs into MCs. Furthermore, microphthalmia-associated transcription factor (Mitf), a key gene involved in MC synthesis, was enriched by FTO in a m6A modification manner and degraded by FTO. Meanwhile, the suppression functions of FTO in the differentiation of NCSCs into MCs were reversed by elevated Mitf. Conclusions: In short, FTO suppressed the differentiating ability of hair follicle-derived NCSCs into MCs by m6A modifying Mitf.

The spatial and temporal disaggregation models of high-accuracy vehicle emission inventory.

A high-accuracy gridding vehicle emission inventory is not only the foundation for developing refined emission control strategies but a necessary input to air quality model as well. An accurate approach to the spatiotemporal disaggregation is the key step to improving the accuracy of gridding emission inventories. The existing spatial disaggregation method considers relatively fewer impact factors, lacking adequate correlation analysis among impact factors. Additionally, the existing temporal disaggregation method does not correspond with the actual travel behavior of residents. This paper proposes a multi-factor spatial disaggregation model by principal component analysis (PCAM), based on a correlation analysis of the main impact factors. Further, a new temporal disaggregation model is proposed based on the congestion delay index combined with the traffic flow fundamental model (CDITF). The results from a case study in Jinan show that the square of correlation coefficients (RSQ) between the model- disaggregated NO2 emissions based on PCAM and the monitored NO2 concentration increased by 34.4% compared to the traditional disaggregation model based on the standard road length, and the RSQ for CO increased by 13%; the NMD and NME of the simulation results based on CMAQ model compared to standard road length model decrease by approximately 33.7% and 35.5%, respectively. The trend of the monthly, daily, and hourly variations of NO2 and CO emissions disaggregated by the proposed temporal disaggregation model is quite consistent with that of the monitored concentration data. The PCAM method and the CDITF proposed in this paper are more in line with the actual situation using the cumulative emissions on road sections. The vehicle emissions in Jinan are found to be concentrated in the center of each district and county and near high-grade roads. The disaggregation results in areas with large road slopes are more realistic for considering road slope factors. The trend of the monthly, daily, and hourly variations of NO2 and CO emissions disaggregated by the proposed temporal disaggregation model is quite consistent with that of the monitored concentration data, however, the monitored concentration data presents a certain degree of time lag. The proposed spatiotemporal disaggregation model in this paper improves the accuracy of gridding vehicle emission inventory, which is of a great significance for developing precise control strategies of vehicle emissions and improving the urban air quality in general.