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This review presents a summary of recent progress in research on the N6-methyladenosine (m6A) modification and regulatory roles in hepatic lipid metabolism. As the most abundant internal modification of eukaryotic RNA, the m6A modification is a dynamic and reversible process of the m6A enzyme system, which includes writers, erasers, and readers. m6A methylation depressed lipid synthesis and facilitated lipolysis in liver. The depletion of m6A methyltransferase Mettl14/Mettl3 raised fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1), acetyl-CoA carboxylase (ACC), and elongase of very long chain fatty acids 6 (ELOVL6) in rodent liver, causing increases in liver weight, triglyceride (TG) production, and content in hepatocytes. FTO catalyzed m6A demethylation and the suppression m6A reader YTHDC2 promoted hepatocellular TG generation and hepatic steatosis in C57BL/6 mice through sterol regulatory element-binding protein 1c (SREBP-1c) signaling pathway, which upregulated the lipogenic genes FAS, SCD1, ACC, recombinant acetyl coenzyme a carboxylase alpha, and cell death-inducing DNA fragmentation factor-like effector C (CIDEC). Furthermore, FTO overexpression did not only enhance mitochondrial fusion to impair mitochondrial function and lipid oxidation but also promoted lipid peroxidation, accompanied by excessive TG in hepatocytes and rodent liver. Elevated m6A modification potently suppressed hepatic lipid accumulation, while the shrinkage of m6A modification arose hepatic lipid deposition. These findings have highlighted the beneficial role of m6A RNA methylation in hepatic lipid metabolism, potentially protecting liver from lipid metabolic disorders. [ABSTRACT FROM AUTHOR]

[Display omitted] Limited evidence exists on the effect of submicronic particulate matter (PM 1) on hypertension hospitalization. Evidence based on causal inference and large cohorts is even more scarce. In 2015, 36,271 participants were enrolled in South China and followed up through 2020. Each participant was assigned single-year, lag0–1, and lag0–2 moving average concentration of PM 1 and fine inhalable particulate matter (PM 2.5) simulated based on satellite data at a 1-km resolution. We used an inverse probability weighting approach to balance confounders and utilized a marginal structural Cox model to evaluate the underlying causal links between PM 1 exposure and hypertension hospitalization, with PM 2.5 -hypertension association for comparison. Several sensitivity studies and the analyses of effect modification were also conducted. We found that a higher hospitalization risk from both overall (HR : 1.13, 95% CI : 1.05–1.22) and essential hypertension (HR : 1.15, 95% CI : 1.06–1.25) was linked to each 1 µg/m3 increase in the yearly average PM 1 concentration. At lag0–1 and lag0–2, we observed a 17%–21% higher risk of hypertension associated with PM 1. The effect of PM 1 was 6%–11% higher compared with PM 2.5. Linear concentration-exposure associations between PM 1 exposure and hypertension were identified, without safety thresholds. Women and participants that engaged in physical exercise exhibited higher susceptibility, with 4%–22% greater risk than their counterparts. This large cohort study identified a detrimental relationship between chronic PM 1 exposure and hypertension hospitalization, which was more pronounced compared with PM 2.5 and among certain groups. [ABSTRACT FROM AUTHOR]

Familial cold autoinflammatory syndrome (FCAS) is the mildest subtype of cryopyrin-associated periodic syndrome (CAPS) and is a rare inherited systemic autoinflammatory disease (SAID). CAPS is the consequence of a rare group of genetic disorders that are mostly reported in European and American populations, but scarcely reported in Chinese populations. NLRP3, NLRP12, PLCG2, and NLRC4 are known pathogenic genes associated with FCAS, and the aim of this study was to identify pathogenic mutations in two intact pedigrees of Chinese FCAS. We performed Sanger sequencing of genomic DNA samples from 25 affected and 32 unaffected members of the two intact pedigrees and analyzed the pathogenic mutations for their conservativeness using multiple sequence alignment tools. In addition, we reviewed previously reported pathogenic genes of FCAS and their pathogenicity classification and summarized the characteristics of different genotypes and phenotypes of FCAS. This study reported two intact FCAS pedigrees with different genotypes and phenotypes, the heterozygous mutation (p.V72M) in NLRP3 in pedigree 1 and the heterozygous mutation (p.R754H) in NLRP12 in pedigree 2. There are no reports targeting p.V72M in NLRP3 in FCAS1, and there are relatively few relevant phenotypic data on the clinical manifestations identified in previous pedigrees. Multiple sequence comparisons of NLRP3 indicate that the p.V72M mutation is highly conserved during evolution. Our study has enriched the understanding of the pathogenesis of FCAS, a rare disease especially in Asian populations. Key Points: •The NLRP3 (p.V72M) variant was first discovered in the Chinese pedigree of FCAS1 •NLRP12 (p.R754H) variants are not conserved in multiple sequence alignments, but they are still co-segregated and expressed in the big Chinese diseased pedigree [ABSTRACT FROM AUTHOR]

Organ transplant recipients exhibit lower rates of immune response to coronavirus disease 2019 (COVID-19) vaccination. Even when they do mount a demonstrable antibody response, it is unclear what degree of protection is conferred against the myriad potential complications of COVID-19 infection. We present here a case of a kidney transplant recipient who was homozygous for APOL1 risk alleles on low-dose immunosuppression who developed an antibody response to COVID-19 vaccination and subsequently acquired COVID-19 infection. Although she experienced relatively minor effects in other organ systems, she developed severe collapsing focal segmental glomerulosclerosis that left her dependent on hemodialysis on hospital discharge. This suggests that COVID-19 vaccination may not provide protection from infection-associated focal segmental glomerulosclerosis in patients with APOL1 risk alleles. [ABSTRACT FROM AUTHOR]

With the continuous development in drilling and blasting technology, smooth wall blasting (SWB) has been widely applied in tunnel construction to ensure the smoothness of tunnel profile, diminish overbreak and underbreak, and preserve the tunnel's interior design shape. However, the complexity of the actual engineering environment and the deficiency of current optimization theories have posed certain challenges to the optimization of SWB parameters under arbitrary geological conditions, on the premise that certain control targets are satisfied. Against the above issue, a genetic algorithm (GA) and back propagation (BP) neural network-based computational model for SWB design parameter optimization is proposed. This computational model can comprehensively reflect the relation among geological conditions, design parameters, and results by training and testing the 285 collected sets of test data samples at different conditions. Moreover, it automatically searches optimal blasting design parameters through the control of SWB targets to acquire the optimal design parameters based on specific geological conditions of surrounding rocks and under the specified control targets. When the optimization algorithm is compared with other current optimization algorithms, it is shown that this algorithm has certain computational superiority over the existing models. When the optimized results are applied in practical engineering, it is shown that in overall consideration of the geological conditions, control targets, and other influencing factors, the proposed GA_BP-based model for SWB parameter optimization has high feasibility and reliability, and that its usage can be generalized to analogous tunneling works. [ABSTRACT FROM AUTHOR]

Background: We introduce a novel preoperative anatomic severity grading system for acute type B aortic dissections and validate the system in a cohort of patients who underwent thoracic endovascular aortic repair.Methods: We identified a cohort of patients who received thoracic endovascular aortic repair (TEVAR) for acute type B aortic dissection from 2008 to 2014. We developed an anatomic severity grading score (ASG) to measure attributes of aortic anatomy that we hypothesized may affect difficulty or durability of repair. Measurements were made using computed tomography angiography images and based on hypothesized severity, giving a potential score range of 0-38.Results: We analyzed the computed tomography angiography images on a cohort of 30 patients with acute type B aortic dissection who underwent TEVAR. We created an area under the receiver operating characteristic curve (AUROC) using anatomic severity grading to predict aortic-related reinterventions. The AUROC was 0.72 (95% CI 0.39 to 1.1). Guided by the AUROC, we divided patients into two groups: a low-score group with anatomic severity grading scores <23 (n = 22), and a high-score group with scores ≥23 (n = 8). With this cutoff, anatomic severity grading exhibited 80% sensitivity and 84% specificity in predicting aortic-related reinterventions, with reinterventions in 50% of high-score patients and 4.5% of low-score patients (P = 0.011). The high score group also had significantly greater blood loss (200 vs 100 mL, P = 0.038), fluoroscopy time (36.0 vs 16.6 min; P = 0.022), and a trend for increased procedure time (164 vs 95 min; P = 0.083) than the low-risk group. Kaplan-Meier analysis revealed that the high-score group had a significantly decreased freedom from aortic-related reinterventions than the low-score group (38% vs 100% at 12-month followup; log rank P = 0.001).Conclusions: A preoperative anatomic severity grading score for acute type B aortic dissections consists of analysis of the proximal landing zone, curvature and tortuosity of the aorta, dissection anatomy, aortic branch vessel anatomy, and supraceliac aorta anatomy. Anatomic severity grading scores ≤23 are an excellent predictor of aortic-related reinterventions. [ABSTRACT FROM AUTHOR]

The incidence and histological type of esophageal cancer are highly variable depending on geographic location and race/ethnicity. Here we want to determine if racial difference exists in the molecular features of esophageal cancer. We firstly confirmed that the incidence rate of esophagus adenocarcinoma (EA) was higher in Whites than in Asians and Blacks, while the incidence of esophageal squamous cell carcinoma (ESCC) was highest in Asians. Then we compared the genome-wide somatic mutations, methylation, and gene expression to identify differential genes by race. The mutation frequencies of some genes in the same pathway showed opposite difference between Asian and White patients, but their functional effects to the pathway may be consistent. The global patterns of methylation and expression were similar, which reflected the common characteristics of ESCC tumors from different populations. A small number of genes had significant differences between Asians and Whites. More interesting, the racial differences of COL11A1 were consistent across multiple molecular levels, with higher mutation frequency, higher methylation, and lower expression in White patients. This indicated that COL11A1 might play important roles in ESCC, especially in White population. Additional studies are needed to further explore their functions in esophageal cancer. [ABSTRACT FROM AUTHOR]

At synapses, the release of neurotransmitter is regulated by molecular machinery that aggregates at specialized presynaptic release sites termed active zones. The complement of active zone proteins at each site is a determinant of release efficacy and can be remodeled to alter synapse function. The small GTPase Rab3 was previously identified as playing a novel role that controls the distribution of active zone proteins to individual release sites at the Drosophila neuromuscular junction. Rab3 has been extensively studied for its role in the synaptic vesicle cycle; however, the mechanism by which Rab3 controls active zone development remains unknown. To explore this mechanism, we conducted a mutational analysis to determine the molecular and structural requirements of Rab3 function at Drosophila synapses. We find that GTP-binding is required for Rab3 to traffick to synapses and distribute active zone components across release sites. Conversely, the hydrolytic activity of Rab3 is unnecessary for this function. Through a structure-function analysis we identify specific residues within the effector-binding switch regions that are required for Rab3 function and determine that membrane attachment is essential. Our findings suggest that Rab3 controls the distribution of active zone components via a vesicle docking mechanism that is consistent with standard Rab protein function. [ABSTRACT FROM AUTHOR]

Conveyor belts are key pieces of equipment for bulk material transport, and they are of great significance to ensure safe operation. With the development of belt conveyors in the direction of long distances, large volumes, high speeds, and high reliability, the use of inspection robots to perform full inspections of belt conveyors has not only improved the efficiency and scope of the inspections but has also eliminated the dependence of the traditional method on the density of sensor arrangement. In this paper, relying on the wireless-power-supply orbital inspection robot independently developed by the laboratory, aimed at the problem of the deviation of the belt conveyor, the methods for the diagnosis of the deviation of the conveyor belt and FPGA (field-programmable gate array) parallel computing technology are studied. Based on the traditional LSD (line segment detection) algorithm, a straight-line extraction IP core, suitable for an FPGA computing platform, was constructed. This new hardware linear detection algorithm improves the real-time performance and flexibility of the belt conveyor diagnosis mechanism. [ABSTRACT FROM AUTHOR]

Background: Normothermic machine perfusion (NMP) provides a novel platform to preserve isolated organs in an artificial condition. Our study aimed to explore the interaction between the liver and kidney at an ex vivo organ level by adding a liver to the kidney NMP circuit. Methods: Porcine kidney and liver obtained from abattoir were subjected to 9 h NMP after suffering 30‐min warm ischemia time and 90‐min cold ischemia time. The liver–kidney NMP group (n = 5) and the single‐kidney NMP group (n = 5) were designed. During the NMP, perfusion parameters, blood gas analysis, and tissue samples were compared. Results: The perfusate of both groups remained stable, and continuous urine production was observed during NMP. In the liver–kidney NMP group, the lactate level was low, while blood urea nitrogen increased and glucose levels decreased. After the NMP, the renal tissue in the liver–kidney group exhibited fewer histological changes such as tubular epithelium vacuolization, along with reduced expression of IL‐6, IL‐8, IL‐1β, NLRP3, and GSDMD. Conclusions: Our results indicated that the expression of renal pro‐inflammatory factors was reduced in the liver–kidney NMP system. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "A novel anatomic severity grading score for acute Type B aortic dissections and correlation to aortic reinterventions after thoracic endovascular aortic repair" which appeared in the June 13, 2017 issue.

Limited evidence exists regarding the association between ambient temperature and blood pressure (BP) level of pregnant women. To investigate the associations of ambient temperature with maternal BP and hypertensive disorders of pregnancy (HDP), we studied 105,063 participants in 38 centers of 17 provinces from November 2017 to December 2021. BP was measured with standardized automated digital sphygmomanometers. Ambient temperature was classified into five classes as very hot, moderate hot, mild, moderate cold, and very cold. Generalized linear mixed models were used to investigate the ambient temperature-BP/HDP associations, controlling for multiple covariates. No significant associations of first-trimester ambient temperature with maternal BP and HDP prevalence were observed. Compared with mild temperature, second-trimester very cold and second-trimester moderate cold were statistically associated with the increase of 1.239 mmHg (95% CI: 0.908, 1.569) and 0.428 mmHg (95% CI: 0.099, 0.757) for second-trimester systolic blood pressure (SBP), respectively. Similar trends were also observed in the association between second-trimester cold exposure and second-trimester diastolic blood pressure (DBP), in the association between second-trimester cold exposure and third-trimester SBP/DBP as well as in the association between third-trimester cold exposure and third-trimester SBP/DBP although some estimates were not statistically significant. Furthermore, in the second and third trimester, very cold [second trimester: adjusted odds ratio (aOR) = 1.298; third trimester: aOR = 1.236) and moderate cold (second trimester: aOR = 1.208; third trimester: aOR = 1.146) exposures also increased the odds of HDP, and these associations were stronger among participants aged ≥35 years or from North China. The second and third trimesters are the critical exposure windows for ambient temperature exposure-BP/HDP associations. During this period, exposure to cold ambient temperature was associated with elevated BP as well as increased HDP prevalence among most Chinese pregnant women, those aged ≥35 years or from North China being more vulnerable. • This was a cross-sectional study of 105,063 pregnant women in China. • The 2nd and 3rd trimesters are critical windows for cold exposure-BP/HDP associations. • Cold exposure is positively associated with blood pressure and HDP prevalence. • Participants aged ≥35 years or from North China appeared to be more vulnerable. • Our study provides novel evidence on ambient temperature-BP/HDP associations. [ABSTRACT FROM AUTHOR]

This study examined the development of new or changes in donor specific antibodies (DSA) mean-fluorescence intensity (MFI) after SARS-CoV-2 vaccination in 100 kidney and 50 heart transplant recipients. The study was performed when the Center for Disease Control and Prevention (CDC) recommended two doses of Pfizer/BioNTech [BNT162b2] and Moderna [mRNA-1273 SARS-CoV-2] vaccine or 1 dose Johnson & Johnson/Janssen [Ad26.COV2·S] vaccines for full vaccination in transplant recipients. A novel assay bead-based platform for detecting antibodies against 4 domains of the SARS-CoV-2 spike protein to determine vaccine response (SA) and one nucleocapsid protein (NC) to determine prior SARS-CoV-2 infection was utilized. These assays were performed on the multiplex, bead-based platform utilized to assay DSA levels. 61/150 patients (40.7%) had successful vaccination. 18 patients had confirmed SARS-CoV-2 infection based on positive NC assay or previous Covid-19 oropharyngeal swab. 138 patients had no DSA prior to vaccination but 3 heart recipients developed new DSA's. Among 12 patients with known DSA prior to vaccination, 4 developed new DSA's or increased MFI. All 7 patients with new or increased DSA had stable graft function without rejection and had no changes in immunosuppression. All 8 patients with stable post vaccine DSA had stable graft function and immunosuppression was not changed. The presence of DSA before vaccination was associated with subsequent development of increased MFI or new DSA's (p = 0.001). There was no association between pre-vaccine DSA and positive vaccine response (NS). There was no association with successful vaccination or prior SARS-CoV-2 infection and DSA changes (NS). [ABSTRACT FROM AUTHOR]

The distinction between Keratoacanthoma (KA) and Cutaneous Squamous Cell Carcinoma (cSCC) is critical yet usually challenging to discriminate clinically and histopathologically. One approach to differentiate KA from cSCC is through assessing the immunohistochemical staining patterns of the three indicators, β-catenin, C-Myc, and CyclinD1, which are critical molecules that play important roles in the Wnt/β-catenin signaling pathway. Ki-67, as a proliferation biomarker for human tumor cells, was also assessed as an additional potential marker for differentiating KA from cSCC. In this report, these four indicators were analyzed in 42 KA and 30 cSCC cases with the use of the computer automated image analysis system. Computer automated image analysis is a time-based and cost-effective method of determining IHC staining in KA and cSCC samples. We found that C-Myc staining was predominantly localized in the nuclei of basal cells within KA patients, whereas cSCC staining was predominantly localized in the nuclei of diffuse cells. This C-Myc staining pattern has a sensitivity of 78.6% and a specificity of 66.7% for identifying KA. Moreover, positive rates of distinct expression patterns of C-Myc and Ki-67 may also serve as a means to clinically distinguish KA from cSCC. Taken together, our results suggest that these markers, in particular C-Myc, may be useful in differentiating KA from cSCC. [ABSTRACT FROM AUTHOR]

Background/aims: Psoriasis is a chronic immune‐mediated inflammatory skin disease characterized by excessive proliferation of keratinocytes. It has a strong genetic predisposition; gene‐gene interactions are important genetic models for common diseases. In this study, we explore pair‐wise interactions among SNPs contributing to psoriasis susceptibility. Methods: We first performed gene interactions with exome‐sequencing, next, we analyzed gene interactions combining the exome sequencing data with the targeted sequencing data. After we sequenced HLA region, we analyzed gene interactions including HLA regions and non‐HLA regions. Results: We found interactions between HLA regions were significant. We observed significant interactions between HLA‐C*06:02 and rs118179173 (snp31443520; p = 8.21 × 10−20, OR = 0.22) and between HLA‐C*06:02 and HLA‐B:AA67 (p = 1.22 × 10−12, OR = 0.45). Conclusion: This study provides evidence that HLA is the most important susceptibility region on the risk of psoriasis and interactions that occur in this region are still significant. [ABSTRACT FROM AUTHOR]

Background: Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods: Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results: A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion: Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene. [ABSTRACT FROM AUTHOR]

Aims and Objectives: To determine the health‐related quality of life (HRQoL) of COVID‐19 patients after discharge and its predicting factors. Background: COVID‐19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID‐19 patients are impaired, but the studies focus on physical and psychological conditions of COVID‐19 patients after discharge from hospital are rare. Design: A multicentre follow‐up study. Methods: This was a multicentre follow‐up study of COVID‐19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow‐up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist. Results: Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID‐19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm (p <.001). Results of logistic regression showed that female (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.04–3.06), older age (≥60 years) (OR: 2.44, 95% CI: 1.33–4.47) and the physical symptom after discharge (OR: 40.15, 95% CI: 9.68–166.49) were risk factors for poor physical component summary; the physical symptom after discharge (OR: 6.68, 95% CI: 4.21–10.59) was a risk factor for poor mental component summary. Conclusions: Health‐related quality of life of discharged COVID‐19 patients did not come back to normal at third month after discharge and affected by age, sex and the physical symptom after discharge. Relevance to clinical practice: Healthcare workers should pay more attention to the physical and psychological rehabilitation of discharged COVID‐19 patients. Long‐term follow‐up on COVID‐19 patients after discharge is needed to determine the long‐term impact of COVID‐19. [ABSTRACT FROM AUTHOR]

With limited evidence on the neurological impact of particulate matter (PM) exposure in China, particularly for PM 1 which is smaller but more toxic, we conducted a large Chinese cohort study using causal inference approaches to comprehensively clarify such impact. A total of 36,271 participants in southern China were recruited in 2015 and followed up through 2020. We obtained the neurological hospitalizations records by linking the cohort data to the electronic reports from 418 medical institutions across the study area. By using high-resolution PM concentrations from satellite-based spatiotemporal models and the cohort data, we performed marginal structural Cox models under causal assumptions to assess the potential causal links between time-varying PM exposure and neurological hospitalizations. Our findings indicated that increasing PM 1 , PM 2.5 , and PM 10 concentrations by 1 μg/m³ were associated with higher overall neurological hospitalization risks, with hazard ratios (HRs) of 1.10 (95% confidence interval (CI) 1.04–1.16), 1.09 (95% CI 1.04–1.14), and 1.03 (95% CI 1.00–1.06), respectively. PM 1 appeared to have a stronger effect on neurological hospitalization, with a 1% and 7% higher impact compared to PM 2.5 and PM 10 , respectively. Additionally, each 1-μg/m3 increase in the annual PM 1 concentration was associated with an elevated risk of hospitalizations for ischemic stroke (HR : 1.15; 95% CI , 1.06–1.26), which tended to be larger than the estimates for PM 2.5 (HR : 1.13, 95% CI , 1.04–1.23) and PM 10 (HR : 1.05, 95% CI , 1.00–1.09). Furthermore, never-married or female individuals tended be at a greater risk compared with their counterparts. Our study provides important insights into the health impact of particles, particularly smaller particles, on neurological hospitalization risk and highlights the need for clean-air policies that specifically target these particles. [Display omitted] • Long-term exposure to PMs increased the risk of neurological hospitalizations. • The hazard ratio for PM 1 tends to be greater on neurological hospitalization. • Long-term exposure to PMs enhanced the risk of ischemic stroke hospitalization. • Unmarried residents might be more vulnerable than their counterparts. • Causal inference models with time-varying exposure minimized confounding bias. [ABSTRACT FROM AUTHOR]

• Higher all-cause mortality was attributed to greater PM 1 , PM 2.5 and PM 10 exposure. • The risk from PM 1 tends to be 1.1% and 1.3% greater than that from PM 2.5 and PM 10. • The elderly, unmarried and less educated ones were more vulnerable to the impact of PMs. • Participants generally at low PM exposures were more susceptible than others. The association between long-term particulate matter (PM) exposure and all-cause mortality has been well-documented. However, evidence is still limited from high-exposed cohorts, especially for PM 1 which is smaller while more toxic than other commonly investigated particles. We aimed to examine the potential casual links of long-term PMs exposure with all-cause mortality in high-exposed areas. A total of 580,757 participants in southern China were enrolled during 2009–2015 and followed up to 2020. The annual average concentration of PM 1 , PM 2.5 , and PM 10 at 1 km2 spatial resolution was assessed for each residential address through validated spatiotemporal models. We used marginal structural Cox models to estimate the PM-mortality associations which were further stratified by sociodemographic, lifestyle factors and general exposure levels. 37,578 deaths were totally identified during averagely 8.0 years of follow-up. Increased exposure to all 3 PM size fractions were significantly associated with increased risk of all-cause mortality, with hazard ratios (HRs) of 1.042 (95 % confidence interval (CI): 1.037–1.046), 1.031 (95 % CI: 1.028–1.033), and 1.029 (95 % CI: 1.027–1.031) per 1 μg/m3 increase in PM 1 , PM 2.5 , and PM 10 concentrations, respectively. We observed greater effect estimates among the elderly (age ≥ 65 years), unmarried participants, and those with low education attainment. Additionally, the effect of PM 1 , PM 2.5 , and PM 10 tend to be higher in the low-exposure group than in the general population. We provided comprehensive evidence for the potential causal links between long-term PM exposure and all-cause mortality, and suggested stronger links for PM 1 compared to large particles and among certain vulnerable subgroups. [ABSTRACT FROM AUTHOR]

Summary Gastrulation of the mouse embryo entails progressive restriction of lineage potency and the organization of the lineage progenitors into a body plan. Here we performed a high-resolution RNA sequencing analysis on single mid-gastrulation mouse embryos to collate a spatial transcriptome that correlated with the regionalization of cell fates in the embryo. 3D rendition of the quantitative data enabled the visualization of the spatial pattern of all expressing genes in the epiblast in a digital whole-mount in situ format. The dataset also identified genes that (1) are co-expressed in a specific cell population, (2) display similar global pattern of expression, (3) have lineage markers, (4) mark domains of transcriptional and signaling activity associated with cell fates, and (5) can be used as zip codes for mapping the position of single cells isolated from the mid-gastrula stage embryo and the embryo-derived stem cells to the equivalent epiblast cells for delineating their prospective cell fates. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic skin disorder with undefined pathogenesis. Several biomarkers for this disease have been identified by proteomic analysis. We explored the whole-proteomic changes in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. A total of 3686 proteins were identified, of which 3008 were quantified. A total of 102 and 124 proteins were upregulated and downregulated in lesional skin, respectively. SART1 (P = 3.55 × 10−5) and GLTP (P = 1.54 × 10−3) were the most significantly down- and upregulated proteins. Nearly 90% of these differentially regulated proteins exhibited the same expression trends as those in an online RNA sequencing dataset for psoriasis; 19 differentially regulated proteins exhibited a negative relationship with DNA methylation data for psoriatic lesions. The differentially expressed proteins were enriched in ribosomes, antigen processing and presentation, immune response, and IL-17 signalling pathways. This study identified multiple differentially regulated proteins in psoriatic lesions, which suggested that changes in the proteome play important regulatory roles in psoriasis-associated processes. Proteomic analysis was performed in 45 pairs of psoriatic and adjacent noninvolved skin tissues in a Chinese population. More than 3000 proteins were quantified, of which 226 were differentially expressed in psoriatic skin tissues. These proteins were mainly enriched in the immune response, antigen processing and presentation and IL-17 signalling pathways, which have been reported to be associated with the pathogenesis of psoriasis. Graphical abstract [Display omitted] • The technology of TMT labeling and LC-MS/MS was used to explore DEPs in skin lesions in a Chinese population. • A total of 3008 proteins were quantified, among which 102 and 124 were up- and down-regulated in psoriatic lesions. • Antigen processing and presentation, ribosome and IL-17 signalling were enriched with up-regulated proteins. [ABSTRACT FROM AUTHOR]

Lysine 2-hydroxyisobutyrylation is a newly discovered posttranslational modification. Although this modification is an important type of protein acylation, its role in psoriasis remains unstudied. We compared lesional and nonlesional psoriasis skin samples from 45 psoriasis patients. The result showed that this highly conserved modification was found in large quantities in both normal and diseased dermal tissues. However, there were a number of clear and significant differences between normal and diseased skin tissue. By comparing, lysine 2-hydroxyisobutyrylation was upregulated at 94 sites in 72 proteins and downregulated at 51 sites in 44 proteins in lesional skin. In particular, the sites with the most significant downregulation of lysine 2-hydroxyisobutyrylation were found in S100A9 (ratio = 0.140, p -value =.000371), while the most upregulated site was found in tenascin (ratio = 3.082, p-value =.0307). Loci associated with psoriasis, including FUBP1, SERPINB2 and S100A9, also exhibited significant regulation. Analyses of proteome data revealed that SERPINB2 and S100A9 were differentially expressed proteins. And bioinformatics analysis suggest that the P13K-Akt signaling pathway was more enriched with lysine 2-hydroxyisobutyrylation in lesional psoriasis skin. Our study revealed that lysine 2-hydroxyisobutyrylation is broadly present in psoriasis skin, suggesting that this modification plays a role in psoriasis pathogenesis. A newly discovered protein posttranslational modification, lysine 2-hydroxyisobutyrylation, has been found to occur in a wide variety of organisms and to participate in some important metabolic processes. In this study, lysine 2-hydroxyisobutyrylation in lesional psoriasis skin and nonlesional psoriasis skin was quantified and compared for the first time. We found a number of differentially modified proteins and sites in our comparisons. Interestingly, some of the identified proteins and pathways with significantly different modifications, such as S100A9 and the PI3K-Akt signaling pathway, have been previously reported to be associated with psoriasis. We hope that this research will provide new insights into psoriasis. Unlabelled Image • For the first time, the occurrence of K hib in skin tissues from patients with psoriasis was quantified and detected. • Significant differences in K hib between lesional psoriasis skin and nonlesional psoriasis skin were found. • Many of the differentially modified proteins we found have previously been reported to be associated with psoriasis. • The results of this study will provide new insights for studies on psoriasis in the future. [ABSTRACT FROM AUTHOR]