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Summary: Background: Genome-wide association studies (GWAS) have revealed many brain disorder-associated SNPs residing in the noncoding genome, rendering it a challenge to decipher the underlying pathogenic mechanisms. Methods: Here, we present an unsupervised Bayesian framework to identify disease-associated genes by integrating risk SNPs with long-range chromatin interactions (iGOAT), including SNP-SNP interactions extracted from ∼500,000 patients and controls from the UK Biobank, and enhancer–promoter interactions derived from multiple brain cell types at different developmental stages. Findings: The application of iGOAT to three psychiatric disorders and three neurodegenerative/neurological diseases predicted sets of high-risk (HRGs) and low-risk (LRGs) genes for each disorder. The HRGs were enriched in drug targets, and exhibited higher expression during prenatal brain developmental stages than postnatal stages, indicating their potential to affect brain development at an early stage. The HRGs associated with Alzheimer's disease were found to share genetic architecture with schizophrenia, bipolar disorder and major depressive disorder according to gene co-expression module analysis and rare variants analysis. Comparisons of this method to the eQTL-based method, the TWAS-based method, and the gene-level GWAS method indicated that the genes identified by our method are more enriched in known brain disorder-related genes, and exhibited higher precision. Finally, the method predicted 205 risk genes not previously reported to be associated with any brain disorder, of which one top-risk gene, MLH1, was experimentally validated as being schizophrenia-associated. Interpretation: iGOAT can successfully leverage epigenomic data, phenotype–genotype associations, and protein–protein interactions to advance our understanding of brain disorders, thereby facilitating the development of new therapeutic approaches. Funding: The work was funded by the National Key Research and Development Program of China (2024YFF1204902), the Natural Science Foundation of China (82371482), Guangzhou Science and Technology Research Plan (2023A03J0659) and Natural Science Foundation of Guangdong (2024A1515011363).

In order to study the effect of magnesium salt (magnesium chloride hexahydrate + magnesium hydroxide) on the retarding characteristics of coal spontaneous combustion, the effects of inhibitor dosage and silane coupling agent on the characteristic temperature and thermal effect of coal spontaneous combustion were studied by synchronous thermal analysis and programmed heating-gas chromatography. The results of simultaneous thermal analysis showed that the inhibitory effect was relatively best when the magnesium salt inhibitor was added at 30%, the pyrolysis temperature T3 was delayed by 40 °C compared with the raw coal sample, and the total heat release was reduced by 165.14 J/mg. F@M30%·G resisted coal sample adding silane coupling agent mainly delayed the occurrence of coal pyrolysis and ignition, in which the pyrolysis temperature T3 was 49 °C higher than that of raw coal, and the ignition temperature T4 was increased by 26 °C. F@M30% inhibited coal samples can reduce the volume fraction of CO, and the effect of inhibiting spontaneous combustion of coal is gradually enhanced with the increase of temperature. After adding silane coupling agent, the volume fraction of CO of inhibited coal samples can be reduced by about 4×10-6. The inhibition rate of F@M30% inhibited coal samples is 30.87%, and that of F@M30%•G inhibited coal samples is as high as 91.57%.

Cyclists' willingness to ride is usually influenced by their subjective perception of the street riding environment. Measuring this perception is crucial for enhancing residents' willingness to ride. We propose an SSB framework (Public Security, Traffic Safety, Scenic Beauty) to quantify cyclists' subjective perception using street view imagery (SVI) and volunteer rating data. To address the issue of imbalanced class distribution in the volunteer rating data and enhance the model's ability to distinguish between positive and negative perception scenes, we employed a combination of the Kmeans Synthetic Minority Over-Sampling Technique (Kmeans-SMOTE) and the Random Forest (RF) classifier. The Kmeans SMOTE-RF model improved Area Under the Curve (AUC) by 0.327 for public safety, 0.2 for traffic safety, and 0.209 for scenic beauty compared to the RF model. Additionally, we incorporated Shapley Additive Explanations (SHAP) to examine how the visual features of SVI impact cyclists' subjective perception. Trees had a positive impact on all dimensions. Fence and sidewalk were key features for enhancing traffic safety perception, while roads positively affected public security and scenic beauty. These insights support urban planners in understanding the relationship between SVI features and cyclists' perceptions, aiding the design of cyclist-friendly street environments.

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Abstract BACKGROUND Mutations in the RAS‐MAPK pathway, such as KRAS, NRAS, and BRAF, are known as high‐risk factors associated with poor prognosis in patients with various cancers, but studies in myeloma have yielded mixed results. METHODS We describe the clinicopathologic, cytogenetic, molecular features, and outcomes of 68 patients with RAS/BRAF‐mutated myeloma, and compare with 79 patients without any mutations. RESULTS We show that KRAS, NRAS, and BRAF were mutated in 16%, 11%, and 5% of cases, respectively. RAS/BRAF‐mutated patients had lower hemoglobin and platelet counts, higher levels of serum lactate dehydrogenase and calcium, higher percentage of bone marrow plasma cells, and more advanced R‐ISS stage. RAS/BRAF mutations were associated with complex karyotype and gain/amplification of CKS1B. The median overall survival and progression‐free survival were significantly shorter for RAS/BRAF‐mutated patients (69.0 vs. 220.7 months, p = 0.0023 and 46.0 vs. 60.6 months, p = 0.0311, respectively). Univariate analysis revealed that KRAS mutation, NRAS mutation, lower hemoglobin, elevated lactate dehydrogenase, higher R‐ISS stage, complex karyotype, gain/amplification of CKS1B, monosomy 13/RB1 deletion and lack of autologous stem cell transplantation were associated with poorer prognosis. Multivariate analysis showed that KRAS mutation, lower hemoglobin level, higher level of serum calcium, higher ISS stage, and lack of autologous stem cell transplantation predict inferior outcome. CONCLUSIONS RAS/BRAF mutations occur in 30%–40% of myeloma cases and are associated with higher tumor burden, higher R‐ISS stage, complex karyotype, and shorter overall survival and progression‐free survival. These findings support testing for RAS/BRAF mutations in myeloma patients and underscore the potential therapeutic benefits of RAS/BRAF inhibitors.

Abstract Background Gliomas are highly refractory intracranial cancers characterized by genetic and transcriptional heterogeneity. However, therapeutic options are limited. In the last years, copper‐induced cell death is becoming a prospective treatment strategy for gliomas and other solid tumors, but copper metabolism‐related genes associated with cancer development remain unclear. Methods We first collected gene expression data from The Cancer Genome Atlas (TCGA) to identify significantly differentially expressed copper metabolism‐related genes in gliomas. Using these genes, we performed COX regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression to construct the prognostic model. The prognostic value of the model was further validated by CGGA testing set. Subsequently, functional analyses were carried out, including gene set enrichment analysis (GSEA), immune infiltration analysis, and mutation analysis. Finally, the expression levels of these genes were verified by immunohistochemical analysis. Results The prognostic model consisted of 7 genes: CDK1, LOXL2, LOXL3, NFE2L2, SLC31A1, SUMF1 and FDX1. According to this prognosis model, glioma patients could be split into the high‐risk group or low‐risk group, and the low‐risk group showed significantly better prognostic survival (p

Abstract Face clustering groups massive unlabeled face images according to their underlying identities and has proven to be a valuable tool for data analysis. Most recent studies have utilized graph convolutional networks (GCNs) to explore the structural properties of faces, thereby effectively achieving improved clustering performance. However, these methods usually suffer from computational intractability for large-scale graphs and tend to be sensitive to some postprocessing thresholds that serve to purify the clustering results. To address these issues, in this paper, we consider each pairwise relationship between two samples as a learning unit and infer clustering assignments by evaluating a group of pairwise connections. Specifically, we propose a novel clustering framework, named structure-enhanced pairwise feature learning (SEPFL), which mixes neighborhood information to adaptively produce pairwise representations for cluster identification. In addition, we design a combined density strategy to select representative pairs, thus ensuring training effectiveness and inference efficiency. The extensive experimental results show that SEPFL achieves better performance than other advanced face clustering techniques.

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

Spatial heterogeneity of human activities (SHHA) is part of the heterogeneity of urban ecosystems, which influences the understanding of ecological processes and landscape functions. Few ecological security pattern (ESP) studies have comprehensively measured SHHA and explicitly explained its effect on ESP planning. It affects the efficiency and landscape functions of ESP planning, leading to challenges in maximizing urban development and ecosystem benefits. In this study, Tencent user density (TUD) data considering human activity for all time periods and point of interest (POI) density with fine-scale human activity location information were fused by using wavelet transform as the spatial distribution of human activities. We applied it to correct the resistance surface for ESP planning, then proposed targeted restoration and conservation policies at a fine scale by combining human activities and POIs. The results revealed that the corrected resistance surface could approach the heterogeneous megacity for spatial and functional structures. More importantly, ESP planning based on the corrected resistance surface could enhance efficiency and landscape functions. This research strengthens our understanding of the effect of SHHA on ESP planning. It may provide important insights for policymakers concerning integrated human-natural systems in landscape planning.

Hemophilia A (HA, OMIM#306700) is an X-linked recessive bleeding disorder caused by the defects in the F8 gene, which encodes coagulation factor VIII (FVIII). Intron 22 inversion (Inv22) is found in about 45% of patients with severe hemophilia A. Here, we reported a male without obvious hemophilia A phenotype but bearing an inherited segmental variant duplication encompassing F8 as well as Inv22. The duplication was approximately 0.16 Mb and involved from exon 1 to intron 22 of F8. This partial duplication and Inv22 in F8 was first found in the abortion tissue of his older sister with recurrent miscarriage. The genetic testing of his family revealed that his phenotypically normal older sister and mother also had this heterozygous Inv22 and a 0.16 Mb partial duplication of F8, while his father was genotypically normal. The integrity of the F8 gene transcript was verified by sequencing of the adjacent exons at the inversion breakpoint, which explained why this male had no phenotype for hemophilia A. Interestingly, although he had no significant hemophilia A phenotype, the expression of C1QA in his mother, sister, and the male subject was only about half of that in his father and normal population. Our report broadens the mutation spectrum of F8 inversion and duplication and its pathogenicity in hemophilia A.

DUSP22 rearrangement (R) has been associated with a favorable outcome in systemic ALK-negative anaplastic large cell lymphoma (ALCL). However, a recent study found that patients with DUSP22-R ALK-negative ALCL have a poorer prognosis than was reported initially. In this study, we compared the clinicopathological features and outcomes of patients with ALKnegative ALCL with DUSP22-R (n=22) versus those without DUSP22-R (DUSP22-NR; n=59). Patients with DUSP22-R ALCL were younger than those with DUSP22-NR neoplasms (P=0.049). DUSP22-R ALK-negative ALCL cases were more often positive for CD15, CD8, and less frequently expressed pSTAT3Tyr705, PD-L1, granzyme B and EMA (all P0.05), but was significantly shorter than that of the patients with ALK-positive ALCL (median overall survival 53 months vs. undefined, P=0.005). Five-year overall survival rates were 40% for patients with DUSP22-R ALCL versus 82% for patients with ALK-positive ALCL. We conclude that DUSP22-R neoplasms represent a distinctive subset of ALK-negative ALCL. However, in this cohort DUSP22-R was not associated with a better clinical outcome. Therefore, we suggest that current treatment guidelines for this subset of ALK-negative ALCL patients should not be modified at present.

The oxygen content in high-silicon austenitic sulfuric acid-resistant stainless steels is one of the most detrimental parameters to their corrosion resistance. Based on the ion-molecular coexistence theory (IMCT), a thermodynamic model of the slag-steel reaction of austenitic stainless steel containing 5.0 wt% Si with CaF2-CaO-Al2O3-MgO-SiO2 pentabasic slag was developed to investigate the deoxidation reaction and the oxygen control mechanism of the steel. The model was validated through experiments proposed in this study. The results of the slag-steel reaction indicated that the equilibrium oxygen content was determined by the greater of two factors: w[O]%, Si obtained from the [Si]-[O] equilibrium reaction controlled by the activity of SiO2 and w[O]%, Al obtained from the [Al]-[O] equilibrium reaction controlled by the activity of Al2O3. The system temperature and the basicity of slag are the most crucial among the multiple variables affecting the equilibrium oxygen content compared with Al2O3 and CaF2 in slag. However, achieving an ultra-low oxygen steel, both a basicity of slag greater than two and a low activity of Al2O3 in slag should be maintained. The total oxygen content in steel can reach a minimum value of 3.4 ppm when the slag composition encompasses w(CaF2)% = 29.38, w(CaO)% = 44.07, w(SiO2)% = 14.69, w(MgO)% = 9.89, w(Al2O3)% = 1.96. The high basicity of slag reduces the total oxygen content of stainless steel, whereas the influence of redox reactions between Si and Al results in a higher Al content in steel and the formation of more inclusions during solidification. Thus, the optimal Al2O3 content is less than 4% and the optimal basicity is 2.4 during the refining process.

Introduction: About 2% of the population in the world are carriers of the thalassemia gene. Thalassemia is highly prevalent in Southern China, and traditional clinical testing methods would cause missed diagnosis of partial static thalassemia. Here, we reviewed and summarized a set of simple and clinically feasible thalassemia detection protocols adopted by the Prenatal Diagnosis and Reproductive Center of our hospital. Methods: From January 1, 2015, to December 31, 2020, 31 512 peripheral blood samples and 3828 prenatal samples were collected in our study. All the peripheral blood samples were performed through thalassemia screening by routine blood tests and hemoglobin electrophoresis and gene detection. The prenatal diagnosis would be implemented for the fetus if the parents were carriers of the same type of thalassemia. Results: A total of 6137 (19.48%) cases were diagnosed as thalassemia, in which 4749 (15.07%) were α-thalassemia, 1196 (3.80%) were β-thalassemia and 192 (0.61%) were co-inheritance of α- and β-thalassemia. For prenatal samples, 3160 (82.55%) cases were diagnosed as thalassemia, in which 2021 (52.80%) were α-thalassemia, 997 (26.05%) were β-thalassemia and 142 (3.71%) were co-inheritance of α- and β-thalassemia. In addition, we also found five novel mutations, including NC_000016.9:g.223681-227492del3812; HBA1: c.301-31_301-24delCTCGGCCCinsG; HBA2: c.95+7C>T for α-thalassemia and HBB: c.263_276delCACTGAGTGAGCTG; HBB: c.315+143G>A for β-thalassemia. Conclusion: The present study updates the epidemiological characteristics and mutation spectrum of thalassemia in Southern China and demonstrated five novel mutations. Our research provides a reference for clinical diagnosis and treatment, prenatal diagnosis, or reproductive genetic counseling for patients with thalassemia in Guangdong.

High-speed rail (HSR) has been proven to drive the development of regional tourism. However, few studies paid attention to the impact of HSR on future tourism land use. In this study, points of interest (POI) were used to obtain the locations and types of tourism facilities, and high-resolution remote sensing images helped us determine the spatial extents of the tourism facilities, so that tourism land could be identified. A system dynamics (SD) model was coupled with the patch-generating land use simulation (PLUS) model to simulate future tourism land by considering two scenarios, including HSR-led development (HRD) and the historical development pattern (HD) scenario. The SD model was employed to project the amount of tourism land and determine the HSR effects via empirical analysis. The PLUS model was applied to simulate the spatial distribution of tourism land and model the HSR effect by adopting a planned tourism area as the development area. The study area is Xinxing County in Guangdong Province, China, a county dominated by rural tourism, with the HSR expected to open in 2025. The results revealed that the SD-PLUS model has great advantages in simulating tourism land use change, and the HRD scenario leads to major changes in the sources of tourism land growth. This research provides new insights for policymakers on making countermeasures for the sustainability of tourism and rural revitalization at the county level.

The development of the county economy in China is a complicated process that is influenced by many factors in different ways. This study is based on multi-source big data, such as Tencent user density (TUD) data and point of interest (POI) data, to calculate the different influencing factors, and employed a multiscale geographically weighted regression (MGWR) model to explore their spatial non-stationarity impact on China’s county economic development. The results showed that the multi-source big data can be useful to calculate the influencing factor of China’s county economy because they have a significant correlation with county GDP and have a good models fitting performance. Besides, the MGWR model had prominent advantages over the ordinary least squares (OLS) and geographically weighted regression (GWR) models because it could provide covariate-specific optimized bandwidths to incorporate the spatial scale effect of the independent variables. Moreover, the effects of various factors on the development of the county economy in China exhibited obvious spatial non-stationarity. In particular, the Yangtze River Delta, the Pearl River Delta, and the Beijing-Tianjin-Hebei urban agglomerations showed different characteristics. The findings revealed in this study can furnish a scientific foundation for future regional economic planning in China.

Background: Large B-cell lymphoma with IRF4 rearrangement (LBCL-IRF4) is a rare subtype of large B-cell lymphoma characterized by strong and uniform IRF4/MUM1 expression resulting from IRF4 rearrangement, mostly with immunoglobulin heavy chain. LBCL-IRF4 was first included as a provisional entity in the revised 4th edition of WHO classification in 2017. Aim: To summarize the updated clinicopathological and cytogenetic molecular findings of LBCL-IRF4 and to help distinguish it from the other lymphomas which may cause diagnostic confusion. Methods: We reviewed: (1) the WHO Classification of Tumor of Hematopoietic and Lymphoid Tissues (4th edition, 2017); (2) the studies of LBCL-IRF4 available on PubMed including those published after the 4th edition of WHO Classification. We also described a case of LBCL-IRF4 including morphology, immunophenotype, and FISH result. Conclusion: LBCL-IRF4 can exhibit a spectrum of morphology and is characterized by strong and uniform IRF4/MUM1 expression. LBCL-IRF4 should be included in the differential diagnosis when a lymphoma has the morphology of diffuse large B-cell lymphoma and/or high-grade follicular lymphoma in the head and neck region of a young patient and coexpression of germinal center B-cell markers and strong IRF4/MUM1. LBCL-IRF4 responds well to chemotherapy and is associated with favorable prognosis.

Background: Primary testicular follicular lymphoma (TFL) is a rare extranodal variant of follicular lymphoma confined to the testis, almost exclusively occurring in children and young adults. TFL has unique clinicopathologic features and excellent prognosis. Distinction of TFL from other neoplasms involving testis and from systemic follicular lymphoma is essential due to major differences in management and outcome. Aim: We aimed to review and summarize the existing literature describing clinical, histopathologic, immunophenotypic and genetic features of TFL. We also include distinguishing characteristics of potential morphologic mimickers of TFL, including usual follicular lymphoma involving the testis as part of systemic disease. Methods: PubMed was searched for relevant studies before December 1, 2021, using keywords “primary testicular lymphoma”, “primary testicular follicular lymphoma” and “follicular lymphoma”. We selected and summarized the results of relevant studies. We also reviewed the latest WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. Conclusions: Primary testicular follicular lymphoma (TFL) is a unique extranodal variant of follicular lymphoma mainly presenting in children and young adults as stage 1E disease. Microscopically, TFL has a follicular or follicular and diffuse growth pattern and is composed predominantly of centroblasts. TFL characteristically lacks the t(14;18)/IGH-BCL2 and BCL2 protein overexpression. Optimal management is not well defined. Nevertheless, after unilateral orchiectomy combined with chemotherapy, TFL has shown excellent prognosis without recurrence. A focal diffuse large B-cell component does not appear to confer adverse prognosis.

With the consideration of the dynamic role of microRNAs (miRNAs) in breast cancer, miRNAs may serve as therapeutic targets, helping to prevent development of therapy resistance, maintain stable disease, and prohibit metastatic spread. We identified the differentially expressed breast cancer-related gene ribonucleotide reductase subunit M2 (RRM2) as the study focus through microarray expression profiles. Next, the upstream regulatory microRNA (miR)-4500 of RRM2 was predicted using bioinformatics website analysis, and their binding was verified by a dual luciferase reporter gene assay. The regulatory effects of miR-4500 on breast cancer cell proliferation, apoptosis, migration, invasion, and capillary-like tube formation of endothelial cells were assessed by gain- and loss-of-function experiments. The experimental data revealed that miR-4500 was downregulated, whereas RRM2 was upregulated in breast cancer cells. Mechanistic analysis revealed that miR-4500 downregulated the RRM2 expression to inactivate the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, miR-4500 exerted anti-tumor effects by targeting RRM2 through suppression of the MAPK signaling pathway in vitro, evidenced by attenuated cancer cell migration and invasion and capillary-like tube formation of endothelial cells. The in vivo experiments further corroborated in vitro results. Collectively, overexpressed miR-4500 could downregulate RRM2 and inhibit activation of the MAPK signaling pathway, thus attenuating breast cancer cell proliferation, invasion, migration, and angiogenesis and promoting breast cancer cell apoptosis.

Abstract Background In order to mitigate the risk of allele dropout (ADO) and ensure the accuracy of preimplantation genetic testing for monogenic disease (PGT-M), it is necessary to construct parental haplotypes. Typically, haplotype resolution is obtained by genotyping multiple polymorphic markers in both parents and a proband or a relative. Sometimes, single sperm typing, or tests on the polar bodies may also be useful. Nevertheless, this process is time-consuming. At present, there was no simple linkage analysis strategy for patients without affected relatives. Method To solve this problem, we established a haplotyping by linked-read sequencing (HLRS) method without the requirement for additional relatives. First, the haplotype of the genetic disease carriers in the family was constructed by linked-read sequencing, and then the informative single nucleotide polymorphisms (SNPs) in upstream and downstream mutation region were selected to construct the embryo haplotype and to determine whether the embryo was carrying the mutation. Two families were selected to validate this method; one with alpha thalassemia and the other with NDP gene disorder. Results The haplotyping by linked-read sequencing (HLRS) method was successfully applied to construct parental haplotypes without recruiting additional family members; the method was also validated for PGT-M. The mutation carriers in these families were sequenced by linked-read sequencing, and their haplotypes were successfully phased. Adjacent SNPs of the mutation gene were identified. The informative SNPs were chosen for linkage analyses to identify the carrier embryos. For the alpha thalassemia family, a normal blastocyst was transferred to the uterus and the accuracy of PGT-M was confirmed by amniocentesis at 16 weeks of gestation. Conclusions Our results suggest that HLRS can be applied for PGT-M of monogenic disorders or de novo mutations where the mutations haplotype cannot be determined due to absence of affected relatives.

Objective. To detect EGFR/KRAS genes in pleural effusion cell-free DNA in patients with advanced non-small-cell lung cancer (NSCLC) and to explore the clinical significance of EGFR/KRAS mutation status in pleural effusion. Methods. A retrospective collection was performed on the specimens of pleural effusion and matched tissues from 50 patients with advanced NSCLC admitted to the hospital between January 2019 and January 2021. DNA mutation status of EGFR/KRAS in different specimens was detected and compared by pyrosequencing. The clinicopathological data and follow-up data of survival were collected. The relationship between DNA mutation and clinicopathological characteristics and prognosis was analyzed. Results. In the 50 pleural effusion specimens, there were 22 cases (44.00%) with EGFR mutations (19/21 exon mutations), including 12 cases with EGFR19 deletion mutation and 10 cases with EGFR21 exon L858R mutation. There were 6 cases (12.00%) with KRAS mutations (single-base substitution mutations), including 4 cases with 12-codon mutation and 2 cases with 13-codon mutation. In the 50 tissue specimens, there were 24 cases (48.00%) with EGFR mutations and 4 cases (8.00%) with KRAS mutations. There was no significant difference between pleural effusion specimens and tissue specimens, with good consistency (kappa = 0.920–0.779, P>0.05). EGFR mutation in pleural effusion was related to smoking history, types of pathological tissues, and lymph node metastasis (P

Abstract The PM2.5 exposure risk assessment is the foundation to reduce its adverse effects. Population survey‐related data have been deficient in high spatiotemporal detailed descriptions. Social media data can quantify the PM2.5 exposure risk at high spatiotemporal resolutions. However, due to the no‐sample characteristics of social media data, PM2.5 exposure risk for older adults is absent. We proposed combining social media data and population survey‐derived data to map the total PM2.5 exposure risk. Hourly exceedance PM2.5 exposure risk indicators based on population modeling (HEPEpmd) and social media data (HEPEsm) were developed. Daily accumulative HEPEsm and HEPEpsd ranged from 0 to 0.009 and 0 to 0.026, respectively. Three peaks of HEPEsm and HEPEpsd were observed at 13:00, 18:00, and 22:00. The peak value of HEPEsm increased with time, which exhibited a reverse trend to HEPEpsd. The spatial center of HEPEsm moved from the northwest of the study area to the center. The spatial center of HEPEpsd moved from the northwest of the study area to the southwest of the study area. The expansion area of HEPEsm was nearly 1.5 times larger than that of HEPEpsd. The expansion areas of HEPEpsd aggregated in the old downtown, in which the contribution of HEPEpsd was greater than 90%. Thus, this study introduced various source data to build an easier and reliable method to map total exceedance PM2.5 exposure risk. Consequently, exposure risk results provided foundations to develop PM2.5 pollution mitigation strategies as well as scientific supports for sustainability and eco‐health achievement.

The background error variance in variational data assimilation can significantly affect a model’s initial field. Around extreme weather events, the variance of the unbalanced control variables have contributed highly to the total variance. This study investigates the effect of flow-dependent unbalanced variance on tropical cyclone (TC) forecasts using the ensemble of data assimilation (EDA) method. The analysis of TC Saudel (October 2020) shows that flow-dependent unbalanced variances can better represent the uncertainty in the background error, which is investigated in terms of magnitude and distribution. The vertical distribution of the temperature-explained variance ratio also shows that the contribution of the vorticity-balanced variance around Saudel is lower than the global average (in the troposphere). Single-observation experiments reveal that the structured flow-dependent errors of unbalanced control variables can also introduce corresponding structural information in analysis increments. As expected, the experiments in which the variances of all variables are flow-dependent in the one-month TC forecast performed better overall. Compared with the reference, these forecasts reduce the average absolute track and intensity errors by approximately 31% and 9%, respectively. The results demonstrate that EDA-based unbalanced variances can indeed improve the mean forecast skills of TC tracks and intensities despite instability at some lead times by improving the forecast of the circulation situation and providing a more appropriate balance relationship between variables.

Delineating urban growth boundaries (UGBs) by combining the land-use/land-cover (LULC) change simulation method has become common in recent studies. However, few of the existing studies have integrated multi-source big data to analyze the driving factors of LULC dynamics in the simulation. Moreover, most of previous studies mainly focused on the UGBs delineation in macroscale areas rather than small-scale areas, such as the county area. In this study, taking Xinxing County of Guangdong Province as the study area, we coupled a system dynamics (SD) model and a patch-generating land-use simulation (PLUS) model to propose a framework for the LULC change simulation and UGBs delineation in the county area. Multi-source big data such as points of interest (POIs), night-time light (NTL) data and Tencent user density (TUD) were integrated to analyze the driving forces of LULC change. The validation results indicate that the coupled model received high accuracy both in the land-use demand projection and LULC distribution simulation. The combination of multi-source big data can effectively describe the influence of human socio-economic factors on the expansion of urban land and industrial land. The UGBs delineation results have similar spatial patterns with the LULC change simulation results, which indicates that the proposed UGBs delineation method can effectively transform the LULC simulation results into available UGBs for the county area. It has been proven that the proposed framework in this study is effective for the LULC change simulation and UGBs delineation in the county area, which can provide insight on territorial spatial planning in the county area.

Abstract Hyperdiploidy (chromosomal number 51‐65) is a common cytogenetic abnormality in pediatric patients with B‐lymphoblastic leukemia (B‐ALL) and belongs to the favorable cytogenetic subgroup. Hyperdiploidy in adult B‐ALL is much less common and its clinical significance has not been well studied. Among the 1205 patients with B‐ALL (1018 adults and 187 children) from our institution, 78 had a hyperdiploid karyotype, including 45 (4.4%) adults and 33 (17.6%) children (P

The programmed death-ligands, PD-L1 and PD-L2, reside on tumor cells and can bind with programmed death-1 protein (PD-1) on T-cells, resulting in tumor immune escape. PD-1 ligands are highly expressed in some CD30+ large cell lymphomas, including classic Hodgkin lymphoma (CHL), primary mediastinal large B-cell lymphoma (PMBL), Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL), and anaplastic large cell lymphoma (ALCL). The genetic alteration of the chromosome 9p24.1 locus, the location of PD-L1, PD-L2, and JAK2 are the main mechanisms leading to PD-L1 and PD-L2 overexpression and are frequently observed in these CD30+ large cell lymphomas. The JAK/STAT pathway is also commonly constitutively activated in these lymphomas, further contributing to the upregulated expression of PD-L1 and PD-L2. Other mechanisms underlying the overexpression of PD-L1 and PD-L2 in some cases include EBV infection and the activation of the mitogen-activated protein kinase (MAPK) pathway. These cellular and molecular mechanisms provide a scientific rationale for PD-1/PD-L1 blockade in treating patients with relapsed/refractory (R/R) disease and, possibly, in newly diagnosed patients. Given the high efficacy of PD-1 inhibitors in patients with R/R CHL and PMBL, these agents have become a standard treatment in these patient subgroups. Preliminary studies of PD-1 inhibitors in patients with R/R EBV+ DLBCL and R/R ALCL have also shown promising results. Future directions for these patients will likely include PD-1/PD-L1 blockade in combination with other therapeutic agents, such as brentuximab or traditional chemotherapy regimens.

Coefficient of restitution is regarded as a dominating parameter in rockfall research. Generally, small-scale experiments were developed without considering interactions between boulder and slope. However, preimpact moving statuses are essential to evaluate rockfall behaviors. To reveal the effect of preimpact interactions on coefficient of restitution, energy dissipation considering initial velocity, surface type, and slope angle is executed based on medium-scale tests. The results show that (1) as the inclination of initial velocity, higher rebound height, and the declining normal coefficient of restitution occur, a determinable linear function could demonstrate relationships among energy dissipation and all coefficient of restitution; when initial velocity exceeds 5 m/s, the recovery ability shows and produces an increasing trend with respect to the variation of kinematic coefficient of restitution and kinetic energy coefficient of restitution. (2) As the surface material varies, slope hardness and rebound ability influence normal coefficient of restitution, and the surface roughness and rotation feature dominate tangential coefficient of restitution; considering preimpact slope and boulder interactions, four types of coefficient of restitution follow declining trend with different material sequence. (3) Slope angle affects normal coefficient of restitution, and tangential coefficient of restitution relatively descends 18% and inclines 10% when the angle ranges from 30° to 75°; regarding preimpact moving status, it differs from bounce times. The correlation between preimpact energy dissipation and four coefficients of restitution can be represented by the same decreasing linear function, when increasing the slope angle.

Platelet hyperactivity is the hallmark of diabetes, and platelet activation plays a crucial role in diabetic vascular complications. Recent studies have shown that upon activation, platelet-derived miRNAs are incorporated into vascular smooth muscle cells (VSMCs), regulating the phenotypic switch of VSMC. Under diabetes, miRNA deficiency in platelets fails to regulate the VSMC phenotypic switch. Therefore, manipulation of platelet-derived miRNAs expression may provide therapeutic option for diabetic vascular complications. We seek to investigate the effect of calpeptin (calpain inhibitor) on the expression of miRNAs in diabetic platelets, and elucidate the downstream signaling pathway involved in protecting from neointimal formation in diabetic mice with femoral wire injury model. Using human cell and platelet coculture, we demonstrate that diabetic platelet deficient of miR-223 fails to suppress VSMC proliferation, while overexpression of miR-223 in diabetic platelets suppressed the proliferation of VSMC to protect intimal hyperplasia. Mechanistically, miR-223 directly targets the insulin-like growth factor-1 receptor (IGF-1R), which inhibits the phosphorylation of GSK3β and activates the phosphorylation of AMPK, resulting in reduced VSMC dedifferentiation and proliferation. Using a murine model of vascular injury, we show that calpeptin restores the platelet expression of miR-223 in diabetes, and the horizontal transfer of platelet miR-223 into VSMCs inhibits VSMC proliferation in the injured artery by targeting the expression of IGF-1R. Our data present that the platelet-derived miR-223 suppressed VSMC proliferation via the regulation miR-223/IGF-1R/AMPK signaling pathways, and inhibition of calpain alleviates neointimal formation by restoring the expression of miR-223 in diabetic platelet.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic neoplasm whose immunophenotype remains incompletely characterized, particularly in terms of distinction from reactive plasmacytoid dendritic cells (PDCs). This limitation complicates detection of low-level involvement by BPDCN as well as minimal residual disease (MRD) assessment following therapy. We conducted the current study to characterize the immunophenotype of BPDCN in a cohort of 39 patients, and compared it to reactive PDCs. We found that, in addition to CD56 expression (97%), BPDCN showed a number of aberrancies, including decreased/negative CD38 (82%), positive CD7 (64%), negative CD2 (81%), negative CD303 (56%), increased HLA-DR (69%) and decreased CD123 (78%). Although BPDCN cells were characterized by CD56 expression, reactive PDCs consistently included a CD56-positive subset, ranging 1.3%-20% (median 4.5%) of total PDCs, challenging MRD detection. These CD56+ reactive PDCs, however, were consistently positive for CD2 and CD303, brightly positive for CD38, and negative for CD7, distinctively different from BPDCN. Based on these findings, we set up a 10-color flow cytometry assay for BPDCN and validated it to a sensitivity of 0.01%. This panel was prospectively tested in 19 bone marrow samples from 7 BPDCN patients, and it effectively distinguished BPDCN cells from background reactive PDCs in all cases. In summary, by understanding the immunophenotype of reactive and neoplastic PDCs, BPDCN can be effectively detected by flow cytometry to a very low level using a panel of markers in addition to CD56, and such assay can be used for initial bone marrow workup as well as MRD detection after therapy.

Mantle cell lymphoma (MCL) with MYC rearrangement (MYC-R) is rare and little is known about the importance of MYC extra copies (EC) in the absence of MYC-R in MCL patients. This study includes 88 MCL patients with MYC tested by fluorescence in situ hybridization and/or conventional cytogenetics, including 27 with MYC-R, 21 with MYC-EC, and 40 with normal (NL) MYC. MCL patients with MYC-R more often had blastoid/pleomorphic morphology; a higher frequency of CD10, MYC, and simultaneous MYC and BCL2 expression; a higher level of MYC; and a higher Ki67 proliferation rate (p

Low-grade myofibroblastic sarcoma (LGMS) is a rare, low-grade, malignant tumor and is mainly composed of myofibroblasts with varying degrees of differentiation. LGMS results in considerable diagnostic difficulty. We report a case of LGMS that occurred in multiple organs, including the diaphragmatic pleura, and head and neck region. A 34-year-old man was hospitalized in 2014 after coughing and shortness of breath for 10 days, and abdominal distension, abdominal pain, and bilateral lower extremity edema for 4 days. Before this admission, he had an abdominal tumor diagnosed in 1994 and 2003, a nasopharynx tumor in 2010, and a temporal lobe tumor in 2013. All tumors were resected surgically and the diagnosis was atypical fibrous histiocytoma and atypical fibrous xanthoma. Before surgeries for these tumors, no positron emission tomography-computed tomography (PET-CT) or whole-body scans were performed, and after surgery, there was no follow-up. After thoracoscopy and PET-CT after the most recent admission, the patient was diagnosed with LGMS with metastasis to the bone, nodes, and thoracic and abdominal cavities. The patient was discharged with albumin infusion treatment. Although LGMS is rare, it is potentially serious. Therefore, clinicians should be aware of such disease and make an early diagnosis and perform close follow-up.

PTEN loss has been associated with poorer prognosis in many solid tumors. However, such investigation in lymphomas is limited. In this study, PTEN cytoplasmic and nuclear expression, PTEN gene deletion, and PTEN mutations were evaluated in two independent cohorts of diffuse large B-cell lymphoma (DLBCL). Cytoplasmic PTEN expression was found in approximately 67% of total 747 DLBCL cases, more frequently in the activated B-cell–like subtype. Nuclear PTEN expression was less frequent and at lower levels, which significantly correlated with higher PTEN mRNA expression. Remarkably, loss of PTEN protein expression was associated with poorer survival only in DLBCL with AKT hyperactivation. In contrast, high PTEN expression was associated with Myc expression and poorer survival in cases without abnormal AKT activation. Genetic and epigenetic mechanisms for loss of PTEN expression were investigated. PTEN deletions (mostly heterozygous) were detected in 11.3% of DLBCL, and showed opposite prognostic effects in patients with AKT hyperactivation and in MYC rearranged DLBCL patients. PTEN mutations, detected in 10.6% of patients, were associated with upregulation of genes involved in central nervous system function, metabolism, and AKT/mTOR signaling regulation. Loss of PTEN cytoplasmic expression was also associated with TP53 mutations, higher PTEN-targeting microRNA expression, and lower PD-L1 expression. Remarkably, low PTEN mRNA expression was associated with down-regulation of a group of genes involved in immune responses and B-cell development/differentiation, and poorer survival in DLBCL independent of AKT activation. Collectively, multi-levels of PTEN abnormalities and dysregulation may play important roles in PTEN expression and loss, and that loss of PTEN tumor-suppressor function contributes to the poor survival of DLBCL patients with AKT hyperactivation.

Understanding the relationship between human activity patterns and urban spatial structure planning is one of the core research topics in urban planning. Since a building is the basic spatial unit of the urban spatial structure, identifying building function types, according to human activities, is essential but challenging. This study presented a novel approach that integrated the eigendecomposition method and k-means clustering for inferring building function types according to location-based social media data, Tencent User Density (TUD) data. The eigendecomposition approach was used to extract the effective principal components (PCs) to characterize the temporal patterns of human activities at building level. This was combined with k-means clustering for building function identification. The proposed method was applied to the study area of Tianhe district, Guangzhou, one of the largest cities in China. The building inference results were verified through the random sampling of AOI data and street views in Baidu Maps. The accuracy for all building clusters exceeded 83.00%. The results indicated that the eigendecomposition approach is effective for revealing the temporal structure inherent in human activities, and the proposed eigendecomposition-k-means clustering approach is reliable for building function identification based on social media data.

Mobile phone data is a typical type of big data with great potential to explore human mobility and individual portrait identification. Previous studies in population classifications with mobile phone data only focused on spatiotemporal mobility patterns and their clusters. In this study, a novel spatiotemporal analytical framework with an integration of spatial mobility patterns and non-spatial behavior, through smart phone APP (applications) usage preference, was proposed to portray citizens’ occupations in Guangzhou center through mobile phone data. An occupation mixture index (OMI) was proposed to assess the spatial patterns of occupation diversity. The results showed that (1) six types of typical urban occupations were identified: financial practitioners, wholesalers and sole traders, IT (information technology) practitioners, express staff, teachers, and medical staff. (2) Tianhe and Yuexiu district accounted for most employed population. Wholesalers and sole traders were found to be highly dependent on location with the most obvious industrial cluster. (3) Two centers of high OMI were identified: Zhujiang New Town CBD and Tianhe Smart City (High-Tech Development Zone). It was noted that CBD has a more profound effect on local as well as nearby OMI, while the scope of influence Tianhe Smart City has on OMI is limited and isolated. This study firstly integrated both spatial mobility and non-spatial behavior into individual portrait identification with mobile phone data, which provides new perspectives and methods for the management and development of smart city in the era of big data.

Abstract Anaplastic multiple myeloma (AMM) is a very rare morphologic variant of multiple myeloma with extremely poor prognosis. The anaplastic morphology of AMM may pose a diagnostic challenge. A thorough workup is critical in reaching the correct diagnosis.

Abstract Although MCC has been reported in patients with CLL/SLL, it is extremely rare to observe these two within the same tumor. MCC's positivity for PAX5 and TdT may pose a diagnostic challenge by mimicking transformed CLL/SLL. A thorough workup is critical in reaching the correct diagnosis.

EDA is a gene located at Xq13.1. It encodes different isoforms of tumor necrosis factor (TNF) superfamily member ectodysplasin A. Ectodysplasin A is a transmembrane protein which can be cleaved to form a secreted form and interact with EDA receptor to mediate the development of ectoderm. Mutations of the EDA gene are related to ectodermal dysplasia and tooth agenesis. Here, we report the establishment of the EDA gene knockout human embryonic stem (hES) cell line by CRISPR-Cas9 technology. This cell line provides good materials for further studies of the roles ectodysplasin A plays in ectoderm differentiation and tooth development.

Dockless bike sharing plays an important role in residents’ daily travel, traffic congestion, and air pollution. Recently, urban greenness has been proven to be associated with bike sharing usage around metro stations using a global model. However, their spatial associations and bike sharing usage on public holidays have seldom been explored in previous studies. In this study, urban greenness was obtained objectively using eye-level greenness with street-view images by deep learning segmentation and overhead view greenness from the normalized difference vegetation index (NDVI). Geographically weighted regression (GWR) was applied to fill the research gap by exploring the spatially varying association between dockless bike sharing usage on weekdays, weekends, and holidays, and urban greenness indicators as well as other built environment factors. The results showed that eye-level greenness was positively associated with bike sharing usage on weekdays, weekends, and holidays. Overhead-view greenness was found to be negatively related to bike usage on weekends and holidays, and insignificant on weekdays. Therefore, to promote bike sharing usage and build a cycling-friendly environment, the study suggests that the relevant urban planner should pay more attention to eye-level greenness exposure along secondary roads rather than the NDVI. Most importantly, planning implications varying across the study area during different days were proposed based on GWR results. For example, the improvement of eye-level greenness might effectively promote bike usage in northeastern and southern Futian districts and western Nanshan on weekdays. It also helps promote bike usage in Futian and Luohu districts on weekends, and in southern Futian and southeastern Nanshan districts on holidays.

Carbon included in coke and coal was used as a reduction agent and fuel in blast furnace (BF) ironmaking processes, which released large quantities of carbon dioxide (CO2). Minimizing the carbon consumption and CO2 output has always the goal of ironmaking research. In this paper, the reduction reactions of iron oxides by carbon, the gasification reaction of carbon by CO2, and the coupling reactions were studied by thermodynamic functions, which were derived from isobaric specific heat capacity. The reaction enthalpy at 298 K could not represent the heat value at the other reaction temperature, so the certain temperature should be confirmed by Gibbs frees energy and gas partial pressure. Based on Hess’ law, the energy consumption of the ironmaking process by carbon was calculated in detail. The decrease in the reduction temperature of solid metal iron has been beneficial in reducing the sensible heat required. When the volume ratio of CO to CO2 in the top gas of the furnace was given as 1.1–1.5, the coupling parameters of carbon gasification were 1.06–1.28 for Fe2O3, 0.71–0.85 for Fe3O4, 0.35–0.43 for FeO, respectively. With the increase in the coupling parameters, the volume fraction of CO2 decreased, and energy consumption and CO2 output increased. The minimum energy consumption and CO2 output of liquid iron production were in the reduction reactions with only CO2 generated, which were 9.952 GJ/t and 1265.854 kg/t from Fe2O3, 9.761 GJ/t and 1226.799 kg/t from Fe3O4, 9.007 GJ/t and 1107.368 kg/t from FeO, respectively. Compared with the current energy consumption of 11.65 GJ/t hot metal (HM) and CO2 output of 1650 kg/tHM of BF, the energy consumption and CO2 of ironmaking by carbon could reach lower levels by decreasing the coupled gasification reactions, lowering the temperature needed to generate solid Fe and adjusting the iron oxides to improve the iron content in the raw material. This article provides a simplified calculation method to understand the limit of energy consumption and CO2 output of ironmaking by carbon reduction iron oxides.

Energy, precision, and multi-functionality have become primary considerations in incubators. For example, if a part of an apparatus must be insulated, while other parts do not, then the specific part can be placed in the multi-functional incubator proposed in this paper to avoid wasting energy. The proposed incubator is composed of various parts including a platform, which is provided for debugging parts to meet the working accuracy of parts. The light windows are adjustable in height to accommodate different heights of light. The incubator is black to prevent stray light in optical experiments. This design can not only insulate but also debug optical or non-optical parts according working accuracy of parts. In this paper, an example incubator is used for an optical experiment was given and the incubator was optimized several times. The temperature fluctuations of the box of the third optimized incubator reached 0.045∘C. To reduce the temperature fluctuations, the relationship between the ambient and target temperature as well as the temperature fluctuations of the box were analyzed, and a formula was proposed. A further experiment provided evidence for this relationship. Based on the formula, the SLITA (small optimized incubator placed in large optimized incubator with the same target temperature) method for improving insulation accuracy was further proposed, and an incubator was designed using this method. The temperature fluctuations were 0.000014∘C by simulation, which was reduced 98.6% compared to previous incubators.

The reduction gas used in the gas-based direct reduction iron-making process contains CH4 in different concentrations, which has an important effect on the gas and heat needed for the reduction of iron oxide. To investigate the influence of CH4 on gas utilization rate and heat needed at 900 °C, the initial conditions are set as H2% + CO% = 90, CH4% + N2% = 10, gas pressure 1–9 atm, and 0.5 mol Fe2O3, and the equilibrium state composition is calculated using the minimum free energy method. The utilization rate of total gas can be improved, and gas demand can be decreased by increasing CH4 concentration or H2 concentration or reducing gas pressure. For the production of per ton of Fe from 25 °C to 900 °C, 6.08–7.29 m3 of reduction gas, and 7.338–8.952 MJ of gas sensible heat can be saved by increasing 1 m3 CH4, while 10.959–11.189 MJ of reaction heat is increased. Compared with 3390.828–3865.760 MJ of the total heat of per ton of Fe for the reduction by H2 + CO, 2.174–3.703 MJ of total heat is increased by increasing 1 m3 CH4, and the increase ratio is 0.065–0.096%. This study is helpful to improve the gas efficiency and lower the pursuit of higher concentration of H2 + CO in reduction gas.

Shrinkage and warping of additive manufacturing (AM) parts are two critical issues that adversely influence the dimensional accuracy especially in powder bed fusion processes such as selective laser sintering (SLS). Powder fusion, material solidification, and recrystallization are the key stages causing volumetric changes of polymeric materials during the abrupt heating–cooling process. In this work, the mechanisms of shrinkage and warping of semi-crystalline polyamide (PA) 12 in SLS are well investigated. Heat-transfer and thermo-mechanical models are established to predict the process-dependent shrinkage and warping. The influence of raw material- and laser-related parameters are considered in the heat-transfer and thermo-mechanical models. Such models are established considering the natural thermal gradient and dynamic recrystallization, which induce internal strain and volumetric change. Moreover, an experimental design via orthogonal approach is introduced to validate the feasibility and accuracy of the proposed models. Finally, the quantitative relationships of process parameters with product shrinkage and warping are established; the dimensional accuracy in part-scale can be well predicted and validated with printed parts in a real experiment.

In this study, high-purity iron with purity of 99.987 wt.% was prepared employing a process of direct reduction–melting separation–slag refining. The iron ore after pelletizing and roasting was reduced by hydrogen to obtain direct reduced iron (DRI). Carbon and sulfur were removed in this step and other impurities such as silicon, manganese, titanium and aluminum were excluded from metallic iron. Dephosphorization was implemented simultaneously during the melting separation step by making use of the ferrous oxide (FeO) contained in DRI. The problem of deoxidization for pure iron was solved, and the oxygen content of pure iron was reduced to 10 ppm by refining with a high basicity slag. Compared with electrolytic iron, the pure iron prepared by this method has tremendous advantages in cost and scale and has more outstanding quality than technically pure iron, making it possible to produce high-purity iron in a short-flow, large-scale, low-cost and environmentally friendly way.

Air pollution in the form of PM _2.5 decreases life expectancy considering its contribution to morbidity and mortality. Therefore, scientific and accurate PM _2.5 exposure risk assessment is essential. However, the considering daily/hourly mean PM _2.5 concentration and overlooking population mobility in exposure risk assessments result in underestimation of its adverse effects. Thus, using social media data and exceedance PM _2.5 concentration, two novel indicators named hourly exceedance PM _2.5 exposure (HEPE) and daily cumulative variation of exceedance PM _2.5 exposure (DCEPE) are developed in our study. Spatiotemporal variation analysis of HEPE showed that the first exceedance PM _2.5 exposure risk was observed at 10:00; this lasted till the end of the day. According to the standard deviation ellipse (SDE) method analysis results, at first, the major spatial tendency direction was northeast-southwest, with the average center (AE) located in the Yuangang Township. Then, the HEPE in the western study area increased dramatically. The major spatial tendency direction shifted from northeast-southwest to east-west. Consequently, the AE of HEPE shifted to central study area. The spatiotemporal variation characteristics led us to investigate the mechanisms. A bivariate LISA was applied to detect the spatial association between DCEPE and city functional zones (CFZs). Results showed that highly spatial associations were found between the DCEPE and CFZs in the southwest of the study area. Residential neighborhoods and transportation services showed a closer relationship with the spatial distribution of DCEPE. Based on these results, we found increasing public health threats posed by PM _2.5 . Thus, HEPE is an essential factor to assess air pollution exposure risk. Moreover, more attention should be paid to the spatial association between DCEPE and city functions, which is important for the development of air pollution mitigation strategies.