The landscape and clinical relevance of intronic polyadenylation in human cancers.

Intronic polyadenylation (IPA) is an RNA 3' end processing event which has been reported to play important roles in cancer development. However, the comprehensive landscape of IPA events across various cancer types is lacking. Here, we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas (TCGA) project. We totally identify 21,835 IPA events, almost half of which are ubiquitously expressed. We identify 2,761 unique dynamically changed IPA events across cancer types. Furthermore, we observe 8,855 non-redundant clinically relevant IPA events, which could potentially be used as prognostic indicators. Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response. Finally, we develop a user-friendly data portal, IPACancer Atlas (http://www.tingni-lab.com/Pancan_IPA/), to search and explore IPAs in cancer.

Exploring trade-offs between residential and industrial functions in rural areas and their ecological impacts across transitioning agricultural systems: Evidence from the metropolitan suburbs of China.

The rapid transition of agricultural systems substantially affects residential and industrial land use systems in rural areas, often generating spatiotemporal trade-offs between residential and industrial functions and producing considerable ecological impacts, which has thus far not been well understood. We conduct an indicator-based assessment of transitioning agriculture systems, and then links the transitioning agricultural systems to trade-offs between residential and industrial functions from 2005 to 2020 by using a case study-the metropolitan suburbs of Beijing, China. Also, the associated ecological impacts of the trade-offs are characterized based on the calculation of the ecological quality index (EQI) and ecological contribution rate. The results show that trade-offs between residential and industrial functions in the metropolitan suburbs have gradually adapted to the different agricultural systems in transition, which can be characterized by increasing industrial function as well as declining residential function, together with the diversification of land use into a mixed pattern. Additionally, along with the transitioning process comes a U shape of the ecological quality curve, which indicates that relentless industrial sprawl into regions where the agricultural system has a low capacity for technology, as well as decay in rural areas attributed to a rural exodus and industrial decline in semi-subsistence agricultural areas, even cause ecological degradation. In general, trade-offs between residential and industrial functions (especially for the non-agricultural production function) in rural areas could partially and temporally generate unfavorable ecological impacts, but it seems to be a favorable phenomenon to promote ecological quality in the long term. Therefore, to achieve rural sustainable planning, it is necessary for land use management to observe the trade-offs between residential and industrial functions while avoiding negative impacts, such as low-density land use patterns, disordered land use functions, and eco-environmental deterioration. Such effective strategies can contribute to the feasible implementation of policies aiming to achieve the compatible development of liveable residences, highly efficient industrial production, and eco-friendly operations in rural areas.

Water quality and microecosystem of water tanks in karst mountainous area, Southwest China.

Karst mountainous areas in Southwest China, the world's largest bare karst area, are faced with growing water shortages. Rainwater harvesting plays an important role in alleviating water shortage. However, there remains a substantial gap in the research regarding the water quality of tanks. Water samples were seasonally collected from ten tanks to investigate the physicochemical properties, microbial communities, and their key influencing factors. The result showed that pH, turbidity, chroma, DOC, and CODMn exceeded drinking water guidelines. The alkaline pH value and the deterioration of sensory properties was the main feature of tank water, from which the over-standard rate of the uncleaned water tanks was higher. Moreover, principal component analyses suggested that tank water quality was influenced by human activities, catchment areas, and material cycling processes within the tanks, of which in-tank microbial activities were the most important driving factors in water quality variation. Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, and Verrucomicrobia were the predominant bacterial phyla in water tanks. Acinetobacter, Cyanobium-PCC-6307, CL500-29-marine-group, Candidatus-Aquiluna, and Exiguobacterium were the most abundant genera. The bacterial communities were significantly affected by the management practices. Higher relative abundance of Cyanobacteria and lower relative abundance of Proteobacteria was detected in the uncleaned tanks, which was a sign of tank water quality deterioration. The microbial community structure was closely related to the environmental factors. There was evidence that the water quality was affected by the existence of a microecosystem dominated by photosynthetic microorganisms in the water tanks. In addition, Acinetobacter, Enterobacter, Pseudomonas, and Legionella identified as the potential opportunistic pathogenic genera were frequently detected but the relative abundances except Acinetobacter were low in the tanks. Overall, our findings indicated that management style influences water quality and bacterial communities of tank water.

Based on bound water characteristics study of microporosity characteristics and mechanical properties evolution of copper-contaminated laterite.

The potential impact of heavy metal ion infiltration on macroscopic and microscopic soil properties is a subject of academic interest. Laterite has an extensive distribution in southern China and is extensively utilized as a vertical containment wall for landfills. Consequently, there is a need to investigate how heavy metal ions affect laterite's microstructure and mechanical properties. To examine the impact of Cu2+ on laterite's microporous characteristics and mechanical properties, laboratory tests were conducted on the permeability, shear strength, microporous characteristics, and strong absorbed water content of Cu2+-contaminated laterite. The results show that Cu2+ hydrolysis generates an acidic environment, which leads to erosion of the cementing substance between the laterite particles, increasing the laterite's porosity and decreasing the soil's cohesive strength, thus affecting the shear strength and permeability of the laterite. When the concentration of Cu2+ is 5.0 g/L, the laterite demonstrated the most significant decrease in shear strength, 43.01%, while the permeability coefficient increased from 3.24 × 10-8 cm/s to 1.32 × 10-7 cm/s. Meanwhile, Cu2+ changes the content of strong absorbed water in laterite. The change of strong absorbed water content will affect the Van der Waals between laterite particles, promote the evolution of soil micropore structure, and lead to a decrease in the proportion of intra-aggregate pores (d < 1 µm) and an increase in the proportion of inter-aggregate pores (1 µm < d < 10 µm), which in turn affects the macroscopic shear strength and permeability. This study has improved our understanding of the mechanisms underlying the microporosity and mechanical property evolution of laterite when subjected to heavy metal attack.

Association of atherogenic index of plasma with early neurological deterioration in patients with acute ischemic stroke.

PURPOSE: To explore the correlation between Atherogenic Index of Plasma (AIP) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). METHODS: A retrospective analysis of 334 patients diagnosed with AIS between January 2021 and May 2023 at the Affiliated Huai'an Hospital of Xuzhou Medical University. Patients were divided into END and non-END groups based on changes in National Institutes of Health Stroke Scale scores (NIHSS) within 7 days of admission, and the differences in the indicators between the two groups were examined using univariate analysis. The patients were then divided into three groups based on the tertile of the AIP (T1: AIP≤ -0.01; T2: 0 ≤AIP≤0.16; AIP≥0.17), and logistic regression analysis was used to examine the association between the AIP and END. Finally, the predictive ability of the AIP was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: A total of 334 patients were included, of which 64 (19.20%) had END. The results of the analysis showed that the AIP was significantly higher in the END group compared to the non-END group. Multivariable logistic regression analysis showed that higher AIP was associated with END in AIS patients (OR=3.259, 95%CI, 1.490-7.125, P = 0.003), especially in large-artery atherosclerosis (LAA) subtype (OR=4.240, 95%CI,1.30-13.87, P = 0.017). ROC analysis revealed that the best predictive cutoff value of AIP was 0.115, and the area under the ROC curves for AIP was 0.681(0.604-0.758). CONCLUSION: Our study uncovered that higher AIP levels were associated with END development in AIS patients.

Predictive effects of S100ß and CRP levels on hemorrhagic transformation in patients with AIS after intravenous thrombolysis: A concise review based on our center experience.

Hemorrhagic transformation (HT) is one of the most dangerous complications after intravenous thrombolysis in patients with acute ischemic stroke (AIS). Therefore, we want to explore the predictive effects of peripheral blood S100ß and C-Reactive Protein (CRP) levels on hemorrhagic transformation after intravenous thrombolysis in AIS patients. Ninety-two AIS patients who had been treated in Huai'an Second People's Hospital from January 2018 to December 2021 were retrospectively selected. Patients were divided into hemorrhagic transformation (HT) groups (24 cases) and no HT groups (68 cases) based on whether there was hemorrhagic transformation within 24 h after intravenous thrombolysis. General clinical data from the HT group and no HT group were compared. A multivariate logistic regression model was used to analyze the potential risk factors of HT after intravenous thrombolysis in patients with AIS. A receiver operating curve (ROC) was used to analyze the predictive value of risk factors for HT. High serum S100ß, CRP levels, and National Institutes of Health Stroke Scale (NIHSS) scores were found to be risk factors for HT after intravenous thrombolysis in patients with AIS (all P < .05). The ROC curve analysis showed that critical value of S100ß, CRP level, and NIHSS score for predicting intravenous thrombolytic HT in AIS patients were 0.335, 8.700, and 14.50, respectively, and their sensitivities were 0.750, 0.971, and 0.333 ( P < .05), respectively. High serum S100ß and CRP levels are risk factors for HT after intravenous thrombolysis in AIS patients and have predictive influence of the occurrence of HT in AIS patients.

Increased Serum S100ß Concentration is Associated with Depression in Parkinson's Disease.

Purpose: To explore the relationship between the serum level of S100 calcium-binding protein, beta chain (S100ß) and Parkinson's disease (PD) with depression. Patients and Methods: A total of 145 patients with PD and 60 healthy controls matched for sex, age, and years of education in our hospital were selected. Fluorescence quantitative immunochromatography was used to quantify the level of S100ß in serum. Clinical manifestations were assessed by Unified Parkinson's Disease Rating Scale part-III (UPDRS-III), Hoehn & Yahr (H-Y) stage and 17-item Hamilton Rating Scale for Depression (HAMD-17). According to the results of HAMD-17, PD patients were divided into PD with depression group and PD without depression group. The relationship between serum S100ß and HAMD-17 scores in PD patients with depression was investigated through correlation analysis and multivariate regression analysis, and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum S100ß. Results: The level of serum S100ß in PD with depression group was significantly higher than that in PD without depression group and control group. In PD patients with depression, serum S100ß level was positively correlated with UPDRS-III score, H-Y Scale and HAMD-17 score. The HAMD-17 score was positively correlated with the UPDRS-III and H-Y scales, and the increase in the HAMD-17 score was associated with women. Elevated serum S100ß level and UPDRS-III score are independent risk factors for PD with depression. Analysis of receiver operating characteristic (ROC) curves showed that the serum S100ß level with a cutoff of 0.28 ng/mL distinguished patients with PD with or without depression with an area under the ROC curve (AUC) of 0.742, sensitivity of 0.696, and specificity of 0.779. Conclusion: The serum S100ß level could be a biomarker of PD with depression.

Characterizing the transitory groundwater-surface water interaction and its environmental consequence of a riverside karst pool.

Exchange between groundwater (GW) and surface water (SW) is a common occurrence in karst water systems through sinking stream disappearance or groundwater emergence. However, the transitory GW-SW interaction caused by river backflowing into a spring is poorly observed and understood. In this study, we present an approach for characterizing the influence of GW-SW interaction in a karst spring by integrating high-resolution hydrology, carefully selected hydrochemistry monitoring and precise microbe measurements. The spring-fed pool water conditions can be distinguished as high, medium, and low-water level periods in a hydrological year. The high-water level accounts for <1 % in a year, while it is associated with the hydrological regimes of backflooding states. The inflow of river backflow was found to be 4.4 times that of the natural discharge of spring water during a rainfall event. The duration of river intrusion into the spring or karst conduit could be assessed by jointly interpreting hydrography and physicochemical signatures, while the lasting environmental consequences should be evaluated together with biotic factors such as Escherichia coli. The GW-SW interaction induced by river backflow has led to the retention of river water in a pool, spring, and karst conduit for 132, 94, and 56 h, respectively. Despite turbidity returning to normal levels after 56 h, E.coli continued to persist for an extended duration. Our study reveals that despite the transient nature of GW-SW induced by river backflow on the hydrograph, they present a lasting risk of contamination from heavy metals, organic matter, and microorganisms. This extended influence can persist within a karst aquifer lacking a hyporheic zone. This research contributes to the quantification of processes involved in transitory GW-SW interaction in a karst spring, and it highlights the underestimation of GW-SW interactions in karst water systems, which might negatively impact water resources management.

Structural characteristics of a novel Bletilla striata polysaccharide and its activities for the alleviation of liver fibrosis.

Liver fibrosis has proven to be the main predisposing factor for liver cirrhosis and liver cancer; however, an effective treatment remains elusive. Polysaccharides, with low toxicity and a wide range of bioactivities, are strong potential candidates for anti-hepatic fibrosis applications. For this study, a new low molecular weight neutral polysaccharide (B. striata glucomannan (BSP)) was extracted and purified from Bletilla striata. The structure of BSP was characterized and its activities for alleviating liver fibrosis in vivo were further evaluated. The results revealed that the structural unit of BSP was likely →4)-ß-D-Glcp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-2ace-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-Manp-(1 â†’ 4)-ß-D-3ace-Manp-(1→, with a molecular weight of only 58.5 kDa. Additionally, BSP was observed to attenuate the passive impacts of liver fibrosis in a manner closely related to TLR2/TLR4-MyD88-NF-κB signaling pathway conduction. In summary, the results of this study provide theoretical foundations for the potential applications of BSP as an anti-liver fibrosis platform.

Impacts of nature reserve policy on regional ecological environment quality: A case study of Sanjiangyuan region.

Uncovering the ecological effectiveness of nature reserve policies will help protect and manage nature reserves in the future. Taking Sanjiangyuan region as an example, we examined the impacts of the spatial layout characteristics of natural reserves on the ecological environment quality by constructing the dynamic degree of land use and land cover change index, and depicted the spatial differences of the ecological effectiveness of natural reserve policies both inside and outside the natural reserves. Combined with ordinary least squares and field survey results, we explored the influencing mechanism of nature reserve policies on ecological environment quality. The results showed that the ecological quality of the whole region of Sanjiangyuan had been improved significantly since the implementation of the nature reserve policies, and that the transformation of unused land into ecological land was the most important type of land use change for the ecological environment quality improvement. The ecological effectiveness of large-scale nature reserves with concentrated and contiguous distribution was obvious, while the ecological effectiveness of small-scale nature reserves with scattered distribution and close to the administrative boundaries was relatively small. Although the ecological effectiveness of nature reserves was better than that of non-reserved areas, the ecological improvement of nature reserves and the surrounding areas was synchronous. The nature reserve policy had significantly improved ecological environment quality by implementing ecological protection and restoration projects in nature reserves. Meanwhile, it had alleviated the pressure of farmers and herdsmen's activities on the ecological environment by taking measures such as grazing restriction and guiding conversion of industry and production. In the future, we should promote the construction of ecosystem integrity protection network system with National Park as the core, strengthen the integrated protection and linkage management of National Park and surrounding areas, and help farmers and herdsmen further broaden their livelihoods.

How to balance protection and development? A comprehensive analysis framework for territorial space utilization scale, function and pattern.

The harmonious coexistence of man and nature is a universally recognized standard to test the rational utilization of multifunctional territorial space, and the planning of territorial space adapted to nature is a scientific guide to balance ecological protection and human development. This study focuses on the inevitable relationship between the scale, function and pattern of territorial space utilization (TSU), and puts forward a process research framework of "background evaluation-advantage comparison-optimization conduction". Based on the evaluation of resource and environment suitability, this paper determines the scale of multifunctional territorial space through the potential conflict identification model of TSU. The location entropy method is used to identify the advantageous functions of the county level, and the matching characteristics of the research results and the current situation are obtained by comparing them with the current plan. Finally, from the county functional zoning to the regional TSU pattern, the corresponding optimization conduction path is designed to form a new development and protection pattern. The empirical results of research area show that: (1) The study area is suitable for urban construction and agricultural production as a whole. The ecological protection is mainly at the general important level, and there is a moderate potential conflict between the development and protection of territorial space. The space scale of urban construction, agricultural production and ecological protection are accounted for 8.77%, 78.71% and 12.52%, respectively. (2) The advantageous function of TSU in county-level administrative units is dominated by single advantageous function, and the number of composite advantageous functions is generally small. The advantageous functional types determined by this research have a high matching with the current plan. (3) Based on the analysis of the scale structure and functional use of territorial space, this paper defines the ecological space that should be strictly protected and the agricultural and urban space that should be moderately developed for production and construction, and sets up elastic development areas. Finally, a strategic pattern of "one corridor, two screens, three circles and four zones" is conducive to the realization of the beautiful vision of the unification of protection and development.

Plasma Lipoprotein-Associated Phospholipase A2 Affects Cognitive Impairment in Patients with Cerebral Microbleeds.

Purpose: The plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker of cerebral microbleeds (CMBs) and may be related to the occurrence, development, and prognosis of cognitive impairment. The present study aimed to investigate the impact of plasma Lp-PLA2 level on the cognitive impairment in patients with CMBs. Methods: In this study, 213 patients with CMBs confirmed by 3.0 T brain magnetic resonance imaging (MRI) were analyzed. Lp-PLA2 levels were determined by magnetic particle chemiluminescence immunoassay technology, and cognitive function was assessed using the Montreal Cognitive Assessment Scale (MoCA). The cognitive functions of patients with CMBs were divided into three groups according to the MoCA scale, including normal cognition (NC), mild cognitive impairment (MCI), and moderate-severe cognitive impairment (MSCI). Clinical, laboratory and radiological data of the three groups were analysed. The relationship between plasma Lp-PLA2 and MoCA score in patients with CMBs was investigated through rank correlation analysis and multivariate regression analysis, and receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of Lp-PLA2. Results: CMBs were detected in 213 (30.2%) of 705 patients who underwent 3.0 T MRI. Multiple comparisons showed that plasma Lp-PLA2 in patients with CMBs with normal cognitive scores was significantly lower than that in the other two groups with cognitive impairment (p < 0.05). In the single factor correlation analysis, high level of plasma Lp-PLA2 was negatively correlated with the decrease of MoCA score in patients with CMBs (r =-0.389, p < 0.01). Multivariate regression analysis showed that high plasma Lp-PLA2 was an independent risk factor for a low MoCA score in patients with CMBs (odds ratio [OR]=1.014; 95% confidence interval [CI], 1.002-1.026; p=0.025). Conclusion: A high level of plasma Lp-PLA2 is positively correlated with the generation of cognitive impairment in patients with CMBs and negatively correlated with the degree of impairment. Plasma Lp-PLA2 is an important indicator of cognitive impairment in patients with CMBs and may provide a therapeutic target for preventing CMB-induced cognitive impairment.

The Allocation Change of Rural Land Consolidation Type Structure under the Influence Factors of Different Geographical and Economic Development of China.

Land consolidation structure reflects land consolidation function, and studies about its spatio-temporal change and driving mechanism can serve for regional management and control land consolidation. At present, the analysis of regional differences, time changes, and driving factors of land consolidation type structure change is relatively lacking. Based on the data of provincial acceptance projects from 2000 to 2014, this paper analyzes the spatio-temporal change of rural land consolidation type structure in China, discusses the impact of relevant policies, and identifies the socio-economic driving factors in key regions by employing correlation analysis and the PLSR (partial least squares regression) method. The results showed that from 2000 to 2014, the proportional increase of land arrangement in China was significantly correlated with the proportional decrease of land reclamation (R2 = 0.93), and the proportional decrease of land development (R2 = 0.99) showed an obvious co-evolution pattern of increase and decrease; TILC (The area of land development/The area of land arrangement) decreased from 2.14 to 0.91 in 2002-2003. Since 2003, the dominant type of land consolidation in China has gradually changed from land development to land arrangement. However, the proportion of land development in QT (Qinghai-Tibet), JY (Jin-Yu), and FGH (Fujian-Guangdong-Hainan) areas is still more than 40%; the change of land consolidation type structure was influenced by policies, social and economic factors, such as urbanization rate, fixed assets investment, industrial proportion, and population density, and the regional difference was significant: the eastern section (JZS, Jiangsu-Zhejiang-Shanghai) is the industry proportion, the central area (HHAJ, Hunan-Hubei-Anhui-Jiangxi) is grain production and fixed assets investment, the western region (NW, Northwest China) has the urbanization rate, grain production, population density, and fixed assets investment. Land consolidation structure should be configured differentially in each region based on the identification of regional function orientation and comprehensive consideration of regional resource endowment and development needs and directions to improve the efficiency of land consolidation.

Developing an Evaluation System Suitable for Coastal Rural Houses' Characteristic Style and Its Inspiration for Rural Revitalization: Case Study of Rongcheng in Shandong Province.

The characteristic style of rural houses is an important manifestation of the historical and cultural values of rural areas and is the key focus of the implementation of the strategy for the construction of beautiful China and the revitalization of rural areas. Taking 17 villages in the Rongcheng of Shandong as an example, this article integrated multidimensional data, including geospatial data, survey data and socio-economic data, and constructed a suitable index system to evaluate the characteristic style of coastal rural houses in 2018 and put forward the characteristic style regionalization of coastal rural houses. The results show that the characteristic style of coastal rural houses can be measured by the overall village environment, coastal architectural value and traditional folk culture, among which the coastal architectural value is the most critical. Two villages scored over 60 points in the comprehensive evaluation, namely the Dongchu Island village and Dazhuang Xujia Community. Different dominant characteristic styles of rural houses were identified according to single-factor evaluation. Based on the evaluation results and factors such as location, nature, social economy and the status quo of protection and development management, characteristic styles of rural houses in the research area can be divided into four continuous areas: historical and cultural characteristics, folk customs and industrial development characteristics, natural scenery characteristics and folk customs characteristics. Combined with regional positioning and development planning, the construction direction of different regional types was defined, and then the protection and improvement measures of rural residential features were put forward. This study not only provides a certain basis for the evaluation, construction and protection of the characteristic features of coastal rural dwellings in Rongcheng City but also provides guidance for the implementation of rural construction planning.

Animal-SNPAtlas: a comprehensive SNP database for multiple animals.

Single-nucleotide polymorphisms (SNPs) as the most important type of genetic variation are widely used in describing population characteristics and play vital roles in animal genetics and breeding. Large amounts of population genetic variation resources and tools have been developed in human, which provided solid support for human genetic studies. However, compared with human, the development of animal genetic variation databases was relatively slow, which limits the genetic researches in these animals. To fill this gap, we systematically identified ∼ 499 million high-quality SNPs from 4784 samples of 20 types of animals. On that basis, we annotated the functions of SNPs, constructed high-density reference panels and calculated genome-wide linkage disequilibrium (LD) matrixes. We further developed Animal-SNPAtlas, a user-friendly database (http://gong_lab.hzau.edu.cn/Animal_SNPAtlas/) which includes high-quality SNP datasets and several support tools for multiple animals. In Animal-SNPAtlas, users can search the functional annotation of SNPs, perform online genotype imputation, explore and visualize LD information, browse variant information using the genome browser and download SNP datasets for each species. With the massive SNP datasets and useful tools, Animal-SNPAtlas will be an important fundamental resource for the animal genomics, genetics and breeding community.

Toward the efficient direct regeneration of spent cathode materials through the effect of residual sodium ions analysis.

Recycling spent lithium-ion batteries is an important means for promoting sustainability within the energy industry. In this study, the effects of residual sodium on the regeneration process and the performance of spent LiNi0.5Co0.2Mn0.3O2 were explored. An appropriate amount of residual sodium was found to improve the properties of the regenerated material, with the best cycle performance and rate performance at a residual sodium of 3 mol %. The first-cycle and 100-cycle discharge capacities were 136.4 mA h g-1 and 120 mA h g-1, respectively, with a capacity retention rate of 87.98% after 100 cycles at a rate of 1 C. The electrochemical performance of the regenerated cathode materials was improved because sodium occupied the lithium sites in the crystal structure, providing a channel for lithium deintercalation. These results indicate that the residual sodium ions should be monitored in appropriate quantities to improve the efficiency of recycling spent lithium-ion batteries.

Dynamic alternative polyadenylation during iPSC differentiation into cardiomyocytes.

Alternative polyadenylation (APA) is an important post-transcription regulatory mechanism widely occurring in eukaryotes and has been associated with special traits/diseases by several studies. However, the dynamic roles and patterns of APA in cell differentiation remain largely unknown. Here, we systematically characterized the APA profiles during the differentiation of induced pluripotent stem cells (iPSCs) to cardiomyocytes by the previously published RNA-seq data across 16 time points. We identified 950 differential APA events and found five dynamic APA patterns with fuzzy c-means clustering analysis. Among them, 3'UTR progressive lengthening is the main APA pattern over time, the genes of which are enriched in cell cycle and mRNA metabolic process pathways. By constructing the linear mixed-effects model, we also indicated that TIA1 plays an important role in regulating APA events with this pattern, including genes essential to cardiac function. Additionally, APA and polyA machinery activity with another pattern can immediately respond to developmental signal-mediated stimuli at the early differentiation stage and result in a sharp shortening of the 3'UTR. Finally, a miRNA-APA network is constructed and several hub miRNAs potentially regulating cardiomyocyte differentiation are detected. Our results show the complex APA mechanisms during the differentiation of iPSCs into cardiomyocytes and provide further insights for the understanding of APA regulation and cell differentiation.

Systematic analysis of the effects of genetic variants on chromatin accessibility to decipher functional variants in non-coding regions.

Genome-wide association study (GWAS) has identified thousands of single nucleotide polymorphisms (SNPs) associated with complex diseases and traits. However, deciphering the functions of these SNPs still faces challenges. Recent studies have shown that SNPs could alter chromatin accessibility and result in differences in tumor susceptibility between individuals. Therefore, systematically analyzing the effects of SNPs on chromatin accessibility could help decipher the functions of SNPs, especially those in non-coding regions. Using data from The Cancer Genome Atlas (TCGA), chromatin accessibility quantitative trait locus (caQTL) analysis was conducted to estimate the associations between genetic variants and chromatin accessibility. We analyzed caQTLs in 23 human cancer types and identified 9,478 caQTLs in breast carcinoma (BRCA). In BRCA, these caQTLs tend to alter the binding affinity of transcription factors, and open chromatin regions regulated by these caQTLs are enriched in regulatory elements. By integrating with eQTL data, we identified 141 caQTLs showing a strong signal for colocalization with eQTLs. We also identified 173 caQTLs in genome-wide association studies (GWAS) loci and inferred several possible target genes of these caQTLs. By performing survival analysis, we found that ~10% caQTLs potentially influence the prognosis of patients. To facilitate access to relevant data, we developed a user-friendly data portal, BCaQTL (http://gong_lab.hzau.edu.cn/caqtl_database), for data searching and downloading. Our work may facilitate fine-map regulatory mechanisms underlying risk loci of cancer and discover the biomarkers or therapeutic targets for cancer prognosis. The BCaQTL database will be an important resource for genetic and epigenetic studies.

Comprehensive functional analysis of the PYL-PP2C-SnRK2s family in Bletilla striata reveals that BsPP2C22 and BsPP2C38 interact with BsPYLs and BsSnRK2s in response to multiple abiotic stresses.

As the core regulation network for the abscisic acid (ABA) signaling pathway, the PYL-PP2C-SnRK2s family commonly exists in many species. For this study, a total of 9 BsPYLs, 66 BsPP2Cs, and 7 BsSnRK2s genes were identified based on the genomic databases of Bletilla striata, which were classified into 3, 10, and 3 subgroups, respectively. Basic bioinformatics analysis completed, including the physicochemical properties of proteins, gene structures, protein motifs and conserved domains. Multiple cis-acting elements related to stress responses and plant growth were found in promoter regions. Further, 73 genes were localized on 16 pseudochromosomes and 29 pairs of paralogous genes were found via intraspecific collinearity analysis. Furthermore, tissue-specific expression was found in different tissues and germination stages. There were two BsPYLs, 10 BsPP2Cs, and four BsSnRK2 genes that exhibited a difference in response to multiple abiotic stresses. Moreover, subcellular localization analysis revealed six important proteins BsPP2C22, BsPP2C38, BsPP2C64, BsPYL2, BsPYL8, and BsSnRK2.4 which were localized in the nucleus and plasma membrane. Finally, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays suggested that BsPP2C22 and BsPP2C38 could interact with multiple BsPYLs and BsSnRK2s proteins. This study systematically reported on the identification and characterization of the PYL-PP2C-SnRK2s family in B. striata, which provided a conceptual basis for deep insights into the functionality of ABA core signal pathways in Orchidaceae.

Surface Growth and Intergranular Separation of Polycrystalline Particles for Regeneration of Stable Single-Crystal Cathode Materials.

The direct regeneration technology has been developed because of its short-range, high efficiency, and green characteristics. However, the existing direct regeneration method is hardly applied in collaborative reconstruction of the damaged crystal and particle of spent polycrystalline layered materials. The single-crystal regeneration with restructuring the morphology and crystal structure was herein achieved for the first time by low-temperature lithium supplementation followed with high-temperature molten salt conversion, which could effectively solve the structural defects of spent polycrystalline layered materials. We found that the realization of single-crystal regeneration with the molten salt process is attributable to that the original crystal growth of primary particles in the polycrystal transfer to the subsequent division along the grain boundary. At the test conditions of 25 °C and 2.8-4.3 V, the capacity retention capacity of the regenerated single-crystal materials reach 83.3% after 200 cycles at 1 C, which is much higher than 20.0% for conventional direct lithiation regeneration and 61.6% for low-temperature molten salt regeneration. Interestingly, the regenerated single-crystal NCM622 in the graphite full-cell test displays a capacity retention rate of 85.24% after 800 cycles at a rate of 1 C at 2.5-4.35 V. This work opens up a new way for the direct regeneration of spent polycrystalline layered cathode materials.