Using Omics to Identify Novel Therapeutic Targets in Heart Failure.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01960946.

MdARF3 switches the lateral root elongation to regulate dwarfing in apple plants.

Apple rootstock dwarfing and dense planting are common practices in apple farming. However, the dwarfing mechanisms are not understood. In our study, the expression of MdARF3 in the root system of dwarfing rootstock 'M9' was lower than in the vigorous rootstock from Malus micromalus due to the deletion of the WUSATAg element in the promoter of the 'M9' genotype. Notably, this deletion variation was significantly associated with dwarfing rootstocks. Subsequently, transgenic tobacco (Nicotiana tabacum) cv. Xanthi was generated with the ARF3 promoter from 'M9' and M. micromalus genotypes. The transgenic apple with 35S::MdARF3 was also obtained. The transgenic tobacco and apple with the highly expressed ARF3 had a longer root system and a higher plant height phenotype. Furthermore, the yeast one-hybrid, luciferase, electrophoretic mobility shift assays, and Chip-qPCR identified MdWOX4-1 in apples that interacted with the pMm-ARF3 promoter but not the pM9-ARF3 promoter. Notably, MdWOX4-1 significantly increased the transcriptional activity of MdARF3 and MdLBD16-2. However, MdARF3 significantly decreased the transcriptional activity of MdLBD16-2. Further analysis revealed that MdARF3 and MdLBD16-2 were temporally expressed during different stages of lateral root development. pMdLBD16-2 was mainly expressed during the early stage of lateral root development, which promoted lateral root production. On the contrary, pMmARF3 was expressed during the late stage of lateral root development to promote elongation. The findings in our study will shed light on the genetic causes of apple plant dwarfism and provide strategies for molecular breeding of dwarfing apple rootstocks.

[Soil microbial carbon pump conceptual framework 2.0]. / 土壤微生物碳泵概念体系2.0.

Microorganisms are essential actors in the biogeochemical cycling of elements within terrestrial ecosystems, with significant influences on soil health, food security, and global climate change. The contribution of microbial anabolism-induced organic compounds is a non-negligible factor in the processes associated with soil carbon (C) storage and organic matter preservation. In recent years, the conceptual framework of soil microbial carbon pump (MCP), with a focus on microbial metabolism and necromass generation process, has gained widespread attention. It primarily describes the processes of soil organic C formation and stabilization driven by the metabolic activities of soil heterotrophic microorganisms, representing an important mechanism and a focal point in current research on terrestrial C sequestration. Here, we reviewed the progress in this field and introduced the soil MCP conceptual framework 2.0, which expands upon the existing MCP model by incorporating autotrophic microbial pathway for C sequestration and integrating the concept of soil mineral C pump. These advancements aimed to enrich and refine our understanding of microbial-mediated terrestrial ecosystem C cycling and sequestration mechanisms. This refined framework would provide theoretical support for achieving China's "dual carbon" goals.

[Accumulation of microbial necromass carbon and their contribution to soil organic carbon in different vegetation types on the Loess Plateau, Northwest China]. / é»„åœŸé«˜åŽŸä¸åŒæ¤è¢«ç±»åž‹åœŸå£¤å¾®ç”Ÿç‰©æ®‹ä½“ç¢³çš„ç§¯ç´¯åŠå ¶å¯¹æœ‰æœºç¢³çš„è´¡çŒ®.

Microbial necromass carbon (MNC) is an important contributor to soil organic carbon (SOC). Soil carbon storage has increased significantly since the return of farmland to forestland (grassland) on the Loess Plateau. However, the contribution of MNC to SOC accumulation in different vegetation types and the influence factors remain unclear. Herein, we used the biomarker (amino sugar) technique to determine the MNC content and analyzed the influencing factors in 0-5 cm and 5-20 cm soil layers of natural grassland, shrubland (Caragana microphylla), and forestland (Quercus liaodongensis) in the Loess Plateau. The results showed that: 1) the soil pH decreased significantly from grassland to shrubland and then to forestland within the same soil layer. However, the SOC, total nitrogen (TN), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN) contents showed a reverse trend, with forestland displaying the highest values followed by shrubland and then grassland. The 0-5 cm had significantly higher values than the 5-20 cm depth. 2) The MNC contents varied 0.69-16.41 g·kg-1 in the two soil horizons of the three vegetation types. There were significant increases in the contents of bacterial necromass carbon (BNC), fungal necromass carbon (FNC), and MNC in the 0-5 cm soil from grassland, shrubland to forestland. The contents of MBC were 1.9 times higher in forestland than in shrubland, and 3.2 times higher in shrubland than in grassland. In the 5-20 cm soil layer, the contents of FNC and MBC were significantly higher in the forestland than in the shrubland and grassland. The FNC content was significantly higher than that of the BNC, ranging from 1.16 to 9.83 times greater than the BNC. 3) The contribution of MNC to SOC was 0.6 and 0.7 times higher in shrubland and forestland than in grassland, respectively, with FNC accounting for 15.2%-42.7%, and BNC accounting for 1.4%-7.4%. 4) pH, TN, MBC, and MBN were important factors that influenced MNC accumulation. In summary, the variation in vegetation type altered soil nutrients, microbial activity, and soil pH, resulting in forestland and shrubland being more beneficial to the formation and accumulation of MNC, which was dominated by fungi, compared to grassland.

Response of the C-fixing bacteria community to precipitation changes and its impact on bacterial necromass accumulation in semiarid grassland.

Climate change-induced warming has the potential to intensify drought conditions in certain regions, resulting in uneven precipitation patterns. However, the impact of precipitation-induced changes on soil C-fixing bacterial community composition to changes and their subsequent effect on the accumulation of microbial necromass in the soil remains unclear. To address this knowledge gap, we conducted an in-situ simulated precipitation control experiment in semi-arid grasslands, encompassing five primary precipitation gradients: ambient precipitation as a control (contr), decreased precipitation by 80% and 40% (DP80, DP40), and increased precipitation by 40% and 80% (IP80, IP40). Our findings indicate that while an increase in precipitation promotes greater total bacterial diversity, it reduces the diversity of cbbM-harboring bacteria. The dominance of drought-tolerant Proteobacteria within the cbbM-harboring bacterial community was responsible for the observed increase in their relative abundance, ranging from 8.9% to 15.6%, under conditions of decreased precipitation. In arid environments characterized by limited soil moisture and nutrient availability, certain dominant genera such as Thiobacillus, Sulfuritalea, and Halothiobacillus, which possess cbbM genes, exhibit strong synergistic effects with other bacteria, thereby leading to a high nutrient use efficiency. Linear regression analysis shows that bacterial necromass C was significantly negatively correlated with cbbM-harboring bacterial diversity but positively correlated with cbbM-harboring bacterial community composition. Consequently, in the extreme drought environment of DP80, the contribution of bacterial necromass C to SOC was dramatically reduced by 75% relative to the control. Although bacterial necromass C was preferentially consumed as nutrients and energy for microorganisms, C-fixing microorganisms supplemented the soil C pool by assimilating atmospheric CO2. Bacterial necromass was primarily controlled by accessible C and N rather than by the total bacterial community composition and relative abundance. Our results provide compelling evidence for the critical role of the composition of the bacterial community and its necromass in the accumulation of SOC in semiarid grassland ecosystems.

Mechanism of polyethylene and biodegradable microplastic aging effects on soil organic carbon fractions in different land-use types.

Microplastics (MPs) are widely present in terrestrial ecosystems, but knowledge about the aging characteristics of MPs in different land-use types and their impact on soil organic carbon fractions is still limited. Polyethylene (PE) and biodegradable MPs (Poly propylene carbonate and Polybutylene adipate terephthalate synthetic material (PPC + PBAT, Bio)), at 0 %, 0.03 %, and 0.3 % (w/w) dosages, were added to grassland, farmland, and facility soils for eight-week incubation. The aging degree of MPs was explored by quantifying the carbonyl index (CI). Soil organic C fractions such as SOC, particulate organic carbon (POC), mineral-associated organic carbon (MAOC), and microbial-derived C were analyzed. MPs underwent rapid aging after incubation, and the CI value for 0.03 % PE-MPs increased from 0.05 to 0.27 (farmland) and 0.26 (facility) (p < 0.05). The aging degree of 0.03 % and 0.3 % Bio-MPs was most significant in grassland, with CI decreasing by 46.6 % and 69.0 %, respectively. The CI of MPs were negatively correlated with their dosage. The 0.03 % and 0.3 % PE-MPs decreased soil organic carbon (SOC) content by 7.4 % and 8.2 % in grassland, and 3.0 % and 6.0 % in the facility (p < 0.05). POC content of farmland and facility soil was negatively correlated with PE-MPs' CI (p < 0.05). The 0.03 % PE and Bio-MPs decreased fungal necromass C (FNC) by 0.40 and 0.05 g kg-1 in grassland and 0.48 and 0.21 g kg-1 in farmland. Besides, the dosage of MPs regulated FNC content through soil pH, nutrients, and extracellular enzyme activity, either directly or indirectly, ultimately affecting the soil C pool. Therefore, this study demonstrates that MPs strongly affect SOC dynamics by influencing soil microbial enzyme activity and fungal necromass.

An Introductory Tutorial on Cardiovascular Pharmacogenetics for Healthcare Providers.

Pharmacogenetics can improve clinical outcomes by reducing adverse drug effects and enhancing therapeutic efficacy for commonly used drugs that treat a wide range of cardiovascular diseases. One of the major barriers to the clinical implementation of cardiovascular pharmacogenetics is limited education on this field for current healthcare providers and students. The abundance of pharmacogenetic literature underscores its promise, but it can also be challenging to learn such a wealth of information. Moreover, current clinical recommendations for cardiovascular pharmacogenetics can be confusing because they are outdated, incomplete, or inconsistent. A myriad of misconceptions about the promise and feasibility of cardiovascular pharmacogenetics among healthcare providers also has halted clinical implementation. Therefore, the main goal of this tutorial is to provide introductory education on the use of cardiovascular pharmacogenetics in clinical practice. The target audience is any healthcare provider (or student) with patients that use or have indications for cardiovascular drugs. This tutorial is organized into the following 6 steps: (1) understand basic concepts in pharmacogenetics; (2) gain foundational knowledge of cardiovascular pharmacogenetics; (3) learn the different organizations that release cardiovascular pharmacogenetic guidelines and recommendations; (4) know the current cardiovascular drugs/drug classes to focus on clinically and the supporting evidence; (5) discuss an example patient case of cardiovascular pharmacogenetics; and (6) develop an appreciation for emerging areas in cardiovascular pharmacogenetics. Ultimately, improved education among healthcare providers on cardiovascular pharmacogenetics will lead to a greater understanding for its potential in improving outcomes for a leading cause of morbidity and mortality.

Impact of MRI resolution for Linac-based stereotactic radiosurgery.

Objective: Magnetic resonance imaging (MRI) is a standard imaging modality in intracranial stereotactic radiosurgery (SRS) for defining target volumes. However, wide disparities in MRI resolution exist, which could directly impact accuracy of target delineation. Here, sequences with various MRI resolution were acquired on phantoms to evaluate the effect on volume definition and dosimetric consequence for cranial SRS. Materials/Methods: Four T1-weighted MR sequences with increasing 3D resolution were compared, including two Spin Echo (SE) 2D acquisitions with 5mm and 3mm slice thickness (SE5mm, SE3mm) and two gradient echo 3D acquisitions (TFE, BRAVO). The voxel sizes were 0.4×0.4×5.0, 0.5×0.5×3.0, 0.9×0.9×1.25, and 0.4×0.4×0.5 mm3, respectively. Four phantoms with simulated lesions of different shape and volume (range, 0.53-25.0 cm3) were imaged, resulting in 16 total sets of MRIs. Four radiation oncologists provided contours on individual MR image set. All observer contours were compared with ground truth, defined on CT image according to the absolute dimensions of the target structure, using Dice similarity coefficient (DSC), Hausdorff distance (HD), mean distance-to-agreement (MDA), and the ratio between reconstructed and true volume (Ratiovol ). For dosimetric consequence, SRS plans targeting observer volumes were created. The true Paddick conformity index ( C I p a d d i c k t r u e ), calculated with true target volume, was correlated with quality of observer volume. Results: All measures of observer contours improved as increasingly higher MRI resolution was provided from SE5mm to BRAVO. The improvement in DSC, HD and MDA was statistically significant (p<0.01). Dosimetrically, C I p a d d i c k t r u e   strongly correlated with DSC of the planning observer volume (Pearson's r=0.94, p<0.00001). Conclusions: Significant improvement in target definition and reduced inter-observer variation was observed as the MRI resolution improved, which also improved the quality of SRS plans. Results imply that high resolution 3D MR sequences should be used to minimize potential errors in target definition, and multi-slice 2D sequences should be avoided.

Comprehensive evaluation of spent mushroom substrate-chicken manure co-composting by garden waste improvement: physicochemical properties, humification process, and the spectral characteristics of dissolved organic matter.

The performance of garden waste on spent mushroom substrate (SMS) and chicken manure (CM) co-composting efficiency and humification is unclear. Therefore, this study investigated the impact of garden waste addition on SMS-CM co-composting physicochemical properties, humification process, and the spectral characteristics of dissolved organic matter (DOM). The results showed that garden waste improved the physicochemical properties of SMS-CM co-compost, the thermophilic period was advanced 2 days, the seed germination index increased by 30.2%, and the total organic carbon and total nitrogen content increased by 8.80% and 15.0%, respectively. In addition, garden waste increased humic substances (HS) and humic acid (HA) contents by 10.62% and 34.52%, respectively; the HI, PHA and DP increased by 31.53%, 43.19% and 55.53%, respectively; and the SUVA254 and SUVA280 of DOM also increased by 6.39% and 4.39%, respectively. In particular, HA content and DOM humification increase rapidly in the first 10 days. The increase of HA accounted for 52% of the total increase during composting. Fourier-transform infrared and two-dimensional correlation analysis further confirmed that garden waste could facilitate the degradation of organic molecules, including amino acids, polysaccharides, carboxyl groups, phenols, and alcohol, and contributed to the preferential utilization of carboxyl groups and polysaccharides and thus enhanced humification.

Biogeographic distribution of autotrophic bacteria was more affected by precipitation than by soil properties in an arid area.

Introduction: Autotrophic bacteria play an important role in carbon dioxide fixation and are widespread in terrestrial ecosystems. However, the biogeographic patterns of autotrophic bacteria and the driving factors still remain poorly understood. Methods: Herein, we conducted a 391-km north to south transect (mean annual precipitation <600 mm) survey in the Loess Plateau of China, to investigate the biogeographic distributions of autotrophic bacteria (RubisCO cbbL and cbbM genes) and the environmental drivers across different latitude sites with clear vegetational and climatic gradients. Results and discussion: The soils in northern region with lower precipitation are dominated by grassland/forest, which is typically separated from the soils in southern region with higher precipitation. The community structure of autotrophic bacterial cbbL and cbbM genes generally differed between the soils in the southern and northern Loess Plateau, suggesting that precipitation and its related land use practices/ecosystem types, rather than local soil properties, are more important in shaping the soil autotrophic microorganisms. The cbbL-containing generalist OTUs were almost equally abundant across the northern and southern Loess Plateau, while the cbbM-containing bacterial taxa were more prevalent in the low precipitation northern region. Such differences indicate differentiate distribution patterns of cbbM- and cbbL-containing bacteria across the north to south transect. Our results suggest that the community composition and the differentiate distributions of soil cbbL- and cbbM-containing bacterial communities depend on precipitation and the related ecosystem types in the north to south transect in the Loess Plateau of China.

ROP signaling regulates spatial pattern of cell division and specification of meristem notch.

The formation of cell polarity is essential for many developmental processes such as polar cell growth and spatial patterning of cell division. A plant-specific ROP (Rho-like GTPases from Plants) subfamily of conserved Rho GTPase plays a crucial role in the regulation of cell polarity. However, the functional study of ROPs in angiosperm is challenging because of their functional redundancy. The Marchantia polymorpha genome encodes a single ROP gene, MpROP, providing an excellent genetic system to study ROP-dependent signaling pathways. Mprop knockout mutants exhibited rhizoid growth defects, and MpROP was localized at the tip of elongating rhizoids, establishing a role for MpROP in the control of polar cell growth and its functional conservation in plants. Furthermore, the Mprop knockout mutant showed defects in the formation of meristem notches associated with disorganized cell division patterns. These results reveal a critical function of MpROP in the regulation of plant development. Interestingly, these phenotypes were complemented not only by MpROP but also Arabidopsis AtROP2, supporting the conservation of ROP's function among land plants. Our results demonstrate a great potential for M. polymorpha as a powerful genetic system for functional and mechanistic elucidation of ROP signaling pathways during plant development.

[Distribution, Risk, and Influencing Factors of Microplastics in Surface Water of Huangshui River Basin].

In order to explore the distribution of microplastics in the freshwater environment of Qinghai-Tibet Plateau, 63 surface water samples were collected in Huangshui River basin of Qinghai province during the wet season, and the distribution characteristics and main influencing factors of microplastics in the surface water were analyzed by means of metallographic microscope, Fourier infrared spectroscopy, field investigation, and image data analysis. The potential ecological risks of microplastics were evaluated using risk index (H) and pollution load index (PLI) models. The abundance of microplastics in surface water ranged from 665-8780 n·m-3, with the highest average abundance of 5414 n·m-3 in Huangyuan County. The abundance of microplastics increased from upstream to downstream. The main colors of microplastics were transparent (67%) and black (17%), and the particle size was less than 50 µm (70%). Polyethylene (66%) and polypropylene (12%) were the main polymer types. The abundance of microplastics was positively correlated with cultivated land area, precipitation, and ultraviolet intensity, but the opposite results were observed in dissolved oxygen, redox potential, and wind speed. Additionally, the potential ecological risk of surface water in the Huangshui River basin was relatively low.

[Influence of Land Use and Land Cover Patterns on Water Quality at Different Spatio-temporal Scales in Hehuang Valley].

Based on the measured water quality data of Huangyuan County, Huzhu Tu Autonomous County, and Minhe Hui Tu Autonomous County in Hehuang Valley of Qinghai province in the normal and wet seasons, the effects of land use and land cover patterns on regional seasonal water quality were analyzed using remote sensing technology and mathematical statistics. The results showed that:① the concentrations of total nitrogen and total phosphorus in the surface water of Hehuang Valley were high. Water pollution areas (Class Ⅳ and Ⅴ) were mainly concentrated in the lower reaches of the river and the junction of tributaries. ② The explanation rate of land use to water quality in the normal season was higher than that in the wet season. The optimal scale was the 200 m buffer scale in the normal season, and farmland and towns were the main influencing factors. The optimal scale in the wet season was the 5 km buffer scale, and the main influencing factor was the forest. ③ In the normal season, the proportion of farmland was positively correlated with the concentration of total nitrogen and permanganate index but negatively correlated with the concentration of total phosphorus. The proportion of town area was positively correlated with the water quality index. The proportion of grassland area in the wet season was positively correlated with the permanganate index. The proportion of forestland area was negatively correlated with water quality index in both periods. Farmland, grassland, and town areas were the "source" landscape of pollutants, but farmland also played a role in intercepting pollutants to a certain extent. Forest land was the "sink" landscape of pollutants. ④ The pattern of forestland in the 200 m buffer zone in the normal season had a high explanatory rate for water quality, and the largest patch index (LPI) and patch density (PD) were the main factors. The study showed that it is an important measure to purify the surface water quality of Hehuang Valley by rationally planning the proportion of residential land and cultivated land and improving the coverage rate and aggregation degree of forestland around the riparian zone.

Microplastics trapped in soil aggregates of different land-use types: A case study of Loess Plateau terraces, China.

Land-use types may affect soil aggregates' stability and organic carbon (OC) distribution characteristics, but little is known about the effects on the distribution characteristics of microplastics (MPs) in the aggregates. Hence, the MPs abundance of soil aggregates and analyzed aggregates' stability, composition, and OC content from two soil layers of four land-use types in Gansu Province were investigated in this study. The total MPs abundances in woodland, farmland (wheat, maize, and potato), orchard, and intercropping (potato + apple orchard) of top and deep soils were 1383.3 and 1477.9, 1324.6 and 931.1, 1757.1 and 1930.9, 2127.2 and 1998.0, 1335.9 and 886.7, and 1777.5 and 1683.3 items kg-1, respectively. The largest MPs abundance was detected in the >5 mm fractions of topsoil in potato (3077.3 items kg-1), followed by maize (3044.7 items kg-1) and intercropping (2718.4 items kg-1). In the topsoil, the total MPs abundance increased significantly with decreasing aggregate stability, and also was positively correlated with bulk density, microbial biomass, and total nitrogen contents of bulk soil. Summarizing, the abundance distribution of MPs correlates with the soil aggregate characteristics of the different land-use types.

Response of cbbL-harboring microorganisms to precipitation changes in a naturally-restored grassland.

The impact of the long-term uneven precipitation distribution model on the diversity and community composition of soil C-fixing microorganisms in arid and semiarid grasslands remains unclear. In 2015, we randomly set up five experimental plots with precipitation gradients on the natural restoration grassland of the Loess Plateau (natural precipitation, NP; ± 40% natural precipitation: decreased precipitation (DP), DP40; increased precipitation (IP), IP40; ± 80% natural precipitation: DP80; IP80). In the third and fifth years after the experimental layout (spanned two years), we explored the cbbL-genes, which are functional genes in the Calvin cycle, harboring microbial diversity and community composition under different precipitation treatments. The results showed that the increase in mean annual precipitation significantly changed the cbbL-harboring microbial alpha diversity, especially when controlling for 40% natural precipitation. The response of the dominant microbial communities to interannual increased precipitation variation shifted from Gammaproteobacteria (Bradyrhizobium) to Betaproteobacteria (Variovorax). The structural equation model showed that precipitation directly affected the cbbL-harboring microbial diversity and community composition and indirectly by affecting soil NO3- (mg N kg -1), soil organic matter, dissolved organic N content, and above- and underground biomass. In conclusion, studying how cbbL-harboring microbial diversity and community composition respond to uneven precipitation variability provides new insights into the ecological processes of C-fixing microbes in semi-arid naturally-restored grasslands dominated by the Calvin cycle.

Siderophore production in pseudomonas SP. strain SP3 enhances iron acquisition in apple rootstock.

AIMS: The purpose of this study was to analyse the effects of siderophore-producing bacteria and bacterial siderophore on the iron nutrition of apple rootstocks under iron-deficient conditions. METHODS AND RESULTS: We isolated three Pseudomonas strains, SP1, SP2 and SP3 from the rhizosphere of the Fe-efficient apple rootstocks using the chrome azurol S agar plate assay. We found that all three strains had the ability to secrete indole acetic acid-like compounds and siderophores, especially SP3. When Fe-inefficient rootstocks treated with SP3 were grown in alkaline soil, an increase in the biomass, root development, and Fe concentration was observed in the plants. In addition, SP3 secreted pyoverdine, a siderophore that can chelate Fe3+ to enhance the bioavailability of Fe for plants. We purified the pyoverdine from the SP3 culture supernatant. Hydroponic experiments were conducted with a Fe-deficient solution supplemented with pyoverdine, resulting in a reduction in the chlorosis caused by Fe deficiency and marked improvement in Fe uptake. CONCLUSIONS: Under iron-deficient conditions, Pseudomonas sp. strain SP3 can effectively promote apple rootstock growth and improve plant iron nutrition by secreting siderophores that enhance Fe availability. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed that plant growth-promoting rhizobacteria from Fe-efficient plants have the potential to improve iron nutrition in Fe-inefficient plants, and Fe-siderophore chelates can be used as an effective source of iron for apple plants. Based on these findings, it may be possible to develop biological agents such as siderophore-producing bacteria for sustainable agricultural and horticultural production.

Lactate Dehydrogenase B and Pyruvate Oxidation Pathway Associated With Carfilzomib-Related Cardiotoxicity in Multiple Myeloma Patients: Result of a Multi-Omics Integrative Analysis.

Multiple myeloma (MM) is the second most frequent hematologic cancer in the United States. Carfilzomib (CFZ), an irreversible proteasome inhibitor being used to treat relapsed and refractory MM, has been associated with cardiotoxicity, including heart failure. We hypothesized that a multi-omics approach integrating data from different omics would provide insights into the mechanisms of CFZ-related cardiovascular adverse events (CVAEs). Plasma samples were collected from 13 MM patients treated with CFZ (including 7 with CVAEs and 6 with no CVAEs) at the University of Florida Health Cancer Center. These samples were evaluated in global metabolomic profiling, global proteomic profiling, and microRNA (miRNA) profiling. Integrative pathway analysis was performed to identify genes and pathways differentially expressed between patients with and without CVAEs. The proteomics analysis identified the up-regulation of lactate dehydrogenase B (LDHB) [fold change (FC) = 8.2, p = 0.01] in patients who experienced CVAEs. The metabolomics analysis identified lower plasma abundance of pyruvate (FC = 0.16, p = 0.0004) and higher abundance of lactate (FC = 2.4, p = 0.0001) in patients with CVAEs. Differential expression analysis of miRNAs profiling identified mir-146b to be up-regulatein (FC = 14, p = 0.046) in patients with CVAE. Pathway analysis suggested that the pyruvate fermentation to lactate pathway is associated with CFZ-CVAEs. In this pilot multi-omics integrative analysis, we observed the down-regulation of pyruvate and up-regulation of LDHB among patients who experienced CVAEs, suggesting the importance of the pyruvate oxidation pathway associated with mitochondrial dysfunction. Validation and further investigation in a larger independent cohort are warranted to better understand the mechanisms of CFZ-CVAEs.

Dosimetric Evaluation of Fractionated Stereotactic Radiation Therapy for Skull Base Meningiomas Using HyperArc and Multicriteria Optimization.

PURPOSE: Treatment planning of skull based meningiomas can be difficult due to the irregular shaped target volumes and proximity to critical optic structures. This study evaluated the use of HyperArc (HA) radiosurgery optimization and delivery in conjunction with multicriteria optimization (MCO) to create conformal and efficient treatment plans for conventionally fractionated radiation therapy to difficult base-of-skull (BOS) lesions. METHODS AND MATERIALS: Twelve patients with BOS meningioma were retrospectively planned with HA-specific optimization algorithm, stereotactic normal tissue objective (SRS-NTO), and conventional automatic normal tissue objective to evaluate normal brain sparing (mean dose and V20 Gy). MCO was used on both SRS-NTO and automatic normal tissue objective plans to further decrease organ-at-risk doses and target dose maximum to within clinically acceptable constraints. Delivery efficiency was evaluated based on planned monitor units. RESULTS: The SRS-NTO in HA can be used to improve the mid- and low-dose spread to normal brain tissue in the irradiation of BOS meningiomas. Improvement in normal brain sparing can be seen in larger, more irregular shaped lesions and less so in smaller spherical targets. MCO can be used in conjunction with the SRS-NTO to reduce target dose maximum and dose to organ at risk without sacrificing the gain in normal brain sparing. CONCLUSIONS: HA can be beneficial both in treatment planning by using the SRS-NTO and in delivery efficiency through the decrease in monitor units and automated delivery.

Response of soil fungal community composition and functions on the alteration of precipitation in the grassland of Loess Plateau.

A change in precipitation caused by climate change is an important factor that affects the biodiversity and ecological function of arid and semi-arid regions, but its influence on the composition and function of the soil fungi community in the grasslands of the Loess Plateau remains unclear. To fill this knowledge gap, we conducted an in-situ simulation experiment using five precipitation gradients (natural precipitation, increased and decreased by 40%, and 80%) in a natural restoration grassland for three years. The composition of soil fungal communities and their functions were analyzed using high-throughput sequencing techniques. Although the change of precipitation did not change the diversity index of soil fungi, it changed the composition and function of dominant fungal community groups. Specifically, decreased precipitation resulted in an increase in the relative abundance of Dothideomycetes and Boeremia by up to 12.17% and 9.93%, respectively, while these decreased with increased precipitation. The abundance of Basidiomycota, Glomeromycota, and Agaricomycetes abundance decreased by up to 11.27%, 6.96%, and 11.46% with decreased precipitation, but also decreased by up to 10.9%, 1.73%, and 10.51% with increased precipitation, respectively. However, the abundance of Ascomycota, Pezizomycetes, and norank_Pezizales increased by up to 22.58%, 7.45%, and 6.95% with decreased precipitation, and increased by up to 12.05%, 8.43%, and 5.81% with increased precipitation, respectively. The number of dominant fungal groups with interactive relationships weakened by 34.93% and 8.7% under decreased precipitation by 80% and increased 80%, respectively. Precipitation change had no significant effect on the proportion of saprotrophs, while a decrease of precipitation increased the endophyte-plant pathogens by up to 58.0% and decreased arbuscular mycorrhizal fungi by up to 92.6%. In brief, the dominant soil fungal communities could adapt and respond to climate change by altering the proportion of different dominant fungal groups by responding to moisture patterns with changes in the interrelationships between microbial communities and the proportional distribution of functional groups.

Bistriazoles with a Biphenyl Core Derivative as an Electron-Favorable Bipolar Host of Efficient Blue Phosphorescent Organic Light-Emitting Diodes.

High-quality host materials are indispensable for the construction in the emitting layer of efficient organic light-emitting diodes (OLEDs), especially in a guest and host system. The good carrier transport and energy transfer between the host and emitters are out of necessity. In this work, a wide bandgap and bipolar organic compound, 2,2'-bis(4,5-diphenyl-(1,2,4)-triazol-3-yl)biphenyl (BTBP), conjugating two electron-transporting triazole moieties on a hole-transporting biphenyl core, was synthesized and characterized. The wide bandgap of 4.0 eV makes the promise in efficient energy transfer between the host and various color emitters to apply as the universal host, especially for blue emitters. The close electron and hole mobilities perform the same order of 10-5 cm2·V-1·s-1, identified as bipolar behavior and benefited for carrier balance at low bias. Although carrier transportation belongs to bipolar behavior at a low electrical field, the electron mobility is much faster than the hole one at a high electrical field and belongs to electron-transporting behavior. Employing the BTBP as the host matrix mixed with a phosphor dopant, iridium(III)bis[4,6-di-fluorophenyl-pyridinato-N,C2]picolinate, a high-efficiency sky-blue phosphorescent organic light-emitting diode (OLED) was achieved with a maximum current efficiency of 65.9 cd/A, maximum power efficiency of 62.8 lm/W, and maximum external quantum efficiency of 30.2%.