Global Profiling Research Articles

Metabolomics in Radiotherapy-Induced Early Adverse Skin Reactions of Breast Cancer Patients.

Early adverse skin reactions (EASRs) are common side effects of radiotherapy (RT) that impact the quality of life of breast cancer patients. This study used global metabolomics profiles of breast cancer populations to identify metabolic pathways and biomarkers significantly associated with RT-induced EASRs to identify potential targets for precision interventions. We used a frequency-matched study design to identify pre-RT urine samples from 60 female breast cancer patients (30 with high and 30 with low EASRs) for metabolomic analysis by Metabolon Inc. using UPLC-MS/MS and GC-MS. Using MetaboAnalyst, we performed metabolomic data analysis and visualization on 84 candidate metabolites from 478 total compounds. We used the Oncology Nursing Society (ONS) Skin Toxicity Criteria (0-6) for EASRs assessment. Seven metabolic pathways were significantly associated with RT-induced EASRs, including alanine, aspartate, and glutamate metabolism (p = 0.0028), caffeine metabolism (p = 0.0360), pentose and glucuronate interconversions (p = 0.0028), glycine, serine, and threonine metabolism (p = 0.0360), beta-alanine metabolism (p = 0.0210), pantothenate and CoA biosynthesis (p = 0.0028), and glutathione metabolism (p = 0.0490). The alanine, aspartate, and glutamate metabolic pathway had the lowest false discovery rate (FDR)-adjusted p-value and the highest impact value of 0.60. Thirteen metabolite biomarkers were significantly associated with RT-induced EASRs. Our data show that the alanine, aspartate, and glutamate metabolism pathways had the highest impact value on RT-induced EASRs. Future larger studies are warranted to validate our findings and facilitate targeted interventions for preventing or mitigating RT-induced EASRs, offering a promising direction for further research and clinical applications.

The miniJPAS Survey: The radial distribution of star formation rates in faint X-ray active galactic nuclei

We study the impact of black hole nuclear activity on both the global and radial star formation rate (SFR) profiles in X-ray-selected active galactic nuclei (AGN) in the field of miniJPAS, the precursor of the much wider J-PAS project. Our sample includes 32 AGN with z < 0.3 detected via the XMM-Newton and Chandra surveys. For comparison, we assembled a control sample of 71 star-forming (SF) galaxies with similar magnitudes, sizes, and redshifts. To derive the global properties of both the AGN and the control SF sample, we used CIGALE to fit the spectral energy distributions derived from the 56 narrowband and 4 broadband filters from miniJPAS. We find that AGN tend to reside in more massive galaxies than their SF counterparts. After matching samples based on stellar mass and comparing their SFRs and specific SFRs (sSFRs), no significant differences appear. This suggests that the presence of AGN does not strongly influence overall star formation. However, when we used miniJPAS as an integral field unit (IFU) to dissect galaxies along their position angle, a different picture emerges. We find that AGN tend to be more centrally concentrated in mass with respect to SF galaxies. Moreover, we find a suppression of the sSFR up to 1Re and then an enhancement beyond 1Re, strongly contrasting with the decreasing radial profile of sSFRs in SF galaxies. This could point to an inside-out quenching of AGN host galaxies. Additionally, we examined how the radial profiles of the sSFRs in AGN and SF galaxies depend on galaxy morphology, by dividing our sample into disk-dominated (DD), pseudo-bulge (PB), and bulge-dominated (BD) systems. In DD systems, AGN exhibit a flat sSFR profile in the central regions and enhanced star formation beyond 1Re, contrasting with SF galaxies. In PB systems, SF galaxies show a decreasing sSFR profile, while AGN hosts exhibit an inside-out quenching scenario. In BD systems, both populations demonstrate consistent flat sSFR profiles. These findings suggest that the reason we do not see differences on a global scale is because star formation is suppressed in the central regions and enhanced in the outer regions of AGN host galaxies. While limited in terms of sample size, this work highlights the potential of the upcoming J-PAS as a wide-field low-resolution IFU for thousands of nearby galaxies and AGN.

Gyrokinetic investigation of toroidal Alfvén eigenmode (TAE) turbulence

Toroidal Alfvén eigenmodes (TAEs) can transport fusion-born energetic particles out of the plasma volume, thereby decreasing plasma self-heating efficiency and possibly damaging reactor walls. Therefore, understanding TAE destabilization and identifying saturation mechanisms are crucial to achieving burning plasma. Here, a fully gyrokinetic study is employed. In the case studied, the primary drive mechanism is identified as the resonance between the magnetic drifts and the TAE, and this is seen to be disrupted by equilibrium flow shear, which can stabilize the mode by rotating it in the poloidal plane. It is found that zonal flows do not play a significant role in the saturation of these TAEs and that there are no saturation mechanisms present in the local gyrokinetic picture, which are able to saturate the mode at physically relevant transport levels in the case of TAE-only turbulence. Instead, we confirm that the global profile flattening of fast-ion density is the key saturation mechanism. The nonlinear excitation of TAEs traveling along the electron diamagnetic direction and its beating with the ion diamagnetic TAE, resulting in large amplitude oscillations that may help detect TAEs more easily in tokamaks, are also reported.

Paradiplomacy and Its Influence on Visitor Trends at Twin World Heritage Sites: A Case Study of Borobudur Temple 2018-2019

Indonesia, recognized for its substantial tourism potential, has leveraged the iconic Borobudur Temple, a premier cultural heritage site, to bolster its international cultural diplomacy and marketing efforts. This study examines the impact of the Twin World Heritage cooperation program implemented by the Indonesian government through PT. Taman Wisata Candi, on visitor numbers at Borobudur Temple during 2018-2019. The program epitomizes a strategic approach to enhancing cultural relations by facilitating cross-border collaborations and the exchange of expertise in cultural preservation and promotion. Situated in Magelang, Central Java, the Twin World Heritage Program at Borobudur Temple has not only elevated the temple's global profile but has also served as a pivotal instrument in strengthening international cultural ties and fostering mutual appreciation and understanding across nations. The empirical data from this study reveal a notable increase in visitor attendance: domestic visitor figures rose from 3,663,054 in 2018 to 3,747,757 in 2019, while foreign visitor numbers increased from 192,231 to 242,082 over the same period. These findings affirm the program's efficacy in harnessing Borobudur's potential and generating significant socio-economic benefits across multiple sectors.

Land Surface Longwave Radiation Retrieval from ASTER Clear-Sky Observations

Surface longwave radiation (SLR) plays a pivotal role in the Earth’s energy balance, influencing a range of environmental processes and climate dynamics. As the demand for high spatial resolution remote sensing products grows, there is an increasing need for accurate SLR retrieval with enhanced spatial detail. This study focuses on the development and validation of models to estimate SLR using measurements from the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor. Given the limitations posed by fewer spectral bands and data products in ASTER compared to moderate-resolution sensors, the proposed approach combines an atmospheric radiative transfer model MODerate resolution atmospheric TRANsmission (MODTRAN) with the Light Gradient Boosting Machine algorithm to estimate SLR. The MODTRAN simulations were performed to construct a representative training dataset based on comprehensive global atmospheric profiles and surface emissivity spectra data. Global sensitivity analyses reveal that key inputs influencing the accuracy of SLR retrievals should reflect surface thermal radiative signals and near-surface atmospheric conditions. Validated against ground-based measurements, surface upward longwave radiation (SULR) and surface downward longwave radiation (SDLR) using ASTER thermal infrared bands and surface elevation estimations resulted in root mean square errors of 17.76 W/m2 and 25.36 W/m2, with biases of 3.42 W/m2 and 3.92 W/m2, respectively. Retrievals show systematic biases related to extreme temperature and moisture conditions, e.g., causing overestimation of SULR in hot humid conditions and underestimation of SDLR in arid conditions. While challenges persist, particularly in addressing atmospheric variables and cloud masking, this work lays a foundation for accurate SLR retrieval from high spatial resolution sensors like ASTER. The potential applications extend to upcoming satellite missions, such as the Landsat Next, and contribute to advancing high-resolution remote sensing capabilities for an improved understanding of Earth’s energy dynamics.

AB-free kava enhances resilience against the adverse health effects of tobacco smoke in mice.

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onsets of numerous preventive diseases, and imposing significant financial burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco smoke-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2 - 4 weeks of daily tobacco smoke exposure. Our comprehensive assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal PKA signaling pathway. As expected, Tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering a unique promise to mitigate tobacco smoke-related health damages. Further pre-clinical evaluation and clinical translation are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms.

Inter-cellular mRNA Transfer Alters Human Pluripotent Stem Cell State.

Inter-cellular transmission of mRNA is being explored in mammalian species using immortal cell lines (1-3). Here, we uncover an inter-cellular mRNA transfer phenomenon that allows for the adaptation and reprogramming of human primed pluripotent stem cells (hPSCs). This process is induced by the direct cell contact-mediated coculture with mouse embryonic stem cells (mESCs) under the condition impermissible for human primed PSC culture. Mouse-derived mRNA contents are transmitted into adapted hPSCs only in the coculture. Transfer-specific mRNA analysis show the enrichment for divergent biological pathways involving transcription/translational machinery and stress-coping mechanisms, wherein such transfer is diminished when direct cell contacts are lost. After 5 days of mESC culture, surface marker analysis, and global gene profiling confirmed that mRNA transfer-prone hPSC efficiently gains a naïve-like state. Furthermore, transfer-specific knockdown experiments targeting mouse-specific transcription factor-coding mRNAs in hPSC show that mouse-derived Tfcp2l1, Tfap2c, and Klf4 are indispensable for human naïve-like conversion. Thus, inter-species mRNA transfer triggers cellular reprogramming in mammalian cells. Our results support that episodic mRNA transfer can occur in cell cooperative and competitive processes(4), which provides a fresh perspective on understanding the roles of mRNA mobility for intra- and inter-species cellular communications.

Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3

KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these mutations may shape epigenomic and transcriptomic landscapes to promote tumorigenesis is largely unknown. Here we describe that deletion of Kmt2c or Kmt2d in non-metastatic murine models of TNBC drives metastasis, especially to the brain. Global chromatin profiling and chromatin immunoprecipitation followed by sequencing revealed altered H3K4me1, H3K27ac and H3K27me3 chromatin marks in knockout cells and demonstrated enhanced binding of the H3K27me3 lysine demethylase KDM6A, which significantly correlated with gene expression. We identified Mmp3 as being commonly upregulated via epigenetic mechanisms in both knockout models. Consistent with these findings, samples from patients with KMT2C-mutant TNBC have higher MMP3 levels. Downregulation or pharmacological inhibition of KDM6A diminished Mmp3 upregulation induced by the loss of histone–lysine N-methyltransferase 2 (KMT2) and prevented brain metastasis similar to direct downregulation of Mmp3. Taken together, we identified the KDM6A–matrix metalloproteinase 3 axis as a key mediator of KMT2C/D loss-driven metastasis in TNBC.

Transcriptomic Insights into the Developmental Dynamics of Eimeria acervulina: A Comparative Study of a Precocious Line and the Wild Type.

Coccidiosis, a parasitic disease caused by single or multiple Eimeria species, leads to significant economic losses in the poultry industry. The Eimeria life cycle includes schizogony, gametogony, and sporogony. To investigate the dynamics of gene expression and regulatory networks during the development of Eimeria acervulina, we employed time-course transcriptomics to rigorously compare the gene expression patterns between a precocious line (PL) and the wild type (WT) of E. acervulina. The results revealed that the PL enters into gametogony 12 h earlier than the WT, and both the PL and WT exhibited distinct clustering patterns during the development phase. A weighted gene co-expression network analysis (WGCNA) identified genes specifically expressed at four distinct developmental stages, schizogony, gametogony, sporulated oocysts, and unsporulated oocysts, clarifying the key biological processes at each stage. This study used global transcriptome profiling to elucidate molecular variations throughout the E. acervulina life cycle, providing critical insights into molecular characterization and valuable resources for investigating other apicomplexan parasites of public health importance.

CODC-v1: a quality-controlled and bias-corrected ocean temperature profile database from 1940–2023

High-quality ocean in situ profile observations are fundamental for ocean and climate research and operational oceanographic applications. Here we describe a new global ocean subsurface temperature profile database named the Chinese Academy of Science (CAS) Oceanography Data Center version 1 (CODC-v1). This database contains over 17 million temperature profiles between 1940–2023 from all available instruments. The major data source is the World Ocean Database (WOD), but CODC-v1 also includes some data from some Chinese institutes which are not available in WOD. The data are quality-controlled (QC-ed) by a new QC system that considers the skewness of local temperature distributions, topographic barriers, and the shift of temperature distributions due to climate change. Biases in Mechanical Bathythermographs (MBTs), eXpendable Bathythermographs (XBTs), and Bottle data (OSD) are all corrected using recently proposed correction schemes, which makes CODC-v1 a bias-corrected dataset. These aspects ensure the data quality of the CODC-v1 database, making it suitable for a wide spectrum of ocean and climate research and applications.

Research on reconstruction of the global sound speed profile combining partial underwater prior information

The sound speed profile (SSP) is an important factor affecting the acoustic propagation characteristics of the ocean, making the accurate acquisition of SSP a crucial step in the interdisciplinary research of oceanography and underwater acoustics. Limited by the cost of in-situ measurement and the performance of the instrument itself, direct measurement of SSP inevitably leads to insufficient depth or even missing information. In this paper, we propose using partial underwater prior information (UWPI) only including underwater sound speed to obtain preliminary reconstruction results of global SSP for the first time. The empirical orthogonal function (EOF) reconstruction algorithm is optimized by employing assimilated SSP as the background SSP to further reduce reconstruction errors. The maximum global average reconstruction error and root mean square error (RMSE) after optimization decrease by >51% and 71%, respectively, which indicates that the performance of the optimized algorithm combined with partial UWPI is further improved. Finally, the performance of the optimized algorithm is discussed from the perspective of acoustic propagation. This research provides a reliable technical approach for SSP reconstruction under incomplete depth conditions, which can be applied in underwater sound field prediction and acoustic detection in the future.

A Level 3 monthly gridded ice cloud dataset derived from 12 years of CALIOP measurements

Abstract. Clouds play important roles in weather, climate, and the global water cycle. The Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) onboard the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) spacecraft has measured global vertical profiles of clouds and aerosols in the Earth’s atmosphere since June 2006. CALIOP provides vertically resolved information on cloud occurrence, thermodynamic phase, and properties. We describe version 1.0 of a monthly gridded ice cloud product derived from over 12 years of global, near-continuous CALIOP measurements. The primary contents are monthly vertically resolved histograms of ice cloud extinction coefficient and ice water content (IWC) retrievals. The CALIOP Level 3 Ice Cloud product is built from the CALIOP Version 4.20 Level 2 5 km Cloud Profile product that, relative to previous versions, features substantial improvements due to more accurate lidar backscatter calibration, better extinction coefficient retrievals, and a temperature-sensitive parameterization of IWC. The gridded ice cloud data are reported as histograms, which provides data users with the flexibility to compare CALIOP’s retrieved ice cloud properties with those from other instruments with different measurement sensitivities or retrieval capabilities. It is also convenient to aggregate monthly histograms for seasonal, annual, or decadal trend and climate analyses. This CALIOP gridded ice cloud product provides a unique characterization of the global and regional vertical distributions of optically thin ice clouds and deep convection cloud tops, and it should provide significant value for cloud research and model evaluation. A DOI has been issued for the product: https://doi.org/10.5067/CALIOP/CALIPSO/L3_ICE_CLOUD-STANDARD-V1-00 (Winker et al., 2018).

Toward a Direct Measurement of the Cosmic Acceleration: The Pilot Observation of HI 21 cm Absorption Line at FAST

This study presents results on detecting neutral atomic hydrogen (H i) 21 cm absorption in the spectrum of PKS PKS1413+13 at redshift z = 0.24670041. The observation was conducted by FAST, with a spectral resolution of 10 Hz, using 10 minutes of observing time. The global spectral profile is examined by modeling the absorption line using a single Gaussian function with a resolution of 10 kHz within a 2 MHz bandwidth. The goal is to determine the rate of the latest cosmic acceleration by directly measuring the redshift evolution of the H i 21 cm absorption line with Hubble flow toward a common background quasar over a decade or longer time span. This will serve as a detectable signal generated by the accelerated expansion of the Universe at redshift z < 1, referred to as redshift drift ż or the SL effect. The measured H i gas column density in this DLA system is approximately equivalent to the initial observation value, considering uncertainties of the spin temperature of a spiral host galaxy. The high signal-to-noise ratio of 57, obtained at a 10 kHz resolution, strongly supports the feasibility of using the H i 21 cm absorption line in DLA systems to accurately measure the redshift drift rate at a precision level of around 10−10 per decade.

PATH-11. FEASIBILITY OF BRAIN TUMOR CLASSIFICATION BY ENZYMATIC DNA METHYLATION SEQUENCING ANALYSIS OF CELL-FREE DNA OBTAINED FROM CEREBROSPINAL FLUID

Abstract BACKGROUND Array-based DNA methylation profiling is the gold standard for molecular classification of brain tumors. However, it relies on significant amount of input DNA extracted from surgical tissue, thus limiting its use for tumors where biopsy is challenging or limited in quantity. Cell-free tumor DNA (cfDNA) in cerebrospinal fluid (CSF) presents alternative opportunities for brain tumor diagnosis and disease monitoring following treatment. Novel enzymatic DNA methylation sequencing (EM-seq) methods may allow us to overcome input DNA limitations and accurately quantify methylation from cfDNA. METHODS We performed methylation sequencing using the NEBNext EM-seq kit on cfDNA from archival CSF samples collected from three brain tumor patients with confirmed histopathological diagnoses. Variable amounts of input cfDNA (0.1ng-10ng) were tested. We utilized the methylseq pipeline for data processing. For tumor classification, data was limited to CpG sites overlapping the MethylationEPIC array before analysis using MNP-Flex, a modified platform-agnostic version of the Heidelberg methylation classifier RESULTS Using the EM-seq method, genomic coverage for 10 and 1ng input DNA samples (average: 46x and 26x, respectively) was sufficient for generating global methylation profiles. Samples with 0.1ng input showed an average coverage of only 5.32x due to high levels of read duplication. However, methylation levels for CpG sites with at least 5x coverage were highly correlated across varying input DNA amounts, suggesting that lower input cfDNA could still be used for tumor classification based on relevant CpG sites. CONCLUSIONS Using the MNP-Flex classifier, which was originally trained with methylation array data from tumor tissue, we successfully predicted brain tumor types (both high-grade glioma and medulloblastoma) with cfDNA methylation data down to only 0.1ng of input cfDNA, matching diagnosis based on tissue methylation and histopathology in this pilot study. Further classification of additional tumor types using CSF cfDNA is required to confirm the clinical utility of this platform.

Global biochemical profiling of fast-growing Antarctic bacteria isolated from meltwater ponds by high-throughput FTIR spectroscopy.

Fourier transform infrared (FTIR) spectroscopy is a biophysical technique used for non-destructive biochemical profiling of biological samples. It can provide comprehensive information about the total cellular biochemical profile of microbial cells. In this study, FTIR spectroscopy was used to perform biochemical characterization of twenty-nine bacterial strains isolated from the Antarctic meltwater ponds. The bacteria were grown on two forms of brain heart infusion (BHI) medium: agar at six different temperatures (4, 10, 18, 25, 30, and 37°C) and on broth at 18°C. Multivariate data analysis approaches such as principal component analysis (PCA) and correlation analysis were used to study the difference in biochemical profiles induced by the cultivation conditions. The observed results indicated a strong correlation between FTIR spectra and the phylogenetic relationships among the studied bacteria. The most accurate taxonomy-aligned clustering was achieved with bacteria cultivated on agar. Cultivation on two forms of BHI medium provided biochemically different bacterial biomass. The impact of temperature on the total cellular biochemical profile of the studied bacteria was species-specific, however, similarly for all bacteria, lipid spectral region was the least affected while polysaccharide region was the most affected by different temperatures. The biggest temperature-triggered changes of the cell chemistry were detected for bacteria with a wide temperature tolerance such Pseudomonas lundensis strains and Acinetobacter lwoffii BIM B-1558.

Wideband PRM: Highly Accurate and Sensitive Method for High-Throughput Targeted Proteomics.

Targeted mass spectrometry (MS) approaches, which are powerful methods for uniquely and confidently quantifying a specific panel of proteins in complex biological samples, play a crucial role in validating and clinically translating protein biomarkers discovered through global proteomic profiling. Common targeted MS methods, such as multiple reaction monitoring (MRM) and parallel-reaction monitoring (PRM), employ specific mass spectrometric technologies to quantify protein levels by comparing the transitions of surrogate endogenous (ENDO) peptides with those of stable isotope-labeled (SIL) peptide counterparts. These methods utilizing amino acid analyzed (AAA) SIL peptides warrant sensitive and precise measurements required for targeted MS assays. Compared with MRM, PRM provides higher experimental throughput by simultaneously acquiring all transitions of the target peptides and thereby compensates for different ion suppressions among transitions of a target peptide. However, PRM still suffers different ion suppressions between ENDO and SIL peptides due to spray instability, as the ENDO and SIL peptides were monitored at different liquid chromatography (LC) retention times. Here we introduce a new targeted MS method, termed wideband PRM (WBPRM), that is designed for high-throughput targeted MS analysis. WBPRM employs a wide isolation window for simultaneous fragmentation of both ENDO and SIL peptides along with multiplexed single ion monitoring (SIM) scans for enhanced MS sensitivity of the target peptides. Compared with PRM, WBPRM was demonstrated to provide increased sensitivity, precision, and reproducibility of quantitative measurements of target peptides with increased throughput, allowing more target peptide measurements in a shortened experiment time. WBPRM is a straightforward adaptation to a manufacturer-provided MS method, making it an easily implementable technique, particularly in complex biological samples where the demand for higher precision, sensitivity, and efficiency is paramount.

A Transcriptomic and Metabolomic Study on the Biosynthesis of Iridoids in Phlomoides rotata from the Qinghai-Tibet Plateau.

Phlomoides rotata is a traditional Chinese herbal medicine that grows in the Qinghai-Tibet Plateau region at a 3100-5000 m altitude. Iridoid compounds are the main active compounds of the P. rotata used as medical ingredients and display anti-inflammatory, analgesic, and hepatoprotective properties. To better understand the biological mechanisms of iridoid compounds in this species, we performed a comprehensive analysis of the transcriptome and metabolome of P. rotata leaves from four different regions (3540-4270 m). Global metabolome profiling detected 575 metabolites, and 455 differentially accumulated metabolites (DAMs) were detected in P. rotata leaves from the four regions. Eight major DAMs related to iridoid metabolism in P. rotata leaves were investigated: shanzhiside methyl ester, 8-epideoxyloganic acid, barlerin, shanzhiside, geniposide, agnuside, feretoside, and catalpin. In addition, five soil physical and chemical indicators in P. rotata rhizosphere soils were analyzed. Four significant positive correlations were observed between alkaline nitrogen and geniposide, exchangeable calcium and geniposide, available potassium and shanzhiside, and available phosphorus and shanzhiside methyl ester. The transcriptome data showed 12 P. rotata cDNA libraries with 74.46 Gb of clean data, which formed 29,833 unigenes. Moreover, 78.91% of the unigenes were annotated using the eight public databases. Forty-one candidate genes representing 23 enzymes involved in the biosynthesis of iridoid compounds were identified in P. rotata leaves. Moreover, the DXS1, IDI1, 8-HGO1, and G10H2 genes associated with iridoid biosynthesis were specifically expressed in P. rotata. The integration of transcriptome and metabolome analyses highlights the crucial role of soil physical and chemical indicators and major gene expression related to iridoid metabolism pathways in P. rotata from different areas. Our findings provide a theoretical foundation for exploring the molecular mechanisms underlying iridoid compound accumulation in P. rotata.

Epidermal growth factor receptor/mitogen-activated kinase inhibitor treatment induces a distinct inflammatory hair follicle response that includes collapse of immune privilege.

Inhibitors of epidermal growth factor receptor (EGFRi) or mitogen-activated kinase (MEKi) induce a folliculitis in 75-90% of patients, the pathobiology of which remains insufficiently understood. To characterize changes in the skin immune status and global transcriptional profile of patients treated with EGFRi; to investigate whether EGFRi affects the hair follicle's (HF) immune privilege (IP); and to identify early proinflammatory signals induced by EGFRi/MEKi in human scalp HFs ex vivo. Scalp biopsies were taken from patients exhibiting folliculitis treated long term with EGFRi ('chronic EGFRi' group, n = 9) vs. healthy scalp skin (n = 9) and patients prior to commencing EGFRi treatment and after 2 weeks of EGFRi therapy ('acute EGFRi' group, n = 5). Healthy organ-cultured scalp HFs were exposed to an EGFRi (erlotinib, n = 5) or a MEKi (cobimetinib, n = 5). Samples were assessed by quantitative immunohistomorphometry, RNA sequencing (RNAseq) and in situ hybridization. The 'chronic EGFRi' group showed CD8+ T-cell infiltration of the bulge alongside a partial collapse of the HF's IP, evidenced by upregulated major histocompatibility complex (MHC) class I, β2-microglobulin (B2 M) and MHC class II, and decreased transforming growth factor-β1 protein expression. Healthy HFs treated with EGFRi/MEKi ex vivo also showed partial HF IP collapse and increased transcription of human leucocyte antigen (HLA)-A, HLA-DR and B2 M transcripts. RNAseq analysis showed increased transcription of chemokines (CXCL1, CXCL13, CCL18, CCL3, CCL7) and interleukin (IL)-26 in biopsies from the 'chronic EGFRi' cohort, as well as increased IL-33 and decreased IL-37 expression in HF biopsies from the 'acute EGFRi' group and in organ-cultured HFs. The data show that EGFRi/MEKi compromise the physiological IP of human scalp HFs and suggest that future clinical management of EGFRi/MEKi-induced folliculitis requires HF IP protection and inhibition of IL-33.

Local structural modelling and local pair distribution function analysis for Zr–Pt metallic glass

In disordered glass structures, the structural modelling and analyses based on local experimental data are not yet established. Here we investigate the icosahedral short-range order (SRO) in a Zr–Pt metallic glass using local structural modelling, which is a reverse Monte Carlo simulation dedicated to two-dimensional angstrom-beam electron diffraction (ABED) patterns, and local pair distribution function (PDF) analysis. The local structural modelling invariably leads to the icosahedral SRO atomic configurations that are similarly distorted by starting from some different initial configurations. Furthermore, the SRO configurations with 11–13 coordination numbers reproduce almost identical ABED patterns, indicating that these SRO structures are similar to each other. Further local PDF analysis explicitly indicates the presence of the wide distribution of atomic bond distances, which is comparable to the global PDF profile, even at the SRO level. The SRO models based on the conventional MD simulation can be strengthened by comparison with those obtained by the present local structural modelling and local PDF analysis based on the ABED data.

Latent Profiles of Acute Symptoms, Cognitive Performance, and Balance in Sport-Related Concussions

Background: A sport-related concussion (SRC) is a common injury that affects multiple clinical domains such as cognition, balance, and nonspecific neurobehavioral symptoms. Although multidimensional clinical assessments of concussion are widely accepted, there remain limited empirical data on the nature and clinical utility of distinct clinical profiles identified by multimodal assessments. Purpose: Our objectives were to (1) identify distinct clinical profiles discernible from acute postinjury scores on the Sport Concussion Assessment Tool (SCAT), composed of a symptom checklist, a cognitive assessment (Standardized Assessment of Concussion), and a balance assessment (Balance Error Scoring System), and (2) evaluate the clinical utility of the identified profiles by examining their association with injury characteristics, neuropsychological outcomes, and clinical management–related outcomes. Study Design: Cohort study (Prognosis); Level of evidence, 2. Methods: Up to 7 latent profiles were modeled for 1885 collegiate athletes and/or military cadets who completed the SCAT at 0 to 12 hours after an injury. Chi-square tests and general linear models were used to compare identified profiles on outcomes at 12 to 72 hours after the injury. Kaplan-Meier analysis was used to investigate associations between clinical profiles and time to return to being asymptomatic and to return to play. Results: There were 5 latent profiles retained: low impairment (65.8%), high cognitive impairment (5.4%), high balance impairment (5.8%), high symptom severity (16.4%), and global impairment (6.5%). The latent profile predicted outcomes at 12 to 72 hours in expectable ways (eg, the high balance impairment profile demonstrated worse balance at 12 to 72 hours after the injury). Time to return to being asymptomatic and to return to play were different across profiles, with the high symptom severity and global impairment profiles experiencing the longest recovery and the high balance impairment profile experiencing an intermediate-length recovery (vs low impairment profile). Conclusion: An SRC is a heterogeneous injury that presents in varying ways clinically in the acute injury period and results in different recovery patterns. These data support the clinical prognostic value of diverse profiles of impairment across symptom, cognitive, and balance domains. By identifying distinct profiles of an SRC and connecting them to differing outcomes, the findings support more evidence-based use of accepted multimodal clinical assessment strategies for SRCs.