Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Benchmarking of a Monte Carlo Dose Engine for Proton Radiation Therapy

Dose calculation algorithms based on Monte Carlo (MC) simulations play a crucial role in radiotherapy. Here, the development and benchmarking of a novel MC dose engine, MonteRay, is presented for proton therapy aiming to support clinical activity at the Heidelberg Ion Beam Therapy center (HIT) and the development of MRI (magnetic resonance imaging)-guided particle therapy. Comparisons against dosimetric data and gold standard MC FLUKA calculations at different levels of complexity, ranging from single pencil beams in water to patient plans, showed high levels of agreement, validating the physical approach implemented in the dose engine. Additionally, MonteRay has been found to match satisfactorily to FLUKA dose predictions in magnetic fields both in homogeneous and heterogeneous scenarios advocating its use for future MRI-guided proton therapy applications. Benchmarked on 150 MeV protons transported on a 2 × 2 × 2 mm3 grid, MonteRay achieved a high computational throughput and was able to simulate the histories of more than 30,000 primary protons per second on a single CPU core.
Genome-Wide Identification of Wheat ZIP Gene Family and Functional Characterization of the TaZIP13-B in Plants

The ZIP (Zn-regulated, iron-regulated transporter-like protein) transporter plays an important role in regulating the uptake, transport, and accumulation of microelements in plants. Although some studies have identified ZIP genes in wheat, the significance of this family is not well understood, particularly its involvement under Fe and Zn stresses. In this study, we comprehensively characterized the wheat ZIP family at the genomic level and performed functional verification of three TaZIP genes by yeast complementary analysis and of TaZIP13-B by transgenic Arabidopsis. Totally, 58 TaZIP genes were identified based on the genome-wide search against the latest wheat reference (IWGSC_V1.1). They were then classified into three groups, based on phylogenetic analysis, and the members within the same group shared the similar exon-intron structures and conserved motif compositions. Expression pattern analysis revealed that the most of TaZIP genes were highly expressed in the roots, and nine TaZIP genes displayed high expression at grain filling stage. When exposed to ZnSO4 and FeCl3 solutions, the TaZIP genes showed differential expression patterns. Additionally, six ZIP genes responded to zinc-iron deficiency. A total of 57 miRNA-TaZIP interactions were constructed based on the target relationship, and three miRNAs were downregulated when exposed to the ZnSO4 and FeCl3 stresses. Yeast complementation analysis proved that TaZIP14-B, TaZIP13-B, and TaIRT2-A could transport Zn and Fe. Finally, overexpression of TaZIP13-B in Arabidopsis showed that the transgenic plants displayed better tolerance to Fe/Zn stresses and could enrich more metallic elements in their seeds than wild-type Arabidopsis. This study systematically analyzed the genomic organization, gene structure, expression profiles, regulatory network, and the biological function of the ZIP family in wheat, providing better understanding of the regulatory roles of TaZIPs and contributing to improve nutrient quality in wheat crops.
Systematic Exploration in Tissue-Pathway Associations of Complex Traits Using Comprehensive eQTLs Catalog

The collection of expression quantitative trait loci (eQTLs) is an important resource to study complex traits through understanding where and how transcriptional regulations are controlled by genetic variations in the non-coding regions of the genome. Previous studies have focused on associating eQTLs with traits to identify the roles of trait-related eQTLs and their corresponding target genes involved in trait determination. Since most genes function as a part of pathways in a systematic manner, it is crucial to explore the pathways’ involvements in complex traits to test potentially novel hypotheses and to reveal underlying mechanisms of disease pathogenesis. In this study, we expanded and applied loci2path software to perform large-scale eQTLs enrichment [i.e., eQTLs’ target genes (eGenes) enrichment] analysis at pathway level to identify the tissue-specific enriched pathways within trait-related genomic intervals. By utilizing 13,791,909 eQTLs cataloged in the Genotype-Tissue Expression (GTEx) V8 data for 49 tissue types, 2,893 pathway sets reported from MSigDB, and query regions derived from the Phenotype-Genotype Integrator (PheGenI) catalog, we identified intriguing biological pathways that are likely to be involved in ten traits [Alzheimer’s disease (AD), body mass index, Parkinson’s disease (PD), schizophrenia, amyotrophic lateral sclerosis, non-small cell lung cancer (NSCLC), stroke, blood pressure, autism spectrum disorder, and myocardial infarction]. Furthermore, we extracted the most significant pathways for AD, such as BioCarta D4-GDI pathway and WikiPathways sulfation biotransformation reaction and viral acute myocarditis pathways, to study specific genes within pathways. Our data presented new hypotheses in AD pathogenesis supported by previous studies, like the increased level of caspase-3 in the amygdala that cleaves GDP dissociation inhibitor and binds to beta-amyloid, leading to increased apoptosis and neuronal loss. Our findings also revealed potential pathogenesis mechanisms for PD, schizophrenia, NSCLC, blood pressure, autism spectrum disorder, and myocardial infarction, which were consistent with past studies. Our results indicated that loci2path′s eQTLs enrichment test was valuable in unveiling novel biological mechanisms of complex traits. The discovered mechanisms of disease pathogenesis and traits require further in-depth analysis and experimental validation.
Meroterpenoids From Ganoderma lucidum Mushrooms and Their Biological Roles in Insulin Resistance and Triple-Negative Breast Cancer

Ganoderma fungi as popular raw materials of numerous functional foods have been extensively investigated. In this study, five pairs of meroterpenoid enantiomers beyond well-known triterpenoids and polysaccharides, dayaolingzhiols I−M (1–5), were characterized from Ganoderma lucidum. Their structures were identified using spectroscopic and computational methods. Structurally, compound 1 features a novel dioxabicyclo[2.2. 2]octan-3-one motif in the side chain. Ethnoknowledge-derived biological evaluation found that (+)-5 could activate Akt and AMPK phosphorylation in insulin-stimulated C2C12 cells, and (+)-5 could activate glucose uptake dose dependently in C2C12 cells. Furthermore, we found that (+)-1 (+)-4, and (–)-4 could significantly inhibit cell migration of the MDA-MB-231 cell line, of which (+)-4 showed significant inhibitory effects against cell migration of the MDA-MB-231 cell line in a dose-dependent manner. These findings revealed the meroterpenoidal composition of G. lucidum and its roles in the prevention of chronic diseases such as diabetes mellitus and triple-negative breast cancer.
The Brain Tracks Multiple Predictions About the Auditory Scene

The predictable rhythmic structure is important to most ecologically relevant sounds for humans, such as is found in the rhythm of speech or music. This study addressed the question of how rhythmic predictions are maintained in the auditory system when there are multiple perceptual interpretations occurring simultaneously and emanating from the same sound source. We recorded the electroencephalogram (EEG) while presenting participants with a tone sequence that had two different tone feature patterns, one based on the sequential rhythmic variation in tone duration and the other on sequential rhythmic variation in tone intensity. Participants were presented with the same sound sequences and were instructed to listen for the intensity pattern (ignore fluctuations in duration) and press a response key to detected pattern deviants (attend intensity pattern task); to listen to the duration pattern (ignore fluctuations in intensity) and make a button press to duration pattern deviants (attend duration pattern task), and to watch a movie and ignore the sounds presented to their ears (attend visual task). Both intensity and duration patterns occurred predictably 85% of the time, thus the key question involved evaluating how the brain treated the irrelevant feature patterns (standards and deviants) while performing an auditory or visual task. We expected that task-based feature patterns would have a more robust brain response to attended standards and deviants than the unattended feature patterns. Instead, we found that the neural entrainment to the rhythm of the standard attended patterns had similar power to the standard of the unattended feature patterns. In addition, the infrequent pattern deviants elicited the event-related brain potential called the mismatch negativity component (MMN). The MMN elicited by task-based feature pattern deviants had a similar amplitude to MMNs elicited by unattended pattern deviants that were unattended because they were not the target pattern or because the participant ignored the sounds and watched a movie. Thus, these results demonstrate that the brain tracks multiple predictions about the complexities in sound streams and can automatically track and detect deviations with respect to these predictions. This capability would be useful for switching attention rapidly among multiple objects in a busy auditory scene.
Prevalence and Impact Factors of COVID-19 Vaccination Hesitancy Among Breast Cancer Survivors: A Multicenter Cross-Sectional Study in China

Cancer patients are at a high risk of being infected with COVID-19 and have a poor prognosis after infection. Breast cancer is one of the most common cancers. Since vaccination is an effective measure to prevent the spread of COVID-19, we studied the vaccination rate among breast cancer survivors and analyzed their characteristics to provide evidence for boosting the vaccination rate. The researchers conducted a multicenter, cross-sectional study on 747 breast cancer survivors from six hospitals in Wuhan city between June 5, 2021, and June 12, 2021. The self-administrated questionnaires based on relevant studies were distributed. The researchers then compared differences in characteristics among vaccinated patients, hesitant patients, and non-vaccinated patients. Moreover, they performed univariable and multivariable logistic regression analyses to identify potential factors associated with vaccination hesitancy. The researchers assessed a total of 744 breast cancer survivors −94 cases in the vaccinated group, 103 in the planning group, 295 in the hesitancy group, and 252 in the refusal group. The vaccination rate was 12.63% (95% CI 10.25–15.02%) and 37.23% (95% CI 27.48–47.82%) patients reported adverse reactions. The vaccination hesitancy/refusal rate was 73.52% (95% CI 70.19–76.66%), which was independently associated with current endocrine or targeted therapy (odds ratio [OR] = 1.52, 95% CI 1.03–2.24), no notification from communities or units (OR = 2.46, 95% CI 1.69–3.59) and self-perceived feel (general vs. good, OR = 1.46, 95% CI 1.01–2.13; bad vs. good, OR = 4.75, 95% CI 1.85–12.16). In the hesitancy/refusal group, the primary reason was “I did not know who to ask whether I can get vaccinated” (46.07%), the person who would most influence decisions of patients was the doctor in charge of treatment (35.83%). Effective interaction between doctors and patients, simple and consistent practical guidelines on vaccination, and timely and positive information from authoritative media could combat misinformation and greatly reduce vaccine hesitancy among breast cancer survivors.
FISH Going Meso-Scale: A Microscopic Search for Chromatin Domains

The intimate relationships between genome structure and function direct efforts toward deciphering three-dimensional chromatin organization within the interphase nuclei at different genomic length scales. For decades, major insights into chromatin structure at the level of large-scale euchromatin and heterochromatin compartments, chromosome territories, and subchromosomal regions resulted from the evolution of light microscopy and fluorescence in situ hybridization. Studies of nanoscale nucleosomal chromatin organization benefited from a variety of electron microscopy techniques. Recent breakthroughs in the investigation of mesoscale chromatin structures have emerged from chromatin conformation capture methods (C-methods). Chromatin has been found to form hierarchical domains with high frequency of local interactions from loop domains to topologically associating domains and compartments. During the last decade, advances in super-resolution light microscopy made these levels of chromatin folding amenable for microscopic examination. Here we are reviewing recent developments in FISH-based approaches for detection, quantitative measurements, and validation of contact chromatin domains deduced from C-based data. We specifically focus on the design and application of Oligopaint probes, which marked the latest progress in the imaging of chromatin domains. Vivid examples of chromatin domain FISH-visualization by means of conventional, super-resolution light and electron microscopy in different model organisms are provided.
Animal Toxicology Studies on the Male Reproductive Effects of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin: Data Analysis and Health Effects Evaluation

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental poison that exist in the environment for many years. However, its effect on the male reproductive system has not been clearly stated. We conducted a meta-analysis of the effect of TCDD on the male reproductive system of rodents about TCDD. Results showed that that TCDD exposure reduced the testis weight (weighted mean difference [WMD]: −0.035, 95% confidence interval [CI]: −0.046 to −0.025), sperm count (WMD: −35, 95% CI: −42.980 to −27.019), and blood testosterone concentration (WMD: −0.171, 95% CI: −0.269 to −0.073). According to our research results, TCDD can cause damage to the male reproductive system of rodents through direct or indirect exposure. In order to further explore the potential hazards of TCDD to humans, more human-related research needs to be carried out.
A Review of the Ethnopharmacology, Phytochemistry, Pharmacology, Application, Quality Control, Processing, Toxicology, and Pharmacokinetics of the Dried Rhizome of Atractylodes macrocephala

The product investigated herein is the dried rhizome of Atractylodes macrocephala Koidz. [Asteraceae] (Baizhu), which is also known as Dongbaizhu, Wuzhu, Yuzhu, Zhezhu, and Zhongzhu, among others. It invigorates the spleen, replenishes qi, and removes dampness, diuresis, and hidroschesis, and impacts fetal safety. It is often used for the treatment of diseases such as spleen function deficiency, abdominal distension, diarrhea, sputum, vertigo, edema, fever, and sweating and also aids cessation of minimal vaginal bleeding during pregnancy. In this study, research pertaining to the ethnopharmacology, application, phytochemistry, analytical methods, quality control, processing, pharmacology, toxicology, and pharmacokinetics of Baizhu has been reviewed. Relevant information and data reported for Baizhu were collected from CNKI, VIP, PubMed, Web of Science, scientific databases, Chinese Medicinal Material Encyclopedia, Chinese herbal medicine classics, Chinese medicine dictionary, doctoral and master’s theses, and so on. Baizhu demonstrates diuretic, antidiuretic, anti-inflammatory effects and antitumor function and aids regulation of gastrointestinal function, hypoglycemic effect, analgesic action, protection on the liver ischemia-reperfusion injury (IRI) in rats, inhibition of aromatase, treatment of bone disease, strengthening myocardial contraction ability, detoxification and cholagogic effect, fall hematic fat action, such as the treatment of acute renal injury, and so on. It also can be an anticoagulant, improve the nervous system disease, affect the immune system, and regulate uterine smooth muscle, antioxidation, antiaging, and antibacterial effect. Sesquiterpenoids, triterpenoids, polyacetylenes, phenylpropanoids, coumarins, flavonoids, flavonoid glycosides, steroids, benzoquinones, polysaccharides, and other compounds were isolated from Baizhu. Among them, sesquiterpenoids, polysaccharides, and polyacetylenes are the main components of Baizhu. Baizhu exhibits a wide range of pharmacological effects and constitutes a considerable proportion of the composition of many proprietary crude drugs. It mainly affects the endocrine, nervous, and urinary systems. The presented information suggests that we should focus on the development of new drugs related to Baizhu, including specific components, to achieve a greater therapeutic potential that can be considered to further explore the information related to Baizhu.
Combinatorial Analysis of AT-Rich Interaction Domain 1A and CD47 in Gastric Cancer Patients Reveals Markers of Prognosis

Background: The AT-rich interaction domain 1A (ARID1A) is thought to be a tumor suppressive gene, and most of its mutations result in loss of expression of ARID1A protein. Combined with SIRPα on the surface of macrophages, CD47 on the surface of cancer cells can send an antiphagocytic “Don’t eat me” signal to the immune system that helps to avoid immune surveillance. However, the relationship between ARID1A and CD47 expression and their prognostic value in gastric cancer (GC) are still unknown. Methods: In this study, we evaluated ARID1A and CD47 expression in 154 GC patients’ tissues using tissue microarray. Expressions of ARID1A and CD47 in GC cell lines were determined by western blot and quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) techniques, and cell membranous CD47 expression was quantified by flow cytometry. In addition, chromatin immunoprecipitation (ChIP)–qPCR was used to determine the aspects of regulation of CD47 by ARID1A. The proportions of tumor-infiltrating immune cells were estimated on The Cancer Genome Atlas (TCGA) data set by using quanTIseq and EPIC algorithms. The infiltration of M1-polarized macrophages, M2-polarized macrophages, and regulatory T cells (Tregs) in GC tissues was determined by multispectral immunofluorescence. Results: A significant correlation was found between loss of ARID1A and high expression of CD47 at protein level in GC. By integrating 375 bulk RNA sequencing samples from TCGA data set, we found that mutated ARID1A correlated with high CD47 expression. In GC cell lines, knockdown of ARID1A significantly increased CD47 expression both at protein and mRNA levels as measured by western blot, qRT-PCR, and flow cytometry. Moreover, ChIP-qPCR revealed that CD47 was a direct downstream target gene of ARID1A in GC. Utilizing univariate and multivariate survival analyses, we found that patients with ARID1AlossCD47high expression had a worse prognosis. Estimation of infiltrating immune cells on TCGA data set showed that a higher infiltration proportion of M2 macrophages and Tregs was found in ARID1AmutatedCD47high expression subgroup. Furthermore, application of multispectral immunofluorescence revealed a higher infiltration proportion of M2 macrophages and Tregs in ARID1AlossCD47high GC tissues. Conclusion: Loss of ARID1A is strongly correlated with high CD47 expression in GC, and combination of ARID1A and CD47 is a promising prognosis factor in GC.
Vegetation Greenness Variations and Response to Climate Change in the Arid and Semi-Arid Transition Zone of the Mongo-Lian Plateau during 1982-2015

Vegetation greenness dynamics in arid and semi-arid regions are sensitive to climate change, which is an important phenomenon in global climate change research. However, the driving mechanism, particularly for the longitudinal and latitudinal changes in vegetation greenness related to climate change, has been less studied and remains poorly understood in arid and semi-arid areas. In this study, we investigated changes in vegetation greenness and the vegetation greenness line (the mean growing season normalized difference vegetation index (NDVI) = 0.1 contour line) and its response to climate change based on AVHRR-GIMMS NDVI3g and the fifth and latest global climate reanalysis dataset from 1982 to 2015 in the arid and semi-arid transition zone of the Mongolian Plateau (ASTZMP). The results showed that the mean growing season NDVI increased from the central west to east, northeast, and southeast in ASTZMP. The vegetation greenness line migrated to the desert during 1982–1994, to the grassland during 1994–2005, and then to the desert during 2005–2015. Vegetation greenness was positively correlated with precipitation and negatively correlated with temperature. The latitudinal variation of the vegetation greenness line was mainly affected by the combination of precipitation and temperature, while the longitudinal variation was mainly affected by precipitation. In summary, precipitation was a key climatic factor driving rapid changes in vegetation greenness during the growing season of the transition zone. These results can provide meaningful information for research on vegetation coverage changes in arid and semi-arid regions.
Multi-Sensor, Active Fire-Supervised, One-Class Burned Area Mapping in the Brazilian Savanna

Increasing efforts are being devoted to understanding fire patterns and changes highlighting the need for a consistent database about the location and extension of burned areas (BA). Satellite-derived BA mapping accuracy in the Brazilian savannas is limited by the underestimation of burn scars from small, fragmented fires and high cloudiness. Moreover, systematic mapping of BA is challenged by the need for human intervention in training sample acquisition, which precludes the development of automatic-generated products over large areas and long periods. Here, we developed a multi-sensor, active fire-supervised, one-class BA mapping algorithm to address several of these limitations. Our main objective is to generate a long-term, detailed BA atlas suitable to improve fire regime characterization and validation of coarse resolution products. We use composite images derived from the Landsat satellite to generate end-of-season maps of fire-affected areas for the entire Cerrado. Validation exercises and intercomparison with BA maps from a semi-automatic algorithm and visual photo interpretation were conducted for the year 2015. Our results improve the BA mapping by reducing omission errors, especially where there is high cloud frequency, few active fires are detected, and burned areas are small and fragmented. Finally, our approach represents at least a 45% increase in BA mapped in the Cerrado, in comparison to the annual extent detected by the current coarse global product from MODIS satellite (MCD64), and thus, it is capable of supporting improved regional emissions estimates.