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PurposeCutaneous malignant melanoma (CMM) always presents as a complex disease process with poor prognosis. The objective of the present study was to explore the influence of solitary or multiple cancers on the prognosis of patients with CMM to better understand the landscape of CMM.MethodsWe reviewed the records of CMM patients between 2004 and 2015 from the Surveillance, Epidemiology, and End Results Program. The cumulative incidence function was used to represent the probabilities of death. A novel causal inference method was leveraged to explore the risk difference to death between different types of CMM, and nomograms were built based on competing risk models.ResultsThe analysis cohort contained 165,043 patients with CMM as the first primary malignancy. Patients with recurrent CMM and multiple primary tumors had similar overall survival status (p = 0.064), while their demographics and cause-specific death demonstrated different characteristics than those of patients with solitary CMM (p < 0.001), whose mean survival times are 75.4 and 77.3 months and 66.2 months, respectively. Causal inference was further applied to unveil the risk difference of solitary and multiple tumors in subgroups, which was significantly different from the total population (p < 0.05), and vulnerable groups with high risk of death were identified. The established competing risk nomograms had a concordance index >0.6 on predicting the probabilities of death of CMM or other cancers individually across types of CMM.ConclusionPatients with different types of CMM had different prognostic characteristics and different risk of cause-specific death. The results of this study are of great significance in identifying the high risk of cause-specific death, enabling targeted intervention in the early period at both the population and individual levels.

Background The rice plant architecture is determined by spatially and temporally domesticated tiller angle. The deeper insight into the genetic mechanism for rice plant architecture will allow more efficient light capture by increasing the planting density, reproducibility, and the ability to survive in a stressful environment. Methods In this study, a natural population of 795 genotypes further divided into japonica and indica subpopulations, was evaluated for tiller angle. A significant variation with a wide range was observed. Genome-wide association analysis was performed by the general linear model (GLM), and compressed mix linear model (cMLM) for three populations to disclose the genomic associations. The population principal components and kinship matrix in 1,000 permutations were used to remove the false positives. The candidate genes were evaluated for their functional annotations and specific molecular pathways. The sequencing-based haplotype analysis was further performed to reveal the functional variation among candidate genomic regions. Results As a result, 37 significant QTLs with 93 annotated loci were identified. Among the loci, a known tiller angle controlling locus TAC1 was also identified. The introduction of the sequence pooling technique was observed fruitful to screen the 12 significant QTLs with 22 annotated loci. For ten of these loci, the functional variations were identified by haplotype analysis. These results were not only providing a better understanding of the genetic bases of rice plant architecture but also provide significant information for future breeding programs.

On March 11, 2011, a serious radionuclide leakage accident occurred at Fukushima Daiichi nuclear power plant, and a large number of radionuclides were released, causing serious pollution to the ocean environment. On August 25, 2021, Japan announced the overall plan for the discharge of radioactive sewage from the Fukushima Daiichi nuclear power plant into the ocean, and the discharge will begin around the spring of 2023. All operational and under-construction nuclear power plants in China are distributed in coastal areas presently. In case of a nuclear leakage accident, radionuclides will diffuse through the ocean and pollute the ecological environment. The study of radionuclide diffusion mechanism in the ocean and emergency response plays an important role in accident mitigation under oceanic radioactive events. A radionuclide diffusion model in the ocean was established and the radionuclide diffusion mechanism in the ocean was analyzed. And then a prediction and monitoring system of radionuclide diffusion in the ocean was proposed. The results show that the short-term radionuclide diffusion is mainly influenced by the source term, flow field and decay of 131I, and the degree of influence decreases in turn. On the whole, influences of the flow field and 131I decay are weakened during the long-term diffusion. At the same time, the influence of 137Cs decay begins to be obvious and the influence of suspended matter is increasing. The influence of ocean organisms is always small. Problems of scientific prediction and protection were analyzed, and the emergency response scheme was given. It is of great significance to improve the capacity of emergency response for oceanic radioactive events.

Regulations for the control of air-pollutant emissions from ships within pollutant emission control areas (ECAs) have been issued for several years, but the lack of practical technologies and fundamental theory in the implementation process remains a challenge. In this study, we designed a model to calculate the nitrogen-oxide-emission intensity of ships and the sulfur content of ship fuels using theoretical deduction from the law of the conservation of mass. The reliability and availability of the derived results were empirically evaluated using measurement data for NOx, SO2, and CO2 in the exhaust gas of a demonstration ship in practice. By examining the model and the measured or registered fuel-oil-consumption rates of ships, a compliance-determination workflow for NOx-emission intensity and fuel-sulfur-content monitoring and supervision in on-voyage ships were proposed. The results showed that the ship fuel’s NOx-emission intensity and sulfur content can be evaluated by monitoring the exhaust-gas composition online and used to assist in maritime monitoring and the supervision of pollutant emissions from ships. It is recommended that uncertainties regarding sulfur content should be considered within 15% during monitoring and supervision. The established model and workflow can assist in maritime monitoring. Meanwhile, all related governments and industry-management departments are advised to actively lead the development of monitoring and supervision technology for ship-air-pollutant control in ECAs, as well as strengthening the quality management of ships’ static data.

Xanthoangelol (XAG), a major chalcone presents in Angelica keiskei, has been employed in research to develop functional supplements or drugs due to its various pharmacological activities. Here, we investigated the underlying mechanism of XAG-induced cell death in hepatocellular carcinoma (HCC). We found that XAG inhibited the cell viability of either HepG2 or HuH7cells, and induced pyroptotic death in HuH7 cell with concomitant activation of NOD-like receptor family pyrin domain containing 3 (NLRP3)/Caspase-1/gasdermin D (GSDMD) pathway. However, in GSDMD-low HepG2 cells, Caspase-1 expression modulated the underlying XAG-induced apoptosis pathway, thereby regulating cell death. VX-765, a special inhibitor of caspase-1, attenuated XAG-induced pyroptosis and apoptosis. Additionally, mitogen-activated protein kinase (MAPK) and NF-κB signaling pathway were suppressed by XAG. These findings suggest that XAG is a promising therapeutic agent through induction of caspase-1 mediated pyroptosis and apoptosis depend on the expression of GSDMD in HCC cells.

Magnetic properties of graphene and its derivatives are very fascinating because of their promising application in spintronics. Among the graphene family materials, graphene oxide is quite typical and special for the magnetic performance. Herein we report a systematic and detailed investigation on the magnetic properties of graphene oxide. Compared to the previous reports on the ferromagnetism, our results show that graphene oxide is indeed only paramagnetic. The magnetic properties can be well described by the Curie-Weiss law. This study is not only revealing the paramagnetism in graphene oxide but also calling a revisit about the magnetic properties of graphene oxides, graphene and the other derivatives of graphene.

Grain of indica rice accumulates more toxic cadmium (Cd) than japonica, but the underlying genetic basis is unclear. Here, the authors show that natural variation of OsCd1 contributes to divergence in grain Cd accumulation and transferring japonica allele to indica rice leads to reduced Cd accumulation.

To dissect the genetic mechanism of multi-seed pod in peanut, we explored the QTL/gene controlling multi-seed pod and analyzed the interaction effect of QTL and environment. Two hundred and forty eight recombinant inbred lines (RIL) from cross Silihong × Jinonghei 3 were used as experimental materials planted in 8 environments from 2012 to 2017. Three methods of analysis were performed. These included individual environment analysis, joint analysis in multiple environments, and epistatic interaction analysis for multi-seed pod QTL. Phenotypic data and best linear unbiased prediction (BLUP) value of the ratio of multi-seed pods per plant (RMSP) were used for QTL mapping. Seven QTL detected by the individual environmental mapping analysis and were distributed on linkage groups 1, 6, 9, 14, 19(2), and 21. Each QTL explained 4.42%–11.51% of the phenotypic variation in multi-seed pod, and synergistic alleles of 5 QTL were from the Silihong parent. One QTL, explaining 4.93% of the phenotypic variation was detected using BLUP data, and this QTL mapped in the same interval as qRMSP19.1 detected in the individual environment analysis. Seventeen additive QTL were identified by joint analysis across multiple environments. A total of 43 epistatic QTL were detected by ICIM-EPI mapping in the multiple environment trials (MET) module, and involved 57 loci. Two main-effect QTL related to multi-seed pod in peanut were filtered. We also found that RMSP had a highly significant positive correlation with pod yield per plant (PY), and epistatic effects were much more important than additive effects. These results provide theoretical guidance for the genetic improvement of germplasm resources and further fine mapping of related genes in peanut. Keywords: Best linear unbiased prediction, BLUP, QTL × environment interaction, Ratio of multi-seed pod, RMSP

Abstract Background Xanthoangelol (XAG) was reported to exhibit antitumor properties in several cancer. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC) and the relevant mechanisms are not known. Methods The effects of XAG on HCC cell proliferation and apoptosis were respectively examined by CCK-8 assay and Annexin V-FITC/PI apoptosis kit. Western blotting was conducted to detect the expression of proteins. The effect of XAG on the development of acidic vesicle organelles was assessed using acridine orange staining. mRFP-GFP-LC3 adenovirus was used to transfect HCC cells and the formation of autolysosome was detected using a confocal microscope. Results Mechanistically, XAG promotes HCC cell death through triggering intrinsic apoptosis pathway, not extrinsic apoptotic pathway. Furthermore, XAG treatment induced autophagy in Bel 7402 and SMMC 7721 cells, as evidenced by an increase in autophagy-associated proteins, including LC3B-II, Beclin-1, and Atg5. Interestingly, inhibition of autophagy with 3-MA, Bafilomycin A1 (Baf A1), or siRNA targeting Atg5 effectively enhanced the apoptotic cell ratio in XAG-treated cells, indicating that protective effect of autophagy induced by XAG in HCC. Moreover, autophagy induced by XAG was mediated by activating endoplasmic reticulum stress (ERS), along with administration of XAG, the expression levels of ERS-associated proteins, including CHOP, GRP78, ATF6, p-eIF2α, IRE1α, and cleaved caspase-12 were significantly increased in HCC cells. Meanwhile, suppressing ERS with chemical chaperones (TUDCA) or CHOP shRNA could effectively abrogate the autophagy-inducing effect of XAG, and increase the apoptotic cell death. Further mechanistic studies showed that ERS-induced autophagy in XAG-treated cells was mediated by activation of JNK/c-jun pathway. XAG treatment resulted in the increase of p-JNK and p-c-jun, while suppressing ERS with TUDCA or CHOP shRNA could effectively reverse it. Meanwhile, SP600125, a JNK inhibitor, effectively reversed XAG-induced protective autophagy and enhanced cell apoptosis in XAG-treated HCC cells. In vivo results demonstrated that XAG exerts potent antitumor properties with low toxicity. Conclusions Collectively, these results suggested that XAG could be served as a promising candidate for the treatment and prevention of HCC.

Online learning has emerged as a fresh method to successfully prevent teacher and student gatherings as well as the propagation of viruses in the context of the ongoing influence of the COVID-19. A problem deserving of consideration is how to increase users’ desire to participate in online learning through online class APPs, identify the variables that affect users’ use of them, and create a useful assessment scale. In this study, user ratings from 68 students who had used an online class APP were collected using the combination of qualitative and quantitative research, and 200 online questionnaires were sent out to complement the interview findings, based on which 328 assessment questionnaires were gathered and 23 valid items were obtained. The influencing elements that had an impact on users’ online learning experiences were identified using factor analysis, and the relationships among the components were investigated using structural equation modeling. Perceived benefits are the main influencing factors, subjective norms and functional quality are the direct factors influencing users’ perceived benefits, and self-efficacy is influenced by subjective norms while promoting the perception of functional quality. The factors influencing users’ use of online class APPs are ultimately identified as perceived benefits, functional quality and self-efficacy. In order to facilitate users’ online learning, user psychological traits, social ties and software functions should be integrated into a cohesive system while designing online class APPs.

Malate dehydrogenase (MDH) is widely present in nature and regulates plant growth and development, as well as playing essential roles, especially in abiotic stress responses. Nevertheless, there is no comprehensive knowledge to date on MDH family members in rice. In this study, a total of 12 MDH members in rice were identified through genome-wide analysis and divided into three groups on the basis of their phylogenetic relationship and protein-conserved motifs. Evolutionary analysis showed that MDH proteins from rice, maize and wheat shared a close phylogenetic relationship, and the MDH family was conserved in the long-term process of domestication. We identified two segmental duplication events involving four genes, which could be the major force driving the expansion of the OsMDH family. The expression profile, cis-regulatory elements and qRT-PCR results of these genes revealed that a few OsMDH showed high tissue specificity, almost all of which had stress response elements in the promoter region, and ten MDH members were significantly induced by salt stress. Through gene-based association analysis, we found a significant correlation between salt tolerance at the seedling stage and the genetic variation of OsMDH8.1 and OsMDH12.1. Additionally, we found that the polymorphism in the promoter region of OsMDH8.1 might be related to the salt tolerance of rice. This study aimed to provide valuable information on the functional study of the rice MDH gene family related to salt stress response and revealed that OsMDH8.1 might be an important gene for the cultivar improvement of salt tolerance in rice.

Wheat nutrition and processing-quality are primarily based on the endosperm ingredients. However, the effect of embryos on grain traits and components remains unclear. In this study, we found that in the cross-pollinated and self-pollinated progenies of the four wheat mtl mutants (mtl-A, mtl-AD, mtl-BD, and mtl-ABD) the haploid induction rates were 0–15.6% and 0–14.1%, and the embryo abortion rates were 0–27.4% and 0–24.1%, respectively, in which mtl-A had no effect on haploid induction and embryo development. The embryoless grains (ELG) were comparable to the normal grains (NG) from mtl-AD, mtl-BD, and mtl-ABD in grain length, grain width and thousand-kernel weight, but the grain traits were significantly less than those in NG from mutant mtl-A. During grain filling period, mtl-ABD had similar ELG ratio and amount of starch granule (SG) and protein body (PB) in ELG and NG. At maturity stage, the morphological features of A-type and B-type SG in ELG were similar to those in NG in mtl mutants; however, amylose, gliadin, and glutenin contents were higher in ELG, and total starch, albumin and globulin contents were higher in NG. Our results clarified the effect of the wheat mtl mutants on haploid induction and grain traits and nutrition composition in this crop, and provided new clues for studying the development of embryo and endosperm and their interaction in plants.

Although it is well-known that human skin aging is accompanied by an alteration in the skin microbiota, we know little about how the composition of these changes during the course of aging and the effects of age-related skin microbes on aging. Using 16S ribosomal DNA and internal transcribed spacer ribosomal DNA sequencing to profile the microbiomes of 160 skin samples from two anatomical sites, the cheek and the abdomen, on 80 individuals of varying ages, we developed age-related microbiota profiles for both intrinsic skin aging and photoaging to provide an improved understanding of the age-dependent variation in skin microbial composition. According to the landscape, the microbial composition in the Children group was significantly different from that in the other age groups. Further correlation analysis with clinical parameters and functional prediction in each group revealed that high enrichment of nine microbial communities (i.e., Cyanobacteria, Staphylococcus, Cutibacterium, Lactobacillus, Corynebacterium, Streptococcus, Neisseria, Candida, and Malassezia) and 18 pathways (such as biosynthesis of antibiotics) potentially affected skin aging, implying that skin microbiomes may perform key functions in skin aging by regulating the immune response, resistance to ultraviolet light, and biosynthesis and metabolism of age-related substances. Our work re-establishes that skin microbiomes play an important regulatory role in the aging process and opens a new approach for targeted microbial therapy for skin aging.

Superconducting niobium nitride (NbN) films with nominal thicknesses of 4 nm, 5 nm, 7 nm, and 9 nm were grown on sapphire substrates using atomic layer deposition (ALD). We observed probed Hall resistance (HR) (Rxy) in external out-of-plane magnetic fields up to 6 T and magnetoresistance (MR) (Rxx) in external in-plane and out-of-plane magnetic fields up to 6 T on NbN thin films in Van der Pauw geometry. We also observed that positive MR dominated. Our study focused on the analysis of interaction and localisation effects on electronic disorder in NbN in the normal state in temperatures that ranged from 50 K down to the superconducting transition temperature. By modelling the temperature and magnetic field dependence of the MR data, we extracted the temperature-dependent Coulomb interaction constants, spin–orbit scattering lengths, localisation lengths, and valley degeneracy factors. The MR model allowed us to distinguish between interaction effects (positive MR) and localisation effects (negative MR) for in-plane and out-of-plane magnetic fields. We showed that anisotropic dephasing scattering due to lattice non-idealities in NbN could be neglected in the ALD-grown NbN thin films.

The fabrication of individual nanowire-based devices and their comprehensive electrical characterization remains a major challenge. Here, we present a symmetric Hall bar configuration for highly p-type germanium nanowires (GeNWs), fabricated by a top-down approach using electron beam lithography and inductively coupled plasma reactive ion etching. The configuration allows two equivalent measurement sets to check the homogeneity of GeNWs in terms of resistivity and the Hall coefficient. The highest Hall mobility and carrier concentration of GeNWs at 5 K were in the order of 100 cm2/(Vs) and 4×1019cm−3, respectively. With a decreasing nanowire width, the resistivity increases and the carrier concentration decreases, which is attributed to carrier scattering in the region near the surface. By comparing the measured data with simulations, one can conclude the existence of a depletion region, which decreases the effective cross-section of GeNWs. Moreover, the resistivity of thin GeNWs is strongly influenced by the cross-sectional shape.

4-hydroxyderricin (4-HD), as a natural flavonoid compound derived from Angelica keiskei, has largely unknown inhibition and mechanisms on liver cancer. Herein, we investigated the inhibitory effects of 4-HD on hepatocellular carcinoma (HCC) cells and clarified the potential mechanisms by exploring apoptosis and cell cycle arrest mediated via the PI3K/AKT/mTOR signaling pathway. Our results show that 4-HD treatment dramatically decreased the survival rate and activities of HepG2 and Huh7 cells. The protein expressions of apoptosis-related genes significantly increased, while those related to the cell cycle were decreased by 4-HD. 4-HD also down-regulated PI3K, p-PI3K, p-AKT, and p-mTOR protein expression. Moreover, PI3K inhibitor (LY294002) enhanced the promoting effect of 4-HD on apoptosis and cell cycle arrest in HCC cells. Consequently, we demonstrate that 4-HD can suppress the proliferation of HCC cells by promoting the PI3K/AKT/mTOR signaling pathway mediated apoptosis and cell cycle arrest.

Plant germplasm underpins much of crop genetic improvement. Millions of germplasm accessions have been collected and conserved ex situ and/or in situ, and the major challenge is now how to exploit and utilize this abundant resource. Genomics-based plant germplasm research (GPGR) or “Genoplasmics” is a novel cross-disciplinary research field that seeks to apply the principles and techniques of genomics to germplasm research. We describe in this paper the concept, strategy, and approach behind GPGR, and summarize current progress in the areas of the definition and construction of core collections, enhancement of germplasm with core collections, and gene discovery from core collections. GPGR is opening a new era in germplasm research. The contribution, progress and achievements of GPGR in the future are predicted.

Abstract Background Most agronomic traits in rice are complex and polygenic. The identification of quantitative trait loci (QTL) for grain length is an important objective of rice genetic research and breeding programs. Results Herein, we identified 99 QTL for grain length by GWAS based on approximately 10 million single nucleotide polymorphisms from 504 cultivated rice accessions (Oryza sativa L.), 13 of which were validated by four linkage populations and 92 were new loci for grain length. We scanned the Ho (observed heterozygosity per locus) index of coupled-parents of crosses mapping the same QTL, based on linkage and association mapping, and identified two new genes for grain length. We named this approach as Ho-LAMap. A simulation study of six known genes showed that Ho-LAMap could mine genes rapidly across a wide range of experimental variables using deep-sequencing data. We used Ho-LAMap to clone a new gene, OsLG3, as a positive regulator of grain length, which could improve rice yield without influencing grain quality. Sequencing of the promoter region in 283 rice accessions from a wide geographic range identified four haplotypes that seem to be associated with grain length. Further analysis showed that OsLG3 alleles in the indica and japonica evolved independently from distinct ancestors and low nucleotide diversity of OsLG3 in indica indicated artificial selection. Phylogenetic analysis showed that OsLG3 might have much potential value for improvement of grain length in japonica breeding. Conclusions The results demonstrated that Ho-LAMap is a potential approach for gene discovery and OsLG3 is a promising gene to be utilized in genomic assisted breeding for rice cultivar improvement.

Low temperature is a major factor limiting productivity in rice. Here the authors show that theCTB4a gene confers cold tolerance to japonicavarieties adapted to cold habitats at the booting stage of development, and propose that CTB4a acts via an interaction with the beta subunit of ATP synthase.

An amendment to this paper has been published and can be accessed via the original article.

A semianalytical three-dimensional (3D) elasticity solution for the vibration of the orthotropic plate is presented under arbitrary boundary conditions. Three-dimensional (3D) elasticity theory provides the theoretical support for the energy function of orthotropic plates. The orthotropic plates which have the arbitrary boundary condition are realized by the way of arranging three sets of linear springs at the edges. With the aim of eliminating the nonsmooth phenomenon at the edges, the admissible displacement function of an orthotropic plate is expressed with a modified Fourier series solution. Under this framework, a change that occurs on the boundary conditions only needs to modify the boundary parameters of the orthotropic plate, without the need for new derivation, thus greatly saving the modeling time. The convergence and accuracy of the proposed method are better than those of the published literature. Lastly, the new vibration results and parametric research of thick orthotropic plates as well as the geometric parameter are also presented.

Autophagy, which is a conserved biological process and essential mechanism in maintaining homeostasis and metabolic balance, enables cells to degrade cytoplasmic constituents through lysosomes, recycle nutrients, and survive during starvation. Autophagy exerts an anticarcinogenic role in normal cells and inhibits the malignant transformation of cells. On the other hand, aberrations in autophagy are involved in gene derangements, cell metabolism, the process of tumor immune surveillance, invasion and metastasis, and tumor drug-resistance. Therefore, autophagy-targeted drugs may function as anti-tumor agents. Accumulating evidence suggests that flavonoids have anticarcinogenic properties, including those relating to cellular proliferation inhibition, the induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, the impairment of cell migration, invasion, tumor angiogenesis, and the reduction of multidrug resistance in tumor cells. Flavonoids, which are a group of natural polyphenolic compounds characterized by multiple targets that participate in multiple pathways, have been widely studied in different models for autophagy modulation. However, flavonoid-induced autophagy commonly interacts with other mechanisms, comprehensively influencing the anticancer effect. Accordingly, targeted autophagy may become the core mechanism of flavonoids in the treatment of tumors. This paper reviews the flavonoid-induced autophagy of tumor cells and their interaction with other mechanisms, so as to provide a comprehensive and in-depth account on how flavonoids exert tumor-suppressive effects through autophagy.