Dt1 inhibits SWEET-mediated sucrose transport to regulate photoperiod-dependent seed weight in soybean.

Soybean is a photoperiod-sensitive short-day crop whose reproductive period and yield are markedly affected by day-length changes. Seed weight is one of the key traits determining the soybean yield; however, the prominent genes that control the final seed weight of soybean and the mechanisms underlying the photoperiod's effect on this trait remain poorly understood. In this study, we identify SW19 as a major locus controlling soybean seed weight by QTL mapping and determine Dt1, an orthologous gene of Arabidopsis TFL1 that is known to govern the soybean growth habit, as the causal gene of the SW19 locus. We showed that Dt1 is highly expressed in developing seeds and regulates photoperiod-dependent seed weight in soybean. Further analyses revealed that the Dt1 protein physically interacts with the sucrose transporter GmSWEET10a to negatively regulate the import of sucrose from seed coat to the embryo, thus modulating seed weight under long days. However, Dt1 does not function in seed development under short days due to its very low expression. Importantly, we discovered a novel natural allelic variant of Dt1 (H4 haplotype) that decouples its pleiotropic effects on seed size and growth habit; i.e., this variant remains functional in seed development but fails to regulate the stem growth habit of soybean. Collectively, our findings provide new insights into how soybean seed development responds to photoperiod at different latitudes, offering an ideal genetic component for improving soybean's yield by manipulating its seed weight and growth habit.

Soybean reduced internode 1 determines internode length and improves grain yield at dense planting.

Major cereal crops have benefitted from Green Revolution traits such as shorter and more compact plants that permit high-density planting, but soybean has remained relatively overlooked. To balance ideal soybean yield with plant height under dense planting, shortening of internodes without reducing the number of nodes and pods is desired. Here, we characterized a short-internode soybean mutant, reduced internode 1 (rin1). Partial loss of SUPPRESSOR OF PHYA 105 3a (SPA3a) underlies rin1. RIN1 physically interacts with two homologs of ELONGATED HYPOCOTYL 5 (HY5), STF1 and STF2, to promote their degradation. RIN1 regulates gibberellin metabolism to control internode development through a STF1/STF2-GA2ox7 regulatory module. In field trials, rin1 significantly enhances grain yield under high-density planting conditions comparing to its wild type of elite cultivar. rin1 mutants therefore could serve as valuable resources for improving grain yield under high-density cultivation and in soybean-maize intercropping systems.

Nomogram for predicting opioid-induced nausea and vomiting for cancer pain patients.

OBJECTIVE: Opioid-induced nausea and vomiting are frequently observed as an adverse effect in the treatment of cancer-related pain. The factors that affect OINV in cancer patients remain unclear. In this study, we developed a nomogram for predicting the occurrence of OINV in this population using retrospective clinical data. METHODS: We collected data from 416 cancer pain patients, 70% of whom used the training set to analyze demographic and clinical variables. We used multivariate logistic regression to identify significant factors associated with OINV. Then, we construct a prediction nomogram. The validation set comprises the remaining 30%. The reliability of the nomogram is evaluated by bootstrap resampling. RESULTS: Using multivariate logistic regression, we identified five significant factors associated with OINV. The C-index was 0.835 (95% confidence interval [CI], 0.828-0.842) for the training set and 0.810 (95% CI, 0.793-0.826) for the validation set. The calibrated curves show a good agreement between the predicted and actual occurrence of OINV. CONCLUSION: In a retrospective study based on five saliency-found variables, we developed and proved a reliable nomogram model to predict OINV in cancer pain patients. Future prospective studies should assess the model's reliability and usefulness in clinical practice.

PH13 improves soybean shade traits and enhances yield for high-density planting at high latitudes.

Shading in combination with extended photoperiods can cause exaggerated stem elongation (ESE) in soybean, leading to lodging and reduced yields when planted at high-density in high-latitude regions. However, the genetic basis of plant height in adaptation to these regions remains unclear. Here, through a genome-wide association study, we identify a plant height regulating gene on chromosome 13 (PH13) encoding a WD40 protein with three main haplotypes in natural populations. We find that an insertion of a Ty1/Copia-like retrotransposon in the haplotype 3 leads to a truncated PH13H3 with reduced interaction with GmCOP1s, resulting in accumulation of STF1/2, and reduced plant height. In addition, PH13H3 allele has been strongly selected for genetic improvement at high latitudes. Deletion of both PH13 and its paralogue PHP can prevent shade-induced ESE and allow high-density planting. This study provides insights into the mechanism of shade-resistance and offers potential solutions for breeding high-yielding soybean cultivar for high-latitude regions.

[Research Progress of Klotho in Lung Neoplasms].

Klotho gene was originally discovered as an anti-aging gene, Klotho protein encoded by Klotho gene is expressed in multiple human tissues, and its most prominent function is the regulation of phosphate homeostasis. Klotho protein possesses various activities, including inhibition of multiple signaling pathways, reducing oxidative stress and suppressing inflammation, and these activities are associated with cancer. Klotho protein is discovered as a universal tumor suppressor, and its expression is associated with tumorigenesis and prognosis of patients. Lung cancer is the most common malignancy tumor, and it is the leading cause of cancer deaths worldwide because of its high incidence and mortality. This article summarizes the research progress of the role of Klotho on pathogenesis, therapeutic effect and prognosis in lung cancer, in order to provide new biomarker and target for diagnosis, treatment and prognosis of lung cancer.
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[Corrigendum] Role of the EZH2/miR­200 axis in STAT3­mediated OSCC invasion.

Following the publication of the above article, an interested reader drew to the authors' attention that, in Figs. 7A and 8A. apparently the same mouse had been featured to represent two different experimental groups, albeit displaying distinct fluorescence values. Moreover, following an independent investigation in the Editorial Office, an additional instance of probable data duplication was also noted, comparing between the 'SCC15 / si­NC' cell migration image in Fig. 2D and the 'SCC15­EV' migration assay image in Fig. 1C. After having consulted their original data, the authors realized that these errors arose during the process of assembling the images for Figs. 2 and 8. First, the image for the DZNep (42d) experiment in Fig. 7A had inadvertently been used for the mimic NC (7d) experiment in Fig. 8A; moreover, the 'SCC15 / si­NC' cell migration image in Fig. 2D had been selected incorrectly. The revised versions of Figs. 2 and 8, showing the correct data for the the 'SCC15 / si­NC' cell migration image in Fig. 2D and the mimic NC (7d) experiment in Fig. 8A, are shown on the next two pages. The authors regret that these errors went unnoticed prior to publication, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Oncology 52: 1149­1164, 2018; DOI: 10.3892/ijo.2018.4293].

Candidate loci for breeding compact plant-type soybean varieties.

Plant height and node number are important agronomic traits that influence yield in soybean (Glycine max L.). Here, to better understand the genetic basis of the traits, we used two recombinant inbred line (RIL) populations to detect quantitative trait loci (QTLs) associated with plant height and node number in different environments. This analysis detected 9 and 21 QTLs that control plant height and node number, respectively. Among them, we identified two genomic regions that overlap with Determinate stem 1 (Dt1) and Dt2, which are known to influence both plant height and node number. Furthermore, different combinations of Dt1 and Dt2 alleles were enriched in distinct latitudes. In addition, we determined that the QTLs qPH-13-SE and qPH-13-DW in the two RIL populations overlap with genomic intervals associated with plant height and the QTL qNN-04-DW overlaps with an interval associated with node number. Combining the dwarf allele of qPH-13-SE/qPH-13-DW and the multiple-node allele of qNN-04-DW produced plants with ideal plant architecture, i.e., shorter main stems with more nodes. This plant type may help increase yield at high planting density. This study thus provides candidate loci for breeding elite soybean cultivars for plant height and node number. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01352-2.

Lyonensinols A - C, 24-Norursane-Type Triterpenoids from the Twigs and Leaves of Lyonia doyonensis and Their Potential Anti-inflammatory and PTP1B Inhibitory Activities.

Lyonia doyonensis is a deciduous shrub native to high-altitude regions of Asia. So far, there is no report on any chemical and biological properties of L. doyonensis. An EtOH extract of L. doyonensis twigs and leaves showed inhibitory activities on protein tyrosine phosphatase 1B and lipopolysaccharide-induced inflammation in BV-2 microglial cells. A phytochemical investigation of this extract led to the isolation of a, so far only ambiguously described, 24-norursane-type triterpenoid, now named lyonensinol A (1: ), along with its two new derivatives, lyonensinols B and C (2: and 3: ), and six known triterpenoids (4 - 9: ). Their structures were elucidated by detailed analysis of spectroscopic data. A combination of chemical conversions, electronic circular dichroism, and Mo2(OAc)4-induced electronic circular dichroism was used to confirm their absolute configurations. Lyonensinols B (2: ) and C (3: ) represent the first examples of norursane-type triterpenoids acylated with a p-coumaroyl moiety. The potential anti-inflammatory and protein tyrosine phosphatase 1B inhibitory activities of all the isolates were evaluated. Compounds 3, 7: , and 8: at 10 µM showed potent inhibitory activities on lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells, with nitric oxide levels decreasing to 31.5, 41.9, and 27.1%, respectively, while compounds 3, 4, 7: , and 8: exhibited notable inhibitory activities against protein tyrosine phosphatase 1B, with IC50 values ranging from 1.7 to 18.2 µM. Interestingly, compounds 3: and 8: , bearing a C-3 trans-p-coumaroyl group, showed not only more potent anti-inflammatory effects, but also exhibited stronger protein tyrosine phosphatase 1B inhibition than their respective stereoisomers (2: and 7: ) with a cis-p-coumaroyl group.

The AP2/ERF transcription factor TOE4b regulates photoperiodic flowering and grain yield per plant in soybean.

Photoperiod-mediated flowering determines the phenological adaptability of crops including soybean (Glycine max). A genome-wide association study (GWAS) identified a new flowering time locus, Time of flowering 13 (Tof13), which defined a gene encoding an AP2/ERF transcription factor. This new transcription factor, which we named TOE4b, is localized in the nucleus. TOE4b has been selected for soybean latitude adaptability. The existing natural variant TOE4bH4 was rare in wild soybean accessions but occurred more frequently in landraces and cultivars. Notably, TOE4bH4 improved high-latitude adaptation of soybean to some extent. The gene-edited TOE4b knockout mutant exhibited earlier flowering, conversely, TOE4b overexpression delayed flowering time. TOE4b is directly bound to the promoters and gene bodies of the key flowering integration factor genes FT2a and FT5a to inhibit their transcription. Importantly, TOE4b overexpression lines in field trials not only showed late flowering but also altered plant architecture, including shorter internode length, more internodes, more branches and pod number per plant, and finally boosted grain yield per plant by 60% in Guangzhou and 87% in Shijiazhuang. Our findings therefore identified TOE4b as a pleiotropic gene to increase yield potential per plant in soybean, and these results provide a promising option for breeding a soybean variety with an idealized plant architecture that promotes high yields.

High-throughput manufacturing of epitaxial membranes from a single wafer by 2D materials-based layer transfer process.

Layer transfer techniques have been extensively explored for semiconductor device fabrication as a path to reduce costs and to form heterogeneously integrated devices. These techniques entail isolating epitaxial layers from an expensive donor wafer to form freestanding membranes. However, current layer transfer processes are still low-throughput and too expensive to be commercially suitable. Here we report a high-throughput layer transfer technique that can produce multiple compound semiconductor membranes from a single wafer. We directly grow two-dimensional (2D) materials on III-N and III-V substrates using epitaxy tools, which enables a scheme comprised of multiple alternating layers of 2D materials and epilayers that can be formed by a single growth run. Each epilayer in the multistack structure is then harvested by layer-by-layer mechanical exfoliation, producing multiple freestanding membranes from a single wafer without involving time-consuming processes such as sacrificial layer etching or wafer polishing. Moreover, atomic-precision exfoliation at the 2D interface allows for the recycling of the wafers for subsequent membrane production, with the potential for greatly reducing the manufacturing cost.

The genetic basis of high-latitude adaptation in wild soybean.

In many plants, flowering time is influenced by daylength as an adaptive response. In soybean (Glycine max) cultivars, however, photoperiodic flowering reduces crop yield and quality in high-latitude regions. Understanding the genetic basis of wild soybean (Glycine soja) adaptation to high latitudes could aid breeding of improved cultivars. Here, we identify the Tof4 (Time of flowering 4) locus, which encodes by an E1-like protein, E1La, that represses flowering and enhances adaptation to high latitudes in wild soybean. Moreover, we found that Tof4 physically associates with the promoters of two important FLOWERING LOCUS T (FT2a and FT5a) and with Tof5 to inhibit their transcription under long photoperiods. The effect of Tof4 on flowering and maturity is mediated by FT2a and FT5a proteins. Intriguingly, Tof4 and the key flowering repressor E1 independently but additively regulate flowering time, maturity, and grain yield in soybean. We determined that weak alleles of Tof4 have undergone natural selection, facilitating adaptation to high latitudes in wild soybean. Notably, over 71.5% of wild soybean accessions harbor the mutated alleles of Tof4 or a previously reported gain-of-function allele Tof5H2, suggesting that these two loci are the genetic basis of wild soybean adaptation to high latitudes. Almost no cultivated soybean carries the mutated tof4 allele. Introgression of the tof4-1 and Tof5H2 alleles into modern soybean or editing E1 family genes thus represents promising avenues to obtain early-maturity soybean, thereby improving productivity in high latitudes.

Self-Adaptive Spherical Search With a Low-Precision Projection Matrix for Real-World Optimization.

Since the last three decades, numerous search strategies have been introduced within the framework of different evolutionary algorithms (EAs). Most of the popular search strategies operate on the hypercube (HC) search model, and search models based on other hypershapes, such as hyper-spherical (HS), are not investigated well yet. The recently developed spherical search (SS) algorithm utilizing the HS search model has been shown to perform very well for the bound-constrained and constrained optimization problems compared to several state-of-the-art algorithms. Nevertheless, the computational burdens for generating an HS locus are higher than that for an HC locus. We propose an efficient technique to construct an HS locus by approximating the orthogonal projection matrix to resolve this issue. As per our empirical experiments, this technique significantly improves the performance of the original SS with less computational effort. Moreover, to enhance SS's search capability, we put forth a self-adaptation technique for choosing the effective values of the control parameters dynamically during the optimization process. We validate the proposed algorithm's performance on a plethora of real-world and benchmark optimization problems with and without constraints. Experimental results suggest that the proposed algorithm remains better than or at least comparable to the best-known state-of-the-art algorithms on a wide spectrum of problems.

Identification of two quantitative genes controlling soybean flowering using bulked-segregant analysis and genetic mapping.

Photoperiod responsiveness is important to soybean production potential and adaptation to local environments. Varieties from temperate regions generally mature early and exhibit extremely low yield when grown under inductive short-day (SD) conditions. The long-juvenile (LJ) trait is essentially a reduction and has been introduced into soybean cultivars to improve yield in tropical environments. In this study, we used next-generation sequencing (NGS)-based bulked segregant analysis (BSA) to simultaneously map qualitative genes controlling the LJ trait in soybean. We identified two genomic regions on scaffold_32 and chromosome 18 harboring loci LJ32 and LJ18, respectively. Further, we identified LJ32 on the 228.7-kb scaffold_32 as the soybean pseudo-response-regulator gene Tof11 and LJ18 on a 301-kb region of chromosome 18 as a novel PROTEIN FLOWERING LOCUS T-RELATED gene, Glyma.18G298800. Natural variants of both genes contribute to LJ trait regulation in tropical regions. The molecular identification and functional characterization of Tof11 and LJ18 will enhance understanding of the molecular mechanisms underlying the LJ trait and provide useful genetic resources for soybean molecular breeding in tropical regions.

Chip-less wireless electronic skins by remote epitaxial freestanding compound semiconductors.

Recent advances in flexible and stretchable electronics have led to a surge of electronic skin (e-skin)-based health monitoring platforms. Conventional wireless e-skins rely on rigid integrated circuit chips that compromise the overall flexibility and consume considerable power. Chip-less wireless e-skins based on inductor-capacitor resonators are limited to mechanical sensors with low sensitivities. We report a chip-less wireless e-skin based on surface acoustic wave sensors made of freestanding ultrathin single-crystalline piezoelectric gallium nitride membranes. Surface acoustic wave-based e-skin offers highly sensitive, low-power, and long-term sensing of strain, ultraviolet light, and ion concentrations in sweat. We demonstrate weeklong monitoring of pulse. These results present routes to inexpensive and versatile low-power, high-sensitivity platforms for wireless health monitoring devices.

Agronomical selection on loss-of-function of GIGANTEA simultaneously facilitates soybean salt tolerance and early maturity.

Salt stress and flowering time are major factors limiting geographic adaptation and yield productivity in soybean (Glycine max). Although improving crop salt tolerance and latitude adaptation are essential for efficient agricultural production, whether and how these two traits are integrated remains largely unknown. Here, we used a genome-wide association study to identify a major salt-tolerance locus controlled by E2, an ortholog of Arabidopsis thaliana GIGANTEA (GI). Loss of E2 function not only shortened flowering time and maturity, but also enhanced salt-tolerance in soybean. E2 delayed soybean flowering by enhancing the transcription of the core flowering suppressor gene E1, thereby repressing Flowering Locus T (FT) expression. An E2 knockout mutant e2CR displayed reduced accumulation of reactive oxygen species (ROS) during the response to salt stress by releasing peroxidase, which functions in ROS scavenging to avoid cytotoxicity. Evolutionary and population genetic analyses also suggested that loss-of-function e2 alleles have been artificially selected during breeding for soybean adaptation to high-latitude regions with greater salt stress. Our findings provide insights into the coupled selection for adaptation to both latitude and salt stress in soybean; and offer an ideal target for molecular breeding of early-maturing and salt-tolerant cultivars.

Simultaneously achieving giant piezoelectricity and record coercive field enhancement in relaxor-based ferroelectric crystals.

A large coercive field (EC) and ultrahigh piezoelectricity are essential for ferroelectrics used in high-drive electromechanical applications. The discovery of relaxor-PbTiO3 crystals is a recent breakthrough; they currently afford the highest piezoelectricity, but usually with a low EC. Such performance deterioration occurs because high piezoelectricity is interlinked with an easy polarization rotation, subsequently favoring a dipole switch under small fields. Therefore, the search for ferroelectrics with both a large EC and ultrahigh piezoelectricity has become an imminent challenge. Herein, ternary Pb(Sc1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 crystals are reported, wherein the dispersed local heterogeneity comprises abundant tetragonal phases, affording a EC of 8.2 kV/cm (greater than that of Pb(Mg1/3Nb2/3)O3-PbTiO3 by a factor of three) and ultrahigh piezoelectricity (d33 = 2630 pC/N; d15 = 490 pC/N). The observed EC enhancement is the largest reported for ultrahigh-piezoelectric materials, providing a simple, practical, and universal route for improving functionalities in ferroelectrics with an atomic-level understanding.

A functionally divergent SOC1 homolog improves soybean yield and latitudinal adaptation.

Soybean (Glycine max) grows in a wide range of latitudes, but it is extremely sensitive to photoperiod, which reduces its yield and ability to adapt to different environments. Therefore, understanding of the genetic basis of soybean adaptation is of great significance for breeding and improvement. Here, we characterized Tof18 (SOC1a) that conditions early flowering and growth habit under both short-day and long-day conditions. Molecular analysis confirmed that the two SOC1 homologs present in soybeans (SOC1a and SOC1b) underwent evolutionary functional divergence, with SOC1a having stronger effects on flowering time and stem node number than SOC1b due to transcriptional differences. soc1a soc1b double mutants showed stronger functional effects than either of the single mutants, perhaps due to the formation of SOC1a and SOC1b homodimers or heterodimers. Additionally, Tof18/SOC1a improves the latitudinal adaptation of cultivated soybeans, highlighting the functional importance of SOC1a. The Tof18G allele facilitates adaptation to high latitudes, whereas Tof18A facilitates adaptation to low latitudes. We demonstrated that SOC1s contribute to floral induction in both leaves and shoot apex through inter-regulation with FTs. The SOC1a-SOC1b-Dt2 complex plays essential roles in stem growth habit by directly binding to the regulatory sequence of Dt1, making the genes encoding these proteins potential targets for genome editing to improve soybean yield via molecular breeding. Since the natural Tof18A allele increases node number, introgressing this allele into modern cultivars could improve yields, which would help optimize land use for food production in the face of population growth and global warming.

Case Report: Dramatic Response to Crizotinib in a Patient With Non-Small Cell Lung Cancer Positive for a Novel ARL1-MET Fusion.

It is imperative to know the status of oncogenic drivers in patients with non-small cell lung cancer (NSCLC). Compared with ALK and ROS1 fusion, MET fusion is relatively rare in NSCLC. In this case, we report the case of a female patient with NSCLC positive for a novel ARL1-MET fusion. The patient achieved about a 5-month progression-free survival (PFS) after receiving crizotinib for unresectable right lung malignancies. To the best of our knowledge, this case provides the first clinical evidence that the novel ARL1-MET fusion might be an actionable mutation in NSCLC.

Parallel selection of distinct Tof5 alleles drove the adaptation of cultivated and wild soybean to high latitudes.

Photoperiod responsiveness is a key factor limiting the geographic distribution of cultivated soybean and its wild ancestor. In particular, the genetic basis of the adaptation in wild soybean remains poorly understood. In this study, by combining whole-genome resequencing and genome-wide association studies we identified a novel locus, Time of Flowering 5 (Tof5), which promotes flowering and enhances adaptation to high latitudes in both wild and cultivated soybean. By genomic, genetic and transgenic analyses we showed that Tof5 encodes a homolog of Arabidopsis thaliana FRUITFULL (FUL). Importantly, further analyses suggested that different alleles of Tof5 have undergone parallel selection. The Tof5H1 allele was strongly selected by humans after the early domestication of cultivated soybean, while Tof5H2 allele was naturally selected in wild soybean, and in each case facilitating adaptation to high latitudes. Moreover, we found that the key flowering repressor E1 suppresses the transcription of Tof5 by binding to its promoter. In turn, Tof5 physically associates with the promoters of two important FLOWERING LOCUS T (FT), FT2a and FT5a, to upregulate their transcription and promote flowering under long photoperiods. Collectively, our findings provide insights into how wild soybean adapted to high latitudes through natural selection and indicate that cultivated soybean underwent changes in the same gene but evolved a distinct allele that was artificially selected after domestication.