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Abstract Objective The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). Methods This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. Results In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p

Abstract Purpose With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. Methods Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (

The catalytic generation of H2 in living cells provides a method for antioxidant therapy. In this study, an [FeFe]-hydrogenase mimic [Ru + Fe2S2@F127(80)] was synthesized by self-assembling polymeric pluronic F-127, catalytic [Fe2S2] sites, and photosensitizer Ru(bpy)32+. Under blue light irradiation, hydrated protons were photochemically reduced to H2, which increased the local pH in living cells (HeLa cells). The generated H2 was subsequently used as an antioxidant to decrease reactive oxygen species (ROS) levels in living cells (HEK 293T, HepG2, MCF-7, and HeLa cells). Our findings revealed that the proliferation of HEK 293T cells increased by a factor of about six times, relative to that of other cells (HepG2, MCF-7, and HeLa cells). Intracellular ROS and pH levels were then monitored using fluorescent cell imaging. Our study showed that cell imaging can be used to evaluate the ability of Ru + Fe2S2@F127 to eliminate oxidative stress and prevent ROS-related diseases.

Abstract We investigated the effect of CYP2C19 polymorphisms on the clinical outcomes of clopidogrel therapy in patients after stenting procedure for cerebral artery stenosis in northeast China. 568 patients performed CYP2C19 genotype screening in the neurosurgery department of our hospital; 154 patients were finally recruited according to the inclusion and exclusion criteria, and followed-up for 6 months. Ischemic events including (1) transient ischemic attack (TIA); (2) stent thrombosis; (3) ischemic stroke; and (4) death were defined as primary clinical endpoints. The frequencies of CYP2C19*1, *2 and *3 alleles in 568 patients were 63.1%, 31.1% and 5.8%, respectively. 154 patients were classified into extensive (65 patients; 42.2%), intermediate (66 patients; 42.9%), and poor (23 patients; 14.9%) metabolizer groups. A χ2 test showed a significant difference in primary clinical endpoints at 6 months (P = 0.04), and a multivariate Cox regression analysis indicated that the CYP2C19 loss-of-function (LOF) alleles associated with post-procedure prognosis. The Kaplan–Meier curve revealed that there was no significant difference in ischemic events between *2 and *3 alleles carriers. Our study verifies that CYP2C19 *2 and *3 have significant impact on the clinical outcomes of clopidogrel therapy in patients with stenting procedure for cerebral artery stenosis in China.

Abstract Calcium (Ca) is an essential mineral nutrient and plays a crucial signaling role in all living organisms. Increasing Ca content in staple foods such as rice is vital for improving Ca nutrition of humans. Here we map a quantitative trait locus that controls Ca concentration in rice grains and identify the causal gene as GCSC1 (Grain Ca and Sr Concentrations 1), which encodes a chloroplast vesicle localized homo-oligomeric protein. GCSC1 exhibits Ca2+ transport activity in heterologous assays in yeast and Xenopus laevis oocytes and is involved in the efflux of Ca2+ from the chloroplast to the cytosol. Knockout of GCSC1 results in increased chloroplast Ca concentration, lower stomatal conductance in leaves and enhanced Ca allocation to grains. Natural variation in grain Ca concentration is attributed to the variable expression of GCSC1 resulting from its promoter sequence variation. Our study identifies a chloroplast localized heavy metal-associated domain containing protein that regulates chloroplast Ca2+ efflux and provides a way to biofortify Ca in rice to benefit human nutrition.

Contamination of paddy soils can lead to toxic arsenic accumulation in rice grains and low levels of the micronutrient selenium. Here the authors show that a gain of function mutant affecting an O-acetylserine (thiol) lyase enhances sulfur and selenium assimilation while reducing arsenic accumulation in grains.

Molybdenum (Mo) is an essential micronutrient for almost all living organisms. The Mo uptake process in plants has been well investigated. However, the mechanisms controlling Mo translocation and remobilization among different plant tissues are largely unknown, especially the allocation of Mo to rice grains that are the major dietary source of Mo for humans. In this study, we characterized the functions of a molybdate transporter, OsMOT1;2, in the interorgan allocation of Mo in rice. Heterologous expression in yeast established the molybdate transport activity of OsMOT1;2. OsMOT1;2 was highly expressed in the blades of the flag leaf and the second leaf during the grain filling stage. Subcellular localization revealed that OsMOT1;2 localizes to the tonoplast. Knockout of OsMOT1;2 led to more Mo accumulation in roots and less Mo translocation to shoots at the seedling stage and to grains at the maturity stage. The remobilization of Mo from older leaves to young leaves under molybdate-depleted condition was also decreased in the osmot1;2 knockout mutant. In contrast, overexpression of OsMOT1;2 enhanced the translocation of Mo from roots to shoots at the seedling stage. The remobilization of Mo from upper leaves to grains was also enhanced in the overexpression lines during grain filling. Our results suggest that OsMOT1;2 may function as a vacuolar molybdate exporter facilitating the efflux of Mo from the vacuole into the cytoplasm, and thus, it plays an important role in the root-to-shoot translocation of Mo and the remobilization of Mo from leaves to grains.

Sulfur, widely present in the soil and atmosphere, is one of the essential elements for plants. Sulfate is a dominant form of sulfur in soils taken up by plant roots. In addition to the assimilation into sulfur compounds essential for plant growth and development, it has been reported recently that sulfate as well as other sulfur containing compounds can also induce stomatal movement. Here, we first summarized the uptake and transport of sulfate and atmospheric sulfur, including H2O and SO2, and then, focused on the effects of inorganic and organic sulfur on stomatal movement. We concluded all the transporters for different sulfur compounds, and compared the expression level of those transporters in guard cells and mesophyll cells. The relationship between abscisic acid and sulfur compounds in regulation of stomatal movement were also discussed.

Background: Considerable proportions of rice grains produced in some areas in southern China contain high concentrations of cadmium (Cd), leading to unsafe levels of dietary Cd intake. Cultivars of Indica rice, widely grown in southern China, are particularly prone to high Cd accumulation in the grain. Effective methods are needed to decrease Cd accumulation in Indica rice. Methods: OsHMA3, encoding a tonoplast Cd transporter, was overexpressed in an elite Indica rice cultivar (Zhongjiazao 17) driven by CaMV 35S promoter. The effects on Cd translocation, accumulation and tolerance, as well as on the agronomic traits and micronutrient concentrations were evaluated. Results: OsHMA3 overexpression markedly decreased Cd translocation from roots to shoots and increased Cd tolerance. OsHMA3 overexpression decreased Cd concentrations in brown rice by 94–98%, to levels just above the detection limit, when rice plants were grown in two Cd-contaminated paddy soils. OsHMA3 overexpression generally had no significant effect on grain yield and the concentrations of the essential micronutrients including zinc, iron, copper and manganese in field trials. Conclusion: Overexpression of OsHMA3 is a highly effective method to reduce Cd accumulation in Indica rice, producing rice grains that were almost Cd free with little effect on grain yield or essential micronutrient concentrations. Keywords: Cadmium, Food safety, OsHMA3, Genetic modification, Rice

Rice provides more than one fifth of daily calories for half of the world’s human population, and is a major dietary source of both essential mineral nutrients and toxic elements. Rice grains are generally poor in some essential nutrients but may contain unsafe levels of some toxic elements under certain conditions. Identification of quantitative trait loci (QTLs) controlling the concentrations of mineral nutrients and toxic trace metals (the ionome) in rice will facilitate development of nutritionally improved rice varieties. However, QTL analyses have traditionally considered each element separately without considering their interrelatedness. In this study, we performed principal component analysis (PCA) and multivariate QTL analyses to identify the genetic loci controlling the covariance among mineral elements in the rice ionome. We resequenced the whole genomes of a rice recombinant inbred line (RIL) population, and performed univariate and multivariate QTL analyses for the concentrations of 16 elements in grains, shoots and roots of the RIL population grown in different conditions. We identified a total of 167 unique elemental QTLs based on analyses of individual elemental concentrations as separate traits, 53 QTLs controlling covariance among elemental concentrations within a single environment/tissue (PC-QTLs), and 152 QTLs which determined covariation among elements across environments/tissues (aPC-QTLs). The candidate genes underlying the QTL clusters with elemental QTLs, PC-QTLs and aPC-QTLs co-localized were identified, including OsHMA4 and OsNRAMP5. The identification of both elemental QTLs and PC QTLs will facilitate the cloning of underlying causal genes and the dissection of the complex regulation of the ionome in rice.

Sulfur (S) is an essential mineral nutrient required for plant growth and development. Plants usually face temporal and spatial variation in sulfur availability, including the heterogeneous sulfate content in soils. As sessile organisms, plants have evolved sophisticated mechanisms to modify their gene expression and physiological processes in order to optimize S acquisition and usage. Such plasticity relies on a complicated network to locally sense S availability and systemically respond to S status, which remains poorly understood. Here, we took advantage of a split-root system and performed transcriptome-wide gene expression analysis on rice plants in S deficiency followed by sulfate resupply. S deficiency altered the expressions of 6749 and 1589 genes in roots and shoots, respectively, accounting for 18.07% and 4.28% of total transcripts detected. Homogeneous sulfate resupply in both split-root halves recovered the expression of 27.06% of S-deficiency-responsive genes in shoots, while 20.76% of S-deficiency-responsive genes were recovered by heterogeneous sulfate resupply with only one split-root half being resupplied with sulfate. The local sulfate resupply response genes with expressions only recovered in the split-root half resupplied with sulfate but not in the other half remained in S deficiency were identified in roots, which were mainly enriched in cellular amino acid metabolic process and root growth and development. Several systemic response genes were also identified in roots, whose expressions remained unchanged in the split-root half resupplied with sulfate but were recovered in the other split-root half without sulfate resupply. The systemic response genes were mainly related to calcium signaling and auxin and ABA signaling. In addition, a large number of S-deficiency-responsive genes exhibited simultaneous local and systemic responses to sulfate resupply, such as the sulfate transporter gene OsSULTR1;1 and the O-acetylserine (thiol) lyase gene, highlighting the existence of a systemic regulation of sulfate uptake and assimilation in S deficiency plants followed by sulfate resupply. Our studies provided a comprehensive transcriptome-wide picture of a local and systemic response to heterogeneous sulfate resupply, which will facilitate an understanding of the systemic regulation of S homeostasis in rice.

Copper (Cu) is an essential mineral nutrient but high concentrations in rice grain can cause toxicity. Here the authors provide evidence that natural variation in rice grain Cu concentration is caused by altered sequestration of Cu into root vacuoles due to a single amino acid substitution in the OsHMA4 transporter.

WRKYs are transcriptional factors involved in stress tolerance and development of plants. In the present study, we characterized OsWRKY28, a group IIa WRKY gene, in rice, because its expression was found to be upregulated by arsenate exposure in previous transcriptomic studies. Subcellular localization using YFP–OsWRKY28 fusion protein showed that the protein was localized in the nuclei. Transgenic rice plants expressing pOsWRKY28::GUS suggested that the gene was expressed in various tissues in the whole plant, with a strong expression in the root tips, lateral roots and reproductive organs. The expression of OsWRKY28 was markedly induced by arsenate and other oxidative stresses. In a hydroponic experiment, loss-of-function mutation in OsWRKY28 resulted in lower accumulation of arsenate and phosphate concentration in the shoots. The mutants showed altered root system architecture, with fewer lateral roots and shorter total root length than wild-type plants. In a soil pot experiment, the mutants produced lower grain yield than wild-type because of reduced fertility and smaller effective tiller numbers. Transcriptomic profiling using RNA-seq showed altered expression in the mutant of genes involved in the biosynthesis of phytohormones, especially jasmonic acid (JA). Exogenous JA treatments mimicked the phenotypes of the oswrky28 mutants with inhibited root elongation and decreased arsenate/phosphate translocation. Our results suggested that OsWRKY28 affected arsenate/phosphate accumulation, root development at the seedling stage and fertility at the reproductive stage possibly by influencing homeostasis of JA or other phytohormones.

Sulphur (S) is an essential element for all living organisms. The uptake, assimilation and metabolism of S in plants are well studied. However, the regulation of S homeostasis remains largely unknown. Here, we report on the identification and characterisation of the more sulphur accumulation1 (msa1-1) mutant. The MSA1 protein is localized to the nucleus and is required for both S-adenosylmethionine (SAM) production and DNA methylation. Loss of function of the nuclear localised MSA1 leads to a reduction in SAM in roots and a strong S-deficiency response even at ample S supply, causing an over-accumulation of sulphate, sulphite, cysteine and glutathione. Supplementation with SAM suppresses this high S phenotype. Furthermore, mutation of MSA1 affects genome-wide DNA methylation, including the methylation of S-deficiency responsive genes. Elevated S accumulation in msa1-1 requires the increased expression of the sulphate transporter genes SULTR1;1 and SULTR1;2 which are also differentially methylated in msa1-1. Our results suggest a novel function for MSA1 in the nucleus in regulating SAM biosynthesis and maintaining S homeostasis epigenetically via DNA methylation.

Genome-wide association (GWA) analyses have generally been used to detect individual loci contributing to the phenotypic diversity in a population by the effects of these loci on the trait mean. More rarely, loci have also been detected based on variance differences between genotypes. Several hypotheses have been proposed to explain the possible genetic mechanisms leading to such variance signals. However, little is known about what causes these signals, or whether this genetic variance-heterogeneity reflects mechanisms of importance in natural populations. Previously, we identified a variance-heterogeneity GWA (vGWA) signal for leaf molybdenum concentrations in Arabidopsis thaliana. Here, fine-mapping of this association reveals that the vGWA emerges from the effects of three independent genetic polymorphisms that all are in strong LD with the markers displaying the genetic variance-heterogeneity. By revealing the genetic architecture underlying this vGWA signal, we uncovered the molecular source of a significant amount of hidden additive genetic variation or "missing heritability". Two of the three polymorphisms underlying the genetic variance-heterogeneity are promoter variants for Molybdate transporter 1 (MOT1), and the third a variant located ~25 kb downstream of this gene. A fourth independent association was also detected ~600 kb upstream of MOT1. Use of a T-DNA knockout allele highlights Copper Transporter 6; COPT6 (AT2G26975) as a strong candidate gene for this association. Our results show that an extended LD across a complex locus including multiple functional alleles can lead to a variance-heterogeneity between genotypes in natural populations. Further, they provide novel insights into the genetic regulation of ion homeostasis in A. thaliana, and empirically confirm that variance-heterogeneity based GWA methods are a valuable tool to detect novel associations of biological importance in natural populations.

Recently, the integrated control systems with computing, Internet, and the electronic equipment with embedded sensors or identification device, called Cyber Physical Systems (CPSs), have gradually attracted more and more attention in a variety of different areas. It is efficient to manage, control, monitor, and query on machinery, equipment, and personnel state. Based on the CPS technology, creating smart living space becomes an important trend of future development. However, the electronic devices nowadays execute different communication protocols, such as Bluetooth, Zigbee, RF, and infrared, and even some traditional devices have no communication function. As a result, the real-time information and status of devices in smart spaces could not be effectively integrated, and thus will increase the difficulties to establish smart living space with CPSs. To improve this problem, this paper designs and implements an Intelligent Control Box to convert different wireless signals. The developed Intelligent Control Box can be treated as a multiple control platform which integrates the systems of lighting, air conditioning, access control, video surveillance, alarm, and so on, further decreasing the difficulties in establishing smart living space with CPSs.