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Background: Multiple myeloma (MM) is a severely debilitating and fatal B-cell neoplastic disease. The discovery of disease-associated proteins with causal genetic evidence offers a chance to uncover novel therapeutic targets. Methods: First, we comprehensively investigated the causal association between 2994 proteins and MM through two-sample mendelian randomization (MR) analysis using summary-level data from public genome-wide association studies of plasma proteome (N = 3301 healthy individuals) and MM (598 cases and 180,756 controls). Sensitivity analyses were performed for these identified causal proteins. Furthermore, we pursued the exploration of enriched biological pathways, prioritized the therapeutic proteins, and evaluated their druggability using the KEGG pathway analysis, MR-Bayesian model averaging analysis, and cross-reference with current databases, respectively. Results: We identified 13 proteins causally associated with MM risk (false discovery rate corrected P < 0.05). Six proteins were positively associated with the risk of MM, including nicotinamide phosphoribosyl transferase (NAMPT; OR [95% CI]: 1.35 [1.18, 1.55]), tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE1; 1.14 [1.06, 1.22]), neutrophil cytosol factor 2 (NCF2; 1.27 [1.12, 1.44]), carbonyl reductase 1, cAMP-specific 3',5'-cyclic phosphodiesterase 4D (PDE4D), platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2). Seven proteins were inversely associated with MM, which referred to suppressor of cytokine signaling 3 (SOCS3; 0.90 [0.86, 0.94]), Fc-gamma receptor III-B (FCGR3B; 0.75 [0.65,0.86]), glypican-1 (GPC1; 0.69 [0.58,0.83]), follistatin-related protein 1, protein tyrosine phosphatase non-receptor type 4 (PTPN4), granzyme B, complement C1q subcomponent subunit C (C1QC). Three of the causal proteins, SOCS3, FCGR3B, and NCF2, were enriched in the osteoclast differentiation pathway in KEGG enrichment analyses while GPC1 (marginal inclusion probability (MIP):0.993; model averaged causal effects (MACE): − 0.349), NAMPT (MIP:0.433; MACE: − 0.113), and NCF2 (MIP:0.324; MACE:0.066) ranked among the top three MM-associated proteins according to MR-BMA analyses. Furthermore, therapeutics targeting four proteins are currently under evaluation, five are druggable and four are future breakthrough points. Conclusions: Our analysis revealed a set of 13 novel proteins, including six risk and seven protective proteins, causally linked to MM risk. The discovery of these MM-associated proteins opens up the possibility for identifying novel therapeutic targets, further advancing the integration of genome and proteome data for drug development. [ABSTRACT FROM AUTHOR]

Changes in serum inflammatory factors occur throughout the onset and multiple myeloma (MM) progression, the feedback loops make it harder to distinguish between causes and effects. In the present study, we performed a bidirectional summary‐level Mendelian randomization (MR) analysis to elucidate the causal relationships of C‐reactive protein (CRP) and inflammatory regulators with MM. Summary‐level data of genetic variants associated with inflammation were extracted from two genome‐wide association studies (GWASs) on CRP and human cytokines, while data on MM was from large meta‐analyses of GWASs among 372 617 UK Biobank participants. The inverse‐variance weighted (IVW) method was used as the primary MR analysis and MR‐Egger, weighted median, and MR‐pleiotropy residual sum and outlier (MR‐PRESSO) were used as the sensitivity analyses. Our results suggested that higher levels of monocyte‐specific chemokine‐3 (IVW estimate odds ratio [ORIVW] per SD genetic cytokines change: 1.24; 95% confidence interval [CI]: 1.03‐1.49; P =.02), vascular endothelial growth factor (1.14, 1.03‐1.27; P =.02), interleukin‐10 (1.33, 1.01‐1.75; P =.04) and interleukin‐7 (1.24, 1.03‐1.48; P =.02) were associated with increased risk of MM, while lower levels of tumor necrosis factor‐β (0.84, 0.74‐0.92; P <.001) was strongly associated with an increased risk of MM. And conversely, genetically predicted MM was related to increased levels of interleukin‐17 (IVW estimate β: 0.051, 95% CI: 0.018‐0.085; P = 2.7 × 10−3). Besides, we observed no such significant associations for other inflammatory factors in our study. Overall, our study provides genetic evidence on the relationships of CRP and systemic inflammatory regulators with MM. Targeted interventions of specific inflammatory factors may have implications to alleviate MM cancer risk. [ABSTRACT FROM AUTHOR]

In recent years, rice–fish coculture has gained more popularity at a growing pace in China. Controlled-release fertilizer can provide nutrients in a timely manner and increase nutrient efficiency. A 2-year field experiment, which adopted both conventional japonica and two indica hybrid rice varieties, was performed to evaluate the effects of controlled-release fertilizer and inorganic compound fertilizer on rice matter accumulation and yield in rice–crayfish coculture and conventional rice farming. The results showed that compared to conventional rice farming, rice–crayfish coculture decreased dry matter accumulation at mature stage and yield by 4.02–8.15% and 4.13–9.34%, respectively. This was mainly due to a decrease in the crop growth rate, net assimilation rate, leaf area index, and light accumulation duration before elongation stage. Compared to inorganic compound fertilizer, controlled-release fertilizer increased dry matter accumulation at the mature stage and yield by 5.02–6.95% and 3.29–6.21%, respectively. Compared to conventional rice farming, rice–crayfish coculture decreased N partial factor productivity and N agronomic use efficiency by 4.13–9.34% and 3.96–8.98%, respectively. Compared to inorganic compound fertilizer, controlled-release fertilizer increased those by 3.29–6.15% and 7.36–14.01%. There was a positive linear correlation between the N partial factor productivity, N agronomic use efficiency, and yield. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to obtain an effective implant with porous structures on its surface, named porous-surfaced implant, which helps to improve the overall stability of the implant and promote the combination of implant and alveolar bone. Design/methodology/approach: Porous-surfaced implants with a porosity of 16%, 21%and 32% were designed and the effect of porosity on the strength of the implant was analyzed by ABAQUS software. Porous-surfaced implants with different porosity were printed by selective laser melting and the surface morphology was observed. Animal experiments of implants with porous structures and coating were carried out in healthy beagle dogs. The experimental group was treated with hydroxyapatite coating and the control group was not treated. Bone volume (BV) and total volume (TV) of the implant surface of the experimental group and control group were calculated by Skyscan CTvol software. Findings: With the increase of porosity of porous-surfaced implants, the neck stress of the porous-surfaced implants increased and their strength decreased. In addition, in animal vivo experiments, the ratio value of BV to TV of the porous-surfaced implants was between 55.38% and 79.86%, which was the largest when the porosity of porous-surfaced implants was 16%. The internal and surrounding bone formation content of porous-surfaced implants with hydroxyapatite coating was higher than porous-surfaced implants without coating. Originality/value: The results of this study show that the pores on the surface of implants can be filled with the new bone and porous-surfaced implants with 16% porosity provide better space for the growth of new bone. The porous structures with hydroxyapatite coating are beneficial to the growth of new bone around implants. The results of this study are helpful to improve the overall stability of implants and to promote the combination of implant and alveolar bone. [ABSTRACT FROM AUTHOR]

Global rice production will be increasingly challenged by providing healthy food for a growing population at minimal environmental cost. In this study, a 2-year field experiment was conducted to investigate the effects of a novel rice cultivation mode (screenhouse cultivation, SHC) and organic material (OM) incorporation (wheat straw and wheat straw-based biogas residue) on methane (CH) and nitrous oxide (NO) emissions and rice yields. In addition, the environmental factors and soil properties were also determined. Relative to the traditional open-field cultivation (OFC), SHC decreased the CH and NO emissions by 6.58-18.73 and 2.51-21.35%, respectively, and the global warming potential (GWP) was reduced by 6.49-18.65%. This trend was mainly because of lower soil temperature and higher soil redox potential in SHC. Although the rice grain yield for SHC were reduced by 2.51-4.98% compared to the OFC, the CH emissions and GWP per unit of grain yield (yield-scaled CH emissions and GWP) under SHC were declined. Compared to use of inorganic fertilizer only (IN), combining inorganic fertilizer with wheat straw (WS) or wheat straw-based biogas residue (BR) improved rice grain yield by 2.12-4.10 and 4.68-5.89%, respectively. However, OM incorporation enhanced CH emissions and GWP, leading to higher yield-scaled CH emissions and GWP in WS treatment. Due to rice yield that is relatively high, there was no obvious effect of BR treatment on them. These findings suggest that apparent environmental benefit can be realized by applying SHC and fermenting straw aerobically before its incorporation. [ABSTRACT FROM AUTHOR]

Background and aims: This study aims to investigate the effect of nitrogen (N) on grain phosphorus (P) accumulation in japonica rice. Methods: Six cultivars with contrasting agronomic traits were grown for 3 years (from 2008 to 2010) of field experiments under seven N treatments and 1 year (in 2010) of pot experiments with five N treatments to study the effect of N on grain phosphorus accumulation and to explore its physiological foundation. Results: Grain total P and phytic acid concentration showed a clearly decreasing trend as N rate increased for both field and pot experiments. Pot experiment revealed that application of N increase plant biomass, but tended to lower plant P uptake, especially for the split topdressing treatments. Both harvest index (HI) and P harvest index (PHI) increased with N rate, but PHI was consistently higher than HI, indicating the larger proportion of P translocation to grain than that of dry matter by N. Further, ratio of PHI/HI differed significantly among genotypes, but was stable across contrasting N treatments. Conclusions: The combination of decreased plant P uptake and dilution effect of increased grain yield by N is proposed as underlying mechanism of the decreased grain P concentration by high N. [ABSTRACT FROM AUTHOR]

Nitrogen plays a central role in rice growth and development because it modulates a wide variety of processes, including cytokinin (CK) metabolism. CK-mediated signaling is also related to nitrogen metabolism. The functional relation between nitrogen and CK are extremely complex and unclear. In this study, a comparative proteomic analysis was carried out to analyze proteins regulated by nitrogen and CK in rice roots. Proteins extracted from rice roots are separated by two-dimensional polyacrylamide gel electrophoresis. Thirty-two protein spots that expressed similarly by nitrogen and CK treatments are selected for identification by mass spectrometry. Of these spots, 28 are successfully identified. These proteins were categorized into classes related to energy, metabolism, disease/defense, protein degradation, signal transduction, transposons, and unclear classification. Energy gives the largest functional category, suggesting that the glycolysis (two enzymes detected) and tricarboxylic acid cycle (six enzymes detected) are accurately regulated by nitrogen and CK, thus promoting the synthesis of amino acid. The identification of novel proteins provides new insights into the coordination of nitrogen and CK in rice. The possible role of these proteins is discussed. [ABSTRACT FROM AUTHOR]

This study aims to quantify nitrogen (N) effect on occurrence of perfect rice kernel (PRK) and imperfect grains which includes white-belly rice kernel (WBRK), white-core rice kernel (WCRK), green rice kernel (GRK), opaque rice kernel (ORK), and other imperfect grains (OTHERS). Two-year field experiments involving six japonica rice cultivars and seven N treatments were performed. The structural differences between white-belly and white-core tissues were compared using scanning electron microscope. Averaged over cultivars, grain yield increased progressively with N rate. PRK increased with N rate in 2008, but decreased with increased N rate in 2009. WBRK and WCRK decreased as N rate increased for both years. High N input resulted in higher occurrence of GRK and OTHERS for both years. Most starch granules in white-belly tissues are intact and surrounded by globular protein bodies, with many air spaces between them; while in white-core tissues, starch granules are easily broken into many single granules and no protein bodies are visible. Our results suggest that N has suppressing influence on chalky grains but favorable effect on other imperfect grains, and indicate different mechanism between WBRK and WCRK. [ABSTRACT FROM AUTHOR]

Hormones play an important role in regulating the growth of rice tiller buds. However, little is known about the hormonal changes that occur during tiller bud growth and the mechanism of hormonal regulation of tiller bud growth. Here, two rice cultivars, Yangdao 6 (Indica) and Nanjing 44 (Japonica), were used to investigate the changes in plant hormones during tiller bud growth and the mechanism that underlies the hormonal regulation of tiller bud growth. In the present study, panicles were removed after heading to stimulate the growth of dormant tiller buds located at the elongated upper internodes. At the same time, external abscisic acid (ABA), gibberellic acid (GA) and α-naphthalene acetic acid (NAA) were applied. The results demonstrated that auxin and cytokinin (CTK) play important and different roles in the regulation of tiller bud growth. Auxin in the nodes inhibits tiller bud growth, while CTK is transferred to the tiller buds to promote growth. The inhibitory effects of GA and NAA on tiller bud growth are mainly due to the control of the indole-3-acetic acid (IAA) or CTK contents in plants. As opposed to auxin and CTK, the ABA contents in nodes and tiller buds remained unchanged before tiller bud growth after panicle removal. Meanwhile, external ABA application only slightly slowed the growth of the tiller buds, suggesting that ABA may not be a key regulator of tiller bud growth. These results indicate that auxin, CTK and ABA together likely play roles in the regulation of tiller bud growth. [ABSTRACT FROM AUTHOR]

In recent years, the application of proteomic approaches as a tool for global expression analysis and protein identification has been highly efficient in the field of plant research. A solution culture experiment involving two nitrogen treatments, 0.14 mM NHNO (low nitrogen (N)) and 1.07 mM NHNO (control), was conducted to investigate the response of rice root to low N stress. Root system architecture changed markedly under low N stress, with more lateral roots occurring on the lower part of adventitious roots and longer lateral roots on the upper part, compared to the control. A proteomic approach was employed to further study the rice responses to low N stress. Proteins extracted from roots were profiled by two-dimensional gel electrophoresis, and differentially expressed proteins were analyzed by mass spectrometry. Twelve protein spots were successfully identified by mass spectrometry, 11 of which had known functions. Of these, four were involved with the tricarboxylic acid cycle, two with adenylate metabolism, two with phenylpropanoid metabolism, and two with protein degradation. These differentially expressed proteins play an important role in the responsive mechanisms of rice root to low N stress, and uncovering how the rice proteins respond to low N stress could contribute to improving the nitrogen use efficiency. [ABSTRACT FROM AUTHOR]