Trimethylamine N-oxide (TMAO) doubly locks the hydrophobic core and surfaces of protein against desiccation stress.

Interactions between proteins and osmolytes are ubiquitous within cells, assisting in response to environmental stresses. However, our understanding of protein-osmolyte interactions underlying desiccation tolerance is limited. Here, we employ solid-state NMR (ssNMR) to derive information about protein conformation and site-specific interactions between the model protein, SH3, and the osmolyte trimethylamine N-oxide (TMAO). The data show that SH3-TMAO interactions maintain key structured regions during desiccation and facilitate reversion to the protein's native state once desiccation stress is even slightly relieved. We identify 10 types of residues at 28 sites involved in the SH3-TMAO interactions. These sites comprise hydrophobic, positively charged, and aromatic amino acids located in SH3's hydrophobic core and surface clusters. TMAO locks both the hydrophobic core and surface clusters through its zwitterionic and trimethyl ends. This double locking is responsible for desiccation tolerance and differs from ideas based on exclusion, vitrification, and water replacement. ssNMR is a powerful tool for deepening our understanding of extremely weak protein-osmolyte interactions and providing insight into the evolutionary mechanism of environmental tolerance.

The superior allele LEA12OR in wild rice enhances salt tolerance and yield.

Soil salinity has negative impacts on food security and sustainable agriculture. Ion homeostasis, osmotic adjustment and reactive oxygen species scavenging are the main approaches utilized by rice to resist salt stress. Breeding rice cultivars with high salt tolerance (ST) and yield is a significant challenge due to the lack of elite alleles conferring ST. Here, we report that the elite allele LEA12OR, which encodes a late embryogenesis abundant (LEA) protein from the wild rice Oryza rufipogon Griff., improves osmotic adjustment and increases yield under salt stress. Mechanistically, LEA12OR, as the early regulator of the LEA12OR-OsSAPK10-OsbZIP86-OsNCED3 functional module, maintains the kinase stability of OsSAPK10 under salt stress, thereby conferring ST by promoting abscisic acid biosynthesis and accumulation in rice. The superior allele LEA12OR provides a new avenue for improving ST and yield via the application of LEA12OR in current rice through molecular breeding and genome editing.

Nacre-mimetic cerium-doped nano-hydroxyapatite/chitosan layered composite scaffolds regulate bone regeneration via OPG/RANKL signaling pathway.

Autogenous bone grafting has long been considered the gold standard for treating critical bone defects. However, its use is plagued by numerous drawbacks, such as limited supply, donor site morbidity, and restricted use for giant-sized defects. For this reason, there is an increasing need for effective bone substitutes to treat these defects. Mollusk nacre is a natural structure with outstanding mechanical property due to its notable "brick-and-mortar" architecture. Inspired by the nacre architecture, our team designed and fabricated a nacre-mimetic cerium-doped layered nano-hydroxyapatite/chitosan layered composite scaffold (CeHA/CS). Hydroxyapatite can provide a certain strength to the material like a brick. And as a polymer material, chitosan can slow down the force when the material is impacted, like an adhesive. As seen in natural nacre, the combination of these inorganic and organic components results in remarkable tensile strength and fracture toughness. Cerium ions have been demonstrated exceptional anti-osteoclastogenesis capabilities. Our scaffold featured a distinct layered HA/CS composite structure with intervals ranging from 50 to 200 µm, which provided a conducive environment for human bone marrow mesenchymal stem cell (hBMSC) adhesion and proliferation, allowing for in situ growth of newly formed bone tissue. In vitro, Western-blot and qPCR analyses showed that the CeHA/CS layered composite scaffolds significantly promoted the osteogenic process by upregulating the expressions of osteogenic-related genes such as RUNX2, OCN, and COL1, while inhibiting osteoclast differentiation, as indicated by reduced TRAP-positive osteoclasts and decreased bone resorption. In vivo, calvarial defects in rats demonstrated that the layered CeHA/CS scaffolds significantly accelerated bone regeneration at the defect site, and immunofluorescence indicated a lowered RANKL/OPG ratio. Overall, our results demonstrate that CeHA/CS scaffolds offer a promising platform for bone regeneration in critical defect management, as they promote osteogenesis and inhibit osteoclast activation.

Genome-wide association studies identify OsWRKY53 as a key regulator of salt tolerance in rice.

Salinity stress progressively reduces plant growth and productivity, while plant has developed complex signaling pathways to confront salt stress. However, only a few genetic variants have been identified to mediate salt tolerance in the major crop rice, and the molecular mechanism remains poorly understood. Here, we identify ten candidate genes associated with salt-tolerance (ST) traits by performing a genome-wide association analysis in rice landraces. We characterize two ST-related genes, encoding transcriptional factor OsWRKY53 and Mitogen-activated protein Kinase Kinase OsMKK10.2, that mediate root Na+ flux and Na+ homeostasis. We further find that OsWRKY53 acts as a negative modulator regulating expression of OsMKK10.2 in promoting ion homeostasis. Furthermore, OsWRKY53 trans-represses OsHKT1;5 (high-affinity K+ transporter 1;5), encoding a sodium transport protein in roots. We show that the OsWRKY53-OsMKK10.2 and OsWRKY53-OsHKT1;5 module coordinate defenses against ionic stress. The results shed light on the regulatory mechanisms underlying plant salt tolerance.

A Paired Phase and Magnitude Reconstruction for Advanced Diffusion-Weighted Imaging.

OBJECTIVE: Multi-shot interleaved echo planer imaging (Ms-iEPI) can obtain diffusion-weighted images (DWI) with high spatial resolution and low distortion, but suffers from ghost artifacts introduced by phase variations between shots. In this work, we aim at solving the ms-iEPI DWI reconstructions under inter-shot motions and ultra-high b-values. METHODS: An iteratively joint estimation model with paired phase and magnitude priors is proposed to regularize the reconstruction (PAIR). The former prior is low-rankness in the k-space domain. The latter explores similar edges among multi-b-value and multi-direction DWI with weighted total variation in the image domain. The weighted total variation transfers edge information from the high SNR images (b-value = 0) to DWI reconstructions, achieving simultaneously noise suppression and image edges preservation. RESULTS: Results on simulated and in vivo data show that PAIR can remove inter-shot motion artifacts very well (8 shots) and suppress the noise under the ultra-high b-value (4000 s/mm2) significantly. CONCLUSION: The joint estimation model PAIR with complementary priors has a good performance on challenging reconstructions under inter-shot motions and a low signal-to-noise ratio. SIGNIFICANCE: PAIR has potential in advanced clinical DWI applications and microstructure research.

Nacre-inspired magnetically oriented micro-cellulose fibres/nano-hydroxyapatite/chitosan layered scaffold enhances pro-osteogenesis and angiogenesis.

In situ regeneration of large-segment bone defects is a difficult clinical problem. Here, we innovatively developed magnetically oriented micro-cellulose fibres using nano-hydroxyapatite/chitosan (CEF/Fe3O4/HA/CS) and loaded an NFκB pathway inhibitor on the surface of magnetically oriented cellulose fibres (CEF/Fe3O4/HA/CS/PQQ) prepared as a layered bioscaffold. CEF/Fe3O4/HA/CS/PQQ was constructed by layering HA/CS sheets. Nano-hydroxyapatite was deposited on the surface of cellulose fibres, then the magnetic nanoparticles on the cellulose fibres were aligned on the surface of chitosan under a magnetic field. Oriented cellulose fibres enhanced the compressive properties of the scaffold, with an average maximum compressive strength of 1.63 â€‹MPa. The CEF/Fe3O4/HA/CS/PQQ layered scaffold was filled into the body, and the acute inflammatory response (IL-1ß and TNF-α) was suppressed through the early sustained release of PQQ. The CEF/Fe3O4/HA/CS/PQQ-layered scaffold further inhibited the osteoclasts differentiation. It was further found that the nano-hydroxyapatite on the surface of oriented cellulose fibres promoted the formation and migration of new blood vessels, accelerated the processing of collagen-I fibres to cartilage, and endochondral ossification. Hence, the development of the CEF/Fe3O4/HA/CS/PQQ layered scaffold with oriented fibres guides bone growth direction and pro-osteogenesis activity and provides a novel strategy for the in situ regeneration of large segmental bone defects.

SrFe12O19-doped nano-layered double hydroxide/chitosan layered scaffolds with a nacre-mimetic architecture guide in situ bone ingrowth and regulate bone homeostasis.

Osteoporotic bone defects result from an imbalance in bone homeostasis, excessive osteoclast activity, and the weakening of osteogenic mineralization, resulting in impaired bone regeneration. Herein, inspired by the hierarchical structures of mollusk nacre, nacre exhibits outstanding high-strength mechanical properties, which are in part due to its delicate layered structure. SrFe12O19 nanoparticles and nano-layered double hydroxide (LDH) were incorporated into a bioactive chitosan (CS) matrix to form multifunctional layered nano-SrFe12O19-LDH/CS scaffolds. The compressive stress value of the internal ordered layer structure matches the trabecular bone (0.18 â€‹MPa). The as-released Mg2+ ions from the nano-LDH can inhibit bone resorption in osteoclasts by inhibiting the NFκB signaling pathway. At the same time, the as-released Sr2+ ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP-2/SMAD signaling pathway. In vivo, the Mg2+ ions released from the SrFe12O19-LDH/CS scaffolds inhibited the release of pro-inflammatory factors (IL-1ß and TNF-α), while the as-released Sr2+ ions promoted osteoblastic proliferation and the mineralization of osteoblasts inside the layered SrFe12O19-LDH/CS scaffolds. Immunofluorescence for OPG, RANKL, and CD31, showed that stable vasculature could be formed inside the layered SrFe12O19-LDH/CS scaffolds. Hence, this study on multifunctional SrFe12O19-LDH/CS scaffolds clarifies the regulatory mechanism of osteoporotic bone regeneration and is expected to provide a theoretical basis for the research, development, and clinical application of this scaffold on osteoporotic bone defects.

OsTUB1 confers salt insensitivity by interacting with Kinesin13A to stabilize microtubules and ion transporters in rice.

Salt stress is one of the major environmental factors limiting plant growth and development. Although microtubule (MT) organization is known to be involved in response to salt stress, few tubulin genes have been identified that confer salt insensitivity in plants. In this study, we identified a MT encoding gene, OsTUB1, that increased the survival rate of rice plants under salt stress by stabilizing MT organization and ion transporters. We found that OsTUB1 interacted with Kinesin13A protein, which was essential for OsTUB1-regulated MT organization under salt stress. Further molecular evidence revealed that a OsTUB1-Kinesin13A complex protected rice from salt stress by sustaining membrane-localized Na+ transporter OsHKT1;5, a key regulator of ionic homeostasis. Our results shed light on the function of tubulin and kinesin in regulating MT organization and stabilizing Na+ transporters and Na+ flux at the plasma membrane in rice. The identification of the OsTUB1-Kinesin13A complex provides novel genes for salt insensitivity rice breeding in areas with high soil salinity.

Favorable osteogenic activity of iron doped in silicocarnotite bioceramic: In vitro and in vivo Studies.

BACKGROUND: Calcium phosphate silicate (Ca5(PO4)2SiO4 or CPS) is a promising bioceramic for bone grafting. Iron (Fe) is a trace element in the human body that has been reported to enhance the mechanical strength of CPS ceramics. However, the exact biofunctions of Fe, combined with another human trace element, viz. silicon (Si), in CPS and the optimal dose for Fe addition must be further investigated. METHODS: In vitro: the morphology, structure and cell adhesion were observed by SEM; the ability to promote osteogenic differentiation and mineralization was explored by ALP and alizarin red staining; the expression of osteogenic-specific genes and proteins was detected by PCR, WB and immunofluorescence. In vivo: Further exploration of bone regeneration capacity by establishing a skull defect model. RESULTS: In vitro, we observed increased content of adhesion-related proteins and osteogenic-related genes expression of Fe-CPS compared with CPS, as demonstrated by immunofluorescence and polymerase chain reaction experiments, respectively. In vivo micro-computed tomography images, histomorphology, and undecalcified bone slicing also showed improved osteogenic ability of Fe-CPS bioceramics. CONCLUSION: With the addition of Fe2O3, the new bone formation rate of the Fe-CPS scaffold after 12 weeks increased from 9.42% to 43.76%. Moreover, both in vitro and in vivo experimental outcomes indicated that Fe addition improved the CPS bioceramics in terms of their osteogenic ability by promoting the expression of osteogenic-related genes. Fe-CPS bioceramics can be employed as a novel material for bone tissue engineering on account of their outstanding new bone formation ability. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study suggests that Fe-CPS bioceramics can be employed as a novel material for bone tissue engineering on account of their outstanding new bone formation ability,which provides promising therapeutic implants and strategies for the treatment of large segmental bone defects.

Ursolic Acid Loaded-Mesoporous Hydroxylapatite/ Chitosan Therapeutic Scaffolds Regulate Bone Regeneration Ability by Promoting the M2-Type Polarization of Macrophages.

PURPOSE: Mesoporous hydroxylapatite (MHAP) might be important for bone regeneration, and ursolic acid (UA) has anti-inflammatory effects. Accordingly, we developed, for the first time, ursolic acid-loaded MHAP-chitosan (MHAP-CS-UA) scaffolds to treat bone defects. METHODS: In vitro, we synthesize biomaterial scaffolds. By SEM, XRD, EDS and FTIR, we test the performance of the hybrid scaffolds. By drug release, flow cytometry, immunofluorescence, alizarin red staining, and Western blotting, we test the anti-inflammatory and osteo-inductive properties of scaffolds. In vivo, we verify osseointegration ability and bone regeneration. RESULTS: The MHAP is a rod-shaped structure with a length of 100~300nm and a diameter of 40~60nm. The critical structure gives the micro-scaffold a property of control release due to the pore sizes of 1.6~4.3 nm in hydroxyapatite and the hydrogen bonding between the scaffolds and UA drugs. The released UA drugs could notably inhibit the polarization of macrophages to pro-inflammatory macrophages (M1 type) and promote the expression of osteogenic-related genes (COL1, ALP and OPG) and osteogenic-related proteins (BMP-2, RUNX2 and COL1). CONCLUSION: The MHAP-CS-UA scaffolds have good anti-inflammatory, osseointegration, osteo-inductivity and bone regeneration. And they will be the novel and promising candidates to cure the bone disease.

Tin Chloride Sulfates A3Sn2(SO4)3-xCl1+2x (A = K, Rb, Cs; x = 0, 1) as Multifunctional Optical Materials.

The series of alkali-metal tin chloride sulfates A3Sn2(SO4)3-xCl1+2x (A = K, Rb, Cs; x = 0, 1), K3Sn2(SO4)3Cl, Rb3Sn2(SO4)2Cl3, and Cs3Sn2(SO4)2Cl3, were successfully synthesized through an improved mild hydrothermal method. Interestingly, in addition to the cation size effect, the structure-directing effect of anions induces different symmetries in the three title compounds, with K3Sn2(SO4)3Cl being noncentrosymmetric, while Rb3Sn2(SO4)2Cl3 and Cs3Sn2(SO4)2Cl3 are centrosymmetric. Powder second-harmonic generation (SHG) measurements indicate that K3Sn2(SO4)3Cl is a nonlinear optical material that is type I phase matchable with a weak SHG response (0.1× KDP). Photoluminescence tests reveal that the three title compounds emit strong greenish yellow, orange, and salmon light, respectively, under UV excitation, indicating that they are promising inorganic solid fluorescent materials. Simultaneously, a detailed structural analysis of all the known tin(II) halide sulfates has been performed, which will guide the systematic exploration of high-performance tin(II)-based functional materials in the future.

Graphene-modified CePO4 nanorods effectively treat breast cancer-induced bone metastases and regulate macrophage polarization to improve osteo-inductive ability.

BACKGROUND: Breast cancer bone metastasis has become one of the most common complications; however, it may cause cancer recurrence and bone nonunion, as well as local bone defects. METHODS: Herein, In vitro, we verified the effect of bioscaffold materials on cell proliferation and apoptosis through a CCK8 trial, staining of live/dead cells, and flow cytometry. We used immunofluorescence technology and flow cytometry to verify whether bioscaffold materials regulate macrophage polarization, and we used ALP staining, alizarin red staining and PCR to verify whether bioscaffold material promotes bone regeneration. In vivo, we once again studied the effect of bioscaffold materials on tumors by measuring tumor volume in mice, Tunel staining, and caspase-3 immunofluorescence. We also constructed a mouse skull ultimate defect model to verify the effect on bone regeneration. RESULTS: Graphene oxide (GO) nanoparticles, hydrated CePO4 nanorods and bioactive chitosan (CS) are combined to form a bioactive multifunctional CePO4/CS/GO scaffold, with characteristics such as photothermal therapy to kill tumors, macrophage polarization to promote blood vessel formation, and induction of bone formation. CePO4/CS/GO scaffold activates the caspase-3 proteasein local tumor cells, thereby lysing the DNA between nucleosomes and causing apoptosis. On the one hand, the as-released Ce3+ ions promote M2 polarization of macrophages, which secretes vascular endothelial growth factor (VEGF) and Arginase-1 (Arg-1), which promotes angiogenesis. On the other hand, the as-released Ce3+ ions also activated the BMP-2/Smad signaling pathway which facilitated bone tissue regeneration. CONCLUSION: The multifunctional CePO4/CS/GO scaffolds may become a promising platform for therapy of breast cancer bone metastases.

Heterosis-associated genes confer high yield in super hybrid rice.

KEY MESSAGE: Heterosis QTLs, including qSS7 and qHD8, with dominance effects were identified through GBS and large-scale phenotyping of CSSLs and hybrid F1 populations in a paddy field. Heterosis has contributed immensely to agricultural production, but its genetic basis is unclear. We evaluated dominance effects by creating two hybrid populations: a B-homo set with a homozygous background and heterozygous chromosomal segments and a B-heter set with a heterozygous background and homozygous segments. This was achieved by crossing a set of 156 backcrossed-derived chromosome segment substitution lines (CSSLs) with their recurrent parent (9311), the male parent of the first super-high-yield hybrid Liangyoupei9 (LYP9), and with the female parent (PA64s) of the hybrid. The CSSLs were subjected to a genotyping-by-sequencing analysis to develop a genetic map of segments introduced from the PA64s. We evaluated the heterotic effects on eight yield-related traits in the hybrid variety and F1 populations in large-scale field experiments over 2 years. Using a linkage map consisting of high-density SNPs, we identified heterosis-associated genes in LYP9. Five candidate genes contributed to the high yield of LYP9, with qSS7 and qHD8 repeatedly detected in both B-hybrid populations. The heterozygous segments harboring qSS7 and qHD8 showed dominance effects that contributed to the heterosis of yield components in the hybrid rice variety Liangyoupei9.

(NH4)3[B(OH)3]2(COOH)3: a graphite-like UV nonlinear optical material with a large birefringence via structural optimization.

A novel noncentrosymmetric (NCS) metal-free formic-borate, (NH4)3[B(OH)3]2(COOH)3, has been discovered, which exhibits an infrequent graphite-like structure. The alliance of two types of π-conjugated planar anions BO33- and COOH- produced an optimized layered structure to maximize the anisotropic polarizability, resulting in an extremely large birefringence (0.156@546 nm), larger than that of the classical commercial UV birefringent material α-BBO (0.122@546 nm). This strategy that structural optimization could enhance birefringence will guide the discovery of large birefringence materials, especially in the UV region.

The effect of induced membranes combined with enhanced bone marrow and 3D PLA-HA on repairing long bone defects in vivo.

The repair of large bone defects has always been a challenge, especially with respect to regeneration capacity and autogenous bone availability. To address this problem, we fabricated a 3D-printed polylactic acid (PLA) and hydroxyapatite (HA) scaffold (3D-printed PLA-HA, providing scaffold) loaded with enhanced bone marrow (eBM, providing seed cells) combined with induced membrane (IM, providing grow factors) to repair large radial defects in rabbits. in vitro assays, we demonstrated that 3D-printed PLA-HA had excellent biocompatibility, as shown by co-culturing with mesenchymal stem cells (MSCs); eBM-derived MSCs exhibited considerable differentiation potential, as shown in trilineage differentiation assays. To investigate bone formation efficacy in vivo, the rabbit radial long bone defect model was established. In the first stage, polymethylmethacrylate (PMMA) was inserted into the bone defect to stimulate the formation of IM; in the second stage, iliac crest bone graft (ICBG) with IM, PLA-HA alone with the removal of IM, PLA-HA with IM, and PLA-HA in conjunction with IM and eBM were sequentially applied to repair the long bone defect. At 8, 12, and 16 weeks, X-ray plain radiography, microcomputed tomography, and histological analysis were performed to evaluate the efficacy of bone repair and bone regeneration in each group. We found that IM combined with PLA-HA and eBM prominently enhanced bone repair and reconstruction, equivalent to that of IM/ICBG. Taken together, the data suggest that PLA-HA loaded with eBM combined with IM can be an alternative to IM with bone autografts for the treatment of large bone defects.

The Recombinant Protein EphB4-Fc Changes the Ti Particle-Mediated Imbalance of OPG/RANKL via EphrinB2/EphB4 Signaling Pathway and Inhibits the Release of Proinflammatory Factors In Vivo.

Aseptic loosening caused by wear particles is one of the common complications after total hip arthroplasty. We investigated the effect of the recombinant protein ephB4-Fc (erythropoietin-producing human hepatocellular receptor 4) on wear particle-mediated inflammatory response. In vitro, ephrinB2 expression was analyzed using siRNA-NFATc1 (nuclear factor of activated T-cells 1) and siRNA-c-Fos. Additionally, we used Tartrate-resistant acid phosphatase (TRAP) staining, bone pit resorption, Enzyme-linked immunosorbent assay (ELISA), as well as ephrinB2 overexpression and knockdown experiments to verify the effect of ephB4-Fc on osteoclast differentiation and function. In vivo, a mouse skull model was constructed to test whether the ephB4-Fc inhibits osteolysis and inhibits inflammation by micro-CT, H&E staining, immunohistochemistry, and immunofluorescence. The gene expression of ephrinB2 was regulated by c-Fos/NFATc1. Titanium wear particles activated this signaling pathway to the promoted expression of the ephrinB2 gene. However, ephrinB2 protein can be activated by osteoblast membrane receptor ephB4 to inhibit osteoclast differentiation. In in vivo experiments, we found that ephB4 could regulate Ti particle-mediated imbalance of OPG/RANKL, and the most important finding was that ephB4 relieved the release of proinflammatory factors. The ephB4-Fc inhibits wear particle-mediated osteolysis and inflammatory response through the ephrinB2/EphB4 bidirectional signaling pathway, and ephrinB2 ligand is expected to become a new clinical drug therapeutic target.

Two-stage evolution from phosphate to sulfate of new KTP-type family members as UV nonlinear optical materials through chemical cosubstitution-oriented design.

KTiOPO4 (KTP) is a classic commercial nonlinear optical (NLO) crystal, but its narrow bandgap (3.52 eV) prevents its practical application in the ultraviolet (UV) region. Many trials to widen the narrow bandgap of KTP have failed in the past few decades. A chemical cosubstitution strategy was implemented to design new members of the KTP-type family as potential UV NLO materials. First, a novel centrosymmetric KTP-type compound NH4SbFPO4·H2O with a sharply enlarged bandgap (5.01 eV) was obtained through three-site aliovalent substitution. Second, the noncentrosymmetric NH4SbF2SO4 was synthesized by the introduction of more F- anions to destroy the crystal symmetry and SO42- to replace PO43- for balancing the charge in NH4SbFPO4·H2O, which realized the transformation from a visible phosphate system to solar blind UV sulfate system for KTP-type family NLO materials. The preliminary experimental results indicated that NH4SbF2SO4 is a promising solar blind UV NLO material. The first-principles calculations revealed that the sharply enlarged bandgap resulted from the substitution of the transition metal cations with the main group metal cations and the introduction of F- anions with high electronegativity.

Quercetin inhibits macrophage polarization through the p-38α/ß signalling pathway and regulates OPG/RANKL balance in a mouse skull model.

Aseptic loosening caused by wear particles is a common complication after total hip arthroplasty. We investigated the effect of the quercetin on wear particle-mediated macrophage polarization, inflammatory response and osteolysis. In vitro, we verified that Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p-38α/ß signalling pathway by using flow cytometry, immunofluorescence assay and small interfering p-38α/ß RNA. We used enzyme-linked immunosorbent assays to confirm that the protein expression of M1 macrophages increased in the presence of Ti particles and that these pro-inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, this could be suppressed, and the protein expression of M2 macrophages was increased by the presence of the quercetin. In vivo, we revealed similar results in the mouse skull by µ-CT, H&E staining, immunohistochemistry and immunofluorescence assay. We obtained samples from patients with osteolytic tissue. Immunofluorescence analysis indicated that most of the macrophages surrounding the wear particles were M1 macrophages and that pro-inflammatory factors were released. Titanium particle-mediated M1 macrophage polarization, which caused the release of pro-inflammatory factors through the p-38α/ß signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.

Genome-wide associated study identifies NAC42-activated nitrate transporter conferring high nitrogen use efficiency in rice.

Over-application of nitrogen fertilizer in fields has had a negative impact on both environment and human health. Domesticated rice varieties with high nitrogen use efficiency (NUE) reduce fertilizer for sustainable agriculture. Here, we perform genome-wide association analysis of a diverse rice population displaying extreme nitrogen-related phenotypes over three successive years in the field, and identify an elite haplotype of nitrate transporter OsNPF6.1HapB that enhances nitrate uptake and confers high NUE by increasing yield under low nitrogen supply. OsNPF6.1HapB differs in both the protein and promoter element with natural variations, which are differentially trans-activated by OsNAC42, a NUE-related transcription factor. The rare natural allele OsNPF6.1HapB, derived from variation in wild rice and selected for enhancing both NUE and yield, has been lost in 90.3% of rice varieties due to the increased application of fertilizer. Our discovery highlights this NAC42-NPF6.1 signaling cascade as a strategy for high NUE and yield breeding in rice.