The OsCPK17-OsPUB12-OsRLCK176 module regulates immune homeostasis in rice.

Plant immunity is fine-tuned to balance growth and defense. However, little is yet known about molecular mechanisms underlying immune homeostasis in rice (Oryza sativa). In this study, we reveal that a rice calcium-dependent protein kinase (CDPK), OsCPK17, interacts with and stabilizes the receptor-like cytoplasmic kinase (RLCK) OsRLCK176, a close homolog of Arabidopsis thaliana BOTRYTIS-INDUCED KINASE 1 (AtBIK1). Oxidative burst and pathogenesis-related gene expression triggered by pathogen-associated molecular patterns are significantly attenuated in the oscpk17 mutant. The oscpk17 mutant and OsCPK17-silenced lines are more susceptible to bacterial diseases than the wild-type plants, indicating that OsCPK17 positively regulates rice immunity. Furthermore, the plant U-box (PUB) protein OsPUB12 ubiquitinates and degrades OsRLCK176. OsCPK17 phosphorylates OsRLCK176 at Ser83, which prevents the ubiquitination of OsRLCK176 by OsPUB12 and thereby enhances the stability and immune function of OsRLCK176. The phenotypes of the ospub12 mutant in defense responses and disease resistance show that OsPUB12 negatively regulates rice immunity. Therefore, OsCPK17 and OsPUB12 reciprocally maintain OsRLCK176 homeostasis and function as positive and negative immune regulators, respectively. This study uncovers positive cross talk between CDPK- and RLCK-mediated immune signaling in plants and reveals that OsCPK17, OsPUB12, and OsRLCK176 maintain rice immune homeostasis.

Nanodrug Hijacking Blood Transferrin for Ferroptosis-Mediated Cancer Treatment.

Ferroptosis as a promising method of cancer treatment heavily relies on the intracellular iron ion level. Herein, a new iron-supplement nanodrug was developed by conjugating transferrin-homing peptide T10 on the surface of cross-linked lipoic acid vesicles (T10@cLAV), which could hijack blood transferrin (Tf) and specifically deliver it to tumor cells to elevate the Fe2+ level. Meanwhile, the intracellular degradation product of cLAV, dihydrolipoic acid, could regenerate Fe2+ to further boost the ferroptosis. The results disclosed that T10@cLAV achieved tumor inhibition comparable to that of cisplatin at a dose as low as 5 mg/kg in the HeLa tumor-bearing nude mice model and caused no toxicity at the dose up to 300 mg/kg. This tactful iron-supplement strategy of hijacking blood Tf is superior to the current strategies: one is the induction of intracellular ferritin degradation, which is limited by the low content of ferritin, and the other is the delivery of iron-based materials, which easily causes adverse effects.

High-Density Dynamic Bonds Cross-Linked Hydrogel with Tissue Adhesion, Highly Efficient Self-Healing Behavior, and NIR Photothermal Antibacterial Ability as Dressing for Wound Repair.

Multifunctional hydrogels with tissue adhesion, self-healing behavior, and antibacterial properties have potential in wound healing applications. However, their inefficient self-healing behavior and antibacterial agents can cause long-term cytotoxicity and drug resistance, considerably limiting their clinical use. Herein, we reported a PDA@LA hydrogel constructed by introducing polydopamine nanoparticles (PDA-NPs) into a high-density dynamic bonds cross-linked lipoic acid (LA) hydrogel that was formed by the polymerization of LA. Because of its rich carboxyl groups, the LA hydrogel could adhere firmly to various tissues. Owing to the high-density dynamic bonds, the cut LA hydrogel exhibited highly inefficient self-healing behavior and recovered to its uncut state after self-healing for 10 min. After the introduction of the PDA-NPs, the hydrogel was able to heat up to more than 40 °C to kill approximately 100% of the Escherichia coli and Staphylococcus aureus under near-infrared (NIR) laser, thus resisting wound infections. Because no toxic antibacterial agent was used, the PDA@LA hydrogel caused mild long-term cytotoxicity or drug resistance. Consequently, the adhesive, highly efficient self-healing, and NIR photothermal antibacterial PDA@LA hydrogel exhibits considerable potential for clinical use.

A confinement-regulated (H3C-NH3)+ ion as a smallest dual-wheel rotator showing bisected rotation dynamics.

On the basis of variable-temperature single-crystal X-ray diffraction, rotational energy barrier analysis, variable-temperature/frequency dielectric response, and molecular dynamics simulations, here we report a new crystalline supramolecular rotor (CH3NH3)(18-crown-6)[CuCl3], in which the (H3C-NH3)+ ion functions as a smallest dual-wheel rotator showing bisected rotation dynamics, while the host 18-crown-6 macrocycle behaves as a stator that is not strictly stationary. This study also provides a helpful insight into the dynamics of ubiquitous -CH3/-NH3 groups confined in organic or organic-inorganic hybrid solids.

Metabolic syndrome increases osteoarthritis risk: findings from the UK Biobank prospective cohort study.

OBJECTIVE: The association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank. METHODS: A prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan-Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk. RESULTS: A total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12-1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5-1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1-1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05-1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02-1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3-1.4). CONCLUSION: MetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.

Natural Antioxidant-Based Nanodrug for Atherosclerosis Treatment.

Natural antioxidants are always considered as candidates for the antioxidative therapy of atherosclerosis (AS) due to their good safety profile. However, restricted to their limited reactive oxygen species (ROS) elimination and rapid metabolism, the natural antioxidants' treatment suffers from the undesirable clinical outcomes. Herein, a new natural antioxidant-based nanodrug (VC@cLAVs) that can overcome above issues is developed to treat AS by loading natural antioxidant vitamin C (VC) into the natural antioxidant lipoic acid (LA)-constructed cross-linked vesicles. This integration not only greatly increases the blood half-life of natural antioxidants, but also amplifies the antioxidation capacity by the mutual recycling of two redox pairs LA/DHLA (reduced form of LA) and VC/DHA (oxidized form of VC). In vivo results disclose that VC@cLAVs decreases the apolipoprotein E-deficient mice's plaque area from 52% to 13%, much lower than those of free VC (≈45%) and LA (≈38%). This natural antioxidant-based nanodrug holds great potential in clinics.

N-Heterocyclic Olefin Type Ionic Liquid with Innate Soft Lewis-Base Character as an Effective Additive for Hybrid Quasi-2D and 3D Perovskite Solar Cells.

In optimizing perovskites with ionic liquid (IL), the comparative study on Lewis acid-base (LAB) and hydrogen-bonding (HB) interactions between IL and perovskite is lacking. Herein, methyl is substituted for hydrogen on 2-position of imidazolium ring of N-heterocyclic carbene (NHC) type IL IdH to weaken HB interactions, and the resulting N-heterocyclic olefin (NHO) type IL IdMe with softer Lewis base character is studied in both hybrid quasi-2D (Q-2D) and 3D perovskites. It is revealed that IdMe participates in constructing high-quality Q-2D perovskite (n = 4) and provides stronger passivation for 3D perovskite compared with IdH. Power conversion efficiency (PCE) of Q-2D PEA2 MA3 Pb4 I13 perovskite solar cells (PVSCs) is boosted to 17.68% from 14.03%. PCE and device stability of 3D PVSCs enhances simultaneously. Both theoretical simulations and experimental results show that LAB interactions between NHO and Pb2+ take the primary optimization effects on perovskite. The success of engineering LAB interactions also offers inspiration to develop novel ILs for high-performance PVSCs.

Aspirin-Loaded Cross-Linked Lipoic Acid Nanodrug Prevents Postoperative Tumor Recurrence by Residual Cancer Cell Killing and Inflammatory Microenvironment Improvement.

In addition to residual cancer cells, the surgery resection-induced hyperinflammatory microenvironment is a key factor that leads to postsurgical cancer recurrence. Herein, we developed a dual-functional nanodrug Asp@cLANVs for postsurgical recurrence inhibition by loading the classical anti-inflammatory drug aspirin (Asp) into cross-linked lipoic acid nanovesicles (cLANVs). The Asp@cLANVs can not only kill residual cancer cells at the doses comparable to common cytotoxic drugs by synergistic interaction between Asp and cLANVs, but also improve the postsurgical inflammatory microenvironment by their strongly synergistic anti-inflammation activity between Asp and cLANVs. Using mice bearing partially removed NCI-H460 tumors, we found that Asp@cLANVs gave a much lower recurrence rate (33.3%) compared with the first-line cytotoxic drug cisplatin (100%), and no mice died for at least 60 days after Asp@cLANV treatment while no mouse survived beyond day 43 in the cisplatin group. This dual-functional nanodrug constructs the first example that combines residual cancer cell killing and postoperative inflammation microenvironment improvement to suppress postsurgical cancer recurrence.

Near-Room-Temperature Synergetic Response of Magnetism, Dielectricity and Luminescence Based on (C5 NH13 Cl)2 MnBr4.

Multifunctional materials with working temperatures near room temperature are crucial for practical applications. Until now, it is still a great challenge to obtain such materials. In this paper, a complex of (C5 NH13 Cl)2 MnBr4 (1) with a structural phase transition near room temperature is reported. The phase transition induces switchable magnetic properties, dielectric anomalies and luminescent response over the same range of temperatures. It is the first time the synergetic effect of magnetism, dielectricity and luminescence near room temperature have been observed in the same molecular complex.

Exploring the Relationship between Perfectionism and Pain in Patients with Temporomandibular Disorders: A Cross-Sectional Study.

Objectives: The purpose of this cross-sectional study was to examine the relationship between perfectionism and pain in patients with temporomandibular disorders (TMDs). Methods: A total of 345 TMD patients were included. A questionnaire consisting of questions of demographic information, the 15-item short form of the Hewitt and Flett Multidimensional Perfectionism Scale, and the Patient Health Questionnaire-4 (PHQ-4) was distributed. According to the diagnostic criteria for TMDs, patients were categorized as pain-related (PT) and non-pain-related (NPT) groups, whereas PT patients were further divided into patients with pain-related TMDs only (OPT) and patients with combined pain-related and intra-articular TMDs (CPT). Data were analyzed using the chi-square test, Spearman's correlation, and logistic regression analysis with the significance level set at p < 0.05. Results: There were 68 patients in the NPT group, 80 in the OPT group, and 197 in the CPT group. PT patients had significantly higher perfectionism scores (63.58 ± 13.63) than NPT patients (56.32 ± 12.95, p < 0.001). The PHQ-4 score in the PT group was also higher. After adjusting the PHQ-4 scores, perfectionism scores of the PT group were 6.11 points higher than those in the NPT group (p < 0.001). There were no statistical differences in all parameters of OPT and CPT groups (p > 0.05). Perfectionism in total, other-oriented perfectionism (OOP), and socially prescribed perfectionism (SPP) showed significant but weak correlations with PHQ-4 scores (p < 0.001), while self-oriented perfectionism (SOP) was also significantly but very weakly correlated with PHQ-4 scores (p < 0.05). Conclusions: Pain-related TMD patients exhibited higher perfectionism scores than NPT patients, and neither their perfectionism nor pain scores were correlated with intra-articular diseases of TMJ. OOP and SOP presented weak correlations with psychological distress in TMD patients. It is suggested that pain-related TMD patients could be screened for perfectionism and perfectionism could be considered when proposing psychological treatment strategies to PT patients.

Reconstruction of Medial Orbital Wall Using Autologous Perpendicular Plate of Ethmoid.

The aim of this study is to investigate the feasibility of perpendicular plate of ethmoid as material for the reconstruction of medial orbital wall. The main outcome measurement was preoperative and postoperative orbital volume. The authors performed a study including 17 patients who have isolated medial orbital wall fracture (blow-out fracture). All the patients were fixed the defect using autologous perpendicular plate of ethmoid under endonasal approach. The authors compared the preoperative and postoperative orbital volume difference (unaffected orbit, affected orbit) of all the patients, and observed the improvement of diplopia or ocular motility disorders after operation. All 17 medial orbital wall reconstruction surgeries were successful with no severe postoperative ophthalmic complications. Statistically significant differences were found between the preoperative and postoperative orbital tissue volumes for the affected orbit. There was no statistically significant difference found between the tissue volume of the contralateral unaffected orbit and the affected orbit after reconstruction. And postoperative computed tomography showed the implant is in place and there is no medial rectus incarceration. Autologous perpendicular plate of ethmoid proved to be safe and effective in the reconstruction of medial orbital wall under endonasal approach with cost-effectivence, low complication rate, high biocompatibility, and minimally invasion.

A Pair of Multifunctional Cu(II)-Dy(III) Enantiomers with Zero-Field Single-Molecule Magnet Behaviors, Proton Conduction Properties and Magneto-Optical Faraday Effects.

Multifunctional materials with a coexistence of proton conduction properties, single-molecule magnet (SMM) behaviors and magneto-optical Faraday effects have rarely been reported. Herein, a new pair of Cu(II)-Dy(III) enantiomers, [DyCu2(RR/SS-H2L)2(H2O)4(NO3)2]·(NO3)·(H2O) (R-1 and S-1) (H4L = [RR/SS] -N,N'-bis [3-hydroxysalicylidene] -1,2-cyclohexanediamine), has been designed and prepared using homochiral Schiff-base ligands. R-1 and S-1 contain linear Cu(II)-Dy(III)-Cu(II) trinuclear units and possess 1D stacking channels within their supramolecular networks. R-1 and S-1 display chiral optical activity and strong magneto-optical Faraday effects. Moreover, R-1 shows a zero-field SMM behavior. In addition, R-1 demonstrates humidity- and temperature-dependent proton conductivity with optimal values of 1.34 × 10-4 S·cm-1 under 50 °C and 98% relative humidity (RH), which is related to a 1D extended H-bonded chain constructed by water molecules, nitrate and phenol groups of the RR-H2L ligand.

Linoleic Acid-Glucosamine Hybrid for Endogenous Iron-Activated Ferroptosis Therapy in High-Grade Serous Ovarian Cancer.

As the most common subtype in ovarian malignancies, high-grade serous ovarian cancer (HGSOC) made less therapeutic progress in past decades due to the lack of effective drug-able targets. Herein, an effective linoleic acid (LA) and glucosamine (GlcN) hybrid (LA-GlcN) was synthesized for the treatment of HGSOC. The GlcN was introduced to recognize the glucose transporter 1 (GLUT 1) overexpressed in tumor cells to enhance the uptake of LA-GlcN, and the unsaturated LA was employed to trigger ferroptosis by iron-dependent lipid peroxidation. Since the iron content of HGSOC was ∼5 and 2 times, respectively, higher than that of the normal ovarian cells and low-grade serous ovarian cancer cells, these excess irons make them a good target to enhance the ferroptosis of LA-GlcN. The in vitro study demonstrated that LA-GlcN could selectively kill HGSOC cells without affecting normal cells; the in vivo study revealed that LA-GlcN at the dose of 50 mg kg-1 achieved a comparable tumor inhibition as doxorubicin hydrochloride (4 mg kg-1) while the overall survival of mice was extended largely due to the low toxicity, and when the dose was increased to 100 mg kg-1, the therapeutic outcomes could be improved further. This dietary hybrid which targets the excess endogenous iron to activate ferroptosis represents a promising drug for HGSOC treatment.

Adsorption Mechanism of Amidoxime Collector on the Flotation of Lepidolite: Experiment and DFT Calculation.

Lepidolite is an important mineral resource of lithium. With the increase in awareness of low-carbon and green travel, the demand for lithium has increased dramatically. Therefore, how to increase the output of lithium has to turn into high precedence. In this paper, amidoxime (DPA) was synthesized and used for the efficient collection of lepidolite. Dodecylamine (DA), a commonly used collector of lepidolite ore, was used for comparison. The collecting performances of DA and DPA for lepidolite were studied by the micro-flotation experiment, and the adsorption mechanism of DPA on lepidolite was verified by contact angle, zeta potential tests, FTIR spectra, and density functional theory (DFT) calculations. The results of flotation experiments showed that at the same collector dosage (3 × 10-4 mol/L), the recovery of lepidolite could reach 90%, while the recovery of lepidolite with DA was only 52.5%, and to achieve the maximum recovery of DA (77.5%), only half of the DPA was added. The contact angle test results showed that DPA could effectively improve the hydrophobicity of lepidolite than DA. FTIR spectra and zeta potential tests suggested that DPA molecules were adsorbed on the lepidolite surface by electrostatic attraction. DFT calculations revealed that DPA reacted with the nucleophilic reagent (lepidolite) by the reactive site of the -CH2NH(CH2)2C(NOH)N+H3 group and more easily absorbed on the surface of lepidolite than DA. Therefore, our new finding will provide an important prospect for the sustainable development and utilization of lithium resources.

Adsorption of Trisiloxane Surfactant for Selective Flotation of Scheelite from Calcite at Room Temperature.

The separation and enrichment of scheelite from calcite are hindered by the similar active Ca2+ sites of scheelite and the calcite with calciferous gangue. Herein, a novel trisiloxane surfactant, N-(2-aminoethyl)-3-aminopropyltrisiloxane (AATS), was first explored and synthesized and recommended as the collector for the flotation separation of scheelite from calcite. The micro-flotation and mixed binary mineral flotation tests showed that AATS had excellent collection performance for scheelite and high selectivity for calcite within a wide pH range. At the same time, contact angle and zeta-potential measurements, Fourier transform infrared (FTIR) analysis, and density functional theory (DFT) calculations revealed the relevant adsorption mechanism. The contact angle measurement showed that AATS can increase the contact angle of the scheelite surface from 41.7 to 95.8°, greatly enhancing the hydrophobicity of the mineral surface. The results of FTIR analysis and zeta-potential measurement explained that AATS was electrostatically adsorbed on the mineral surface, and DFT calculation further verified that the -N+H3-positive group in AATS was adsorbed on the negatively charged scheelite surface. Therefore, AATS can realize the expectation of high efficiency and selectivity of minerals and enhance the adhesion between the surface of scheelite minerals and bubbles, providing a fresh approach to industrial production.

Sociodemographic and Policy Factors Associated with the Transmission of COVID-19: Analyzing Longitudinal Contact Tracing Data from a Northern Chinese City.

To examine how sociodemographic characteristics and non-pharmaceutical interventions affect the transmission of COVID-19, we analyze patient profiles and contact tracing data from almost all cases in an outbreak in Shijiazhuang, China, from January to February 2021. Because of universal testing and digital tracing, the data are of high quality. Results from negative binomial models indicate that the counts of close contacts and secondary infections vary with the cases' age and occupation. Notably, cases under age 18 are causing an increased infection rate among their close contacts and leading to more within-neighborhood secondary infections than adults aged 18-49. Also, county-wide interventions and lockdown are found to be effective at containing the spread of COVID-19. These measures can reduce the number of close contacts that each case has and largely restrict the remaining infections to the case's neighborhood. These results suggest that transmission risks of COVID-19 are associated with the case's sociodemographic characteristics and can be reduced with interventions at the county level. Implications on mitigation measures and reopening plans are discussed.

Nitroreductase-induced bioorthogonal ligation for prodrug activation: A traceless strategy for cancer-specific imaging and therapy.

Prodrug development is of great interest in cancer therapy. From bio-friendly standpoints, traceless prodrug activation would be an ideal approach for cancer treatment owning to the avoidance of byproduct which might induce side effects in living system. Here, we report a fully traceless strategy for cancer imaging and therapy via a metal-free bioorthogonal ligation triggered by nitroreductase (NTR) overexpressed in solid tumors. The reduction of nitro substrates to amines by NTR and further condensation of amines with aldehydes can be seamlessly combined to yield imine-based resveratrol (RSV) with water as the only byproduct. In comparison with RSV, this precursor exhibited not only the same level of anticancer efficiency both in vitro and in vivo under hypoxia, but also a high sensitivity to hypoxia and much lower perturbation towards normal cells, which holds a great potential of theranostic prodrug for cancer therapy.

Application of digital subtraction angiography in canine hindlimb arteriography.

OBJECTIVES: Research in the field of lower extremity vascular disease has increased in popularity over the years. To adequately characterize and validate the effectiveness of vascular interventions, in vivo experimentation in large animals is required. Thus, it is necessary to find a method to detect the shape and density of blood vessels in the lower extremities that can evaluate and verify the treatment measures' effectiveness and have high accuracy and repeatability. This study characterized factors that determined both the accuracy and overall value of digital subtraction angiography in lower limb arteriography using a canine animal model. METHODS: Six beagle dogs were anesthetized and immobilized on the motorized table. The femoral artery was accessed using an indwelling needle. A bolus of contrast agent was injected into the access site, and digital subtraction angiography with bolus chase technology was used to collect contrast images for analysis. At the end of the procedure, the anesthetized dogs were euthanized using an overdose of potassium chloride. After confirming the euthanasia of the dogs, the cadavers were taken to the experimental animal center of Xinjiang Medical University and processed by qualified institutional personnel. RESULTS: The final arteriographic images of the hind limbs from all six dogs were precise, and the branches of small vessels could be distinguished without any visible artifacts. CONCLUSIONS: These results suggested that arteriography using digital subtraction angiography could reveal the shape and density of blood vessels in canine animal models. This method has great potential to significantly improve research related to limb ischemia due to its simple and reproducible results.

Genome-wide identification and expression analysis of mitogen-activated protein kinase (MAPK) genes in response to salinity stress in channel catfish (Ictalurus punctatus).

The mitogen-activated protein kinase (MAPK) gene family has been systematically described in several fish species, but less so in channel catfish (Ictalurus punctatus), which is an important global aquaculture species. In this study, 16 MAPK genes were identified in the channel catfish genome and classified into three subfamilies based on phylogenetic analysis, including six extracellular signal regulated kinase (ERK) genes, six p38-MAPK genes and four C-Jun N-terminal kinase (JNK) genes. All MAPK genes were distributed unevenly across 10 chromosomes, of which three (IpMAPK8, IpMAPK12 and IpMAPK14) underwent teleost-specific whole genome duplication during evolution. Gene expression profiles in channel catfish during salinity stress were analysed using transcriptome sequencing and qRT-PCR (quantitative reverse transcription PCR). Results from reads per kilobase million (RPKM) analysis showed IpMAPK13, IpMAPK14a and IpMAPK14b genes were differentially expressed when compared with other genes between treatment and control groups. Furthermore, three of these genes were validated by qRT-PCR, of which IpMAPK14a expression levels were significantly upregulated in treatment groups (high and low salinity) when compared with the control group, with the highest expression levels in the low salinity group (P < 0.05). Therefore, IpMAPK14a may have important response roles to salinity stress in channel catfish.

A New RING Finger Protein, PLANT ARCHITECTURE and GRAIN NUMBER 1, Affects Plant Architecture and Grain Yield in Rice.

Developing methods for increasing the biomass and improving the plant architecture is important for crop improvement. We herein describe a gene belonging to the RING_Ubox (RING (Really Interesting New Gene) finger domain and U-box domain) superfamily, PLANT ARCHITECTURE and GRAIN NUMBER 1 (PAGN1), which regulates the number of grains per panicle, the plant height, and the number of tillers. We used the CRISPR/Cas9 system to introduce loss-of-function mutations to OsPAGN1. Compared with the control plants, the resulting pagn1 mutant plants had a higher grain yield because of increases in the plant height and in the number of tillers and grains per panicle. Thus, OsPAGN1 may be useful for the genetic improvement of plant architecture and yield. An examination of evolutionary relationships revealed that OsPAGN1 is highly conserved in rice. We demonstrated that OsPAGN1 can interact directly with OsCNR10 (CELL NUMBER REGULATOR10), which negatively regulates the number of rice grains per panicle. A transcriptome analysis indicated that silencing OsPAGN1 affects the levels of active cytokinins in rice. Therefore, our findings have clarified the OsPAGN1 functions related to rice growth and grain development.