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Flowering time (heading date) is a critical agronomic trait that determines the yield and regional adaptability of crops. Heading date 1 (Hd1) is a central regulator of photoperiodic flowering in rice (Oryza sativa). However, how the homeostasis of Hd1 protein is achieved is poorly understood. Here, we report that the nuclear autophagy pathway mediates Hd1 degradation in the dark to regulate flowering. Loss of autophagy function results in an accumulation of Hd1 and delays flowering under both short-day and long-day conditions. In the dark, nucleus-localized Hd1 is recognized as a substrate for autophagy and is subjected to vacuolar degradation via the autophagy protein OsATG8. The Hd1-OsATG8 interaction is required for autophagic degradation of Hd1 in the dark. Our study reveals a new mechanism by which Hd1 protein homeostasis is regulated by autophagy to control rice flowering. Our study also indicates that the regulation of flowering by autophagic degradation of Hd1 orthologs may have arisen over the course of mesangiosperm evolution, which would have increased their flexibility and adaptability to the environment by modulating flowering time.

Pathogen infection induces massive reprogramming of host primary metabolism. Lipid and fatty acid metabolism is generally disrupted by pathogens and co-opted for their proliferation. Lipid droplets (LDs) that play important roles in regulating cellular lipid metabolism are utilized by a variety of pathogens in mammalian cells. However, the function of LDs during pathogenic infection in plants remains unknown. We show here that infection by rice black streaked dwarf virus (RBSDV) affects the lipid metabolism of maize, which causes elevated accumulation of C18 polyunsaturated fatty acids (PUFAs) leading to viral proliferation and symptom development. Overexpression of one of the two novel LD-associated proteins (LDAPs) of maize (ZmLDAP1 and ZmLDAP2) induces LD clustering. The core capsid protein P8 of RBSDV interacts with ZmLDAP2 and prevents its degradation through the ubiquitin-proteasome system mediated by a UBX domain-containing protein, PUX10. In addition, silencing of theZmLDAP2down-regulates expression of fatty acid desaturase genes in maize, leading to a decrease in C18 PUFAs levels and suppression of RBSDV accumulation. Our findings reveal that the plant virus recruits LDAP to regulate cellular fatty acid metabolism to promote viral multiplication and infection. These results expand the knowledge of the LD functions and viral infection mechanism in plants.One Sentence SummaryRice black streaked dwarf virus recruits a lipid droplet-associated protein to regulate cellular fatty acid metabolism for promoting viral multiplication and infection.

BACKGROUND The aim of our study is to investigate the impact of the simple breathing exercises (LHP's respiratory rehabilitation for pulmonary fibrosis, LHP's RRPF) on patients with idiopathic pulmonary fibrosis (IPF). METHODS (I) The safety and effectiveness of LHP's RRPF were first verified in 20 healthy individuals. (II) A total of 101 patients with IPF administrated in Shanghai Pulmonary Hospital between January 2015 and May 2017 were screened, and 82 cases were randomly assigned to receive a 12-month LHP's RRPF program (exercise group) or usual medical care (control group). Lung function, chest X-ray, 6-minute walk distance (6MWD), quality of life (St. George's Respiratory Questionnaire, SGRQ), and EKG were measured at the 6th and 12th month during the trial. RESULTS At the 6th month visit, the exercise group showed improved SGRQ score and lung function parameters (FVC, FEV1, and DLCO). At the 12th months visit, the exercise group had significantly improved SGRQ score, 6MWD, and lung function (FVC, FEV1, and DLCO) compared to the control group (P

Background In the general population, TG/HDL-C is as a marker of cardiovascular (CV) events and death. However, studies on TG/HDL-C in haemodialysis (HD) patients are limited, and the results are controversial. This study investigated the TG/HDL-C ratio and all-cause and CV mortality in HD patients. Methods In this retrospective cohort study, 582 HD patients were enrolled from June 2015 to September 2016 and followed through September 2021. The outcomes were all-cause death and CV mortality. The optimal threshold for the TG/HDL-C ratio was determined by Youden's index in receiver-operating characteristic curve analyses, and the Kaplan–Meier method and log rank test were applied to assess groups. The association between TG/HDL-C and mortality was analysed by adjusted multivariate Cox proportional hazard regression models. Results During the median follow-up of 68 months, 159 patients died, with 82 (51.6%) classified as CV death. The optimal threshold of the TG/HDL-C ratio was determined to be 1.71. Kaplan–Meier curves confirmed that patients with TG/HDL-C ≥1.71 had significantly lower all-cause mortality (log rank test, p = 0.007) and cardiovascular mortality (log rank test, p = 0.006). After adjusting for confounders, multivariate Cox regression analysis showed that TG/HDL-C ≥1.71 was associated with decreased all-cause mortality (adjusted hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.47-0.95, P=0.026) and cardiovascular mortality (adjusted HR: 0.59; 95% CI: 0.36-0.99; P=0.045) in HD patients. Conclusion TG/HDL-C is an independent protective factor for mortality in HD patients. High TG/HDL-C was associated with decreased all-cause and CV mortality in HD patients.

BH3120 is a heterodimeric bispecific antibody, designed to target 4-1BB and PD-L1 simultaneously with Pentambody™ platform, to stimulate anti-tumor immune response in a tumor microenvironment (TME) specific manner. BH3120 showed strong antitumor efficacy in multiple tumor models, and combination of BH3120 with a PD-1 antagonist showed synergic effects eradicating tumor. While BH3120 consistently activates T cells, both as a monotherapy and in combination with a PD-1 antagonist, modulation of immune system in the tumor tissue is clearly de-coupled from that in peripheral blood, suggesting reduced risks of immune related adverse events (irAEs) with BH3120. To verify this hypothesis, BH3120 was compared with reference bispecific antibodies. Combination of BH3120 with a PD-1 antogonist does not result in elevation of transaminase enzymes, while the reference bispecific antibodies, when combined with the same PD-1 antagonist, show significant increase of the enzymes and macrophage in liver. In the toxicology studies conducted so far with cynomolgus monkeys, NOAEL of BH3120 was determined to be 200 mg/kg (QW X 5). Citation Format: Jing Wang, Jun Wang, Yang Liu, Yan Pang, Aihong Zhang, Jie Feng, Aibo Sun, Xiao Ma, Jingmei Cai, Jiangcheng Xu, Jiawang Liu, Kyoungwoo Lee. BH3120, a bispecific antibody targeting 4-1BB and PD-L1 simultaneously, stimulates T cells in tumor tissue preferred manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1799.

Fleshy fruits undergo a complex ripening process, developing organoleptic fruit traits that attract herbivores and maximize seed dispersal. Ripening is the terminal stage of fruit development and involves a series of physiological and biochemical changes. In fleshy fruits, ripening always involves a drastic color change triggered by the accumulation of pigments and degradation of chlorophyll, softening caused by cell wall remodeling, and flavor formation as acids and sugars accumulate alongside volatile compounds. The mechanisms underlying fruit ripening rely on the orchestration of ripening-related transcription factors, plant hormones, and epigenetic modifications. In this review, we discuss current knowledge of the transcription factors that regulate ripening in conjunction with ethylene and environmental signals (light and temperature) in the model plant tomato (Solanum lycopersicum) and other fleshy fruits. We emphasize the critical roles of epigenetic regulation, including DNA methylation and histone modification as well as RNA m6A modification, which has been studied intensively. This detailed review was compiled to provide a comprehensive description of the regulatory mechanisms of fruit ripening and guide new strategies for its effective manipulation.

Background. Mortality from noncancer causes in patients with prostate cancer (PCa) is unclear. This study assesses the causes and risks of noncancer death with each follow-up time period after PCa diagnosis. Methods. Data from the Surveillance, Epidemiology, and End Results (SEER) program were analyzed for noncancer causes of death in PCa patients from 2000 to 2016. The standard mortality ratio (SMR) was calculated for noncancer mortality. Results. Altogether, 752,352 patients with PCa were identified, and 180,862 (24.0%) died during follow-up. The largest proportion of deaths from noncancer causes (36%) occurred within 5 to 10 years after diagnosis. The most common causes of noncancer death are cardiovascular and cerebrovascular diseases and chronic obstructive pulmonary disease (COPD). Compared with the general age-matched male population, patients with PCa had a higher risk of death from any noncancer cause within 5 years, in particular other infectious diseases and suicide and self-inflicted injury. However, the risk of death from noncancer causes of PCa for more than 5 years is lower, except for Alzheimer’s disease and hypertension from 5 to 10 years after diagnosis. In addition, the risk of death from noncancer causes was influenced by treatment, ethnicity, and staging differences. In particular, compared with the general population, many noncancer causes of death have higher risk of death in patients with or without treatment within 1 to 5 years after diagnosis, whereas patients undergoing radical prostatectomy (RP) with or without radiotherapy (RT) or chemotherapy (CTx) are not at high risk of death from COPD, pneumonia and influenza, nephritis, nephrotic syndrome and nephrosis, septicemia, and atherosclerosis. Conclusion. The risk of death from noncancer causes gradually decreased in all patients with PCa during each follow-up period after diagnosis In addition, the risk of dying from noncancer causes are influenced by differences in stage, ethnicity, and treatment. In particular, patients undergoing RP±RT/CTx and RT/CTx have a lower risk of death compared to the general population. These findings provide important implications for the healthcare management of patients with PCa.

Using the commercially available antidiabetic drug exenatide (exendin-4) as a model peptide, we designed a novel exenatide derivative, termed LEX-1, comprising a 12-mer albumin-binding peptide, a protease-sensitive linker and a native exenatide. In addition, site-specific PEGylation was performed using LEX-1 as a lead sequence to generate four exenatide derivatives (LEX-2 to LEX-5). Moreover, we determined the optimal molecular weight of maleimide-derivatized PEG for the site-specific PEGylation of LEX-1 by an in vitro stability assay and an in vivo hypoglycemic efficacy test. As a result, LEX-3 (PEG10 kDa) exerted enhanced proteolytic stability, rational release rate of free exenatide and the best glucose-stabilizing capability compared with others. In addition, the prolonged hypoglycemic effects of LEX-1 and LEX-3 were demonstrated in type 2 diabetic mice by multiple OGTTs and a hypoglycemic duration test. Furthermore, a pharmacokinetic test was conducted using Sprague Dawley (SD) rats; LEX-3 (PEG10 kDa) showed the best circulating t1/2 of ∼119.7 h for exenatide release from LEX-3, suggesting that LEX-3 has the potential to be developed into a once-weekly antidiabetic agent. The consecutive 8 week treatment of both LEX-1 and LEX-3 exhibited enhanced beneficial efficacies on body weight gain, cumulative food intake, % fat and hemoglobin A1c (HbA1c) reduction compared with exenatide treatment. Meanwhile, the chronic administration of LEX-1 and LEX-3 also effectively improved the blood biochemical indexes. Our results indicate the enhanced antidiabetic effects of LEX-1 and LEX-3, and our strategy of PEGylation and albumin conjugation can be applied to other bioactive agents.

Protein-mediated RNA stabilization plays profound roles in chloroplast gene expression. Genetic studies have indicated that chloroplast ndhA transcripts, encoding a key subunit of the NADH dehydrogenase-like complex that mediates photosystem I cyclic electron transport and facilitates chlororespiration, are stabilized by PPR53 and its orthologs, but the underlying mechanisms are unclear. Here, we report that CHLOROPLAST RNA SPLICING 2 (CRS2)-ASSOCIATED FACTOR (CAF) proteins activate SUPPRESSOR OF THYLAKOID FORMATION 1 (SOT1), an ortholog of PPR53 in Arabidopsis thaliana, enhancing their affinity for the 5′ ends of ndhA transcripts to stabilize these molecules while inhibiting the RNA endonuclease activity of the SOT1 C-terminal SMR domain. In addition, we established that SOT1 improves the splicing efficiency of ndhA by facilitating the association of CAF2 with the ndhA intron, which may be due to the SOT1-mediated stability of the ndhA transcripts. Our findings shed light on the importance of PPR protein interaction partners in moderating RNA metabolism.

BACKGROUND: At present, the low risk of bladder cancer (BCa)-specific death has allowed for investigation into treatment-related cardiotoxicity. To aid clinicians in selecting appropriate cardiovascular disease screening strategies and interventions, this study explored the heart-specific mortality and prognostic factors of patients with BCa after radical cystectomy (RC), radiotherapy (RT), or chemotherapy (CT), and compared their long-term heart-specific mortality with that of the general male population. METHODS: We identified three different treatments for BCa patients from the Surveillance, Epidemiology, and End Results (SEER) database: RC, RT, and CT. Patients were included from 2000 to 2012 and followed through 2015. A cumulative mortality curve and competitive risk regression model were applied to evaluate the prognostic factors of heart-specific mortality, and standardized mortality ratios (SMRs) were calculated. RESULTS: Of 39,500 men, 30.3%, 18.8%, and 50.9% received RC, RT, and CT, respectively. For patients with a survival period of less than 50 months, tumor-specific death exhibited a rapidly increasing trend, which subsequently flatlined. However, the rates heart-specific mortality and other causes exhibited a tendency to increase stably. The heart-specific and all-cause mortality rates of patients in any age group treated with the three abovementioned strategies were higher than those of the general population. The heart-specific mortality of patients with carcinoma in situ treated with RC and CT exceeded their all-cause mortality, while that of other tumor stages did not. The risks of heart-specific [sub-distribution hazard ratio (SHR) =1.38; 95% confidence interval (CI): 1.22–1.57] and tumor-specific (SHR =1.68; 95% CI: 1.60–1.77) deaths in patients who received RT were higher than those of patients who underwent CT. CONCLUSIONS: The risks of heart-specific and tumor-specific deaths in patients who received RT were higher than those of the RC and CT groups, especially in patients over 65 years of age who received RT.

Efforts to remove highly toxic haloacetonitriles (HANs) is an important step to reduce health risks associated with disinfection by product exposure. Zero valent iron (ZVI) is a versatile material, whose reductant, sorbent and coagulant role has been well understood. However, their catalytic role is less known. In this study, the degradation and transformation of HANs in ZVI system were investigated. Significant decreases of the four HANs in ZVI system were observed, and haloacetamides and haloacetic acids (hydrolysis products of HANs) were the dominant transformation products of HANs. However dehalogenated HANs, Fe (II) and Fe (III) were rarely detected after reaction, indicating that the ZVI acted as a catalyst to promote the hydrolysis of HANs, rather than other previously reported causes (dehalogenation or redox reaction). The HAN degradation rates were dramatically affected by the initial pH, ZVI doses and initial HAN concentration. Kinetic analysis indicated that HAN removal was enhanced with the increase of initial pH (5-9), ZVI doses (1-10 g/L), and initial HAN concentration (25-200 μg/L). ZVI induced the transformation of HANs to haloacetamides, haloacetic acids and other de-halogenated compounds, which reduced the cytotoxicity and genotoxicity by 88% and 85%, respectively. This study helped to understand the fate of HAN during the transmission in cast iron pipes, and provided a theoretical foundation for future HAN control and monitoring efforts.

Human epidermal growth factor receptor 2 (HER2) has been established as an approved druggable target for the treatment of patients with diverse gynecological tumors such as ovarian, cervical and breast cancers. The mitogen-inducible gene 6 (MIG6) protein is a negative regulator of HER2 signaling by using its Seg1 segment to disrupt the allosteric dimerization of HER2 kinase domain. Previous studies found that the Seg1 adopts three separated hotspots to interact with the HER2 dimerization interface, in which the third hotspot (H3) is located at the core region of the interface but its derived H3 peptide (356PK Y VS360) and Tyr358Phe mutant (356PK F VS360) cannot bind effectively to the interface in an independent manner. In this study, we demonstrate that the H3 peptide can be converted from nonbinder to a moderate binder of HER2 by just adding an orthogonal noncovalent interaction system (X⋯O┄H) between a halogen bond (X⋯O) and a hydrogen bond (H┄O) involving peptide Phe358 residue and HER2 Val948/Trp951 residues. High-level calculations are utilized to rigorously characterize and rationally design the X⋯O┄H system, which is then optimized with different halogen atoms and at different substituting positions. It is revealed that there is a synergistic effect between the X⋯O and H┄O of the orthogonal interaction system; formation of the halogen bond can enhance the interaction strength of the hydrogen bond. In silico analysis and in vitro assay reach a consistence that Br-substitution at the m-position of peptide Phe358 phenyl moiety is the best choice that can render strong interaction for the X⋯O┄H system, which also makes the peptide ‘bindable’ to HER2 kinase domain, while F/Cl/I-substitution at the same position can only improve the peptide affinity moderately or modestly. In contrast, the Br-substitution at the o- and p-positions of peptide Phe358 phenyl moiety cannot define effective X⋯O┄H interaction and thus does not confer additional affinity to the HER2–peptide complex.

The alternative disinfectant chloramine can lower the formation of carbonaceous DBPs (C-DBPs) but promote the formation of nitrogenous DBPs (N-DBPs), which are more cytotoxic and genotoxic. In this study, the combination of thermally activated persulfate pre-oxidation and post-chloramination (TA/PS-NH2Cl) was proposed to control the formation and reduce the toxicity of both C-DBPs and N-DBPs. The formation, speciation and toxicity of trihalomethanes, haloacetic acids, haloaldehydes, haloacetonitriles, halonitromethanes and haloacetamides, collectively defined as CX3R-type DBPs, under TA/PS-NH2Cl process were compared with processes of chlorination alone (Cl2), chloramination alone (NH2Cl) and coupled thermally activated persulfate pre-oxidation with post-chlorination (TA/PS-Cl2). Results showed that chloramination could reduce formation of C-DBPs and total organic halogen (TOX) while increase N-DBP formation, and the introduction of TA/PS pretreatment process slightly increased the formation of C-DBPs and TOX but sharply reduced the formation of N-DBPs with higher toxicity as well as brominated CX3R-type DBPs that are more toxic than their chlorinated analogues. By comprehensive toxicity calculation, an outright decline of both cytotoxicity and genotoxicity risk of CX3R-type DBPs was observed during TA/PS-NH2Cl process compared with Cl2, NH2Cl, and TA/PS-Cl2 processes. In summary, TA/PS-NH2Cl process was a potential effective method for integrally controlling the formation of CX3R-type DBPs and their toxicity and is suggested to be used to treat raw waters containing no bromide or low levels of bromide considering bromate caused by TA/PS pre-oxidation. The study may provide a feasible and economical method for DBP control on the background of global warming.

In recent years, enzyme-linked immunosorbent assay (ELISA) plate fabricated on paper (P-ELISA) has been well developed. However, low sensitivity is its main disadvantage and has limited its use. In...

A newly modified paper-based enzyme-linked immunosorbent assay (P-ELISA) was established by immobilizing more proteins on the paper surface through an atom transfer radical polymerization (ATRP) reaction. In addition, introducing graphene oxide (GO) sheets, Au nanoparticles (AuNps) and two primary antibodies (Ab1s) led to signal amplification and cost reduction. Electronic supplementary material The online version of this article (10.1186/s13065-019-0622-7) contains supplementary material, which is available to authorized users.

Eucalyptus urophylla, Acacia mangium, and Pinus caribaea are the primary species for the wood industry in Vietnam. Wood residues of these species were used to reinforce high-density polyethylene (HDPE) composites. The flexural or bending property, impact strength and surface color were evaluated after exposure to accelerated ultraviolet weathering up to 2000 h. The weathered surface was characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The results indicate that A. mangium/HDPE composites had the lowest color change and least fading, and remained stable after 1500 h exposure. FTIR spectroscopy showed that the oxidation of the composites increased in parallel with duration of exposure by assessing the concentration of carbonyl groups on the surfaces. SEM showed that all three species reinforced composites exhibited similar severe cracks after 1000 h; however, at the end of the weathering test, E. urophylla and P. caribaea composites were more severely cracked than A. mangium composites. A. mangium also had the highest flexural strength, impact strength and crystallinity during weathering. A. mangium is the most preferable among the three species to reinforce HDPE.

4-1BB (CD137, TNFSF9) is a promising co-stimulatory signaling mediator of T cells and NK cells, and agonistic monoclonal antibodies targeting 4-1BB are under clinical investigations aiming to observe sufficient and prolonged anti-tumor efficacy. However, these trials have resulted in limited efficacy or safety, and different bispecific approaches are being explored to improve the profiles. BH3120, a bivalent bispecific antibody generated by Pentambody(TM) platform targeting 4-1BB and PD-L1 simultaneously, demonstrates strong and prolonged antitumor efficacy as monotherapy in in vivo studies, and favorable safety profiles up to 200mg/kg/dose in non-human primates. Moreover, combination of BH3120 with an immune checkpoint inhibitor shows synergistically enhanced anti-tumor efficacy. Supported by these results, IND enabling studies of BH3120 are on-going and clinical evaluations are planned from later in 2022. Citation Format: Jiangcheng Xu, Yang Liu, Jing Wang, Fei Fan, Haitao Gu, Lanxin Zhang, Jun Wang, Ding Song, Ailong Guo, Hongjuan Zhang, Kaixuan Su, Jiaojiao Su, Lijuan Li, Jingmei Cai, Aihong Zhang, Jiawang Liu, Kyoungwoo Lee. BH3120: A novel bispecific antibody targeting 4-1BB and PD-L1 with well balanced efficacy and safety profiles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5605.

Recent evidence indicates that macrophages at the maternal-fetal interface adapt to a phenotype characterized by alternative activation (M2 polarization) and exhibit immunosuppressive functions that favor the maintenance of pregnancy. The bias of M2 decidual macrophages toward M1 has been clinically linked to pregnancy-related complications, such as preeclampsia and preterm delivery. The aim of this study was to investigate the effect of Toxoplasma gondii PRU strain infection on the bias of decidual macrophage polarization and its contribution to adverse pregnancy outcomes. A mouse model with adverse pregnancy outcome was established by infection with T. gondii PRU strain and the expression levels of functional molecules in decidual macrophages of mice were measured. The results showed that T. gondii infection caused seriously adverse pregnancy outcome in mice. The placentae of infected mice showed obvious congestion and inflammatory cell infiltration. The expression of CD206, MHC-II, and arginase-1 considered as M2 markers was decreased in decidual macrophages after T. gondii infection, whereas the expression of CD80, CD86, iNOS, and cytokines TNF-α and IL-12 considered as M1 markers was increased. Furthermore, iNOS-positive expression was observed in the decidua basalis of infected mice. Our results indicated that T. gondii infection was responsible for the bias of M2 decidual macrophages toward M1, which changes the immunosuppressive microenvironment at the maternal-fetal interface and contributes to adverse pregnancy outcomes.

Rationale: No approved pharmacotherapies are available for patients with interstitial pneumonia with autoimmune features (IPAF). Objective: In the present work, we aimed to evaluate the efficacy and safety of pirfenidone for the treatment of IPAF.Methods: A retrospective cohort study consisting of patients who met diagnostic criteria for IPAF was performed after a multidisciplinary review, and the patients receiving pirfenidone were compared with those in the non-pirfenidone group. The baseline data and diagnostic characteristics of patients were assessed. Pulmonary function and prednisone dose were analyzed by a mix-effects model.Results: A total of 184 patients, who met the diagnostic criteria of IPAF, were divided into two groups: pirfenidone group (n=81) and non-pirfenidone group (n=103). Patients in the pirfenidone group had a lower forced vital capacity (FVC%, P< 0.001) and a lower diffusion capacity for carbon monoxide (DLCO%, P=0.003). The pirfenidone group exhibited a greater increase of FVC% at 6 (P=0.003), 12 (P=0.013), and 24 (P=0.003) months. After adjustment for sex, age, UIP pattern, baseline FVC% and DLCO%, patients in the pirfenidone group continued to show a greater improvement in FVC% (χ2 (1) =4.59, P=0.032). Subgroup analysis identified superior therapeutic effects of pirfenidone in patients with dosage > 600 mg/day (P = 0.010) and medication course > 12 months (P = 0.007). Besides, the pirfenidone group had a lower prednisone dose than the non-pirfenidone group after 12 months of treatment (P=0.002). Moreover, 17 patients (19.32%) experienced side effects after taking pirfenidone, including one case of anaphylactic shock.Conclusions: Pirfenidone (600-1,800 mg/day) might help improve FVC, with an acceptable safety and tolerability profile in IPAF patients.

The grain-filling process is crucial for cereal crop yields, but how the caryopsis of such plants is supplied with sugars, which are produced by photosynthesis in leaves and then transported long distance, is largely unknown. In rice (Oryza sativa), various SWEET family sucrose transporters are thought to have important roles in grain filling. Here, we report that OsSWEET14 plays a crucial part in this process in rice. ossweet14 knockout mutants did not show any detectable phenotypic differences from the wild type, whereas ossweet14;ossweet11 double-knockout mutants had much more severe phenotypes than ossweet11 single-knockout mutants, including strongly reduced grain weight and yield, reduced grain-filling rate, and increased starch accumulation in the pericarp. Both OsSWEET14 and OsSWEET11 exhibited distinct spatiotemporal expression patterns between the early stage of caryopsis development and the rapid grain-filling stage. During the rapid grain-filling stage, OsSWEET14 and OsSWEET11 localized to four key sites: vascular parenchyma cells, the nucellar projection, the nucellar epidermis, and cross cells. These results demonstrate that OsSWEET14 plays an important role in grain filling, and they suggest that four major apoplasmic pathways supply sucrose to the endosperm during the rapid grain-filling stage via the sucrose effluxers SWEET14 and SWEET11.

Rice black streaked dwarf virus (RBSDV) is an important agent causing maize rough dwarf disease, whereas the host factors responding to RBSDV infection are poorly understood. To uncover the molecular interactions between RBSDV and maize, a yeast two-hybrid screen of a maize cDNA library was carried out using the viral P8 protein as a bait. ZmAKIN&beta, &gamma, 1 and ZmAKIN&beta, 2 (&beta, subunit of Arabidopsis SNF1 kinase homolog in maize) possessing high sequence similarities (encoded by two gene copies) were identified as interaction partners. Their interactions with P8 were confirmed in both Nicotiana benthamiana cells and maize protoplasts by bimolecular fluorescence complementation assay. The accumulation levels of ZmAKIN&beta, mRNAs were upregulated at the stage of the viral symptoms beginning to appear and then downregulated. ZmAKIN&beta, s are putative regulatory subunits of the SnRK1 complex, a core regulator for energy homeostasis. Knockdown of ZmAKIN&beta, s in maize regulated the expression levels of the genes involved in sugar synthesis or degradation, and also the contents of both glucose and sucrose. Importantly, downregulation of ZmAKIN&beta, s expressions facilitated the accumulation of RBSDV in maize. These results implicate a role of ZmAKIN&beta, s in the regulation of primary carbohydrate metabolism, and in the defense against RBSDV infection.

Background: How to accurately assess IPF severity and predict prognosis remains a problem. This study aimed to develop a new method, which can be easily used to assess pulmonary fibrosis severity.Method:1. Development of a HRCT combined pulmonary function & physiological parameter (CTPF) assessment method: The method included two parts. 1) CT-based fibrosis staging: Four representative lung CT sections were selected and evenly divided into 100 small areas. The percentage of honeycomb lesion area in the four sections was determined fibrosis stage,2) PF-based severity grade: FVC%pred,DLco%pred,SpO2% age and gender were used to assess PF severity grade. 2. Validation of the new method: The method was used to assess 192 patients with IPF. Two radiologists used the CT-based fibrosis staging method to determine the fibrosis stage. Pulmonologist determined the PF severity grade. 3. Statistical analyses: By Intra-group correlation coefficient and Spearman correlation coefficient to estimate the consistency between the CT scores from the two radiologists and the correlation between CT scores and lung function parameters. Using the competitive risk Fine–Gray model to analyze the relationship between CT-based stage/PF-based grade and prognosis. CT-based stage, PF-based grade, and GAP stage were used as predictor models to predicted the death risk. Results: 1. The intra-group correlation coefficient of the CT scores of the two radiologists was 0.95, PConclusion: Combined CT-based staging and PF-based grading methods CTPF can be adopted easily in clinical practice, and can assess IPF severity and predict death risk more accurately.