GL9 from Oryza glumaepatula controls grain size and chalkiness in rice

Grain size is a key factor influencing grain yield and appearance quality in rice.We identified twelve quantitative trait loci(QTL)for grain length(GL),nine for grain width(GW),and nine for 1000-kernel weight(TKW)using GLU-SSSLs,which are single-segment substitution lines with Oryza glumaepatula as donor parent and Huajingxian 74(HJX74)as recipient parent.Among the QTL,qGL1-2,qGL1-4,qGL9-2,qGW2-2,qGW9-1 and qTKW9-2 contributed to high grain yield.GL9 was identified as a candidate gene for qGL9-2 by map-based cloning and sequencing,and is a novel allele of GS9.The kernel of NIL-gl9was slenderer and longer than that of HJX74,and the TKW and grain yield per plant of NIL-gl9 were higher than those of HJX74.The proportion of grain chalkiness of NIL-gl9 was much lower than that of HJX74.Thus,gl9 increased grain yield and appearance quality simultaneously.Three pyramid lines,NIL-gs3/gl9,NIL-GW7/gl9 and NIL-gw8/gl9,were developed and the kernel of each was longer than that of the corresponding recipient parent lines.The gl9 allele may be beneficial for breeding rice varieties with high grain yield and good appearance quality.

A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models

Cancer cell membrane(CCM)derived nanotechnology functionalizes nanoparticles(NPs)to recognize homologous cells,exhibiting translational potential in accurate tumor therapy.However,these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts(CDX),ignoring the tumor heterogeneity and differentiation from inter-and intra-individuals and microenvironments between heterotopic-and orthotopic-tumors,limiting the therapeutic efficiency of such nanoplatforms.Herein,various biomimetic nanoplatforms(CCM-modified gold@Carbon,i.e.,Au@C-CCM)were fabricated by coating CCMs of head and neck squamous cell carcinoma(HNSCC)cell lines and patient-derived cells on the surface of Au@C NP.The generated Au@C-CCMs were evaluated on corresponding CDX,tongue orthotopic xenograft(TOX),immunecompetent primary and distant tumor models,and patient-derived xenograft(PDX)models.The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death.The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency,far above those with mismatched CCMs,resulting in distinct tumor ablation and tumor growth inhibition in all four models.This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC,can be further extended to other malignant tumors therapy.

Exercise as a prescription for patients with various diseases

A growing understanding of the benefits of exercise over the past few decades has prompted researchers to take an interest in the possibilities of exercise therapy.Because each sport has its own set of characteristics and physiological complications that tend to occur during exercise training,the effects and underlying mechanisms of exercise remain unclear.Thus,the first step in probing the effects of exercise on different diseases is the selection of an optimal exercise protocol.This review summarizes the latest exercise prescription treatments for 26 different diseases:musculoskeletal system diseases(low back pain,tendon injury,osteoporosis,osteoarthritis,and hip fracture),metabolic system diseases(obesity,type 2 diabetes,type 1 diabetes,and nonalcoholic fatty liver disease),cardio-cerebral vascular system diseases(coronary artery disease,stroke,and chronic heart failure),nervous system diseases(Parkinson’s disease,Huntington’s disease,Alzheimer’s disease,depression,and anxiety disorders),respiratory system diseases(chronic obstructive pulmonary disease,interstitial lung disease,and after lung transplantation),urinary system diseases(chronic kidney disease and after kidney transplantation),and cancers(breast cancer,colon cancer,prostate cancer,and lung cancer).Each exercise prescription is displayed in a corresponding table.The recommended type,intensity,and frequency of exercise prescriptions are summarized,and the effects of exercise therapy on the prevention and rehabilitation of different diseases are discussed.

OsPEX1,a leucine-rich repeat extensin protein,functions in the regulation of caryopsis development and quality in rice

Rice caryopses are enclosed by outer glumes.The size and dimension of the outer glume are the main determinants of caryopsis size.However,it is unclear whether caryopsis development is completely dependent on the size of the glume,or whether it can grow and expand autonomously despite the constraint of glume enclosure.We report the identification of a mutant line that produces normal-sized glumes with smaller mature caryopses that do not fill the entire glume cavity.The caryopsis phenotype in the pex1 mutant is caused by a reduction in cell size.Os PEX1,a leucine-rich repeat extensin gene,was highly expressed in the developing caryopsis.Overexpression of Os PEX1 driven by a constitutive promoter recapitulated the mutant phenotype,showing that the small-caryopsis phenotype is caused by overexpression of the Os PEX1 gene.Free amino acids,including several essential amino acids,and crude protein were increased in pex1 relative to the wild type,endowing pex1 with improved nutritional quality.Our results suggest that caryopsis development can be genetically uncoupled from maternally controlled glume development and that Os PEX1 might be a new resource for improving nutritional quality of rice cultivars.

Insights into therapeutic peptides in the cancerimmunity cycle:Update and challenges

Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy.As vital biological mediators,peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies(CITs).However,physicochemical peptide features such as conformation and stability pose challenges to their on-target efficacy.This review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle(CIC),including tumor antigen presentation,immune cell regulation,and immune checkpoint signaling.Particular attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical progress.Furthermore,possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.

Astragaloside IV derivative HHQ16 ameliorates infarctioninduced hypertrophy and heart failure through degradation of lncRNA4012/9456

Reversing ventricular remodeling represents a promising treatment for the post-myocardial infarction(MI)heart failure(HF).Here,we report a novel small molecule HHQ16,an optimized derivative of astragaloside IV,which effectively reversed infarction-induced myocardial remodeling and improved cardiac function by directly acting on the cardiomyocyte to reverse hypertrophy.The effect of HHQ16 was associated with a strong inhibition of a newly discovered Egr2-affliated transcript Inc9456 in the heart.While minimally expressed in normal mouse heart,Inc9456 was dramatically upregulated in the heart subjected to left anterior descending coronary artery ligation(LADL)and in cardiomyocytes subjected to hypertrophic stimulation.The critical role of Inc9456 in cardiomyocyte hypertrophy was confirmed by specific overexpression and knockout in vitro.A physical interaction between Inc9456 and G3BP2 increased NF-kB nuclear translocation,triggering hypertrophy-related cascades.HHQ16 physically bound to Inc9456 with a high-affinity and induced its degradation.Cardiomyocyte-specific Inc9456 overexpression induced,but knockout prevented LADL-induced,cardiac hypertrophy and dysfunction.HHQ16 reversed the effect of Inc9456 overexpression while lost its protective role when Inc9456 was deleted,further confirming Inc9456 as the bona fide target of HHQ16.We further identified the human ortholog of Inc9456,also an Egr2-affliated transcript,Inc4012.Similarly,Inc4012 was significantly upregulated in hypertrophied failing hearts of patients with dilated cardiomyopathy.HHQ16 also specifically bound to Inc4012 and caused its degradation and antagonized its hypertrophic effects.Targeted degradation of pathological increased Inc4012/lnc9456 by small molecules might serve as a novel promising strategy to regress infarction-induced cardiac hypertrophy and HF.

Fuzzy Comprehensive Analysis of Static Mixers Used for Selective Catalytic Reduction in Diesel Engines

The proper selection of a relevant mixer generally requires an effective assessment of several models against theapplication requirements. This is a complex task, as traditional evaluation methods generally focus only on a single aspect of performance, such as pressure loss, mixing characteristics, or heat transfer. This study assesses aurea-based selective catalytic reduction (SCR) system installed on a ship, where the installation space is limitedand the distance between the urea aqueous solution injection position and the reactor is low;therefore, the staticmixer installed in this pipeline has special performance requirements. In particular, four evaluation indices areused in this study: The B value, C value, pressure loss correction factor (Z′), and the ratio of the required distanceto the equivalent diameter of the pipe (LV/D) when the velocity field after the mixer attains uniformity. Six typesof static mixers were simulated with varying concentrations, flow speeds, and positions. A fuzzy comprehensiveevaluation method was introduced to evaluate and compare the related advantages and disadvantages. The resultsshowed that 1) mixing performance was related to the shape of the mixer and had no direct relationship with flowvelocity. 2) For the same mixer position, the lower the urea concentration, the greater the difficulty of evenly mixing the solution. 3) At a constant urea concentration, the mixing performance improved when the mixer was closer to the injection inlet. 4) The installation of a GK mixer in the SCR system of a 9L20C diesel engine was best.

Combating COVID-19 with integrated traditional Chinese and Western medicine in China

COVID-19,an infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has spread throughout the world.China has achieved rapid containment of this highly infectious disease following the principles of early detection,early quarantine and early treatment with integrated traditional Chinese and Western medicine.The inclusion of traditional Chinese medicine(TCM)in the Chinese protocol is based on its successful historic experience in fighting against pestilence.Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events,improve clinical recovery and help alleviate symptoms such as cough or fever.To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine.The three Chinese patent medicines(Lianhua Qingwen Keli/Jiaonang(Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules),Jinhua Qinggan Keli(Honeysuckle Flower ColdRelieving Granules)and Xuebijing(Stasis-Resolving&Toxin-Removing)Injection were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication.The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.

Bruceine D inhibits HIF-1α-mediated glucose metabolism in hepatocellular carcinoma by blocking ICAT/β-catenin interaction

Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-related deaths,characterized by highly hypoxic tumor microenvironment.Hypoxia-inducible factor-1α(HIF-1α)is a major regulator involved in cellular response to changes of oxygen levels,supporting the adaptation of tumor cells to hypoxia.Bruceine D(BD)is an isolated natural quassinoid with multiple anti-cancer effects.Here,we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism.Using biophysical proteomics approaches,we identified inhibitor of β-catenin and T-cell factor(ICAT)as the functional target of BD.By targeting ICAT,BD disrupted the interaction of bcatenin and ICAT,and promoted β-catenin degradation,which in turn induced the decrease of HIF-1α expression.Furthermore,BD could inhibit HCC cells proliferation and tumor growth in vivo,and knockdown of ICAT substantially increased resistance to BD treatment in vitro.Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.