Wide grain 4,encoding an alpha-tubulin,regulates grain size by affecting cell expansion in rice

Rice is one of the three most important food crops in the world.Increasing rice yield is an effective way to ensure food security.Grain size is a key factor affecting rice yield;however,the genetic and molecular mechanisms regulating grain size have not been fully investigated.In this study,we identified a rice mutant,wide grain 4-D(wg4-D),that exhibited a significant increase in grain width and a decrease in grain length.Histological analysis demonstrated that WG4 affects cell expansion thereby regulating grain size.MutMap-based gene mapping and complementary transgenic experiments revealed that WG4 encodes an alpha-tubulin,OsTubA1.A SNP mutation in WG4 affected the arrangement of cortical microtubules and caused a wide-grain phenotype.WG4 is located in nuclei and cytoplasm and expressed in various tissues.Our results provide insights into the function of tubulin in rice and identifies novel targets the regulation of grain size in crop breeding.

qGW11a/OsCAT8,encoding an amino acid permease,negatively regulates grain size and weight in rice

Grain size is a key factor influencing grain weight in rice.In this study,a chromosome segment substitution line(CSSL9-17)was identified,that exhibits a significant reduction in both grain size and weight compared to its donor parent 93-11.Further investigation identified two quantitative trait loci(QTL)on chromosome 11,designated qGW11a and qGW11b,which contribute to 1000-grain weight with an additive effect.LOC_Os11g05690,encoding the amino acid permease OsCAT8,is the target gene of qGW11a.Overexpression of OsCAT8 resulted in decreased grain weight,while OsCAT8 knockout mutants exhibited increased grain weight.The 287-bp located within the OsCAT8 promoter region of 93-11 negatively regulates its activity,which is subsequently correlated with an increase in grain size and weight.These results suggest that OsCAT8 functions as a negative regulator of grain size and grain weight in rice.

Effectiveness of cardioneuroablation in different subtypes of vasovagal syncope

BACKGROUND Cardioneuroablation(CNA)has shown encouraging results in patients with vasovagal syncope(VVS).However,data on different subtypes was scarce.METHODS This observational study retrospectively enrolled 141 patients[mean age:40±18 years,51 males(36.2%)]with the diagnosis of VVS.The characteristics among different types of VVS and the outcomes after CNA were analyzed.RESULTS After a mean follow-up of 4.3±1.5 years,41 patients(29.1%)experienced syncope/pre-syncope events after CNA.Syncope/pre-syncope recurrence significantly differed in each subtype(P=0.04).The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure(n=6,16.7%),followed by mixed(n=26,30.6%)and vasodepressive(n=9,45.0%).Additionally,a significant difference was observed in the analyses of the Kaplan-Meier survival curve(P=0.02).Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type(P<0.01).Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity(DC)level than those without(7.4±1.0 ms vs.9.0±1.6 ms,P=0.01).Patients with DC<8.4 ms had an 8.1(HR=8.1,95%CI:2.2-30.0,P=0.02)times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC≥8.4 ms,and this association still existed after adjusting for age and sex(HR=8.1,95%CI:2.2-30.1,P=0.02).CONCLUSIONS Different subtypes exhibit different event-free rates.The vasodepressive type exhibited the lowest event-free rate,but those patients with DC≥8.4 ms might benefit from CNA.

Drilling Combined with Adipose-derived Stem Cells and Bone Morphogenetic Protein-2 to Treat Femoral Head Epiphyseal Necrosis in Juvenile Rabbits

This study was designed to evaluate the effects of drilling through the growth plate and using adipose-derived stem cells （ADSCs） and bone morphogenetic protein-2 （BMP-2） to treat femoral head epiphyseal ischemic necrosis, which can be done in juvenile rabbits. Passagefour bromodeoxyuridine （BrdU）-labeled ADSCs were cultured, assayed with MTT to determine their viability and stained with alizarin red dye to determine their osteogenic ability. Twomonth-old, healthy male rabbits （1.2 to 1.4 kg, n=45） underwent ischemic induction and were randomly divided into five groups （group A： animal model control; group B： drilling; group C： drilling ＆ ADSCs; group D： drilling ＆ BMP-2; and group E： drilling ＆ ADSCs ＆ BMP-2）. Magnetic resonance imaging （MRI）, X-ray imaging, hematoxylin and eosin staining and BrdU immunofluorescence detection were applied 4, 6 and 10 weeks after treatment. Approximately 90% of the ADSCs were labeled with BrdU and showed good viability and osteogenic ability. Similar results were observed in the rabbits in groups C and E at weeks 6 and 10. The animals of groups C and E demonstrated normal hip structure and improved femoral epiphyseal quotients and trabecular areas compared with those of the groups A and B （P〈0.01）. Group D demonstrated improved femoral epiphyseal quotients and trabecular areas compared with those of groups A and B （P〈0.05）. In summary, drilling through the growth plate combined with ADSC and BMP-2 treatments induced new bone formation and protected the femoral head epiphysis from collapsing in a juvenile rabbit model of femoral head epiphyseal ischemic necrosis.

A natural allele of TAW1 contributes to high grain number and grain yield in rice

Grain number per panicle (GNP) is a complex trait controlled by quantitative trait loci (QTL),directly determining grain yield in rice.Identifying GNP-associated QTL is desirable for increasing rice yield.A rice chromosome segment substitution line (CSSL),F771,which showed increased panicle length and GNP,was identified in a set of CSSLs derived from a cross between two indica cultivars,R498 (recipient) and WY11327 (donor).Genetic analysis showed that the panicle traits in F771 were semidominant and controlled by multiple QTL.Six QTL were consistently identified by QTL-seq analysis.Among them,the major QTL q PLN10 for panicle length and GNP was localized to a 121-kb interval between markers N802 and N909 on chromosome 10.Based on quantitative real-time PCR and sequence analysis,TAWAWA1(TAW1),a known regulator of rice inflorescence architecture,was identified as the candidate gene for q PLN10.A near-isogenic line,NIL-TAW1,was developed to evaluate its effects.In comparison with the recurrent parent R498,NIL-TAW1 showed increased panicle length (14.0%),number of secondary branches (20.9%) and GNP (22.0%),and the final grain yield per plant of NIL-TAW1 was increased by18.6%.Transgenic experiments showed that an appropriate expression level of TAW1 was necessary for panicle development.Haplotype analysis suggested that the favorable F771-type (Hap 13) of TAW1was introduced from aus accessions and had great potential value in high-yield breeding both in indica and japonica varieties.Our results provide a promising genetic resource for rice grain yield improvement.

Effect of renal denervation for patients with isolated systolic hypertension:a systematic review and meta-analysis

BACKGROUND Renal denervation(RDN)is a promising treatment based on catheter intervention for patients with refractory hypertension.However,the effect in patients with isolated systolic hypertension(ISH)remains controversial.The aim of this meta-analysis was to determine the blood pressure lowing effect of RDN in patients with ISH compared with combined systolic/diastolic hypertension(CH)patients.METHODS PubMed,Embase,Cochrane and ClinicalTrials.gov were searched for prospective clinical studies that included RDN.The outcomes of interest were the change of 24-hour ambulatory systolic blood pressure(SBP)from baseline.We used the fixed effects model to calculate weighted mean difference(WMD)with 95%confidence interval(CI).RESULTS Six trials were included,with 1405 participants,including 597 patients with ISH and 808 patients with CH.Mean follow-up was five months.The reduction of 24-hour ambulatory SBP was significantly greater for the CH patients than the ISH patients(WMD=3.89,95%CI:2.32–5.45,P<0.0001).RDN also showed a greater reduction in office SBP in the CH patients compared to the ISH patients(WMD=10.24,95%CI:4.24–15.74,P=0.0003).And the effect was independent of age,length of follow-up,and ablation device.CONCLUSIONS RDN provides superior blood pressure control in the CH patients compared with the ISH patients,and the CH patients may be the best suitable population for which RDN is indicated.

Venovenous bypass ahead of mobilization of the liver in orthotopic liver transplantation

BACKGROUND: To evaluate feasibility and safety of venovenous bypass prior to mobilization of the liver during orthotopic liver transplantation (OLT). METHODS: Fifty-four patients were classified into two groups. Group A consisted of 23 patients receiving OLT with classical venovenous bypass. Group B consisted of 31 patients who received a modified-procedure: venovenous bypass ahead of the mobilization of the liver during ULT. The blood loss, duration of venovenous bypass, cold ischemia time, anhepatic phase, and transfusion during operation in the two groups were compared. Complications after the operation were also compared between the two groups. RESULTS: The duration of venovenous bypass and cold ischemia time in group A were longer than those in group B [(99.78±21.36 min) vs (96.32±22.25 min) and (484.78±134.01 min) vs (443.15± 85.27 min)]. The anhepatic phase lasted for about 100 min averagely in the two groups. The volumes of blood loss and transfusion during the operation were larger in group A than in group B [(5096±4243 ml) vs (1726±1125 ml) and (3676±2938.74 ml) vs (1217.69±829.72 ml)]. Postoperative complications occurred in 26 patients of group A and in 19 patients of group B. CONCLUSION: This modified-procedure or venovenous bypass ahead of mobilization of the liver in OLT can reduce the blood loss during OLT and the incidence of postoperative complications without prolongation of the anhepatic phase and duration of venovenous bypass.

Fiber Grating-Based Strain Sensor Array for Health Monitoring of Pipelines

Pipelines are one of the most important modern energy transportation methods,used especially for the transportation of certain dangerous energy media materials such as crude oil,natural gas,and chemical raw materials.New requirements have been put forward for the health monitoring and early security warning of pipelines because of the large-scale and complicated development trend of the pipe network system.To achieve an accurate assessment of the health conditions of pipeline infrastructure,obtaining as many precise operating parameters as possible,particularly at some critical parts of the pipeline,is necessary.Therefore,a novel type of fiber grating strain sensor array is proposed herein to monitor the pipeline hoop strain.The sensor utilizes fiber grating characteristics such as light weight,corrosion resistance,remote transmission,and strong environmental adaptability.The fiber containing the grating measurement points is implanted into the composite material to complete the sensitization encapsulation and protection of the bare fiber grating.The design of the sensor array fulfills the requirements for monitoring pipeline mass data,making it easy to form a pipeline health monitoring sensor network.The sensor sensitivity is researched by using a combination of theoretical and experimental analysis.A sensitivity test,as well as linearity and stability tests,are performed on the sensor.The experimental results show that the average sensitivity of the sensor is 14.86 pm/με,and the error from the theoretical calculation analysis value is 8.75%.Due to its high reliability,good linear response and long-term stability,and the ability to reflect the exact strain change of the outer wall of the pipeline,the designed sensor can support longterm online pipeline monitoring.The fiber grating sensor array network has successfully realized the monitoring of the pipeline’s internal operation by using external strain changes.In addition to the performance benefits,there are other merits associated with the applicability of the sensor namely simple structure,compact size,manufacturing ease,and exterior installation ease.

Deep-Learning-Based Production Decline Curve Analysis in the Gas Reservoir through Sequence Learning Models

Production performance prediction of tight gas reservoirs is crucial to the estimation of ultimate recovery,which has an important impact on gas field development planning and economic evaluation.Owing to the model’s simplicity,the decline curve analysis method has been widely used to predict production performance.The advancement of deep-learning methods provides an intelligent way of analyzing production performance in tight gas reservoirs.In this paper,a sequence learning method to improve the accuracy and efficiency of tight gas production forecasting is proposed.The sequence learning methods used in production performance analysis herein include the recurrent neural network(RNN),long short-term memory(LSTM)neural network,and gated recurrent unit(GRU)neural network,and their performance in the tight gas reservoir production prediction is investigated and compared.To further improve the performance of the sequence learning method,the hyperparameters in the sequence learning methods are optimized through a particle swarm optimization algorithm,which can greatly simplify the optimization process of the neural network model in an automated manner.Results show that the optimized GRU and RNN models have more compact neural network structures than the LSTM model and that the GRU is more efficiently trained.The predictive performance of LSTM and GRU is similar,and both are better than the RNN and the decline curve analysis model and thus can be used to predict tight gas production.

A single nucleotide substitution at 5'-UTR of GSN1 represses its translation and leads to an increase of grain length in rice

Rice grain size is an important trait that affects rice yield and quality, and thus the identification of genes related to grain size is of great significance for improving rice yield and quality. Many genes related to grain size, such as DEP1(Huang et al., 2009),GW5(Liu et al., 2017).

Remodeling “cold” tumor immune microenvironment via epigenetic-based therapy using targeted liposomes with in situ formed albumin corona

There is a close connection between epigenetic regulation,cancer metabolism,and immunology.The combination of epigenetic therapy and immunotherapy provides a promising avenue for cancer management.As an epigenetic regulator of histone acetylation,panobinostat can induce histone acetylation and inhibit tumor cell proliferation,as well as regulate aerobic glycolysis and reprogram intratumoral immune cells.JQ1 is a BRD4 inhibitor that can suppress PD-L1 expression.Herein,we proposed a chemo-free,epigenetic-based combination therapy of panobinostat/JQ1 for metastatic colorectal cancer.A novel targeted binary-drug liposome was developed based on lactoferrin-mediated binding with the LRP-1 receptor.It was found that the tumor-targeted delivery was further enhanced by in situ formation of albumin corona.The lactoferrin modification and endogenous albumin adsorption contribute a dual-targeting effect on the receptors of both LRP-1 and SPARC that were overexpressed in tumor cells and immune cells(e.g.,tumor-associated macrophages).The targeted liposomal therapy was effective to suppress the crosstalk between tumor metabolism and immune evasion via glycolysis inhibition and immune normalization.Consequently,lactic acid production was reduced and angiogenesis inhibited;TAM switched to an anti-tumor phenotype,and the anti-tumor function of the effector CD8+T cells was reinforced.The strategy provides a potential method for remodeling the tumor immune microenvironment(TIME).

Improving the efficiency of hybrid combination preparation in rice breeding by a modified flowering stimulant

The utilization of hybrid vigor is an important breakthrough in the history of rice breeding.To select the best hybrid combinations,breeders manually perform extensive testing of hybridizations between restorer and sterile lines,which is a laborious and time-consuming process.Here,we report that a modified flowering stimulant containing methyl jasmonate(MeJA),6-benzylamine adenine and kinetin effectively promotes the flowering and seed set of male-sterile rice lines.Different concentrations of the ingredients were tested to identify an optimal formulation.Seed quality evaluation indicated that hybrid seeds from plants sprayed with the flowering stimulant had a higher germination rate than seeds from plants prepared by glume-cutting.In summary,the modified flowering stimulant described in this study may help reduce the labor requirement associated with hybrid rice breeding and improve yield and efficiency.

The self-assemblies of a newly designed star-shaped molecule end-capped with bromine atoms studied by scanning tunneling microscopy

A new star-shaped molecule StOF-Br_3 containing oligofluorenes and halogen atoms(Bromine) has been synthesized and studied by Scanning Tunneling Microscopy(STM) at the highly oriented pyrolytic graphite(HOPG) surface.We have obtained the high-resolution self-assembled STM images,from which the highly ordered and closely packed non-porous arrangements of the StOF-Br_3 molecular selfassemblies at the heptanoic acid/HOPG surface could be observed.The molecular models and selfassembled StOF-Br_3 architectures have been given in the following text.Besides,we have also figured out the surface free energy by the density functional theory(DFT) calculation,which proved that the halogen...halogen interaction was strong enough to stabilize the ordered molecular self-assemblies.This work verifies the existence of bromine...bromine interactions,and meanwhile provides a kind of effective approach for quickly building ordered molecular nanoarchitectures with large areas and different geometries.

Localized delivery of nanomedicine and antibodies for combating COVID-19

The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has been a major health burden in the world.So far,many strategies have been investigated to control the spread of COVID-19,including social distancing,disinfection protocols,vaccines,and antiviral treatments.Despite the significant achievement,due to the constantly emerging new variants,COVID-19 is still a great challenge to the global healthcare system.It is an urgent demand for the development of new therapeutics and technologies for containing the wild spread of SARS-CoV-2.Inhaled administration is useful for the treatment of lung and respiratory diseases,and enables the drugs to reach the site of action directly with benefits of decreased dose,improved safety,and enhanced patient compliance.Nanotechnology has been extensively applied in the prevention and treatment of COVID-19.In this review,the inhaled nanomedicines and antibodies,as well as intranasal nanodrugs,for the prevention and treatment of COVID-19 are summarized.

Terminus-immobilization effect on peptide conformations and peptide–peptide interactions

Peptide-modified delivery systems are enabling the improvement of the targeting specificity,biocompatibility,stability,etc.However,the precise design of a peptide-decorated surface for a designated function has remained to be challenging due to a lack of mechanistic understanding of the interactions between surface-bound peptide ligands and their receptors.Enlightened by the recent report on pairwise interactions between peptides in the solution state and surface-immobilized state,we used computational simulations to explore the contributing mechanisms underlining the observed binding affinity characteristics.Molecular dynamics simulations were performed to sample and compare conformations of homo-octapeptides free in solution(mobile peptides)and bound to the surface(N-terminal fixed peptides).We found that peptides converged to more extended and rigid conformations when immobilized to the surface and confirmed that the extended structures could increase the space available to counter-interacting peptides during the peptide–peptide interactions.In addition,studies on interactions between stationary and mobile peptides revealed that main-chain/side-chain and side-chain/side-chain hydrogen bonds play an important role.The presented efforts in this work may provide supportive references for peptide design and modification on the nanoparticle surface as well as guidance for analyzing peptide–receptor interactions through an emphasis on hydrogen bonds during peptide design and an understanding of the influence on the binding affinity by the sequence-dependant conformational changes after peptide immobilization.

Author correction to"Neutralization of SARSCoV-2 pseudovirus using ACE2-engineered extracellular vesicles"[Acta Pharmaceutica Sinica B 12(2022)1523-1533]

The authors regret in the initially published version of this article,there is a misapplied image in Fig.3C.The corrected Fig.3 is provided below.

OsSPL18 controls grain weight and grain number in rice

Grain weight and grain number are two important traits directly determining grain yield in rice. To date,a lot of genes related to grain weight and grain number have been identified; however, the regulatory mechanism underlying these genes remains largely unknown. In this study, we studied the biological function of OsSPL18 during grain and panicle development in rice. Knockout (KO) mutants of OsSPL18exhibited reduced grain width and thickness, panicle length and grain number, but increased tiller number. Cytological analysis showed that OsSPL18 regulates the development of spikelet hulls by affecting cell proliferation. qRT-PCR and GUS staining analyses showed that OsSPL18 was highly expressed in developing young panicles and young spikelet hulls, in agreement with its function in regulating grain and panicle development. Transcriptional activation experiments indicated that OsSPL18is a functional transcription factor with activation domains in both the N-terminus and C-terminus, and both activation domains are indispensable for its biological functions. Quantitative expression analysis showed that DEP1, a major grain number regulator, was significantly down-regulated in OsSPL18 KO lines.Both yeast one-hybrid and dual-luciferase (LUC) assays showed that OsSPL18 could bind to the DEP1promoter, suggesting that OsSPL18 regulates panicle development by positively regulating the expression of DEP1. Sequence analysis showed that OsSPL18 contains the OsmiR156k complementary sequence in the third exon; 5?RLM-RACE experiments indicated that OsSPL18 could be cleaved by OsmiR156k. Taken together, our results uncovered a new OsmiR156k-OsSPL18-DEP1 pathway regulating grain number in rice.

Loss of Gn1a/OsCKX2 confers heavy-panicle rice with excellent lodging resistance

Significant achievements have been made in breeding programs for the heavy-panicle-type(HPT)rice(Oryza sativa) in Southwest China. The HPT varieties now exhibit excellent lodging resistance,allowing them to overcome the greater pressures caused by heavy panicles. However, the genetic mechanism of this lodging resistance remains elusive. Here, we isolated a major quantitative trait locus, Panicle Neck Diameter 1(PND1), andidentified the causal gene as GRAIN NUMBER 1 A/CYTOKININ OXIDASE 2(Gn1 A/Os CKX2). The null gn1 a allele from rice line R498(gn1 aR498) improved lodging resistance through increasing the culm diameter and promoting crown root development.Loss-of-function of Gn1 a/Os CKX2 led to cytokinin accumulation in the crown root tip and accelerated the development of adventitious roots. Gene pyramiding between the null gn1 aR498 allele with two gain-of-function alleles, STRONG CULM 2(SCM2)and SCM3, further improved lodging resistance.Moreover, Gn1 a/Os CKX2 had minimal influence on overall rice quality. Our research thus highlights the distinct genetic components of lodging resistance of HPT varieties and provides a strategy for tailormade crop improvement of both yield and lodging resistance in rice.

Neutralization of SARS-CoV-2 pseudovirus using ACE2-engineered extracellular vesicles

The spread of coronavirus disease 2019(COVID-19)throughout the world has resulted in stressful healthcare burdens and global health crises.Developing an effective measure to protect people from infection is an urgent need.The blockage of interaction between angiotensin-converting enzyme 2(ACE2)and S protein is considered an essential target for anti-severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)drugs.A full-length ACE2 protein could be a potential drug to block early entry of SARS-Co V-2 into host cells.In this study,a therapeutic strategy was developed by using extracellular vesicles(EVs)with decoy receptor ACE2 for neutralization of SARS-Co V-2.The EVs embedded with engineered ACE2(EVs-ACE2)were prepared;the EVs-ACE2 were derived from an engineered cell line with stable ACE2 expression.The potential effect of the EVs-ACE2 on anti-SARS-Co V-2 was demonstrated by both in vitro and in vivo neutralization experiments using the pseudovirus with the S protein(S-pseudovirus).EVs-ACE2 can inhibit the infection of S-pseudovirus in various cells,and importantly,the mice treated with intranasal administration of EVs-ACE2 can suppress the entry of S-pseudovirus into the mucosal epithelium.Therefore,the intranasal EVs-ACE2 could be a preventive medicine to protect from SARS-Co V-2 infection.This EVs-based strategy offers a potential route to COVID-19 drug development.

Aza-BODIPY molecular assembly at the liquid-solid interface driven by Br…F-BF interactions

In this work,two aza-BODIPY derivatives,3,5-diphenyl-1,7-di(p-dodecyloxyphenyl)-aza-BODIPY(CJF)and 3,5-di(p-bromophenyl)-1,7-di(p-dodecyloxyphenyl)-aza-BODIPY(2Br-CJF)acted as model molecules to form the self-assembly monolayers on the solid-liquid interface.With the utilizing of scanning tunnelling microscope(STM),we demonstrated that intermolecular Br…F-BF interactions existed in 2Br-CJF self-assembly structure and played an important role in strengthening the stability of 2Br-CJF self-assembly structure.This result is supported by density functional theory(DFT)calculation.