Identification and validation of major and stable quantitative trait locus for falling number in common wheat (Triticum aestivum L.).

KEY MESSAGE: A major and stable QTL, QFn.sau-1B.2, which can explain 13.6% of the PVE in FN and has a positive effect on resistance in SGR, was mapped and validated. The falling number (FN) is considered one of the most important quality traits of wheat grain and is the most important quality evaluation index for wheat trade worldwide. The quantitative trait loci (QTLs) for FN were mapped in three years of experiments. 23, 30, and 58 QTLs were identified using the ICIM-BIP, ICIM-MET, and ICIM-EPI methods, respectively. Among them, seven QTLs were considered stable. QFn.sau-1B.2, which was mapped to the 1BL chromosome, can explain 13.6% of the phenotypic variation on average and is considered a major and stable QTL for FN. This QTL was mapped in a 1 cM interval and is flanked by the markers AX-110409346 and AX-108743901. Epistatic analysis indicated that QFN.sau-1B.2 has a strong influence on FN through both additive and epistatic effects. The Kompetitive Allele-Specific PCR marker KASP-AX-108743901, which is closely linked to QFn.sau-1B.2, was designed. The genetic effect of QFn.sau-1B.2 on FN was successfully confirmed in Chuannong18 × T1208 and CN17 × CN11 populations. Moreover, the results of the additive effects of favorable alleles for FN showed that the QTLs for FN had significant effects not only on FN but also on the resistance to spike germination. Within the interval of QFn.sau-1B.2, 147 high-confidence genes were found. According to the gene annotation and the transcriptome data, four genes might be associated with FN. QFn.sau-1B.2 may provide a new resource for the high-quality breeding of wheat in the future.

RNA editing events and expression profiles of mitochondrial protein-coding genes in the endemic and endangered medicinal plant, Corydalis saxicola.

Corydalis saxicola, an endangered medicinal plant endemic to karst habitats, is widely used in Traditional Chinese Medicine to treat hepatitis, abdominal pain, bleeding hemorrhoids and other conditions. However, to date, the mitochondrial (mt) genome of C. saxicola has not been reported, which limits our understanding of the genetic and biological mechanisms of C. saxicola. Here, the mt genome of C. saxicola was assembled by combining the Nanopore and Illumina reads. The mt genome of C. saxicola is represented by a circular chromosome which is 587,939 bp in length, with an overall GC content of 46.50%. 40 unique protein-coding genes (PCGs), 22 tRNA genes and three rRNA genes were identified. Codon usage of the PCGs was investigated and 167 simple sequence repeats were identified. Twelve homologous fragments were identified between the mt and ct genomes of C. saxicola, accounting for 1.04% of the entire mt genome. Phylogenetic examination of the mt genomes of C. saxicola and 30 other taxa provided an understanding of their evolutionary relationships. We also predicted 779 RNA editing sites in 40 C. saxicola mt PCGs and successfully validated 506 (65%) of these using PCR amplification and Sanger sequencing. In addition, we transcriptionally profiled 24 core mt PCGs in C. saxicola roots treated with different concentrations of CaCl2, as well as in other organs. These investigations will be useful for effective utilization and molecular breeding, and will also provide a reference for further studies of the genus Corydalis.

Antiviral efficacy of RAY1216 monotherapy and combination therapy with ritonavir in patients with COVID-19: a phase 2, single centre, randomised, double-blind, placebo-controlled trial.

Background: This study aimed to evaluate the efficacy and safety of RAY1216, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in adults with coronavirus disease 2019 (COVID-19). Methods: This phase 2, single centre, randomised, double-blind, placebo-controlled trial included hospitalised patients between August 14, 2022, and September 26, 2022, in Sanya Central Hospital (The Third People's Hospital of Hainan Province) in China with no severe symptoms if they had laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for not more than 120 h (5 days) and a real-time quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) value of ≤30 for both the open reading frames 1 ab (ORF1ab) and nucleocapsid (N) genes within 72 h before randomisation. Half of the participants (n = 30) were randomly assigned (2:1) to receive either RAY1216 or a matched placebo three times a day (TID) for 5 days (15 doses in total), while the other half received RAY1216 plus ritonavir (RAY1216 plus RTV) or a matched placebo every 12 h for 5 days (10 doses in total). The primary endpoint was the time of viral clearance. Secondary outcomes included the changes of the SARS-CoV-2 RNA viral load, the positivity rate of the nucleic acid test, and the recovery time of clinical symptoms. A safety evaluation was performed to record and analyse all adverse events that occurred during and after drug administration as well as any cases in which dosing was halted because of these events. Clinicaltrials.gov identifier: ChiCTR2200062889. Findings: The viral shedding times in the RAY1216 and RAY1216 plus RTV groups were 166 h (95% confidence interval (CI): 140-252) and 155 h (95%CI: 131-203), respectively, which were 100 h (4.2 days) and 112 h (4.6 days) shorter than that of the placebo group, respectively (RAY1216 group vs. Placebo p = 0.0060, RAY1216 plus RTV group vs. Placebo p = 0.0001). At 24 h, 72 h, and 120 h after administration, the viral RNA loads in the RAY1216 and RAY1216 plus RTV groups were significantly less than those of the placebo groups. At 280 h (11.5 days) after administration, the nucleic acid test results in the RAY1216 and RAY1216 plus RTV groups were both negative. The common adverse events related to the investigational drugs were mild and self-limiting laboratory examination abnormalities. Interpretation: Our findings suggest that RAY1216 monotherapy and RAY1216 plus ritonavir both demonstrated significant antiviral activity and reduced the duration of COVID-19 while maintaining a satisfactory safety profile. Considering the limited clinical application of RTV, it is recommended to use RAY1216 alone to further verify its efficacy and safety. Funding: This study was sponsored by the Key Research and Development Program of China (2022YFC0868700).

The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in patients worldwide. Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC. It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC. Here, we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients. We found that DMRTA1 was extremely upregulated in the non-pathologic complete response (non-pCR) group. The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression, which could increase cisplatin sensitivity in ESCC. Additionally, suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells. Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2, which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback. Therefore, DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.

Tumor-homing bacterium-adsorbed liposomes encapsulating perfluorohexane/doxorubicin enhance pulsed-focused ultrasound for tumor therapy.

Objective: To make up for the insufficient ultrasound ablation of tumors, the energy output or synergist is increased but faces the big challenge of normal tissue damage. In this study, we report a tumor-homing bacterium, Bifidobacterium bifidum (B. bifidum), adsorbing liposomes that encapsulate perfluorohexane (PFH) and doxorubicin (DOX) to enhance the pulsed-focused ultrasound (PFUS) for tumor therapy, so as to improve the efficacy, safety and controllability of ultrasound treatment. Methods: The PFH and DOX co-loaded cationic liposomal nanoparticles (CL-PFH-DOX-NPs) were prepared for ultrasound (US) imaging, cell-killing, and B. bifidum adsorption for the reactive oxygen species (ROS) testing. The aggregation of B. bifidum and CL-PFH-DOX-NPs is called tumor-homing aggregation (B. bifidum@CL-PFH-DOX-NPs) in this study, and the synergistic effects of B. bifidum@CL-PFH-DOX-NPs were analyzed in vivo. Results: Comprehensive studies validated that CL-PFH-DOX-NPs can enhance US imaging and cell-killing and B. bifidum can promote ROS, and B. bifidum@CL-PFH-DOX-NPs achieve PFUS synergism in vivo. Importantly, active homing of B. bifidum facilitated the delivery and retention of CL-PFH-DOX-NPs in tumors, reducing dispersion in normal tissues, achieving the targeting ability of B. bifidum@CL-PFH-DOX-NPs. The best sonication time was chosen according to the distribution of CL-PFH-DOX-NPs in vivo to achieve efficient therapy. Especially, B. bifidum@CL-PFH-DOX-NPs amplified cavitation and the immune-boosting effects. Conclusion: Multifunctional B. bifidum@CL-PFH-DOX-NPs were successfully constructed with well targeting, which not only realized US imaging monitoring, strong cavitation and complementary killing during PFUS, but also achieved immunity enhancement after PFUS. The combination of PFUS, B. bifidum and CL-PFH-DOX-NPs provides a new idea for the potential application of ultrasound therapy in solid tumors.

Novel role for integrin ß4 in asthmatic children infected with Mycoplasma pneumoniae.

Objectives: The regulatory role of integrin ß4 (ITGB4) in asthmatic children infected with Mycoplasma pneumoniae (MP) was analyzed, and its potential molecular mechanisms and function were studied.Methods: We collected epidemiological data from 70,455 asthmatic children. The immunofluorescence assay was used to test 9 index IgMs against respiratory tract pathogens for 736 serum samples. Then, 98 children with severe asthma were treated via fiberoptic bronchoscope examination. During the surgery, the patients' lavage fluid was collected. Additionally, differences in transforming growth factor-beta (TGF-ß) expression between the MP-infected and noninfected groups were examined. Experiments were performed using white blood cell counting methods and flow cytometry for 98 asthmatic children.Results: We tested 736 specimens, and the percentages of MP, RSV, and ADV infections were 50.27%, 11.68%, and 10.05%, respectively. The percentage of eosinophils was increased significantly in the AS-I-MP group, and their TGF-ß expression levels were increased, which was related to tissue fibrosis. Furthermore, MP infection exacerbated the decreasing trend of ITGB4 expression in patients' blood compared with the noninfected group.Conclusions: There might be a chain reaction from MP infection to an increase in ITGB4, a decrease in TGF-ß, a large accumulation of eosinophils and the development of asthma in children.

Long-term efficacy of no-touch radiofrequency ablation in the treatment of single small hepatocellular carcinoma: A single center long-term follow-up study.

OBJECTIVE: To evaluate the long-term efficacy of no-touch radiofrequency ablation (NT-RFA) for treating single hepatocellular carcinoma (HCC) less than 3 cm. METHODS: A total of 331 patients with HCC less than 3 cm undergoing RFA in Southwest Hospital from 2015 to 2020 were analyzed retrospectively. All patients were divided into NT-RFA group (n = 113) and conventional RFA (C-RFA) group (n = 218). The survival rate, local tumor progression (LTP) and intrahepatic distant recurrence (IDR) of the two groups were calculated and compared. RESULTS: A significant difference was observed in ablation range (p = 0.000) and safety margin (p = 0.000) between the two groups. The 1-, 2-, 3-, 4-and 5-year overall survival (OS) rates in NT-RFA and C-RFA group were 99.12%, 93.73%, 76.18%, 57.00%, 45.17% and 99.08%, 89.91%, 71.26%, 54.28%, 41.77%, respectively. There was no significant difference between the two groups (p = 0.281). The 1-, 2-, 3-, 4-and 5-year recurrence-free survival (RFS) rates in NT-RFA and C-RFA group were 78.51%, 52.59%, 41.02%, 34.36%, 30.92% and 68.81%, 44.95%, 30.88%, 23.73%, 22.88%, respectively. The two groups differed significantly (p = 0.044). The 1-, 3-and 5-year LTP-free survival rates in NT-RFA and C-RFA group were 87.12%, 74.99%, 72.32% and 75.75%, 65.52%, 65.52%, respectively. The two groups also differed significantly (p = 0.024). Furthermore, the RFS rates of D ≤ 2 cm subgroups in NT-RFA and C-RFA groups differed significantly (p = 0.037), while the RFS rates of 2 cm < D ≤ 3 cm subgroups in two groups showed no significant difference (p = 0.578). CONCLUSIONS: The RFS rates of single HCC less than 3 cm treated by NT-RFA was significantly higher than that of C-RFA. Due to a larger ablation range and safety margin, NT-RFA could significantly reduce LTP and improve RFS. Dual-electrode NT-RFA can significantly improve the RFS rate of patients with HCC less than 2 cm, but there is no obvious advantage compared with C-RFA in the treatment of HCC over 2 cm.

Identification of a stable major-effect quantitative trait locus for pre-harvest sprouting in common wheat (Triticum aestivum L.) via high-density SNP-based genotyping.

KEY MESSAGE: A major and stable QTL cQSGR.sau.3D, which can explain 33.25% of the phenotypic variation in SGR, was mapped and validated, and cQSGR.sau.3D was found to be independent of GI. In this study, a recombinant inbred line (RIL) population containing 304 lines derived from the cross of Chuan-nong17 (CN17) and Chuan-nong11 (CN11) was genotyped using the Wheat55K single-nucleotide polymorphism array. A high-density genetic map consisting of 8329 markers spanning 4131.54 cM and distributed across 21 wheat chromosomes was constructed. QTLs for whole spike germination rate (SGR) were identified in multiple years. Six and fourteen QTLs were identified using the Inclusive Composite Interval Mapping-Biparental Populations and Multi-Environment Trial methods, respectively. A total of 106 digenic epistatic QTLs were also detected in this study. One of the additive QTLs, cQSGR.sau.3D, which was mapped in the region from 3.5 to 4.5 cM from linkage group 3D-2 on chromosome 3D, can explain 33.25% of the phenotypic variation in SGR and be considered a major and stable QTL for SGR. This QTL was independent of the seeds' germination traits, such as germination index. One Kompetitive Allele-Specific PCR (KASP) marker, KASP-AX-110772653, which is tightly linked to cQSGR.sau.3D, was developed. The genetic effect of cQSGR.sau.3D on SGR in the RIL and natural populations was successfully confirmed. Furthermore, within the interval in which cQSGR.sau.3D is located in Chinese Spring reference genomes, thirty-seven genes were found. cQSGR.sau.3D may provide new resources for pre-harvest sprouting resistance breeding of wheat in the future.

Genetically engineered bacteria-mediated multi-functional nanoparticles for synergistic tumor-targeting therapy.

Focused ultrasonic ablation surgery (FUAS) for tumor treatment has emerged as an effective non-invasive therapeutic approach, but its widespread clinical utilization is limited by its low therapeutic efficiency caused by inadequate tumor targeting, single imaging modality, and possible tumor recurrence following surgery. Therefore, this study aimed to develop a biological targeting synergistic system consisting of genetically engineered bacteria and multi-functional nanoparticles to overcome these limitations. Escherichia coli was genetically modified to carry an acoustic reporter gene encoding the formation of gas vesicles (GVs) and then target the tumor hypoxic environment in mice. After E. coli producing GVs (GVs-E. coli) colonized the tumor target area, ultrasound imaging and collaborative FUAS were performed; multi-functional nanoparticles were then enriched in the tumor target area through electrostatic adsorption. Multi-functional cationic lipid nanoparticles containing IR780, perfluorohexane, and banoxantrone dihydrochloride (AQ4N) were coloaded in the tumor to realize targeted multimodal imaging and enhance the curative effect of FUAS. AQ4N was stimulated by the tumor hypoxic environment and synergistically cooperated with FUAS to kill tumor cells. In sum, synergistic tumor therapy involving multi-functional nanoparticles mediated by genetically engineered bacteria overcomes the limitations and improves the curative effect of existing FUAS. STATEMENT OF SIGNIFICANCE: Inadequate tumor targeting, single image monitoring mode, and prone tumor recurrence following surgery remain significant challenges yet critical for tumor therapy. This study proposes a strategy for genetically engineered bacteria-mediated multifunctional nanoparticles for synergistic tumor therapy. The multifunctional genetically engineered biological targeting synergistic agent can accomplish tumor-targeting therapy, synergistic FUAS ablation, hypoxia-activated chemotherapy combined with FUAS ablation, and multiple-imaging guidance and monitoring all at the same time, thereby compensating for the shortcomings of FUAS treatment. This strategy could pave the way for the progress of tumor therapy.

A new polysaccharide platform constructs self-adjuvant nanovaccines to enhance immune responses.

BACKGROUND: Nanovaccines have shown the promising potential in controlling and eradicating the threat of infectious diseases worldwide. There has been a great need in developing a versatile strategy to conveniently construct diverse types of nanovaccines and induce potent immune responses. To that end, it is critical for obtaining a potent self-adjuvant platform to assemble with different types of antigens into nanovaccines. RESULTS: In this study, we identified a new natural polysaccharide from the rhizomes of Bletilla striata (PRBS), and used this polysaccharide as a platform to construct diverse types of nanovaccines with potent self-adjuvant property. In the construction process of SARS-CoV-2 nanovaccine, PRBS molecules and RBD protein antigens were assembled into ~ 300 nm nanoparticles by hydrogen bond. For HIV nanovaccine, hydrophobic effect dominantly drove the co-assembly between PRBS molecules and Env expression plasmid into ~ 350 nm nanospheres. Importantly, PRBS can potently activate the behaviors and functions of multiple immune cells such as macrophages, B cells and dendritic cells. Depending on PRBS-mediated immune activation, these self-adjuvant nanovaccines can elicit significantly stronger antigen-specific antibody and cellular responses in vivo, in comparison with their corresponding traditional vaccine forms. Moreover, we also revealed the construction models of PRBS-based nanovaccines by analyzing multiple assembly parameters such as bond energy, bond length and interaction sites. CONCLUSIONS: PRBS, a newly-identified natural polysaccharide which can co-assemble with different types of antigens and activate multiple critical immune cells, has presented a great potential as a versatile platform to develop potent self-adjuvant nanovaccines.

US/MR Bimodal Imaging-Guided Bio-Targeting Synergistic Agent for Tumor Therapy.

Purpose: Breast cancer is detrimental to the health of women due to the difficulty of early diagnosis and unsatisfactory therapeutic efficacy of available breast cancer therapies. High intensity focused ultrasound (HIFU) ablation is a new method for the treatment of breast tumors, but there is a problem of low ablation efficiency. Therefore, the improvement of HIFU efficiency to combat breast cancer is immediately needed. This study aimed to describe a novel anaerobic bacteria-mediated nanoplatform, comprising synergistic HIFU therapy for breast cancer under guidance of ultrasound (US) and magnetic resonance (MR) bimodal imaging. Methods: The PFH@CL/Fe3O4 nanoparticles (NPs) (Perfluorohexane (PFH) and superparamagnetic iron oxides (SPIO, Fe3O4) with cationic lipid (CL) NPs) were synthesized using the thin membrane hydration method. The novel nanoplatform Bifidobacterium bifidum-mediated PFH@CL/Fe3O4 NPs were constructed by electrostatic adsorption. Thereafter, US and MR bimodal imaging ability of B. bifidum-mediated PFH@CL/Fe3O4 NPs was evaluated in vitro and in vivo. Finally, the efficacy of HIFU ablation based on B. bifidum-PFH@CL/Fe3O4 NPs was studied. Results: B. bifidum combined with PFH@CL/Fe3O4 NPs by electrostatic adsorption and enhanced the tumor targeting ability of PFH@CL/Fe3O4 NPs. US and MR bimodal imaging clearly displayed the distribution of the bio-targeting nanoplatform in vivo. It was conducive for accurate and effective guidance of HIFU synergistic treatment of tumors. Furthermore, PFH@CL/Fe3O4 NPs could form microbubbles by acoustic droplet evaporation and promote efficiency of HIFU ablation under guidance of bimodal imaging. Conclusion: A bio-targeting nanoplatform with high stability and good physicochemical properties was constructed. The HIFU synergistic agent achieved early precision imaging of tumors and promoted therapeutic effect, monitored by US and MR bimodal imaging during the treatment process.

The complete chloroplast genome of the newly recorded species Tainia acuminata Averyanov (Orchidaceae) from China.

The complete chloroplast genome sequence of Tainia acuminata Averyanov was assembled and the phylogenetic relationship of the species to other taxa in Subtrib. Bletlinae was inferred in this study. The length of the complete chloroplast sequence is 157,603 bp, and it contains a large single-copy (LSC) region of 86,336 bp, a small single-copy (SSC) region of 18,129 bp, and two inverted repeat (IRA and IRB) regions of 26,569 bp. A total of 134 genes were annotated including 89 protein-coding genes, 37 tRNA, and eight rRNA. Phylogenetic analysis showed that T. acuminata was closely related to T. cordifolia, and the genus was closely related to a clade consisting of Calanthe, Phaius, and Cephalantheropsis.

Bioinformatics and Screening of a Circular RNA-microRNA-mRNA Regulatory Network Induced by Coxsackievirus Group B5 in Human Rhabdomyosarcoma Cells.

Hand, foot and mouth disease (HFMD) caused by Coxsackievirus Group B5 (CVB5) is one of the most common herpetic diseases in human infants and children. The pathogenesis of CVB5 remains unknown. Circular RNAs (CircRNAs), as novel noncoding RNAs, have been shown to play a key role in many pathogenic processes in different species; however, their functions during the process of CVB5 infection remain unclear. In the present study, we investigated the expression profiles of circRNAs using RNA sequencing technology in CVB5-infected and mock-infected human rhabdomyosarcoma cells (CVB5 virus that had been isolated from clinical specimens). In addition, several differentially expressed circRNAs were validated by RT-qPCR. Moreover, the innate immune responses related to circRNA-miRNA-mRNA interaction networks were constructed and verified. A total of 5461 circRNAs were identified at different genomic locations in CVB5 infections and controls, of which 235 were differentially expressed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis demonstrated that the differentially expressed circRNAs were principally involved in specific signaling pathways related to ErbB, TNF, and innate immunity. We further predicted that novel_circ_0002006 might act as a molecular sponge for miR-152-3p through the IFN-I pathway to inhibit CVB5 replication, and that novel_circ_0001066 might act as a molecular sponge for miR-29b-3p via the NF-κB pathway and for the inhibition of CVB5 replication. These findings will help to elucidate the biological functions of circRNAs in the progression of CVB5-related HFMD and identify prospective biomarkers and therapeutic targets for this disease.

Drug-loaded nanoparticles conjugated with genetically engineered bacteria for cancer therapy.

Drug-loaded nanoparticles have been widely used as synergists in high-intensity focused ultrasound (HIFU) tumor ablation therapy. However, these synergists have certain limitations, such as poor tumor targeting and low accumulation at the tumor site, that restrict the therapeutic efficacy of HIFU. In this study, we utilized drug-loaded nanoparticles conjugated with genetically engineered bacteria which can selectively colonize the hypoxic areas of tumor to facilitate HIFU ablation. Genetically modified Escherichia coli carrying gas vesicles (GVs-E. coli), which were gas-filled protein nanostructures, had a negatively charged surface and could specifically target into the tumor. In contrast, paclitaxel (PTX) and perfluorohexane (PFH) co-loaded cationic lipid nanoparticles (PTX-CLs) had a positively charged surface, hence, GVs-E. coli was used as a vehicle by conjugating with PTX-CLs via electrostatic adsorption and subsequently attracting more PTX-CLs to the tumor site. To improve the therapeutic efficiency of HIFU, the GVs in GVs-E. coli and PFH encapsulated in PTX-CLs could act as cavitation nuclei to enhance the HIFU cavitation effect, while PTX entrapped in PTX-CLs was released at the tumor site under HIFU irradiation, enhancing the therapeutic efficacy of HIFU and chemo-synergistic therapy. This novel combination strategy has great potential for cancer treatment.

Identification and validation of quantitative trait loci for the functional stay green trait in common wheat (Triticum aestivum L.) via high-density SNP-based genotyping.

KEY MESSAGE: This study identified QTLs associated with the functional stay green trait by a high-density genetic map. Two large effect QTLs, QSg.sau-2B.1 and QSg.sau-6A.2, were identified in multiple years and one of them was successfully validated. The functional stay green phenotype enables wheat to acclimate to stressful environments and prolongs the effectiveness of photosynthesis during the end-of-crop season. Despite the fact that stay green mutants in wheat have been reported, our knowledge of loci for the functional stay green trait remains limited. In this study, an RIL population containing 371 lines genotyped using the Wheat55K SNP array was used to map QTLs controlling the functional stay green trait in multiple years. In total, 21 and 19 QTLs were mapped using the BIP or MET modules of the ICIM method, respectively. Among them, two QTLs, QSg.sau-2B.1 and QSg.sau-6A.2, were considered large effect QTLs for the stay green trait and explained 11.43% and 15.27% of phenotypic variation on average, respectively. Two KASP markers were developed and tightly linked to QSg.sau-2B.1 and QSg.sau-6A.2, respectively, and the genetic effects of different genotypes in the RIL population were successfully confirmed. QSg.sau-2B.1 was also validated by linked KASP marker in different genetic backgrounds. QSg.sau-2B.1 and QSg.sau-6A.2 may influence heredity of the stay green trait and also exhibited a positive effect on the grain filling content. In the interval where QSg.sau-2B.1 and QSg.sau-6A.2 were located on the Chinese Spring and T. turgidum ssp. dicoccoides reference genomes, several genes associated with the leaf senescence process were identified. Altogether, our results identified two QTLs associated with the functional stay green trait and will be useful for the fine mapping and cloning of genes for stay green in the future.

QTL Mapping and Validation for Kernel Area and Circumference in Common Wheat via High-Density SNP-Based Genotyping.

As an important component, 1,000 kernel weight (TKW) plays a significant role in the formation of yield traits of wheat. Kernel size is significantly positively correlated to TKW. Although numerous loci for kernel size in wheat have been reported, our knowledge on loci for kernel area (KA) and kernel circumference (KC) remains limited. In the present study, a recombinant inbred lines (RIL) population containing 371 lines genotyped using the Wheat55K SNP array was used to map quantitative trait loci (QTLs) controlling the KA and KC in multiple environments. A total of 54 and 44 QTLs were mapped by using the biparental population or multienvironment trial module of the inclusive composite interval mapping method, respectively. Twenty-two QTLs were considered major QTLs. BLAST analysis showed that major and stable QTLs QKc.sau-6A.1 (23.12-31.64 cM on 6A) for KC and QKa.sau-6A.2 (66.00-66.57 cM on 6A) for KA were likely novel QTLs, which explained 22.25 and 20.34% of the phenotypic variation on average in the 3 year experiments, respectively. Two Kompetitive allele-specific PCR (KASP) markers, KASP-AX-109894590 and KASP-AX-109380327, were developed and tightly linked to QKc.sau-6A.1 and QKa.sau-6A.2, respectively, and the genetic effects of the different genotypes in the RIL population were successfully confirmed. Furthermore, in the interval where QKa.sau-6A.2 was located on Chinese Spring and T. Turgidum ssp. dicoccoides reference genomes, only 11 genes were found. In addition, digenic epistatic QTLs also showed a significant influence on KC and KA. Altogether, the results revealed the genetic basis of KA and KC and will be useful for the marker-assisted selection of lines with different kernel sizes, laying the foundation for the fine mapping and cloning of the gene(s) underlying the stable QTLs detected in this study.

Bifidobacterium bifidum-Mediated Specific Delivery of Nanoparticles for Tumor Therapy.

PURPOSE: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for Bifidobacterium bifidum (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer. METHODS: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF in vivo. Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor. RESULTS: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects. CONCLUSION: We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.

Effects of electromyography biofeedback for patients after knee surgery: A systematic review and meta-analysis.

There has been no systematic review evaluating the efficacy of electromyography (EMG) biofeedback after knee surgery recently. This meta-analysis aimed to determine whether EMG-biofeedback is effective for improving the range of motion (ROM), physical function, and pain relief in patients after knee. Randomized controlled trials (RCTs) assessing the effect of EMG-biofeedback after any knee surgery were retrieved from EMBASE, PubMed, Cochrane Library, Physiotherapy Evidence Database, ClinicalTrials.gov, ProQuest. This review identified 773 unique studies, and six RCTs were in the final meta-analysis. EMG-Biofeedback treatment has a significant difference compared to other rehabilitation therapy in knee ROM improving (SMD = -0.48, 95% CI = -0.82 to -0.14, p = 0.006, I2 = 37%). Moreover, there was no significant difference in pain (SMD = -0.33, 95% CI = -0.67 to0.02, p = 0.07, I2 = 41%) and physical function scores (MD = 1.83, 95% CI = -3.48 to7.14, p = 0.50, I2 = 0%). The results illustrate that EMG-biofeedback can improve knee ROM in patients after knee surgery. However, it is not superior to other rehabilitation methods for pain relief and physical function improvement.

Research Trends on the Rotator Cuff Tendon: A Bibliometric Analysis of the Past 2 Decades.

BACKGROUND: Clinical research on the rotator cuff tendon is increasing, and new approaches are being applied to rotator cuff disease. Considering the integration of research resources and research trends, it is necessary to conduct an analysis of recent research on the topic. PURPOSE: To identity the research trends, influential journals, key researchers, and core countries of rotator cuff tendon research between 2000 and 2019. STUDY DESIGN: Cross-sectional study. METHODS: All the literature related to rotator cuff tendon research was retrieved from the Web of Science Core Collection on January 7, 2020. Qualitative and quantitative analyses were processed based on Web of Science and CiteSpace. RESULTS: A total of 4131 studies, which included 3830 articles and 301 reviews, were obtained. There was an upward trend of studies on the topic, with small fluctuations in the past 2 decades. The United States had the most studies, and the number of studies from other countries increased over the study period. Most of the funding sources came from the United States. Articles in the Journal of Shoulder and Elbow Surgery had the most citations for rotator cuff research. Frontier topics, such as arthroscopic repair, mesenchymal stem cell, and "platelet-rich plasma, were identified. The number of citations in 2018 (r = 0.280; P = .005) and 2019 (r = 0.307; P = .002) had a weak positive correlation with publication date, indicating that the more recently published articles had a higher number of citations. CONCLUSION: Valuable information on rotator cuff research based on bibliometric analysis was identified. Arthroscopic repair, mesenchymal stem cell, and platelet-rich plasma might be the research frontiers in this field, and researchers should focus on these topics in future studies.