Identification and functional analysis of a chromosome 2D fragment harboring TaFPF1 gene with the potential for yield improvement using a late heading wheat mutant.

KEY MESSAGE: A chromosome fragment influencing wheat heading and grain size was identified using mapping of m406 mutant. The study of TaFPF1 in this fragment provides more insights into wheat yield improvement. In recent years, wheat production has faced formidable challenges driven by rapid population growth and climate change, emphasizing the importance of improving specific agronomic traits such as heading date, spike length, and grain size. To identify potential genes for improving these traits, we screened a wheat EMS mutant library and identified a mutant, designated m406, which exhibited a significantly delayed heading date compared to the wild-type. Intriguingly, the mutant also displayed significantly longer spike and larger grain size. Genetic analysis revealed that a single recessive gene was responsible for the delayed heading. Surprisingly, a large 46.58 Mb deletion at the terminal region of chromosome arm 2DS in the mutant was identified through fine mapping and fluorescence in situ hybridization. Thus, the phenotypes of the mutant m406 are controlled by a group of linked genes. This deletion encompassed 917 annotated high-confidence genes, including the previously studied wheat genes Ppd1 and TaDA1, which could affect heading date and grain size. Multiple genes in this region probably contribute to the phenotypes of m406. We further investigated the function of TaFPF1 using gene editing. TaFPF1 knockout mutants showed delayed heading and increased grain size. Moreover, we identified the direct upstream gene of TaFPF1 and investigated its relationship with other important flowering genes. Our study not only identified more genes affecting heading and grain development within this deleted region but also highlighted the potential of combining these genes for improvement of wheat traits.

Facet-Dependent Fe2O3/BiVO4(110)/BiVO4(010)/Fe2O3 Dual S-Scheme Photocatalyst as an Efficient Visible-Light-Driven Peroxymonosulfate Activator for Norfloxacin Degradation.

A lack of eco-friendly, highly active photocatalyst for peroxymonosulfate (PMS) activation and unclear environmental risks are significant challenges. Herein, we developed a double S-scheme Fe2O3/BiVO4(110)/BiVO4(010)/Fe2O3 photocatalyst to activate PMS and investigated its impact on wheat seed germination. We observed an improvement in charge separation by depositing Fe2O3 on the (010) and (110) surfaces of BiVO4. This enhancement is attributed to the formation of a dual S-scheme charge transfer mechanism at the interfaces of Fe2O3/BiVO4(110) and BiVO4(010)/Fe2O3. By introducing PMS into the system, photogenerated electrons effectively activate PMS, generating reactive oxygen species (ROS) such as hydroxyl radicals (·OH) and sulfate radicals (SO4·-). Among the tested systems, the 20% Fe2O3/BiVO4/Vis/PMS system exhibits the highest catalytic efficiency for norfloxacin (NOR) removal, reaching 95% in 40 min. This is twice the catalytic efficiency of the Fe2O3/BiVO4/PMS system, 1.8 times that of the Fe2O3/BiVO4 system, and 5 times that of the BiVO4 system. Seed germination experiments revealed that Fe2O3/BiVO4 heterojunction was beneficial for wheat seed germination, while PMS had a significant negative effect. This study provides valuable insights into the development of efficient and sustainable photocatalytic systems for the removal of organic pollutants from wastewater.

Overexpression of rice OsNRT1.1A/OsNPF6.3 enhanced the nitrogen use efficiency of wheat under low nitrogen conditions.

MAIN CONCLUSION: Overexpression of OsNRT1.1A promotes early heading and increases the tolerance in wheat under nitrogen deficiency conditions. The application of inorganic nitrogen (N) fertilizers is a major driving force for crop yield improvement. However, the overuse of fertilizers significantly raises production costs and leads to environmental problems, making it critical to enhance crop nitrogen use efficiency (NUE) for the sake of sustainable agriculture. In this study, we created a series of transgenic wheat lines carrying the rice OsNRT1.1A gene, which encodes a nitrate transporter, to investigate its possible application in improving NUE in wheat. The transgenic wheat exhibited traits such as early maturation that were highly consistent with the overexpression of OsNRT1.1A in Arabidopsis and rice. However, we also observed that overexpression of the OsNRT1.1A gene in wheat can facilitate the growth of roots under low N conditions but has no effect on other aspects of growth and development under normal N conditions. Thus, it may lead to the improvement of wheat low N tolerance,which is different from the effects reported in other plants. A field trial analysis showed that transgenic wheat exhibited increased grain yield per plant under low N conditions. Moreover, transcriptome analysis indicated that OsNRT1.1A increased the expression levels of N uptake and utilization genes in wheat, thereby promoting plant growth under low N conditions. Taken together, our results indicated that OsNRT1.1A plays an important role in improving NUE in wheat with low N availability.

Bajitianwan formula extract ameliorates bone loss induced by iron overload via activating RAGE/PI3K/AKT pathway based on network pharmacology and transcriptomic analysis.

Osteoporosis (OP) is closely related to iron overload. Bajitianwan (BJTW) is a traditional Chinese medicine formulation used for treating senile diseases such as dementia and osteoporosis. Modern pharmacological researches have found that BJTW has beneficial effect on bone loss and memory impairment in aging rats. This paper aimed to explore the role and mechanism of BJTW in ameliorating iron overload-induced bone loss. Furthermore, BJTW effectively improved the bone micro-structure of the femur in mice, and altered bone metabolism biomarkers alkaline phosphatase (ALP) and osteocalcin (OCN) in serum, as well as oxidative indexes superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) glutathione (GSH) and malondialdehyde (MDA) in liver. As for network pharmacology, 73 components collected from BJTW regulated 99 common targets merged in the BJTW and OP. The results of RNA-seq indicated that there were 418 potential targets in BJTW low dose group (BJTW-L) and 347 potential targets in BJTW high dose group (BJTW-H). Intriguingly, both PI3K-AKT signaling pathway and the AGEs-RAGE signaling pathway were contained in the KEGG pathways enrichment results of network pharmacology and transcriptomics, which were considered as the potential mechanism. Additionally, we verified that BJTW regulated the expression of related proteins in RAGE/PI3K-AKT pathways in MC3T3-E1 cells. In summary, BJTW has potent effect on protecting against iron overload-induced OP, and its mechanism may be related to the activation of the RAGE/PI3K-AKT signaling pathways.

[Application of convolutional neural networks for the classification of metaphase chromosomes].

OBJECTIVE: To train a deep convolutional neural networks (CNN) using a labeled data set to classify the metaphase chromosomes and test its accuracy for chromosomal identification. METHODS: Three thousand and three hundred individuals undergoing surveillance for chromosomal disorders at the Laboratory for Comprehensive Prevention and Treatment of Birth Defects, Ningbo Maternal and Child Health Care Hospital from January 2013 to July 2019 were enrolled. A total of 3 300×46 chromosome images were included, of which 70% were used as the training set and 30% were used as the test set for the deep CNN. The accuracy of chromosome counting and "cutting + recognition + arrangement + automatic analysis" of the model were respectively evaluated. Another 80 images were collected to record the time and accuracy of chromosome classification by geneticists and the model, respectively, so as to assess the practical value of the model. RESULTS: The CNN model was used to count the chromosomes with an accuracy of 61.81%, and the "cutting + recognition + arrangement + automatic analysis" accuracy of the model was 96.16%. Compared with manual operation, the classification time of the CNN model has been greatly reduced, and its karyotyping accuracy was only 3.58% lower than that of geneticists. CONCLUSION: The CNN model has a high performance for chromosome classification and can significantly reduce the work load involved with the segmentation and classification and improve the efficiency of chromosomal karyotyping, thereby has a broad application prospect.

Unraveling the role of Xist in X chromosome inactivation: insights from rabbit model and deletion analysis of exons and repeat A.

X chromosome inactivation (XCI) is a process that equalizes the expression of X-linked genes between males and females. It relies on Xist, continuously expressed in somatic cells during XCI maintenance. However, how Xist impacts XCI maintenance and its functional motifs remain unclear. In this study, we conducted a comprehensive analysis of Xist, using rabbits as an ideal non-primate model. Homozygous knockout of exon 1, exon 6, and repeat A in female rabbits resulted in embryonic lethality. However, X∆ReAX females, with intact X chromosome expressing Xist, showed no abnormalities. Interestingly, there were no significant differences between females with homozygous knockout of exons 2-5 and wild-type rabbits, suggesting that exons 2, 3, 4, and 5 are less important for XCI. These findings provide evolutionary insights into Xist function.

EUS­guided antegrade stenting for malignant jaundice following Roux­en­Y reconstruction: the treatment of multiple biliary strictures.

Multiple malignant biliary strictures are rare, and the application of multiple stents can achieve better drainage. EUS-guided biliary drainage (EUS-BD) can be offered as an alternative technique when ERCP unsuccessful. We applied Endoscopic ultrasonic guided antegrade stenting technique to treat a case of multiple biliary strictures following Roux-en-Y reconstruction.

SARS-CoV-2 Nsp1 cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA.

A better mechanistic understanding of virus-host dependencies can help reveal vulnerabilities and identify opportunities for therapeutic intervention. Of particular interest are essential interactions that enable production of viral proteins, as those could target an early step in the virus lifecycle. Here, we use subcellular proteomics, ribosome profiling analyses and reporter assays to detect changes in protein synthesis dynamics during SARS-CoV-2 (CoV2) infection. We identify specific translation factors and molecular chaperones that are used by CoV2 to promote the synthesis and maturation of its own proteins. These can be targeted to inhibit infection, without major toxicity to the host. We also find that CoV2 non-structural protein 1 (Nsp1) cooperates with initiation factors EIF1 and 1A to selectively enhance translation of viral RNA. When EIF1/1A are depleted, more ribosomes initiate translation from a conserved upstream CUG start codon found in all genomic and subgenomic viral RNAs. This results in higher translation of an upstream open reading frame (uORF1) and lower translation of the main ORF, altering the stoichiometry of viral proteins and attenuating infection. Replacing the upstream CUG with AUG strongly inhibits translation of the main ORF independently of Nsp1, EIF1, or EIF1A. Taken together, our work describes multiple dependencies of CoV2 on host biosynthetic networks and proposes a model for dosage control of viral proteins through Nsp1-mediated control of translation start site selection.

The Pivotal Radical Intermediate [Au21(SR)15]+ in the Ligand-Exchange-Induced Size-Reduction of [Au23(SR)16]- to Au16(SR)12.

The atomic precision of sub-nanometer-sized metal nanoclusters makes it possible to elucidate the kinetics of metal nanomaterials from the molecular level. Herein, the size reduction of an atomically precise [Au23(CHT)16]- (HCHT = cyclohexanethiol) cluster upon ligand exchange with HSAdm (1-adamantanethiol) has been reported. During the 16 h conversion of [Au23(CHT)16]- to Au16(SR)12, the neutral 6e Au21(SR)15, and its 1e-reduction state, i.e. the 5e, cationic radical, [Au21(SR)15]+, are active intermediates to account for the formation of thermodynamically stable Au16 products. The combination of spectroscopic monitoring (with UV-vis and ESI-MS) and DFT calculations indicates the preferential size-reduction on the corner Au atoms on the core surface and the terminal Au atoms on longer AunSn+1 staples. This study provides a reassessment on the electronic state of the Au21 structure and highlights the single electron transfer processes in cluster systems and thus the importance of the EPR analysis on the mechanistic issues.

Effect of black wolfberry anthocyanin and maltitol on the gelation and microstructural properties of curdlan/gellan gum hybrid gels.

BACKGROUND: Laboratory scale experiments have shown that curdlan and gellan gum gelled together as curdlan/gellan gum (CG) hybrid gels showed better gel properties than the individual curdlan and gellan gum. In this study, CG and black wolfberry anthocyanin (BWA), CG and maltitol (ML) hybrid gels were constructed using CG hybrid gel as matrix. The effects of BWA or ML on the gel properties and microstructure of CG hybrid gels were investigated and a confectionery gel was developed. RESULTS: The presence of BWA increased the storage modulus (G') value of CG at 0.1 Hz, whereas ML had little effect on the G' value of CG. The addition of BWA (5 g L-1 ) and ML (0.3 mol L-1 ) increased the melting and gelling temperatures of CG hybrid gels to 42.4 °C and 34.1 °C and 44.2 °C and 33.2 °C, respectively. Meanwhile, the relaxation time T22 in CG-ML and CG-BWA hybrid gels was reduced to 91.96 and 410.27 ms, indicating the strong binding between BWA and CG, ML and CG. The hydrogen bond interaction between BWA or ML and CG was confirmed by the shift in the hydroxyl stretching vibration peak. Moreover, the microstructures of CG-ML and CG-BWA hybrid gels were denser than that of CG. In addition, confectionery gel containing CG-BWA-ML has good chewing properties. CONCLUSION: These results indicated that the incorporation of BWA or ML could improve the structure of CG hybrid gels and assign a sustainability potential for the development of confectionery gels based on CG complex. © 2024 Society of Chemical Industry.

Transduodenal accessory papillary Rendezvous technique assisted ERCP in the treatment of severe pancreatic duct stenosis caused by chronic pancreatitis in children.

Chronic pancreatitis in children is an irreversible inflammatory disease, which can cause intractable abdominal pain and abnormal internal and external secretion function of the pancreas, seriously affecting the growth and development of children and the quality of life. ERCP has become the first choice because of its good effect and less trauma. However, the severe stenosis of pancreatic duct caused by chronic pancreatitis may make ERCP more difficult. Here we used the rendezvous technique to assist ERCP to complete the treatment of severe pancreatic duct stenosis and abdominal pain.

The transplant rejection response involves neutrophil and macrophage adhesion-mediated trogocytosis and is regulated by NFATc3.

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.

EUS-guided bridging technique for treatment of biliary-enteric anastomotic stenosis after pancreaticoduodenectomy.

Biliary-enteric anastomotic stenosis is one of the main long-term complications after pancreaticoduodenectomy, with an incidence of 2%-8%. Although the relevant reports and studies are relatively few, the consequences such as biliary obstruction and refractory cholangitis seriously affect the quality of life of patients. In this case, the patient is not willing to receive conventional surgery again. This paper provides a bridge technique of EUS-guided Biliary Drainage (EUS-BD) to treat biliary-enteric anastomotic stenosis and solve the problem of obstructive jaundice in the patient.

A computational method for small molecule-RNA binding sites identification by utilizing position specificity and complex network information.

Some computational methods have been given for small molecule-RNA binding site identification due to that it plays a significant role in revealing biology function researches. However, it is still challenging to design an accurate model, especially for MCC. We designed a feature extraction technology from two aspects (position specificity and complex network information). Specifically, complex network was employed to express the space topological structure and sequence position information for improving prediction effect. Then, the features fused position specificity and complex network information were input into random forest classifier for model construction. The AUC of 88.22%, 77.92% and 81.46% were obtained on three independent datasets (RB19, CS71, RB78). Compared with the existing method, the best MCC were obtained on three datasets, which were 8.19%, 0.59% and 4.35% higher than the state-of-the-art prediction methods, respectively. The outstanding performances show that our method is a powerful tool to identify RNA binding sites, helping to the design RNA-targeting small molecule drugs. The data and resource codes are available at https://github.com/Kangxiaoneuq/PCN_RNAsite.

Gel properties and interactions of hydrogels constructed with low acyl gellan gum and puerarin.

To develop composite hydrogels based on low acyl gellan gum (GG), the effect of puerarin (PUE) on the gel properties of GG was investigated. The results showed that the maximum storage modulus (G') of the 1.2 % GG/0.8 % PUE composite hydrogel was 377.4 Pa at 0.1 Hz, which was enhanced by 4.7-fold compared with that of 1.2 % GG. The melting temperature of this composite hydrogel increased from 74.1 °C to >80.0 °C. LF-NMR results showed that a significant amount of free water was present in the hydrogel matrix. The surface structure aggregation and the shrinkage of the honeycomb meshes in the composite hydrogel proved the cross-linking of PUE and GG. XRD, FTIR and molecular simulation results illustrated that hydrogen bonds were the most important factor controlling the interaction between GG and PUE. Thus, the GG/PUE composite hydrogel has good elasticity, thermal stability and water retention, which lays a good foundation for further application in the food industry.

Nitric oxide-induced endoplasmic reticulum stress of Schistosoma japonicum inhibits the worm development in rats.

Schistosomiasis, caused by Schistosoma spp., is a zoonotic parasitic disease affecting human health. Rattus norvegicus (rats) are a non-permissive host of Schistosoma, in which the worms cannot mature and cause typical egg granuloma. We previously demonstrated that inherent high levels of nitric oxide (NO), produced by inducible NO synthase (iNOS), is a key molecule in blocking the development of S. japonicum in rats. To further explore the mechanism of NO inhibiting S. japonicum development in rats, we performed S-nitrosocysteine proteomics of S. japonicum collected from infected rats and mice. The results suggested that S. japonicum in rats may have undergone endoplasmic reticulum (ER) stress. Interestingly, we found that the ER of S. japonicum in rats showed marked damage, while the ER of the worm in iNOS-/- rats and mice were relatively normal. Moreover, the expression of ER stress markers in S. japonicum from WT rats was significantly increased, compared with S. japonicum from iNOS-/- rats and mice. Using the NO donor sodium nitroprusside in vitro, we demonstrated that NO could induce ER stress in S. japonicum in a dose-dependent manner, and the NO-induced ER stress in S. japonicum could be inhibited by ER stress inhibitor 4-Phenyl butyric acid. We further verified that inhibiting ER stress of S. japonicum in rats promoted parasite development and survival. Furthermore, we demonstrated that NO-induced ER stress of S. japonicum was related to the efflux of Ca2+ from ER and the impairment of mitochondrial function. Collectively, these findings show that high levels of NO in rats could induce ER stress in S. japonicum by promoting the efflux of Ca2+ from ER and damaging the mitochondrial function, which block the worm development. Thus, this study further clarifies the mechanism of anti-schistosome in rats and provides potential strategies for drug development against schistosomiasis and other parasitosis.

A novel fusion technology utilizing complex network and sequence information for FAD-binding site identification.

Flavin adenine dinucleotide (FAD) binding sites play an increasingly important role as useful targets for inhibiting bacterial infections. To reveal protein topological structural information as a reasonable complement for the identification FAD-binding sites, we designed a novel fusion technology according to sequence and complex network. The specially designed feature vectors were combined and fed into CatBoost for model construction. Moreover, due to the minority class (positive samples) is more significant for biological researches, a random under-sampling technique was applied to solve the imbalance. Compared with the previous methods, our methods achieved the best results for two independent test datasets. Especially, the MCC obtained by FADsite and FADsite_seq were 14.37 %-53.37 % and 21.81 %-60.81 % higher than the results of existing methods on Test6; and they showed improvements ranging from 6.03 % to 21.96 % and 19.77 %-35.70 % on Test4. Meanwhile, statistical tests show that our methods significantly differ from the state-of-the-art methods and the cross-entropy loss shows that our methods have high certainty. The excellent results demonstrated the effectiveness of using sequence and complex network information in identifying FAD-binding sites. It may be complementary to other biological studies. The data and resource codes are available at https://github.com/Kangxiaoneuq/FADsite.