Unveiling the Genetic Basis Underlying Rice Anther Culturability via Segregation Distortion Analysis in Doubled Haploid Population.

Anther culture (AC) is a valuable technique in rice breeding. However, the genetic mechanisms underlying anther culturability remain elusive, which has hindered its widespread adoption in rice breeding programs. During AC, microspores carrying favorable alleles for AC are selectively regenerated, leading to segregation distortion (SD) of chromosomal regions linked to these alleles in the doubled haploid (DH) population. Using the AC method, a DH population was generated from the japonica hybrid rice Shenyou 26. A genetic map consisting of 470 SNPs was constructed using this DH population, and SD analysis was performed at both the single- and two-locus levels to dissect the genetic basis underlying anther culturability. Five segregation distortion loci (SDLs) potentially linked to anther culturability were identified. Among these, SDL5 exhibited an overrepresentation of alleles from the female parent, while SDL1.1, SDL1.2, SDL2, and SDL7 displayed an overrepresentation of alleles from the male parent. Furthermore, six pairs of epistatic interactions (EPIs) that influenced two-locus SDs in the DH population were discovered. A cluster of genetic loci, associated with EPI-1, EPI-3, EPI-4, and EPI-5, overlapped with SDL1.1, indicating that the SDL1.1 locus may play a role in regulating anther culturability via both additive and epistatic mechanisms. These findings provide valuable insights into the genetic control of anther culturability in rice and lay the foundation for future research focused on identifying the causal genes associated with anther culturability.

Self-emulsifying System Co-loaded with Paclitaxel and Coix Seed Oil Deeply Penetrated to Enhance Efficacy in Cervical Cancer.

BACKGROUND: Paclitaxel (PTX), voted as the promising natural medicine molecule, is widely used in the treatment of cancers. Nevertheless, its clinical application is strictly limited by its poor water solubility. OBJECTIVE: CP-MEs (Paclitaxel-coix seed oil coloaded microemulsion), a small-sized self-emulsifying nanoemulsion formed from a combination of PTX and coix seed oil (CSO), was developed in order to improve the solubility of paclitaxel and enhance anti-cervical cancer efficacy in vitro. CSO was selected as the oil phase to replace conventional organic solvents and achieve a synergistic anti-tumor effect with paclitaxel. METHODS: Pseudoternary phase diagram was applied to the study of CP-MEs formulation. CP-MEs were prepared and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The encapsulation efficiency and drug loading efficiency (EE and LE) were detected by HPLC. MTT was adopted to evaluate the cytotoxicity of CP-MEs against HeLa cells. The cellular uptake and apoptotic ratio of CP-MEs were evaluated by flow cytometry. Notably, HeLa 3D tumor spheroid was adopted to evaluate tumor permeability of different size microemulsions as the model. RESULTS: The best self-emulsifying ability was exhibited by HS 15: PEG 400 combination. The appearance of CP-MEs was clear and transparent, which exhibited a small size (30.28 ± 0.36) and a slight negative surface charge (-4.40 ± 1.13) mV. The EE and LE of CP-MEs were 98.80% and 0.978%, respectively. The cumulative release rate within 48 h of the CP-MEs was 80.21%. In cellular studies, the uptake of fluorescein isothiocyanate (FITC) labeled CP-MEs (FITC/C-MEs) was 17.86-fold higher than the free FITC group, leading to significant synergistic anticancer activity in terms of cytotoxicity and apoptosis induction in vitro. The apoptotic rate of CP-MEs treated was 1.70-fold higher than PTXtreated. Notably, the penetration of CP-MEs in the HeLa 3D tumor sphere model was enhanced, which was related to deeply penetrated microemulsion of small size mediated at the tumor site. CONCLUSION: With the advantage of the small-sized self-emulsifying system, CP-MEs hold great potential to become an efficient nano drug delivery system for cervical cancer treatment in the clinic.

MNK/eIF4E inhibition overcomes anlotinib resistance in non-small cell lung cancer.

Anlotinib is approved for refractory cases in advanced non-small-cell lung cancer (NSCLC). This is a novel oral multitarget tyrosine kinase inhibitor, but patients inevitably face prospects of drug resistance during the treatment process. Using anlotinib-resistant NSCLC models, this work investigated the underlying molecular mechanism and systematically addressed the issue of anlotinib resistance. We demonstrated that expression and activity of eukaryotic translation initiation factor 4E (eIF4E) were upregulated in NSCLC cells due to prolonged exposure to anlotinib. eIF4E depletion resulted in significant effects to anlotinib-resistant cells, showing proliferation inhibition and apoptosis inducement. We further showed that MAP kinase interacting serine/threonine kinase (MNK)-dependent eIF4E inhibition by cercosporamide was active against anlotinib-resistant cells and significantly augmented anlotinib's efficacy in parental NSCLC cells. Importantly, observations from in-vitro experiments are consistent in in vivo anlotinib-resistant and anlotinib-sensitive NSCLC cancer xenograft mouse models. Our work is the first to reveal that eIF4E is involved intimately in anlotinib resistance development in NSCLC, and this eIF4E activation can be reversed by cercosporamide or other MNK inhibitors.

CRISPR/Cas12a Coupled With Recombinase Polymerase Amplification for Sensitive and Specific Detection of Aphelenchoides besseyi.

Aphelenchoides besseyi (A. besseyi), a seed-borne parasitic nematode, is the causal agent of rice white tip disease (RWTD), which may result in a drastic loss of rice yield. Seed treatments are currently considered to be the most effective means of preventing the spread of RWTD. Therefore, the rapid, highly specific, and accurate detection of A. besseyi from rice seeds is crucial for the surveillance, prevention, and control of RWTD. Here, we describe a novel detection assay that combines recombinase polymerase amplification (RPA) and CRISPR/Cas12a to detect A. besseyi (termed RPA-Cas12a-Ab), with a low limit of detection (LOD) of 1 copy/µl of plasmid or 1:107 diluted DNA extracted from individual nematodes. To improve the user-friendliness, lateral flow strip assay (LFA) was adopted to visualize the detection result. The LOD of the RPA-Cas12a-Ab LFA assay was 1,000 copies/µl plasmid or 1:10 diluted DNA extracted from individual nematodes. The assay developed in this study was able to identify A. besseyi in 45 min with high accuracy and sensitivity without cross reaction with three closely related non-A. besseyi species. Thus, RPA-Cas12a-Ab is a rapid, sensitive, and specific detection system that requires no sophisticated equipment and shows promise for on-site surveillance of A. besseyi.

Integral membrane protein 2A enhances sensitivity to chemotherapy via notch signaling pathway in cervical cancer.

As the second most common cancer among women, cervical cancer is a huge threat to their health all over the world. Integral membrane protein 2A (ITM2A), a member of the Type II Integral Membrane protein (ITM2) family, has been reported to act as a tumor suppressor in breast cancer and ovarian cancer. Moreover, the low expression of ITM2A was associated with cervical adenocarcinoma. However, the function of ITM2A in drug resistance in cervical cancer remains unclear. Here, we used bioinformatics methods to screen differentially expressed genes (DEGs) closely related to chemotherapeutic relapse cervical carcinoma. ITM2A is downregulated in cervical tumor tissues and is associated with poor survival. Furthermore, ITM2A is also downregulated in cervical cancer cells with cisplatin resistance. Overexpression of ITM2A increases the cisplatin sensitivity of cervical cancer cells. Mechanically, ITM2A upregulation mediates the sensitivity of cervical cancer cell through Notch signaling pathway. Our study suggests that ITM2A may serve as a target in mediating cisplatin-resistant cervical cancer.

Circular RNA hsa_circRNA_103809 promoted hepatocellular carcinoma development by regulating miR-377-3p/FGFR1/ERK axis.

In the last decade, circular RNAs (circRNAs) emerge as important regulators in multiple biological processes. Lately, it is reported hsa_circRNA_103809 could play vital parts in several types of cancers. Based on the analysis of GEO data (GSE97332), hsa_circRNA_103809 was found to be dysregulated in hepatocellular carcinoma (HCC). However, the biological function and underlying regulatory mechanisms of hsa_circRNA_103809 in HCC remain unclear. Our results suggested that hsa_circRNA_103809 was overexpressed in HCC patients, and hsa_circRNA_103809 knockdown remarkably inhibited the proliferation, cycle progression, and migration of HCC cells. The investigations of molecular showed that hsa_circRNA_103809 could elevate the protein expression of a miR-377-3p target, fibroblast growth factor receptor 1 (FGFR1), through interacting with miR-377-3p and decreasing its expression level. Additionally, in vivo assays revealed hsa_circRNA_103809 short hairpin RNA served as a tumor suppressor through downregulating FGFR1 in HCC. This study systematically investigated novel regulatory signaling of hsa_circRNA_103809/miR-377-3p/FGFR1 axis, providing insights into hepatocellular carcinoma treatment from bench to clinic.

Dual-Mode Long-Lived Luminescence of Mn2+-Doped Nanoparticles for Multilevel Anticounterfeiting.

Luminescent nanoparticles with dual-mode long-lived luminescence are of great importance for their attractive applications in biosensing, bioimaging, and data encoding. Herein, we report the realization of up- and downconversion emission of Mn2+ dopants in multilayer nanoparticles of NaGdF4:Yb/Tm@NaGdF4:Ce/Mn@NaYF4 upon excitation at 980 and 254 nm, respectively. The dual-mode emission of the Mn2+ dopants at 531 nm have a long-lived lifetime up to ∼30 ms as a result of the spin-forbidden optical transition of Mn2+ within the 3d5 configuration. After ceasing steady excitation at the two wavelengths, the long-lived feature of Mn2+ luminescence allows a longer persistent time than lanthanide emissions, thereby enabling the ease of data decoding by a cell phone camera under a burst mode. The long-lived green upconversion emission also permits the generation of a long green tail emission upon dynamic excitation at 980 nm. These attributes make the as-prepared Mn2+-doped multilayer nanoparticles particularly attractive for multilevel anticounterfeiting.

Isoprenylcysteine carboxylmethyltransferase is associated with nasopharyngeal carcinoma chemoresistance and Ras activation.

Development of chemo-resistance in nasopharyngeal carcinoma (NPC) poses the therapeutic challenge and its mechanisms are still poorly understood. In this work, we demonstrate that targeting isoprenylcysteine carboxylmethyltransferase (Icmt) is a therapeutic strategy to overcome NPC chemo-resistance. We found that Icmt mRNA and protein levels were increased in NPC cells after prolonged exposure to chemotherapy. Using pharmacological inhibitor cysmethynil or genetic siRNA approaches, we showed that Icmt inhibition was more effective against chemoresistant compared to chemosensitive NPC cells, suggesting that chemoresistant NPC cells is more dependent on Icmt function. The combination of Icmt inhibition with 5-FU or cisplatin resulted in greater efficacy than single chemotherapeutic agent alone in NPC. Notably, we demonstrated that the in vitro observations were translatable to in vivo NPC cancer xenograft mouse model. Mechanism analysis indicated that Icmt inhibition decreased Ras and RhoA activities, leading to the suppression of Ras and RhoA-mediated downstream signaling in NPC cells. The reverse of the inhibitory effects of cysmethynil by constitutively active Ras suggests that Ras is the critical effector of Icmt in NPC cells. Our work is the first to show that Icmt plays an important role in the development of NPC chemoresistance. Our findings also suggest that targeting Icmt represents a promising strategy to inhibit Ras function.

miR-197 is downregulated in cervical carcinogenesis and suppresses cell proliferation and invasion through targeting forkhead box M1.

Cervical cancer is the second most common type of cancer in females worldwide. It has been demonstrated that microRNAs (miRs) serve important roles in the occurrence and development of various types of cancer, including cervical cancer. The results of the present study revealed that miR-197 was downregulated in cervical cancer tissues and cell lines. Restoration of miR-197 expression significantly inhibited cell viability and invasion of cervical cancer. Additionally, forkhead box M1 (FOXM1) was identified as a direct target gene of miR-197. Bioinformatic analysis revealed that FOXM1 was a potential target gene of miR-197. Luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that miR-197 decreased FOXM1 expression through direct binding to its 3'-untranslated region. Furthermore, the effects of FOXM1 underexpression were comparable with the effects induced by miR-197 overexpression in cervical cancer cells, suggesting that FOXM1 acted as a downstream effector in miR-197-mediated proliferation and invasion of cervical cancer cells. The results of the present study suggested that miR-197 inhibited growth and metastasis of cervical cancer by directly targeting FOXM1.

Ag1 Pd1 Nanoparticles-Reduced Graphene Oxide as a Highly Efficient and Recyclable Catalyst for Direct Aryl C-H Olefination.

The efficient and selective palladium-catalyzed activation of C-H bonds is of great importance for the construction of diverse bioactive molecules. Despite significant progress, the inability to recycle palladium catalysts and the need for additives impedes the practical applications of these reactions. Ag1 Pd1 nanoparticles-reduced graphene oxide (Ag1 Pd1 -rGO) was used as highly efficient and recyclable catalyst for the chelation-assisted ortho C-H bond olefination of amides with acrylates in good yields with a broad substrate scope. The catalyst can be recovered and reused at least 5 times without losing activity. A synergistic effect between the Ag and Pd atoms on the catalytic activity was found, and a plausible mechanism for the AgPd-rGO catalyzed C-H olefination is proposed. These findings suggest that the search for such Pd-based bimetallic alloy nanoparticles is a new method towards the development of superior recyclable catalysts for direct aryl C-H functionalization under mild conditions.

Copper-Catalyzed Direct Acyloxylation of C(sp2)-H Bonds in Aromatic Amides.

Copper-catalyzed ortho-acyloxylation of the sp2 C-H bond of aryl amides with carboxylic acids is reported. Benzoic acids, cinnamic acids, and aliphatic acids can be involved, and the desired products were obtained in moderate to good yields. This procedure is compatible with a wide range of functional groups and heteroarenes without the use of any ligands or additives. This method provides an operationally simple approach for the synthesis of benzoate and cinnamate.

Cu2O-Au nanocomposites for enzyme-free glucose sensing with enhanced performances.

A facile method for the synthesis of Cu(2)O-Au nanocomposites has been reported by injecting Cu(2)O nanocubes into Au precursor directly with the assistance of ultrasound radiation at room temperature. The ultrasound radiation is not a necessary requirement but can make the distribution of Au nanoparticles more homogenous. The formation of Cu(2)O-Au nanocomposites is attributed to following two reasons. The first one is the difference in the reduction potential between Cu(2+)/Cu(2)O and AuCl(4)(-)/Au, which can also be considered as the driving force for the redox reaction. The other one is the low lattice mismatch between (200) planes of Cu(2)O and (200) facets of Au, which is favorable for the formation of heterostructure. The electrochemical investigation demonstrates that the performances of Cu(2)O nanocubes in enzyme-free glucose sensing have been improved significantly after the decoration of Au nanoparticles which may be derived from the polarization effect provided by Au nanoparticles. As-prepared Cu(2)O-Au nanocomposites have great potential in enzyme-free glucose sensing.

Aligned ZnO nanorods: a useful film to fabricate amperometric glucose biosensor.

A novel amperometric glucose biosensor has been fabricated on the basis of aligned ZnO nanorod film grown on ITO directly. Glucose oxidase immobilized on the surface of ZnO nanorods are very stable with highly catalytic activity during the measurements, Because of the novel properties of ZnO, such as biocompatibility, non-toxicity, chemical stability, electrochemical activities and high isoelectric point, and the protection effect of Nifion membrane cast on the surface of the film. This biosensor displays excellent analytical performance over a wide linear range along with good selectivity. Interference from uric acid and ascorbic acid which usually coexist with glucose in practical samples has been found to be negligible. This method may be used to construct other amperometric biosensors using aligned nanorod/nanowire films.

Carboxyl enriched monodisperse porous Fe3O4 nanoparticles with extraordinary sustained-release property.

Carboxyl-enriched monodisperse porous Fe3O4 nanoparticles with diameters of about 85-nm have been synthesized via a simple hydrothermal method. The porous structure of the product is confirmed further by transmission electron microscopy (TEM) observation and nitrogen sorption measurement with a Brunauer-Emmett-Teller (BET) surface area about 36.61 m2/g. An IR spectrum of the sample identifies that abundant carboxylate groups are formed on the surface of the nanoparticles as well as the pore surface. Because of the confined effect of the nanochannels in the nanoparticles and carboxyl-functionalized Fe3O4 nanoparticles, and the strong interaction between ibuprofen and COO-, as-prepared porous nanoparticles show a more extraordinary sustained-release property than that of hollow silica nanoparticles in vitro. This result suggests that as-prepared porous nanoparticles can also be used for the targeted delivery of other aromatic acid drugs.

Magnetic chitosan nanocomposites: a useful recyclable tool for heavy metal ion removal.

Magnetic chitosan nanocomposites have been synthesized on the basis of amine-functionalized magnetite nanoparticles. These nanocomposites can be removed conveniently from water with the help of an external magnet because of their exceptional properties. The nanocomposites were applied to remove heavy metal ions from water because chitosan that is inactive on the surface of the magnetic nanoparticles is coordinated with them. The interaction between chitosan and heavy metal ions is reversible, which means that those ions can be removed from chitosan in weak acidic deionized water with the assistance of ultrasound radiation. On the basis of the reasons referred to above, synthesized magnetic chitosan nanocomposites were used as a useful recyclable tool for heavy metal ion removal. This work provides a potential platform for developing a unique route for heavy metal ion removal from wastewater.