Endoplasmic reticulum protein ALTERED MERISTEM PROGRAM 1 negatively regulates senescence in Arabidopsis.

Plant senescence is a highly regulated developmental program crucial for nutrient reallocation and stress adaptation in response to developmental and environmental cues. Stress-induced and age-dependent natural senescence share both overlapping and distinct molecular responses and regulatory schemes. Previously, we have utilized a carbon-deprivation (C-deprivation) senescence assay using Arabidopsis (Arabidopsis thaliana) seedlings to investigate senescence regulation. Here we conducted a comprehensive time-resolved transcriptomic analysis of Arabidopsis wild type seedlings subjected to C-deprivation treatment at multiple time points, unveiling substantial temporal changes and distinct gene expression patterns. Moreover, we identified ALTERED MERISTEM PROGRAM 1 (AMP1), encoding an endoplasmic reticulum protein, as a potential regulator of senescence based on its expression profile. By characterizing loss-of-function alleles and overexpression lines of AMP1, we confirmed its role as a negative regulator of plant senescence. Genetic analyses further revealed a synergistic interaction between AMP1 and the autophagy pathway in regulating senescence. Additionally, we discovered a functional association between AMP1 and the endosome-localized ABNORMAL SHOOT3 (ABS3)-mediated senescence pathway and positioned key senescence-promoting transcription factors downstream of AMP1. Overall, our findings shed light on the molecular intricacies of transcriptome reprogramming during C-deprivation-induced senescence and the functional interplay among endomembrane compartments in controlling plant senescence.

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Mitochondria are the main site of energy metabolism within cells, generating a substantial amount of ATP to supply energy to the human body. Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia, suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy. Therefore, understanding the research progress on the genetic mechanisms, pathological processes, image manifestations of schizophrenia and mitochondrial quality control, and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia, can provide references for further research.

Combined exposure to decabromodiphenyl ether and nano zero-valent iron aggravated oxidative stress and interfered with metabolism in earthworms.

Decabromodiphenyl ether (BDE-209) is a common brominated flame retardant in electronic waste, and nano zero-valent iron (nZVI) is a new material in the field of environmental remediation. Little is known about how BDE-209 and nZVI combined exposure influences soil organisms. During the 28 days study, we determined the effects of single and combined exposures to BDE-209 and nZVI on the oxidative stress and metabolic response of earthworms (Eisenia fetida). On day 7, compared to CK, malondialdehyde (MDA) content increased in most combined exposure groups. To remove MDA and reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities were induced in most combined exposure groups. On day 28, compared to CK, the activities of SOD and CAT were inhibited, while POD activity was significantly induced, indicating that POD plays an important role in scavenging ROS. Combined exposure to BDE-209 and nZVI significantly affected amino acid biosynthesis and metabolism, purine metabolism, and aminoacyl-tRNA biosynthesis pathways, interfered with energy metabolism, and aggravated oxidative stress in earthworms. These findings provide a basis for assessing the ecological impacts of using nZVI to remediate soils contaminated with BDE-209 from electronic waste.

TRANSPARENT TESTA GLABRA2 defines trichome cell shape by modulating actin cytoskeleton in Arabidopsis thaliana.

The Arabidopsis (Arabidopsis thaliana) TRANSPARENT TESTA GLABRA2 (TTG2) gene encodes a WRKY transcription factor that regulates a range of development events like trichome, seed coat, and atrichoblast formation. Loss-of-function of TTG2 was previously shown to reduce or eliminate trichome specification and branching. Here, we report the identification of an allele of TTG2, ttg2-6. In contrast to the ttg2 mutants described before, ttg2-6 displayed unique trichome phenotypes. Some ttg2-6 mutant trichomes were hyper-branched, whereas others were hypo-branched, distorted, or clustered. Further, we found that in addition to specifically activating R3 MYB transcription factor TRIPTYCHON (TRY) to modulate trichome specification, TTG2 also integrated cytoskeletal signaling to regulate trichome morphogenesis. The ttg2-6 trichomes displayed aberrant cortical microtubules (cMTs) and actin filaments (F-actin) configurations. Moreover, genetic and biochemical analyses showed that TTG2 could directly bind to the promoter and regulate the expression of BRICK1 (BRK1), which encodes a subunit of the actin nucleation promoting complex suppressor of cyclic AMP repressor (SCAR)/Wiskott-Aldrich syndrome protein family verprolin homologous protein (WAVE). Collectively, taking advantage of ttg2-6, we uncovered a function for TTG2 in facilitating cMTs and F-actin cytoskeleton-dependent trichome development, providing insight into cellular signaling events downstream of the core transcriptional regulation during trichome development in Arabidopsis.

Insight into the differential toxicity of PFOA and PFBA based on a 3D-cultured MDA-MB-231 cell model.

Perfluoroalkyl substances (PFASs) are a category of high-concerned emerging contaminants which are suspected to correlate with various human adverse health outcomes including tumors. It is also a question whether short-chain PFASs are qualified alternatives under the regulation of long-chain PFASs. In this study, a three-dimensional (3D) culture system based on Gelatin methacrylate (GelMA) hydrogel matrix was used to investigate the impacts of 120-h perfluorooctanoic acid (PFOA) and perfluorobutanoic acid (PFBA) exposure of MDA-MB-231 cells. The results showed that PFOA exposure promoted the proliferation, migration, and invasion of MDA-MB-231 cells in an environmentally relevant concentration range (0.1 to 10 µM), exhibiting a clear malignant-promoting risk. In contrast, PFBA only showed a trend to induce non-invasive cell migration. Hippo/YAP signaling pathway was identified as the contributor to the differences between the two PFASs. PFOA but PFBA reduced YAP phosphorylation and increased the nuclear content of YAP, which further facilitated abundant key factors of epithelial-mesenchymal transition (EMT) process. Our results provided a new idea for the carcinogenicity of PFOA using a 3D-based paradigm. Although the effects by PFBA were much milder than PFOA in the current test duration, the cell model suitable for longer exposure is still necessary to better assess the safety of alternative short-chain PFASs.

BDE-47 Causes Depression-like Effects in Zebrafish Larvae via a Non-Image-Forming Visual Mechanism.

Depression is a high-incidence mood disorder that is frequently accompanied by sleep disturbances, which can be triggered by the non-image-forming (NIF) visual system. Therefore, we hypothesize that polybrominated diphenyl ethers are known to induce visual impairment that could promote depression by disrupting the NIF visual pathway. In this study, zebrafish larvae were exposed to BDE-47 at environmentally relevant concentrations (2.5 and 25 µg/L). BDE-47 caused melanopsin genes that dominate the NIF visual system that fell at night (p < 0.05) but rose in the morning (p < 0.05). Such bidirectional difference transmitted to clock genes and neuropeptides in the suprachiasmatic nucleus and impacted the adjacent serotonin system. However, indicative factors of depression, including serta, htr1aa, and aanat2, were unidirectionally increased 1.3- to 1.6-fold (p < 0.05). They were consistent with the increase in nighttime thigmotaxis (p < 0.05) and circadian hypoactivity (p < 0.05). The results of melanopsin antagonism also indicated that these consequences were possibly due to the combination of direct photoentrainment by melanopsin and circadian disruption originating from melanopsin. Collectively, our findings revealed that BDE-47 exposure disrupted the NIF visual pathway and resulted in depression-like effects, which may further exert profound health effects like mood disorders.

Dynamics and mechanisms of bioaccumulation and elimination of nonylphenol in zebrafish.

Nonylphenol (NP) has been widely concerned for its endocrine disrupting effects. In this study, we investigated the accumulation and elimination of NP for the whole body and trunk of zebrafish (Danio rerio). The results show that the LC50 values of NP in zebrafish ranged from 474 µg·L-1 (24-h exposure) to 238 µg·L-1 (96-h exposure). Meanwhile, the NP concentrations in zebrafish during the depuration stage fitted the first-order kinetic model well, and the depuration rate constant (K2) was reduced from 0.412 d-1 to 0.2827 d-1 with higher NP. The half-life (t1/2) of NP was 1.75-2.45 d in the whole fish and 0.56-0.86 d in the trunk under low to high NP, respectively. Both the accumulation and elimination of NP in trunk were faster than those in whole fish, indicating the preferential transfer from viscera to muscle and rapidly diffusion in reverse. The bioconcentration factors (BCFSS) of NP were 104-112 L·kg-1 in whole body and 76-104 L·kg-1 in trunk, respectively, suggesting that the muscle was a major position for NP storage.

Tumor-suppressive miR-323a inhibits pancreatic cancer cell proliferation and glycolysis through targeting HK-2.

Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 85% of all malignant pancreatic exocrine tumors and is one of the main causes of cancer-related fatalities. PDAC is characterized by a high glycolytic rate to ensure its survival as a result of hypovascularization and the desmoplastic reaction. In this study, microRNA 323a (miR-323a) was shown to be downregulated within pancreatic cancer tissues and cells, and enriched in the glucose metabolism pathway. In vitro, overexpression of miR-323a suppressed cell viability, DNA synthesis, and colony formation; in vivo, miR-323a overexpression suppressed the tumor growth within a xenograft mouse model. Regarding cellular glycolysis, miR-323a overexpression decreased glucose-6-phosphate levels, inhibited glucose uptake, and reduced lactate and adenosine triphosphate production. miR-323a was found to directly target hexokinase 2 (HK-2) and negatively regulated HK-2 expression. HK-2 overexpression exerted oncogenic effects on pancreatic cancer cells and promoted cellular glycolysis; more importantly, HK-2 overexpression partially eliminated the effects of miR-323a overexpression. In conclusion, miR-323a is downregulated within pancreatic cancer and serves as a tumor-suppressive miRNA through inhibiting cancer cell proliferation and glycolysis. miR-323a exerts its tumor-suppressive effects through targeting HK-2.

The wheat TaIQD3D-6 gene encodes a microtubule-associated protein and regulates cell morphogenesis in Arabidopsis.

A plethora of microtubule-associated proteins (MAPs) modulate the dynamics of microtubules (MTs) to ensure the proper elaboration of developmental programs in plants. Among the plant-specific MAPs are the IQ67 domain (IQD) family proteins. Despite the great progress in elucidating IQD protein functions, the majority of IQD proteins, especially IQDs in crop species, remain to be functionally explored. In this study, we identified 78 putative IQD family genes in the genome of hexaploid wheat (Triticum aestivum). Phylogenetic analysis of wheat and Arabidopsis IQDs supports the previous notion that the expansion of the IQD family coincides with plant terrestrialization. Further characterization of one TaIQD, TaIQD3D-6, revealed that TaIQD3D-6 directly binds to MTs and free tubulins in vitro and is associated with cortical MTs in interphase cells in vivo. Overexpressing TaIQD3D-6 in Arabidopsis leads to a spectrum of phenotypes that are indicative of perturbed MT homeostasis, including spiral growth, hypersensitivity to MT-destabilizing drugs, defects in cell morphogenesis, and altered organization of cMT arrays. Finally, we determined that TaIQD3D-6-GFP localizes to the expanding cell plate during cytokinesis and the overexpression of TaIQD3D-6 interferes with asymmetric cell division in the stomatal lineage in Arabidopsis. In summary, our findings establish that TaIQD3D-6 is a MAP that regulates plant cell and organ morphogenesis and provide new insights into the functions of crop IQD proteins.

Optimizing the dynamic treatment regime of in-hospital warfarin anticoagulation in patients after surgical valve replacement using reinforcement learning.

OBJECTIVE: Warfarin anticoagulation management requires sequential decision-making to adjust dosages based on patients' evolving states continuously. We aimed to leverage reinforcement learning (RL) to optimize the dynamic in-hospital warfarin dosing in patients after surgical valve replacement (SVR). MATERIALS AND METHODS: 10 408 SVR cases with warfarin dosage-response data were retrospectively collected to develop and test an RL algorithm that can continuously recommend daily warfarin doses based on patients' evolving multidimensional states. The RL algorithm was compared with clinicians' actual practice and other machine learning and clinical decision rule-based algorithms. The primary outcome was the ratio of patients without in-hospital INRs >3.0 and the INR at discharge within the target range (1.8-2.5) (excellent responders). The secondary outcomes were the safety responder ratio (no INRs >3.0) and the target responder ratio (the discharge INR within 1.8-2.5). RESULTS: In the test set (n = 1260), the excellent responder ratio under clinicians' guidance was significantly lower than the RL algorithm: 41.6% versus 80.8% (relative risk [RR], 0.51; 95% confidence interval [CI], 0.48-0.55), also the safety responder ratio: 83.1% versus 99.5% (RR, 0.83; 95% CI, 0.81-0.86), and the target responder ratio: 49.7% versus 81.1% (RR, 0.61; 95% CI, 0.58-0.65). The RL algorithms performed significantly better than all the other algorithms. Compared with clinicians' actual practice, the RL-optimized INR trajectory reached and maintained within the target range significantly faster and longer. DISCUSSION: RL could offer interactive, practical clinical decision support for sequential decision-making tasks and is potentially adaptable for varied clinical scenarios. Prospective validation is needed. CONCLUSION: An RL algorithm significantly optimized the post-operation warfarin anticoagulation quality compared with clinicians' actual practice, suggesting its potential for challenging sequential decision-making tasks.

Effects of TiZn3 and TiZn16 components on the microstructure and mechanical performance of Ti-6Al-4 V alloy joints formed via ultrasonic assisted brazing using pre-galvanized workpieces.

While the use of a Zn interlayer has been demonstrated to reduce the temperature required for joining easily oxidized metal alloys in atmospheric environments, the effects of reactions between the titanium alloy workpieces and the Zn interlayer on the mechanical performance of the finished joints are poorly understood. The present work addresses this issue by evaluating the chemical compositions at the interfaces of pre-galvanized Ti-6Al-4 V alloys joined at 420 °C in an atmospheric environment by ultrasonic-assisted brazing, and relating the observed compositions to the mechanical performances of the joints. The Ti-6Al-4 V alloy workpieces are first wetted by pure Zn using an ultrasonic assisted hot dip galvanizing (U-HDG). The obtained ultrasonic excitations are demonstrated to destroy the oxide film on the surfaces of the Ti-6Al-4 V workpieces and promote reactions between Ti and Zn at the interfaces. The plating of Zn on the workpiece surfaces is demonstrated to be realized by the formation of intermetallic compounds (IMCs) comprising a uniform TiZn3 layer in contact with the Ti-6Al-4 V surface, followed by a mixed TiZn3 + TiZn16 layer and a η-Zn layer at the outer surface. Application of the ultrasonic-assisted brazing process is demonstrated to maintain uniform TiZn3 layers next to the Ti-6Al-4 V surfaces, while the concentration of the TiZn16 phase near the midpoint of the joints increases with increasing ultrasonic treatment time (UST) from 5 s to 20 s, and the corresponding concentration of the η-Zn phase decreases. The results of mechanical testing demonstrate that the shear strength of the joint obtained with a TiZn3 layer thickness of 8-12 µm and a UST of 10 s is 210 MPa, which is 3.55 times greater than that obtained for joints processed without pre-galvanization.

MOR1/MAP215 acts synergistically with katanin to control cell division and anisotropic cell elongation in Arabidopsis.

The MAP215 family of microtubule (MT) polymerase/nucleation factors and the MT severing enzyme katanin are widely conserved MT-associated proteins (MAPs) across the plant and animal kingdoms. However, how these two essential MAPs coordinate to regulate plant MT dynamics and development remains unknown. Here, we identified novel hypomorphic alleles of MICROTUBULE ORGANIZATION 1 (MOR1), encoding the Arabidopsis thaliana homolog of MAP215, in genetic screens for mutants oversensitive to the MT-destabilizing drug propyzamide. Live imaging in planta revealed that MOR1-green fluorescent protein predominantly tracks the plus-ends of cortical MTs (cMTs) in interphase cells and labels preprophase band, spindle and phragmoplast MT arrays in dividing cells. Remarkably, MOR1 and KATANIN 1 (KTN1), the p60 subunit of Arabidopsis katanin, act synergistically to control the proper formation of plant-specific MT arrays, and consequently, cell division and anisotropic cell expansion. Moreover, MOR1 physically interacts with KTN1 and promotes KTN1-mediated severing of cMTs. Our work establishes the Arabidopsis MOR1-KTN1 interaction as a central functional node dictating MT dynamics and plant growth and development.

Occurrence of veterinary antibiotics in animal manure, compost, and agricultural soil, originating from different feedlots in suburbs of Shanghai, East China.

The present study aims to monitor and assess the occurrence of veterinary antibiotics (VAs) in animal manure, compost, and fertilized soil, originating from different large-scale feedlots. The corresponding concentrations of 39 types of VAs in 8 large-scale feedlots of pig, dairy cow, and poultry were sampled in different seasons and analyzed using LC-MS. The results indicated that 17 types, 16 types, and 5 types of VAs were detected in the swine manure, compost, and fertilized soil with the concentrations of 0.003-17.82, 0.002-9.59, and 0.004-0.007 mg kg-1 (dry matter), respectively; 3 types, 2 types, and 1 type of VAs were detected in the dairy manure, compost, and fertilized soil with the concentrations of 0.003-1.94, 0.014-0.044, and 0.025 mg kg-1 (dry matter), respectively; 7 types, 5 types, and 1 type of VAs were detected in the poultry manure, compost, and fertilized soil with the concentrations of 0.035-1.06, 0.018-0.049, and 0.019 mg kg-1 (dry matter), respectively. The main antibiotic classes persisted in the animal manure and their composting product and fertilized soil were sulfonamides (SAs), macrolides (MAs), and tetracyclines (TCs). Thus, this study would help to adopt strategies in pollution control of VAs and environmental protection of agriculture.

Azithromycin alleviates the severity of rheumatoid arthritis by targeting the unfolded protein response component of glucose-regulated protein 78 (GRP78).

BACKGROUND AND PURPOSE: Azithromycin is a macrolide antibiotic with anti-inflammatory properties. We aim to substantiate the treatment potential of azithromycin in rheumatoid arthritis. EXPERIMENTAL APPROACH: Gene expression profiles were collected by RNA sequencing and the effects of azithromycin were assessed by in vitro and in vivo assays on the effects of azithromycin-mediated blockade of glucose-regulated protein 78 (GRP78). Anti-inflammatory activity of azithromycin was measured in fibroblast-like synoviocytes from rheumatoid arthritis patients and in collagen-induced arthritis in DBA/1 mice. Characterization of the binding of azithromycin to GRP78 was performed using drug affinity responsive target stability, proteomics and cellular thermal shift assays. Azithromycin-mediated inhibition of GRP78 and its relationship to its anti-arthritic activity was assessed. KEY RESULTS: Azithromycin reduced proinflammatory factor production, cell migration, invasion and chemoattraction and enhanced apoptosis, reducing the deleterious inflammatory response of rheumatoid arthritis fibroblast-like synoviocytes in vitro. Azithromycin ameliorated the severity of collagen-induced arthritis lesions as efficiently as the TNFα inhibitor etanercept. Transcriptional analyses suggested that azithromycin treatment impairs signalling cascades associated with cholesterol and lipid biosynthesis. GRP78 was identified as a novel target of azithromycin. Azithromycin-mediated activation of the unfolded protein response via the inhibition of GRP78 activity is required not only for inducing the expression of C/EBP-homologous protein (ChOP) but also for the activating sterol-regulatory element binding protein (SREBP) and its targeted genes involved in cholesterol and lipid biosynthetic processes. Furthermore, deletion of GRP78 abolished the anti-arthritic activity of azithromycin. CONCLUSION AND IMPLICATIONS: These findings indicate that azithromycin can used to treat rheumatoid arthritis.

All-Trans Retinoic Acid Enhances Chemosensitivity to 5-FU by Targeting miR-378c/E2F7 Axis in Colorectal Cancer.

Colorectal carcinoma (CRC), a life-threatening malignancy, has been found to present resistance to 5-fluorouracil (5-FU) and cause a poor prognosis for patients. Previous studies have proved that all-trans retinoic acid (ATRA) could inhibit the development of CRC cells. In addition, miR-378c was discovered to exert a vital role in various cancers. In this study, we utilized MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), transwell assay, and flow cytometry to confirm that ATRA was able to enhance the inhibitory effects of 5-FU on HCT116 cells effectively by promoting cell apoptosis. Then, ENCORI database (http://starbase.sysu.edu.cn/) was employed to predict that miR-378c was downregulated dramatically in CRC and E2F7 was the direct target of miR-378c. QRT-PCR (quantitative real-time polymerase chain reaction) was conducted to verify that the expression level of miR-378c was decreased while E2F7 expression was upregulated in CRC tissues compared with para-carcinoma tissues. Additionally, treatment of 5-FU combined with ATRA could increase miR-378c expression, whereas it decreased the expression of E2F7. Dual-Luciferase Reporter assay results revealed that miR-378c could regulate the load of E2F7 by binding to its 3'UTR directly. Furthermore, miR-378c inhibitor or vector with E2F7 partially counteracted the effects of 5-FU combined with ATRA on viability, migration, invasion, and apoptosis of HCT116 cells. In conclusion, our study aims to confirm that ATRA enhances chemosensitivity to 5-FU of patients with CRC and expound the potential molecular mechanisms.

Bioaccessibility evaluation of pharmaceuticals in market fish with in vitro simulated digestion.

The consumption of pharmaceuticals-contaminated aquatic products could pose risks to human health, and risk assessments considering bioaccessibility can provide better dietary recommendations. In this study, the bioaccessibility of 6 pharmaceuticals (sulfadiazine (SD), sulfapyridine (SPD), roxithromycin (ROX), tylosin (TYL), diclofenac (DIC) and carbamazepine (CMZP)) in several fish species collected from Shanghai markets was evaluated using in vitro simulated digestion. The total mixed pharmaceuticals concentration in freshwater fish were lower than those in marine fish, and statistics showed that the total concentrations of SD, SPD and CMZP in freshwater fish were significantly lower than those of marine fish (p < 0.05). The bioaccessible concentration of each pharmaceutical accounted for 26.3% (TYL) to 101.5% (CMZP) of the total concentration in market fish (n = 70). The bioaccessibility of 6 pharmaceuticals in species of fish was 18.8% (cutlassfish) to 99.6% (bream), which may be related to the physical-chemical properties of the pharmaceutical and the characteristics of the matrix (e.g. lipid content). According to health risk assessments, the consumption of market fish in Shanghai posed no remarkable risk to human health (hazard quotient < 0.099). Ignoring the bioaccessibility of pharmaceuticals in aquatic products might overestimate the human health risks by dietary exposure.

CAR-T Cell Therapy: Challenges and Optimization.

Immunotherapy has emerged as a potent and effective treatment for multiple cancer types. For example, the engineering of T cells through the expression of chimeric antigen receptor (CAR) against tumors has shown remarkable potential. This review outlines clinical applications of CAR-T cell therapy in hematological malignancies and solid tumors, with a focus on the main challenges related to the safety and efficacy of the current CAR-T cell therapy and the promising strategies to maximize antitumor efficacy while minimizing adverse events. Finally, we present the future outlook of CAR-T cell therapy for the treatment against malignancies. We believe that potential problems can be overcome by strategies to further facilitate effective clinical translation and improve the efficacy, especially through the combination of different approaches.

MicroRNA-758 acts as a tumor inhibitor in colorectal cancer through targeting PAX6 and regulating PI3K/AKT pathway.

Recently, a number of microRNAs (miRNAs) have been reported to play different roles in human cancers, including colorectal cancer (CRC). However, the specific role of miR-758 has not been clarified in CRC. Therefore, the aim of the present study was to explore the role of miR-758 in CRC. RT-qPCR and western blot analysis were used to quantify the expression of miR-758 and genes. The function of miR-758 in CRC was investigated using Transwell, CCK-8 and luciferase reporter assays. According to the results, the downregulation of miR-758 expression was associated with aggressive behavior and poor prognosis in CRC patients. miR-758 was shown to restrain the cell viability and metastasis in CRC. In addition, it was confirmed that miR-758 directly targets PAX6 and inhibits CRC progression through targeting PAX6. The results also revealed that miR-758 blocked EMT and PI3K/AKT pathway in CRC. In conclusion, miR-758 acts as a tumor suppressor in CRC by downregulating PAX6.

Over-Expression of a 14-3-3 Protein From Foxtail Millet Improves Plant Tolerance to Salinity Stress in Arabidopsis thaliana.

In plants, 14-3-3 proteins are recognized as mediators of signal transduction and function in both development and stress response. However, there are only a few preliminary functional researches in the C4 crop foxtail millet. Here, phylogenetic analysis categorized foxtail millet 14-3-3s (SiGRFs) into 10 discrete groups (Clusters I to X). Transcriptome and qPCR analyses showed that all the SiGRFs responded to at least one abiotic stress. All but one SiGRF-overexpressing (OE) Arabidopsis thaliana line (SiGRF1) exhibited insensitivity to abiotic stresses during seed germination and seedling growth. Compared with the Col-0 wild-type, SiGRF1-OEs had slightly lower germination rates and smaller leaves. However, flowering time of SiGRF1-OEs occurred earlier than that of Col-0 under high-salt stress. Interaction of SiGRF1 with a foxtail millet E3 ubiquitin-protein ligase (SiRNF1/2) indicates that the proteinase system might hydrolyze SiGRF1. Further investigation showed that SiGRF1 localized in the cytoplasm, and its gene was ubiquitously expressed in various tissues throughout various developmental stages. Additionally, flowering-related genes, WRKY71, FLOWERING LOCUS T, LEAFY, and FRUITFULL, in SiGRF1-OEs exhibited considerably higher expression levels than those in Col-0 under salinity-stressed conditions. Results suggest that SiGRF1 hastens flowering, thereby providing a means for foxtail millet to complete its life cycle and avoid further salt stress.

miR-522 facilitates the prosperities of endometrial carcinoma cells by directly binding to monoamine oxidase B.

It is well known that microRNAs (miRNAs) are crucial regulatory factors in tumorigenesis, as tumor suppressors or cancer-promoting factors. However, the study of endometrial carcinoma relevance in miR-522 is rare, indicating an undefined molecular mechanism for its role. Therefore, we performed this study to examine the role of miR-522 on the biological behaviors of endometrial carcinoma. In this work, we found that miR-522 was highly expressed in endometrial carcinoma and negatively regulated monoamine oxidase B (MAOB) expression. They also have the opposite effect on prognosis of endometrial carcinoma patients. More importantly, miR-522 could decreased MAOB expression by binding to MAOB with a putative site, thereby promoting cell proliferation, migration, and invasion through in vitro functional analyses, including MTT assay, wound-healing and transwell invasion experiments. Upregulation of MAOB rescued the impacts of miR-522 mimic on cell behaviors. In conclusion, our observations demonstrated that miR-522 accelerated the progression of endometrial carcinoma by inhibiting MAOB, which might lead to a novel therapeutic therapy for endometrial carcinoma.