The WD40 repeat-containing F-box proteins (FBXWs) family belongs to three major classes of F-box proteins. Consistent with the function of other F-box proteins, FBXWs are E3 ubiquitin ligases to mediate protease-dependent protein degradation. However, the roles of several FBXWs remain elusive. In the present study, via integrative analysis of transcriptome profiles from The Cancer Genome Atlas (TCGA) datasets, we found that FBXW9 was upregulated in the majority of cancer types, including breast cancer. FBXW expression was correlated with the prognosis of patients with various types of cancers, especially for FBXW4, 5, 9, and 10. Moreover, FBXWs were associated with infiltration of immune cells, and expression of FBXW9 was associated with poor prognosis of patients receiving anti-PD1 therapy. We predicted several substrates of FBXW9, and TP53 was the hub gene in the list. Downregulation of FBXW9 increased the expression of p21, a target of TP53, in breast cancer cells. FBXW9 was also strongly correlated with cancer cell stemness, and genes correlated with FBXW9 were associated with several MYC activities according to gene enrichment analysis in breast cancer. Cell-based assays showed that silencing of FBXW9 inhibited cell proliferation and cell cycle progression in breast cancer cells. Our study highlights the potential role of FBXW9 as a biomarker and promising target for patients with breast cancer. Full article

The MYB (v-MYB avian myeloblastosis viral oncogene homolog) transcription factor (TF) family has numerous members with complex and diverse functions, which play an indispensable role in regulating the response of plants to stress. In this study, a new 1R-MYB TF gene was obtained from Fragaria vesca (a diploid strawberry) by cloning technology and given a new name, FvMYB114. According to the subcellular localization results, FvMYB114 protein was a nuclear localization protein. Overexpression of FvMYB114 greatly enhanced the adaptability and tolerance of Arabidopsis thaliana to salt and low temperature. Under salt and cold stress, the transgenic plants had greater proline and chlorophyll contents and higher activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) than the wild-type (WT) and unloaded-line (UL) A. thaliana. However, malondialdehyde (MDA) was higher in the WT and UL lines. These results suggested that FvMYB114 may be involved in regulating the response of A. thaliana to salt stress and cold stress. FvMYB114 can also promote the expression of genes, such as the genes AtSOS1/3, AtNHX1 and AtLEA3 related to salt stress and the genes AtCCA1, AtCOR4 and AtCBF1/3 related to cold stress, further improving the tolerance of transgenic plants to salt and cold stress. Full article

Mixed-phenotype acute leukemia (MPAL), a rare and heterogeneous category of acute leukemia, is characterized by cross-lineage antigen expression. Leukemic blasts in MPAL can be represented either by one population with multiple markers of different lineages or by several single-lineage populations. In some cases, a major blast population may coexist with a smaller population that has minor immunophenotypic abnormalities and may be missed even by an experienced pathologist. To avoid misdiagnosis, we suggest sorting doubtful populations and leukemic blasts and searching for similar genetic aberrations. Using this approach, we examined questionable monocytic populations in five patients with dominant leukemic populations of B-lymphoblastic origin. Cell populations were isolated either for fluorescence in situ hybridization or for clonality assessment by multiplex PCR or next-generation sequencing. In all cases, monocytic cells shared the same gene rearrangements with dominant leukemic populations, unequivocally confirming the same leukemic origin. This approach is able to identify implicit cases of MPAL and therefore leads to the necessary clinical management for patients. Full article

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the occurrence of cognitive deficits. With no effective treatments available, the search for new effective therapies has become a major focus of interest. In the present study, we describe the potential therapeutic effect of Artemisia annua (A. annua) extract on AD. Nine-month-old female 3xTg AD mice were treated with A. annua extract for three months via oral administration. Animals assigned to WT and model groups were administrated with an equal volume of water for the same period. Treated AD mice significantly improved the cognitive deficits and exhibited reduced Aβ accumulation, hyper-phosphorylation of tau, inflammatory factor release and apoptosis when compared with untreated AD mice. Moreover, A. annua extract promoted the survival and proliferation of neural progenitor cells (NPS) and increased the expression of synaptic proteins. Further assessment of the implicated mechanisms revealed that A. annua extract regulates the YAP signaling pathway in 3xTg AD mice. Further studies comprised the incubation of PC12 cells with Aβ_1–42 at a concentration of 8 μM with or without different concentrations of A. annua extract for 24 h. Obtained ROS levels, mitochondrial membrane potential, caspase-3 activity, neuronal cell apoptosis and assessment of the signaling pathways involved was performed using western blot and immunofluorescence staining. The obtained results showed that A. annua extract significantly reversed the Aβ_1–42-induced increase in ROS levels, caspase-3 activity and neuronal cell apoptosis in vitro. Moreover, either inhibition of the YAP signaling pathway, using a specific inhibitor or CRISPR cas9 knockout of YAP gene, reduced the neuroprotective effect of the A. annua extract. These findings suggest that A. annua extract may be a new multi-target anti-AD drug with potential use in the prevention and treatment of AD. Full article

Extracellular vesicles (EVs) from allogeneic-tissue-derived mesenchymal stem cells (MSCs) are promising to improve Sjögren’s syndrome (SS) treatment, but their application is hindered by high variations in and limited expandability of tissue MSCs. We derived standardized and scalable MSCs from iPS cells (iMSCs) and reported that EVs from young but not aging iMSCs (iEVs) inhibited sialadenitis onset in SS mouse models. Here, we aim to determine cellular mechanisms and optimization approaches of SS-inhibitory effects of iEVs. In NOD.B10.H2^b mice at the pre-disease stage of SS, we examined the biodistribution and recipient cells of iEVs with imaging, flow cytometry, and qRT-PCR. Intravenously infused iEVs accumulated in the spleen but not salivary glands or cervical lymph nodes and were mainly taken up by macrophages. In the spleen, young but not aging iEVs increased M2 macrophages, decreased Th17 cells, and changed expression of related immunomodulatory molecules. Loading miR-125b inhibitors into aging iEVs significantly improved their effects on repressing sialadenitis onset and regulating immunomodulatory splenocytes. These data indicated that young but not aging iEVs suppress SS onset by regulating immunomodulatory splenocytes, and inhibiting miR-125b in aging iEVs restores such effects, which is promising to maximize production of effective iEVs from highly expanded iMSCs for future clinical application. Full article

Despite the wide application of radiotherapy in HCC, radiotherapy efficacy is sometimes limited due to radioresistance. Although radioresistance is reported with high glycolysis, the underlying mechanism between radioresistance and cancer metabolism, as well as the role of cathepsin H (CTSH) within it, remain unclear. In this study, tumor-bearing models and HCC cell lines were used to observe the effect of CTSH on radioresistance. Proteome mass spectrometry, followed by enrichment analysis, were used to investigate the cascades and targets regulated by CTSH. Technologies such as immunofluorescence co-localization flow cytometry and Western blot were used for further detection and verification. Through these methods, we originally found CTSH knockdown (KD) perturbed aerobic glycolysis and enhanced aerobic respiration, and thus promoted apoptosis through up-regulation and the release of proapoptotic factors such as AIFM1, HTRA2, and DIABLO, consequently reducing radioresistance. We also found that CTSH, together with its regulatory targets (such as PFKL, HK2, LDH, and AIFM1), was correlated with tumorigenesis and poor prognosis. In summary, our study found that the cancer metabolic switch and apoptosis were regulated by CTSH signaling, leading to the occurrence of radioresistance in HCC cells and suggesting the potential value of HCC diagnosis and therapy. Full article

Fer and its sperm and cancer specific variant, FerT, are non-receptor tyrosine kinases which play roles in cancer progression and metastasis. Recent studies have shed light on the regulatory role of these kinases in ensuring proper sperm function. Comparison of the regulatory cascades in which Fer and FerT are engaged in sperm and cancer cells presents an interesting picture, in which similar regulatory interactions of these enzymes are integrated in a similar or different regulatory context in the two cell types. These diverse compositions extend from the involvement of Fer in modulation of actin cytoskeleton integrity and function, to the unique regulatory interactions of Fer with PARP-1 and the PP1 phosphatase. Furthermore, recent findings link the metabolic regulatory roles of Fer and FerT in sperm and cancer cells. In the current review, we discuss the above detailed aspects, which portray Fer and FerT as new regulatory links between sperm and malignant cells. This perspective view can endow us with new analytical and research tools that will deepen our understanding of the regulatory trajectories and networks that govern these two multi-layered systems. Full article

The synthesis of four pentacoordinated organotin(IV) complexes prepared in a one-pot reaction from 2-hydroxy-1-naphthaldehyde, 2-amino-3-hydroxypyridine and organotin oxides is reported. The complexes were characterized by UV-Vis, IR, MS, ¹H, ¹³C and ¹¹⁹Sn NMR techniques. The compound based on 2,2-diphenyl-6-aza-1,3-dioxa-2-stannanaphtho[1,2-h]pyrido[3,2-d]cyclononene revealed the formation of a monomeric complex with a distorted five-coordinated molecular geometry intermediate between the trigonal bipyramidal and square pyramidal. In order to find possible applications in photovoltaic devices, hybrid films of organotin(IV) complexes embedded in poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) with graphene were deposited. The topographic and mechanical properties were examined. The film with the complex integrated into the cyclohexyl substituent has high plastic deformation, with a maximum stress of 1.69 × 10⁷ Pa and a Knoop hardness of 0.061. The lowest values of 1.85 eV for the onset gap and 3.53 eV for the energy gap were obtained for the heterostructure having the complex with the phenyl substituent. Bulk heterojunction devices were fabricated; these devices showed ohmic behavior at low voltages and a space-charge-limited current (SCLC) conduction mechanism at higher voltages. A value of 0.02 A was found for the maximum carried current. The SCLC mechanism suggests hole mobility values of between 2.62 × 10⁻² and 3.63 cm²/V^.s and concentrations of thermally excited holes between 2.96 × 10¹⁸ and 4.38 × 10¹⁸ m⁻³. Full article

Feline calicivirus (FCV) is a feline pathogen that can cause severe upper respiratory tract disease in cats, thus posing a major threat to their health. The exact pathogenic mechanism of FCV is still unclear, although it has been identified as having the ability to induce immune depression. In this study, we discovered that FCV infection triggers autophagy and that its non-structural proteins, P30, P32, and P39, are responsible for initiating this process. Additionally, we observed that altering autophagy levels via chemical modulation resulted in different influences on FCV replication. Moreover, our findings indicate that autophagy can modify the innate immunity induced by FCV infection, with increased autophagy further suppressing FCV-induced RIG-I signal transduction. This research provides insights into the mechanism of FCV replication and has the potential to aid in the development of autophagy-targeted drugs to inhibit or prevent FCV infection. Full article

The root is an important organ for obtaining nutrients and absorbing water and carbohydrates, and it depends on various endogenous and external environmental stimulations such as light, temperature, water, plant hormones, and metabolic constituents. Auxin, as an essential plant hormone, can mediate rooting under different light treatments. Therefore, this review focuses on summarizing the functions and mechanisms of light-regulated auxin signaling in root development. Some light-response components such as phytochromes (PHYs), cryptochromes (CRYs), phototropins (PHOTs), phytochrome-interacting factors (PIFs) and constitutive photo-morphorgenic 1 (COP1) regulate root development. Moreover, light mediates the primary root, lateral root, adventitious root, root hair, rhizoid, and seminal and crown root development via the auxin signaling transduction pathway. Additionally, the effect of light through the auxin signal on root negative phototropism, gravitropism, root greening and the root branching of plants is also illustrated. The review also summarizes diverse light target genes in response to auxin signaling during rooting. We conclude that the mechanism of light-mediated root development via auxin signaling is complex, and it mainly concerns in the differences in plant species, such as barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.), changes of transcript levels and endogenous IAA content. Hence, the effect of light-involved auxin signaling on root growth and development is definitely a hot issue to explore in the horticultural studies now and in the future. Full article

The presence of cancer stem cells (CSCs) has been associated with the induction of drug resistance and disease recurrence after therapy. 5-Fluorouracil (5FU) is widely used as the first-line treatment of colorectal cancer (CRC). However, its effectiveness may be limited by the induction of drug resistance in tumor cells. The Wnt pathway plays a key role in the development and CRC progression, but it is not clearly established how it is involved in CSCs resistance to treatment. This work aimed to investigate the role played by the canonical Wnt/β-catenin pathway in CSCs resistance to 5FU treatment. Using tumor spheroids as a model of CSCs enrichment of CRC cell lines with different Wnt/β-catenin contexts, we found that 5FU induces in all CRC spheroids tested cell death, DNA damage, and quiescence, but in different proportions for each one: RKO spheroids were very sensitive to 5FU, while SW480 were less susceptible, and the SW620 spheroids, the metastatic derivative of SW480 cells, displayed the highest resistance to death, high clonogenic capacity, and the highest ability for regrowth after 5FU treatment. Activating the canonical Wnt pathway with Wnt3a in RKO spheroids decreased the 5FU-induced cell death. But the Wnt/β-catenin pathway inhibition with Adavivint alone or in combination with 5FU in spheroids with aberrant activation of this pathway produced a severe cytostatic effect compromising their clonogenic capacity and diminishing the stem cell markers expression. Remarkably, this combined treatment also induced the survival of a small cell subpopulation that could exit the arrest, recover SOX2 levels, and re-grow after treatment. Full article

Cannabis is the most used drug of abuse worldwide. It is well established that the most abundant phytocannabinoids in this plant are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These two compounds have remarkably similar chemical structures yet vastly different effects in the brain. By binding to the same receptors, THC is psychoactive, while CBD has anxiolytic and antipsychotic properties. Lately, a variety of hemp-based products, including CBD and THC, have become widely available in the food and health industry, and medical and recreational use of cannabis has been legalized in many states/countries. As a result, people, including youths, are consuming CBD because it is considered “safe”. An extensive literature exists evaluating the harmful effects of THC in both adults and adolescents, but little is known about the long-term effects of CBD exposure, especially in adolescence. The aim of this review is to collect preclinical and clinical evidence about the effects of cannabidiol. Full article

Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated; 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline; 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer’s disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment. Full article

Naturally brown colored cotton (NBCC) is becoming increasingly popular due to its natural properties of coloration. However, poor fiber quality and color fading are key issues that are hindering the cultivation of naturally colored cotton. In this study, based on transcriptome and metabolome of 18 days post-anthesis (DPA), we compared the variations of pigment formation in two brown cotton fibers (DCF and LCF), with white cotton fiber (WCF) belonging to a near-isogenic line. A transcriptome study revealed a total of 15,785 differentially expressed genes significantly enriched in the flavonoid biosynthesis pathway. Furthermore, for flavonoid biosynthesis-related genes, such as flavonoid 3′5′-hydroxylase (F3′5′H), anthocyanidin synthase (ANS), anthocyanidin reductase (ANR), chalcone synthase (CHS), dihydroflavonol 4-reductase (DFR), and chalcone isomerase (CHI), their expressions significantly increased in LCF compared with DCF and WCF. Moreover, transcription factors MYB and bHLH were significantly expressed in LCF and DCF. Most flavonoid-related metabolites (myricetin naringenin, catechin, epicatechin-epiafzelechin, and epigallocatechin) were found to be more highly up-regulated in LCF and DCF than WCF. These findings reveal the regulatory mechanism controlling different brown pigmentation in cotton fibers and elucidate the need for the proper selection of high-quality brown cotton fiber breeding lines for promising fiber quality and durable brown color pigmentation. Full article

This study covers the analysis of isomeric forms of nitrophthalic acids with pyridine. This work dwells on the complementary experimental (X-ray, IR and Raman) and theoretical (Car-Parrinello Molecular Dynamics (CPMD) and Density Functional Theory (DFT)) studies of the obtained complexes. The conducted studies showed that steric repulsion between the nitro group in ortho-position and the carboxyl group causes significant isomeric changes. Modeling of the nitrophthalic acid—pyridine complex yielded a short strong intramolecular hydrogen bond (SSHB). The transition energy from the isomeric form with an intermolecular hydrogen bond to the isomeric form with an intramolecular hydrogen bond was estimated. Full article