Rice false smut caused by the biotrophic fungal pathogen Ustilaginoidea virens has become one of the most important diseases in rice. The large effector repertory in U. virens plays a crucial role in virulence. However, current knowledge of molecular mechanisms how U. virens effectors target rice immune signaling to promote infection is very limited. In this study, we identified and characterized an essential virulence effector, SCRE4 (Secreted Cysteine-Rich Effector 4), in U. virens. SCRE4 was confirmed as a secreted nuclear effector through yeast secretion, translocation assays and protein subcellular localization, as well as up-regulation during infection. The SCRE4 gene deletion attenuated the virulence of U. virens to rice. Consistently, ectopic expression of SCRE4 in rice inhibited chitin-triggered immunity and enhanced susceptibility to false smut, substantiating that SCRE4 is an essential virulence factor. Furthermore, SCRE4 transcriptionally suppressed the expression of OsARF17, an auxin response factor in rice, which positively regulates rice immune responses and resistance against U. virens. Additionally, the immunosuppressive capacity of SCRE4 depended on its nuclear localization. Therefore, we uncovered a virulence strategy in U. virens that transcriptionally suppresses the expression of the immune positive modulator OsARF17 through nucleus-localized effector SCRE4 to facilitate infection. Full article

Calmodulin-binding transcription activator (CAMTA) is a transcription factor family containing calmodulin (CaM) binding sites and is involved in plant development. Although CAMTAs in Arabidopsis have been extensively investigated, the functions of CAMTAs remain largely unclear in peaches. In this study, we identified five peach CAMTAs which contained conserved CG-1 box, ANK repeats, CaM binding domain (CaMBD) and IQ motifs. Overexpression in tobacco showed that PpCAMTA1/2/3 were located in the nucleus, while PpCAMTA4 and PpCAMTA5 were located in the plasma membrane. Increased expression levels were observed for PpCAMTA1 and PpCAMTA3 during peach fruit ripening. Expression of PpCAMTA1 was induced by cold treatment and was inhibited by ultraviolet B irradiation (UV-B). Driven by AtCAMTA3 promoter, PpCAMTA1/2/3 were overexpressed in Arabidopsis mutant. Here, we characterized peach PpCAMTA1, representing an ortholog of AtCAMTA3. PpCAMTA1 expression in Arabidopsis complements the developmental deficiencies of the camta2,3 mutant, and restored the plant size to the wild type level. Moreover, overexpressing PpCAMTA1 in camta2,3 mutant inhibited salicylic acid (SA) biosynthesis and expression of SA-related genes, resulting in a susceptibility phenotype to Pst DC3000. Taken together, our results provide new insights for CAMTAs in peach fruit and indicate that PpCAMTA1 is associated with response to stresses during development. Full article

Pulmonary fibrosis is a chronic progressive form of interstitial lung disease, characterized by the histopathological pattern of usual interstitial pneumonia. Apart from aberrant alterations of protein-coding genes, dysregulation of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs (circRNAs), is crucial to the initiation and progression of pulmonary fibrosis. CircRNAs are single-stranded RNAs that form covalently closed loops without 5′ caps and 3′ tails. Different from canonical splicing of mRNA, they are produced from the back-splicing of precursor mRNAs and have unique biological functions, as well as potential biomedical implications. They function as important gene regulators through multiple actions, including sponging microRNAs and proteins, regulating transcription, and splicing, as well as protein-coding and translation in a cap-independent manner. This review comprehensively summarizes the alteration and functional role of circRNAs in pulmonary fibrosis, with a focus on the involvement of the circRNA in the context of cell-specific pathophysiology. In addition, we discuss the diagnostic and therapeutic potential of targeting circRNA and their regulatory pathway mediators, which may facilitate the translation of recent advances from bench to bedside in the future. Full article

Taking into consideration the items of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this study reviews application of mechanochemical approaches to the modification of polysaccharides. The ability to avoid toxic solvents, initiators, or catalysts during processes is an important characteristic of the considered approach and is in line with current trends in the world. The mechanisms of chemical transformations in solid reactive systems during mechanical activation, the structure and physicochemical properties of the obtained products, their ability to dissolve and swell in different media, to form films and fibers, to self-organize in solution and stabilize nanodispersed inorganic particles and biologically active substances are considered using a number of polysaccharides and their derivatives as examples. Full article

Polymers remain an integral part of denture fabrication materials, specifically polymethylmetacrylate (PMMA). PMMA has been extensively used, particularly in construction as a denture base material. Nonetheless, various challenges, including microbial threats in the form of candidiasis occurrence, still remain a biological challenge to denture wearers. The present article comprehensively reviews the biomodifications introduced to denture components, in particular denture base material, to improve the overall biological properties, together with physical, mechanical, structural integrity, and optical properties. In addition, fundamental information specifically to PMMA as a conventional denture base material and the causative aetiological microbial agents for biological threat to dentures are explored. Full article

In the cohort of Russian patients with cystic fibrosis, the p.[Leu467Phe;Phe508del] complex allele (legacy name [L467F;F508del]) of the CFTR gene is understudied. In this research, we present the results of frequency evaluation of the [L467F;F508del] complex allele in the Russian Federation among patients with a F508del/F508del genotype, its effect on the clinical course of cystic fibrosis, the intestinal epithelium ionic channel function, and the effectiveness of target therapy. The frequency of the [L467F;F508del] complex allele among patients with homozygous F508del was determined with multiplex ligase-dependent probe amplification followed by polymerase chain reaction and fragment analysis. The function of ionic channels, including the residual CFTR function, and the effectiveness of CFTR modulators was analyzed using intestinal current measurements on rectal biopsy samples and the forskolin-induced swelling assay on organoids. The results showed that the F508del/[L467F;F508del] genotype is present in 8.2% of all Russian patients with F508del in a homozygous state. The clinical course of the disease in patients with the F508del/[L467F;F508del] genotype is severe and does not vary from the course in the cohort with homozygous F508del, although the CFTR channel function is significantly lower. For patients with the F508del/[L467F;F508del] genotype, we can recommend targeted therapy using a combined ivacaftor + tezacaftor + elexacaftor medication. Full article

We previously found that cordycepin inhibits the growth and metastasis formation of MDA-MB-231 cells through the Hedgehog pathway but has not validated this in vivo. In this study, we confirmed cordycepin’s anti-triple-negative breast cancer (TNBC) effect in nude mice and documented its mechanism. We found that cordycepin reduced the volume and weight of MDA-MB-231 xenografts and affected the expression of proliferation-, apoptosis-, epithelial–mesenchymal transition-, and matrix metalloproteinase-related proteins without side effects. RNA sequencing screening, pathway enrichment, and the protein network interaction analysis revealed enriched pathways and targets mainly concentrated on the Hedgehog pathway and its core components of SHH and GLI2. This indicates that the Hedgehog pathway plays a central role in the cordycepin-mediated regulation of growth and metastasis formation in TNBC. The database analysis of the Hedgehog pathway markers (SHH, PTCH1, SMO, GLI1, and GLI2) revealed that the Hedgehog pathway is activated in breast cancer tissues, and its high expression is not conducive to a patient’s survival. Finally, we verified that cordycepin effectively inhibited the Hedgehog pathway in TNBC through Western blotting and immunohistochemistry. This study found that cordycepin could regulate the growth and metastasis formation of TNBC through the Hedgehog pathway in vivo, which provides new insights for targeting and treating breast cancer. Full article

Toll-like receptors (TLR) play an eminent role in the regulation of immune responses to invading pathogens during sepsis. TLR genetic variants might influence individual susceptibility to developing sepsis. The current study aimed to investigate the association of genetic polymorphisms of the TLR2 and TLR4 with the risk of developing sepsis with both a pilot study and in silico tools. Different in silico tools were used to predict the impact of our SNPs on protein structure, stability, and function. Furthermore, in our prospective study, all patients matching the inclusion criteria in the intensive care units (ICU) were included and followed up, and DNA samples were genotyped using real-time polymerase chain reaction (RT-PCR) technology. There was a significant association between TLR2 Arg753Gln polymorphisms and sepsis under the over-dominant model (p = 0.043). In contrast, we did not find a significant difference with the TLR4 Asp299Gly polymorphism with sepsis. However, there was a significant association between TLR4 Asp299Gly polymorphisms and Acinetobacter baumannii infection which is quite a virulent organism in ICU (p = 0.001) and post-surgical cohorts (p = 0.033). Our results conclude that the TLR2 genotype may be a risk factor for sepsis in adult patients. Full article

Furan-oxadiazole structural hybrids belong to the most promising and biologically active classes of oxygen and nitrogen containing five member heterocycles which have expanded therapeutic scope and potential in the fields of pharmacology, medicinal chemistry and pharmaceutics. A novel series 5a–j of benzofuran-oxadiazole molecules incorporating S-alkylated amide linkage have been synthesized using ultrasonic irradiation and screened for bacterial tyrosinase inhibition activity. Most of the synthesized furan-oxadiazole structural motifs exhibited significant tyrosinase inhibition activity in the micromolar range, with one of the derivatives being more potent than the standard drug ascorbic acid. Among the tested compounds, the scaffold 5a displayed more tyrosinase inhibition efficacy IC₅₀ (11 ± 0.25 μM) than the ascorbic acid IC₅₀ (11.5 ± 0.1 μM). Compounds 5b, 5c and 5d efficiently inhibited bacterial tyrosinase with IC₅₀ values in the range of 12.4 ± 0.0–15.5 ± 0.0 μM. The 2-fluorophenylacetamide containing furan-oxadiazole compound 5a may be considered as a potential lead for tyrosinase inhibition with lesser side effects as a skin whitening and malignant melanoma anticancer agent. Full article

Antiviral type I interferons (IFN) produced in the early phase of viral infections effectively inhibit viral replication, prevent virus-mediated tissue damages and promote innate and adaptive immune responses that are all essential to the successful elimination of viruses. As professional type I IFN producing cells, plasmacytoid dendritic cells (pDC) have the ability to rapidly produce waste amounts of type I IFNs. Therefore, their low frequency, dysfunction or decreased capacity to produce type I IFNs might increase the risk of severe viral infections. In accordance with that, declined pDC numbers and delayed or inadequate type I IFN responses could be observed in patients with severe coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as compared to individuals with mild or no symptoms. Thus, besides chronic diseases, all those conditions, which negatively affect the antiviral IFN responses lengthen the list of risk factors for severe COVID-19. In the current review, we would like to briefly discuss the role and dysregulation of pDC/type I IFN axis in COVID-19, and introduce those type I IFN-dependent factors, which account for an increased risk of COVID-19 severity and thus are responsible for the different magnitude of individual immune responses to SARS-CoV-2. Full article

Progesterone is a steroid hormone that performs important functions in mammals. However, studies on its physiological functions in plants have gradually increased in recent years. Therefore, this review summarizes the regulatory functions of progesterone on plant growth and development, as well as its response to stress. Moreover, the plant metabolic processes of progesterone are also discussed. Overall, progesterone is ubiquitous in plants and can regulate numerous plant physiological processes at low concentrations. Since progesterone shares similar characteristics with plant hormones, it is expected to become a candidate for plant hormone. However, most of the current research on progesterone in plants is limited to the physiological level, and more molecular level research is needed to clarify progesterone signaling pathways. Full article

Fusarium wilt caused by Fusarium oxysporum f. sp. lycopersici (Fol) is a common disease that affects tomatoes, which can cause the whole plant to wilt and seriously reduce the production of tomatoes in greenhouses. In this study, the morphological indexes, photosynthetic performance and incidence rate of NSY50 under Fol infection were evaluated. It was found that NSY50 could improve the growth of tomato seedlings and significantly reduce the incidence rate of Fusarium wilt. However, the molecular mechanism of NSY50 that induces resistance to Fusarium wilt is still unclear. We used transcriptomic methods to analyze NSY50-induced resistance to Fol in tomatoes. The results showed that plant defense related genes, such as PR and PAL, were highly expressed in tomato seedlings pretreated with NSY50. At the same time, photosynthetic efficiency, sucrose metabolism, alkaloid biosynthesis and terpene biosynthesis were significantly improved, which played a positive role in reducing the damage caused by Fol infection and enhancing the disease tolerance of seedlings. Through transgenic validation, we identified an important tomato NAC transcription factor, SlNAP1, which was preliminarily confirmed to be effective in relieving the detrimental symptoms induced by Fol. Our findings reveal that P. polymyxa NSY50 is an effective plant-growth-promoting rhizosphere bacterium and also a biocontrol agent of soil-borne diseases, which can significantly improve the resistance of tomato to Fusarium wilt. Full article

Depressive disorders are among the most disabling diseases experienced around the world, and their incidence has significantly increased over the last few decades due to multiple environmental, social, and biological factors. The search for new pharmacological alternatives to treat depression is a global priority. In preclinical research, molecules obtained from plants, such as flavonoids, have shown promising antidepressant-like properties through several mechanisms of action that have not been fully elucidated, including crossing of the blood brain barrier (BBB). This review will focus on discussing the main findings related to the participation of the serotonergic system and brain-derived neurotrophic factor (BDNF) on the antidepressant-like effect of some flavonoids reported by behavioral, neurochemical, and molecular studies. In this sense, evidence shows that depressive individuals have low levels of serotonin and BDNF, while flavonoids can reverse it. Finally, the elucidation of the mechanism used by flavonoids to modulate serotonin and BDNF will contribute to our understanding of the neurobiological bases underlying the antidepressant-like effects produced by these natural compounds. Full article

The western flower thrips, Frankliniella occidentalis Pergande, is an invasive pest that damages agricultural and horticultural crops. The induction of plant defenses and RNA interference (RNAi) technology are potent pest control strategies. This study investigated whether the anti-adaptive ability of F. occidentalis to jasmonic acid (JA)- and methyl jasmonate (MeJA)-induced defenses in kidney bean plants was attenuated after glutathione S-transferase (GST) gene knockdown. The expression of four GSTs in thrips fed JA- and MeJA-induced leaves was analyzed, and FoGSTd1 and FoGSTs1 were upregulated. Exogenous JA- and MeJA-induced defenses led to increases in defensive secondary metabolites (tannins, alkaloids, total phenols, flavonoids, and lignin) in leaves. Metabolome analysis indicated that the JA-induced treatment of leaves led to significant upregulation of defensive metabolites. The activity of GSTs increased in second-instar thrips larvae fed JA- and MeJA-induced leaves. Co-silencing with RNAi simultaneously knocked down FoGSTd1 and FoGSTs1 transcripts and GST activity, and the area damaged by second-instar larvae feeding on JA- and MeJA-induced leaves decreased by 62.22% and 55.24%, respectively. The pupation rate of second-instar larvae also decreased by 39.68% and 39.89%, respectively. Thus, RNAi downregulation of FoGSTd1 and FoGSTs1 reduced the anti-adaptive ability of F. occidentalis to JA- or MeJA-induced defenses in kidney bean plants. Full article

Resveratrol is a naturally occurring polyphenol which has various beneficial effects, such as anti-inflammatory, anti-tumor, anti-aging, antioxidant, and neuroprotective effects, among others. The anti-cancer activity of resveratrol has been related to alterations in sphingolipid metabolism. We analyzed the effect of resveratrol on the enzymes responsible for accumulation of the two sphingolipids with highest functional activity—apoptosis promoting ceramide (CER) and proliferation-stimulating sphingosine-1-phosphate (S1P)—in human lung adenocarcinoma A549 cells. Resveratrol treatment induced an increase in CER and sphingosine (SPH) and a decrease in sphingomyelin (SM) and S1P. Our results showed that the most common mode of CER accumulation, through sphingomyelinase-induced hydrolysis of SM, was not responsible for a CER increase despite the reduction in SM in A549 plasma membranes. However, both the activity and the expression of CER synthase 6 were upregulated in resveratrol-treated cells, implying that CER was accumulated as a result of stimulated de novo synthesis. Furthermore, the enzyme responsible for CER hydrolysis, alkaline ceramidase, was not altered, suggesting that it was not related to changes in the CER level. The enzyme maintaining the balance between apoptosis and proliferation, sphingosine kinase 1 (SK1), was downregulated, and its expression was reduced, resulting in a decrease in S1P levels in resveratrol-treated lung adenocarcinoma cells. In addition, incubation of resveratrol-treated A549 cells with the SK1 inhibitors DMS and fingolimod additionally downregulated SK1 without affecting its expression. The present studies provide information concerning the biochemical processes underlying the influence of resveratrol on sphingolipid metabolism in A549 lung cancer cells and reveal possibilities for combined use of polyphenols with specific anti-proliferative agents that could serve as the basis for the development of complex therapeutic strategies. Full article