To systematically analyze mitogen‐activated protein (MAP) kinase gene families and their expression profiles in sugarcane (Saccharum spp. hybrids; Sh) under diverse biotic and abiotic stresses, we ...identified 15 ShMAPKs, 6 ShMAPKKs and 16 ShMAPKKKs genes in the sugarcane cultivar R570 genome. These were also confirmed in one S. spontaneum genome and two transcriptome datasets of sugarcane trigged by Acidovorax avenae subsp. avenae (Aaa) and Xanthomonas albilineans (Xa) infections. Phylogenetic analysis revealed that four subgroups were present in each ShMAPK and ShMAPKK family and three sub‐families (RAF, MEKK and ZIK) presented in the ShMAPKKK family. Conserved protein motif and gene structure analyses supported the evolutionary relationships of the three families inferred from the phylogenetic analysis. All of the ShMAPK, ShMAPKK and ShMAPKKK genes identified in Saccharum spp. R570 were distributed on chromosomes 1–7 and 9–10. RNA‐seq and qRT‐PCR analyses indicated that ShMAPK07 and ShMAPKKK02 were defense‐responsive genes in sugarcane challenged by both Aaa and Xa stimuli, while some genes were upregulated specifically by Aaa and Xa infection. Additionally, ShMAPK05 acted as a negative regulator under drought and salinity stress, but served as a positive regulator under salicylic acid (SA) treatment. ShMAPK07 plays a positive role under drought stress, but a negative role under SA treatment. ShMAPKKK01 was negatively modulated by both salinity stress and SA treatment, whereas ShMAPKKK06 was positively regulated by both of the two stress stimuli. Our results suggest that members of MAPK cascade gene families regulate adverse stress responses through multiple signal transduction pathways in sugarcane.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Characteristically, cancer cells metabolize glucose through aerobic glycolysis, known as the Warburg effect. Accumulating evidence suggest that during cancer formation, microRNAs (miRNAs) could ...regulate such metabolic reprogramming. In the present study, miR‐9‐1 was identified as significantly hypermethylated in nasopharyngeal carcinoma (NPC) cell lines and clinical tissues. Ectopic expression of miR‐9‐1 inhibited NPC cell growth and glycolytic metabolism, including reduced glycolysis, by reducing lactate production, glucose uptake, cellular glucose‐6‐phosphate levels, and ATP generation in vitro and tumor proliferation in vivo. HK2 (encoding hexokinase 2) was identified as a direct target of miR‐9‐1 using luciferase reporter assays and Western blotting. In NPC cells, hypermethylation regulates miR‐9‐1 expression and inhibits HK2 translation by directly targeting its 3' untranslated region. MiR‐9‐1 overexpression markedly reduced HK2 protein levels. Restoration of HK2 expression attenuated the inhibitory effect of miR‐9‐1 on NPC cell proliferation and glycolysis. Fluorescence in situ hybridization results indicated that miR‐9‐1 expression was an independent prognostic factor in NPC. Our findings revealed the role of the miR‐9‐1/HK2 axis in the metabolic reprogramming of NPC, providing a potential therapeutic strategy for NPC.
The miR‐9‐1 promoter is hypermethylated in nasopharyngeal carcinoma (NPC), thus decreasing its expression. Reduced miR‐9‐1 expression increases HK2 levels, thus increasing glycolysis. FISH score analysis showed that miR‐9‐1 is an independent prognostic factor in NPC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Ginsenoside Rk1 and Rg5 are minor ginseng saponins that have received more attention recently because of their high oral bioavailability. Each of them can effectively inhibit the survival and ...proliferation of human liver cancer cells, but the underlying mechanism remains largely unknown. Network pharmacology and bioinformatics analysis demonstrated that G-Rk1 and G-Rg5 yielded 142 potential targets, and shared 44 putative targets associated with hepatocellular carcinoma. Enrichment analysis of the overlapped genes showed that G-Rk1 and G-Rg5 may induce apoptosis of liver cancer cells through inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signal pathways. Methyl thiazolyl tetrazolium (MTT) assay was used to confirm the inhibition of cell viability with G-Rk1 or G-Rg5 in highly metastatic human cancer MHCC-97H cells. We evaluated the apoptosis of MHCC-97H cells by using flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining. The translocation of Bax/Bak led to the depolarization of mitochondrial membrane potential and release of cytochrome c and Smac. A sequential activation of caspase-9 and caspase-3 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed after that. The levels of anti-apoptotic proteins were decreased after treatment of G-Rk1 or G-Rg5 in MHCC-97H cells. Taken together, G-Rk1 and G-Rg5 promoted the endogenous apoptotic pathway in MHCC-97H cells by targeting and regulating some critical liver cancer related genes that are involved in the signal pathways associated with cell survival and proliferation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nucleotide excision repair (NER) of ultraviolet (UV)‐induced DNA lesions known as cyclobutane pyrimidine dimer (CPD) and (6–4)‐pyrimidine‐pyrimidone (6‐4PP) photoproducts depends on the activities of ...multiple anti‐UV radiation (RAD) proteins in budding yeast. However, NER remains poorly known in filamentous fungi, whose DNA lesions are photorepaired by one or two photolyases, namely CPD‐specific Phr1 and/or 6‐4PP‐specific Phr2. Previously, the white collar proteins WC1 and WC2 were proven to regulate expressions of phr2 and phr1 and photorepair 6‐4PP and CDP DNA lesions, respectively, in Metarhizium robertsii, a filamentous entomopathogenic‐phytoendophytic fungus. We report here high activities of orthologous Rad1 and Rad10 in 5‐h photoreactivation of UVB‐injured or UVB‐inactivated conidia but a severely compromised capability of their reactivating those conidia via 24‐h dark incubation in M. robertsii. The null mutants of rad1 and rad10 were much more compromised in conidial UVB resistance and photoreactivation capability than the previous null mutants of phr1, phr2, wc1 and wc2. Multiple protein–protein (Rad1‐Rad10, Rad1‐WC2, Rad10‐Phr1, WC1‐Phr1/2 and WC2‐Phr1/2) interactions detected suggest direct/indirect links of Rad1 and Rad10 to Phr1/2 and WC1/2 and an importance of the links for their photoreactivation activities. Conclusively, Rad1 and Rad10 photoreactivate UVB‐impaired M. robertsii through their interactions with the DNA photorepair‐required proteins.
The anti‐UV proteins Rad1 and Rad10 photoreactivate solar UV‐injured M. robertsii conidia by their links to DNA photorepair‐required proteins.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Summary
This study aims to investigate the bonding performance of novel composite specially shaped concrete‐filled steel tubes (CFSTs). Seven novel composite L‐shaped CFST specimens were designed ...utilizing variations in steel tube wall thickness, steel tube length, and concrete strength as the primary parameters. Their failure modes, load–slip relationships, and longitudinal strain distribution patterns were examined through push‐out tests. Additionally, finite element models of the members were established using nonlinear spring elements based on the experimental data and subjected to numerical analysis. The research findings indicate that the ultimate bond strength of the composite L‐shaped CFSTs is positively correlated with steel tube wall thickness, steel tube length, and concrete strength. The strain distributions on the concave and convex faces of the L‐shaped steel tubes are identical. The results obtained from the finite element analysis closely match the experimental findings.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Adherence of conidia to insect integument is crucial for initiation of fungal infection through cuticular penetration and was previously reported to rely upon the
Metarhizium
-type adhesin Mad1 ...rather than Mad2, another adhesin crucial for conidial adherence of
Metarhizium anisopliae
to plant root surface. Mad1 and Mad2 have since been considered to function in fungal insect pathogenesis and plant root colonization respectively. Here, three adhesins were characterized in
Beauveria bassiana
, including Adh1/Mad1, Adh2/Mad2, and Adh3 known as filamentous hemagglutinin/adhesin and virulence factor in animal-pathogenic bacteria. Among those, only Adh2 was found to play a substantial role in sustaining the fungal virulence and some phenotypes associated with biological control potential. Disruption of
adh2
resulted in decreased conidial adherence to insect wing cuticle, attenuated virulence via normal cuticle infection or cuticle-bypassing infection (injection), reduced blastospore production in an insect hemolymph-mimicking broth, largely reduced conidiation capacity, impaired conidial quality indicative of lowered viability, hydrophobicity, and UV resistance, but no growth defects on rich and scant media under normal or stressful culture conditions. The main phenotypic changes correlated well with repressed expression of developmental activator genes required for aerial conidiation and submerged blastospore production and of key hydrophobin genes essential for hydrophobin synthesis and assembly into rodlet bundles of conidial coat crucial for conidial adherence. In contrast, either
adh1
or
adh3
disruption caused insignificant changes in all phenotypes examined. These findings offer novel insight into a significance of Adh2, but a dispensability of Adh1 or Adh3, for insect-pathogenic lifecycle of
B. bassiana
.
Key points
• Three adhesins (Adh1–3) of Beauvera bassiana are functionally characterized.
• Adh2 plays a role in sustaining virulence and lifecycle-related cellular events.
• Either Adh1 or Adh3 is dispensable for insect-pathogenic lifecycle of B. bassiana.
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CEKLJ, DOBA, EMUNI, FZAB, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The balance between oxidative and nonoxidative glucose metabolism is essential for a number of pathophysiological processes. By deleting enzymes that affect aerobic glycolysis with different ...potencies, we examine how modulating glucose metabolism specifically affects hematopoietic and leukemic cell populations. We find that a deficiency in the M2 pyruvate kinase isoform (PKM2) reduces the levels of metabolic intermediates important for biosynthesis and impairs progenitor function without perturbing hematopoietic stem cells (HSCs), whereas lactate dehydrogenase A (LDHA) deletion significantly inhibits the function of both HSCs and progenitors during hematopoiesis. In contrast, leukemia initiation by transforming alleles putatively affecting either HSCs or progenitors is inhibited in the absence of either PKM2 or LDHA, indicating that the cell-state-specific responses to metabolic manipulation in hematopoiesis do not apply to the setting of leukemia. This finding suggests that fine-tuning the level of glycolysis may be explored therapeutically for treating leukemia while preserving HSC function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Endometriosis is defined as an oestrogen‐dependent and inflammatory gynaecological disease of which the pathogenesis remains unclear. This study aimed to investigate the cellular heterogeneity and ...reveal the effect of CD8+ T cells on the progress of endometriosis. Three ovarian endometriosis patients were collected, and single‐cell RNA sequencing (scRNA‐seq) progressed and delineated the cellular landscape of endometriosis containing five cell clusters. The endometrial cells (EMCs) were the major component, of which the mesenchymal cells were preponderant and characterized with increased inflammation and oestrogen synthesis in endometriosis. The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. Correspondingly, the coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis‐promoted metabolism reprogramming. The endometriotic lesions were larger in nude mouse models with T‐cell deficiency than the normal mouse models. The inhibition of T cells via CD90.2 or CD8A antibody increased the endometriotic lesions in mouse models, and the supplement of T cells to nude mouse models diminished the lesion sizes. In conclusion, this study revealed the global cellular variation of endometriosis among which the cellular count and physiology of EMCs and T cells were significantly changed. The depressed cytotoxicity and aberrant metabolism of CD8+ T cells were induced by ESCs with the activation of STAT1/PDCD1 pathway resulting in immune survival to promote endometriosis.
The proportion of T cells, mainly CD8+ T cells rather than CD4+, was reduced in endometriotic lesions, and the cytokines and cytotoxicity of ectopic T cells were depressed. CD8+ T cells depressed the proliferation of ESCs through inhibiting CDK1/CCNB1 pathway to arrest the cell cycle and triggered inflammation through activating STAT1 pathway. The coculture with ESCs resulted in the dysfunction of CD8+ T cells through upregulating STAT1/PDCD1 pathway and glycolysis‐promoted metabolism reprogramming.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Development of an efficient catalyst for degradation of organophosphorus toxicants is highly desirable. Herein, an MIL-101(Cr)LZn catalyst was fabricated by incorporating polypyridine zinc complexes ...into a MOF to achieve the spatial isolation of active sites. Compared with a terpyridine zinc complex without an MIL-101 support, this catalyst was highly active for detoxification of diethyl-4-nitrophenylphosphate.
To achieve the spatial isolation of active sites, zinc polypyridine complexes were incorporated into MIL-101(Cr). Compared with zinc complex without MOF support, the resulting catalyst was highly active for degradation of a nerve agent simulant.
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