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As a structural, catalytic, and signaling component, zinc is necessary for the growth and development of plants, animals, and microorganisms. Zinc is also essential for the growth of pathogenic microorganisms and is involved in their metabolism as well as the regulation of various virulence factors. Additionally, zinc is necessary for infection and colonization of pathogenic microorganisms in the host. Upon infection in healthy organisms, the host sequesters zinc both intracellularly and extracellularly to enhance the immune response and prevent the proliferation and infection of the pathogen. Intracellularly, the host manipulates zinc levels through Zrt/Irt-like protein (ZIP)/ZnT family proteins and various zinc storage proteins. Extracellularly, members of the S100 protein family, such as calgranulin C, sequester zinc to inhibit microbial growth. In the face of these nutritional limitations, bacteria rely on an efficient zinc transport system to maintain zinc supplementation for proliferation and disruption of the host defense system to establish infection. Here, we summarize the strategies for zinc uptake in conditional pathogenic Pseudomonas aeruginosa, including known zinc uptake systems (ZnuABC, HmtA, and ZrmABCD) and the zinc uptake regulator (Zur). In addition, other potential zinc uptake pathways were analyzed. This review systematically summarizes the process of zinc uptake by P. aeruginosa to provide guidance for the development of new drug targets.

It is urgent to develop low-cost but efficient oxygen reduction reaction (ORR) catalysts for the emerging clean energy devices of fuel cells based on proton exchange membrane. Herein, we report a facile method to covert the biomass of black fungus into an efficient ORR catalyst. The black fungus undergoes hydrothermal and pyrolysis processes to transform into carbon-based materials. The as-obtained BF-N-950 catalyst shows prominent ORR catalytic activities in both acidic and alkaline electrolytes with a half-wave potential reaching 0.77 and 0.91 V, respectively. A membrane electrolyte assembly was fabricated with the as-obtained BF-N-950 as the cathode catalyst which shows a high peak power density of 255 mW cm−2. The study shows the potential of converting conventional biomass into low-cost ORR catalyst, which is promising for the fuel cell technology.

To further explore the structure activity relationships (SARs) of our previously discovered antifungal lead compound (1), a series of biphenyl imidazole analogues were designed, synthesized and evaluated for their in vitro antifungal activity. Many of the synthesized compounds showed excellent activity against Candida albicans and Candida tropicalis. Among these compounds, 2-F substituted analogue 12m displayed the most remarkable in vitro activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and itraconazole. Notably, the compound 12m exhibited low inhibition profiles for various human cytochrome P450 isoforms and showed low toxicity to mammalian A549 cells and U87 cells. The SARs and binding mode established in this study will be useful for further lead optimization.

N6-methyladenine (6mA), as a newly reported epigenetic marker, plays significant roles in regulation of various biological processes in eukaryotes. However, the effect of 6mA on human DNA replication remain elusive. In this work, we used Y-family human DNA polymerase η as a model to investigate the kinetics of bypass of 6mA by hPol η. We found 6mA and its intermediate hypoxanthine (I) on template partially inhibited DNA replication by hPol η. dTMP incorporation opposite 6mA and dCMP incorporation opposite I can be considered as correct incorporation. However, both 6mA and I reduced correct incorporation efficiency, next-base extension efficiency, and the priority in extension beyond correct base pair. Both dTMP incorporation opposite 6mA and dCTP opposite I showed fast burst phases. However, 6mA and I reduced the burst incorporation rates (kpol) and increased the dissociation constant (Kd,dNTP), compared with that of dTMP incorporation opposite unmodified A. Biophysical binding assays revealed that both 6mA and I on template reduced the binding affinity of hPol η to DNA in binary or ternary complex compared with unmodified A. All the results explain the inhibition effects of 6mA and I on DNA replication by hPol η, providing new insight in the effects of epigenetically modified 6mA on human DNA replication.

Low-phosphorus (LP) stress is a major factor limiting the growth and yield of soybean. Circular RNAs (circRNAs) are novel noncoding RNAs that play a crucial role in plant responses to abiotic stress. However, how LP stress mediates the biogenesis of circRNAs in soybean remains unclear. Here, to explore the response mechanisms of circRNAs to LP stress, the roots of two representative soybean genotypes with different P-use efficiency, Bogao (a LP-sensitive genotype) and Nannong 94156 (a LP-tolerant genotype), were used for the construction of RNA sequencing (RNA-seq) libraries and circRNA identification. In total, 371 novel circRNA candidates, including 120 significantly differentially expressed (DE) circRNAs, were identified across different P levels and genotypes. More DE circRNAs were significantly regulated by LP stress in Bogao than in NN94156, suggesting that the tolerant genotype was less affected by LP stress than the sensitive genotype was; in other words, NN94156 may have a better ability to maintain P homeostasis under LP stress. Moreover, a positive correlation was observed between the expression patterns of P stress-induced circRNAs and their circRNA-host genes. Gene Ontology (GO) enrichment analysis of these circRNA-host genes and microRNA (miRNA)-targeted genes indicated that these DE circRNAs were involved mainly in defense responses, ADP binding, nucleoside binding, organic substance catabolic processes, oxidoreductase activity, and signal transduction. Together, our results revealed that LP stress can significantly alter the genome-wide profiles of circRNAs and indicated that the regulation of circRNAs was both genotype and environment specific in response to LP stress. LP-induced circRNAs might provide a rich resource for LP-responsive circRNA candidates for future studies.

To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compound 1, a series of benzoheterocycle analogues were designed, synthesized and evaluated for their in vitro antifungal activity. The most promising compounds 13s and 14a exhibited excellent antifungal activity against C. albicans, C. neoformans, A. fumigatus and fluconazole-resistant C. albicans strains, that was superior or comparable to those of the reference drugs fluconazole and voriconazole. GC-MS analyses suggested that the novel compound 13s might have a similar mechanism to fluconazole by inhibiting fungal lanosterol 14α-demethylase (CYP51). Furthermore, compounds 13s and 14a exhibited low inhibition profiles for various human cytochrome P450 isoforms as well as excellent blood plasma stability.

To further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (1), a series of aromatic heterocyclic derivatives were designed, synthesized and evaluated for in vitro antifungal activity. Many of the target compounds showed good inhibitory activity against Candida albicans and Cryptococcus neoformans. In particular, the isoxazole nuclei were more suited for improving the activity against Aspergillus spp. Among these compounds, 2-F substituted analogues 23g and 23h displayed the most remarkable in vitro activity against Candida spp., C. neoformans, A. fumigatus and fluconazole-resistant C.alb. strains, which is superior or comparable to the activity of the reference drugs fluconazole and voriconazole. Notably, the compounds 23g and 23h exhibited low inhibition profiles for various isoforms of human cytochrome P450 and excellent blood plasma stability.

Fungal infections have became a serious medical problem due to their high incidence and mortality. We describe the discovery and structure-activity relationships studies (SARs) of a series of novel biphenyl imidazole derivatives with excellent antifungal activities against Candida albicans and Cryptococcus neoformans. The most promising compounds 12f-g and 19a-b exhibited excellent activity with minimum inhibitory concentration (MIC) values in the range of 0.03125-2μg/mL. Preliminary mechanism studies showed that the potent antifungal activity of compound 12g stemed from inhibition of CYP51 in Candida albicans. Furthermore, compounds 12g and 19b exhibited low inhibition profiles for various human cytochrome P450 isoforms. The SARs and binding mode established in this study will be useful for further lead optimization.

Gastric cancer (GC), one of the most common malignant tumors and the second most common leading cause of cancer-related death worldwide, is a biologically heterogeneous disease accompanied by various genetic and epigenetic alterations. However, the molecular mechanisms underlying this disease are complex and not completely understood. Increasing studies have shown that aberrant microRNA (miRNA) expression is associated with GC tumorigenesis and growth. MiR-1297 has been confirmed to be a cancer suppressor in diverse tumors in humans. However, to date, the function and mechanism of miR-1297 in GC have not been determined. Here, we found that the expression of miR-1297 was significantly reduced in GC tissues or GC cell lines compared with paracarcinoma normal tissue or normal cell lines. Exogenic overexpression of miR-1297 in GC cell lines can inhibit cell proliferation and colony formation and induce apoptosis, and inhibition of miR-1297 in GC cell lines can promote cell proliferation and colony formation, and reduce apoptosis in vitro. We further confirmed that miR-1297 acted as a tumor suppressor through targeting cell division control protein 6 (CDC6) in GC. Moreover, the inverse relationship between miR-1297 and CDC6 was verified in GC cell lines. Our results indicated that miR-1297 is a potent tumor suppressor in GC, and its antiproliferative and gene-regulatory effects are, in part, mediated through its downstream target gene, CDC6. These findings implied that miR-1297 might be used as a novel therapeutic target of GC.

Application of nitrogen (N) fertilizer usually increases grain yield (GY) and grain protein content (GPC) simultaneously. But low GPC is desirable in soft wheat (Triticum aestivum L.). To break the unexpected link, we investigated the combined effects of reduced N rate, increased plant density on GY, nitrogen agronomic efficiency (NAE) and GPC targeting biscuit-making of two soft wheat cultivars. The field experiments involved four N rates (240, 180, 120 and 0 kg N ha−1) and three plant densities (180, 240 and 300 × 104 plants ha−1). Reducing N rate improved grain quality for biscuit-making and NAE in soft wheat, but resulted in lower dry matter accumulation and caused a significant GY loss. With the N rate ranged from 240 to 0 kg N ha−1, GY loss of 16.28–18.54 kg ha−1 was observed for every 1 kg N ha−1 reduction. Increasing plant density significantly enhanced the population dry matter accumulation and partially compensated for GY loss caused by reduced N via increasing the number of effective ears, meanwhile further improved grain quality and NAE. When the plant density increased from 180 to 300 × 104 plants ha–1, increasing 1.0 × 104 plants ha–1 led to an increment in average GY of 4.79, 6.78 and 3.98 kg ha–1 under 180, 120 and 0 kg N ha−1, respectively. The reduction of 1 kg N ha–1 was replaced by increasing app. 2.40–4.09 × 104 plants ha–1 to maintain same GY. The decrease in GPC by the combination of reduced N rate and increased plant density was mainly attributed to the variations in pre-anthesis accumulated N in vegetative organs as well as the whole plant. Moreover, reducing N rate showed a more remarkable effect on GPC than increasing plant density, and their interaction effect was significant. Our study therefore provided an agronomic approach to balance GY and GPC targeting biscuit-making in soft wheat production by the combination of low N rate and high plant density.

It has previously been demonstrated that miRNA (miR)‑647 exhibits an important role in various cancers, and is aberrantly expressed in gastric cancer (GC). However, the exact role of miR‑647 in GC still remains unclear. The present study aimed to investigate the functional significance of miR‑647 and its target gene in GC. TargetScan and Miranda databases were used to predict the putative targets, and the prediction was validated by Dual‑luciferase Reporter Assays. To investigate whether miR‑647 affects GC cell behavior, a stable miR‑647‑overexpression/low‑expression cell line was generated by transfection with miR‑647 mimic/inhibitor. MTT, Flow Cytometry and Transwell invasion assays were performed to investigate the proliferation, cell apoptosis, migration and invasion properties of MGC‑803 cells. Additionally, reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to detect the mRNA and protein expression levels of the apoptosis‑associated genes. The results suggested that tumor protein P73 (TP73) is a target gene of miR‑647. TP73 was markedly decreased following miR‑647 overexpression and significantly increased following miR‑647 inhibition. Following overexpression of miR‑647, the proliferation, migration and invasion of MGC‑803 cells were significantly increased, whereas the percentage of apoptotic cells decreased. Conversely, the proliferation, migration and invasion of MGC‑803 cells were significantly declined, and the percentage of apoptotic cells increased following miR‑647 inhibition. In addition, the B cell lymphoma (Bcl)‑2 Associated X, Apoptosis Regulator/Bcl‑2 ratio was markedly decreased when miR‑647 was overexpressed by miRNA mimics, and significantly increased when miR‑647 expression was inhibited via an miRNA inhibitor. Overall, miR‑647 functions as a tumor promoter in GC by repressing TP73.

A homogeneous and uniform array of nanotubes with a diameter of about 70 nm was produced on titanium (Ti) surface by anodic oxidation. The wall thickness of the nanotubes was around 20 nm, and the depth was about 200 nm. The biological properties of the anodized Ti surface were investigated by simulated body fluid (SBF) soaking test and in vitro cell culture test. The mechanical properties were evaluated by instrumented nanoindentation test and friction-wear test. The results showed that the anodized Ti surface can induce the formation of bone-like apatite after immersion in SBF for four weeks, enhance cell adhesion, proliferation and gene expression, it also showed decreased friction coefficient, similar stiffness and Young's modulus to those of the cortical bone. Based on these results, it can be concluded that anodic oxidation endowed the Ti surface with improved biological and mechanical properties, which was attributed to the formation of nanostructured surface.

A series of compounds with benzothiazole and amide-imidazole scaffolds were designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. The antifungal activity of these compounds was evaluated in vitro , and their structure-activity relationships (SARs) were evaluated. The synthesized compounds showed excellent inhibitory activity against Candida albicans and Cryptococcus neoformans . The most potent compounds 14o , 14p , and 14r exhibited potent activity, with minimum inhibitory concentration (MIC) values in the range of 0.125–2 μg/mL. Preliminary mechanism studies revealed that the compound 14p might act by inhibiting the CYP51 of Candida albicans . The SARs and binding mode established in this study are useful for further lead optimization.

Previous studies have revealed a significant genetic relationship between phosphorus (P)-efficiency and photosynthesis-related traits in soybean. In this study, we used proteome profiling in combination with expression analysis, biochemical investigations, and leaf ultrastructural analysis to identify the underlying physiological and molecular responses. The expression analysis and ultrastructural analysis showed that the photosynthesis key genes were decreased at transcript levels and the leaf mesophyll and chloroplast were severely damaged after low-P stress. Approximately 55 protein spots showed changes under low-P condition by mass spectrometry, of which 17 were involved in various photosynthetic processes. Further analysis revealed the depression of photosynthesis caused by low-P stress mainly involves the regulation of leaf structure, adenosine triphosphate (ATP) synthesis, absorption and transportation of CO2, photosynthetic electron transport, production of assimilatory power, and levels of enzymes related to the Calvin cycle. In summary, our findings indicated that the existence of a stringent relationship between P supply and the genomic control of photosynthesis in soybean. As an important strategy to protect soybean photosynthesis, P could maintain the stability of cell structure, up-regulate the enzymes&rsquo, activities, recover the process of photosystem II (PSII), and induce the expression of low-P responsive genes and proteins.

Straw mulching is an effective measure to improve soil properties, crop growth, and yield. To further understand the advantage mechanisms of straw mulching, a field experiment with seven straw mulching levels (0 to 18 000 kg ha-1) was conducted to study the effects of straw mulching on maize (Zea mays L.) photosynthesis and rhizosphere soil micro-ecological environment. Results showed that maize chlorophyll content was evidently affected by straw mulching, and the highest chlorophyll content was at 12 000 kg ha-1 (M4). Straw mulching could significantly improve the photosynthetic characteristics of maize, and the difference between M4 and 0 kg ha-1 (M0) was significant. There was as trend change in soil microbe quantity; it first increased and then decreased with increasing straw mulching levels, and the most suitable straw mulching level for different types of microorganisms was 9000 kg ha-1 (M3) or M4. Straw mulching significantly enhanced soil enzyme urease, invertase, dehydrogenase, and protease activities, but when the straw mulching level reached a certain level, the effect of straw mulching was no longer apparent and even had some adverse effects at straw mulching levels higher than 15 000 kg ha-1 (M5). Yield in M4 (10 186.84 kg ha-1) was the highest compared with M0 (9365.12 kg ha-1), and yield significantly increased by 8.8%. Correlation analyses indicated that the soil microbe quantity and aforementioned enzyme activities were all significantly and positively correlated with maize chlorophyll content, photosynthetic rate, and yield. Findings suggest that straw mulching can apparently increase soil microbe quantity and enzyme activities and improve crop photosynthesis and yield; the M4 level is the most reasonable straw mulching level in this study under comprehensive consideration, and a straw mulching level that is too high (over M5) will have some negative effects.

Heritable epigenetic variants of genes, termed epialleles, can broaden genetic and phenotypic diversity in eukaryotes. Epialleles may also provide a new source of beneficial traits for crop breeding, but very few epialleles related to agricultural traits have been identified in crops. Here, we identified Epi-rav6, a gain-of-function epiallele of rice (Oryza sativa) RELATED TO ABSCISIC ACID INSENSITIVE3 (ABI3)/VIVIPAROUS1 (VP1) 6 (RAV6), which encodes a B3 DNA-binding domain-containing protein. The Epi-rav6 plants show larger lamina inclination and smaller grain size; these agronomically important phenotypes are inherited in a semidominant manner. We did not find nucleotide sequence variation of RAV6. Instead, we found hypomethylation in the promoter region of RAV6, which caused ectopic expression of RAV6 in Epi-rav6 plants. Bisulfite analysis revealed that cytosine methylation of four CG and two CNG loci within a continuous 96-bp region plays essential roles in regulating RAV6 expression; this region contains a conserved miniature inverted repeat transposable element transposon insertion in cultivated rice genomes. Overexpression of RAV6 in the wild type phenocopied the Epi-rav6 phenotype. The brassinosteroid (BR) receptor BR INSENSITIVE1 and BR biosynthetic genes EBISU DWARF, DWARF11, and BR-DEFICIENT DWARF1 were ectopically expressed in Epi-rav6 plants. Also, treatment with a BR biosynthesis inhibitor restored the leaf angle defects of Epi-rav6 plants. This indicates that RAV6 affects rice leaf angle by modulating BR homeostasis and demonstrates an essential regulatory role of epigenetic modification on a key gene controlling important agricultural traits. Thus, our work identifies a unique rice epiallele, which may represent a common phenomenon in complex crop genomes.