Comparative transcriptome analysis revealed that auxin and cell wall biosynthesis play important roles in the formation of hollow hearts in cucumber.

BACKGROUND: Hollow heart is a kind of physiological defect that seriously affects the yield, quality, and economic value of cucumber. However, the formation of hollow hearts may relate to multiple factors in cucumber, and it is necessary to conduct analysis. RESULTS: In this study, hollow and non-hollow fruits of cucumber K07 were used for comparative transcriptome sequencing and analysis. 253 differentially expressed genes and 139 transcription factors were identified as being associated with the formation of hollow hearts. Hormone (auxin) signaling and cell wall biosynthesis were mainly enriched in GO and KEGG pathways. Expression levels of key genes involved in indole-3-acetic acid biosynthesis in carpel were lower in the hollow fruits than non-hollow fruits, while there was no difference in the flesh. The concentration of indole-3-acetic also showed lower in the carpel than flesh. The biosynthetic pathway and content analysis of the main components of the cell wall found that lignin biosynthesis had obvious regularity with hollow heart, followed by hemicellulose and cellulose. Correlation analysis showed that there may be an interaction between auxin and cell wall biosynthesis, and they collectively participate in the formation of hollow hearts in cucumber. Among the differentially expressed transcription factors, MYB members were the most abundant, followed by NAC, ERF, and bHLH. CONCLUSIONS: The results and analyses showed that the low content of auxin in the carpel affected the activity of enzymes related to cell wall biosynthesis at the early stage of fruit development, resulting in incomplete development of carpel cells, thus forming a hollow heart in cucumber. Some transcription factors may play regulatory roles in this progress. The results may enrich the theory of the formation of hollow hearts and provide a basis for future research.

Descriptor-Based Volcano Relations Predict Single Atoms for Hydroxylamine Electrosynthesis.

Hydroxylamine (NH2OH) is an important feedstock in fuels, pharmaceuticals, and agrochemicals. Nanostructured electrocatalysts drive green electrosynthesis of hydroxylamine from nitrogen oxide species in water. However, current electrocatalysts still suffer from low selectivity and manpower-consuming trial-and-error modes, leaving unclear selectivity/activity origins and a lack of catalyst design principles. Herein, we theoretically analyze key determinants of selectivity/activity and propose the adsorption energy of NHO (Gad(*NHO)) as a performance descriptor. A weak *NH2OH binding affinity and a favorable reaction pathway (*NHO pathway) jointly enable single-atom catalysts (SACs) with superior NH2OH selectivity. Then, an activity volcano plot of Gad(*NHO) is established to predict a series of SACs and discover Mn SACs as optimal electrocatalysts that exhibit pH-dependent activity. These theoretical prediction results are also confirmed by experimental results, rationalizing our Gad(*NHO) descriptor. Furthermore, Mn-Co geminal-atom catalysts (GACs) are predicted to optimize Gad(*NHO) and are experimentally proved to enhance NH2OH formation.

Galangin as a direct inhibitor of vWbp protects mice from Staphylococcus aureus-induced pneumonia.

The surge in multidrug resistance in Staphylococcus aureus (S. aureus) and the lag in antibiotic discovery necessitate the development of new anti-infective strategies to reduce S. aureus infections. In S. aureus, von Willebrand factor-binding protein (vWbp) is not only the main coagulase that triggers host prothrombin activation and formation of fibrin cables but also bridges the bacterial cell wall and von Willebrand factor, thereby allowing S. aureus to bind to platelets and endothelial cells, playing a vital role in pathogenesis of S. aureus infections. Here, we have identified that galangin, a bioactive compound found in honey and Alpinia officinarum Hance, is a potent and direct inhibitor of vWbp by coagulation activity inhibition assay, thermal shift assay and biolayer interferometry assay. Molecular dynamic simulations and verification experiments revealed that the Trp-64 and Leu-69 residues are necessary for the binding of galangin to vWbp. Significantly, galangin attenuated S. aureus virulence in a mouse S. aureus-induced pneumonia model. In addition, we also identified that galangin can enhance the therapeutic effect of latamoxef on S. aureus-induced pneumonia. Taken together, the results suggest that galangin may be used for the development of therapeutic drugs or utilized as adjuvants to combine with antibiotics to combat S. aureus-related infections.

Effects of hydrolysable tannins from Terminalia citrina on type III secretion system (T3SS) and their intestinal metabolite urolithin B represses Salmonella T3SS through Hha-H-NS-HilD-HilC-RtsA-HilA regulatory pathway.

Gamma-proteobacteria is a class of gram-negative opportunistic pathogens existing in the intestinal flora, often leading to diarrhea and intestinal infectious diseases, and plays an important role in maintaining intestinal homeostasis. Type III secretion system (T3SS), an important virulence system, is closely related to the adhesion and invasion and pathogenicity to host cells. Therefore, anti-virulence agents targeting T3SS are important strategies for controlling pathogenic infections. In this study, the anti-Salmonella T3SS active compounds neochebulagic acid (1), ellagic acid (2) and urolithin M5 (3) were isolated from seed extract of Terminalia citrina by activity-guided isolation method. Based on the fact that urolithins are the main and stable intestinal microbiota metabolites of hydrolysable tannins, we found that the metabolite urolithin B repressed translation and secretion of SipC through the Hha-H-NS-HilD-HilC-RtsA-HilA regulatory pathway. The results provide evidence for Terminalia seeds and ellagitannin-rich berries and nuts in regulating intestinal homeostasis and treating bacterial infection.

Restricted Phased Space Thermodynamics for Black Holes in Higher Dimensions and Higher Curvature Gravities.

The recently proposed restricted phase space thermodynamics is shown to be applicable to a large class of higher dimensional higher curvature gravity models coupled to Maxwell field, which are known as black hole scan models and are labeled by the spacetime dimension d and the highest order k of the Lanczos-Lovelock densities appearing in the action. Three typical example cases with (d,k)=(5,1),(5,2) and (6,2) are chosen as example cases and studied in some detail. These cases are representatives of Einstein-Hilbert, Chern-Simons and Born-Infield like gravity models. Our study indicates that the Einstein-Hilbert and Born-Infield like gravity models have similar thermodynamic behaviors, e.g., the existence of isocharge T-S phase transitions with the same critical exponents, the existence of isovoltage T-S transitions and the Hawking-Page like transitions, and the similar high temperature asymptotic behaviors for the isocharge heat capacities, etc. However, the Chern-Simons like (5,2)-model behaves quite differently. Neither isocharge nor isovoltage T-S transitions could occur and no Hawking-Page like transition is allowed. This seems to indicate that the Einstein-Hilbert and Born-Infield like models belong to the same universality class while the Chern-Simons like models do not.

Targeting staphylocoagulase with isoquercitrin protects mice from Staphylococcus aureus-induced pneumonia.

Staphylocoagulase (Coa) is a virulence factor of Staphylococcus aureus (S. aureus) that promotes blood coagulation by activating prothrombin to convert fibrinogen to fibrin. Coa plays a crucial role in disease pathogenesis and is a promising target for the treatment of S. aureus infections. Here, we identified that isoquercitrin, a natural flavonol compound, can markedly reduce the activity of Coa at concentrations that have no effect on bacterial growth. Mechanistic studies employing molecular dynamics simulation revealed that isoquercitrin binds to Coa by interacting with Asp-181 and Tyr-188, thereby affecting the binding of Coa to prothrombin. Importantly, in vivo studies showed that isoquercitrin treatment significantly reduced the bacterial burden, pathological damage, and inflammation of lung tissue and improved the percentage of survival of mice infected with S. aureus Newman strain. These data suggest that isoquercitrin is a promising inhibitor of Coa that can be used for the development of therapeutic drugs to combat S. aureus infections.Key Points• Staphylocoagulase plays a key role in the pathogenesis of S. aureus infection.• We identified that isoquercitrin is a direct inhibitor of staphylocoagulase.• Isoquercitrin treatment can significantly attenuate S. aureus virulence in vivo.

Event-related alpha power in early stage of facial expression processing in social anxiety: Influence of language context.

Accurate interpretation of the emotional information conveyed by others' facial expressions is crucial for social interactions. Event-related alpha power, measured by time-frequency analysis, is a frequently used EEG index of emotional information processing. However, it is still unclear how event-related alpha power varies in emotional information processing in social anxiety groups. In the present study, we recorded event-related potentials (ERPs) while participants from the social anxiety and healthy control groups viewed facial expressions (angry, happy, neutral) preceded by contextual sentences conveying either a positive or negative evaluation of the subject. The impact of context on facial expression processing in both groups of participants was explored by assessing behavioral ratings and event-related alpha power (0-200 ms after expression presentation). In comparison to the healthy control group, the social anxiety group exhibited significantly lower occipital alpha power in response to angry facial expressions in negative contexts and neutral facial expressions in positive contexts. The influence of language context on facial expression processing in individuals with social anxiety may occur at an early stage of processing.

Rs12976445 polymorphism is associated with the risk of post-SAH re-bleeding by modulating the expression of microRNA-125 and ET-1.

This study aimed to study the association between rs12976445 polymorphism and the incidence of IA re-bleeding. Genotype and allele frequency analysis was performed to study the association between rs12976445 polymorphism and the risk of IA re-bleeding. Western blot, ELISA and real-time RT-PCR were conducted to measure the relative expression of miR-125a, ET1 mRNA and ET1 protein. Computational analysis and luciferase assays were utilized to investigate the association between the expression of miR-125a and ET1 mRNA. No significant differences were observed between IA patients with or without symptoms of re-bleeding. Subsequent analyses indicated that the T allele was significantly associated with the reduced risk of IA re-bleeding. In patients carrying the CC genotype, miR-125a level was up-regulated while ET1 mRNA/protein levels were reduced compared with those in patients carrying the CT or TT genotype. And ET1 mRNA was identified as a virtual target gene of miR-125a with a potential miR-125a binding site located on its 3'UTR. Accordingly, the ET mRNA/protein levels could be suppressed by the transfection of miR-125a precursors, but the transfection of ET1 siRNA exhibited no effect on the expression of miR-125a. Therefore, an increased level of miR-125a can lead to the increased risk of IA re-bleeding. Since miR-125a level is higher in CC-genotyped patients, it can be concluded that the presence of T allele in the rs12976445 polymorphism is associated with a lower risk of IA re-bleeding, and miR-125a may be used as a novel diagnostic and therapeutic target for IA rupture.

Urolithins and intestinal health.

There are trillions of microorganisms in the human intestine. They can react to the intestinal microenvironment by metabolizing food or producing small molecular compounds to affect the host's digestive ability and resist the risk of infection and autoimmune diseases. Many studies have revealed that intestinal flora and its metabolites play an important role in human physiology and the development of diseases. Urolithins are kind of intestinal microbiota metabolites of ellagitannins (ETs) and ellagic acid (EA) with potent biological activity in vivo. However, different individuals have different intestinal flora. According to the different metabolites from ETs and EA, it is divided into three metabo-types including UM-A, UM-B and UM-0. This paper reviews the origin of urolithins, the urolithin producing microorganisms and the effects of urolithins on regulating intestinal diseases. This review will provide a theoretical basis for the regulation of urolithins in the homeostasis of intestinal flora and a reference for the scientific utilization of urolithins and foods rich in ETs and EA.

Microbial Responses to Various Types of Chemical Regents during On-Line Cleaning of UF Membranes.

Ultrafiltration is widely used to treat various environmental waters, and on-line membrane cleaning with various chemical reagents is frequently employed to sustain the filtration flux. However, the residue of cleaning agents in the ultrafiltration system is unavoidable, which may affect microbiological properties and biofilm formation during the next-round filtration. By investigating the changes in microbial characteristics, and their biofouling behaviors after exposure to HCl, NaOH, NaClO, citric acid (CA), and sodium dodecyl sulfonate (SDS), this study fills a knowledge gap in microbial responses to various types of chemical cleaning agents in an ultrafiltration system. The result shows that HCl, NaOH, and NaClO affect the bacterial properties and subsequent attachment on the membrane surface, while CA and SDS have no obvious influence on microorganisms. Specifically, HCl, NaOH, and NaClO reduce the hydrophobicity and mean size of suspended microorganisms, increase the extracellular polymeric substances (EPS) release, and trigger intracellular reactive oxygen species (ROS) generation, resulting in the death of a large quantity of microorganisms. Due to the self-protecting strategy, plenty of living cells aggregate on the membrane surface and form a cake layer with a stratified structure, causing more severe membrane biofouling.

Influence of affective verbal context on emotional facial expression perception of social anxiety.

Previous studies have shown that the perception of ambiguous facial expressions for individuals with social anxiety was influenced by the affective verbal context. However, it is still unknown how emotional facial expressions are perceived by individuals with social anxiety in the context of the verbal context. In this study, we used event-related potentials (ERPs) technology to examine how individuals with social anxiety perceive emotional facial expressions in positive and negative contexts. The results showed that: (1) Within the negative verbal contexts, the amplitude of P1 induced by facial expressions in the social anxiety group was significantly higher than that induced by the healthy control group; The N170 amplitude induced by facial expressions in social anxiety group was less negative than that in the healthy control group, and was not affected by the context. (2) The social anxiety group had significantly higher LPP in negative contexts elicited by angry expressions than by happy expressions. This study proved that the perception of emotional facial expressions was influenced by top-down information in the early and late stages of visual perception for individuals with social anxiety.

Porphyromonas gingivalis-Derived Lipopolysaccharide Promotes Glioma Cell Proliferation and Migration via Activating Akt Signaling Pathways.

Periodontitis is significantly associated with the risk of cancers in the lung and the digestive system. Emerging evidence shows a plausible link between periodontitis and several types of brain diseases. However, the association between periodontal infection and glioma remains unclear. In the cultured GL261 glioma cells, P. gingivalis lipopolysaccharide (LPS) significantly promoted cell proliferation at concentrations ranging from 10 to 1000 ng/mL. It promoted cell migration at a higher concentration (100 and 1000 ng/mL). Additionally, exposure to 100 ng/mL P. gingivalis LPS induced a significant increase in the expression of TNF-α, TGF-ß, MMP2, and MMP9, as well as the phosphorylation level of Akt at Ser473. These changes induced by P. gingivalis LPS were significantly antagonized by the Akt inhibitor. Furthermore, a total of 48 patients with brain tumors were enrolled to investigate their periodontal status before receiving tumor management. Poor periodontal status [probing depth (PD) ≥ 6 mm and attachment loss (AL) >5 mm] was found in 42.9% (9/21) of patients with glioma, which was significantly higher than that in patients with benign tumors and the relevant data in the 4th National Oral Health Survey in China. The glioma patients with both AL > 5 mm and PD ≥ 6 mm had a higher ki-67 labeling index than those with AL ≤ 5 mm or PD < 6 mm. These findings support the association between periodontal infection and glioma progression.

Baicalein mediates protection against Staphylococcus aureus-induced pneumonia by inhibiting the coagulase activity of vWbp.

The emergence and spread of multidrug-resistant Staphylococcus aureus (S. aureus) necessitate the research on therapeutic tactics which are different from classical antibiotics in overcoming resistance andtreatinginfections. In S. aureus, von Willebrand factor-binding protein (vWbp) is one of the key virulence determinants because it mediates not only the activation of thrombin to convert fibrinogen to fibrin, thereby enabling S. aureus to escape from the host immune clearance, but also the adhesion of S. aureus to host cells. Thus, vWbp is regarded as a promising druggable target to treat S. aureus-associated infections. Here we identify that baicalein, a natural compound isolated from the Chinese herb Scutellaria baicalensis, can effectively block the coagulase activity of vWbp without inhibiting the growth of the bacteria. Through thermal shift and fluorescence quenching assays, we demonstrated that baicalein directly binds to vWbp. Molecular dynamics simulations and mutagenesis assays revealed that the Asp-75 and Lys-80 residues are necessary for baicalein binding to vWbp. Importantly, we demonstrated that baicalein treatment attenuates the virulence of S. aureus and protects mice from S. aureus-induced lethal pneumonia. In addition, baicalein can improve the therapeutic effect of penicillin G by 75% in vivo. These findings indicate that baicalein might be developed as a promising therapeutic agent against drug-resistant S. aureus infections.

The combination of salvianolic acid A with latamoxef completely protects mice against lethal pneumonia caused by methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus (S. aureus), especially methicillin-resistant Staphylococcus aureus (MRSA), is a major cause of pneumonia, resulting in severe morbidity and mortality in adults and children. Sortase A (SrtA), which mediates the anchoring of cell surface proteins in the cell wall, is an important virulence factor of S. aureus. Here, we found that salvianolic acid A (Sal A), which is a natural product that does not affect the growth of S. aureus, could inhibit SrtA activity (IC50 = 5.75 µg/ml) and repress the adhesion of bacteria to fibrinogen, the anchoring of protein A to cell wall, the biofilm formation, and the ability of S. aureus to invade A549 cells. Furthermore, in vivo studies demonstrated that Sal A treatment reduced inflammation and protected mice against lethal pneumonia caused by MRSA. More significantly, full protection (a survival rate of 100%) was achieved when Sal A was administered in combination with latamoxef. Together, these results indicate that Sal A could be developed into a promising therapeutic drug to combat MRSA infections while limiting resistance development.