Secretory IgA reduced the ergosterol contents of Candida albicans to repress its hyphal growth and virulence.

Candida albicans, one of the most prevalent conditional pathogenic fungi, can cause local superficial infections and lethal systemic infections, especially in the immunocompromised population. Secretory immunoglobulin A (sIgA) is an important immune protein regulating the pathogenicity of C. albicans. However, the actions and mechanisms that sIgA exerts directly against C. albicans are still unclear. Here, we investigated that sIgA directs against C. albicans hyphal growth and virulence to oral epithelial cells. Our results indicated that sIgA significantly inhibited C. albicans hyphal growth, adhesion, and damage to oral epithelial cells compared with IgG. According to the transcriptome and RT-PCR analysis, sIgA significantly affected the ergosterol biosynthesis pathway. Furthermore, sIgA significantly reduced the ergosterol levels, while the addition of exogenous ergosterol restored C. albicans hyphal growth and adhesion to oral epithelial cells, indicating that sIgA suppressed the growth of hyphae and the pathogenicity of C. albicans by reducing its ergosterol levels. By employing the key genes mutants (erg11Δ/Δ, erg3Δ/Δ, and erg3Δ/Δ erg11Δ/Δ) from the ergosterol pathway, sIgA lost the hyphal inhibition on these mutants, while sIgA also reduced the inhibitory effects of erg11Δ/Δ and erg3Δ/Δ and lost the inhibition of erg3Δ/Δ erg11Δ/Δ on the adhesion to oral epithelial cells, further proving the hyphal repression of sIgA through the ergosterol pathway. We demonstrated for the first time that sIgA inhibited C. albicans hyphal development and virulence by affecting ergosterol biosynthesis and suggest that ergosterol is a crucial regulator of C. albicans-host cell interactions. KEY POINTS: • sIgA repressed C. albicans hyphal growth • sIgA inhibited C. albicans virulence to host cells • sIgA affected C. albicans hyphae and virulence by reducing its ergosterol levels.

Au Nanoparticles Decorated CoP Nanowire Array: A Highly Sensitive, Anticorrosive, and Recyclable Surface-Enhanced Raman Scattering Substrate.

Metal-semiconductor composites are promising candidates for surface-enhanced Raman scattering (SERS) substrates, but their inert basal plane, poor active sites, and limited stability hamper their commercial prospects. Herein, we report a three-dimensional CoP nanowire array decorated with Au nanoparticles on carbon cloth (Au@CoP/CC) as a self-supporting flexible SERS substrate. The Au nanoparticles spontaneously grew on the surface of the CoP nanowire array to form efficient SERS hot spots by a redox reaction with HAuCl4 without any additional reducing agents. Such Au@CoP/CC substrate exhibited a limit of detection of 10-11 M using rhodamine 6G as a model dye with outstanding corrosion resistance ability even under extreme acid and alkali conditions, which is better than many recently reported Au-based SERS substrates. Finite-difference time-domain simulation results demonstrated that Au@CoP/CC can provide a high density of regions with intense local electric field enhancement. Moreover, Au@CoP/CC can degrade target organic dyes for the self-cleaning and reproduction of SERS-active substrates under visible light irradiation. This work provides a novel means of using the plasmonic metal-transition metal phosphide composites for high-performance SERS sensing and photodegradation.

Novel "Turn-On" Luminescent Chemosensor for Arginine by Using a Lanthanide Metal-Organic Framework Photosensitizer.

Arginine is considered as a biomarker of cystinuria and other diseases, and thus, it is of urgency to develop a simple and rapid method with high sensitivity and selectivity for arginine detection to meet the demand of on-site analysis and bedside diagnosis. In this work, a lanthanide metal-organic framework, La(TATB), was prepared using a triazine-based planar ligand, 4,4',4″-s-triazine-2,4,6-triyltribenzoate (H3TATB), and lanthanide ion (La3+). La(TATB) can be used as a highly photosensitive agent to activate molecular oxygen to 1O2 to achieve efficient photosensitive oxidation of arginine accompanied by strong blue fluorescence emission under 302 nm UV irradiation. Due to the porous structure and high specific surface area of La(TATB), short-life 1O2 can effectively approach and react with amino acid substrate molecules, thus leading to higher sensitivity than other systems. Therefore, the "turn-on" fluorescence sensing of trace arginine can be realized, with a measured linear response range of 10-20,000 nM and a limit of detection as low as 7 nM. This method can be used for the detection of trace arginine in urine, which is conducive to the bedside diagnosis and rapid screening of cystinuria and other diseases. The proposed method not only expands the application scope of Ln-MOFs but also provides a new construction strategy for "turn-on" luminescence sensors.

Sensitive detection of histamine utilizing the SERS platform combined with an azo coupling reaction and a composite hydrophobic layer.

Herein, the surface-enhanced Raman scattering (SERS) platform was combined with an azo coupling reaction and an aluminum alloy covered with a hydrophobic layer of praseodymium oxide and stearic acid complexes for the detection of histamine. The praseodymium oxide on aluminum alloy was successfully synthesized by the rare-earth-salt-solution boiling bath method and modified by stearic acid. Its surface exhibits a water contact angle (WCA) of 125.0°. Through the azo derivatization reaction with 3-amino-5-mercapto-1,2,4-triazole (AMTA) diazonium salts, histamine can be converted into the derivatization product with higher Raman activity. The mixture of the derivatization product and ß-cyclodextrin-modified Ag nanoparticles (ß-CD-AgNPs) were dropped onto the surface of an aluminum alloy covered with a hydrophobic layer of praseodymium oxide and stearic acid complexes, and dried for SERS measurement. The intensity ratio between the SERS peaks at 1246 cm-1 and 1104 cm-1 (I1246/I1104) of the derivatization product was used for the quantification of histamine. Under the selected conditions, the limit of detection (LOD) and the limit of quantification (LOQ) for this method were 7.2 nM (S/N = 3) and 24 nM (S/N = 10), respectively. The relative standard deviation (RSD) of this method for the determination of 1 µM histamine was 6.1 % (n = 20). The method was also successfully used for the determination of histamine in fish samples with recoveries ranging from 92 % to 111 %. The present method is simple, sensitive, reliable, and may provide a new approach for preparing the composite hydrophobic layer that can enhance SERS signals through hydrophobic condensation effect. Meanwhile, it may have a promising future in the determination of small molecular compounds containing an imidazole ring.

Holotoxin A1 from Apostichopus japonicus inhibited oropharyngeal and intra-abdominal candidiasis by inducing oxidative damage in Candida albicans.

BACKGROUND AND PURPOSE: The holotoxin A1, isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A1 against Candida albicans and in murine oropharyngeal and intra-abdominal candidiasis. EXPERIMENTAL APPROACH: The antifungal effect of holotoxin A1 against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A1, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. Effectiveness and systematic toxicity of holotoxin A1 in vivo was assessed in the oropharyngeal and intra-abdominal candidiasis models in mice. KEY RESULTS: Holotoxin A1 was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A1 inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A1 induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A1 directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of complex I, against C. albicans. Meanwhile, the complex I subunit NDH51 null mutants showed a decreased susceptibility to holotoxin A1. Furthermore, holotoxin A1 significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis in murine models. CONCLUSION AND IMPLICATIONS: Holotoxin A1 is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra-abdominal candidiasis, especially when caused by drug-resistant strains.

Thiol-ene click derivatization reaction coupled with ratiometric surface-enhanced Raman scattering for reproducible and accurate determination of acrylamide.

Acrylamide (AA) is a carcinogen mainly ingested through food and drinking water, making its accurate determination crucial for both food safety and environmental protection. Herein, we proposed a derivatization-based ratiometric surface-enhanced Raman scattering (SERS) method for the quantification of AA. High density Au NPs were anchored to the surface of Cu-TCPP MOF nanosheets (MOFNs) to form the SERS sensor. The abundant Raman "hot spots" at the nanogaps generated by the Au NPs and the internal standard (IS) signal provided by Cu-TCPP MOFNs improved the sensitivity and quantitative accuracy of the method. Following the thiol-ene click derivatization reaction between p-aminothiophenol (PATP) and AA, the Raman peak intensity ratio (I1080/I395) was employed to quantify AA. The linear range was 0.1 nM to 10 µM, and the limit of detection (LOD) was as low as 0.08 nM. Trace amounts of AA in food and water samples were successfully determined using this method.

Akkermansia muciniphila inhibited the periodontitis caused by Fusobacterium nucleatum.

Periodontitis is the most important cause of tooth loss in adults and is closely related to various systemic diseases. Its etiologic factor is plaque biofilm, and the primary treatment modality is plaque control. Studies have confirmed that Fusobacterium nucleatum can cause periodontitis through its virulence factors and copolymerizing effects with other periodontal pathogens, such as the red complex. Inhibiting F. nucleatum is an essential target for preventing periodontitis. The time-consuming and costly traditional periodontal treatment, periodontal scaling, and root planing are a significant burden on individual and public health. Antibiotic use may lead to oral microbial resistance and microbiome imbalance, while probiotics regulate microbial balance. Akkermansia muciniphila is a critical probiotic isolated from the human intestine. It can protect the integrity of the epithelial barrier, regulate and maintain flora homeostasis, improve metabolism, and colonize the oral cavity. Its abundance is inversely correlated with various diseases. We hypothesized that A. muciniphila could inhibit the effects of F. nucleatum and alleviate periodontitis. Bacterial co-culture experiments showed that A. muciniphila could inhibit the expression of the virulence gene of F. nucleatum. After treating gingival epithelial cells (GECs) with F. nucleatum and A. muciniphila, transcriptome sequencing and ELISA experiments on medium supernatant showed that A. muciniphila inhibited the inflammatory effect of F. nucleatum on GECs by inhibiting TLR/MyD88/NF-κB pathway modulation and secretion of inflammatory factors. Finally, animal experiments demonstrated that A. muciniphila could inhibit F. nucleatum-induced periodontitis in BALB/c mice.

Artemisinins inhibit oral candidiasis caused by Candida albicans through the repression on its hyphal development.

Candida albicans is the most abundant fungal species in oral cavity. As a smart opportunistic pathogen, it increases the virulence by switching its forms from yeasts to hyphae and becomes the major pathogenic agent for oral candidiasis. However, the overuse of current clinical antifungals and lack of new types of drugs highlight the challenges in the antifungal treatments because of the drug resistance and side effects. Anti-virulence strategy is proved as a practical way to develop new types of anti-infective drugs. Here, seven artemisinins, including artemisinin, dihydroartemisinin, artemisinic acid, dihydroartemisinic acid, artesunate, artemether and arteether, were employed to target at the hyphal development, the most important virulence factor of C. albicans. Artemisinins failed to affect the growth, but significantly inhibited the hyphal development of C. albicans, including the clinical azole resistant isolates, and reduced their damage to oral epithelial cells, while arteether showed the strongest activities. The transcriptome suggested that arteether could affect the energy metabolism of C. albicans. Seven artemisinins were then proved to significantly inhibit the productions of ATP and cAMP, while reduced the hyphal inhibition on RAS1 overexpression strain indicating that artemisinins regulated the Ras1-cAMP-Efg1 pathway to inhibit the hyphal development. Importantly, arteether significantly inhibited the fungal burden and infections with no systemic toxicity in the murine oropharyngeal candidiasis models in vivo caused by both fluconazole sensitive and resistant strains. Our results for the first time indicated that artemisinins can be potential antifungal compounds against C. albicans infections by targeting at its hyphal development.

Sensitive detection of trace 4-methylimidazole utilizing a derivatization reaction-based ratiometric surface-enhanced Raman scattering platform.

Herein, a facile and fast surface-enhanced Raman scattering (SERS) method with ratiometric strategy was developed for detection of 4-methylimidazole (4-MI). Via a chemical derivatization reaction with 3-amino-5-mercapto-1,2,4-triazole (AMTA) diazonium salts, 4-MI could be converted to SERS-sensitive species. The SERS intensity ratio between the peaks at 1243 cm-1 and 1110 cm-1 (I1243/I1110) was used for the quantification of 4-MI. In addition, the method sensitivity was further improved by the aggregation of beta-cyclodextrin-modified Ag nanoparticles (beta-CD-AgNPs). Under the optimal conditions, the limit of detection (LOD) and the limit of quantification (LOQ) for 4-MI were 1.7 nM (S/N = 3) and 5.7 nM (S/N = 10), respectively. The relative standard deviation (RSD) for 0.5 µM 4-MI was 8.2% (n = 20). This method was successfully used for the determination of 4-MI in cola samples with recoveries ranging from 92% to 106%. The present method is convenient, sensitive, selective, reliable and may have a promising application in determination of the compounds with an imidazole ring containing active hydrogen atoms.

A facile photochemical strategy for the synthesis of high-performance amorphous MoS2 nanoparticles.

It is difficult to avoid the formation of polysulfides by traditional chemical methods, and the synthesis of high purity amorphous MoS2 nanomaterials under ambient conditions is still a challenging task. Here we present a new and facile photochemical strategy for the synthesis of amorphous MoS2 nanomaterials, which is achieved by irradiating a mixed solution containing ammonium molybdate, formic acid and sodium sulfide simply with a Xe lamp for 3 min. The mechanism study reveals that the key step in this synthesis is the photolysis of formic acid to produce free radicals which can rapidly reduce Mo6+ to Mo4+, which then combines with S2- to form MoS2 and inhibits the formation of S-S2- by preventing S2- from participating in the reduction reaction. In addition, the results of a series of experiments indicate that the as-prepared amorphous MoS2 features a small particle size, uniform morphology and relatively large specific surface area, and shows excellent performance in the removal of inorganic heavy metal ions (mercury, lead and cadmium ions) and organic pollutants (rhodamine B and tetracycline), catalase catalysis and a lithium battery anode, showing its great potential and broad application prospects in the fields of environmental remediation, clean energy and green catalysis.