Lipidomic signatures in patients with early-onset and late-onset Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific clinical syndrome and can be subdivided into early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE) according to the gestational age of delivery. Patients with preeclampsia have aberrant lipid metabolism. This study aims to compare serum lipid profiles of normal pregnant women with EOPE or LOPE and screening potential biomarkers to diagnose EOPE or LOPE. METHODS: Twenty normal pregnant controls (NC), 19 EOPE, and 19 LOPE were recruited in this study. Untargeted lipidomics based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to compare their serum lipid profiles. RESULTS: The lipid metabolism profiles significantly differ among the NC, EOPE, and LOPE. Compared to the NC, there were 256 and 275 distinct lipids in the EOPE and LOPE, respectively. Furthermore, there were 42 different lipids between the LOPE and EOPE, of which eight were significantly associated with fetal birth weight and maternal urine protein. The five lipids that both differed in the EOPE and LOPE were DGTS (16:3/16:3), LPC (20:3), LPC (22:6), LPE (22:6), PC (18:5e/4:0), and a combination of them were a potential biomarker for predicting EOPE or LOPE. The receiver operating characteristic analysis revealed that the diagnostic power of the combination for distinguishing the EOPE from the NC and for distinguishing the LOPE from the NC can reach 1.000 and 0.992, respectively. The association between the lipid modules and clinical characteristics of EOPE and LOPE was investigated by the weighted gene co-expression network analysis (WGCNA). The results demonstrated that the main different metabolism pathway between the EOPE and LOPE was enriched in glycerophospholipid metabolism. CONCLUSIONS: Lipid metabolism disorders may be a potential mechanism of the pathogenesis of preeclampsia. Lipid metabolites have the potential to serve as biomarkers in patients with EOPE or LOPE. Furthermore, lipid metabolites correlate with clinical severity indicators for patients with EOPE and LOPE, including fetal birth weight and maternal urine protein levels.

Diversity in people's reluctance to use medical artificial intelligence: Identifying subgroups through latent profile analysis.

Medical artificial intelligence (AI) is important for future health care systems. Research on medical AI has examined people's reluctance to use medical AI from the knowledge, attitude, and behavioral levels in isolation using a variable-centered approach while overlooking the possibility that there are subpopulations of people who may differ in their combined level of knowledge, attitude and behavior. To address this gap in the literature, we adopt a person-centered approach employing latent profile analysis to consider people's medical AI objective knowledge, subjective knowledge, negative attitudes and behavioral intentions. Across two studies, we identified three distinct medical AI profiles that systemically varied according to people's trust in and perceived risk imposed by medical AI. Our results revealed new insights into the nature of people's reluctance to use medical AI and how individuals with different profiles may characteristically have distinct knowledge, attitudes and behaviors regarding medical AI.

Covalent organic framework based nanoagent for enhanced mild-temperature photothermal therapy.

Photothermal therapy effectively ablates tumors by hyperthermia (>50 °C) under laser irradiation. However, the hyperthermia may inevitably diffuse to the surrounding healthy tissues to induce additional damage. Thus, effective cancer therapy by mild photothermal therapy at low temperatures is greatly desirable. In this study, a nanoagent (COF-GA) was designed to inhibit HSP90 for enhanced photothermal therapy against cancer at low temperatures. The nanoscale covalent organic frameworks (COFs) were able to increase the temperature of the tumor tissue under laser irradiation, which can transfer the energy of laser into heat for cancer cell killing. Gambogic acid (GA), as an inhibitor of HSP90, was used to overcome the heat resistance of tumor, achieving efficient mild-temperature photothermal therapy. As an excellent candidate for the photothermal therapy agent, COF-GA can induce the temperature to elevate as the exposure time increased when irradiated with laser. In vivo tests further demonstrated that the tumor growth was able to be significantly suppressed after being treated with COF-GA. The mild-temperature photothermal therapy exhibits an excellent antitumor efficacy at a relatively low temperature and minimizes the nonspecific thermal damage to normal tissues. This COF-GA nanoagent also enriches our understanding towards the various applications of COFs, particularly in the biomedicine field.

Thermochromism and piezochromism of an atomically precise high-nuclearity silver sulfide nanocluster.

A novel high-nuclearity silver sulfide nanocluster [Ag50S7(SC6H4F)36(dppp)6]·4DMI, (hereafter abbreviated as 1⋅4DMI) was synthesised. Solvent-free crystals of 1 displayed a completely reversible narrowing and broadening of the optical band gap that was accompanied by visual thermochromism and piezochromism changeovers, when stimulated by varying temperatures between 113 and 413 K or by changing the pressure from 1 atm to 7.5 GPa.

A hybrid transition metal nanocrystal-embedded graphitic carbon nitride nanosheet system as a superior oxygen electrocatalyst for rechargeable Zn-air batteries.

In this study, we, for the first time, demonstrate a general solid-phase pyrolysis method to synthesize hybrid transition metal nanocrystal-embedded graphitic carbon nitride nanosheets, namely M-CNNs, as a highly efficient oxygen electrocatalyst for rechargeable Zn-air batteries (ZABs). The ratios between metallic acetylacetonates and the g-C3N4 precursor can be controlled where Fe-CNNs-0.7, Ni-CNNs-0.7 and Co-NNs-0.7 composites have been optimized to exhibit superior ORR/OER bifunctional electrocatalytic activities. Specifically, Co-CNNs-0.7 exhibited not only a comparable half-wave potential (0.803 V vs. RHE) to that of the commercial Pt/C catalyst (0.832 V) with a larger current density for the ORR but also a lower overpotential (440 mV) toward the OER compared with the commercial IrO2 catalyst (460 mV), revealing impressive application in rechargeable ZABs. As a result, ZABs using Co-CNNs-0.7 as the cathode exhibited an excellent peak power density of 85.3 mW cm-2 with a specific capacity of 675.7 mA h g-1 and remarkable cycling stability of 1000 cycles, outperforming the commercially available Pt/C + IrO2 catalysts. This study highlights the synergy from heterointerfaces in oxygen electrocatalysis, thus providing a promising approach for advanced metal-air cathode materials.

Celastrol ameliorates Aspergillus fumigatus keratitis via inhibiting LOX-1.

PURPOSE: To investigate the effect of Celastrol (CLT) on Aspergillus fumigatus (A. fumigatus) keratitis. METHODS: Primary peritoneal macrophages of C57BL/6 mice were pretreated with CLT before A. fumigatus hyphae stimulation. C57BL/6 mice were infected with A. fumigatus. Mice corneas were treated with CLT from 1 day post infection. Clinical score, PCR, ELISA and Western blot were used to test expression of anti-inflammatory mediators, proinflammatory mediators and Lectin-like oxidized low-density lipoprotein receptor 1(LOX-1). The protein levels of p38MAPK after pretreated with CLT in macrophages of C57BL/6 mice challenged with A. fumigatus were tested by Western blot. RESULTS: C57BL/6 mice treated with CLT from 1 day post infection showed decreased disease, IL-1ß, TNF-α, IL-10, TGF-ß, MIP-2 and LOX-1 levels. CLT treatment markedly inhibiting mRNA and proteins levels of anti-inflammatory mediators, proinflammatory mediators and LOX-1 in macrophages of C57BL/6 mice compared with control group. CLT pretreatment before A. fumigatus stimulation obviously inhibiting protein levels of p38MAPK versus DMSO pretreated group in macrophages of C57BL/6 mice challenged with A. fumigatus. CONCLUSION: These data provide evidences that CLT ameliorates A. fumigatus keratitis of C57BL/6 mice via inhibiting LOX-1. CLT pretreatment before A. fumigatus stimulation decreased levels of inflammation in macrophages of C57BL/6 mice, which may be regulated by p-p38MAPK.

Nuclear-Targeted Photothermal Therapy Prevents Cancer Recurrence with Near-Infrared Triggered Copper Sulfide Nanoparticles.

Clinical cancer treatments nowadays still face the challenge of recurrence due to the residual cancer cells and minute lesions in surgeries or chemotherapies. To effectively address the problem, we introduce a strategy for constructing cancer cell nuclear-targeted copper sulfide nanoparticles (NPs) with a significant photothermal effect to completely kill residual cancer cells and prevent local cancer recurrence. The NPs could directly target the tumor cells and further enter the nucleus by the surface modification of RGD and TAT peptides. Under the irradiation of 980 nm near-infrared laser, the NPs rapidly increase the temperature of the nucleus, destroy the genetic substances, and ultimately lead to an exhaustive apoptosis of the cancer cells. In vivo experiments show that the designed NPs could effectively treat cancer and prevent the return of cancer with a single laser irradiation for 5 min. The photothermal therapy strategy with nuclear targeting for cancer therapy and anti-recurrence will provide more possibilities to develop efficient platforms for treating cancer.

A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite.

Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen (1O2) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.

Transglutaminase-set colloidal properties of wheat gluten with ultrasound pretreatments.

The low solubility of wheat gluten limits its accessibility. This work aimed to study the impact of ultrasonic pretreatments on the gelation of wheat gluten. The pretreatments included ultrasound combined with alkali, urea, Na2SO3, with or without the addition of transglutaminase (TGase). The gel strength of wheat gluten was 287g/cm2 after treatment with Na2SO3/ultrasound/TGase. The free sulfhydryl and disulfide bond content was significantly affected by ultrasound treatment. After treatments including TGase crosslinking, the molecular weight of wheat gluten complexes became larger. The network formed by the wheat gluten was transformed into a dense and homogenous structure after the pretreatment with Na2SO3/ultrasound/TGase. The content of random coil of wheat gluten increased. The gelation of wheat gluten could also be significantly enhanced by Na2SO3/ultrasound treatment followed by TGase treatment. Using physical and chemical pretreatments to allow TGase to enhance the gelation of wheat gluten may increase its uses as a food additive.

Heterologous production of an acidic thermostable lipase with broad-range pH activity from thermophilic fungus Neosartorya fischeri P1.

Thermophilic Neosartorya fischeri P1 is an excellent lipase producer and harbors seven lipase genes. All genes were found to be functional after heterologous expression in Escherichia coli. One of them, LIP09, showed high-level expression in Pichia pastoris with the yield of 2.0 g/L in a 3.7-L fermentor. Deduced amino acid sequence of LIP09 consists of a putative signal peptide (residues 1-19) and a mature polypeptide (residues 20-562). Compared with other fungal counterparts, purified recombinant LIP09 has some superior properties. It exhibited maximum activity at 60°C and pH 5.0, had broad pH adaptability (>60% activity at pH 3.5-8.0) and stability (retaining >90% activity after incubation at pH 3.0-7.0 for 1 h at 40°C), and was highly thermostable (retaining >96% activity after incubation at 50°C for 30 min). The r-LIP09 had a preference for the medium-chain length p-nitrophenyl esters (C12) rather than short and long-chain length substrates. The high-level expression and excellent properties make LIP09 a potential enzyme candidate in food and feed industries.

Effects of partial hydrolysis and subsequent cross-linking on wheat gluten physicochemical properties and structure.

The rheological behavior and thermal properties of wheat gluten following partial hydrolysis using Alcalase and subsequent microbial transglutaminase (MTGase) cross-linking were investigated. The wheat gluten storage modulus (G') and thermal denaturation temperature (Tg) were significantly increased from 2.26 kPa and 54.43°C to 7.76 kPa and 57.69°C, respectively, by the combined action of partial hydrolysis (DH 0.187%) and cross-linking. The free SH content, surface hydrophobicity, and secondary structure analysis suggested that an appropriate degree of Alcalase-based hydrolysis allowed the compact wheat gluten structure to unfold, increasing the ß-sheet content and surface hydrophobicity. This improved its molecular flexibility and exposed additional glutamine sites for MTGase cross-linking. SEM images showed that a compact 3D network formed, while SDS-PAGE profiles revealed that excessive hydrolysis resulted in high-molecular-weight subunits degrading to smaller peptides, unsuitable for cross-linking. It was also demonstrated that the combination of Alcalase-based partial hydrolysis with MTGase cross-linking might be an effective method for modifying wheat gluten rheological behavior and thermal properties.

A Near-Infrared Triggered Nanophotosensitizer Inducing Domino Effect on Mitochondrial Reactive Oxygen Species Burst for Cancer Therapy.

Photodynamic therapy (PDT) is a well-established modality for cancer therapy, which locally kills cancer cells when light irradiates a photosensitizer. However, conventional PDT is often limited by the extremely short lifespan and severely limited diffusion distance of reactive oxygen species (ROS) generated by photosensitizer, as well as the penetration depth of visible light activation. Here, we develop a near-infrared (NIR) triggered nanophotosensitizer based on mitochondria targeted titanium dioxide-coated upconversion nanoparticles for PDT against cancer. When irradiated by NIR laser, the nanophotosensitizer could produce ROS in mitochondria, which induced the domino effect on ROS burst. The overproduced ROS accumulated in mitochondria, resulting in mitochondrial collapse and irreversible cell apoptosis. Confocal fluorescence imaging indicated that the mitochondrial targeting and real-time imaging of ROS burst could be achieved in living cells. The complete removal of tumor in vivo confirmed the excellent therapeutic effect of the nanophotosensitizer.