Strategy to Empower Nontargeted Metabolomics by Triple-Dimensional Combinatorial Derivatization with MS-TDF Software.

Chemical derivatization is a widely employed strategy in metabolomics to enhance metabolite coverage by improving chromatographic behavior and increasing the ionization rates in mass spectroscopy (MS). However, derivatization might complicate MS data, posing challenges for data mining due to the lack of a corresponding benchmark database. To address this issue, we developed a triple-dimensional combinatorial derivatization strategy for nontargeted metabolomics. This strategy utilizes three structurally similar derivatization reagents and is supported by MS-TDF software for accelerated data processing. Notably, simultaneous derivatization of specific metabolite functional groups in biological samples produced compounds with stable but distinct chromatographic retention times and mass numbers, facilitating discrimination by MS-TDF, an in-house MS data processing software. In this study, carbonyl analogues in human plasma were derivatized using a combination of three hydrazide-based derivatization reagents: 2-hydrazinopyridine, 2-hydrazino-5-methylpyridine, and 2-hydrazino-5-cyanopyridine (6-hydrazinonicotinonitrile). This approach was applied to identify potential carbonyl biomarkers in lung cancer. Analysis and validation of human plasma samples demonstrated that our strategy improved the recognition accuracy of metabolites and reduced the risk of false positives, providing a useful method for nontargeted metabolomics studies. The MATLAB code for MS-TDF is available on GitHub at https://github.com/CaixiaYuan/MS-TDF.

Drug repositioning and ovarian cancer, a study based on Mendelian randomisation analysis.

Background: The role of drug repositioning in the treatment of ovarian cancer has received increasing attention. Although promising results have been achieved, there are also major controversies. Methods: In this study, we conducted a drug-target Mendelian randomisation (MR) analysis to systematically investigate the reported effects and relevance of traditional drugs in the treatment of ovarian cancer. The inverse-variance weighted (IVW) method was used in the main analysis to estimate the causal effect. Several MR methods were used simultaneously to test the robustness of the results. Results: By screening 31 drugs with 110 targets, FNTA, HSPA5, NEU1, CCND1, CASP1, CASP3 were negatively correlated with ovarian cancer, and HMGCR, PLA2G4A, ITGAL, PTGS1, FNTB were positively correlated with ovarian cancer. Conclusion: Statins (HMGCR blockers), lonafarnib (farnesyltransferase inhibitors), the anti-inflammatory drug aspirin, and the anti-malarial drug adiponectin all have potential therapeutic roles in ovarian cancer treatment.

Ginger inhibits the invasion of ovarian cancer cells SKOV3 through CLDN7, CLDN11 and CD274 m6A methylation modifications.

BACKGROUND: Ginger is a common aromatic vegetable with a wide range of functional ingredients and considerable medicinal and nutritional properties. Numerous studies have shown that ginger and its active ingredients have suppressive effects on manifold tumours, including ovarian cancer (OC). However, the molecular mechanism by which ginger inhibits OC is not clear. The aim of this study was to investigate the function and mechanism of ginger in OC. METHODS: The estimation of n6-methyladenosine (m6A) levels was performed using the m6A RNA Methylation Quantification Kit, and RT-qPCR was used to determine the expression of m6A-related genes and proteins. The m6A methylationome was detected by MeRIP-seq, following analysis of the data. Differential methylation of genes was assessed utilizing RT-qPCR and Western Blotting. The effect of ginger on SKOV3 invasion in ovarian cancer cells was investigated using the wound healing assay and transwell assays. RESULTS: Ginger significantly reduced the m6A level of OC cells SKOV3. The 3'UTR region is the major site of modification for m6A methylation, and its key molecular activities include Cell Adhesion Molecules, according to meRIP-seq results. Moreover, it was observed that Ginger aids significantly in downregulating the CLDN7, CLDN11 mRNA, and protein expression. The results of wound healing assay and transwell assay showed that ginger significantly inhibited the invasion of OC cells SKOV3. CONCLUSIONS: Ginger inhibits ovarian cancer cells' SKOV3 invasion by regulating m6A methylation through CLDN7, CLDN11, and CD274.

Could nutrition status predict fatigue one week before in patients with nasopharynx cancer undergoing radiotherapy?

BACKGROUND: Patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy experience significant fatigue, which is frequently underestimated due to the lack of objective indicators for its evaluation. This study aimed to explore the longitudinal association between fatigue and nutrition status 1 week in advance. METHODS: From January 2021 to June 2022, a total of 105 NPC patients who received intensity-modulated radiation therapy were enrolled in the observational longitudinal study. The significant outcomes, including the Piper Fatigue Scale-12 (PFS-12), the Scored Patient-Generated Subjective Global Assessment (PG-SGA), four body composition indices, and the Hospital Anxiety and Depression Scale (HADS), were assessed weekly from pre-treatment until the completion of radiotherapy (T0-T7) to explore their relationship. RESULTS: The trajectories of PFS-12 and all dimensions for 105 participants reached a peak during the fifth week. Sensory fatigue consistently received the highest scores (T0 = 1.60 ± 2.20, T5 = 6.15 ± 1.57), whereas behavior fatigue exhibited the fastest increase over time (T0 = 1.11 ± 1.86, T5 = 5.47 ± 1.70). Higher PG-SGA scores were found to be weakly explainable for aggravating fatigue (ß = 0.02 ~ 0.04). Unlike generalized additive mixed models, marginal structural models (MSM) produced larger effect values (ß = 0.12 ~ 0.21). Additionally, body composition indices showed weakly negative relationships with fatigue in MSMs one week in advance. CONCLUSIONS: The PG-SGA may be a more accurate predictor of future-week fatigue than individual body composition indicators, particularly when HADS is controlled for as a time-dependent confounder.

Natural flavonols as probes for direct determination of borax: From conventional fluorescence analysis to paper-based smartphone sensing.

Borax is strictly regulated in the food processing and pharmaceutical industry due to its physiological toxicity, and the development of a direct analytical method is essential for effectively monitoring the borax abuse. In this work, the fluorescence properties of flavonoids, including flavones, isoflavones and flavonols, were systematically investigated from aqueous to borax solutions, and it was found that the weak intrinsic fluorescence of flavonols could be pervasively sensitized by borax. A natural flavonol, morin, was subsequently chosen as a representative probe to develop a turn-on fluorescence sensing method for borax analysis, which achieved a linear response spanning four orders of magnitude with a detection limit of 1.07 µM (0.22 µg mL-1 in terms of Na2B4O7 content). Furthermore, a smartphone-assisted paper-based test device was designed and constructed by 3D printing technology. Using morin-impregnated test strips as the carrier, the borax could be visually detected by the RGB signals of the captured images, with a detection limit of 0.13 mM (27.05 µg mL-1 for Na2B4O7). Combining ion exchange treatment for food samples and sodium periodate oxidation for drug samples, the developed methods were successfully applied for the direct analysis of borax in various products with the recoveries of 86.9-106.3% for traditional fluorescence analysis and 82.7-108.8% for smartphone-assisted fluorescence sensing. The fluorescence property of the morin-borax system was studied using time-dependent density functional theory, and the sensing mechanism was discussed in conjunction with experimental research.

Mechanisms of action of Shizhenqing granules for eczema treatment: Network pharmacology analysis and experimental validation.

Background: Jiuwan decoction has been used to treat chronic eczema since the Qing Dynasty. According to clinical experience, Shizhenqing granules (SZQG), derived from the Jiuwan decoction, exert beneficial clinical effects on acute eczema and reduce recurrence. Therefore, we elucidated the underlying mechanisms of SZQG through network pharmacology, molecular docking, and experimental validation. Methods: The main chemical components of SZQG were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). And the targets of SZQG against eczema were screened out through online databases. Then, the regulatory network map of the "herbal compound-potential target" and the target protein-protein interaction (PPI) network was constructed. The Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using by R language. Additionally, the interaction between the active compounds and the targets was verified by molecular docking technology. Finally, an experiment in vivo was used to verify the effect and mechanism of SZQG on eczema. Results: Using UHPLC-MS/MS, 158 main chemical compounds of SZQG were identified, and 72 compounds were selected according to the criteria for further analysis. All 237 potential targets of SZQG in eczema were explored using multiple online databases. The network with 14 core targets was screened out, including STAT3, RELA, TNF, JUN, MAPK3, IL-6, PIK3CA, STAT1, MAPK14, MAPK1, IL-4, NFKBIA, IL1B, and MYC. KEGG analyses indicated that the therapeutic effects of SZQG on eczema were predominantly associated with cytokine-cytokine receptor interaction, TNF, MAPK, NF-κB, toll-like receptor, T cell receptor, and Th1 and Th2 cell differentiation signaling pathways. Furthermore, the good affinity between the core compounds and core targets was verified by molecular docking technology, particularly for RELA and MAPK. Animal experiments revealed that SZQG downregulated MAPK14, RELA, T-bet, and GATA3 mRNA expression, reduced immunoglobulin E (IgE) and interleukin-4 (IL-4) serum concentrations, and improved eczema-like lesions in model rats. Conclusion: This study identified potential targets and signaling pathways of SZQG in the treatment of eczema, whereby RELA and MAPK14 may constitute the main therapeutic targets of SZQG in cytokine regulation and reduction of inflammatory responses.

Circ_BLNK is a Unique Molecular Marker in Non-small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) patients are characterized by distant metastasis and poor prognosis. Growing evidence has implied that circular RNAs (circRNAs) are involved in multiple tumor progression, including NSCLC. The objective of the present study was to functionally dissect the role and mechanism of circ_BLNK in NSCLC development and progression. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of circ_BLNK, miR-942-5p, and forkhead box protein O1 (FOXO1) in NSCLC tissues and cells. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay detected cell proliferation; the protein expression levels were tested by western blot assay; cell apoptosis was measured by flow cytometry, and transwell assay detected cell migration and invasion. The molecular targeting relationship was determined by dual-luciferase reporter assay. The effect of circ_BLNK overexpression on tumor growth was detected by in vivo experiments and immunohistochemistry. Circ_BLNK was dramatically decreased in NSCLC, and overexpression of circ_BLNK inhibited proliferation, migration, and invasion of NSCLC cells and promoted cell apoptosis. Circ_BLNK level was negatively correlated with miR-942-5p expression and positively correlated with FOXO1 expression. Moreover, circ_BLNK acted as a sponge for miR-942-5p, which targeted FOXO1. Rescue assays presented that miR-942-5p reversed the anticancer action of circ_BLNK in NSCLC. Besides that, miR-942-5p inhibition suppressed the oncogenic behaviors, which were attenuated by FOXO1 knockdown. Animal experiments exhibited that circ_BLNK upregulation repressed tumor growth in vivo. Our study demonstrated a novel regulatory mechanism that circ_BLNK/miR-942-5p/FOXO1 axis adjusted non-small cell lung cancer development.

A density functional theory study on the mechanism of toluene from dimethylcyclopentane catalyzed by the [GaH]2+ active site of Ga-ZSM-5.

The ONIOM (ωb97xd/6-31G(d,p):pm6) method was used to study the reaction mechanism of dimethylcyclopentane to toluene by the [GaH]2+ active site of Ga-ZSM-5. The results showed that the rate-determining step in the dimethylcyclopentane aromatization process is the ring expansion process. Compared to those of methylcyclopentane to benzene (D. D. Zhang, H. Y. Liu, L. X. Ling, H. R. Zhang, R. G. Zhang, P. Liu and B. J. Wang, Phys. Chem. Chem. Phys., 2021, 23, 10988-11003.), the free energy barriers of dimethylcyclopentane to toluene are significantly decreased, indicating that toluene is easier to produce than benzene, which confirmed the experimental results that a higher proportion of toluene than benzene is produced in the MTA process.

Self-assembly embedding of curcumin by alkylated rice bran protein.

Lysine-rich rice bran protein (RBP) can be used as raw material for alkylation modification to improve the self-assembly performance of protein. The results of 1H NMR, degree of alkylation, and DSC analysis showed that the alkyl chain was successfully attached to the RBP. The surface hydrophobicity and absolute ζ-potential increased. The three-dimensional structure of the alkylated RBP (ARBP) become more porous and ARBP-2 was selected as the material for embedding curcumin. The XRD results revealed that curcumin induced self-aggregation of ARBP-2 and the inclusion of curcumin was attained. The maximum encapsulation efficiency of curcumin was 82.67 % and the maximum loading amount was 171.37 g/100 g RBP. The results of atomic force microscopy (AFM), particle size, and polydispersity index (PDI) analyses revealed that the particles in the system were aggregated after curcumin was added. Curcumin was well protected by encapsulation in the self-assembled particles. Thus, this study provides a new strategy for the embedding and delivery of curcumin.

Investigations of the reaction mechanism of sodium with hydrogen fluoride to form sodium fluoride and the adsorption of hydrogen fluoride on sodium fluoride monomer and tetramer.

CONTEXT: The reaction between Na and HF is a typical harpooning reaction which is of great interest due to its significance in understanding the elementary chemical reaction kinetics. This work aims to investigate the detailed reaction mechanisms of sodium with hydrogen fluoride and the adsorption of HF on the resultant NaF as well as the (NaF)4 tetramer. The results suggest that the reaction between Na and HF leads to the formation of sodium fluoride salt NaF and hydrogen gas. Na interacts with HF to form a complex HF···Na, and then the approaching of F atom of HF to Na results in a transition state H···F···Na. Accompanied by the broken of H-F bond, the bond forms between F and Na atoms as NaF, then the product NaF is yielded due to the removal of H atom. The resultant NaF can further form (NaF)4 tetramer. The interaction of NaF with HF leads to the complex NaF···HF; the form I as well as II of (NaF)4 can interact with HF to produce two complexes (i.e., (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF), but the form III of (NaF)4 can interact with HF to produce only one complex (NaF)4(III)···HF. These complexes were explored in terms of noncovalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses. NCI analyses confirm the existences of attractive interactions in the complexes HF···Na, NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF. QTAIM analyses suggest that the F···Na interaction forms in the HF···Na complex while the F···H hydrogen bonds form in NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF complexes. Natural bond orbital (NBO) analyses were also applied to analyze the intermolecular donor-acceptor orbital interactions in these complexes. These results would provide valuable insight into the chemical reaction of Na and HF and the adsorption interaction between sodium fluoride salt and HF. METHODS: The calculations were carried out at the M06-L/6-311++G(2d,2p) level of theory which were performed using the Gaussian16 program. Intrinsic reaction coordinate (IRC) calculations were carried out at the same level of theory to confirm that the obtained transition state was true. The molecular surface electrostatic potential (MSEP) was employed to understand how the complex forms. Quantum theory of atoms in molecules (QTAIM) and noncovalent interaction (NCI) analysis was used to know the topology parameters at bond critical points (BCPs) and intermolecular interactions in the complex and intermediate. The topology parameters and the BCP plots were obtained by the Multiwfn software.

An integrated approach for studying the metabolic profiling of herbal medicine in mice using high-resolution mass spectrometry and metabolomics data processing tools.

Analysis of exposure to traditional Chinese medicine (TCM) in vivo based on mass spectrometry is helpful for the screening of effective ingredients of TCM and the development of new drugs. The method of screening biomarkers through metabolomics technology is a nontargeted research method to explore the differential components between two sets of biological samples. By taking this advantage, this study aims to takes Forsythia suspensa, which is a TCM also known as Lian Qiao (LQ), as the research object and to study its in vivo exposure by using metabolomics technology. By comparing the significant differences between biological samples before and after administration, it could be focused on the components that were significantly upregulated, where a complete set of analysis strategies for nontargeted TCM in vivo exposure mass spectrometry was established. Furthermore, the threshold parameters for peak extraction, parameter selection during statistical data analysis, and sample concentration multiples in this method have also been optimized. More interestingly, by using the established analysis strategy, we found 393 LQ-related chemical components in mice after administration, including 102 prototypes and 291 LQ-related metabolites, and plotted their metabolic profiles in vivo. In short, this study has obtained a complete mass spectrum of LQ exposure in mice in vivo for the first time, which provides a reference for research on the active ingredients of LQ in vivo. More importantly, compared with other methods, the analysis strategy of nontargeted exposure of TCM in vivo-based mass spectrometry, constructed by using this research method, has good universality and does not require self-developed postprocessing software. It is worth mentioning that, for the identification and characterization of trace amounts of metabolites in vivo, this analysis strategy has no discrimination and has a detection capability similar to that of highly exposed components.

Research progress on antisepsis effect of apigenin and its mechanism of action.

Sepsis is an abnormal immune response to infections and can trigger MODS. Despite the availability of advanced clinical techniques and monitoring methods, the mortality rate of the disease is still high, posing a heavy burden to patients and the whole society. Hence, the research on novel drugs and targets is particularly important. As a natural phyto-flavonoid, apigenin boasts anti-inflammatory, antioxidant, anti-cancer, anti-viral, and anti-bacterial effects. Besides, in-vitro experiments and animal models have also revealed the crucial role of apigenin in the treatment of infectious diseases and sepsis. In this context, this paper reviews the pharmacological activity and underlying mechanisms of action of apigenin in sepsis treatment and organ protection, as well as the potential apigenin-based therapeutic strategies against sepsis. Therefore, this review will shed new light on the scientific research and clinical treatment of sepsis.

PVP-capped silver nanoparticles for efficient SERS detection of adenine based on the stabilizing and enrichment roles of PVP.

A polyvinylpyrrolidone-capped (PVP-capped) strategy is reported to synthesize Ag NPs on silicon wafers via galvanic replacement reaction for SERS detection of adenine, where PVP acts as stabilizing agent in synthesis and efficient enrichment in detection. The morphologies of Ag NPs are optimized with uniform particle size by adjusting synthesis conditions, which hold excellent SERS performances like a high enhancement factor of 1.42 × 106, good uniform, reproducibility, and transferable nature. With the protection of the capped PVP, the Ag NPs keep excellent SERS properties even against harsh conditions of high temperature (100 ℃) and strong acid and base for 24 h. Utilizing the structural feature of PVP with abundant carbonyl groups, the PVP-capped Ag NPs achieve efficient enrichment of adenine through hydrogen bonding and π-interactions, which is analyzed by density functional theory. Quantitative detection of adenine is performed with a wide linear range from 10-4 to 10-8 M and a low limit of detection of 1 nM. Detection of adenine in human urine samples is achieved with a recovery of 99.1-103.4% and an RSD of less than 5%.

Self-powered biosensor using photoactive ternary nanocomposite: Testing the phospholipid content in rhodotorula glutinis oil.

In the field of oil refining, the presence of excessive residual phosphorus in crude oil can significantly impact its quality, thereby emphasizing the necessity for compact and convenient testing equipment. This study primarily focuses on developing of self-powered biosensor (SPB) using immobilizing Choline Oxidase with a photoactive ternary nanocomposite complex (CHOx-BiOI-rGO-Fe3O4 NPs-ITO) as the anode and utilizing a Pt electrode as the cathode. The successful preparation of the ternary composite photoelectrode for the anode was confirmed through a range of characterization techniques, including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), N2 absorption/desorption, Dynamic light scattering (DLS), and Ultraviolet-visible diffuse reflection spectrometer (UV-vis DRS). The electrochemical and photoelectrochemical properties were assessed using an electrochemical workstation, revealing a significant enhancement photoelectrical responsiveness attributed to the formation of heterojunction structures. The SPB exhibited a remarkable linear relationship between the instantaneous photocurrent and phosphatidylcholine (PC) concentration, with a regression equation of I (µA) = 39.62071C (mM) + 3.47271. The linear range covered a concentration range of 0.01-10 mM, and the detection limit (S/N = 3) was determined to be 0.008 mM. It demonstrated excellent reproducibility and storage stability, positioning it a promising alternative to High-performance liquid chromatography (HPLC) for accurate quantification of PC content in rhodotorula glutinis oil. The standard recovery PC content ranged from 98.48% to 103.53%, with a relative standard deviation (RSD) ranging from 1.4% to 2.4%. This research presents a convenient and precise detection device that has the potential to address the issue of lagging detection in the oil refining process.

RNA m6A methylation regulators in sepsis.

N6-methyladenosine (m6A) modification is a class of epitope modifications that has received significant attention in recent years, particularly in relation to its role in various diseases, including sepsis. Epigenetic research has increasingly focused on m6A modifications, which is influenced by the dynamic regulation of three protein types: ?Writers" (such as METTL3/METTL14/WTAP)-responsible for m6A modification; ?Erasers" (FTO and ALKBH5)-involved in m6A de-modification; and ?Readers" (YTHDC1/2, YTHDF1/2/3)-responsible for m6A recognition. Sepsis, a severe and fatal infectious disease, has garnered attention regarding the crucial effect of m6A modifications on its development. In this review, we attempted to summarize the recent studies on the involvement of m6A and its regulators in sepsis, as well as the significance of m6A modifications and their regulators in the development of novel drugs and clinical treatment. The potential value of m6A modifications and modulators in the diagnosis, treatment, and prognosis of sepsis has also been discussed.

Focused ultrasound-mediated brain genome editing.

Gene editing in the brain has been challenging because of the restricted transport imposed by the blood-brain barrier (BBB). Current approaches mainly rely on local injection to bypass the BBB. However, such administration is highly invasive and not amenable to treating certain delicate regions of the brain. We demonstrate a safe and effective gene editing technique by using focused ultrasound (FUS) to transiently open the BBB for the transport of intravenously delivered CRISPR/Cas9 machinery to the brain.

Advances on the anti-tumor mechanisms of the carotenoid Crocin.

Saffron is located in the upper part of the crocus stigma of iridaceae, which has a long history of medicinal use. Crocin (molecular formula C44H64O24) is a natural floral glycoside ester compound extracted from saffron, which is a type carotenoid. Modern pharmacological studies have shown that crocin has multiple therapeutic effects including anti-inflammatory, anti-oxidant, anti-hyperlipidemic and anti-stone effects. In recent years, crocin has been widely noticed due to its considerable anti-tumor effects manifested by the induction of tumor cell apoptosis, inhibition of tumor cell proliferation, inhibition of tumor cell invasion and metastasis, enhancement of chemotherapy sensitivity and improvement of immune status. The anti-tumor effects have been shown in various malignant tumors such as gastric cancer, liver cancer, cervical cancer, breast cancer and colorectal cancer. In this review, we compiled recent studies on the anti-tumor effects of crocin and summarized its anti-tumor mechanism for developing ideas of treating malignancies and exploring anti-tumor drugs.

Effects of electric field intensity regulation on protein aggregation behaviour and foaming property of soybean 7S globulin.

In this study, the aggregation behaviour of soybean 7S globulin after moderate electric field (MEF) treatment was investigated, and the influence of the electric field and temperature field on the structure and foaming property of the aggregates were analysed and compared with conventional water bath (COV). The results showed that MEF treatment enhanced the properties of the aggregates. The properties of the treated aggregates were significantly better than those of native 7S globulin. At an electric field strength of 8 V/cm, the solubility, turbidity, and particle size increased from 95.81 % to 99.37 %, 0.097 to 0.189 and 61.97 nm to 113.21 nm, respectively, and the absolute value of potential decreased from 23.56 mV to 22.12 mV. The SDS-PAGE and size exclusion chromatography (SEC) results showed that the electric field had a positive effect on the aggregate formation of the Fourier-transform infrared spectroscopy (FTIR), fluorescence spectroscopy, surface hydrophobicity (H0) and total sulfhydryl (SHT) results indicated that the spatial structure of the protein was changed by MEF treatment. The protein ß-sheet content was reduced, and the Try that was originally buried inside the molecule was exposed, resulting in an increase in H0 and a decrease in SHT. The foaming property of the 7S globulin aggregates was improved by MEF treatment.

PTK2B regulates immune responses of neutrophils and protects mucosal inflammation in ulcerative colitis.

Neutrophils participate in the pathogenesis of ulcerative colitis (UC) through regulating the intestinal homeostasis. Several inflammatory diseases are reported to be regulated by proline-rich tyrosine kinase 2B (PTK2B). However, the role of PTK2B in regulating the function of neutrophils and the pathogenesis of UC remains unknown. In this study, the mRNA and protein levels of PTK2B in the colonic tissues from UC patients were measured by using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. TAE226, a PTK2B inhibitor, was used to inhibit the activity of PTK2B in neutrophils, and then, the pro-inflammatory factors were analyzed by using qRT-PCR and ELISA. To determine the role of PTK2B in intestinal inflammation, a dextran sulfate sodium (DSS)-induced colitis model was established in PTK2B gene knockout (PTK2B KO) and wild-type (WT) mice. We found that compared with healthy donor controls, the expression level of PTK2B was significantly elevated in inflamed mucosa from UC patients. In addition, expression of PTK2B was positively correlated with the severity of disease. Pharmacological inhibition of PTK2B could markedly reduce the generation of reactive oxygen species (ROS), myeloperoxidase (MPO), and antimicrobial peptides (S100a8 and S100a9) in neutrophils. The vitro study showed that tumor necrosis factor (TNF)-α is involved in promoting the expression of PTK2B in neutrophils. As expected, UC patients treated with infliximab, an anti-TNF-α agent, showed significantly reduced level of PTK2B in neutrophils, as well as in the intestinal mucosa. Of note, compared with DSS-treated WT mice, DSS-treated PTK2B KO mice showed more severe colitis symptoms. Mechanistically, PTK2B could enhance neutrophil migration by regulating CXCR2 and GRK2 expression via the p38 MAPK pathway. Additionally, mice treated with TAE226 exhibited the same effects. In conclusion, PTK2B is involved in the pathogenesis of UC by promoting the migration of neutrophils and inhibiting mucosal inflammation, highlighting PTK2B as a new potential therapeutic target to treat UC.

Observation on the aerosol and ozone precursors in suburban areas of Shenzhen and analysis of potential source based on MAX-DOAS.

Long-term stereoscopic observations of aerosol, NO2, and HCHO were carried out at the Yangmeikeng (YMK) site in Shenzhen. Aerosol optical depths and NO2 vertical column concentration (NO2 VCD) derived from MAX-DOAS were found to be consistent with other datasets. The total NO2 VCD values of the site remained low, varying from 2 × 1015 to 8 × 1015 mol/cm2, while the HCHO VCD was higher than NO2 VCD, varying from 7 × 1015 to 11 × 1015 mol/cm2. HCHO VCD was higher from September to early November than that was from mid-late November to December and during February 2021, in contrast, NO2 VCD did not change much during the same period. In January, NO2 VCD and HCHO VCD were both fluctuating drastically. High temperature and HCHO level in the YMK site is not only driving the ozone production up but also may be driving up the ozone concentration as well, and the O3 production regime in the YMK site tends to be NOx-limited. At various altitudes, backward trajectory clustering analysis and Potential Source Contribution Function (PSCF) were utilized to identify possible NO2 and HCHO source locations. The results suggested that the Huizhou-Shanwei border and the Daya Bay Sea area were the key potential source locations in the lower (200 m) and middle (500 m) atmosphere (WPSCF > 0.6). The WPSCF value was high at the 1000 m altitude which was closer to the YMK site than the near ground, indicating that the pollution transport capability in the upper atmosphere was limited.