Experimental Investigation of Water Vapor Concentration on Fracture Properties of Asphalt Concrete.

The effect of moisture on the fracture resistance of asphalt concrete is a significant concern in pavement engineering. To investigate the effect of the water vapor concentration on the fracture properties of asphalt concrete, this study first designed a humidity conditioning program at the relative humidity (RH) levels of 2%, 50%, 80%, and 100% for the three types of asphalt concrete mixtures (AC-13C, AC-20C, and AC-25C).The finite element model was developed to simulate the water vapor diffusion and determine the duration of the conditioning period. The semi-circular bending (SCB) test was then performed at varying temperatures of 5 °C, 15 °C, and 25 °C to evaluate the fracture energy and tensile strength of the humidity-conditioned specimens. The test results showed that the increasing temperature and the RH levels resulted in a lower peak load but greater displacement of the mixtures. Both the fracture energy and tensile strength tended to diminish with the rising temperature. It was also found that moisture had a significant effect on the tensile strength and fracture energy of asphalt concrete. Specifically, as the RH level increased from 2% to 100% (i.e., the water vapor concentration rose from 0.35 g/m3 to 17.27 g/m3), the tensile strength of the three types of mixtures was reduced by 34.84% on average, which revealed that the water vapor led to the loss of adhesion and cohesion within the mixture. The genetic expression programming (GEP) model was developed to quantify the effect of water vapor concentrations and temperature on the fracture indices.

Systematically uncovering the absorbed effective substances of Radix Scutellaria-licorice drug pair in rat plasma against COVID-19 using a combined UHPLC-Q-TOF-MS analysis and target network pharmacology.

Radix Scutellaria-Licorice drug pair (RSLDP), a frequently used herbal pair with the effect of clearing heat and detoxifying, is the commonly employed drug pair in TCM prescriptions for the treatment of COVID-19. Until now, the metabolism feature and anti-COVID-19 mechanism of RSLDP have not been fully elucidated. In this study, a sensitive and rapid method was developed for the separation and identification of the absorbed constituents of RSLDP in the rat plasma by UHPLC-QTOF-MS. Additionally, we optimized the conventional methodologies of network pharmacology and proposed a new concept called target network pharmacology (T-NP). It used the absorbed constituents and the corresponding targets to generate a compound-target network, and compared to conventional network pharmacology, it could reduce false-positive results. A total of 85 absorbed constituents were identified or tentatively characterized in dosed plasma, including 32 components in the group of Radix Scutellaria, 27 components in the group of Licorice, and 65 components in the group of RSLDP. The results showed that the compatibility of Radix Scutellaria and Licorice increased the number of components in vivo. We found that 106 potential targets among the 61 active compounds in RSLDP were related to COVID-19. And 12 targets (STAT3, AKT1, EGFR, HSP9AA1, MAPK3, JUN, IL6, VEGFA, TNF, IL2, RELA, and STAT1) could be core targets for RSLDP in treating COVID-19. Results from these targets indicate that RSLDP treatment of COVID-19 mainly involves response to chemical stress, response to oxygenates, positive regulation of cytokines, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway for diabetic complications, virus-related pathways such as novel coronavirus and human cytomegalovirus infection, inflammatory immune-related pathways, and so on. The metabolism feature of RSLDP in vivo was systematically uncovered. The combined use of the T-NP method could discover potential drug targets and disclose the biological processes of RSLDP, which will clarify the potential mechanisms of RSLDP in the treatment of COVID-19.

Study on mechanism of hepatoprotective effect of Chrysanthemum morifolium Ramat. based on metabolomics with network analysis and network pharmacology.

Hangju (HJ), the dried flower heads of Chrysanthemum morifolium Ramat., has a significant hepatoprotective effect. However, its underlying protection mechanism against acute liver injury (ALI) has been unclear. An integrated strategy based on metabolomics with network analysis and network pharmacology was developed to explore the potential molecular mechanism of HJ on ALI protection. Firstly, differential endogenous metabolites were screened and identified by metabolomics approach and metabolic pathway analysis was performed by MetaboAnalyst. Secondly, marker metabolites were used to construct metabolite-response-enzyme-gene networks and discover hub metabolites and potential gene targets in network analysis. Thirdly, hub genes through the protein-protein interaction (PPI) network were acquired by the aid of network pharmacology. Finally, the gene targets were taken to intersect with the relevant active ingredients for validation by molecular docking. In total, 48 flavonoids were identified in HJ, which were associated with 8 potential therapeutic targets in network pharmacological analysis. Biochemistry and histopathology analysis demonstrated that HJ exerted hepatoprotective effects. 28 biomarkers were successfully identified as possible biomarkers for the prevention of ALI. The sphingolipid metabolic pathway and the glycerophospholipid metabolic pathway was considered a crucial signaling pathway by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, phosphatidylcholine and sphingomyelin were considered as hub metabolites. Twelve enzymes and 38 genes were considered as potential targets in the network analysis. Based on the combined analysis above, HJ was shown to modulate 2 key upstream targets, including PLA2G2A and PLA2G4A. Molecular docking showed that active compounds of HJ had high binding affinity with these key targets. In conclusion, the flavonoid components of HJ can inhibit PLA2 and regulate glycerophospholipid and sphingolipid metabolism pathway to delay the pathological process of ALI, which may be a potential mechanism of HJ against ALI.

A practical technique for rapid characterisation of ent-kaurane diterpenoids in Isodon serra (Maxim.) Hara by UHPLC-Q-TOF-MS/MS.

INTRODUCTION: The diterpenoids are the most important active constituents that contribute to the pharmacological efficacy of Isodon serra (Maxim.) Hara. Clinical studies have revealed that diterpenoids possess multiple features, e.g. antitumour, antitubercular and anti-ischemic activities. Therefore, the identification and detection of diterpenoids may be equally important for understanding the pharmacological basis of diterpenoids and enhancing the product quality control of I. serra. OBJECTIVES: The purpose of this study was to develop a practical analysis approach of rapid characterisation using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) for the structure characterisation of the ent-kaurane diterpenoids from I. serra. METHODOLOGY: The analytical strategy was as follows: first, ent-kaurane diterpenoids were detected by a novel on-line data acquisition approach, i.e. sequential window acquisition of all theoretical fragment-ion spectra (SWATH). Second, the MS of eight ent-kaurane diterpenoids was explored, and their mass spectrum cleavage pathways were summarised and determined. Finally, the methanol extract of I. serra was studied using SWATH and identified by extracted ion chromatography (XIC). RESULTS: Compared to the traditional information-dependent acquisition (IDA) method, SWATH significantly improved the hit rate of ent-kaurane diterpenoids. With support from UHPLC separation and specific detection by tandem mass spectrometry (MS/MS), 48 ent-kaurane diterpenoids were successfully characterised and classified as ent-kaurane diterpenoids from a complex matrix. CONCLUSIONS: These combined qualitative methods were used to provide a potential approach for the characterisation of traditional Chinese medicine (TCM) and its preparations. Meanwhile, the SWATH provided a novel and reliable method for the structural characterisation of ent-kaurane diterpenoids from other complicated TCMs.

Chronic Progression of Lung Cancer Recurrence After Surgery: Warning Role of Postoperative Pneumonia.

PURPOSE: The association between the process of postoperative pneumonia and lung cancer recurrence remains elusive in lung cancer surgery. Herein, the association between postoperative pneumonia and lung cancer recurrence was investigated, emphasizing the warning role of postoperative specific pneumonia in primary lung cancer resection patients. METHODS: The occurrence of postoperative pneumonia was assessed in 4-6 months (PPFS), 7-12 months (PPST), and lung cancer recurrence within 1 year (LRO) in 332 patients. The primary outcome was the development of PPST and LRO according to PPFS occurrence. The relevant risk factors of PPFS, PPST, and LRO were identified through multivariable regression analysis. RESULTS: During follow-up, 151 (45.48%) participants experienced PPFS. Irrespective of the existing postoperative pneumonia in 1-3 months (PPOT), PPFS significantly increased the risk of PPST (P < 0.01) and LRO (P < 0.01), and persistent PPST further increased the risk of LRO (P < 0.001). The generalized estimating equation identified chemotherapy as an independent risk factor for PPFS and PPST. CONCLUSION: PPFS was associated with the increased risk of PPST and LRO. Postoperative pulmonary inflammation assessed 4 months post-surgery also significantly influenced LRO development, indicating a need for close follow-up of lung inflammatory conditions to improve patient outcomes.

1H-NMR spectroscopy identifies potential biomarkers in serum metabolomic signatures for early stage esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent types of upper gastrointestinal malignancies. Here, we used 1H nuclear magnetic resonance spectroscopy (1H-NMR) to identify potential serum biomarkers in patients with early stage ESCC. METHODS: Sixty-five serum samples from early stage ESCC patients (n = 25) and healthy controls (n = 40) were analysed using 1H-NMR spectroscopy. We distinguished between different metabolites through principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis (OPLS-DA) using SIMCA-P+ version 14.0 software. Receiver operating characteristic (ROC) analysis was conducted to verify potential biomarkers. RESULTS: Using OPLS-DA, 31 altered serum metabolites were successfully identified between the groups. Based on the area under the ROC curve (AUROC), and the biomarker panel with AUROC of 0.969, six serum metabolites (α-glucose, choline, glutamine, glutamate, valine, and dihydrothymine) were selected as potential biomarkers for early stage ESCC. Dihydrothymine particularly was selected as a new feasible biomarker associated with tumor occurrence. CONCLUSIONS: 1H-NMR spectroscopy may be a useful tumour detection approach in identifying useful metabolic ESCC biomarkers for early diagnosis and in the exploration of the molecular pathogenesis of ESCC.

Exploring potential biomarkers of early stage esophageal squamous cell carcinoma in pre- and post-operative serum metabolomic fingerprint spectrum using 1H-NMR method.

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent types of upper gastrointestinal malignancy. Here, we used 1H nuclear magnetic resonance spectroscopy (1H-NMR) to identify potential pre- and post-operative serum biomarkers in patients with early stage ESCC using metabolomic fingerprint spectrum. Serum samples from preoperative patients with ESCC (ESCC, n = 25), postoperative patients with ESCC (PO, n = 24), and controls (n = 40) were analysed using 1H-NMR spectroscopy. Using orthogonal partial least squares-discriminant analysis, 31 altered serum metabolites were successfully identified among the three groups. These metabolites are indicative of the changes that occur with glycometabolism, the metabolism of fatty acids, amino acids, choline, ketone bodies, nucleotides, and lipids. Based on receiver operating characteristic (ROC) curve analysis and a biomarker panel with an area under the curve (AUC) of 0.969, six serum metabolites (α-glucose, choline, glutamine, glutamate, valine, and dihydrothymine) were selected as potential diagnostic biomarkers for early stage ESCC. Additionally, four potential PO biomarkers (α-glucose, pyruvate, glutamate, and valine) with an AUC of 0.985 were selected to distinguish ESCC and PO. Many metabolites trended towards normalisation in PO patients, with only choline remaining high with an AUC of 0.858, suggesting that it may be a valuable potential biomarker for neoplasm progression, recurrence, chemoradiotherapy, and prognosis. 1H-NMR spectroscopy may be a useful tumour detection approach in the early diagnosis of ESCC. These results also indicate that it is useful to differentiate pre- and post-operative ESCC, evaluate surgery therapeutic responses, and monitor postoperative chemoradiotherapy.