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This investigation was conducted to examine the effect of the designed composite agent (DCA) on the shrinkage performance of the concrete high-volume natural pozzolans (PHVNC). Based on an economic-cost analysis, it was determined that natural pozzolans (NP) were a suitable replacement for fly ash (FA) in the production of sustainable concrete for high-speed railway concrete slab track design. The results confirmed that the inclusion of DCA effectively improved the early-age shrinkage performance of PHVNC with 30% or 50% NP content. As a result, the concrete containing high-volume NP and DCA (PHVNDC) exhibited a smaller crack density compared to PHVNC, and even outperformed concrete with a high volume of FA (PHVFC). In terms of the effect of DCA on the drying shrinkage performance of mixes containing NP, a similar trend was observed, where the mixes that included both NP and DCA exhibited lower levels of dry shrinkage and mass loss at 28 days compared to mixes with either NP or FA. The results from phase transformation and microstructure analysis further indicated that adding DCA can enhance the mechanical and shrinkage performance of the mixes containing high-volume NP. This enhancement is attributed to the optimization of the hydration reaction rate, increased production of hydration products, and an overall improvement in the microstructure performance of the mixes with NP. Hence, DCA can serve as a valuable support in preserving the characteristics of NP-based mixtures, making it a valuable discovery for implementing high-volume NP in practical engineering projects with abundant NP resources.

Background and aim: Triple-negative breast cancer (TNBC) is a highly invasive type of breast cancer with a poor prognosis. Currently, there are no effective management strategies for TNBC. Earlier, our lab reported the percolation of Spatholobus suberectus for the treatment of breast cancer. Lipid metabolic reprogramming is a hallmark of cancer. However, the anti-TNBC efficiency of S. suberectus extract and its causal mechanism for preventing lipogenesis have not been fully recognized. Hence, the present study aimed to investigate the inhibitory role of S. suberectus extract on lipogenesis and tumorigenesis in TNBC in vitro and in vivo by activating AMPK-ACC and K-Ras-ERK signaling pathways using lipidomic and metabolomic techniques. Experimental procedure: Dried stems of S. suberectus extract inhibited lipogenesis and tumorigenesis and promoted fatty acid oxidation as demonstrated by the identification of the metabolites and fatty acid markers using proteomic and metabolomic analysis, qPCR, and Western blot. Results and conclusion: The results indicated that S. suberectus extract promotes fatty acid oxidation and suppresses lipogenic metabolites and biomarkers, thereby preventing tumorigenesis via the AMPK-ACC and K-Ras-ERK signaling pathways. On the basis of this preclinical evidence, we suggest that this study represents a milestone and complements Chinese medicine. Further studies remain underway in our laboratory to elucidate the active principles of S. suberectus extract. This study suggests that S. suberectus extract could be a promising therapy for TNBC.

Graphene oxide (GO) has been generally accepted can improve the microstructure of concrete because it can promote cement hydration, this nano-enhancement strategy is valuable for improving the weak interfacial transition zone in recycled aggregate concrete (RAC). This paper review aims to provide a comprehensive understanding and comparison of the impact of GO on the performance and microstructure of RAC through various modification methods. Initially, the characteristics of GO and its utilization in preparing RAC are introduced. Subsequently, the effects of admixing GO on the performance of RAC and its roles within the RAC system are analyzed and discussed. Furthermore, an economic, environmental evaluation, and research limitations of GO-modified RAC are analyzed. Finally, the conclusions and potential research prospects for future investigations are outlined. The findings of this review have the potential to expand the understanding of GO-modified RAC and can serve as a source of inspiration for future research endeavors.

Background: The sustainability and generalizability of China’s dynamic zero-COVID strategy on eliminating SARS-CoV-2 transmission has casted doubt globally, mainly because it has exacted high social and economic cost. This study aimed to estimate the disease burden during the first wave of Omicron in China and compared the cost-effectiveness of implementing a Real-world strategy (adjusted dynamic zero-COVID strategy) with two simulated strategies (routine and stricter dynamic zero-COVID strategy) to inform appropriate strategies for COVID-19 pandemic control. Methods: A dynamic state-transition simulation model was developed to compare the health and cost outcomes between different dynamic zero-COVID strategies. Omicron-related healthcare costs were estimated from the societal perspective. Epidemiological parameter values were derived from data of real-world or generated by model calibration; costs and effectiveness parameter values were informed either by local data or published literature. The primary outcomes were total social cost, disability adjusted life-years (DALYs) and net monetary benefit (NMB). Deterministic sensitivity analyses (DSA) and scenario analyses were performed to assess the model robustness. Results: The first wave of Omicron in Shanghai resulted in 47,646 DALYs lost and 415 billion RMB losses. At a willingness-to-pay threshold of 173,630 RMB (the GDP per capita of Shanghai in 2021) per DALY saved, the Real-world strategy was considered as the most cost-effective strategy due to its highest NMB (−407 billion). Results from DSA confirmed the robustness of our findings. Conclusion: Our finding supported the Real-world strategy taken by the Shanghai Municipal Government between March 1 and May 21, 2022 to control the first wave of Omicron outbreak. Moreover, our results indicated that whether the Stricter dynamic zero-COVID strategy is worth implementing at the beginning of the COVID-19 outbreak mainly depended on the infection rate of COVID-19 among primary contacts. Our analysis provides important evidence to inform policy makers to make appropriate decisions regarding COVID-19 pandemic management.

Yinlan lipid regulatory capsule (YL) is a composite traditional Chinese medicine (TCM) new drug to alleviate hyperlipidemia, while its therapeutic mechanism in vivo was not clarified with nontargeted metabolomics investigation. An animal model was established in rats fed a high-fat diet, and their body weights, body mass index (BMI) and blood cholesterol levels were measured. Serum, liver and kidney tissue samples were also extracted for PXR-CYP3A4-ABCB1-FXR signaling pathway research using PCR and UHPLC–MS. The obtained plasma samples were analyzed by UHPLC-Q-TOF-MS metabolomic investigation, which revealed PXR-CYP3A4-related metabolites and changes induced by YL. Finally, the key metabolites were chosen as index components, and their levels in the serum, liver, small intestine and bile were used for simultaneous UHPLC–MS-MS determination. The results indicated that YL was effective in rebalancing blood TG and TC levels (compared to controls). With respect to the PXR-CYP3A4-ABCB1 pathway, as a result of YL’s effect, gene expression or activity of the two targets decreased significantly in both the liver and kidney. The same trend was observed in the serum samples mentioned above. Metabolomics screening and data revealed that 44 metabolites can be regarded as biomarkers related to hyperlipidemia, fatty acids synthesis, and body energy consumption, as well as synthesis, transportation and exertion of cholesterol. YL’s treatment focused on 26 of them, primarily bile acids, indicating that the antihyperlipidemic effect of this drug lies in its inhibitory activity of cholesterol metabolism. Subsequent analysis of those in vivo components revealed that significant increases (compared to the model group) occurred in the blood, liver, small intestine and bile in groups that received medium and high doses of YL (while the low dose was relatively unchanged). Those target components exhibit a close relationship with PXR and/or CYP3A4. The use of YL repressed PXR expression and subsequently decreased CYP3A4 activity. As a result, synthesis of related bile acids increased, while cholesterol levels decreased, consequently leading to the attenuation of hyperlipidemia. This study comprehensively investigated the antihyperlipidemia mechanism of YL based on its repression of PXR-CYP3A4 activity and related metabolite yield, establishing an accurate method for evaluating the therapeutic effect of YL.

Background: Yinlan capsule is a complex TCM formulation that is prescribed for the treatment and prevention of hyperlipidemia. Our previous study indicated that one of the key targets of Yinlan is the Pregnane X Receptor (PXR). Purpose: To verify that PXR is the main active target for Yinlan's anti-hyperlipidemia effect, and to discover the agonists and antagonists with both suitable content and pharmacokinetic profile accordingly. Methods: an UHPLC-TOF-MS method was first applied to screen components in Yinlan capsule, peaks found in the ion current chromatogram were identified by the database (AB Sciex Analyst Software 1.6), and those with obvious responses were set as candidates; cytobiological experiment was carried out in the subsequent step, using HepG2 cell incubated with midazolam and monomer of the candidate compounds, yield of 1’-hydroxy- midazolam was used as an index to evaluate the PXR-CYP3A4 regulation activity of each component; a UHPLC-MS method was used for determination of the candidates showed obvious changes in 1’-hydroxy- midazolam yield, and compounds had suitable content in Yinlan capsule were validated for their PXR regulatory activities by QT-PCR; then components with both good PXR/CYP3A4 regulatory activity and suitable content underwent pharmacokinetic research to evaluate their in-body movements, compounds with acceptable pharmacokinetic parameters were finally chosen as quality marker of Yinlan's anti-hyperlipidemia effect via regulation of PXR activity. Comparisons of results in each step of evaluation were carried out using SPSS software, and the compounds with obvious difference (p

The aim of this study was to develop a new efficient strategy that uses the Vector form Intrinsic Finite-element (VFIFE) method to conduct the static and dynamic analyses of marine pipes. Nonlinear problems, such as large displacement, small strain, and contact and collision, can be analyzed using a unified calculation process in the VFIFE method according to the fundamental theories of point value description, path element, and reverse motion. This method enables analysis without the need to integrate the stiffness matrix of the structure, because only motion equations of particles established according to Newton's second law are required. These characteristics of the VFIFE facilitate the modeling and computation efficiencies in analyzing the nonlinear dynamic problem of flexible pipe with large deflections. In this study, a three-dimensional (3-D) dynamical model based on 3-D beam element was established according to the VFIFE method. The deep-sea flexible pipe was described by a set of spatial mass particles linked by 3-D beam element. The motion and configuration of the pipe are determined by these spatial particles. Based on this model, a simulation procedure to predict the 3-D dynamical behavior of flexible pipe was developed and verified. It was found that the spatial configuration and static internal force of the mining pipe can be obtained by calculating the stationary state of pipe motion. Using this simulation procedure, an analysis was conducted on the static and dynamic behaviors of the flexible mining pipe based on a 1000-m sea trial system. The results of the analysis proved that the VFIFE method can be efficiently applied to the static and dynamic analyses of marine pipes.

Background: Propolis and its preparations are components of TCM and functional food sources for antihyperlipidemia therapy. However, due to the metabolic properties of propolis, its individual components remain ambiguous, especially those that are therapeutically active. Purpose: The study presented here identified the primary target (PXR/CYP3A4) of propolis activity against hyperlipidemia and evaluated individual compounds of propolis to select a quality control marker based on this activity. Methods: Mice fed a high-fat diet were used to study the efficacy of propolis, followed by identification of substantially influenced glycolipid regulatory target(s) by propolis. Since propolis had the strongest effect on PXR expression, we took advantage of its downstream target CYP3A4, the drug metabolism activity of such enzyme is affected by alterations in PXR expression. Thus, we used the production of 1’-hydroxy-midazolam as an indicator. Compounds found by UHPLC-TOF-MS were added to a HepG2 cell solution (transfected by PXR mRNA and the CYP3A4 plasmid to simulate drug metabolism in the body) in the form of a monomer, followed by the addition of midazolam. Changes in the amount of “indicator” were used to investigate each compound's qualitative (promote or suppress) and quantitative activity. Compounds with obvious effects were quantified in propolis extract, as confirmed via Western Blot analysis regarding their PXR regulatory activity, and subjected to pharmacokinetic analysis to biter understand their metabolism in the body. Finally, components passing these screens could be regarded as quality control markers capable of indicating the efficacy of antihyperlipidemic activity via PXR/CYP3A4 regulation. Results: The use of propolis was effective in lowering TG and TC levels in mice, as well as in repairing their injured livers; its activity was comparable to the chemical and TCM positive controls. Propolis mainly suppressed PXR expression compared with other regulatory targets that were tested. Most of the individual compounds from propolis (13 out of 15) showed obvious regulatory activity of PXR/CYP3A4; however, content quantification and pharmacokinetic analyses narrowed the selection to 2 compounds, kaempferol and chrysin, as the main active components responsible for the antihyperlipidemic effect of propolis. In other words, this study suggested that propolis mainly acts on the PXR/CYP3A4 pathway to regulate glycolipid metabolism, and the 2 compounds mentioned above can be used as quality control markers (QM) to evaluate the efficacy of this activity. Conclusion: Propolis's antihyperlipidemic effect relies on its regulation of PXR/CYP3A4 expression. Kaempferol and chrysin can be regarded as QMs. In addition, the metabolite-based method for evaluating regulatory activity is much faster, more effective, and more reliable than the conventional screening method, paving the way for its future applications.