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Abstract Background Tanshinone IIA (Tan IIA) is a diterpene quinone extracted from the root of Salvia miltiorrhiza, a Chinese traditional herb. Although previous studies have reported the anti-tumor effects of Tan IIA on various human cancer cells, the underlying mechanisms are not clear. The current study was undertaken to investigate the molecular mechanisms of Tan IIA's apoptotic effects on leukemia cells in vitro. Methods The cytotoxicity of Tan IIA on different types of leukemia cell lines was evaluated by the 3-[4,5-dimethylthiazol-2,5]-diphenyl tetrazolium bromide (MTT) assay on cells treated without or with Tan IIA at different concentrations for different time periods. Cellular apoptosis progression with and without Tan IIA treatment was analyzed by Annexin V and Caspase 3 assays. Gene expression profiling was used to identify the genes regulated after Tan IIA treatment and those differentially expressed among the five cell lines. Confirmation of these expression regulations was carried out using real-time quantitative PCR and ELISA. The antagonizing effect of a PXR inhibitor L-SFN on Tan IIA treatment was tested using Colony Forming Unit Assay. Results Our results revealed that Tan IIA had different cytotoxic activities on five types of leukemia cells, with the highest toxicity on U-937 cells. Tan IIA inhibited the growth of U-937 cells in a time- and dose-dependent manner. Annexin V and Caspase-3 assays showed that Tan IIA induced apoptosis in U-937 cells. Using gene expression profiling, 366 genes were found to be significantly regulated after Tan IIA treatment and differentially expressed among the five cell lines. Among these genes, CCL2 was highly expressed in untreated U-937 cells and down-regulated significantly after Tan IIA treatment in a dose-dependent manner. RT-qPCR analyses validated the expression regulation of 80% of genes. Addition of L- sulforaphane (L-SFN), an inhibitor of Pregnane × receptor (PXR) significantly attenuated Tan IIA's effects using colony forming assays. Conclusions Tan IIA has significant growth inhibition effects on U-937 cells through the induction of apoptosis. And Tan IIA-induced apoptosis might result from the activation of PXR, which suppresses the activity of NF-κB and lead to the down-regulation of CCL2 expression.

Abstract Background Upon initial infection with mycobacteria, macrophages secrete multiple cytokines and chemokines, including interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α), to mediate host immune responses against the pathogen. Mycobacteria also induce the production of IL-10 via PKR activation in primary human monocytes and macrophages. As an anti-inflammatory cytokine, over-expression of IL-10 may contribute to mycobacterial evasion of the host immunity. Radix Paeoniae Rubra (RPR, Chishao), a Chinese medicinal herb with potentials of anti-inflammatory, hepatoprotective and neuroprotective effects, is used to treat tuberculosis. This study investigates the immunoregulatory effects of RPR on primary human blood macrophages (PBMac) during mycobacterial infection. Methods The interaction of Bacillus Calmette-Guerin (BCG) with PBMac was used as an experimental model. A series of procedures involving solvent extraction and fractionation were used to isolate bioactive constituents in RPR. RPR-EA-S1, a fraction with potent immunoregulatory effects was obtained with a bioactivity guided fractionation scheme. PBMac were treated with crude RPR extracts or RPR-EA-S1 before BCG stimulation. The expression levels of IL-6, IL-8, IL-10 and TNF-α were measured by qPCR and ELISA. Western blotting was used to determine the effects of RPR-EA-S1 on signaling kinases and transcriptional factors in the BCG-activated PBMac. Results In BCG-stimulated macrophages, crude RPR extracts and fraction RPR-EA-S1 specifically inhibited IL-10 production while enhanced IL-8 expression at both mRNA and protein levels without affecting the expressions of IL-6 and TNF-α. Inhibition of BCG-induced IL-10 expression by RPR-EA-S1 occurred in a dose- and time-dependent manner. RPR-EA-S1 did not affect the phosphorylation of cellular protein kinases including MAPK, Akt and GSK3β. Instead, it suppressed the degradation of IκBα in the cytoplasm and inhibited the translocation of transcription factor NF-κB1 p50 to the nucleus. Conclusion RPR crude extracts and its fraction RPR-EA-S1 inhibited anti-inflammatory cytokine IL-10 and enhanced pro-inflammatory chemokine IL-8 expression in BCG-activated PBMac. The inhibitory effects of RPR-EA-S1 on IL-10 expression in BCG-activated PBMac may be due to the reduced nuclear translocation of NF-κB1 p50.

The development of intrinsically stretchable polymer semiconductor holds substantial promise in the field of wearable electronics. However, charge transport mobility is typically compromised in existing stretchable semiconductors to achieve the desired stretchability. Herein, a novel "regional conjugation" strategy is proposed to design an intrinsically stretchable polymer semiconductor oligo‐diketopyrrolopyrrole‐thieno[3,2‐b]thiophene (DPPTT)–urethane, in which oligo‐DPPTT conjugated units and alkyl urethane nonconjugated units are introduced. The regional conjugation of oligo‐DPPTT in the polymer backbone endows DPPTT–urethane with good molecular packing, leading to a high mobility of up to 1.7 cm2 V−1 s−1. Additionally, incorporating alkyl urethane nonconjugated units in the backbone can reduce film crystallinity and chain aggregation, which contribute to the stretchability of the polymer thin film. Consequently, fully stretchable transistors retain carrier mobility even at 100% biaxial tensile strain. Furthermore, the fully stretchable organic field‐effect transistor arrays show remarkable charge transport reversibility and durability after 1000 stretch–release cycles at 25% strain. Additionally, the device exhibits extraordinary electrical stability in air atmosphere. Overall, these results indicate that the "regional conjugation" strategy provides an effective and promising methodology to design intrinsically stretchable and high‐performance polymer semiconductor that can advance the development of soft and wearable electronics. [ABSTRACT FROM AUTHOR]

Objective To characterize the epidemiological features of public health emergencies that occurred in Changping District of Beijing City in recent years, to provide scientific support for promoting prevention and control levels and strengthening response capability on such episodes. Methods Public health emergencies and related information reported in Changping District (January 2006 to December 2023) were obtained from the National Public Health Emergency Reporting and Management System. A descriptive epidemiological analysis was conducted on factors such as event level, type, and temporal and spatial distribution in the emergency episodes. Results From 2006 to 2023, a total of 1 219 public health emergencies were reported in Changping District (an annual average of 68 incidents), involving 2,097 cases (an annual average of 117 cases), showing an overall decreasing trend in the annual number of incidents. The emergencies were mainly classified as general level (Class IV, 31 incidents, all infectious disease events) and unclassified events (1 183 incidents, including 1 141 non-occupational carbon monoxide poisoning episodes and 34 infectious disease episodes); there were no major level (Class III), significant level (Class II), or particularly significant level (Class I) public health emergencies. Non-occupational carbon monoxide poisoning accounted for the highest proportion of public health emergencies, occurring predominantly in winter months (November to March), with incidents mainly occurring in households (1 091, 95.62%). Infectious disease emergencies mainly emerged in February and summer months (June to August), with incidents mainly occurring in households (42 cases, 60.00%) and schools (25 cases, 35.71%), involving diseases such as cholera, chickenpox, type A influenza (H1N1), and novel coronavirus infection. Meanwhile, the emergencies were mostly located in the streets/towns with higher population density and larger numbers of floating populations, such as Huilongguan Street, Dongxiaokou Street, Beiqijia Street, and Shahe Town. The median reporting time for public health emergencies in Changping District during 2006-2023 was 0.29 days, with a positive correlation between the discovery-to-reporting time and the duration of infectious disease outbreaks (rs=0.429, P<0.01). Conclusions Non-occupational carbon monoxide poisoning and infectious disease outbreaks are the major causes as well as priorities of public health emergencies in Changping District. The urban-rural fringe areas are high-risk and key areas for the management of such emergencies. For public health emergencies caused by cholera, chicken pox, novel coronavirus infection, and other infectious diseases, comprehensive measures such as strengthening epidemic monitoring, expanding vaccination coverage, and improving handling capacity should be taken to enhance the response capability and raise the prevention and control level on such emergencies. [ABSTRACT FROM AUTHOR]

Surgical resection is the preferred option for hepatocellular carcinoma (HCC), but surgical navigation technology using indocyanine green still has some drawbacks such as non‐specific imaging, thus it is very important to develop new fluorescence imaging technology. All‐cis hexaphenyl‐1,3‐butadiene derivative (ZZ‐HPB‐NC) with aggregation‐induced emission (AIE) feature has been reported to be quickly turned‐on fluorescent response in the intraoperative frozen‐section slides of HCC. However, the probe did not respond to normal liver tissue around HCC. In order to enhance the diagnostic rate and elucidate the response mechanism, all‐trans configuration EE‐HPB‐NC, was furtherly synthesized. Within two minutes, non‐cancer tissues could be fluorescently labeled by EE‐HPB‐NC by spraying, showing the same effect with ZZ‐HPB‐NC to HCC. The results indicated that the configuration‐induced cross‐identification fluorescence imaging strategy was achieved through the combination of ZZ‐ and EE‐HPB‐NC. Then the mechanism of HPB‐NC localization in HCC lesions was explored, and the binding of HPB‐NC with specific proteins in cells resulted in the AIE effect to label HCC cells. On this basis, the accuracy of specific fluorescence imaging for HCC was further verified on the mouse hepatic neoplasm models, indicating that it has clinical application potential for surgical fluorescence real‐time navigation. [ABSTRACT FROM AUTHOR]

Natural vegetation protects, maintains, and improves the environment through its ecological functions and is, thus, an important component of Earth's ecosystems. The distribution of natural vegetation and its corresponding ecological roles vary with the topographic gradient. Understanding this role is essential for effective ecosystem management and conservation efforts. This study analyzes vegetation composition across altitude gradients and the spatiotemporal evolution of water conservation, soil conservation, and carbon storage in the southern hill and mountain belt of China. We then explored the drivers of the ecological functions of vegetation at different altitude gradients. The results showed that water conservation increased by 108.56%, soil conservation increased by 97.04%, and carbon storage increased only slightly. The ecological functions of vegetation varied across altitude gradients, with the 500–800 m gradient exhibiting markedly higher ecological functions than the other gradients. The effect of precipitation on soil conservation increases with altitude. In addition, at higher altitudes, evergreen coniferous forests had a greater effect on carbon storage. Based on the results, we propose vegetation management measures for different altitudes. This study provides a reference for decision-makers to develop and adjust ecological restoration programs in mountainous areas for the improvement of the local ecological environment. [ABSTRACT FROM AUTHOR]

Affected by the near-fault pulse-like ground motions, the tunnels emerged in adverse geology, especially in an inhomogeneous strata are more vulnerable. However, the quantitative index effects on tunnel response during pulse identification are unclear and the propagation features of the near-fault pulse-like waves in a soft soil interlayer site are seldom revealed. In view of this, an improved energy-based pulse identification was used in this study to quantitatively extract the potential pulse energies emerged in velocity time-histories of ground motions. Subsequently, a series of numerical simulations were carried out to consider the critical parameters of soft soil layer and input ground motions. Finally, the dynamic response of the tunnel and interaction differences of soil and tunnel subjected to three types of ground motions were revealed. The result showed that the near-fault pulse-like ground motions pose a commonly severe damage to the tunnel, especially in the high pulse period ground motions based on the energy-based pulse identification method. The pulse energy of ground motions is an effective pulse index to analyze the seismic effects on tunnel when pulse periods of two different ground motions are uniform, and the index affects the tunnel in dynamic internal forces. More importantly, the existence of soft soil layer severely affects the propagation of input ground motions. At frequency domain, the ground response increases at high frequency component in the near-fault pulse-like ground motion, while the response shows a decreasing at low frequency component. [ABSTRACT FROM AUTHOR]