Reprogrammable Magnetic Soft Actuators with Microfluidic Functional Modules via Pixel-Assembly.

Magnetic soft actuators and robots have attracted considerable attention in biomedical applications due to their speedy response, programmability, and biocompatibility. Despite recent advancements, the fabrication process of magnetic actuators and the reprogramming approach of their magnetization profiles continue to pose challenges. Here, a facile fabrication strategy is reported based on arrangements and distributions of reusable magnetic pixels on silicone substrates, allowing for various magnetic actuators with customizable architectures, arbitrary magnetization profiles, and integration of microfluidic technology. This approach enables intricate configurations with decent deformability and programmability, as well as biomimetic movements involving grasping, swimming, and wriggling in response to magnetic actuation. Moreover, microfluidic functional modules are integrated for various purposes, such as on/off valve control, curvature adjustment, fluid mixing, dynamic microfluidic architecture, and liquid delivery robot. The proposed method fulfills the requirements of low-cost, rapid, and simplified preparation of magnetic actuators, since it eliminates the need to sustain pre-defined deformations during the magnetization process or to employ laser heating or other stimulation for reprogramming the magnetization profile. Consequently, it is envisioned that magnetic actuators fabricated via pixel-assembly will have broad prospects in microfluidics and biomedical applications.

HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma.

Renal cell carcinoma (RCC) is responsible for most cases of the kidney cancer. Previous research showed that low serum levels of cholesterol level positively correlate with poorer RCC-specific survival outcomes. However, the underlying mechanisms and functional significance of the role of cholesterol in the development of RCC remain obscure. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) plays a pivotal role in RCC development as it is the key rate-limiting enzyme of the cholesterol biosynthetic pathway. In this study, we demonstrated that the inhibition of HMGCR could accelerate the development of RCC tumors by lactate accumulation and angiogenesis in animal models. We identified that the inhibition of HMGCR led to an increase in glycolysis via the regulated HSP90 expression levels, thus maintaining the levels of a glycolysis rate-limiting enzyme, pyruvate kinase M2 (PKM2). Based on these findings, we reversed the HMGCR inhibition-induced tumor growth acceleration in RCC xenograft mice by suppressing glycolysis. Furthermore, the coadministration of Shikonin, a potent PKM2 inhibitor, reverted the tumor development induced by the HMGCR signaling pathway.

Gastrodin protects endothelial cells against high glucose-induced injury through up-regulation of PPARß and alleviation of nitrative stress.

In diabetes mellitus (DM), high glucose can result in endothelial cell injury, and then lead to diabetic vascular complications. Gastrodin, as the mainly components of Chinese traditional herb Tianma (Gastrodia elata Bl.), has been widely used for cardiovascular diseases. However, the known of the effect of gastrodin on endothelial cell injury is still limited. In this study, we aimed to investigate the effect and possible mechanism of gastrodin on high glucose-injured human umbilical vein endothelial cells (HUVEC). High glucose (30 mmol/L) treatment caused HUVEC injury. After gastrodin (0.1, 1, 10 µmol/L) treatment, compared with the high glucose group, the cell proliferation ability increased in a dose-dependent manner. Meanwhile, gastrodin (10 µmol/L) up-regulated the mRNA and protein expressions of PPARß and eNOS, decreased the expressions of iNOS, also reduced the protein expression of 3-nitrotyrosine, and lowed the level of ONOO-, increased NO content. Both the PPARß antagonist GSK0660 (1 µmol/L) and the eNOS inhibitor L-NAME (10 µmol/L) were able to block the above effects of gastrodin. In conclusion, gastrodin protectes vascular endothelial cells from high glucose injury, which may be, at least partly, mediated by up-regulating the expression of PPARß and negatively regulating nitrative stress.

Functional identification of PhMATE1 in flower color formation in petunia.

Multidrug and toxic compound extrusion (MATE) transporter proteins are a class of secondary transporter proteins that can transport flavonoids. Anthocyanins, a kind of flavonoid, are important secondary metabolites widely found in higher plants; they determine the flower color of most angiosperms. TT12 in Arabidopsis was the first MATE protein identified to be involved in flavonoid transport. Petunia (Petunia hybrida) is an important ornamental plant and is one of the ideal plants for studying plant flower color. However, there are few reports on anthocyanin transport in petunia. In this study, we characterized a homolog of Arabidopsis TT12 in the petunia genome, PhMATE1, that shares the highest amino acid sequence identity with Arabidopsis TT12. PhMATE1 protein contained 11 transmembrane helices. PhMATE1 showed a high transcription level in corollas. The silencing of PhMATE1 mediated by both virus-induced gene silence and RNA interference changed flower color and reduced anthocyanin content in petunia, suggesting that PhMATE1 is involved in anthocyanin transport in petunia. Furthermore, PhMATE1 silencing downregulated the expression of the structural genes of the anthocyanin synthesis pathway. The results of this study supported the hypothesis that MATEs are involved in the sequestration of anthocyanins during flower color formation.

Effects of different interventions on prognosis and quality of life in patients with atrial fibrillation.

OBJECTIVE: To compare the effects of different intervention measures on prognosis and quality of life in patients with atrial fibrillation, in order to provide clinical basis for diagnosis and treatment. METHODS: A total of 160 patients who visited several hospitals including Shanghai Xinhua Hospital from June 2019 to June 2021 were selected. Among them, 40 cases were in the drug treatment group (DRUG group), 40 cases in the radiofrequency ablation group (Radiofrequency ablation, RFA group), and 40 cases in the catheter ablation combined with percutaneous left atrial appendage occlusion group (""one-stop"" procedure group) and 40 cases in the percutaneous left atrial appendage closure group (Left atrial appendage closure, LAAC group). The Minnesota quality of life score (MLHFQ), ejection fraction (LVEF), and left atrial anterior and posterior diameters (LAD) were compared between the groups at 1-year follow-up, and the differences in adverse events were compared between the groups. RESULTS: (1) After a 1-year follow-up, overall comparison, the MLHFQ scores and the LVEF and the LAD among the four groups were statistically different (p < .01); (2) Multiple comparisons, ① the MLHFQ scores: The RFA group was the lowest, the "one-stop" operation group was lower than the DRUG group, the LAAC group was the highest (p < .01). ② LVEF: The RFA group was the highest, the "one-stop" procedure group was higher than the drug treatment group, the LAAC group was the lowest (p < .01). ③ LAD: the RFA group and the "one-stop" procedure group were smaller than the DRUG group, the DRUG group was smaller than the LAAC group (p < .01).(3) Compared with the baseline data after 1-year follow-up in each group, in the RFA group and in the "one-stop" procedure group, the MLHFQ scores was decreased, the LVEF was increased, and the LAD was decreased (p < .01); in the DRUG group: the difference was not statistically significant (p > .05); in the LAAC group, the MLHFQ scores was increased, the LVEF was decreased, and the LAD was increased (p < .01). (4) There were significant differences in the incidence of adverse events among the four groups (p < .01), the lowest in the RFA group and the highest in the LAAC group. CONCLUSION: Compared with drug treatment, radiofrequency ablation and "one-stop" procedure group can improve the quality of life of patients with atrial fibrillation, improve cardiac function, and reduce the occurrence of adverse events. Percutaneous left atrial appendage occlusion affects patients' quality of life and improves cardiac function, and increases the incidence of adverse events.

Application of 3D-Printed Personalized Guide for Lateral Femoral Positioning in Anterior Cruciate Ligament Reconstruction of the Knee.

Objective: This research aims to investigate the effectiveness of 3D computer-assisted customized guided positioning of the lateral femoral tunnel compared to conventional methods for Anterior Cruciate Ligament (ACL) reconstruction surgery. Methods: A total of 80 patients with a complete ACL tear who underwent arthroscopic reconstruction with autologous tendon transplantation (semitendinosus-gracilis tendon) were included in this study. The patients were admitted to our hospital between March 2020 and January 2022 and were randomly divided into two groups: the conventional group (n = 40) and the personalized guide group (n = 40), based on the positioning method. The conventional group underwent ACL restoration using standard surgical techniques, while the personalized guide group opted for the more precise computer-assisted personalized guide method. The lateral femoral tunnel times were compared between both groups. Additionally, the International Knee Documentation Committee (IKDC) and Lysholm scores were assessed, and the lateral femoral location was evaluated using X-ray imaging at 2 weeks postoperatively. Results: After surgery, both groups showed a statistically significant increase (P < .05) in Lysholm and IKDC scores compared to their pre-surgery scores. However, the two groups had no evident difference (P > .05). X-ray evaluation at 2 weeks post-surgery revealed no significant difference between the two groups in NL/ML, AL/BL, α, and ß angles (P > .05). The preparation time for the femoral tunnel was significantly shorter in the personalized guide group (6.18 ± 0.92 min) compared to the traditional group (15.94 ± 3.12 min) (P < .05). Conclusions: The computer-assisted 3D personalized guide positioning method is more effective in locating the lateral femoral tunnel for ACL reconstruction of the knee and can substantially reduce the positioning time. This study provides valuable insights for clinicians when selecting surgical methods.

MIMO 5G Smartphone Antenna with Tri-Band and Decoupled Elements.

In this article, a miniaturized antenna is proposed for 4G/5G multiple input, multiple output (MIMO) applications for smartphones. The proposed antenna is composed of an inverted L-shaped antenna with decoupled elements to cover 4G (2000-2600 MHz), and a planar inverted-F antenna (PIFA) with a J-slot to cover 5G (3400-3600 MHz and 4800-5000 MHz). Furthermore, to achieve the purposes of miniaturization and decoupling, the structure adopts a feeding stub, shorting stub, and outstanding floor, additionally adding the slot to the PIFA, to generate additional frequency bands. Due to the advantages such as multiband operation, MIMO configuration for 5G communications, high isolation, and a compact structure, the proposed antenna design is attractive for 4G/5G smartphones. The antenna array is printed on an FR4 dielectric board, measuring 140 × 70 × 0.8 mm3, with the 4G antenna located on a top 15 mm-long headroom.

UWB Frequency-Selective Surface Absorber Based on Graphene Featuring Wide-Angle Stability.

In this paper, an ultra-wideband and polarization-insensitive frequency-selective surface absorber is presented with oblique incident stable behavior. Different from conventional absorbers, the absorption behavior is much less deteriorated with the increase in the incidence angle. Two hybrid resonators, which are realized by symmetrical graphene patterns, are employed to obtain the desired broadband and polarization-insensitive absorption performance. The optimal impedance-matching behavior is designed at the oblique incidence of electromagnetic waves, and an equivalent circuit model is used to analyze and facilitate the mechanism of the proposed absorber. The results indicate that the absorber can maintain a stable absorption performance with a fractional bandwidth (FWB) of 136.4% up to 40°. With these performances, the proposed UWB absorber could be more competitive in aerospace applications.

Correlation between posterior paraspinal muscle atrophy and lumbar intervertebral disc degeneration in patients with chronic low back pain.

BACKGROUND: Although enormous studies have been devoted to solving the problem of intervertebral disc degeneration/herniation, little attention is paid to the effect of paraspinal muscles on it. We aimed to investigate the correlation between paraspinal muscle atrophy and lumbar disc degeneration to recognize paraspinal muscle atrophy and its importance to the spine. PATIENTS AND METHODS: A total of 107 patients were enrolled in the study (65 females, 42 males; age 50.87 ± 15.391 years old). Cross-sectional area, functional cross-sectional area, and fatty infiltration of the posterior paraspinal muscles were measured at the level of L4/5, and the degree of facet joint degeneration was evaluated at the levels of L3/4, L4/5, and L5/S1 by MRI. After controlling the confounding factors by multiple linear regression, the correlations among paraspinal muscle atrophy, disc degeneration, and facet joint degeneration were analyzed. Meanwhile, Pearson/Spearson rank analysis was used to analyze the correlation between clinical symptoms (VAS and ODI) and paraspinal muscle atrophy. RESULTS: There was a strong correlation between paraspinal muscle atrophy and disc degeneration after controlling the confounding factors (p < 0.05, R > 0.5). There was a weak correlation between paraspinal muscle atrophy and facet joint degeneration (p < 0.05, R < 0.5). There was a significant correlation between facet joint degeneration and intervertebral disc degeneration (p < 0.05, R > 0.7). The fatty infiltration of paraspinal muscle was weakly correlated with ODI (p < 0.05, R < 0.3), but VAS was not. CONCLUSIONS: The degree of paraspinal muscle atrophy increased with lumbar disc degeneration and facet joint degeneration and fatty infiltration of multifidus was more susceptible to weight.

Palladium-Catalyzed Regioselective B(3,4)-H Acyloxylation of o-Carboranes.

We disclose herein an efficient regioselective B(3,4)-H activation via a ligand strategy, affording B(3)-monoacyloxylated and B(3,4)-diacyloxylated o-carboranes. The identification of amino acid and phosphoric acid ligands is crucial for the success of B(3)-mono- and B(3,4)-diacyloxylation, respectively. This ligand approach is compatible with a broad range of carboxylic acids. The functionalization of complex drug molecules is demonstrated. Other acyloxyl sources, including sodium benzoate, benzoic anhydride, and iodobenzene diacetate, are also tolerated.

Stretch-driven microfluidic chip for nucleic acid detection.

Molecular diagnosis is an essential means to detect pathogens. The portable nucleic acid detection chip has excellent prospects in places where medical resources are scarce, and it is also of research interest in the field of microfluidic chips. Here, the article developed a new type of microfluidic chip for nucleic acid detection where stretching acts as the driving force. The sample entered the chip by applying capillary force. The strain valve was opened under the action of tensile force, and the spring pump generated the power to drive the fluid to flow to the detection chamber in a specific direction. The detection of coronavirus disease 2019 (COVID-19) was realized on the chip. The RT-LAMP amplification system was adopted to observe the liquid color in the detection chamber to decide whether the sample tested positive or negative qualitatively.

An integrated microfluidic detection system for the automated and rapid diagnosis of high-risk human papillomavirus.

Human papillomavirus (HPV) causes the prevalent sexually transmitted infection that accounts for the majority of cervical cancer incidences. Therefore, the development of a rapid, accurate, automatic and affordable nucleic acid detection strategy is urgently required for HPV tests, among which microfluidic chip is a promising diagnostic method. In this work, we developed a microfluidic detection system consisting of a microfluidic chip and the corresponding detection equipment to diagnose high-risk HPV. The proposed method integrates nucleic acid purification, isothermal amplification and real-time fluorescence detection into one device. Moreover, it demonstrates good detection performance such as high specificity of primer sets (100%) and exceptional stability (coefficient of variation <6%) among five HPV genotypes. Besides, the microfluidic loop-mediated isothermal amplification (LAMP) assay is accurate (specificity of 91.7% and sensitivity of 100%) and fast (average time threshold = 10.56 minutes) when considering the conventional qPCR assay as the gold standard. The integrated microfluidic detection system offers automated and rapid diagnosis within 40 minutes and shows broad potential to deliver point-of-care detection in resource-limited circumstances owing to its simplicity and affordability.

Autophagy inhibitors increase the susceptibility of KRAS-mutant human colorectal cancer cells to a combined treatment of 2-deoxy-D-glucose and lovastatin.

RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation. In this study we investigated the effect of a combination of 2-deoxy-D-glucose with lovastatin (a known inhibitor of mevalonate pathway and oxidative phosphorylation) on growth of KRAS-mutant human colorectal cancer cell lines HCT116 and LoVo. A combination of lovastatin (>3.75 µM) and 2-deoxy-D-glucose (>1.25 mM) synergistically reduced cell viability, arrested cells in the G2/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels. Energy depletion markedly activated AMPK, inhibited mTOR and RAS signaling pathways, eventually inducing autophagy, the cellular pro-survival process under metabolic stress, whereas inhibition of autophagy by chloroquine (6.25 µM) enhanced the cytotoxic effect of the combination of lovastatin and 2-deoxy-D-glucose. These in vitro experiment results were reproduced in a nude mouse xenograft model of HCT116 cells. Our findings suggest that concurrently targeting glycolysis, oxidative phosphorylation, and autophagy may be a promising regimen for the management of RAS-driven colorectal cancers.

Effects of PPARs/20-HETE on the renal impairment under diabetic conditions.

Diabetic nephropathy (DN) is one of the most severe complications of diabetes mellitus. The pathomolecular events behind DN remain uncertain. Peroxisome proliferator-activated receptors (PPARs) play essential functions in the development of DN. Meanwhile, 20-hydroxyeicosatetraenoic acid (20-HETE) also plays central roles in the regulation of renal function. However, the relationship between PPARs and 20-HETE is rarely studied in DN. It was revealed in our study that both PPARs expression and CYP4A-20-HETE level were decreased under DN conditions in vivo and in vitro. Supplementation with bezafibrate, a PPAR pan-agonist, improved the damage of kidney in DN mice and in high glucose-induced NRK-52E cells, following the up-regulation of PPARs and the increase of CYP4A-20-HETE. PPARα antagonist (MK886), PPARß antagonist (GSK0660), and PPARγ antagonist (GW9662) reversed the protection of bezafibrate in NRK-52E, and abrogated the up-regulation of CYP4A-20-HETE produced by bezafibrate. Noteworthily, 20-HETE synthetase inhibitor, HET0016, also blocked the bezafibrate-mediated improvement of NRK-52E, and abolished the up-regulation of PPARs expression. Collectively, our data suggest that the concurrent down-regulation and interaction of PPARs and 20-HETE play crucial roles in the pathogenesis process of DN, and we provide a novel evidence that PPARs/20-HETE signaling may be served as a therapeutic target for DN patients.

Naringenin exhibits the protective effect on cardiac hypertrophy via EETs-PPARs activation in streptozocin-induced diabetic mice.

Cardiac hypertrophy is one of the key structural changes in diabetic cardiomyopathy. Naringenin, a dihydroflavonoid extracted from citrus plants with multiple pharmacological activities, yet the underlying effects on diabetic cardiac hypertrophy remain unclear. This study aimed to evaluate the potential effects of naringenin on cardiac hypertrophy in diabetic mice. Long-term high-fat feeding combined with streptozotocin resulted in cardiac hypertrophy after a diabetic model has been established for 4 weeks in mice, which were improved by naringenin supplementation (25 or 75 mg/kg/day, i. g.) for another 4 weeks. The protein and mRNA expressions of PPARs were down-regulated, the protein express of CYP2J3 and level of 14, 15-EET were decreased following diabetic cardiac hypertrophy. Naringenin administration up-regulated PPARs expression, elevated CYP2J3 protein and 14,15-EET content. In conclusion, naringenin can improve cardiac hypertrophy in diabetic mice, which may be related to up-regulate the expression of CYP2J3, elevate the level of EETs, and activate the expression of PPARs.

Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse.

The aim of this study was to establish a robust model of diabetic myocardial hypertrophy in Mus musculus castaneus mice. Mice were fed a high-fat diet for four weeks and then given streptozotocin (STZ, 40 mg kg-1  d-1 for 5 days, intraperitoneally) and fasting blood glucose (FBG) levels were tested after seven days. Mice with FBG levels above 11.1 mmol/L were considered diabetic. Diabetic mice continued to have access to the high-fat diet until cardiac hypertrophy developed. FBG and body weight (BW) were measured weekly. Myocardial hypertrophy was confirmed by left ventricle (LV) hypertrophy index (LVHI), LV/BW, LV histopathological observation and atrial natriuretic factor (ANF) mRNA expression. Serum insulin and plasma haemoglobin A1c (HbA1c) levels, total cholesterol (TCH) and triglyceride (TG) were measured, and then an insulin resistance index (HOMA.IR) was calculated. The level of FBG in the model group remained above 11.1 mmol/L, and the BW showed significant weight loss, compared with the control group (P < 0.01). The high levels of HbA1c, HOME.IR, TCH and TG, and the low level of insulin suggested that glucose metabolism was not balanced with insulin resistance; meanwhile, higher TCH and TG showed that dyslipidaemia had also developed. After the diabetic mice were kept on the high-energy diet for another four  weeks, histopathological observation showed myocardial injuries, much more surface area and collagen fibres, higher LVHI and LV/BW, and elevated expression of ANF mRNA (P < 0.01), suggesting that myocardial hypertrophy had appeared in Mus musculus castaneus mice under the current experimental conditions. Thus a robust model of diabetic myocardial hypertrophy was established four  weeks after confirmation of diabetes, which was induced by feeding a high-fat diet for four weeks combined with a repeated low-dose STZ exposure, in Mus musculus castaneus mice.

Novel oxazolxanthone derivatives as a new type of α-glucosidase inhibitor: synthesis, activities, inhibitory modes and synergetic effect.

Xanthone derivatives have shown good α-glucosidase inhibitory activity and have drawn increased attention as potential anti-diabetic compounds. In this study, a series of novel oxazolxanthones were designed, synthesized, and investigated as α-glucosidase inhibitors. Inhibition assays indicated that compounds 4-21 bearing oxazole rings exhibited up to 30-fold greater inhibitory activity compared to their corresponding parent compound 1b. Among them, compounds 5-21 (IC50 = 6.3 ±â€¯0.4-38.5 ±â€¯4.6 µM) were more active than 1-deoxynojirimycin (IC50 = 60.2 ±â€¯6.2 µM), a well-known α-glucosidase inhibitor. In addition, the kinetics of enzyme inhibition measured by using Lineweaver-Burk analysis shows that compound 4 is a competitive inhibitor, while compounds 15, 16 and 20 are non-competitive inhibitors. Molecular docking studies showed that compound 4 bound to the active site pocket of the enzyme while compounds 15, 16, and 20 did not. More interestingly, docking simulations reveal that some of the oxazolxanthone derivatives bind to different sites in the enzyme. This prediction was further confirmed by the synergetic inhibition experiment, and the combination of representative compounds 16 and 20 at the optimal ratio of 4:6 led to an IC50 value of 1.9 ±â€¯0.7 µM, better than the IC50 value of 7.1 ±â€¯0.9 µM for compound 16 and 8.6 ±â€¯0.9 µM for compound 20.

Enhanced catalytic activities and modified substrate preferences for taxoid 10ß-O-acetyl transferase mutants by engineering catalytic histidine residues.

OBJECTIVES: Taxoid 10ß-O-acetyl transferase (DBAT) was redesigned to enhance its catalytic activity and substrate preference for baccatin III and taxol biosynthesis. RESULTS: Residues H162, D166 and R363 were determined as potential sites within the catalytic pocket of DBAT for molecular docking and site-directed mutagenesis to modify the activity of DBAT. Enzymatic activity assays revealed that the kcat/KM values of mutant H162A/R363H, D166H, R363H, D166H/R363H acting on 10-deacetylbaccatin III were about 3, 15, 26 and 60 times higher than that of the wild type of DBAT, respectively. Substrate preference assays indicated that these mutants (H162A/R363H, D166H, R363H, D166H/R363H) could transfer acetyl group from unnatural acetyl donor (e.g. vinyl acetate, sec-butyl acetate, isobutyl acetate, amyl acetate and isoamyl acetate) to 10-deacetylbaccatin III. CONCLUSION: Taxoid 10ß-O-acetyl transferase mutants with redesigned active sites displayed increased catalytic activities and modified substrate preferences, indicating their possible application in the enzymatic synthesis of baccatin III and taxol.

Neo-tanshinlactone selectively inhibits the proliferation of estrogen receptor positive breast cancer cells through transcriptional down-regulation of estrogen receptor alpha.

Breast cancer, the most frequent cancer in women, is the second leading cause of cancer-related death. Estrogens and estrogen receptors are well recognized to play predominant roles in breast cancer development and growth. Neo-tanshinlactone is a natural product isolated from Salvia miltiorrhiza and showed selective growth inhibition of ER+ breast cancer cell lines as demonstrated by cell proliferation assay and colony formation assay. The selective anti-proliferative effect of neo-tanshinlactone was associated with the induction of apoptosis in ER+ breast cancer cells. We also found that neo-tanshinlactone decreased steady state ESR1 mRNA levels in ER+ breast cancer cells, which was further confirmed by analysis of ER protein levels as well as the mRNA levels of target genes of this transcription factor, such as ESR2, BRCA1, CCND1, GREB1, TFF1, SERPINB9 and ABCA3. Furthermore, analysis of heterogeneous nuclear RNA (hnRNA) demonstrated that neo-tanshinlactone inhibited ESR1 mRNA de novo synthesis. The decrease of steady state ESR1 mRNA upon neo-tanshinlactone treatment was not abolished by protein synthesis inhibitor cycloheximide. And inhibition of mRNA synthesis with actinomycin D revealed no significant effect of neo-tanshinlactone on ESR1 mRNA stability. These results indicated that transcriptional down-regulation of ESR1 mRNA could contribute to the selective activity of neo-tanshinlactone on ER+ breast cancer cells. And as expected, the combination of neo-tanshinlactone and antiestrogen reagent tamoxifen showed a synergistic effect on growth of ER+ MCF7 cells. Our results suggest that neo-tanshinlactone is a promising regimen for ER+ breast tumors.