Empagliflozin ameliorates vascular calcification in diabetic mice through inhibiting Bhlhe40-dependent NLRP3 inflammasome activation.

Type 2 diabetes mellitus (T2DM) patients exhibit greater susceptibility to vascular calcification (VC), which has a higher risk of death and disability. However, there is no specific drug for VC therapy. NLRP3 inflammasome activation as a hallmark event of medial calcification leads to arterial stiffness, causing vasoconstrictive dysfunction in T2DM. Empagliflozin (EMPA), a sodium-glucose co-transporter 2 inhibitor (SGLT2i), restrains hyperglycemia with definite cardiovascular benefits. Given the anti-inflammatory activity of EMPA, herein we investigated whether EMPA protected against VC in the aorta of T2DM mice by inhibiting NLRP3 inflammasome activation. Since db/db mice receiving a normal diet developed VC at the age of about 20 weeks, we administered EMPA (5, 10, 20 mg·kg-1·d-1, i.g) to 8 week-old db/db mice for 12 weeks. We showed that EMPA intervention dose-dependently ameliorated the calcium deposition, accompanied by reduced expression of RUNX2 and BMP2 proteins in the aortas. We found that EMPA (10 mg·kg-1·d-1 for 6 weeks) also protected against VC in vitamin D3-overloaded mice, suggesting the protective effects independent of metabolism. We showed that EMPA (10 mg·kg-1·d-1) inhibited the abnormal activation of NLRP3 inflammasome in aortic smooth muscle layer of db/db mice. Knockout (KO) of NLRP3 significantly alleviated VC in STZ-induced diabetic mice. The protective effects of EMPA were verified in high glucose (HG)-treated mouse aortic smooth muscle cells (MOVASs). In HG-treated NLRP3 KO MOVASs, EMPA (1 µM) did not cause further improvement. Bioinformatics and Western blot analysis revealed that EMPA significantly increased the expression levels of basic helix-loop-helix family transcription factor e40 (Bhlhe40) in HG-treated MOVASs, which served as a negative transcription factor directly binding to the promotor of Nlrp3. We conclude that EMPA ameliorates VC by inhibiting Bhlhe40-dpendent NLRP3 inflammasome activation. These results might provide potential significance for EMPA in VC therapy of T2DM patients.

Water-Driven Synthesis of Deep-Blue Perovskite Colloidal Quantum Wells for Electroluminescent Devices.

Perovskite colloidal quantum wells (QWs) are promising to realize narrow deep-blue emission, but the poor optical performance and stability suppress their practical application. Here, we creatively propose a water-driven synthesis strategy to obtain size-homogenized and strongly confined deep-blue CsPbBr3 QWs, corresponding to three monolayers, which emit at the deep-blue wavelength of 456 nm. The water controls the orientation and distribution of the ligands on the surface of the nanocrystals, thus inducing orientated growth through the Ostwald ripening process by phagocytizing unstable nanocrystals to form well-crystallized QWs. These QWs present remarkable stability and high photoluminescence quantum yield of 94 %. Furthermore, we have prepared light-emitting diodes based on the QWs via the all-solution fabrication strategy, achieving an external quantum efficiency of 1 % and luminance of 2946 cd m-2 , demonstrating state-of-the-art brightness for perovskite QW-based LEDs.

FYCO1 regulates migration, invasion, and invadopodia formation in HeLa cells through CDC42/N-WASP/Arp2/3 signaling pathway.

FYCO1, an autophagy adaptor, plays an essential role in the trafficking toward the plus-end of microtubules and the fusion of autophagosomes. Autophagic dysfunction is involved in numerous disease states, including cancers. Previous studies have implicated FYCO1 as one of the critical genes involved in the adenoma to carcinoma transition, but the biological function and mechanism of FYCO1 in carcinogenesis remain unclear. This study aims to elucidate the role and mechanism of up- and downregulation of FYCO1 in mediating tumor effects in HeLa cells. Functionally, FYCO1 promotes cellular migration, invasion, epithelial-mesenchymal transition, invadopodia formation, and matrix degradation, which are detected through wound healing, transwell, immunofluorescence, and Western blot approaches. Interestingly, the data show that although FYCO1 does not affect HeLa cell proliferation, cell cycle distribution, nor vessels' formation, FYCO1 can block the apoptotic function. FYCO1 inhibits cleavage of PARP, caspase3, and caspase9 and increases Bcl-2/Bax ratio. Then, we used CK666, an Arp2/3 specific inhibitor, to confirm that FYCO1 may promote the migration and invasion of HeLa cells through the CDC42/N-WASP/Arp2/3 signaling pathway. Taken together, these results provide a new insight that FYCO1, an autophagy adaptor, may also be a new regulator of tumor metastasis.

Identification and functional analysis of two GJA8 variants in Chinese families with eye anomalies.

In this study, we report on two different GJA8 variants related to congenital eye anomalies in two unrelated families, respectively. GJA8 (or Cx50) encoding a transmembrane protein to form lens connexons has been known as a common causative gene in congenital cataracts and its variants have recently been reported related to a wide phenotypic spectrum of eye defects. We identified two GJA8 variants, c.134G>T (p.Try45Leu, W45L) detected in a cataract family by Sanger sequencing and c.281G>A (p.Gly94Glu, G94E) found in a family with severe eye malformations including microphthalmia by whole-exome sequencing. These two variants were absent in healthy population and predicted deleterious by bioinformatic analysis. Furthermore, we compared the expression in cell lines between these mutants and the wildtype to explore their potential mechanism. Cell counting kit-8 assay showed that overexpression of either W45L or G94E decreased cell viability compared with wild-type Cx50 and the control. A lower protein level in W45L found by western blotting and fewer punctate fluorescent signals showed by fluorescence microscopy suggested that W45L may have less protein expression. A higher G94E protein level and abundant dotted distribution indicated that G94E may cause aberrant protein degradation and accumulation. Such results from in vitro assays confirmed the impact of these two variants and gave us a hint about their different pathogenic roles in different phenotypes. In conclusion, our study is the first to have the functional analysis of two GJA8 variants c.134G>T and c.281G>A in Chinese pedigrees and explore the impact of these variants, which can help in prenatal diagnosis and genetic counseling as well in basic studies on GJA8.

Degradation mechanisms of perovskite nanocrystals in color-converted InGaN micro-light-emitting diodes.

The metal halide perovskite nanocrystals (NCs) have attracted much attention because of their excellent optical properties and potential for application in optoelectronic devices. However, their photo- and thermostability are still practical challenges and need further optimization. Here, we have studied the degradation behaviors of CsPbI3 NCs utilized as optical conversion layer in InGaN based blue micro-LEDs in situ. Furthermore, the effects of temperature and light irradiation on perovskite NCs were investigated respectively. The results indicate that both blue light irradiation and high temperature can cause the increased nonradiative recombination rate, resulting in the degradation of perovskite NCs and reduction of the photoluminescence quantum yield (PLQY). Especially in high-temperature condition, both the single-exciton nonradiative recombination rate and the biexciton nonradiative recombination rate are increased, causing the significant reduction of PLQY of perovskite NCs in high temperature environment than blue light irradiation. Our work provides a detailed insight about the correlation between the light irradiation and temperature consequences for CsPbI3 NCs and may help to pave the way toward optoelectronic device applications.

Identification and functional study of FOXC1 variants in Chinese families with glaucoma.

This study aimed to identify the disease-causing gene of three Chinese families with glaucoma. Whole exome sequencing was performed on the probands and detected three different variants (c.405C>A (p.Cys135Ter), c.851G>T (p.Ser284Ile), and c.392C>T (p.Ser131Leu)) in FOXC1 as a causative gene of glaucoma, and Sanger sequencing was performed for verification and cosegregation analysis. Three in silico tools all predicted these two missense variants to be probably disease-causing. Western blot analysis, immunofluorescence, and dual-luciferase assay were further used to evaluate the effect of FOXC1 missense variants, and demonstrated that the two variants resulted in decreased transactivation activity of FOXC1 although the variants had no effect on the protein amount and the nucleus subcellar localization of FOXC1 compared with the wild type, which implies that both of two variants may be probably pathogenic. In this study, we reported two novel FOXC1 variants as well as a reported variant and the phenotypes associated to these variants, which expands the spectrum and relevant phenotypes of FOXC1 variants. Additionally, the functional analysis of FOXC1 variants provides further insight into the possible pathogenesis of anterior segment anomaly related to FOXC1.

A Facile Probe for Fluorescence Turn-on and Simultaneous Naked-Eyes Discrimination of H2S and biothiols (Cys and GSH) and Its Application.

Hydrogen sulfide and biothiol molecules such as Cys and GSH acted important roles in many physiological processes. To simultaneously detect and distinguish them was quite necessary by a suitable fluorescent probe. A novel chemosensor 4-(4-(benzo[d]thiazol-2-yl)-2-methoxyphenoxy)-7-nitrobenzo[c][1,2,5]oxadiazole (BMNO) was designed to detect H2S/Cys/GSH using the combination of nitrobenzofurazan (NBD) and benzothiazole fluorophores linked by a facile ether bond. The probe BMNO was developed for simultaneous identification of H2S, Cys and GSH. Noticeably, the color changes (from colorless to light purple, light orange and light yellow) of probe BMNO solutions for sensing H2S, Cys and GSH could be observed by naked eyes, respectively. The probe BMNO exhibited high selectivity and sensitivity for H2S, Cys and GSH showing distinct optical signal with detection limit as low as 0.15 µM, 0.03 µM and 0.14 µM, respectively. The sensing mechanism was clarified by spectrum analysis and some controlled experiments. In addition, these outstanding properties of probe BMNO enabled its practical applications in detection H2S in beer, and in cell imaging for Cys and GSH as well.

Periostin promotes arterial calcification through PPARγ-related glucose metabolism reprogramming.

Extracellular matrix (ECM) exerts a series of biological functions and contributes to almost 30% of the osteogenic process. Periostin is a secreted protein that can alter ECM remodeling in response to vascular injury. However, the role of periostin in vascular calcification has yet to be fully investigated. As found in this study, recombinant periostin accelerated the thoracic aortas calcification, increased the expression of glycolysis key enzymes, and disturbed the normal oxidative phosphorylation (OXPHOS) ex vivo, which could be alleviated by the peroxisome proliferation-activated receptor γ (PPARγ) agonist pioglitazone. In vascular smooth muscle cells (VSMCs), periostin promoted VSMC-osteoblastic phenotype transition and calcium deposition and suppressed PPARγ expression. Mechanistically, periostin caused overactivation of glycolysis and mitochondrial dysfunction in VSMCs as assessed by extracellular acidification rate, oxygen consumption rate, and mitochondrial respiratory chain complex activities. Targeted glycolysis inhibitors reduced mitochondrial calcium overload, apoptosis, and periostin-induced VSMCs calcification. PPARγ agonists preserved glycolysis and OXPHOS in the stimulated microenvironment and reversed periostin-promoted VSMC calcification. Furthermore, plasma periostin, lactate, and matrix Gla protein levels were measured in 274 patients undergoing computed tomography to determine coronary artery calcium score (Agatston score). Plasma periostin and lactate levels were both linked to an Agatston score in patients with coronary artery calcification (CAC). There was also a positive correlation between plasma periostin and lactate levels. This study suggests that downregulation of PPARγ is involved in the mechanism by which periostin accelerates arterial calcification partly through excessive glycolysis activation and unbalanced mitochondrial homeostasis.NEW & NOTEWORTHY Periostin caused arterial calcification, overactivated glycolysis, and damaged OXPHOS. PPARγ agonists alleviated periostin-promoted arterial calcification and corrected abnormal glycolysis and unbalanced mitochondrial homeostasis. There exists a relationship between periostin and lactate in patients with CAC.

Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy.

Arterial media calcification is related to mitochondrial dysfunction. Protective mitophagy delays the progression of vascular calcification. We previously reported that lactate accelerates osteoblastic phenotype transition of VSMC through BNIP3-mediated mitophagy suppression. In this study, we investigated the specific links between lactate, mitochondrial homeostasis, and vascular calcification. Ex vivo, alizarin S red and von Kossa staining in addition to measurement of calcium content, RUNX2, and BMP-2 protein levels revealed that lactate accelerated arterial media calcification. We demonstrated that lactate induced mitochondrial fission and apoptosis in aortas, whereas mitophagy was suppressed. In VSMCs, lactate increased NR4A1 expression, leading to activation of DNA-PKcs and p53. Lactate induced Drp1 migration to the mitochondria and enhanced mitochondrial fission through NR4A1. Western blot analysis of LC3-II and p62 and mRFP-GFP-LC3 adenovirus detection showed that NR4A1 knockdown was involved in enhanced autophagy flux. Furthermore, NR4A1 inhibited BNIP3-related mitophagy, which was confirmed by TOMM20 and BNIP3 protein levels, and LC3-II co-localization with TOMM20. The excessive fission and deficient mitophagy damaged mitochondrial structure and impaired respiratory function, determined by mPTP opening rate, mitochondrial membrane potential, mitochondrial morphology under TEM, ATP production, and OCR, which was reversed by NR4A1 silencing. Mechanistically, lactate enhanced fission but halted mitophagy via activation of the NR4A1/DNA-PKcs/p53 pathway, evoking apoptosis, finally accelerating osteoblastic phenotype transition of VSMC and calcium deposition. This study suggests that the NR4A1/DNA-PKcs/p53 pathway is involved in the mechanism by which lactate accelerates vascular calcification, partly through excessive Drp-mediated mitochondrial fission and BNIP3-related mitophagy deficiency.

Fucoidan exerts antidepressant-like effects in mice via regulating the stability of surface AMPARs.

The inflammatory hypothesis is one of the most important mechanisms of depression. Fucoidan is a bioactive sulfated polysaccharide abundant in brown seaweeds with anti-inflammatory activity. However, the antidepressant effects of fucoidan on chronic stress-induced depressive-like behaviors have not been well elucidated. Here, we used two different depressive-like mouse models, lipopolysaccharide (LPS) and chronic restraint stress (CRS) models, to explore the detailed molecular mechanism underlying its antidepressant-like effects in C57BL/6J mice by combining multiple behavioral, molecular and immunofluorescence experiments. Adenovirus-mediated overexpression of caspase-1 and pharmacological inhibitors were also used to clarify the antidepressant mechanisms of fucoidan. We found that acute administration of fucoidan did not produce antidepressant effects in the tail suspension test (TST) and forced swim test (FST). Interestingly, chronic fucoidan administration not only dose-dependently reduced stress-induced depressive-like behaviors in the TST, FST, sucrose preference test (SPT), and novelty-suppressed feeding test (NSFT), but also alleviated the downregulation of brain-derived neurotrophic factor (BDNF)-dependent synaptic plasticity via inhibiting caspase-1-mediated inflammation in the hippocampus of mice. Moreover, fucoidan significantly ameliorated behavioral and synaptic plasticity abnormalities in the overexpression of caspase-1 in the hippocampus of mice. Furthermore, blocking BDNF abolished the antidepressant-like effects of fucoidan in mice. Therefore, our findings clearly indicate that fucoidan provides a potential supplementary noninvasive treatment for depression by inhibition of hippocampal inflammation.

Using probiotics for type 2 diabetes mellitus intervention: Advances, questions, and potential.

Type 2 diabetes mellitus (T2DM) has become one of the most prevalent diseases on earth and several treatments have been developed. However, the current intervention approaches have not been as effective as expected. One promising supplementary strategy is the use of probiotics through direct or indirect approaches. Probiotics are microbial food cultures conferring health-promoting properties. In this review, we summarized the current theories and mechanisms of T2DM intervention using probiotics and hypothesize that probiotics intervene T2DM during its onsetting, developing, and complicating. For the first time, we comprehensively analyzed T2DM intervention in animal models using both wide-type probiotics in different forms and using recombinant probiotics. Then, probiotic intervention in T2DM patients was reviewed and the main results were compared with that obtained from animal studies. Finally yet importantly, remaining questions that are important such as in which form and in which state, as well as the future potential of probiotic intervention in T2DM were discussed from a perspective of food microbiologists. In conclusion, probiotic intervention in T2DM is promising but there are still many important issues unsolved yet. Critical review of the advances, questions, and potential of probiotic intervention in T2DM promotes the development of this approach for further application in humans.

Remarkable adsorption performance of MOF-199 derived porous carbons for benzene vapor.

Volatile organic compounds (VOCs) are perceived as serious pollutants due to their great threat to both environment and human health. Recovery and removal of VOCs is of great significance. Herein, novel MOF-199 derived porous carbon materials (MC-T-n) were prepared by using MOF-199 as precursor, glucose as additional carbon source and KOH as activator, and then characterized. Adsorption performance of MC-T-n materials for benzene vapor was investigated. Isotherms of MC-T-n samples towards benzene and water vapor were measured. The adsorption selectivities of benzene/water were estimated by DIH (difference of the isosteric heats) equation. Results indicated that BET surface area and pore volume of MC-T-n materials reached separately 2320 m2/g and 1.05 m3/g. Benzene adsorption capacity of MC-T-n materials reached as high as 12.8 mmol/g at 25 °C, outperforming MOF-199 and some conventional adsorbents. Moreover, MC-T-n materials presented type-V isotherms of water vapor, suggesting their excellent water resistance. The isosteric heats of benzene adsorption on MC-500-6 were much greater than that of water adsorption, leading to a preferential adsorption for C6H6 over H2O. The adsorption selectivity of C6H6/H2O on MC-500-6 reached up to 16.3 superior to some previously reported MOFs. Therefore, MC-500-6 was a promising candidate for VOC adsorption and seperation. This study provides a strong foundation for MOF derived porous carbons as adsorbents for VOC removal.

Novel covalent organic framework/PVDF ultrafiltration membranes with antifouling and lead removal performance.

Membrane separation technology is recognized as a competitive approach to remove Pb2+ from water system due to its high efficiency and low operating cost. In present study, a simple and facile approach was developed to fabricate covalent organic framework (COF) modified PVDF ultrafiltration membranes with comprehensive antifouling property and superior Pb2+ removal ability. Herein, COF was synthesised in a homogenous PVDF/DMAc solution to fabricate hydrophilic COF modified PVDF ultrafiltration membranes with the Pb2+ removal property. The filtration test demonstrated that the COF modified PVDF ultrafiltration membranes exhibited excellent antifouling property and high water flux. Moreover, the membranes showed remarkable potential for treating Pb2+-containing water. The removal efficiency was determined at 92.4%, and its removal efficiency was 87.5% at the fourth treatment cycle with Pb2+-containing water. The present work provides a valuable platform for further development of efficient composite membranes for the treatment of Pb2+-containing water.

Proton Conduction in Organically Templated 3D Open-Framework Vanadium-Nickel Pyrophosphate.

A new proton-conducting material (C6H14N2)[NiV2O6H8(P2O7)2]·2H2O (1) was hydrothermally synthesized by using 1,4-diazabicyclo[2,2,2]octane (DABCO) as the template. Its inorganic framework, determined by single crystal X-ray diffraction, is constructed by the connection of V/NiO6 octahedral to P2O7 pyrophosphate units through sharing oxygen atoms, giving rise to three-dimensional (3D) intersecting 6-, 8-, and 12-ring channels along the [100], [010], and [001] directions, respectively, in which there are ordered protonated DABCO cations balancing negative charge of the framework and disordered water molecules. Complex impedance measurements on polycrystalline samples gave proton conductivities of 4.9 × 10-3 and 2.0 × 10-2 S cm-1 at 25 and 60 °C under high humidity conditions, respectively. The activation energy is 0.38 eV.

A Highly Selective Fluorescence "Turn on" and Absorbance-Ratiometric Detection of Al3+ in Totally H2O and its Application in Test Paper.

A novel naphthalene based fluorescence probe NBDH was designed and synthesized. Probe NBDH exhibited highly selective and sensitive responses towards Al3+ in HEPES-NaOH buffer solution (pH = 7.4). In addition, the detection of NBDH to Al3+ could be achieved through dual channels embodied in significant fluorescent turn-on signal and ratiometric absorbance response. The stoichiometry ratio of NBDH-Al3+ was 1:1 by fluorescence job' plot and binging mechanism was further varified by the FT-IR, NMR titration and HRMS. Furthermore, NBDH was achieved in real sample detection, and a series of color test paper were developed for visual detecting Al3+ ions.

A Benzothiazole-Based Fluorescent Probe for Ratiometric Detection of Al3+ and Its Application in Water Samples and Cell Imaging.

An easily prepared benzothiazole-based probe (BHM) was prepared and characterized by general spectra, including 1H NMR, 13C NMR, HRMS, and single-crystal X-ray diffraction. Based on the synergistic mechanism of the inhabitation of intramolecular charge transfer (ICT), the BHM displayed high selectivity and sensitivity for Al3+ in DMF/H2O (v/v, 1/1) through an obvious blue-shift in the fluorescent spectrum and significant color change detected by the naked eye, respectively. The binding ratio of BHM with Al3+ was 1:1, as determined by the Job plot, and the binding details were investigated using FT-IR, 1H NMR titration, and ESI-MS analysis. Furthermore, the BHM was successfully applied in the detection of Al3+ in the Songhua River and on a test stripe. Fluorescence imaging experiments confirmed that the BHM could be used to monitor Al3+ in human stromal cells (HSC).

A New 3-D Open-Framework Zinc Borovanadate with Catalytic Potentials in α-Phenethyl Alcohol Oxidation.

A novel 3-D open-framework zinc borovanadate [Zn6(en)3][(VIVO)6(VVO)6O6(B18O36(OH)6)·(H2O)]2·14H2O (1, en = ethylenediamine) was hydrothermally obtained and structurally characterized. The framework was built from [V12B18O54(OH)6(H2O)]10- polyanion clusters bridged by Zn(en) complex fragments. The compound not only possessed a three-dimensional open-framework structure with unique plane-shaped channels, but also exhibited excellent catalytic activities for the oxidation of α-phenethyl alcohol.

CDKN1C (P57): one of the determinants of human endometrial stromal cell decidualization.

Decidualization is regulated by crosstalk of progesterone and the cAMP pathway. It involves extensive reprogramming of gene expression and includes a wide range of functions. To investigate how cell cycle regulatory genes drive the human endometrial stromal cell (ESC) exit cell cycle and enter differentiation, primary cultured ESC was treated with 8-Br-cAMP and MPA and cell cycle distribution was investigated by flow cytometry. High-throughput cell cycle regulatory gene expression was also studied by microarray. To validate the results of microarray chip, immunohistochemistry and semi-quantitative method of optical density were used to analyze the expression of cell cycle regulator proteins in proliferative phase of endometrium (n = 6) and early pregnancy decidua (n = 6). In addition, we selected cyclin-dependent kinase inhibitor 1c (CDKN1C, also known as P57) and cyclin-dependent kinase inhibitor 2b (CDKN2B, also known as P15) in order to study their role in the process of decidualization by the RNAi method. ESC was arrested at G0/G1 checkpoints during decidualization. Cell cycle regulatory genes P57 and P15 were upregulated, while cyclin D1 (CCND1), cyclin-dependent kinase 2 (CDK2), and cell division cycle protein 2 homolog (CDC2) were downregulated during ESC differentiation both in vitro and vivo. P57 siRNA impaired ESC decidualization and caused different morphological and ultrastructural changes as well as a relatively low secretion of prolactin, but P15 siRNA had no effects. We concluded that P15, CCND1, CDK2, and CDC2 may participate in ESC withdraw from the cell cycle and go into differentiation both in vitro and in vivo. P57 is one of the key determinants of ESC differentiation due to its effect on the cell cycle distribution, but its association with the decidua-specific transcription factor needs further investigation.

A Highly Selective Naphthalimide-Based Chemosensor: "Naked-Eye" Colorimetric and Fluorescent Turn-On Recognition of Al3+ and Its Application in Practical Samples, Test Paper and Logic Gate.

A novel naphthalimide-based colorimetric and fluorescent turn-on chemosensor for Al3+ was synthesized and characterized with spectroscopic techniques. In MeOH solution, BPAM showed high selectivity and sensitivity to Al3+ by a 60-fold fluorescence enhancement and blue-shift absorption with visible color changes attributed to the contribution of chelation enhanced fluorescence (CHEF) and inhibition of intramolecular charge transfer (ICT). A 1:1 BPAM-Al3+ complex confirmed by job's plot and HRMS with a binding constant of 6.37 × 104 M- 1, and the detection limit for Al3+ was as low as 1.59 × 10- 7 M. BPAM was successfully applied in real sample detection and assessing the existence of Al3+ by a colorimetric method on filter paper. Furthermore, the fluorescent signals of BPAM were designed to construct an INHIBIT molecular logic gate.

Fructus Ligustri Lucidi modulates estrogen receptor expression with no uterotrophic effect in ovariectomized rats.

BACKGROUND: Accumulating evidence suggests that Fructus Ligustri Lucidi (FLL) plays a beneficial role in preventing the development of osteoporosis. However, the effects of FLL on estrogen receptor (ER) α and ERß expressions remain unknown. Therefore, in the current study we attempted to probe into the effects of FLL on ERα and ERß expressions in femurs, tibias and uteri of ovariectomized (OVX) rats. METHODS: The OVX rats were orally administrated with FLL water extract (3.5 g/kg/day) for 12 weeks. The uteri, femurs, tibias and serum were harvested from rats. The serum levels of estrogen (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by ELISA. The expressions of ERα and ERß in the femurs and tibias as well as uteri were analysed by western blot and immunohistochemical staining. RESULTS: FLL treatment did not increase uterus relative weight in OVX rats. Further, FLL treatment increased ERα expression in the femurs and tibias, and enhanced ERß expression in the uteri of OVX rats. However, the resulted expression of ERα was stronger than that of ERß in OVX rats in response to FLL treatment. Meanwhile, administration with FLL to OVX rats increased FSH and LH but did not increase E2 level in the serum. CONCLUSION: FLL treatment shows tissue selection on ERα and ERß expressions in the femurs and tibias as well as uteri of OVX rats without uterotrophic effect, which may offer the scientific evidence of the efficiency and safety of its clinical application.