Highly-Efficient 2D Nonfullerene Acceptors Enabled by Subtle Molecular Tailoring Engineering.

The conjugate expansion of nonfullerene acceptors is considered to be a promising approach for improving organic photovoltaic performance because of its function in tuning morphological structure and molecular stacking behavior. In this work, two nonfullerene acceptors are designed and synthesized using a 2D π-conjugate expansion strategy, thus enabling the construction of highly-efficient organic solar cells (OSCs). Compared with YB2B (incorporating dibromophenanthrene on the quinoxaline-fused core), YB2T (incorporating dibromobenzodithiophene on the quinoxaline-fused core) has red-shifted spectral absorption and better charge transport properties. Moreover, the more orderly and tightly intermolecular stacking of YB2T provides the possibility of forming a more suitable phase separation morphology in blend films. Through characterization and analysis, the YB2T-based blend film is found to have higher exciton dissociation efficiency and less charge recombination. Consequently, the power conversion efficiency (PCE) of 17.05% is achieved in YB2T-based binary OSCs, while YB2B-based devices only reached 10.94%. This study demonstrates the significance of the aromatic-ring substitution strategy for regulating the electronic structure and aggregation behavior of 2D nonfullerene acceptors, facilitating the development of devices with superior photovoltaic performance.

Exploring Electronic Characteristics of Acceptor-Donor-Acceptor-Type Molecules by Single-Molecule Charge Transport.

The electronic characteristics of organic optoelectronic materials determine the performance of corresponding devices. Clarifying the relationship between molecular structure and electronic characteristics at the single-molecule level can help to achieve high performance for organic optoelectronic materials and devices, especially for organic photovoltaics. In this work, a typical acceptor-donor-acceptor (A-D-A)-type molecule is explored by combining theoretical and experimental studies to reveal the intrinsic electronic characteristics at the single-molecule level. Specifically, the A-D-A-type molecule with 1,1-dicyano methylene-3-indanone (INCN) acceptor units exhibits an enhanced conductance in single-molecule junctions when compared with the control donor molecule, because the acceptor units of the A-D-A-type molecule contribute additional transport channels. In addition, through opening the S∙∙∙O noncovalent conformational lock by protonation to expose the -S anchoring sites, the charge transport of the D central part is detected, proving that the conductive orbitals contributed by the INCN acceptor groups can penetrate the whole A-D-A molecule. These results provide important insights into the development of high-performance organic optoelectronic materials and devices toward practical applications.

Prevalence of Hypertension and Its Association with Cardiovascular Risk Factors in College Students in Hunan, China.

Background: Although the prevalence of hypertension has been well studied in middle age and elderly populations, few studies have systematically investigated the prevalence of hypertension and its association with cardiovascular and cerebrovascular risk factors in young populations. Objective: This study examined the prevalence of hypertension in college students and its correlation with cardiovascular and cerebrovascular risk factors, such as neck circumference and body mass index (BMI). Methods: This population-based study recruited a total of 1719 students (723 were junior, 502 were sophomore, and 494 were freshman), including 996 males (average age: 20.8 years) and 723 females (average age: 20.4 years). Hypertension was defined by the 2018 revised edition of the Chinese Guidelines for Prevention and Treatment of Hypertension. Blood and pulse pressure were measured using standard protocols. Circulating levels of lipids, glucose, glycosylated hemoglobin (GHb), leptin, and adiponectin were determined using standard methods. The Chi-squared (χ2) test was used for comparison of significant differences between groups. Linear and logistic regression analyses were used to explore risk factors that significantly influence hypertension. Findings: The prevalence of hypertension was 10.59% in the total cohort, and sophomores had a higher prevalence of hypertension than freshmen and juniors (χ2 = 19.372; P < 0.001). In addition, male students had a significantly higher prevalence of hypertension (10.24%) and abnormal pulse pressure (8.13%) than female students (1.4% and 0.83%) (χ2 = 327.424, P < 0.001 for high SBP and χ2 = 60.49, P < 0.001 for high DBP, respectively). Correlation analysis revealed that hypertension was significantly correlated with neck circumference and BMI (r = 0.509, P < 0.001; r = 0.474, P < 0.001), but not significantly correlated with the other parameters examined. Conclusion: The prevalence of hypertension in college students is closely correlated with two obesity indicators, neck circumference and BMI.

GMP development and preclinical validation of CAR-T cells targeting a lytic EBV antigen for therapy of EBV-associated malignancies.

Introduction: Epstein-Barr virus (EBV) is a widely spread pathogen associated with lymphoproliferative diseases, B/ T/ NK cell lymphomas, nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). EBV lytic reactivations contribute to the genomic instability, inflammation and tumorigenesis of NPC, promoting cancer progression. Patients with NPC refractory to standard therapies show dismal survival. EBV gp350 is an envelope protein detectable in NPC specimens intracellularly and on the cell membrane of malignant cells, and is a potential viral antigen for T cell-directed immunotherapies. The potency of T cells engineered with a chimeric antigen receptor (CAR) targeting gp350 against EBV+ lymphoproliferative disease was previously shown. Methods: Here, we advanced towards preclinical and non-clinical developments of this virus-specific CAR-T cell immunotherapy against NPC. Different gp350CAR designs were inserted into a lentiviral vector (LV) backbone. Results: A construct expressing the scFv 7A1-anti-gp350 incorporating the CD8 transmembrane and CD28.CD3ζ signaling domain (ZT002) was selected. High titer ZT002 (~1x108 TU/ml) was manufactured in HEK 293T/17 suspension cells in serum free media as large-scale production under good manufacturing practices (GMP). A LV multiplicity of infection (MOI) of 1 resulted in high frequencies of functional gp350CAR+ T cells (>70%) at a low (<2) vector copy numbers in the genome. ZT002 was therefore used to establish gp350CAR-T batch run production methods. GMP upscaling and validation of T cell transduction and expansion in several runs resulted in average 3x109 gp350CAR-T cells per batch. >80% CD3+ gp350CAR-T cells bound to purified gp350 protein. In vitro cytotoxicity and cytokine secretion assays (IFN-γ and TNF-α) confirmed the specificity of gp350CAR-T cells against gp350+ NPC, GC and lymphoma cell targets. Immunocompromised B-NDG mice (NOD.CB17-PrkdcscidIl2rgtm1/Bcgen) were challenged s.c. with a EBV+ NPC C666.1 cell line expressing gp350 and then treated with escalating doses of gp350CAR-T cells or with non-transduced T cells. gp350CAR-T cells promoted antitumor responses, bio-distributed in several tissues, infiltrated in tumors and rejected gp350+ tumor cells. Discussion: These results support the use of gp350CAR-T cells generated with ZT002 as an Innovative New Drug to treat patients with solid and liquid EBV-associated malignancies.

Possible causes of atherosclerosis: lncRNA COLCA1 induces oxidative stress in human coronary artery endothelial cells and impairs wound healing.

Background: Atherosclerosis is the most common cause of cardiovascular disease, accompanied by high mortality and poor prognosis. Low-density lipoprotein (LDL) and its oxidized form oxidized low-density lipoprotein (oxLDL) play an important role in atherosclerosis. This article will explore the role of the lncRNA COLCA1 (colorectal cancer associated 1)/hsa-miR-371a-5p/SPP1 (secreted phosphoprotein 1) pathway in oxLDL in causing human coronary artery endothelial cells (HCAECs) inflammation and related biological function changes. Methods: OxLDL was used to stimulate HCAECs. The inflammatory response and biological function changes of HCAECs were analyzed, total RNA-seq was performed on HCAECs before and after stimulation, and RT-Qpcr (real-time quantitative PCR) was used to verify the differential genes. Interference of the expression of COLCA1 in HCAECs was performed by siRNA interference technology to verify the role of COLCA1 in the biological function changes of HCAECs after oxLDL stimulation, and further prove that COLCA1 affects SPP1 through hsa-miR-371a-5p. Results: OxLDL can affect the oxidative stress response of HCAECs, which in turn affects the apoptosis and wound healing ability of HCAECs. COLCA1 and SPP1 were highly expressed after oxLDL stimulation, while hsa-miR-371a-5p was the opposite. After COLCA1 interference, the oxidative stress level of HCAECs stimulated by oxLDL decreased, the apoptosis level also significantly decreased, and the wound healing ability was enhanced. After simultaneous COLCA1 interference and recovery of the expression of hsa-miR-371a-5p, these improved functions disappeared. The dual-luciferase assay confirmed that hsa-miR-371a-5p and COLCA1, hsa-miR-371a-5p and SPP1 has binding targets. Conclusions: OxLDL can up-regulate the expression of COLCA1 in HCAECs, which in turn affects the intracellular COLCA1/hsa-miR-371a-5p/SPP1 pathway to regulate the level of oxidative stress in cells. This in turn affects the level of apoptosis and wound healing ability, which causes cells to produce a continuous inflammatory response.

All-Small-Molecule Organic Solar Cells with Efficiency Approaching 16% and FF over 80.

Molecule engineering has been demonstrated as a valid strategy to adjust the active layer morphology in all-small-molecule organic solar cells (ASM-OSCs). In this work, two non-fullerene acceptors (NFAs), FO-2Cl and FO-EH-2Cl, with different alkyl side chains are reported and applied in ASC-OSCs. Compared with FO-2Cl, FO-EH-2Cl is designed by replacing the octyl alkyl chains with branched iso-octyl alkyl chains, leading to an enhanced molecular packing, crystallinity, and redshifted absorption. With a small molecule BSFTR as donor, the device of BSFTR:FO-EH-2Cl obtains a better morphology and achieves a higher power conversion efficiency (PCE) of 15.78% with a notable fill factor (FF) of 80.44% than that of the FO-2Cl-based device with a PCE of 15.27% and FF of 78.41%. To the authors' knowledge, the FF of 80.44% is the highest value in ASM-OSCs. These results demonstrate a good example of fine-tuning the molecular structure to achieve suitable active layer morphology with promising performance for ASM-OSCs, which can provide valuable insight into material design for high-efficiency ASM-OSCs.

Phenanthroline-imine ligands for iron-catalyzed alkene hydrosilylation.

Iron-catalyzed organic reactions have been attracting increasing research interest but still have serious limitations on activity, selectivity, functional group tolerance, and stability relative to those of precious metal catalysts. Progress in this area will require two key developments: new ligands that can impart new reactivity to iron catalysts and elucidation of the mechanisms of iron catalysis. Herein, we report the development of novel 2-imino-9-aryl-1,10-phenanthrolinyl iron complexes that catalyze both anti-Markovnikov hydrosilylation of terminal alkenes and 1,2-anti-Markovnikov hydrosilylation of various conjugated dienes. Specifically, we achieved the first examples of highly 1,2-anti-Markovnikov hydrosilylation reactions of aryl-substituted 1,3-dienes and 1,1-dialkyl 1,3-dienes with these newly developed iron catalysts. Mechanistic studies suggest that the reactions may involve an Fe(0)-Fe(ii) catalytic cycle and that the extremely crowded environment around the iron center hinders chelating coordination between the diene and the iron atom, thus driving migration of the hydride from the silane to the less-hindered, terminal end of the conjugated diene and ultimately leading to the observed 1,2-anti-Markovnikov selectivity. Our findings, which have expanded the types of iron catalysts available for hydrosilylation reactions and deepened our understanding of the mechanism of iron catalysis, may inspire the development of new iron catalysts and iron-catalyzed reactions.

Periostin contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts.

Background and aims: Adventitial remodeling is an important pathological process of atherosclerosis, but cues implicated in adventitial remodeling are far from fully understood. Periostin (POSTN), a matricellular protein, has been demonstrated to have multiple roles in cardiovascular diseases. The aim of the study was to explore the function of POSTN in adventitial remodeling during atherosclerosis. Methods: An atherosclerosis model was constructed based on ApoE-/- mice fed a high-fat and high-cholesterol diet. The expression of POSTN in the adventitia of mouse atherosclerotic vascular specimens was detected by immunohistochemical staining. The roles of POSTN in regulating adventitial fibroblast activation were assessed by cell contractility and activation marker α-smooth muscle actin (α-SMA) expression evaluation in adventitial fibroblasts overexpressing POSTN. In addition, we performed quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to examine the expression of the proinflammatory chemokines transforming growth factor-ß1 (TGF-ß1) and monocyte chemotactic protein 1 (MCP1), as well as some extracellular matrix (ECM)-related proteins, in POSTN-overexpressing adventitial fibroblasts. Finally, the integrin-related signaling pathway was detected upon POSTN overexpression in adventitial fibroblasts. Results: POSTN was highly expressed in the adventitia of atherosclerotic aortae in the mouse atherosclerosis model and promoted the activation and contraction of adventitial fibroblasts. Meanwhile, POSTN also induced adventitial fibroblasts to express TGF-ß1, monocyte chemotactic protein-1 (MCP1), and ECM-related proteins and activated the phosphorylation of focal adhesion kinase (FAK) and Src. Conclusions: Our results revealed that POSTN is elevated in adventitia during atherosclerosis and contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts.

Photocatalyzed Dehydroxylative Amination of Phenols: A Ring-Expansion Approach for Medium-Sized Benzolactams.

An efficient photopromoted dehydroxylative ring-expansion approach to eight-membered benzolactams that employ phthalocyanine iron(II) as the photosensitizer has been developed. This cascade reaction protocol, featuring a visible-light-promoted dehydroxylative amination and oxidative ring-expansion lactamization of 4-hydroxyphenols with N-alkyl-4-piperidinones, provides a green and reliable approach to a diverse array of valuable eight-membered benzolactams with high chemo- and regioselectivity.

Research on residual strength characteristics of high water materials based on improved H-B criterion.

To develop a new gangue polymer filling material with low compressive ratio, this paper intends to add high water cementing material to the gangue for backfilling. Uniaxial and tri-axial bearing experiments were conducted to study its bearing characteristics and residual strength. Based on Hock-Brown model theory, it is proposed that friction angle φr can be introduced to substitute model parameter mi, and the degree of cohesion loss can characterize the value of s. So the improved H-B model is established to characterize the residual strength of materials with ductile failure characteristics. The results show that the compressive strength of high water filling material increases linearly corresponding to the rise of confining pressure, and its strength characteristics conform to Mohr-Coulomb strength criterion. The ductile failure characteristics of the sample endow it with high residual strength, which in turn qualifies it for underground filling. After the introduction of cohesion and friction angle, the improved H-B criterion can fit the residual strength curve of the high water filling material more competently. The fitting coefficient of the samples with three water contents is 1.00, 0.99, and 1.00, respectively. The improved H-B model of residual strength demonstrates the change rule of residual strength of the samples corresponding to the change of confining pressure; under tri-axial loading, the angle between fracture surface and axial direction becomes larger as the confining pressure rises; and the failure mode of the material transforms from splitting failure to shear failure.

MiR-302b-5p enhances the neuroprotective effect of IGF-1 in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease by regulating inducible nitric-oxide synthase.

Parkinson's disease (PD) is a neurodegenerative disease which results in damage in neuronal cells. Insulin-like growth factor (IGF)-1 was previously reported to play a role of neuroprotection in some diseases. Nitric oxide (NO) can also regulate neuronal cells. However, the mechanisms underlying IGF-1 and NO in PD still need to be elucidated. In present study, we explored the interaction between IGF-1 and inducible Nitric-Oxide Synthase (iNOS) in PD progression. We firstly constructed PD models by methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or MPP+ treatment. Then RT-qPCR revealed that IGF-1 expression was downregulated while iNOS expression was upregulated in MPTP model. Moreover, IGF-1 elevation or iNOS depletion enhanced cell viability and blocked cell apoptosis. Rescue assay disclosed iNOS overexpression reversed the effect on viability and apoptosis mediated by IGF-1 upregulation. Furthermore, IGF-1 was identified to positively regulate miR-302b-5p which could target iNOS. MiR-302b-5p could abolish the inhibitory function IGF-1 exerted on cell apoptosis and iNOS could counteract miR-302b-5p upregulation-triggered inhibition on cell apoptosis as well. Besides, we observed the deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice. To sum up, present study proved that miR-302b-5p enhanced the neuroprotective effect of IGF-1 in MPTP-induced PD by regulating iNOS, recommending a novel therapeutic target for PD treatment. SIGNIFICANCE OF THE STUDY: In this study, we mainly explored that IGF-1 was decreased while iNOS was boosted in MPTP-induced PD mice model; IGF-1 suppressed while iNOS promoted MPP+ -induced toxicity and apoptosis in SH-SY5Y cells; miR-302b-5p ehanhced the neuroprotective effect of IGF-1 via targeting Inos; deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice.

Double C-N bond cleavages of N-alkyl 4-oxopiperidinium salts: access to unsymmetrical tertiary sulfonamides.

In this paper, regiospecific, double intraannular C-N bond cleavages of N-alkyl 4-oxopiperidinium salts are presented. The reaction sequence involves a charge-transfer complex, in situ formed between sulfonyl chloride and N-methylmorpholine, which induces S-Cl bond homolysis of sulfonyl chloride, yielding a reactive sulfonyl radical that further induces the double C-N bond cleavages of N-alkyl 4-oxopiperidinium salt. The secondary amine thus produced was trapped by sulfonyl chloride to yield the desired sulfonamide product. The key feature of this protocol is that two intraannular C-N bonds of the 4-oxopiperidine ring are cleaved in one step under metal- and oxidant-free conditions.

Semisynthetic Derivatives of Fradcarbazole A and Their Cytotoxicity against Acute Myeloid Leukemia Cell Lines.

Fourteen derivatives of the marine-derived fradcarbazole A were synthesized from staurosporine. Their structures were identified by NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS). The derivatives were screened in vitro for antiproliferative activity against three human leukemic cell lines (MV4-11, HL-60, K562). All of the derivatives displayed cytotoxicity against the human FLT-3 internal tandem duplication (ITD) mutant acute myeloid leukemia (AML) cell line MV4-11 with IC50 values of 0.32-0.96 µM. The mechanism of action studies indicated that the most effective 3-chloro-5‴-fluorofradcarbazole A (6) induced apoptosis of the MV4-11 cells and arrested the cell cycle at the G0/G1 phase. Furthermore, compound 6 can reduce the expression of FLT-3, CDK2, and c-kit. The results suggest that 3-chloro-5‴-fluorofradcarbazole A (6) is a potential candidate for developing novel anti-AML agents in the future.

Reinforcement of Polylactic Acid for Fused Deposition Modeling Process with Nano Particles Treated Bamboo Powder.

The focus of this report was to understand the tensile properties and dynamic mechanical properties of bamboo powder (BP) reinforced polylactic acid (PLA) composite filaments which were treated with nano calcium carbonate (CaCO3), cellulose nanofibers (CNF), and micro-crystalline cellulose (MCC) using impregnation modification technology. The storage modulus (E') of nano CaCO3-BP/PLA, MCC-BP/PLA, and CNF-BP/PLA composite filaments increased compared with BP/PLA composite filaments before the glass transition temperature Tg. When the temperature was above Tg, the reinforcement effect of nano CaCO3, MCC, and CNF gradually became less apparent. The loss modulus (E'') and loss factor (tan δmax) of the nano CaCO3-BP/PLA, MCC-BP/PLA, and CNF-BP/PLA composite filaments was higher than that of BP/PLA composite filaments produced by the "one-step" method. The tensile strength (TS) results showed a similar trend. Compared with the control samples, the TS of nano CaCO3-BP/PLA, MCC-BP/PLA, and CNF-BP/PLA composite filaments produced by the "one-step" method (and the "two-step" method) increased by 40.33% (and 10.10%), 32.35% (and -8.61%), and 12.32% (and -12.85%), respectively. The TS of nano CaCO3-BP/PLA, MCC-BP/PLA, and CNF-BP/PLA composite filaments produced by the "one-step" method was slightly higher than those produced by the "two-step" method. The elongation at break (EAB) of BP/PLA composite filaments was higher than that of BP/PLA samples treated with nano CaCO3, MCC, or CNF. The PLA and modified BP were readily accessible through a simple mixing process. The rheological investigation of such mixtures showed that nano CaCO3, CNF, and MCC have different effects on the processability and rheological properties of composites.

Sulfonylation of 1,4-Diazabicyclo[2.2.2]octane: Charge-Transfer Complex Triggered C-N Bond Cleavage.

A novel charge-transfer complex triggered sulfonylation of 1,4-diazabicyclo[2.2.2]octane (DABCO) with mild reaction conditions has been developed. The formation of a charge-transfer complex between electron-withdrawing (hetero)aryl sulfonyl chloride and DABCO allows the synthesis of N-ethylated piperazine sulfonamide in good yields. The reaction has a high functional group tolerance. Spectroscopic studies confirmed the charge-transfer complex formation between sulfonyl chlorides and DABCO, which facilitates the C-N bond cleavage of DABCO.

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1.

Osteosarcoma has become one of the most common primary malignant tumors affecting children and adolescents. Although increasing evidence has indicated that microRNAs (miRNAs or miRs) play important roles in the development of osteosarcoma, the expression of miR­27a­3p and its effects on osteosarcoma are not yet fully understood. In the present study, our data demonstrated that the expression of miR­27a­3p in osteosarcoma cell lines was significantly higher than that in the normal human osteoblastic cell line, hFOB 1.19 cell (P<0.01). In order to explore the role of miR­27a­3p in the development and progression of osteosarcoma, the expression of miR­27a­3p was inhibited by transfection of the MG-63 cells with miR­27a­3p inhibitor. The results revealed that the cell proliferative ability significantly decreased (P<0.01), the number of apoptotic cells significantly increased (P<0.01) and the number of cells passing through the Transwell membrane was significantly reduced in the group transfected with the miR­27a­3p inhibitor (P<0.01). At the same time, the expression of E-cadherin and α-catenin was significantly upregulated (P<0.01), while the expression of vimentin was significantly downregulated in the group transfected with the miR­27a­3p inhibitor (P<0.01). Our results also revealed that the mRNA expression of ten-eleven translocation 1 (TET1) in the osteosarcoma cells was significantly downregulated compared with that in the hFOB 1.19 cells (P<0.01). Luciferase reporter system analysis indicated that miR­27a­3p recognized the TET1 3'-UTR. The protein expression of TET1 significantly increased in the group transfected with the miR­27a­3p inhibitor. The results from CCK-8 assay, flow cytometric assay and Transwell invasion analysis revealed that TET1 knockdown inhibited the biological effects induced by the downregulation of miR­27a­3p. Taken together, the findings of this study indicate that miR­27a­3p is upregulated, while TET1 is downregulated in human osteosarcoma cells. miR­27a­3p inhibition suppresses the proliferation and invasion of osteosarcoma cells, and promotes cell apoptosis via the negative regulation of TET1. miR­27a­3p/TET1 may thus be a potential target for the treatment of osteosarcoma.

Downregulation of 14-3-3ß inhibits proliferation and migration in osteosarcoma cells.

The 14-3-3 protein isoform ß (14­3­3ß), which is an intracellular adaptor protein that exists in all eukaryotic organisms, is highly expressed in many cancer tissues, including glioma, lung carcinoma and breast cancer. However, 14­3­3ß expression and function in osteosarcoma progression remain unknown. In the present study, the endogenous expression of 14­3­3ß was assessed in osteosarcoma samples and the effect of 14­3­3ß knockdown was examined in human osteosarcoma MG63 cells using small interfering RNA (siRNA). mRNA and protein expression levels for 14­3­3ß were detected by reverse transcription­quantitative polymerase reaction and western blotting, respectively. The results demonstrated that endogenous 14­3­3ß mRNA and protein were highly expressed in human osteosarcoma tissues and osteosarcoma cell lines (U2OS, MG63 and SaOs­2), but not in normal bone tissues or normal osteoblast hFOB1.19 cells. These data suggested that increased expression of 14­3­3ß may be significantly associated with the development and progression of osteosarcoma. Therefore, the effect of 14­3­3ß knockdown in MG63 cells was further examined in vitro. Knockdown of 14­3­3ß by siRNA significantly decreased cell viability, and inhibited cell proliferation and invasion. In addition, 14­3­3ß knockdown significantly decreased the protein expression levels of ß­catenin, cyclin D1, v­myc avian myelocytomatosis viral oncogene homolog and matrix metallopeptidase 9 in osteosarcoma MG63 cells. These results suggested that the anticancer effects of 14­3­3ß knockdown in MG63 cells might be mediated by the inhibition of the Wnt/ß­catenin signaling pathway. In summary, 14­3­3ß knockdown decreased proliferation and invasion in MG63 cells, which suggests a potential therapeutic application for 14­3­3ß as a novel target for the treatment of osteosarcoma patients.

Effects of Raloxifene on the Proliferation and Apoptosis of Human Aortic Valve Interstitial Cells.

We aimed to explore the effects of raloxifene (RAL) on the proliferation and apoptosis of human aortic valve interstitial cells (AVICs). Different concentrations of RAL were used to act on AVICs. MTS kit is used to test the effects of different concentrations of RAL on the proliferation of AVICs. Cell cycle and apoptosis test used flow cytometry after seven-day treatment. The relative expression levels of caspase-3 and caspase-8 are tested with RT-qPCR and Western blot. The results of MTS testing revealed that the absorbance value (OD value) of the cells in the concentration groups of 10 and 100 nmol/L RAL at a wavelength of 490 nm at five, seven, and nine days significantly decreased compared with that in the control group. Meanwhile, the results of flow cytometry of the cells collected after seven days showed that the ratio of the S stage and the cell apoptosis rate of AVICs can be significantly reduced by RAL in the concentration groups of 10 and 100 nmol/L. The mRNA and protein expressions of caspase-3 and caspase-8 were significantly decreased compared with those in the control group. This study laid the foundation for further treatment of aortic valve disease by using RAL.

Simulation of Bacillus subtilis biofilm growth on agar plate by diffusion-reaction based continuum model.

Various species of bacteria form highly organized spatially-structured aggregates known as biofilms. To understand how microenvironments impact biofilm growth dynamics, we propose a diffusion-reaction continuum model to simulate the formation of Bacillus subtilis biofilm on an agar plate. The extended finite element method combined with level set method are employed to perform the simulation, numerical results show the quantitative relationship between colony morphologies and nutrient depletion over time. Considering that the production of polysaccharide in wild-type cells may enhance biofilm spreading on the agar plate, we inoculate mutant colony incapable of producing polysaccharide to verify our results. Predictions of the glutamate source biofilm's shape parameters agree with the experimental mutant colony better than that of glycerol source biofilm, suggesting that glutamate is rate limiting nutrient for Bacillus subtilis biofilm growth on agar plate, and the diffusion-limited is a better description to the experiment. In addition, we find that the diffusion time scale is of the same magnitude as growth process, and the common-employed quasi-steady approximation is not applicable here.