M2 Macrophage Membrane-Camouflaged Fe3 O4 -Cy7 Nanoparticles with Reduced Immunogenicity for Targeted NIR/MR Imaging of Atherosclerosis.

Atherosclerosis （AS） is the primary reason behind cardiovascular diseases, leading to approximately one-third of global deaths. Developing a novel multi-model probe to detect AS is urgently required. Macrophages are the primary cells from which AS genesis occurs. Utilizing natural macrophage membranes coated on the surface of nanoparticles is an efficient delivery method to target plaque sites. Herein, Fe3 O4 -Cy7 nanoparticles (Fe3 O4 -Cy7 NPs), functionalized using an M2 macrophage membrane and a liposome extruder for Near-infrared fluorescence and Magnetic resonance imaging, are synthesized. These macrophage membrane-coated nanoparticles (Fe3 O4 @M2 NPs) enhance the recognition and uptake using active macrophages. Moreover, they inhibit uptake using inactive macrophages and human coronary artery endothelial cells. The macrophage membrane-coated nanoparticles (Fe3 O4 @M0 NPs, Fe3 O4 @M1 NPs, Fe3 O4 @M2 NPs) can target specific sites depending on the macrophage membrane type and are related to C-C chemofactor receptor type 2 protein content. Moreover, Fe3 O4 @M2 NPs demonstrate excellent biosafety in vivo after injection, showing a significantly higher Fe concentration in the blood than Fe3 O4 -Cy7 NPs. Therefore, Fe3 O4 @M2 NPs effectively retain the physicochemical properties of nanoparticles and depict reduced immunological response in blood circulation. These NPs mainly reveal enhanced targeting imaging capability for atherosclerotic plaque lesions.

The role of lysine-specific demethylase 6A (KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy.

Histone demethylation is a key post-translational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Lysine specific demethylase 6A (KDM6A, also known as UTX) is an Fe2+- and α-ketoglutarate- dependent oxidase which belongs to KDM6 Jumonji histone demethylase subfamily, and it can remove mono-, di- and tri-methyl groups from methylated lysine 27 of histone H3 (H3K27me1/2/3). Mounting studies indicate that KDM6A is responsible for driving multiple human diseases, particularly cancers and pharmacological inhibition of KDM6A is an effective strategy to treat varieties of KDM6A-amplified cancers in cellulo and in vivo. Although there are several reviews on the roles of KDM6 subfamily in cancer development and therapy, all of them only simply introduce the roles of KDM6A in cancer without systematically summarizing the specific mechanisms of KDM6A in tumorigenesis, which greatly limits the advances on the understanding of roles KDM6A in varieties of cancers, discovering targeting selective KDM6A inhibitors, and exploring the adaptive profiles of KDM6A antagonists. Herein, we present the structure and functions of KDM6A, simply outline the functions of KDM6A in homeostasis and non-cancer diseases, summarize the role of KDM6A and its distinct target genes/ligand proteins in development of varieties of cancers, systematically classify KDM6A inhibitors, sum up the difficulties encountered in the research of KDM6A and the discovery of related drugs, and provide the corresponding solutions, which will contribute to understanding the roles of KDM6A in carcinogenesis and advancing the progression of KDM6A as a drug target in cancer therapy.

The transversus abdominis plane block in conjunction with intrathecal morphine use after cesarean section in women with severe pre-eclampsia: a randomized controlled trial.

BACKGROUND: The transversus abdominis plane (TAP) block in conjunction with intrathecal morphine has been demonstrated to provide more superior postcesarean analgesia to intrathecal morphine alone. However, the analgesia efficacy of their conjunction has not been demonstrated in patients with severe pre-eclampsia. The study aimed to compare the postcesarean analgesia of TAP block in conjunction with intrathecal morphine versus intrathecal morphine alone in women with severe pre-eclampsia. METHODS: Pregnant women with severe pre-eclampsia undergoing planned cesarean section were randomly allocated into 2 groups to receive TAP block with 20 ml of 0.35% Ropivacaine (TAP group) or with the same volume of 0.9% saline (Sham group) after undergoing elective cesarean section under spinal anaesthesia with 15 mg of 0.5% Ropivacaine plus 0.1 mg of morphine. The outcomes for this analysis include the visual analog scale (VAS) pain score at rest and with movement at 4,8,12,24 h after TAP block was performed, times of use of intravenous patient-controlled analgesia (PCA) within 12 h after anesthesia, the occurrence of maternal side effects, maternal satisfaction, and Apgar score at 1 and 5 min of newborns. RESULTS: 119 subjects receive TAP block with 0.35% Ropivacaine (n = 59)or 0.9% saline (n = 60). At 4,8, 12 h after TAP block, the TAP group reported lower VAS score at rest [at 4 h: 1(0,1) vs. 1(1,2), P < 0.001; at 8 h:1(1,1) vs. 1(1.5,2),P < 0.001; at 12 h:1(1,2) vs. 2(1,2),P = 0.001] and higher satisfaction [53(89.9%) vs.45(75.0%), P < 0.05]. There were no differences between groups in VAS score at 24 h at rest and at all time points above with movement, times of use of PCA within 12 h after anesthesia, maternal side-effect, and Apgar score at 1 and 5 min of newborns. CONCLUSIONS: In conclusion, The TAP block performed in conjunction with intrathecal morphine may not reduce opioid consumption, but it could reduce VAS scores at rest in the first 12 h after cesarean section in women with severe pre-eclampsia, and improve maternal satisfaction, which is worthy of clinical promotion. TRIAL REGISTRATION: Registered at Chinese Clinical Trial Registry( http://www.chictr.org.cn ) on 13/12/2021: ChiCTR2100054293.

Repression of FBXW7 by HES5 contributes to inactivation of the TGF-ß signaling pathway and alleviation of endometriosis.

Endometriosis (EMS) is a gynecologic disorder associated with infertility and characterized by the endometrial-type mucosa outside the uterine cavity. Currently available treatment modalities are limited to undesirable effects. Thus, in the present study, we sought to study the pathogenesis mechanism of EMS. For this purpose, the ectopic and eutopic endometrial tissues were resected from 86 patients with EMS and 54 infertile patients without EMS, respectively. The regulatory mechanism among HES family bHLH transcription factor 5 (HES5), transforming growth factor-beta (TGF-ß)-induced factor 1 (TGIF1), F-box, and WD repeat domain containing 7 (FBXW7) was studied by performing co-immunoprecipitation, dual-luciferase reporter gene assay, and chromatin immunoprecipitation, respectively. A mouse model of EMS was established to verify the aforementioned regulatory mechanism in vivo. Upregulation of HES5 and TGIF1, as well as downregulation of FBXW7, was observed in EMS endometrial tissues and human endometrial stromal cells (hESCs), respectively. The overexpression of HES5 was found to suppress the FBXW7 transcription and TGIF1 degradation, resulting in the inactivation of the TGF-ß signaling pathway, as well as inhibition of hESC proliferation and invasion, thereby enhancing apoptosis. Results from a mouse model of EMS showed that the presence of HES5 contributed to the alleviation of EMS. Collectively, we attempted to provide a mechanistic insight into the unrecognized roles of the HES5/FBXW7 in EMS progression.

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma.

Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases. CAR T cells were i.v. infused after lymphodepleting chemotherapy. Two delivery methods, three infusions versus one infusion of the total CAR T dose, were tested in, respectively, 8 and 9 cases. No response differences were noted among the two delivery subgroups. Together, after CAR T cell infusion, 10 cases experienced a mild cytokine release syndrome (CRS), 6 had severe but manageable CRS, and 1 died of a very severe toxic reaction. The abundance of BCMA and cytogenetic marker del(17p) and the elevation of IL-6 were the key indicators for severe CRS. Among 17 cases, the overall response rate was 88.2%, with 13 achieving stringent complete response (sCR) and 2 reaching very good partial response (VGPR), while 1 was a nonresponder. With a median follow-up of 417 days, 8 patients remained in sCR or VGPR, whereas 6 relapsed after sCR and 1 had progressive disease (PD) after VGPR. CAR T cells were high in most cases with stable response but low in 6 out of 7 relapse/PD cases. Notably, positive anti-CAR antibody constituted a high-risk factor for relapse/PD, and patients who received prior autologous hematopoietic stem cell transplantation had more durable response. Thus, biepitopic CAR T against BCMA represents a promising therapy for R/R MM, while most adverse effects are clinically manageable.

Homocysteine (HCY) levels in patients with atrial fibrillation (AF): A meta-analysis.

PURPOSE: Atrial fibrillation (AF) is one of the most common persistent arrhythmia, and its complications include cerebral embolism, arterial embolism and heart failure. Some studies have found that elevated Homocysteine (HCY) levels is a new risk factor for AF. Currently, there is no meta-analysis to explore whether the HCY levels is related to AF. Therefore, a meta-analysis was conducted to evaluate the relationship between the HCY levels and AF, in order to draw the attention of clinicians to the HCY levels. METHODS: A meta-analysis was performed in the study to evaluated the association between the HCY levels and AF. In order to identify eligible original articles, The EMBASE, PubMed, and web of science were systematically searched until November 2020. All data were analyzed with Review Manager 5.3. The meta-analysis results were evaluated depending on standardized mean differences (SMD) with 95% confidence intervals (CI). Moreover, the subgroup analysis and sensitivity analysis were also analyzed. RESULTS: The HCY levels was significantly associated with AF (WMD = 0.81, 95% CI: 0.58 to 1.03; P < .00001). In the analysis, there was a medium degree of heterogeneity (I2 = 73%). Subgroup analysis showed that female < 60, BMI≥25, BMI <25, age ≥60 and publication year ≥2010 were identified as possible sources of heterogeneity. Sensitivity analysis showed that the main results remained unchanged after omitting any single study or converting the random effects model (REM) to fixed effects model (FEM). CONCLUSIONS: The meta-analysis showed that there is a significant correlation between the HCY levels and AF, and the role of HCY in AF patients should not be ignored in clinical.

Multicomponent Self-Assembly of a Giant Heterometallic Polyoxotungstate Supercluster with Antitumor Activity.

The hierarchical aggregation of molecular nanostructures from multiple components is a grand synthetic challenge, which requires highly selective linkage control. We demonstrate how two orthogonal linkage groups, that is, organotin and lanthanide cations, can be used to drive the aggregation of a giant molecular metal oxide superstructure. The title compound {[(Sn(CH3 )2 )2 O]4 {[CeW5 O18 ] [TeW4 O16 ][CeSn(CH3 )2 ]4 [TeW8 O31 ]4 }2 }46- (1 a) features dimensions of ca. 2.2×2.3×3.4 nm3 and a molecular weight of ca. 25 kDa. Structural analysis shows the hierarchical aggregation from several independent subunits. Initial biomedical tests show that 1 features an inhibitory effect on the proliferation of HeLa cells based on an apoptosis pathway. In vivo experiments in mice reveal the antiproliferative activity of 1 and open new paths for further development of this new compound class.

Flavonoids with Inhibitory Effects on NLRP3 Inflammasome Activation from Millettia velutina.

Eight new flavonoids, including two ß-hydroxy/methoxychalcones, velutones A and B (1 and 2), two 1,3-diarylpropan-1-ols, velutols C and D (3 and 4), a dihydroxychalcone, velutone E (5), a chalcone, velutone F (6), a furanoflavanone, velutone G (7), and a furanoflavonol, velutone H (8), and 14 known compounds were isolated from Millettia velutina. Their structures were determined by high-resolution electrospray ionisation mass spectrometry (HR-ESIMS) and spectroscopic data analyses and time-dependent density functional theory electronic circular dichroism (TD-DFT-ECD) calculations. Among the isolated constituents, compound 6 exhibited the most potent inhibitory effect (IC50: 1.3 µM) against nigericin-induced IL-1ß release in THP-1 cells. The initial mechanism of action study revealed that compound 6 suppressed NLRP3 inflammasome activation via blocking ASC oligomerization without affecting the priming step, which subsequently inhibited caspase-1 activation and IL-1ß secretion. Most importantly, compound 6 exerted potent protective effects in the LPS-induced septic shock mice model by improving the survival rate of mice and suppressing serum IL-1ß release. These results demonstrated that compound 6 had the potential to be developed as a broad-spectrum NLRP3 inflammasome inhibitor for the treatment of NLRP3-related disease.

Modulation of LPS-induced inflammation in RAW264.7 murine cells by novel isoflavonoids from Millettia pulchra.

Millettia pulchra is a renowned anti-inflammatory herbal medicine in southeast provinces of China. However, the underlying anti-inflammation mechanism remained incompletely understood. Herein, four new isoflavones, pulvones A-D and eleven reported constituents were isolated from the stems of Millettia pulchra with their structures being elucidated by HRMS and NMR analysis. The anti-inflammatory activities of pulvones A and C were further evaluated due to the better inhibitory activity on nitric oxide production in LPS-stimulated RAW264.7 cells and no obvious cytotoxicity to RAW264.7 cells. Western blot showed that pulvones A significantly decreased the levels of iNOS and COX-2 proteins and pulvones C only decreased the level of iNOS protein. ELISA analysis demonstrated that pulvones A inhibited the production of both interleukin-6 (IL-6) and IL-1ß while pulvones C showed better suppression effect on IL-1ß production in LPS-stimulated RAW264.7 cells. Then, their potential inhibitory effects on NF-κB pathway were tested in LPS-stimulated RAW264.7 cells. Immunofluorescence and western blot assay showed that pulvones A and C reduced the nuclear translocation of NF-κB(p65) and interrupted IκB phosphorylation. The ADP-Glo™ kinase assay showed pulvones A and C could directedly inhibit the IKKß kinase activity with the inhibitory rate of 40%, which were also verified by docking study. Collectively, these results suggested that pulvones A and C's anti-inflammatory effects were relevant to the interruption of NF-κB activation by inhibiting IKKß kinase.

A novel discovery of a long terminal repeat retrotransposon-induced hybrid weakness in rice.

Hybrid weakness is a post-zygotic hybridization barrier frequently observed in plants, including rice. In this study, we describe the genomic variation among three temperate japonica rice (Oryza sativa ssp. japonica) varieties 'Aranghyangchalbyeo' ('CH7'), 'Sanghaehyangheolua' ('CH8') and 'Shinseonchalbyeo' ('CH9'), carrying different hybrid weakness genes. The reciprocal progeny obtained from crossing any two varieties displayed characteristic hybrid weakness traits. We mapped and cloned a new locus, Hwc3 (hybrid weakness 3), on chromosome 4. Sequence analysis identified that a long terminal repeat (LTR) retrotransposon was inserted into the promoter region of the Hwc3 gene in 'CH7'. A 4-kb DNA fragment from 'CH7' containing the Hwc3 gene with the inserted LTR retrotransposon was able to induce hybrid weakness in hybrids with 'CH8' plants carrying the Hwc1 gene by genetic complementation. We investigated the differential gene expression profile of F1 plants exhibiting hybrid weakness and detected that the genes associated with energy metabolism were significantly down-regulated compared with the parents. Based on our results, we propose that LTR retrotransposons could be a potential cause of hybrid weakness in intrasubspecific hybrids in japonica rice. Understanding the molecular mechanisms underlying intrasubspecific hybrid weakness is important for increasing our knowledge on reproductive isolation and could have significant implications for rice improvement and hybrid breeding.

Two Ce3+-Substituted Selenotungstates Regulated by N, N-Dimethylethanolamine and Dimethylamine Hydrochloride.

Two multi-Ce3+-substituted selenotungstates (STs), [HDMEA][H2N(CH3)2]4H3Na4[Ce2(H2O)6(DMEA)W4O9(α-SeW9O33)3]·26H2O (1) and [H2N(CH3)2]10H4Na10[Ce2W4O9(H2O)7(α-SeW9O33)3]2·63H2O (2), were prepared by the one-pot approach of sodium tungstate, sodium selenite, and lanthanide nitrate in an acidic water solution in the presence of N, N-dimethylethanolamine (DMEA) or dimethylamine hydrochloride (DMAHC). 1 was obained in the presence of DMEA, whereas 2 was synthesized in the presence of DMAHC. The trimeric polyoxoanion of 1 contains an unusual V-shaped [Se3W29O103]20- group embracing a prominent heterometal oxide fragment, [Ce2(H2O)6(DMEA)W2O5]8+, and the hexameric polyoxoanion of 2 is constructed from two equivalent trimeric [Ce2W4O9(H2O)7(SeW9O33)3]224- subunits through two -O-W-O-Ce-O- linkages. The most worthy of attention is that the polyoxoanion of 1 can be approximatively viewed as a half of the polyoxoanion of 2 because of the coordination and blocking effect of DMEA. The stability of 1 and 2 in different water pH values was studied by electrospray ionization mass spectroscopy (ESI-MS), and the results manifest that 1 and 2 are stable in pH = 3.5-7.5 and 3.5-7.0, respectively. The oxidation reactions of aromatic sulfides catalyzed by H2O2 were studied when 1 or 2 worked as a catalyst, and experimental results reveal that 1 or 2 can serve as available catalysts for the oxidation of aromatic sulfides under mild conditions.

Anti-inflammatory Ellagitannins from Cleidion brevipetiolatum for the Treatment of Rheumatoid Arthritis.

Six new ellagitannins, brevipetins B-G (5 and 7-11), and a new phenolic glucoside, brevipetin A (4), along with six known compounds were isolated from the traditional Chinese medicinal plant Cleidion brevipetiolatum. Their structures and absolute configurations were determined by spectroscopic analyses, chemical methods, and TD-DFT-ECD calculations. Compounds 5-11 exhibited NO inhibitory effects with IC50 values of 1.9-8.2 µM, and 9 showed the most potent inhibitory effect (IC50: 1.9 µM). An in vivo anti-inflammatory assessment of 9 showed that it exerts therapeutic effects in both the carrageenan-induced rat paw edema and collagen-induced arthritis (CIA) models at 50 mg/kg oral administration. The enhanced protein and mRNA expression levels of iNOS (inducible nitric oxide synthase) and COX-2 (cyclooxygenase-2) in LPS-stimulated RAW 264.7 cells were dose-dependently suppressed by 9. An anti-inflammatory mechanistic study revealed that 9 suppressed NF-κB activity by inhibiting IκBα phosphorylation and blocking translocation of p65 from the cytosol to the nucleus. Therefore, 9 might have the potential to be developed as a lead compound for relieving rheumatoid arthritis.

Correlation between pre-treatment serum carcinoembryonic antigen levels and genotypes in a large population of Chinese people with advanced lung adenocarcinoma.

BACKGROUND: A positive correlation between serum carcinoembryonic antigen (CEA) levels and epidermal growth factor receptor (EGFR) mutations has been reported in lung adenocarcinoma patients. AIM: To investigate retrospectively whether serum CEA levels are also associated with genotypes in a large population of advanced lung adenocarcinoma. METHODS: A large cohort of 701 patients with advanced lung adenocarcinoma was studied retrospectively. RESULTS: EGFR mutations were found in 47.5% (333/701) of advanced lung adenocarcinoma patients, being identified at high frequencies in never-smokers, females, and in patients with abnormal pre-treatment serum CEA levels (53.1% vs 37.5%, P < 0.001). In contrast, anaplastic lymphoma kinase gene rearrangements were found in 7.8% (55/701) of patients, being identified at high frequencies in younger patients, and in patients with normal CEA levels (11.5% vs 5.8%, P = 0.012). Serum CEA levels were divided into four groups: <5, 5-19, 20-99 and ≥100 ng/mL. The rate of EGFR mutations significantly increased as the serum CEA levels increased (37.5%, 49.5%, 53.9% and 57.7%, respectively, P < 0.001). Anaplastic lymphoma kinase gene rearrangements showed the opposite result (11.5%, 7.1%, 5.7% and 4.1%, respectively, P = 0.044). A multivariate analysis revealed that higher pre-treatment serum CEA levels were independently associated with EGFR mutations (95% CI: 1.291-2.487, P < 0.001), but normal serum CEA levels were independently associated with anaplastic lymphoma kinase gene rearrangements (95% CI: 0.275-0.842, P = 0.010). CONCLUSION: Our study demonstrated that a significant association exists between the serum CEA levels and genotypes in patients with advanced lung adenocarcinoma.

α-Expansin EXPA4 Positively Regulates Abiotic Stress Tolerance but Negatively Regulates Pathogen Resistance in Nicotiana tabacum.

Since they function as cell wall-loosening proteins, expansins can affect plant growth, developmental processes and environmental stress responses. Our previous study demonstrated that changes in Nicotiana tabacum α-expansin 4 (EXPA4) expression affect the sensitivity of tobacco to Tobacco mosaic virus [recombinant TMV encoding green fluorescent protein (TMV-GFP)] infection by Agrobacterium-mediated transient expression. In this study, to characterize the function of tobacco EXPA4 further, EXPA4 RNA interfernce (RNAi) mutants and overexpression lines were generated and assayed for their tolerance to abiotic stress and resistance to pathogens. First, the differential phenotypes and histomorphology of transgenic plants with altered EXPA4 expression indicated that EXPA4 is essential for normal tobacco growth and development. By utilizing tobacco EXPA4 mutants with abiotic stress, it was demonstrated that RNAi mutants have increased hypersensitivity to salt and drought stress. In contrast, the overexpression of EXPA4 in tobacco conferred greater tolerance to salt and drought stress, as indicated by less cell damage, higher fresh weight, higher soluble sugar and proline accumulation, and higher expression levels of several stress-responsive genes. In addition, the overexpression lines were more susceptible to the viral pathogen TMV-GFP when compared with the wild type or RNAi mutants. The induction of the antioxidant system, several defense-associated phytohormones and gene expression was down-regulated in overexpression lines but up-regulated in RNAi mutants when compared with the wild type following TMV-GFP infection. In addition, EXPA4 overexpression also accelerated the disease development of Pseudomonas syringae DC3000 on tobacco. Taken together, these results suggested that EXPA4 appears to be important in tobacco growth and responses to abiotic and biotic stress.

Tobacco alpha-expansin EXPA4 plays a role in Nicotiana benthamiana defence against Tobacco mosaic virus.

MAIN CONCLUSION: Tobacco EXPA4 plays a role in Nicotiana benthamiana defence against virus attack and affects antioxidative metabolism and phytohormone-mediated immunity responses in tobacco. Expansins are cell wall-loosening proteins known for their endogenous functions in cell wall extensibility during plant growth. The effects of expansins on plant growth, developmental processes and environment stress responses have been well studied. However, the exploration of expansins in plant virus resistance is rarely reported. In the present study, virus-induced gene silencing (VIGS) and Agrobacterium-mediated transient overexpression were conducted to investigate the role of Nicotiana tabacum alpha-expansin 4 (EXPA4) in modulating Tobacco mosaic virus (TMV-GFP) resistance in Nicotiana benthamiana. The results indicated that silencing of EXPA4 reduced the sensitivity of N. benthamiana to TMV-GFP, and EXPA4 overexpression accelerated virus reproduction on tobacco. In addition, our data suggested that the changes of virus accumulation in response to EXPA4 expression levels could further affect the antioxidative metabolism and phytohormone-related pathways in tobacco induced by virus inoculation. EXPA4-silenced plants with TMV-GFP have enhanced antioxidant enzymes activities, which were down-regulated in virus-inoculated 35S:EXPA4 plants. Salicylic acid accumulation and SA-mediated defence genes induced by TMV-GFP were up-regulated in EXPA4-silenced plants, but depressed in 35S:EXPA4 plants. Furthermore, a VIGS approach was used in combination with exogenous phytohormone treatments, suggesting that EXPA4 has different responses to different phytohormones. Taken together, these results suggested that EXPA4 plays a role in tobacco defence against viral pathogens.

Design, synthesis and antibacterial evaluation of honokiol derivatives.

Staphylococcus aureus is a major and dangerous human pathogen that causes a range of clinical manifestations of varying severity, and is the most commonly isolated pathogen in the setting of skin and soft tissue infections, pneumonia, suppurative arthritis, endovascular infections, foreign-body associated infections, septicemia, osteomyelitis, and toxic shocksyndrome. Honokiol, a pharmacologically active natural compound derived from the bark of Magnolia officinalis, has antibacterial activity against Staphylococcus aureus which provides a great inspiration for the discovery of potential antibacterial agents. Herein, honokiol derivatives were designed, synthesized and evaluated for their antibacterial activity by determining the minimum inhibitory concentration (MIC) against S. aureus ATCC25923 and Escherichia coli ATCC25922 in vitro. 7c exhibited better antibacterial activity than other derivatives and honokiol. The structure-activity relationships indicated piperidine ring with amino group is helpful to improve antibacterial activity. Further more, 7c showed broad spectrum antibacterial efficiency against various bacterial strains including eleven gram-positive and seven gram-negative species. Time-kill kinetics against S. aureus ATCC25923 in vitro revealed that 7c displayed a concentration-dependent effect and more rapid bactericidal kinetics better than linezolid and vancomycin with the same concentration. Gram staining assays of S. aureus ATCC25923 suggested that 7c could destroy the cell walls of bacteria at 1×MIC and 4×MIC.

First Dimethyltin-Functionalized Rare-Earth Incorporated Tellurotungstates Consisting of {B-α-TeW7O28} and {W5O18} Mixed Building Units.

The facile one-step assembly reaction of Na2WO4·2H2O, Sn(CH3)2Cl2, RE(NO3)3·6H2O and K2TeO3 in the presence of dimethylamine hydrochloride as an organic solubilizing agent in acidic aqueous solution resulted in a family of dimethyltin-functionalized rare-earth (RE) incorporated tellurotungstates consisting of {B-α-TeW7O28} and {W5O18} mixed building units [H2N(CH3)2]8Na4H2[RE2(OH)(B-α-TeW7O28)Sn2(CH3)4(W5O18)]2·18H2O [RE = ErIII (1), YbIII (2), HoIII (3), YIII (4)]. The most striking structural characteristic of 1-4 is that they all contain a novel tetrameric S-shaped [RE2(OH)(B-α-TeW7O28)Sn2(CH3)4(W5O18)]214- moiety simultaneously including two pentavacant Keggin [B-α-TeW7O28]12- and two monovacant Lindqvist [W5O18]6- fragments connected by RE and dimethyltin linkers. To the best of our knowledge, such dimethyltin-functionalized RE-containing tellurotungstates have not been reported before. The visible or NIR solid-state emission spectra of 1 and 3 display the characteristic emission bands arising from ErIII and HoIII centers. Moreover, various 1-Er/Yb co-doped samples were prepared by controlling different mass ratio of Er(NO3)3·6H2O/Yb(NO3)·6H2O in the range of 0.96:0.04-0.02:0.98. In the visible region, the emission intensity of the 1-Er0.40/Yb0.60 co-doped sample reaches the maximum at the mass ratio of Er(NO3)3·6H2O/Yb(NO3)·6H2O being 0.40:0.60, and this observation is mainly derived from the fact that the Yb3+ ions can sensitize the Er3+ ions to enhance the emission intensity in the visible region. However, no such phenomenon for the 1-Er/Yb co-doped samples is seen in the NIR region. Besides, the upconversion spectra of the 1-Er/Yb co-doped samples were first observed. In addition, the thermal stabilities of 1-4 were also investigated on the crystalline samples and the thermal decomposition process of 1 has been deeply studied.

Aggregation of Giant Cerium-Bismuth Tungstate Clusters into a 3D Porous Framework with High Proton Conductivity.

The exploration of high nuclearity molecular metal oxide clusters and their reactivity is a challenge for chemistry and materials science. Herein, we report an unprecedented giant molecular cerium-bismuth tungstate superstructure formed by self-assembly from simple metal oxide precursors in aqueous solution. The compound, {[W14 CeIV6 O61 ]([W3 Bi6 CeIII3 (H2 O)3 O14 ][B-α-BiW9 O33 ]3 )2 }34- was identified by single-crystal X-ray diffraction and features 104 metal centers, a relative molar mass of ca. 24 000 and is ca. 3.0×2.0×1.7 nm3 in size. The cluster anion is assembled around a central {Ce6 } octahedron which is stabilized by several molecular metal oxide shells. Six trilacunary Keggin anions ([B-α-BiW9 O33 ]9- ) cap the superstructure and limit its growth. In the crystal lattice, water-filled channels with diameters of ca. 0.5 nm are observed, and electrochemical impedance spectroscopy shows pronounced proton conductivity even at low temperature.

Structural Transformation from Dimerization to Tetramerization of Serine-Decorated Rare-Earth-Incorporated Arsenotungstates Induced by the Usage of Rare-Earth Salts.

Three types of serine-decorated rare- earth-containing arsenotungstate [H2 N(CH3 )2 ]6 NaH[RE2 W4 O10 (H2 O)8 (Ser)2 (B-α-AsW9 O33 )2 ]⋅30 H2 O (RE3+ =Eu3+ , Gd3+ , Tb3+ , Dy3+ , Ho3+ , Er3+ , Tm3+ , Yb3+ , and Y3+ ; 1), [H2 N(CH3 )2 ]6 Na6-x REx H4-2 x [RE4 W8 O19 (H2 O)10+y (OH)2 (Ser)2 (B-α-AsW9 O33 )4 ]⋅n H2 O (RE3+ =Tb3+ , x=1, y=2, n=36; RE3+ =Dy3+ , Ho3+ , Er3+ , Yb3+ , Y3+ , x=0, y=0, n=38; RE3+ = Tm3+ , x=1, y=0, n=38; Ser=serine; 2), and [H2 N(CH3 )2 ]6-2 x Na2+3 x REx H10-6 x+y [RE4 W8 O19 (H2 O)8 (OH)2 (Ser)4 (B-α-AsW9 O33 )4 ]⋅Cly ⋅n H2 O (RE3+ =Ce3+ , Pr3+ , x=1, y=0, n=65; RE3+ =Nd3+ , Sm3+ , x=0, y=0, n=65; RE3+ =Eu3+ , Gd3+ , x=1, y=2, n=45; 3) were synthesized with the participation of the organic solubilizers dimethylamine hydrochloride and l-serine and were structurally characterized. The use of different amounts of rare-earth salts results in the structural transformation from dimerization to tetramerization of types 1-3. Type 1 is a dimeric sandwich-type assembly of a dual-Ser-participating [RE2 W4 O10 (H2 O)8 (Ser)2 ]10+ entity sandwiched by two [B-α-AsW9 O33 ]9- moieties, whereas types 2 and 3 have a tetrameric square structure formed by four [B-α-AsW9 O33 ]9- moieties that anchor a dual/tetra- Ser-participating [RE4 W8 O19 (H2 O)10+y (OH)2 (Ser)2 ]20+ or [RE4 W8 O19 (H2 O)8 (OH)2 (Ser)4 ]20+ core. The solid-state luminescence properties and lifetime-decay behaviors of these compounds were investigated. The chromaticity coordinates, dominant wavelengths, color purities, and correlated color temperatures were also calculated.