Evaluating mAbs binding abilities to Omicron subvariant RBDs: implications for selecting effective mAb therapies.

The ongoing evolution of the Omicron lineage of SARS-CoV-2 has led to the emergence of subvariants that pose challenges to antibody neutralization. Understanding the binding dynamics between the receptor-binding domains (RBD) of these subvariants spike and monoclonal antibodies (mAbs) is pivotal for elucidating the mechanisms of immune escape and for advancing the development of therapeutic antibodies. This study focused on the RBD regions of Omicron subvariants BA.2, BA.5, BF.7, and XBB.1.5, employing molecular dynamics simulations to unravel their binding mechanisms with a panel of six mAbs, and subsequently analyzing the origins of immune escape from energetic and structural perspectives. Our results indicated that the antibody LY-COV1404 maintained binding affinities across all studied systems, suggesting the resilience of certain antibodies against variant-induced immune escape, as seen with the mAb 1D1-Fab. The newly identified mAb 002-S21F2 showed a similar efficacy profile to LY-COV1404, though with a slightly reduced binding to BF.7. In parallel, mAb REGN-10933 emerged as a potential therapeutic candidate against BF.7 and XBB.1.5, reflecting the importance of identifying variant-specific antibody interactions, akin to the binding optimization observed in BA.4/5 and XBB.1.5. And key residues that facilitate RBD-mAb binding were identified (T345, L441, K444, V445, and T500), alongside residues that hinder protein-protein interactions (D420, L455, K440, and S446). Particularly noteworthy was the inhibited binding of V445 and R509 with mAbs in the presence of mAb 002-S21F2, suggesting a mechanism for immune escape, especially through the reduction of V445 hydrophobicity. These findings enhance our comprehension of the binding interactions between mAbs and RBDs, contributing to the understanding of immune escape mechanisms. They also lay the groundwork for the design and optimization of antiviral drugs and have significant implications for the development of treatments against current and future coronaviruses.

Computational analysis of PD-L1 dimerization mechanism induced by small molecules and potential dynamical properties.

The design of small molecule inhibitors that target the programmed death ligand-1 (PD-L1) is a forefront issue in immune checkpoint blocking therapy. Small-molecule inhibitors have been shown to exert therapeutic effects by inducing dimerization of the PD-L1 protein, however, the specific mechanisms underlying this dimerization process remain largely unexplored. Furthermore, there is a notable lack of comparative studies examining the binding modes of structurally diverse inhibitors. In view of the research gaps, this work employed molecular dynamics simulations to meticulously examine the interactions between two distinct types of inhibitors and PD-L1 in both monomeric and dimeric forms, and predicted the dimerization mechanism. The results revealed that inhibitors initially bind to a PD-L1 monomer, subsequently attracting another monomer to form a dimer. Notably, symmetric inhibitors observed superior binding efficiency compared to other inhibitors. Key residues, including Ile54, Tyr56, Met115 and Tyr123 played a leading role in binding. Structurally, symmetric inhibitors were capable of thoroughly engaging the binding pocket, promoting a more symmetrical formation of PD-L1 dimers. Furthermore, symmetric inhibitors formed more extensive hydrophobic interactions with protein residues. The insights garnered from this research are expected to significantly contribute to the rational design and optimization of small molecule inhibitors targeting PD-L1.

Advanced molecular mechanisms of modified DRV compounds in targeting HIV-1 protease mutations and interrupting monomer dimerization.

HIV-1 protease (PR) plays a crucial role in the treatment of HIV as a key target. The global issue of emerging drug resistance is escalating, and PR mutations pose a substantial challenge to the effectiveness of inhibitors. HIV-1 PR is an ideal model for studying drug resistance to inhibitors. The inhibitor, darunavir (DRV), exhibits a high genetic barrier to viral resistance, but with mutations of residues in the PR, there is also some resistance to DRV. Inhibitors can impede PR in two ways: one involves binding to the active site of the dimerization protease, and the other involves binding to the PR monomer, thereby preventing dimerization. In this study, we aimed to investigate the inhibitory effect of DRV with a modified inhibitor on PR, comparing the differences between wild-type and mutated PR, using molecular dynamics simulations. The inhibitory effect of the inhibitors on PR monomers was subsequently investigated. And molecular mechanics Poisson-Boltzmann surface area evaluated the binding free energy. The energy contribution of individual residues in the complex was accurately calculated by the alanine scanning binding interaction entropy method. The results showed that these inhibitors had strong inhibitory effects against PR mutations, with GRL-142 exhibiting potent inhibition of both the PR monomer and dimer. Improved inhibitors could strengthen hydrogen bonds and interactions with PR, thereby boosting inhibition efficacy. The binding of the inhibitor and mutation of the PR affected the distance between D25 and I50, preventing their dimerization and the development of drug resistance. This study could accelerate research targeting HIV-1 PR inhibitors and help to further facilitate drug design targeting both mechanisms.

Entropy driven cooperativity effect in multi-site drug optimization targeting SARS-CoV-2 papain-like protease.

Papain-like protease (PLpro), a non-structural protein encoded by SARS-CoV-2, is an important therapeutic target. Regions 1 and 5 of an existing drug, GRL0617, can be optimized to produce cooperativity with PLpro binding, resulting in stronger binding affinity. This work investigated the origin of the cooperativity using molecular dynamics simulations combined with the interaction entropy (IE) method. The regions' improvement exhibits cooperativity by calculating the binding free energies between the complex of PLpro-inhibitor. The thermodynamic integration method further verified the cooperativity generated in the drug improvement. To further determine the specific source of cooperativity, enthalpy and entropy in the complexes were calculated using molecular mechanics/generalized Born surface area and IE. The results show that the entropic change is an important contributor to the cooperativity. Our study also identified residues P248, Q269, and T301 that play a significant role in cooperativity. The optimization of the inhibitor stabilizes these residues and minimizes the entropic loss, and the cooperativity observed in the binding free energy can be attributed to the change in the entropic contribution of these residues. Based on our research, the application of cooperativity can facilitate drug optimization, and provide theoretical ideas for drug development that leverage cooperativity by reducing the contribution of entropy through multi-locus binding.

Engineered and Durable Antimicrobial Polymer via Controllable Immobilization of Ionic Liquids onto the Poly(lactic acid) Chains.

Nowadays, the development of effective modification methods for PLA has gained significant interest because of the wide application of antimicrobial PLA materials in the medical progress. Herein, the ionic liquid (IL) 1-vinyl-3-butylimidazolium bis(trifluoromethylsulfonyl)imide, has been grafted onto the PLA chains successfully in the PLA/IL blending films via electron beam (EB) radiation for the miscibility between PLA and IL. It was found that the existence of IL in the PLA matrix can significantly improve the chemical stability under EB radiation. The Mn of PLA-g-IL copolymer did not change obviously but was just decreased from 6.80 × 104 g/mol to 5.20 × 104 g/mol after radiation with 10 kGy. The obtained PLA-g-IL copolymers showed excellent filament forming property during electrospinning process. The spindle structure on the nanofibers can be completely eliminated after feeding only 0.5 wt % ILs for the improvement of ionic conductivity. Specially, the prepared PLA-g-IL nonwovens exhibited outstanding and durable antimicrobial activity for the enrichment of immobilized ILs on the nanofiber surface. This work provides a feasible strategy to realize the modification of functional ILs onto PLA chains with low EB radiation doses, which may have huge potential application in the medical and packaging industry.

Synthesis of KH550-Modified Hexagonal Boron Nitride Nanofillers for Improving Thermal Conductivity of Epoxy Nanocomposites.

In this work, KH550 (γ-aminopropyl triethoxy silane)-modified hexagonal boron nitride (BN) nanofillers were synthesized through a one-step ball-milling route. Results show that the KH550-modified BN nanofillers synthesized by one-step ball-milling (BM@KH550-BN) exhibit excellent dispersion stability and a high yield of BN nanosheets. Using BM@KH550-BN as fillers for epoxy resin, the thermal conductivity of epoxy nanocomposites increased by 195.7% at 10 wt%, compared to neat epoxy resin. Simultaneously, the storage modulus and glass transition temperature (Tg) of the BM@KH550-BN/epoxy nanocomposite at 10 wt% also increased by 35.6% and 12.4 °C, respectively. The data calculated from the dynamical mechanical analysis show that the BM@KH550-BN nanofillers have a better filler effectiveness and a higher volume fraction of constrained region. The morphology of the fracture surface of the epoxy nanocomposites indicate that the BM@KH550-BN presents a uniform distribution in the epoxy matrix even at 10 wt%. This work guides the convenient preparation of high thermally conductive BN nanofillers, presenting a great application potential in the field of thermally conductive epoxy nanocomposites, which will promote the development of electronic packaging materials.

Reinforced Structure Effect on Thermo-Oxidative Stability of Polymer-Matrix Composites: 2-D Plain Woven Composites and 2.5-D Angle-Interlock Woven Composites.

The thermo-oxidative stability of carbon fiber polymer matrix composites with different integral reinforced structures was investigated experimentally and numerically. Specimens of 2-D plain woven composites and 2.5-D angle-interlock woven composites were isothermally aged at 180 °C in hot air for various durations up to 32 days. The thermal oxidative ageing led to the degradation of the matrix and the fiber/matrix interface. The degradation mechanisms of the matrix were examined by ATR-FTIR and thermal analysis. The interface cracks caused by thermal oxidative ageing were sensitive to the reinforced structure. The thermo-oxidative stability of the two composites was numerically compared in terms of matrix shrinking and crack evolution and then experimentally validated by interlaminar shear tests.

Construction of carbon-based flame retardant composite with reinforced and toughened property and its application in polylactic acid.

To simultaneously improve the flame retardancy, strength and toughness of polylactic acid (PLA) fibers, a composite flame retardant CNTs-H-C was prepared with carbon nanotubes (CNTs) as the core, hexachlorocyclotriphosphazene as linker, and chitosan grafted on the surface. The prepared CNTs-H-C was introduced into a PLA matrix to obtain CNTs-H-C/PLA composites and fibers via a melt-blending method. The morphology, structure, flame retardant properties and mechanical properties were thoroughly characterized, and the flame retardant mechanism was studied. Results showed that the prepared CNTs-H-C displayed a nanotube-like morphology with good compatibility and dispersion in the PLA matrix. After blending with PLA, CNTs-H-C/PLA composites exhibited outstanding flame retardancy with limiting oxygen index (LOI) increasing from 20.0% to 27.3%, UL94 rating reaching V-0. More importantly, the introduction of CNTs-H-C did not affect the spinnability of PLA. Compared with pure PLA fibers, the LOI of CNTs-H-C/PLA fibers with a CNTs-H-C content of 1.0 wt% increased by 32.5%, and meanwhile the breaking strength and elongation increased by 28.2% and 30.4%, respectively. Mechanism study revealed that CNTs-H-C/PLA possessed a typical condensed phase flame retardancy mechanism. In short, we have developed a CNT-based composite flame retardant with reinforced and toughened properties for the PLA matrix. The prepared CNTs-H-C showed great potential in polymer flame retardancy and mechanical enhancement.

GR-α and GR-ß mRNA levels in peripheral blood mononuclear cells of acute myelitis patients can assist in the identification of glucocorticoid sensitivity and are correlated with glucocorticoid therapeutic effect.

Acute myelitis (AM) is a rare neuro-immune spinal cord disease. This study sought to explore the transcription level of glucocorticoid (GC) receptors α and ß (GR-α/GR-ß) in peripheral blood mononuclear cells (PBMCs) and their correlation with GC efficacy and sensitivity in AM patients. AM patients were grouped into the GC-sensitive group (N = 80) and GC-refractory group (N = 67). The GR-α and GR-ß mRNA levels in PBMCs were detected. The differentiating value of GR-α, GR-ß, and GR-α + GR-ß on GC sensitivity and resistance in AM patients was assessed. The independent correlation between GR-α and GR-ß mRNA levels and GC sensitivity in AM patients,t and the correlation between GR-α and GR-ß mRNA levels and spinal function after GC treatment were analyzed. GR-α mRNA level in PBMCs of GC-refractory patients was lower than that of GC-sensitive patients, while GR-ß mRNA level was higher than that of GC-sensitive patients. GR-α + GR-ß mRNA had a high diagnostic value for GC sensitivity and resistance in AM patients (area under the ROC curve = 0.881, sensitivity = 79.1%, specificity = 85.0%). GR-α and GR-ß mRNA levels were independently correlated with GC sensitivity. GR-α and GR-ß mRNA levels were correlated with the spinal function of AM patients after GC treatment. Overall, GR-α and GR-ß mRNA levels in PBMCs of AM patients can assist in the identification of GC sensitivity and are correlated with GC efficacy.

Investigation on Tribological and Thermo-Mechanical Properties of Ti3C2 Nanosheets/Epoxy Nanocomposites.

In this study, two-dimensional Ti3C2 nanosheets were employed to improve the tribological and thermo-mechanical properties of epoxy resin. The Ti3C2 nanosheets were prepared by ultrasound-assisted delamination of multilayered Ti3C2 microparticles, and the Ti3C2 nanosheets/epoxy (Ti3C2/epoxy) nanocomposites were fabricated through physical blending and curing reaction. Scanning electron microscopy results showed that the Ti3C2 nanosheets were dispersed uniformly in the epoxy matrix. Tribological test results showed that the wear rate of Ti3C2/epoxy nanocomposites was only 6.61 × 10-14 m3/(N m) at a 1% mass fraction, which was reduced by 72.1% compared to that of neat epoxy. The morphologies of worn surfaces revealed that the wear form of Ti3C2/epoxy nanocomposites transformed gradually from fatigue wear to adhesive wear with the increase of mass fraction of Ti3C2 nanosheets. Moreover, the results of thermo-mechanical properties indicated that incorporation of Ti3C2 nanosheets effectively improved the storage modulus and glass-transition temperature (T g) of epoxy resin. This work provides guidance for improving the tribological and thermo-mechanical properties of epoxy resin.

Anti-inflammatory effects of kaempferol-3-O-rhamnoside on HSV-1 encephalitis in vivo and in vitro.

BACKGROUND: Herpes simplex virus encephalitis (HSE) is an acute central nervous system infectious disease caused by herpes simplex virus (HSV). Currently, there is no effective treatment for HSE infection, which produces many pro-inflammatory factors. Kaempferol-3-O-rhamnoside (K-3-rh) is a plant flavonoid. This study was investigated the anti-inflammatory effect of K-3-rh on encephalitis induced by HSV-1. METHODS: HSV-1 was co-cultured with VERO cells. Cells were divided into four groups, including the control group, virus group, K-3-rh group, Astragalus polysaccharide (APS) group and dexamethasone group. Flow cytometry were utilized to determine cell apoptosis, respectively. Proteins and mRNAs were estimated by western blot and qRT-PCR, respectively. RESULTS: After viral infection, the cytokines were significantly increased. After K-3-rh intervention, the expression of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), and nitric oxide (NO) in microglia were reduced contrast with those in the virus group, and the expression of interleukin-10 (IL-10) did not change. After viral infection, the apoptotic rate increased significantly, and K-3-rh could inhibit viral-induced apoptosis in the microglial cell line. The induction of microglia apoptosis was achieved by cytochrome c and caspase-9-mediated mitochondrial pathway. Also, the pathological changes of brain tissue in mice of each drug intervention group were alleviated. CONCLUSIONS: In conclusion, K-3-rh had the potential to reduce HSV-1-induced brain injury by reducing the secretion of microglial pro-inflammatory factors, inducing apoptosis of microglia cells, and through cytochrome C and caspase-3 pathway.

Tribological and Thermo-Mechanical Properties of TiO2 Nanodot-Decorated Ti3C2/Epoxy Nanocomposites.

The micromorphology of fillers plays an important role in tribological and mechanical properties of polymer matrices. In this work, a TiO2-decorated Ti2C3 (TiO2/Ti3C2) composite particle with unique micro-nano morphology was engineered to improve the tribological and thermo-mechanical properties of epoxy resin. The TiO2/Ti3C2 were synthesized by hydrothermal growth of TiO2 nanodots onto the surface of accordion-like Ti3C2 microparticles, and three different decoration degrees (low, medium, high density) of TiO2/Ti3C2 were prepared by regulating the concentration of TiO2 precursor solution. Tribological test results indicated that the incorporation of TiO2/Ti3C2 can effectively improve the wear rate of epoxy resin. Among them, the medium density TiO2/Ti3C2/epoxy nanocomposites gained a minimum wear rate. This may be ascribed by the moderate TiO2 nanodot protuberances on the Ti3C2 surface induced a strong mechanical interlock effect between medium-density TiO2/Ti3C2 and the epoxy matrix, which can bear a higher normal shear stress during sliding friction. The morphologies of worn surfaces and wear debris revealed that the wear form was gradually transformed from fatigue wear in neat epoxy to abrasive wear in TiO2/Ti3C2/epoxy nanocomposites. Moreover, the results of thermo-mechanical property indicated that incorporation of TiO2/Ti3C2 also effectively improved the storage modulus and glass transition temperature of epoxy resin.

Polarization behavior of bone marrow-derived macrophages on charged P(VDF-TrFE) coatings.

The immune response of bone implants is closely related to the interaction between macrophages and biomaterial surfaces. In this work, the polarization behavior of mouse bone marrow-derived macrophages (BMDMs), including their morphology and expression of phenotypic markers, genes and cytokines, on charged surfaces with different potential intensities was systematically explored. We found that the charged surface could effectively promote BMDM polarization, and a higher potential intensity was conducive to the upregulation of the polarization of BMDMs into the M2 phenotype. Based on the analysis of the signaling pathways involved in integrins (αMß2 and α5ß1) and the potassium ion channel (Kv1.3), a possible underlying mechanism revealed that the integrin originated signaling pathways could more dominantly regulate macrophage polarization to the M2 phenotype. The present work therefore demonstrates that the surface charge, as a physicochemical property of material surfaces, could effectively regulate macrophage polarizations, which may provide an immunoregulation view for the surface design of biomaterials.

Enhanced cellular osteogenic differentiation on CoFe2O4/P(VDF-TrFE) nanocomposite coatings under static magnetic field.

Cellular responses can be regulated and manipulated through combining stimuli-responsive biomaterial with external stimulus. In this present, the magneto-responsive CoFe2O4/P(VDF-TrFE) nanocomposite coatings were designed to understand cell behaviors of preosteoblasts, as well as get insight into the underlying mechanism of osteogenic differentiation under static magnetic field (SMF). CoFe2O4/P(VDF-TrFE) nanocomposite coatings with differential magnetic property (low, medium and high magnetization) were prepared by incorporation of different mass fraction of CoFe2O4 nanoparticles (6%, 13 %, 20 %) into P(VDF-TrFE) matrix. Cell experiments indicated that all nanocomposite coatings with the assistance of SMF could promote the cell attachment, proliferation and osteogenic differentiation of MC3T3-E1 cells. Among different nanocomposite coatings, low magnetization coating (6%) showed a higher ALP activity and gene expression of Runx2, Col-I, OCN. Molecular biology assays demonstrated that the combination of nanocomposite coatings and SMF could significantly up-regulate the expression level of α2ß1 integrin and p-ERK. Whereas, the addition of inhibitor U0126 down-regulated sharply the expression level of p-ERK, which indicated that cellular osteogenic differentiation of MC3T3-E1 cells was governed through α2ß1 integrin-mediated MEK/ERK signaling pathways during CoFe2O4/P(VDF-TrFE) nanocomposite coatings were combined with SMF. This work provided a promising strategy to enhance cellular osteogenic differentiation through a remote-control manner, which exhibited great potential in the application of bone tissue repair and regeneration.

Magnetic-Field-Assisted Cellular Osteogenic Differentiation on Magnetic Zinc Ferrite Coatings via MEK/ERK Signaling Pathways.

Combining an external stimulus and stimuli-responsive biomaterials can regulate cellular behaviors. In this paper, a magneto-responsive zinc ferrite (ZnFe2O4) coating was designed to gain insight into the preosteoblasts behaviors and osteogenic differentiation mechanism under a static magnetic field (SMF). ZnFe2O4 coatings with distinct magnetization (low, medium, and high magnetizations) were prepared by being annealed at different temperatures. Cellular biology experiments indicated that all ZnFe2O4 coatings with the assistance of SMF could promote the early proliferation (3 days) and osteogenic differentiation of MC3T3-E1 cells. Among different ZnFe2O4 samples, low and medium magnetization of ZnFe2O4 showed a higher osteogenesis-related gene expression (Runx2, Col-I, OCN) than that of high magnetization ZnFe2O4 under SMF, while cellular adhesion and proliferation cultured on different ZnFe2O4 samples presented insignificant differences. Molecular biology tests showed that the combination of ferromagnetic ZnFe2O4 and SMF could significantly improve the expression level of α2ß1 integrin and p-ERK. However, the addition of the inhibitor U0126 sharply reduced the expression level of p-ERK, which indicated that α2ß1 integrin-mediated MEK/ERK signaling pathways play a key role in SMF-assisted cellular osteogenic differentiation over ZnFe2O4 coatings. This work provides an attractive strategy to enhance cellular osteogenic differentiation in a remote-control way, which exhibited enormous potential in the field of bone tissue repair and regeneration.

Allele-aware chromosome-level genome assembly and efficient transgene-free genome editing for the autotetraploid cultivated alfalfa.

Artificially improving traits of cultivated alfalfa (Medicago sativa L.), one of the most important forage crops, is challenging due to the lack of a reference genome and an efficient genome editing protocol, which mainly result from its autotetraploidy and self-incompatibility. Here, we generate an allele-aware chromosome-level genome assembly for the cultivated alfalfa consisting of 32 allelic chromosomes by integrating high-fidelity single-molecule sequencing and Hi-C data. We further establish an efficient CRISPR/Cas9-based genome editing protocol on the basis of this genome assembly and precisely introduce tetra-allelic mutations into null mutants that display obvious phenotype changes. The mutated alleles and phenotypes of null mutants can be stably inherited in generations in a transgene-free manner by cross pollination, which may help in bypassing the debate about transgenic plants. The presented genome and CRISPR/Cas9-based transgene-free genome editing protocol provide key foundations for accelerating research and molecular breeding of this important forage crop.

The seasonal development dynamics of the yak hair cycle transcriptome.

BACKGROUND: Mammalian hair play an important role in mammals' ability to adapt to changing climatic environments. The seasonal circulation of yak hair helps them adapt to high altitude but the regulation mechanisms of the proliferation and differentiation of hair follicles (HFs) cells during development are still unknown. Here, using time series data for transcriptome and hormone contents, we systematically analyzed the mechanism regulating the periodic expression of hair development in the yak and reviewed how different combinations of genetic pathways regulate HFs development and cycling. RESULTS: This study used high-throughput RNA sequencing to provide a detailed description of global gene expression in 15 samples from five developmental time points during the yak hair cycle. According to clustering analysis, we found that these 15 samples could be significantly grouped into three phases, which represent different developmental periods in the hair cycle. A total of 2316 genes were identified in these three consecutive developmental periods and their expression patterns could be divided into 9 clusters. In the anagen, genes involved in activating hair follicle growth are highly expressed, such as the WNT pathway, FGF pathway, and some genes related to hair follicle differentiation. In the catagen, genes that inhibit differentiation and promote hair follicle cell apoptosis are highly expressed, such as BMP4, and Wise. In the telogen, genes that inhibit hair follicle activity are highly expressed, such as DKK1 and BMP1. Through co-expression analysis, we revealed a number of modular hub genes highly associated with hormones, such as SLF2, BOP1 and DPP8. They may play unique roles in hormonal regulation of events associated with the hair cycle. CONCLUSIONS: Our results revealed the expression pattern and molecular mechanisms of the seasonal hair cycle in the yak. The findings will be valuable in further understanding the alpine adaptation mechanism in the yak, which is important in order to make full use of yak hair resources and promote the economic development of pastoral plateau areas.

The sequence and de novo assembly of the wild yak genome.

Vulnerable populations of wild yak (Bos mutus), the wild ancestral species of domestic yak, survive in extremely cold, harsh and oxygen-poor regions of the Qinghai-Tibetan Plateau (QTP) and adjacent high-altitude regions. In this study, we sequenced and assembled its genome de novo. In total, six different insert-size libraries were sequenced, and 662 Gb of clean data were generated. The assembled wild yak genome is 2.83 Gb in length, with an N50 contig size of 63.2 kb and a scaffold size of 16.3 Mb. BUSCO assessment indicated that 93.8% of the highly conserved mammal genes were completely present in the genome assembly. Annotation of the wild yak genome assembly identified 1.41 Gb (49.65%) of repetitive sequences and a total of 22,910 protein-coding genes, including 20,660 (90.18%) annotated with functional terms. This first construction of the wild yak genome provides a variable genetic resource that will facilitate further study of the genetic diversity of bovine species and accelerate yak breeding efforts.

Identification of Xanthones from the Mangosteen Pericarp that Inhibit the Growth of Ralstonia solanacearum.

Bacterial wilt caused by Ralstonia solanacearum is one of the most destructive bacterial diseases in agriculture. There is no effective control method, although chemical pesticides are used to prevent this disease, but they may lead to serious problems of environmental pollution. Natural products from plants can be rich and environmentally friendly sources for a broad spectrum biological control of bacteria. This study focuses on the pericarp of mangosteen (Garcinia mangostana) using bioactivity-guided analysis of different fractions and liquid chromatography-mass spectrometry combined with multivariate analysis to determine markers of active fractions. Six prenyl xanthones, including two new xanthones, garcimangosxanthones H and I, were isolated and identified by NMR and HRESIMS. The biomarker γ-mangostin displayed significant activity against the phytopathogen R. solanacearum with an IC50 of 34.7 ± 1.5 µg/mL; γ-mangostin affected the bacterial morphology at a concentration of 16.0 µg/mL as seen with a scanning electron microscope image, and it significantly repressed the virulence-associated genes HrpB, FihD, and PilT of R. solanacearum. γ-Mangostin also reduced the symptoms of bacterial wilt disease effectively that is caused by R. solanacearum in tomato and tobacco seedlings in vitro. These results suggested that the use of γ-mangostin from the mangosteen pericarp against R. solanacearum may be used as a natural bacteriostatic agent in agriculture.

Comprehensive Evaluation of Surface Potential Characteristics on Mesenchymal Stem Cells' Osteogenic Differentiation.

The surface electric potential of biomaterials has been extensively proven to play a critical role in stem cells' fate. However, there are ambiguous reports on the relation of stem cells' osteogenic capacity to surface potential characteristics (potential polarity and intensity). To address this, we adopted a surface with a wide potential range and both positive/negative polarity in a comprehensive view to get insight into surface potential-regulating cellular osteogenic differentiation. Tb xDy1- xFe2 alloy/poly(vinylidene fluoride-trifluoroethylene) magnetoelectric films were prepared, and the film could provide controllable surface potential characteristics with positive or negative polarity and potential (ϕME) intensity variation from 0 to ±120 mV as well as keep the surface chemical composition and microstructure unchanged. Cell culture results showed that osteogenic differentiation of mesenchymal stem cells on both positive and negative potential films was obviously upregulated when the /ϕME/ intensities were set from 0-55 mV. Differently, the highest upregulated osteogenic differentiation on the positive potential films corresponded to the /ϕME/ intensity from 35-55 mV and was better than that on the negative potential films whereas the highest on the negative potential films corresponded to the /ϕME/ intensity from 0-35 mV and was better than that on the positive potential films. This fact could illustrate why previous reports appeared ambiguously; i.e., the comparative result in osteogenic differentiation between the positive and negative potential films strongly depends on the selection of surface potential intensity. On the basis of assaying of the exposed functional sites (RGD and PHSRN) of the adsorbed fibronectin (FN) and the expression of cellular integrin α5 and ß1 subunits, the difference in the behavior between the positive and negative potential films was attributed to the distinct conformation of adsorbed fibronectin (FN) and the opposite changing trend with /ϕME/ for the two films, which triggers the osteogenesis-related FAK/ERK signaling pathway to a different extent. This study could provide new cognition for the in-depth understanding of the regulation mechanism underlying surface potential characteristics in cell behaviors.