Multi-Stimuli-Responsive Nanoparticles Formed of POSS-PEG for the Delivery of Boronic Acid-Containing Therapeutics.

Polymeric vehicles often exhibit batch-to-batch variations due to polydispersity, limiting their reproducibility for biomedical applications. In contrast, polyhedral oligomeric silsesquioxane (POSS) has emerged as an attractive candidate for drug delivery due to its precise chemical structure and rigid molecular shape. A promising strategy to enhance drug efficacy while reducing systemic toxicity is the development of multi-stimuli-responsive delivery systems capable of targeted drug release at a disease site. Herein, we developed a drug delivery platform based on POSS-polymer conjugates. By functionalizing the POSS with amino groups and establishing B-N coordination with boronic acids, the nanoparticles (NPs) exhibit responsive behavior to stimuli, including adenosine-5'-triphosphate (ATP), acidic pH, and nucleophilic reagents. We successfully encapsulated two boronic acid-containing molecules: tetraphenylethylene (TPE), serving as a fluorescent probe, and bortezomib (BTZ), an anticancer drug. The TPE@NPs were employed to visualize the cellular uptake of NPs by tumor cells, while the BTZ@NPs exhibited increased cytotoxicity in tumor cells compared with normal cells. This POSS-PEG conjugate offers a nanoparticle platform for encapsulating versatile boronic acid-containing molecules, thereby enhancing drug efficacy while minimizing systemic toxicity. Given the wide-ranging applications of boronic acid-containing molecules in biomedicine, our platform holds significant promise for the development of intelligent drug delivery systems for diagnostics and therapeutics.

Solvent-Free Templated Synthesis of Core-Crosslinked Star-Shaped Polymers in Supramolecular Body-Centered Cubic Phase.

This study reports the exploration of a solvent-free supramolecular templated synthesis strategy toward highly core-cross-linked star-shaped polymers (CSPs). To achieve this, a kind of cross-linkable giant surfactant, based on a functionalized polyhedral oligomeric silsesquioxanes (POSS) head tethered with a diblock copolymer tail containing reactive benzocyclobutene groups, is designed and prepared. By varying the volume fraction of linear block copolymer tail, these giant surfactants can self-assemble into a body-centered cubic (BCC) structure in bulk, in which the supramolecular spheres are composed of a core of POSS cages, a middle shell of crosslinkable poly(4-vinylbenzocyclobutene) (PBCB) blocks, and a corona of inert polystyrene (PS) blocks. The solvent-free thermally induced cross-linking reaction of the benzocyclobutene groups can be finished in 5 min upon heating, resulting in well-defined polymeric spheres with over 90 linear chains surrounding the cross-linked cores. The outer PS blocks serve as the protection corona to ensure that cross-linking of giant surfactants occurs in each supramolecular spherical domain. Given the modular design and diversity of the POSS-based giant surfactants, it is believed that the strategy may enable access to a wide range of CSPs.

First report of Dickeya dadantii causing bacterial soft rot of Scindapsus pictus in Taiwan.

Scindapsus pictus (satin pothos or silver vine) is an evergreen climbing plant belonging to the Araceae family, subfamily Monstereae (Bown, 2000), which is also cultivated as a foliage ornamental (Masnira et al. 2019). In September of 2022, soft rot symptoms were observed on potted S. pictus plants grown in a greenhouse in Nantun District, Taichung, Taiwan, in which soft rot of another aroid (philodendron) has also been reported (Wu et al. 2023). The symptoms appeared on the petioles and most of them tended to extend to the leaf blades; the colors of leaf lesions ranged from dark brown to gray (Fig. S1). Some 70% of the plants in the greenhouse showed similar symptoms and losses were estimated to be 15-30%. Four symptomatic plants were sampled. Macerated tissues from rotting petioles were soaked in 10 mM MgCl2 and observed under a light microscope (Nikon, Japan) at 400 x magnification. Motile, rod-shaped bacteria were observed, and 1-2 loopfuls of undiluted sample suspension were streaked onto nutrient agar (NA; Gibco, USA). After culturing at 28°C for 1 day, all samples yielded round, creamy-white colonies (0.9 mm in diameter) and from each of the four samples a pure culture was obtained (Spi1-Spi4). All isolates exhibited oxidative and fermentative metabolism of glucose (Schaad et al. 2001). They caused pitting on crystal violet pectate agar, induced maceration on potato tuber and were tested positive for phosphatase activity and indigoidine production (Lee and Yu 2006; Schaad et al. 2001). Polymerase chain reaction tests using Dickeya-specific primers 5A and 5B (Chao et al. 2006) amplified the expected amplicon (0.5 kb) in extracted DNA samples of all isolates. Identification of the strains was achieved by amplifying and sequencing fragments of the housekeeping genes gyrB, recN, dnaA, dnaJ, and dnaX (Marrero et al. 2013); the lengths of the five gene fragments analyzed were 822, 762, 720, 672, and 450 bp, respectively (accession nos. OP985528-OP985532). The five sequences were concatenated for every isolate; the resulting 3,426 bp sequences were aligned with ClustalW and found to be identical. A maximum-likelihood analysis was conducted using the 3,426-bp sequences and those of known Dickeya species' type strains. Spi1 to Spi4 clustered with D. dadantii subsp. dieffenbachiae NCPPB 2976T and D. dadantii subsp. dadantii CFBP 1269T (Fig. S2) with sequence identities of 98.4 and 98%, respectively. To fulfil Koch's Postulates, stab inoculations of the four isolates into the petioles of cutting propagated, 38-day-old S. pictus plants (3 plants per isolate) were conducted using sterile toothpicks. The amounts of bacteria used was approximately 106 cfu per toothpick; the bacterial loads were estimated by suspending the cells in 10 mM MgCl2 and spread-plating diluted suspensions on NA. Sterile toothpicks were used as control. All tested plants were sealed in plastic bags (containing wet paper towel) and kept in a growth chamber (28°C; 12-h photoperiod). After 1 day, all isolates induced soft rot symptoms resembling those observed under natural conditions in the greenhouse. Bacteria were re-isolated, and they all shared the same dnaX sequence with strains Spi1 to Spi4. This is the first report of S. pictus affected by D. dadantii in Taiwan. Further investigation is needed to determine whether Spi1-Spi4 belong to D. dadantii subsp. dieffenbachiae. Dickeya dadantii has been found infecting different aroids (Lee and Chen 2021; Lin et al. 2012). The species has also been reported in Taiwan on poinsettia (Wei et al., 2019) and philodendron (Wu et al. 2023). Because these plants are often grown closely in the same facilities, growers should be wary of D. dadantii's spread among these plants. Reduction of environmental humidity and avoiding overhead irrigation may be effective in preventing the pathogen's transmission.

Design of self-assembly dipeptide hydrogels and machine learning via their chemical features.

Hydrogels that are self-assembled by peptides have attracted great interest for biomedical applications. However, the link between chemical structures of peptides and their corresponding hydrogel properties is still unclear. Here, we showed a combinational approach to generate a structurally diverse hydrogel library with more than 2,000 peptides and evaluated their corresponding properties. We used a quantitative structure-property relationship to calculate their chemical features reflecting the topological and physicochemical properties, and applied machine learning to predict the self-assembly behavior. We observed that the stiffness of hydrogels is correlated with the diameter and cross-linking degree of the nanofiber. Importantly, we demonstrated that the hydrogels support cell proliferation in culture, suggesting the biocompatibility of the hydrogel. The combinatorial hydrogel library and the machine learning approach we developed linked the chemical structures with their self-assembly behavior and can accelerate the design of novel peptide structures for biomedical use.

First report of Pectobacterium carotovorum and Pectobacterium brasiliense causing bacterial soft rot of bok choy in Taiwan.

Bok choy (Brassica rapa var. chinensis) is one of the most popular leafy green vegetables in Asia (Wang et al. 2019; Zhang et al. 2014). In May 2022, disease resembling bacterial soft rot was observed in a commercial greenhouse located in Xiluo, Yunlin County, Taiwan. Affected plants exhibited maceration, primarily close to the base of the plants (Fig. S1). Almost all bok choy plants (about 1,800 plants in total) on site were symptomatic. Macerated tissues were collected from six plants. The samples were homogenized in 10 mM MgCl2 and bacteria were isolated on nutrient agar (NA) by streak plating. After 1 day of culturing at 28°C, creamy-white, round colonies were consistently grown on all the plates, and six strains (Br1 to Br6) were obtained; each isolated from a different plant. The strains were able to ferment glucose and induced maceration on potato tuber slices (Schaad et al. 2001) but could not produce indigoidine on NGM medium (NA added with glycerol and MnCl2; Lee and Yu 2006). The DNA samples of these strains were tested with Pectobacterium-specific primers Y1 and Y2 (Darrasse et al. 1994) and all samples produced the expected amplicon. To identify the isolated pathogens, 1,592-bp sequences concatenated from fragments of the leuS (452 bp), dnaX (492 bp), and recA (648 bp) genes (GenBank accession nos. OP360013-OP360021) were obtained for each strain as previously described (Portier et al. 2019). Three genotypes were detected, the sequences of strains Br1, Br2, Br4, and Br5 were identical, while strains Br3 and Br6 each belong to a different genotype. The sequence identity between Br3 and Br6 was 98.2%. The concatenated sequences (dnaX-leuS-recA), along with those of type strains from known Pectobacterium species, were subjected to maximum likelihood analysis. The reconstructed trees showed that strains Br1, Br2, Br4, and Br5 grouped with P. carotovorum CFBP2046T (Fig. S2); the sequence identity between the isolated strains and the type strain was 98.7%. Strains Br3 and Br6 clustered with P. brasiliense CFBP6617T (Fig S2); the sequence identity between CFBP6617T and Br3 and Br6 were 97.5% and 98.4%, respectively. The six strains were inoculated onto 55-day-old bok choy plants using previously described prick inoculation methods (Wei et al. 2019). Autoclaved toothpicks, each carrying 9.3 x 106- 5.6 x 107 cfu of bacteria, were used to inoculate the base of plant leaves. All six strains were tested, and each strain had three replicates. Plants in the control group were stabbed with bacteria-free toothpicks. The plants were enclosed in clear plastic bags during the assay to maintain humidity and kept in a growth chamber (27/25°C day/night; 14-h photoperiod). After 1 d, all inoculated plants produced soft rot symptoms resembling those observed in the sampling site. No noticeable differences were observed among symptoms produced by different strains. The controls were symptomless. One strain was re-isolated from each treatment group and their identity were confirmed by sequencing the dnaX gene. All re-isolated strains shared the same sequences with those of the original strains tested. This is the first report of P. brasiliense and P. carotovorum causing bacterial soft rot of bok choy in Taiwan. Importantly, the findings showed that different Pectobacterium species and genotypes could induce symptoms on a crop in the same facility at the same time, highlighting the potential complexity of interactions among different soft rot bacteria in the environment.

First report of bacterial soft rot on Epipremnum aureum caused by Pectobacterium aroidearum in Taiwan.

Pothos (Epipremnum aureum) is an Araceae foliage plant with great ornamental values, which has long been enjoyed by consumers (Chen et al. 2010). In September 2021, pothos showing soft rot symptoms were found in 2 nurseries in Taichung, Taiwan. The petioles of the infected plants were macerated; some lesions extended to the leaves (Figure S1). The disease incidence was 50% in one nursery and 37.5% in the other; two and three plants were respectively collected from the two sites. Macerated tissues were homogenized in 10 mM MgCl2 and the samples were observed microscopically without dyeing. Motile, rod-shaped bacteria were observed in the samples, and the bacteria were isolated onto nutrient agar (NA) and grown at 28°C for 2 days. Fast-growing, round, creamy colonies were isolated from all 5 plants. One strain was isolated from each plant and the strains were named Ea1 to Ea5. The bacteria could ferment glucose and induce maceration on potato tuber slices (Schaad et al. 2001), but did not produce indigoidine on NGM medium (Lee and Yu 2006) and were tested negative for phosphatase activity (Schaad et al. 2001). The bacteria's DNA samples were tested using primers specific to Pectobacterium (Y1/Y2; Darrasse et al. 1994). The expected 434-bp amplicon was amplified in all five strains. Multilocus sequence analysis was conducted as previously described (Portier et al. 2019). A concatenated sequence (1,592 bp) comprising partial dnaX (492 bp), leuS (452 bp) and recA (648 bp) sequences was obtained for each strain. Two genotypes were detected among the strains; Ea1 and Ea2 belonged to one genotype (i.e., they had identical sequences), while Ea3, Ea4 and Ea5 belonged to the other (GenBank accession nos. OK416015-OK416020). Phylogenetic analysis was conducted using these data and those of representative strains of known Pectobacterium species (Klair et al. 2022). A maximum-likelihood tree showed that Ea1 to Ea5 clustered with P. aroidearum CFBP8168T (Figure S2). Sequence comparison (Table S1) showed that the similarity between the two genotypes' concatenated sequences was 99.1% (Ea1 vs. Ea3; 1,578/1,592 bp); Ea1 and Ea3 shared 99.2% and 99.3% sequence similarity with P. aroidearum CFBP8168T, respectively. The sequences obtained in this work were searched against GenBank and all of their top hits were those of strains belonging to P. aroidearum (supplementary information). Koch's Postulates were fulfilled by stab inoculating cutting-propagated pothos (8-cm tall) using toothpicks carrying bacteria grown on NA. The pathogen loads used were estimated by suspending cells (attached to individual toothpicks) in 10 mM MgCl2 and spread-plating them onto NA (after dilution); the loads were 5.5 x 106 - 2.2 x 107 CFU. Three plants were inoculated for each strain (3 petioles per plant). Control plants were stabbed with sterile toothpicks. Each plant was then bagged and placed in a growth chamber (28°C; 14 h light). After 24 h, all inoculated plants produced symptoms resembling those found in the nurseries, and the controls did not. For every treatment group, a strain was re-isolated onto NA; each of them shared the same recA sequence with the original strain inoculated. This is first report of P. aroidearum causing pothos soft rot in Taiwan. Local nurseries often grow pothos and other Araceae plants together in humid areas. Since other Araceae species are also known to be susceptible to P. aroidearum (Xu et al. 2020), growers should be cautious of the pathogen's spread across hosts.

Mass Spectrometry and Ion Mobility Characterization of Bioactive Peptide-Synthetic Polymer Conjugates.

The bioconjugate BMP2-(PEO-HA)2, composed of a dendron with two monodisperse poly(ethylene oxide) (PEO) branches terminated by a hydroxyapatite binding peptide (HA), and a focal point substituted with a bone growth stimulating peptide (BMP2), has been comprehensively characterized by mass spectrometry (MS) methods, encompassing matrix-assisted laser desorption ionization (MALDI), electrospray ionization (ESI), tandem mass spectrometry (MS2), and ion mobility mass spectrometry (IM-MS). MS2 experiments using different ion activation techniques validated the sequences of the synthetic, bioactive peptides HA and BMP2, which contained highly basic amino acid residues either at the N-terminus (BMP2) or C-terminus (HA). Application of MALDI-MS, ESI-MS, and IM-MS to the polymer-peptide biomaterial confirmed its composition. Collision cross-section measurements and molecular modeling indicated that BMP2-(PEO-HA)2 exists in several folded and extended conformations, depending on the degree of protonation. Protonation of all basic sites of the hybrid material nearly doubles its conformational space and accessible surface area.

Valency-dependent affinity of bioactive hydroxyapatite-binding dendrons.

Hydroxyapatite (HA)-coated surfaces are used widely as stationary phase for protein and enzyme purification, coatings for dental and orthopedic implants, and composite materials for tissue engineering substrates. More advanced applications are envisioned, but progress has been slowed by the limited ability to controllably functionalize the surface of HA with biomolecules in a translationally relevant manner. Herein we report the synthesis and characterization of a series of multivalent, HA-binding peptide bioconjugates with variable valency and tether length which afford the ability to precisely tune the desired binding behavior. The respective binding affinities of the multivalent constructs to HA surface were characterized by quartz crystal microbalance with dissipation monitoring (QCM-D) techniques, and the relationship between dendron structure and binding affinity was revealed. Tetravalent constructs of HA-binding peptides show a 100-fold enhancement in binding affinity compared to HA-binding peptide sequences reported previously. Both biotin and bone morphogenic protein-2 (BMP-2) derivative peptide were successfully linked to the focal point as initial demonstrations.

Peptide-functionalized oxime hydrogels with tunable mechanical properties and gelation behavior.

We demonstrate the formation of polyethylene glycol (PEG) based hydrogels via oxime ligation and the photoinitiated thiol-ene 3D patterning of peptides within the hydrogel matrix postgelation. The gelation process and final mechanical strength of the hydrogels can be tuned using pH and the catalyst concentration. The time scale to reach the gel point and complete gelation can be shortened from hours to seconds using both pH and aniline catalyst, which facilitates the tuning of the storage modulus from 0.3 to over 15 kPa. Azide- and alkene-functionalized hydrogels were also synthesized, and we have shown the post gelation "click"-type Huisgen 1,3 cycloaddition and thiolene-based radical reactions for spatially defined peptide incorporation. These materials are the initial demonstration for translationally relevant hydrogel materials that possess tunable mechanical regimes attractive to soft tissue engineering and possess atom neutral chemistries attractive for post gelation patterning in the presence or absence of cells.

Gold nanoparticles: promising biomaterials for osteogenic/adipogenic regulation in bone repair.

Bone defects are a common bone disease, which are usually caused by accidents, trauma and tumors. However, the treatment of bone defects is still a great clinical challenge. In recent years, research on bone repair materials has continued with great success, but there are few reports on the repair of bone defects at a high lipid level. Hyperlipidemia is a risk factor in the process of bone defect repair, which has a negative impact on the process of osteogenesis, increasing the difficulty of bone defect repair. Therefore, it is necessary to find materials that can promote bone defect repair under the condition of hyperlipidemia. Gold nanoparticles (AuNPs) have been applied in the fields of biology and clinical medicine for many years and developed to modulate osteogenic differentiation and adipogenic differentiation. In vitro and vivo studies displayed that they promoted bone formation and inhibited fat accumulation. Further, the metabolism and mechanisms of AuNPs acting on osteogenesis/adipogenesis were partially revealed by researchers. This review further clarifies the role of AuNPs in osteogenic/adipogenic regulation during the process of osteogenesis and bone regeneration by summarizing the related in vitro and in vivo research, discussing the advantages and challenges of AuNPs and highlighting several possible directions for future research, with the aim to provide a new strategy for dealing with bone defects in hyperlipidemic patients.

The velvet proteins CsVosA and CsVelB coordinate growth, cell wall integrity, sporulation, conidial viability and pathogenicity in the rubber anthracnose fungus Colletotrichum siamense.

Colletotrichum siamense, a member of Colletotrichum gloeosporioides complex species, is the primary pathogen causing rubber anthracnose, which leads to significant economic loss in natural rubber production. Velvet family proteins are fungal-specific proteins and play an essential role in regulating development and secondary metabolism. In this study, we characterized two velvet proteins CsVosA and CsVelB in C. siamense as the orthologs of VosA and VelB in Aspergillus nidulans. CsVosA is located in the nucleus, and CsVelB displays a localization in both the nucleus and the cytoplasm. Deleting CsvosA or CsvelB results in a slow growth rate, and the CsvelB-knockout mutants also exhibit low mycelial density. CsVosA and CsVelB are involved in regulating chitin metabolism and distribution, leading to the variation in the cell wall integrity of C. siamense. Furthermore, disruption of CsvosA or CsvelB can decrease conidial production and viability, and the ΔCsvosA and ΔCsvelB mutants also lose the ability to produce fruiting bodies. Pathogenicity assays show that deleting CsvosA or CsvelB can lower the virulence, and the two velvet genes are essential for the full virulence of C. siamense. Based on the results of the yeast two-hybrid analysis and bimolecular fluorescence complementation assays, CsVosA can interact with CsVelB and form the complex CsVosA-CsVelB in the conidia of C. siamense, which may play essential roles in maintaining the cell wall integrity and conidial viability. In addition, CsVelB is also involved in regulating melanin production of C. siamense. In conclusion, CsVosA and CsVelB regulate vegetative growth, cell wall integrity, asexual/sexual sporulation, conidial viability and virulence in C. siamense.

Preparation of polyvinyl alcohol/chitosan nanofibrous films incorporating graphene oxide and lanthanum chloride by electrospinning method for potential photothermal and chemical synergistic antibacterial applications in wound dressings.

Electrospun fibres have been widely used as skin dressings due to their unique structur. However, due to the lack of intrinsic antimicrobial activity, it is easy for the wound to become infected. Bacterial infection, which leads to chronic inflammation, severely hinders the normal process of skin regeneration. In this study, a polyvinyl alcohol/chitosan (PVA/CS) composite films with chemical sterilization and near-infrared (NIR) photothermal antibacterial activity was fabricated by electrospinning. Graphene oxide (GO), a photosensitiser, was incorporated into the films, and lanthanum chloride (Lacl3) as a chemical antibacterial agent was also doped in the electrospun films. The structure, morphology, mechanical properties, wettability, and antimicrobial and photothermal antibacterial activity of the PVA/CS-based fibre films were investigated. The results showed that the addition of Lacl3 to the PVA/CS/GO nanofibres (PVA/CS/GO-La) improved the hydrophilicity, tensile strength and resistance to elastic deformation of the nanofibres. The PVA/CS/GO-La12.5 mM sample exhibited the best antibacterial performance, showing high inhibition against Staphylococcus aureus (82% antibacterial efficacy) and Escherichia coli (99.7% antibacterial efficacy). Furthermore, the antibacterial efficacy of the films surface was further enhanced after exposure to NIR light (808 nm, 0.01 W) for 20 min. In addition, the nanofibre films showed no cytotoxicity against human skin fibroblasts (HSFs), indicating its potential application in the field of broad-spectrum antibacterial materials.

Foxtail millet MYB-like transcription factor SiMYB16 confers salt tolerance in transgenic rice by regulating phenylpropane pathway.

R2R3-MYB transcription factors play an important role in the synthesis of phenylpropanoid-derived compounds, which in turn provide salt tolerance in plant. In this study, we found that the expression of foxtail millet R2R3-MYB factor SiMYB16 can be induced by salt and drought. SiMYB16 is localized in the nucleus and acts as a transcriptional activator. Phylogenetic analysis indicates that SiMYB16 belongs to the R2R3-MYB transcription factor family subgroup 24. Transgenic rice expressing SiMYB16 (OX16) had a higher survival rate, lower malondialdehyde content, and heavier fresh weight compared with type (WT) under salt stress conditions. The transgenic plants also had a higher germination rate in salt treatment conditions and higher yield in the field compared with wild-type plants. Transcriptome analysis revealed that the up-regulated differential expression genes in the transgenic rice were mainly involved in phenylpropanoid biosynthesis, fatty acid elongation, phenylalanine metabolism, and flavonoid biosynthesis pathways. Quantitative real-time PCR analysis also showed that the genes encoding the major enzymes in the lignin and suberin biosynthesis pathways had higher expression level in SiMYB16 transgenic plants. Correspondingly, the content of flavonoid and lignin, and the activity of fatty acid synthase increased in SiMYB16 transgenic rice compared with wild-type plants under salt stress treatment. These results indicate that SiMYB16 gene can enhance plant salt tolerance by regulating the biosynthesis of lignin and suberin.

Lipid droplet-hitchhiking probe creates Trojan foam cells for fluorescence/photoacoustic imaging of atherosclerotic plaques.

Since atherosclerosis, a disease characterized by abnormal arterial lipid deposition, may lead to fatal cardiovascular diseases, imaging of atherosclerotic plaques is of great value for their pathological assessment. In this study, we propose a lipid droplet (LD)-hitchhiking strategy to in situ create Trojan foam cells for fluorescence/photoacoustic imaging of atherosclerotic plaques via homologous targeting effect. In our design, functional liposomes (DCP liposomes) composed of phospholipid dioleoylphosphatidylserine (DOPS), a novel LD inducer we found, and Cypate-PC, a synthesized lipid-like molecular probe, have demonstrated great capability of inducing LDs in monocytes/macrophages while being enveloped into the resulting Trojan foam cells. Taking advantage of homologous targeting effect, the imaging probe hitchhikes on the LDs in Trojan foam cells for targeted transport to the plaque sites. Moreover, the confinement in highly hydrophobic LDs endows the imaging probe with high efficiency in light absorption, enabling greatly intensified fluorescence/photoacoustic signals. The DCP liposomes have shown great potency in inducing the generation of Trojan foam cells, and eventually ex vivo fluorescence imaging and in vivo photoacoustic imaging of atherosclerotic plaques. The proposed strategy provides more insights into the design of targeted imaging methodologies, and also an effective avenue to facilitate the evaluation and subsequent treatment of atherosclerotic plaques.

[A Meta-analysis of the effect of non-surgical periodontal therapy on inflammatory factors in patients with chronic kidney disease and periodontitis].

OBJECTIVE: A study was conducted to systematically evaluate the clinical efficacy of inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. METHODS: We searched the databases of CNKI, Wanfang, CBM, PubMed, Embase, and Cochrane Library from inception to December 2019. Two reviewers independently collected all literature related to inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. These factors include C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The literature was screened according to the inclusion and exclusion criteria. The quality of the studies was strictly evaluated, and the data were extracted. The literature of randomized controlled trials in accordance with the standards was Meta-analyzed with Revman 5.3 software. RESULTS: Six randomized controlled trials were included. Compared with the control groups, the results of meta-analysis showed that non-surgical periodontal therapy significantly reduced the levels of CRP [MD=-0.58, 95%CI (-1.13, -0.02), P=0.04] and IL-6 [MD=-2.76, 95%CI (-5.15, -0.37), P=0.02] in these patients but not that of TNF-α [MD=-3.87, 95%CI (-8.79, 1.05), P=0.12]. CONCLUSIONS: Simultaneous regular renal treatment and non-surgical periodontal therapy can help relieve the periodontal damage on patients with chronic kidney disease and periodontitis. Moreover, it can improve the status of some inflammatory factors. This finding is conducive to the control and treatment of chronic kidney disease and periodontitis and needs to be a focus of research and in clinical operation.

Reversibly-regulated drug release using poly(tannic acid) fabricated nanocarriers for reduced secondary side effects in tumor therapy.

Numerous nanocarriers with pH-responsive properties have been designed and fabricated to reduce the adverse side effects of traditional chemotherapeutics, but these traditional nanocarriers are rarely reversible; this may cause "secondary" side effects on normal tissues, because the nanocarriers cannot be sealed again to prevent the leakage of incompletely released drugs after re-entering blood circulation. To overcome these limitations, we report herein the synthesis of a reversibly pH-responsive drug delivery system, which can achieve regulated drug release in a "release-stop-release" manner corresponding to changes in pH. Specifically, poly(tannic acid) as the "gatekeeper" was firstly deposited and polymerized on the surface of mesoporous silica nanoparticles (MSNs) via a modified mussel-inspired method similar to dopamine, and the formed polymer shell can be easily decorated with a targeting ligand HER2 antibody for the selective delivery of drugs to specific cells. The resulting nanocomposites exhibited good colloidal stability, good biocompatibility, high drug loading capacity and accurate HER2 antibody mediated targeting ability. Interestingly, a series of experiments fully demonstrated that the fabricated nanocomposites possessed intelligent reversible pH-responsive controlled release behavior through adjusting the density of the "gatekeeper" under different pH conditions, thereby achieving reversible switching from "on" to "off". Furthermore, in vitro and in vivo experiments verified that the fabricated targeting nanoparticles could efficiently inhibit tumor growth with minimal side effects. Meanwhile, these nanocarriers exhibited excellent reusability, in vitro cytotoxicity and minimal in vivo myocardial damage. Collectively, the reversible pH-operated nanovalve on the MSNs constructed here could serve as a nanoplatform to solve the problem of "secondary" side effects caused by residual drugs in irreversible "gatekeeper" systems.

Biodegradation of lignocellulosic agricultural residues by a newly isolated Fictibacillus sp. YS-26 improving carbon metabolic properties and functional diversity of the rhizosphere microbial community.

A new isolated cellulolytic bacterium from a soft coral was named as Fictibacillus sp YS-26 based on the morphologic and molecular characteristics. It can degrade different lignocellulosic agricultural residues by producing cellulolytic enzymes, α-amylase, protease, pectinase and xylanase. Especially, Fictibacillus sp. YS-26 exhibited the highest cellulolytic activities in the soybean meal medium. By contrast, the fermentation broth of Fictibacillus sp. YS-26 significantly enhanced utilization efficiency of carboxylic acids and polymers by soil microorganisms as well as the microbial metabolism function and community diversity in rhizosphere soil of banana plantlets. The fermentation broth also improved soil characters and increased the growth of banana plantlets. We found that soil total nitrogen and electrical conductivity had a positive relationship with the increase of microbial diversity. Hence, Fictibacillus sp. YS-26 will be a promising candidate for biodegradating lignocellulosic biomass and improving the soil microbial diversity.

[Study on DNA methylation profiles in non-syndromic cleft lip/palate based on bioinformatics].

PURPOSE: To study DNA methylation patterns of non-syndromic cleft lip/palate(NSCL/P) using bioinformatic methods, including methylated positions and regions. METHODS: Whole blood DNA methylation data of NSCL/P samples was download from Gene Expression Omnibus(GEO) database, including 67 NSCL/P cases and 59 controls without birth defects. Data analysis included ①data cleaning, such as probes filtering, quality control and normalization; ②differential methylation analysis, including methylated positions and regions; ③Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on differential methylated genes. R 3.4.3 software was used for data cleaning, differential methylated positions and regions analysis. DAVID6.8 tool was used for GO and KEGG analysis. RESULTS: 814 differential methylated positions were detected (adjusted P＜0.001，|Δß|＞0.125）, of which 178 were hypermethylated in NSCL/P patients, and 636 were hypomethylated. In addition, 386 differential methylated regions were identified (P＜0.05), of which 204 were hypermethylation regions and 182 were hypomethylation regions. GO analysis showed that 38 differential methylated genes were involved in 7 kinds of biological processes, 163 differential methylated genes were involved in 3 kinds of molecular functions, and 114 differential methylated genes were involved in 3 kinds of cellular components (P＜0.01). KEGG analysis showed that 59 differential methylated genes were involved in 9 kinds of signal pathways. CONCLUSIONS: Abnormal DNA methylation patterns of NSCL/P might be an important epigenetic mechanism affecting the development of NSCL/P. This study might contribute to the identification of identification of biomarkers and targeted interventions of NSCL/P.

Hyaluronic acid conjugated polydopamine functionalized mesoporous silica nanoparticles for synergistic targeted chemo-photothermal therapy.

The integration of chemotherapy and photothermal therapy into one nanoplatform has attracted much attention for synergistic tumor treatment, but the practical clinical applications were usually limited by their synergistic effects and low selectivity for disease sites. To overcome these limitations, a tumor-specific and pH/NIR dual-responsive multifunctional nanocarrier coated with mussel inspired polydopamine and further conjugated with targeting molecular hyaluronic acid (HA) was designed and fabricated for synergistic targeted chemo-photothermal therapy. The synthesized versatile nanoplatform displayed strong near-infrared absorption because of the successful formation of polydopamine coating. Furthermore, the nanosystem revealed high storage capacity for drugs and pH/NIR dual-responsive release performance, which could effectively enhance the chemo-photothermal therapy effect. With this smart design, in vitro experimental results confirmed that the drug loaded multifunctional nanoparticles could be efficiently taken up by cancer cells, and exhibited remarkable tumor cell killing efficiency and excellent photothermal properties. Meanwhile, significant tumor regression in the tumor-bearing mice model was also observed due to the combination of chemotherapy and photothermal therapy. Thus, this work indicated that the simple multifunctional nanoplatform can be applied as an efficient therapeutic agent for site-specific synergistic chemo-photothermal therapy.

A Rapid Detection Method for Morphological Characteristics of Biological Cells Based on Phase Imaging.

This paper presents a rapid label-free method for the identification of morphological characteristics of biological cells. Based on quantitative phase microscopy as well as the connotation of phase value, the gradient operator of phase and the associated analytic processing are employed to determine the edge of different parts of the samples. A heterogeneous biological cell model is established by simulation to show the mechanism of this method and a polystyrene bead is selected as a sample to confirm its validity by optical experiment. The result agrees well with the actual situation and this approach is proved to have good antinoise ability. Furthermore, a neutrophil is investigated by this method. Based on the optical experiment and the related analysis, the basic structure characteristics of the cell are obtained. It is indicated that the method presented in this paper could be applied to rapid identification and classification of living cells.