Preparation, characterization, and anticancer effects of an inclusion complex of coixol with ß-cyclodextrin polymers.

CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

DNA Thioaptamer with Homing Specificity to Lymphoma Bone Marrow Involvement.

Selective drug accumulation in the malignant tissue is a prerequisite for effective cancer treatment. However, most drug molecules and their formulated particles are blocked en route to the destiny tissue due to the existence of multiple biological and physical barriers including the tumor microvessel endothelium. Since the endothelial cells on the surface of the microvessel wall can be modulated by inflammatory cytokines and chemokines secreted by the tumor or stromal cells, an effective drug delivery approach is to enhance interaction between the drug particles and the unique spectrum of surface proteins on the tumor endothelium. In this study, we performed in vivo screening for thioaptamers that bind to the bone marrow endothelium with specificity in a murine model of lymphoma with bone marrow involvement (BMI). The R1 thioaptamer was isolated based on its high homing potency to bones with BMI, and 40-60% less efficiency in accumulation to healthy bones. In cell culture, R1 binds to human umbilical vein endothelial cells (HUVEC) with a high affinity ( Kd ≈ 3 nM), and the binding affinity can be further enhanced when cells were treated with a mixture of lymphoma cell and bone marrow cell conditioned media. Cellular uptake of R1 is through clathrin-mediated endocytosis. Conjugating R1 on to the surface of liposomal doxorubicin nanoparticles resulted in 2-3-fold increase in drug accumulation in lymphoma BMI. Taking together, we have successfully identified a thioaptamer that preferentially binds to the endothelium of lymphoma BMI. It can serve as an affinity moiety for targeted delivery of drug particles to the disease organ.

Highly-purified exosomes and shed microvesicles isolated from the human colon cancer cell line LIM1863 by sequential centrifugal ultrafiltration are biochemically and functionally distinct.

Secretion and exchange of extracellular vesicles (EVs) by most cell types is emerging as a fundamental biological process. Although much is known about EVs, there is still a lack of definition as to how many naturally occurring EV subtypes there are and how their properties and functionalities might differ. This vexing issue is critical if EVs are to be fully harnessed for therapeutic applications. To address this question we have developed and describe here a sequential centrifugal ultrafiltration (SCUF) method to examine, in an unbiased manner, what EV subtypes are released in vitro into cell culture medium using the human colon carcinoma cell line LIM1863 as a model system. Using the culture medium from ∼7.2×10(9) LIM1863 cells, SCUF was performed using hydrophilic PVDF membranes with low protein binding properties (Millipore Durapore™ Ultrafree-CL filters with 0.1, 0.22, 0.45 and 0.65 µm pore size). EV particle sizing was measured using both dynamic light scattering and cryo-electron microscopy. Comparative proteome profiling was performed by GeLC-MS/MS and qualitative protein differences between EV subtypes determined by label-free spectral counting. The results showed essentially two EV subtypes; one subtype (fraction Fn1) comprised heterogeneous EVs with particle diameters of 30-1300 nm, the other (fraction Fn5) being homogeneous EVs of 30-100 nm diameter; based on cryo-EM both EV subtypes were round shaped. Western blot analysis showed Fn5 (SCUF-Exos) contained traditional exosome marker proteins (Alix(+), TSG101(+), CD81(+), CD63(+)), while Fn1 (SCUF-sMVs) lacked these protein markers. These findings were consistent with sMVs isolated by differential centrifugation (10,000 g, DC-sMVs) and exosomes (100,000 g EVs depleted of 10,000 g material). The buoyant density of sMVs determined by OptiPrep™ density gradient centrifugation was 1.18-1.19 g/mL and exosomes 1.10-1.11 g/mL. Comparative protein profiling of SCUF-Exos/-sMVs revealed 354 and 606 unambiguous protein identifications, respectively, with 256 proteins in common. A salient finding was the first report of 350 proteins uniquely identified in sMVs may of which have the potential to enable discrimination of this EV subtype from exosomes (notably, members of the septin family, kinesin-like protein (KIF23), exportin-2/chromosome segregation like-1 protein (CSE1L), and Rac GTPase-activating protein 1 (RACGAP1)). We report for the first time that both SCUF-Exos and SCUF-sMVs isolated from LIM1863 colon cancer cells induce invasion of recipient NIH3T3 cells. Interestingly, the SCUF-sMVs promote invasion to a significantly greater extent (3-fold) than SCUF-Exos. This analytical SCUF method for fractionating EVs is potentially scalable using tangential flow filtration, thereby providing a solid foundation for future in-depth functional studies of EV subtypes using diverse cell types and functional assays.

Three novel species of Aquapteridospora (Distoseptisporales, Aquapteridosporaceae) from freshwater habitats in Tibetan Plateau, China.

During an investigation of lignicolous freshwater fungi in the Tibetan Plateau, three Aquapteridospora taxa were collected from freshwater habitats in Xizang, China. The new species possess polyblastic, sympodial, denticles conidiogenous cells and fusiform, septate, with or without sheath conidial, that fit within the generic concept of Aquapteridospora, and multi-gene phylogeny placed these species within Aquapteridospora. Detailed morphological observations clearly demarcate three of these from extant species and are hence described as new taxa. The multi-gene phylogeny of the combined LSU, TEF1-α, and ITS sequence data to infer phylogenetic relationships and discuss phylogenetic affinities with morphologically similar species. Based on morphological characteristics and phylogenetic analyses, three new species viz. A.linzhiensis, A.yadongensis, and A.submersa are introduced. Details of asexual morphs are described, and justifications for establishing these new species are also provided in this study.

Embedded Bioprinting of Tissue-like Structures Using κ-Carrageenan Sub-Microgel Medium.

Embedded three-dimensional (3D) bioprinting utilizing a granular hydrogel supporting bath has emerged as a critical technique for creating biomimetic scaffolds. However, engineering a suitable gel suspension medium that balances precise bioink deposition with cell viability and function presents multiple challenges, particularly in achieving the desired viscoelastic properties. Here, a novel κ-carrageenan gel supporting bath is fabricated through an easy-to-operate mechanical grinding process, producing homogeneous sub-microscale particles. These sub-microgels exhibit typical Bingham flow behavior with small yield stress and rapid shear-thinning properties, which facilitate the smooth deposition of bioinks. Moreover, the reversible gel-sol transition and self-healing capabilities of the κ-carrageenan microgel network ensure the structural integrity of printed constructs, enabling the creation of complex, multi-layered tissue structures with defined architectural features. Post-printing, the κ-carrageenan sub-microgels can be easily removed by a simple phosphate-buffered saline wash. Further bioprinting with cell-laden bioinks demonstrates that cells within the biomimetic constructs have a high viability of 92% and quickly extend pseudopodia, as well as maintain robust proliferation, indicating the potential of this bioprinting strategy for tissue and organ fabrication. In summary, this novel κ-carrageenan sub-microgel medium emerges as a promising avenue for embedded bioprinting of exceptional quality, bearing profound implications for the in vitro development of engineered tissues and organs.

Liposomal ATM siRNA delivery for enhancing triple-negaitive breast cancer immune checkpoint blockade therapy.

Triple-negative breast cancer (TNBC), which accounts for 10%-20% of breast cancer cases, is characterized by a higher metastasis rate, higher recurrence risk, and worse prognosis. Traditional treatments such as chemotherapy, surgery, and radiotherapy have limited therapeutic effects. Although immune checkpoint blockade (ICB) therapy represented by anti-programmed death 1 (aPD-1) antibody has made further progress in treating TNBC, its therapeutic effect is still not optimistic. Ataxia telangiectasia mutated (ATM) is a critical factor in the DNA damage response (DDR) pathway, which is associated with the development of tumors. Recent studies have found that it can regulate the tumor immune microenvironment, affecting ICB responsiveness. Inhibition of ATM could enhance ICB therapy by promoting mitochondrial DNA cytoplasmic leakage and activating the innate immune signaling pathway. To explore the effect of ATM siRNA(siATM) on the ICB responsiveness of TNBC, we designed and synthesized nanoparticles using 1,2-dioleoyl-glycero-3-phosphatidylcholine (DOPC) liposomes to deliver siATM. In vitro and in vivo experiments demonstrated that DOPC/siATM could enhance the ability of siRNA to enter tumor cells and effectively inhibit the expression of ATM protein. Our study found that nanoparticles carrying siATM could activate cytotoxic T lymphocytes and regulate the immunosuppressive tumor microenvironment (ITM) by activating the cGAS-STING pathway. Its combination with aPD-1 may be a potential way to improve the efficacy of TNBC.

Evaluation of a novel primer containing isocyanate group on dentin bonding durability.

OBJECTIVES: To evaluate the benefits of a novel dentin-bonding primer, namely, isocyanate-terminated urethane methacrylate precursor (UMP), which can form covalent bonds with demineralized dentin collagen. METHODS: The synthesized and purified UMP monomer was characterized and tested its effects on the degree of conversion (DC) and wettability of an acetone-based dental adhesive. Then UMP primers of different concentrations were formulated and used to prepare adhesive specimens, which were compared with solvent-treated groups. Primer-treated specimens with and without aging were also compared. To evaluate the bonding interface, microtensile strength tests, nano-indentation tests and nanoleakage- eavaluation were performed using a field-emission scanning electron microscope and nano-indenter. Data were analyzed using SPSS 20.0 software with significance set at α = 0.05 using one-way analysis of variance (ANOVA) and two-way ANOVA to characterize the effects of the primer. RESULTS: Treatment with the UMP primer promoted the DC and wettability of the adhesive on the demineralized dentin surface (P < 0.05); it also increased the bond strength of the aged dentin bonding interface (P < 0.05). Nanoleakage was reduced; the bonding interface became more stable, and the continuity and strength of the hybrid layer improved (P < 0.05) following UMP treatment. The application of 5 mM UMP as a primer for dentin bonding could lead to a stable bonding interface and long-lasting bonding effects. SIGNIFICANCE: The use of 5 mM UMP primer developed in this study could improve dentin bonding durability and has excellent clinical application prospects.

A mussel glue-inspired monomer-etchant cocktail for improving dentine bonding.

OBJECTIVES: The humid oral environment adversely affects the interaction between a functionalised primer and dentine collagen after acid-etching. Robust adhesion of marine mussels to their wet substrates instigates the quest for a strategy that improves the longevity of resin-dentine bonds. In the present study, an etching strategy based on the incorporation of biomimetic dopamine methacrylamide (DMA) as a functionalised primer into phosphoric acid etchant was developed. The mechanism and effect of this DMA-containing acid-etching strategy on bond durability were examined. METHODS: Etchants with different concentrations of DMA (1, 3 or 5 mM) were formulated and tested for their demineralisation efficacy. The interaction between DMA and dentine collagen, the effect of DMA on collagen stability and the collagenase inhibition capacity of the DMA-containing etchants were evaluated. The effectiveness of this new etching strategy on resin-dentine bond durability was investigated. RESULTS: All etchants were capable of demineralising dentine and exposing the collagen matrix. The latter strongly integrated with DMA via covalent bond, hydrogen bond and Van der Waals' forces. These interactions significantly improve collagen stability and inhibited collagenase activity. Application of the etchant containing 5 mM DMA achieved the most durable bonding interface. CONCLUSION: Dopamine methacrylamide interacts with dentine collagen in a humid environment and improves collagen stability. The monomer effectively inactivates collagenase activity. Acid-etching with 5 mM DMA-containing phosphoric acid has the potential to prolong the longevity of bonded dental restorations without compromising clinical operation time. CLINICAL SIGNIFICANCE: The use of 5 mM dopamine methacrylamide-containing phosphoric acid for etching dentine does not require an additional clinical step and has potential to improve the adhesive performance of bonded dental restorations.

Development of robust organosilica membranes for reverse osmosis.

Hybrid organically bridged silica membranes have attracted considerable attention because of their high performances in a variety of applications. Development of robust reverse osmosis (RO) membranes to withstand aggressive operating conditions is still a major challenge. Here, a new type of microporous organosilica membrane has been developed and applied in reverse osmosis. Sol-gel derived organosilica RO membranes reject isopropanol with rejection higher than 95%, demonstrating superior molecular sieving ability for neutral solutes of low molecular weight. Due to the introduction of an inherently stable hybrid network structure, the membrane withstands higher temperatures in comparison with commercial polyamide RO membranes, and is resistant to water to at least 90 °C with no obvious changes in filtration performance. Furthermore, both an accelerated chlorine-resistance test and Fourier transform infrared analysis confirm excellent chlorine stability in this material, which demonstrates promise for a new generation of chlorine-resistant RO membrane materials.

Effective separation of water-DMSO through solvent resistant membrane distillation (SR-MD).

The treatment of organic waste or wastewater with high organic solvent content has been challenging in industries as it cannot be done effectively using conventional wastewater treatment technologies such as biodegradation and advanced oxidation process. Solvent resistant membrane distillation (SR-MD) was proposed as an energy-efficient alternative to treat these waste streams but its application is hampered by the lack of solvent-resistant membranes, and there is a research gap in studying the feeds with water-solvent mixtures. In this work, ceramic tubular membranes with different pore sizes and structures were molecularly grafted with 1H,1H,2H,2H-perfluorodecyltriethoxysilane to obtain hydrophobic ceramic membranes for SR-MD. The modified membranes exhibited excellent hydrophobicity and solvent resistant properties, and they were tested for SR-MD performance with a wide range of dimethyl sulfoxide (DMSO) feed concentrations, from 3.5 to 85 wt%. The membranes exhibited a high DMSO rejection of >98% and the separation factor of >170, with permeation flux >4.4 kg m-2 h-1 when the DMSO concentration in feed was below 65 wt%. The separation performance was found strongly dependent on the evaporation step and the vapour-liquid equilibrium near the interface. The DMSO rejection was also comparable to pervaporation while the permeation flux was much higher at the feed concentration of 50 wt%. This study establishes the strategy of using SR-MD as a promising membrane process in treating complex industrial wastes with high organic solvent content.

Bioaugmentation improves the anaerobic co-digestion of cadmium-containing plant residues and cow manure.

Phytoremediation causes a large quantity of phytoremediation residues rich in heavy metals (HMs). This kind of plant residue can be used as a substrate for anaerobic digestion (AD) to reduce the content of HM-containing biomass, but high concentrations of HMs will inhibit the digestion efficiency and reduce the conversion efficiency of plant residues. Bioaugmentation may be an effective method to improve the degradation efficiency and methane yield of plant residues rich in HMs. In this study, a cellulose-degrading anaerobic bacteria Paracoccus sp. Termed strain LZ-G1 was isolated from cow dung, which can degrade cellulose and simultaneously adsorb Cd2+. The Cd2+ (10 mg/L)-adsorbtion efficiency and cellulose (463.12 g/kg)-degradation rate were 65.1 % and 60.59 %, respectively. In addition, using the strain LZ-G1 bioaugmented Cd2+-containing plant residues and cow manure mixed AD system, the system's biogas and methane production significantly increased (98.97 % and 142.03 %, respectively). During the AD process, the strain LZ-G1 was successfully colonized in the digestion system. Furthermore, the microbial community analysis revealed that LZ-G1 bioaugmentation alleviates the toxicity of free Cd2+ to the microbial community in the AD system, regulates and restores the archaea genus dominant in the methanogenesis stage, and restores the relative abundance of dominant bacteria associated with biomass hydrolysis. The restoration of the microbial community increased the biogas yield and methane production rate. Thus, bioaugmentation provides an easy and a feasible method for the actual on-site treatment of HM-rich phytoremediation residues.

Recent Advances in Oral Nano-Antibiotics for Bacterial Infection Therapy.

Bacterial infections are the main infectious diseases and cause of death worldwide. Antibiotics are used to treat various infections ranging from minor to life-threatening ones. The dominant route to administer antibiotics is through oral delivery and subsequent gastrointestinal tract (GIT) absorption. However, the delivery efficiency is limited by many factors such as low drug solubility and/or permeability, gastrointestinal instability, and low antibacterial activity. Nanotechnology has emerged as a novel and efficient tool for targeting drug delivery, and a number of promising nanotherapeutic strategies have been widely explored to overcome these obstacles. In this review, we explore published studies to provide a comprehensive understanding of the recent progress in the area of orally deliverable nano-antibiotic formulations. The first part of this article discusses the functions and underlying mechanisms by which nanomedicines increase the oral absorption of antibiotics. The second part focuses on the classification of oral nano-antibiotics and summarizes the advantages, disadvantages and applications of nanoformulations including lipid, polymer, nanosuspension, carbon nanotubes and mesoporous silica nanoparticles in oral delivery of antibiotics. Lastly, the challenges and future perspective of oral nano-antibiotics for infection disease therapy are discussed. Overall, nanomedicines designed for oral drug delivery system have demonstrated the potential for the improvement and optimization of currently available antibiotic therapies.

Precise and tunable time-controlled drug release system using layer-by-layer films as erodible coatings.

Unlike conventional drug carriers, time-controlled release systems do not release drug immediately, but start to release drug after a predetermined lag time. Coating a drug-loaded core with an erodible barrier is a valid way to defer drug release, however, the complicated erosion behavior of the erodible coatings makes it difficult to predict and tune the lag time. Herein we proposed that dynamic layer-by-layer films, using hydrogen-bonded poly(ethylene glycol)/tannic acid (PEG/TA) film as an example, are ideal erodible coatings, because their erosion mechanism is clear and simple, and they disintegrate at constant rate. As a proof, we demonstrated that the release of bovine serum albumin (BSA) from BMS spheres can be deferred by PEG/TA coating. More importantly, the lag time can be simply tuned by the thickness of the coating. By mixing bimodal mesoporous silica (BMS) spheres coated with different thickness PEG/TA films, multiple pulse release was achieved. Similar release patterns were also successfully achieved in vivo.

Differentiation of Neural Crest Stem Cells in Response to Matrix Stiffness and TGF-ß1 in Vascular Regeneration.

The neural crest stem cells derived from human induced pluripotent stem cells (iPSC-NCSCs) are a valuable autologous cell source for tissue engineering and regenerative medicine. In this study, we investigated how iPSC-NCSCs could be regulated to regenerate arteries by microenvironmental factors, including the physical factor of matrix stiffness, and the chemical factor of transforming growth factor beta-1 (TGF-ß1). We found that, compared to soft substrate, stiff substrate drove iPSC-NCSCs differentiation into smooth muscle cells, which was further enhanced by TGF-ß1. To investigate the regulatory role of TGF-ß1 in vivo, we fabricated vascular grafts composed of electrospun nanofibrous scaffolds, collagen gel, iPSC-NCSCs, and TGF-ß1, and implanted them into athymic rats. The results showed that TGF-ß1 significantly promoted extracellular matrix synthesis and increased mechanical strength of vascular grafts. This study presents a proof of concept that iPSC-NCSCs can be used as a promising autologous cell source for vascular regeneration when combined with physical and chemical engineering.

Eszopiclone for the treatment of primary insomnia: a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials.

STUDY OBJECTIVE: In this study, we performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the efficacy and safety of eszopiclone for the treatment of primary insomnia. METHODS: We searched MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials and PubMed from inception to June 2018. Additionally, we searched the ClinicalTrials.gov trials register for other relevant trials. According to participants, intervention, comparison, outcome (PICO) criteria, studies were included that focused on: adults diagnosed with primary insomnia, aged 18-65 and > 65 years; eszopiclone for the treatment of primary insomnia; comparison were made between eszopiclone and placebo; as well as primary outcomes, secondary outcomes, and adverse effects. RESULTS: A total of six randomized trials involving 2809 patients with primary insomnia were included in our analysis. Our analysis suggested that eszopiclone was associated with significant improvements in subjective sleep latency, wake after sleep onset, number of awakenings, total sleep time at one week, two weeks, one month, three months and six months. Meanwhile, eszopiclone was associated with increased quality of sleep, ability to function, daytime alertness and sense of physical well-being at one week, one month, three months and six months. Dizziness and unpleasant taste were the most common adverse effects in elderly subgroup. Alternately, non-elderly patients may be more prone to adverse effects such as infection, pharyngitis, somnolence, unpleasant taste and dry mouth. CONCLUSION: This meta-analysis showed that eszopiclone is an effective and safe therapy option for patients with primary insomnia, especially in elderly patients. However, due to the high clinical heterogeneity in some outcomes, further standardized preparation, large-scale and rigorously designed trials are needed.

High proportion of coxsackievirus B3 genotype A in hand, foot and mouth disease in Zhenjiang, China, 2011-2016.

BACKGROUND: Hand, foot and mouth disease (HFMD) is usually caused by EVA71 and CVA16 except for a few cases that are caused by non-EVA71 non-CAV16 enteroviruses. Coxsackievirus B3 (CVB3) is mostly associated with myocarditis, occasionally with HFMD. METHODS: The partial VP1 gene of enteroviruses were amplified and sequenced from 610 throat swabs from clinically confirmed HFMD children. All available CVB3 near full-length genomic and VP1 sequences were downloaded from GenBank. Phylogenetic and distance analyses were performed using MEGA 7.0. RESULTS: A total of 238 partial VP1 sequences were obtained, including 93 EVA71 (39%), 79 CAV16 (33%), 29 CVB3 (12%), 24 CVA6 (10%), and 13 other enterovirus serotypes (5.5%). CVB3 is classified into seven genotypes A-G according to phylogenetic and distance analyses. All CVB3 strains from Zhenjiang belonged to genotype A. In contrast to other genotypes that are prevalent in Europe and other regions of China, and often associated with aseptic meningitis and myocarditis, CVB3 genotype A strains identified in Zhenjiang were only detected among HFMD patients. CONCLUSIONS: This high prevalence of CVB3 genotype A among HFMD children has never been reported. This phenomenon has revealed a new epidemic trend of CVB3 among HFMD in China, and it has epidemiological implications for monitoring the epidemic risk of CVB3.

Distribution of an intravenous injectable nimodipine nanosuspension in mice.

The distribution of an intravenous injectable nimodipine nanosuspension with mean particle size of both 300 and 650 nm in mice was systemically investigated compared with that of a nimodipine ethanol formulation (Nimotop) and a nanosuspension coated with Tween-80. The results showed that the 650-nm nanoparticles provided significantly higher drug concentrations in the liver, spleen and lungs because of their capture by Kupffer cells in the mononuclear phagocyte system, but lower drug concentrations in the brain compared with Nimotop and smaller nanoparticles. These nanoparticles failed to give increased brain concentrations even when coated with Tween-80. The 300-nm nanoparticles could effectively increase drug concentrations in the brain and remarkably reduce drug concentrations in the liver, spleen and lungs, indicating that the nimodipine nanosuspension may be a promising formulation with no ethanol, but the particle size must be small.

Lignin depolymerization and utilization by bacteria.

Lignin compound wastes are generated as a result of agricultural and industrial practices. Microorganism-mediated bio-catalytic processes can depolymerize and utilize lignin eco-friendly. Although fungi have been studied since several decades for their ability to depolymerize lignin, strict growth conditions of fungus limit it's industrial application. Compared with fungi, bacteria can tolerate wider pH, temperature, oxygen ranges and are easy to manipulate. Several studies have focused on bacteria involved in the process of lignin depolymerization and utilization. Pseudomonas have been used for paper mill wastewater treatment while Rhodococcus are widely reported to accumulate lipid. In this review, the recent studies on bacterial utilization in paper wastewater treatment, lignin conversion to biofuels, bioplastic, biofertilizers and other value-added chemicals are summarized. As bacteria possess remarkable advantages in industrial production, they may play a promising role in the future commercial lignin utilization.

A Novel DNA Aptamer for Dual Targeting of Polymorphonuclear Myeloid-derived Suppressor Cells and Tumor Cells.

Aptamers have the potential to be used as targeting ligands for cancer treatment as they form unique spatial structures. Methods: In this study, a DNA aptamer (T1) that accumulates in the tumor microenvironment was identified through in vivo selection and validation in breast cancer models. The use of T1 as a targeting ligand was evaluated by conjugating the aptamer to liposomal doxorubicin. Results: T1 exhibited a high affinity for both tumor cells and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Treatment with T1 targeted doxorubicin liposomes triggered apoptosis of breast cancer cells and PMN-MDSCs. Suppression of PMN-MDSCs, which serve an immunosuppressive function, leads to increased intratumoral infiltration of cytotoxic T cells. Conclusion: The cytotoxic and immunomodulatory effects of T1-liposomes resulted in superior therapeutic efficacy compared to treatment with untargeted liposomes, highlighting the promise of T1 as a targeting ligand in cancer therapy.

Quantitative anatomic study of atlanto-odontoid joint and design of an artificial atlanto-odontoid joint for the orthopedic clinic.

OBJECTIVE: To observe and measure morphological parameters of the Chinese atlanto-odontoid joint anatomically in order to provide an anatomic data for designing artificial atlanto-odontoid joint used for substituting the destroyed atlanto-odontoid joint in the orthopedic clinic. METHODS: The relative anatomic parameters of 32 sets of fresh Chinese adults'atlanto-odontoid joint specimens were measured with a digital caliper and a goniometer, including the width of anterior arch of atlas (AW), the thickness of atlas at the junction of anterior arch and lateral mass (AD), the thickness and height of anterior tubercle of atlas (AT and AH), the middle height, length and width of the lateral mass (MHL, L and LW), the height, transverse and anteroposterior distance of odontoid process (DH, DW and DD), the retroversion angle of odontoid process (beta degree),the facial angle of odontoid process (theta degree) and so on. The data were statistically analyzed in order to ascertain the morphological parameter ranges of artificial atlanto-odontoid joint. An artificial atlanto-odontoid joint was designed according to these data. The operations of anlanto-odontoid joint arthroplasty were conducted in 3 cases of adult cadaver specimens. RESULTS: The width of AW was (20.45+/-1.53) mm, AD (3.91+/-1.32) mm, AT and AH (9.43+/-1.93)mm and (10.23+/-1.32) mm, respectively, MHL and LW (13.68+/-1.38) mm and (12.98+/-1.52) mm, respectively, DH (15.25+/-2.11) mm, DW and DD (9.69+/-1.38) mm and (11.26+/-1.02) mm, respectively, beta degree (12.23+/-4.27) degree, theta degree (65.48+/-2.17) degree. The prosthesis was composed of atlas part, axis part and accessories. Neither the vertebral artery nor the medulla oblongata was injured. CONCLUSIONS: The design of artificial atlanto-odontoid joint is feasible according to these parameters. The artificial joint can not only rebuild the stability of atlanto-axial joint, but also reserve the rotation function between atlas and axis. Every part of the joint has their own parameter ranges in purpose to firm fixation, convenient operation and good motion without further injury. The prosthesis can be used for patients suffering from compression of medulla oblongata and resection of dens when it is required.