Advanced Smart Biomaterials for Regenerative Medicine and Drug Delivery Based on Phosphoramidite Chemistry: From Oligonucleotides to Precision Polymers.

Over decades of development, while phosphoramidite chemistry has been known as the leading method in commercial synthesis of oligonucleotides, it has also revolutionized the fabrication of sequence-defined polymers (SDPs), offering novel functional materials in polymer science and clinical medicine. This review has introduced the evolution of phosphoramidite chemistry, emphasizing its development from the synthesis of oligonucleotides to the creation of universal SDPs, which have unlocked the potential for designing programmable smart biomaterials with applications in diverse areas including data storage, regenerative medicine and drug delivery. The key methodologies, functions, biomedical applications, and future challenges in SDPs, have also been summarized in this review, underscoring the significance of breakthroughs in precisely synthesized materials.

[Thoughts on the Biological Evaluation of Biodegradable Cardiovascular Implants].

In recent years, new degradable materials have been applied to cardiovascular implants. Cardiovascular implants with different physicochemical properties and degradation properties have special endpoints for their biological evaluation. In this study, the end points of biological evaluation of degradable cardiovascular implants were reviewed by taking vascular stents and occluders as examples.

[Evaluation of Lubrication Coatings for Intravascular Catheters, Wires, and Delivery System].

Lubrication coating is widely used to reduce the friction between the interventional devices and the blood vessels, improves the surface biocompatibility of the interventional device, and also brings the coating stability problems and related risks. This paper describes the coating-related content from the equipment description, performance verification, technical requirements, etc., to reduce the risk of the coating to an acceptable level.

Short versus standard implants for single-crown restorations in the posterior region: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Whether implant-supported crowns on short or standard implants have similar clinical outcomes in the posterior alveolar bone is unclear. PURPOSE: The purpose of this systematic review and meta-analysis was to compare clinical outcomes, including survival rates, marginal bone loss (MBL), and complications associated with short implants and standard implants supporting a single crown in the posterior alveolar bone. MATERIAL AND METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) principles and was registered with PROSPERO (CRD42018112978). The authors identified eligible trials published before August 2019 by searching PubMed, EMBASE, and the Cochrane Library. Only randomized controlled trials (RCTs) were included in the study, and quality assessment was performed by using the Cochrane Collaboration Risk of Bias tool. Relevant information was extracted by using a standardized form, and a meta-analysis was performed by using a software program. RESULTS: A total of 1954 references were identified. Five eligible trials were included in the quantitative synthesis. The survival rate of the short implants (≤6 mm) was similar to that of longer implants (>6 mm) in the short term (P=.72; RR: 0.99; 95% CI: 0.97-1.02); however, long-term follow-up showed that short implants had a poorer survival rate than standard implants (P=.01; RR: 0.94; 95% CI: 0.90-0.99). There was no significant difference in the MBL (P=.94; MD: 0.00; 95% CI: -0.10 to 0.11). CONCLUSIONS: The present study suggested that, although short implants have a higher crown-to-implant (C/I) ratio, they do not affect MBL. However, long-term follow-up comparisons indicated that short implants (≤6 mm) have a poorer survival rate than standard implants (>6 mm) (P=.01). Nonsplinted crowns supported by short implants should be used with caution in the posterior alveolar bone.

An Inorganic Biopolymer Polyphosphate Controls Positively Charged Protein Phase Transitions.

Polyphosphate (PolyP) is one of the most compact inorganic polyanionic biopolymers that participates in various physiological processes. However, the mechanism of the interaction between polyP and proteins remains poorly understood. Herein, we report that polyP can interact with positively charged green fluorescent protein, +36GFP, resulting in liquid-liquid phase separation (LLPS) by intermolecular electrostatic interactions in cells. Upon nutrient deprivation, genetically engineered Citrobacter freundii accumulates intracellular polyP at a rate of 210 µm min-1 , resulting in the compartmentation of +36GFP at the cell poles within 1 h. Medium chain-length polyP (60-mer) could induce the formation of +36GFP coacervates in vitro at a protein concentration as low as 200 nm, which is of the same magnitude as native proteins. In contrast, shorter polyP (14-mer) could not induce LLPS under the same conditions. This may offer a general approach to manipulate protein-protein interactions through LLPS.

Synergistic Effects of Selenophene and Extended Ladder-Type Donor Units for Efficient Polymer Solar Cells.

Two pairs of polymer donor materials based on indacenodithiophene (IDT) and indacenodithieno[3,2-b]thiophene (IDTT) as the donor units are synthesized. Thiophene or selenophene is introduced as the π-bridge units and electron-deficient fluorine-substituted quinoxaline is used as acceptor unit. Selenophene-containing polymers PIDT-DFQ-Se and PIDTT-DFQ-Se show redshifted absorption and narrower bandgaps. Combined with IDTT donor unit, PIDTT-DFQ-Se shows the highest absorption coefficient. Both the IDTT unit and selenophene unit have positive effects on the hole mobilities, making PIDTT-DFQ-Se the highest one. The best power conversion efficiency of 7.4% is obtained from devices based on PIDTT-DFQ-Se:[6,6]-phenyl C71 butyric acid methyl ester (PC71 BM) with a Jsc of 12.6 mA cm-2 , a Voc of 0.89 V, and a fill factor (FF) of 0.66.

The Influence of Oxygen Atoms on Conformation and π-π Stacking of Ladder-Type Donor-Based Polymers and Their Photovoltaic Properties.

A novel ladder-type donor pyran-bridged indacenodithiophene (IDTP) is developed by introducing two oxygen atoms into indacenodithiophene unit. IDTP possesses a twisted backbone and leads to facially asymmetric arrangement of side chains, resulting in enhanced local π-π stacking of according polymer poly[(5,5,11,11-tetrakis(4-octylphenyl)-5,11-dihydrothieno[2',3':5,6]pyrano[3,4-g]thieno[3,2-c]isochromene)-alt-4,7-(5-fluoro-2,1,3-benzothiadiazole)] (PIDTP)-FBT, which shows extended absorption range. Moreover, oxygen atoms render deeper highest occupied molecular orbital (HOMO) levels of poly[indacenodithiophene-alt-4,7-(5-fluoro-2,1,3-benzothiadiazole)] (PIDTP)-FBT compared with PIDT-FBT, therefore bringing a higher open-circuit voltage (Voc ).

Preparation of Amyloid Immuno-Nanoparticles as Potential MRI Contrast Agents for Alzheimer's Disease Diagnosis.

Alzheimer's disease (AD) is the most common form of dementia which is caused by accumulation in the brain of plaques made up of amyloid beta-peptide (Abeta). Research on nanosized systems indicated that nanoparticles (NPs) could pass across the blood-brain barrier (BBB) and improve the visibility of internal body structures in magnetic resonance imaging (MRI), which made it possible to aid the early diagnosis of AD. In this research study we synthesized magnetite nanoparticles by high-temperature solution-phase reaction, transferred into water based on a ligand exchange process and coated with meso-2,3-dimercaptosuccinic (DMSA). Subsequently, the anti-amyloid Abeta immunomagnetic nanoparticles (IMNPs) were prepared by grafting anti-amyloid antibodies on the surface of the DMSA-coated magnetic nanoparticles (MNPs). The enzyme linked immunosorbent assay (ELISA) method was introduced to evaluate the IMNPs activity and conjugation amount of antibodies. The biocompatibility of the IMNPs was tested by colony-forming assay. The results showed that the anti-amyloid Abeta IMNPs were biocompatible and biologically active, as well as effective in enhancing MRI solution, indicating that the IMNPs could be used as potential MRI contrast agents and targeted carriers for AD early diagnosis and therapy.

Anatomic study on mental canal and incisive nerve canal in interforaminal region in Chinese population.

PURPOSE: This study was aimed to detect the positions of mental canal and incisive nerve canal as well as the prolongation of mandibular canal in interforaminal region in Chinese population to supply the reference data of the surgical safe zone in chin for clinicians. MATERIALS AND METHODS: A total of 80 formalin-fixed semi-mandibles of Chinese adult cadavers were dissected, the positions and courses of mental canal and incisive nerve canal as well as the prolongation of mandibular canal in interforaminal region were measured. RESULTS: The mental foramina were present in all cases (100 %), and most of them were located below 2nd premolar (58.75 %). Accessory mental foramina were observed in 5 %. The anterior end of mandibular canal, extending along the course of 7.37 ± 1.10 mm above the lower border of mandible to interforaminal region about 3.54 ± 0.70 mm medial to the mental foramen, most often ended below between the two premolars (73.75 %), where it continued as the incisive nerve canal (100 %) and the mental canal (96.25 %). Mental canal, with the wall formed by compact bone, being 2.60 ± 0.60 mm in diameter and 4.01 ± 1.20 mm in length, opened into mental foramen. Incisive nerve canal, with the wall formed by thin compact bone and/or partly or completely by spongy bone, being 1.76 ± 0.27 mm in diameter and 24.87 ± 2.23 mm in length, extended to the incisor region along the course of 9.53 ± 1.43 mm above the lower border of mandible, and most often ended below the lateral incisor (70.00 %). CONCLUSION: This research recommended for chin operations in Chinese population: the surgical safe zone could be set in the region about over 4 mm anterior to the mental foramen, and over 12 mm above inferior border of mandible for anterior alveolar surgery, or within 9 mm above inferior border of mandible for genioplasty.

Genetically Programmed Temperature-Responsive Barnacle-Derived Protein with an Enhanced Adhesion Ability.

There is an emerging strong demand for smart environmentally responsive protein-based biomaterials with improved adhesion properties, especially underwater adhesion for potential environmental and medical applications. Based on the fusion of elastin-like polypeptides (ELPs), SpyCatcher and SpyTag modules, biosynthetic barnacle-derived protein was genetically engineered and self-assembled with an enhanced adhesion ability and temperature response. The water resistance ability of the synthetic protein biopolymer with a network structure increased to 98.8 from 58.5% of the original Cp19k, and the nonaqueous adhesion strength enhanced to 1.26 from 0.68 MPa of Cp19k. The biopolymer showed an improved adhesion ability toward hydrophilic and hydrophobic surfaces as well as diatomite powders. The combination of functional module ELPs and SpyTag/SpyCatcher could endow the biosynthetic protein with temperature response, an insoluble form above 42 °C and a soluble form at 4 °C. The combinational advantages including temperature response and adhesion performance make the self-assembled protein an excellent candidate in surgical adhesion, underwater repair, and surface modification of various coatings. Distinct from the traditional approach of utilizing solely ELPs, the integration of short ELPs with Spy partners exhibited a synergistic enhancement in the temperature response. The synergistic effects of two functional modules provide a technical method and insight for designing smart self-assembled protein-based biopolymers.

Adsorption behavior and mechanism of heavy metals onto microplastics: A meta-analysis assisted by machine learning.

Microplastics (MPs) have the potential to adsorb heavy metals (HMs), resulting in a combined pollution threat in aquatic and terrestrial environments. However, due to the complexity of MP/HM properties and experimental conditions, research on the adsorption of HMs onto MPs often yields inconsistent findings. To address this issue, we conducted a comprehensive meta-analysis assisted with machine learning by analyzing a dataset comprising 3340 records from 134 references. The results indicated that polyamide (PA) (ES = -1.26) exhibited the highest adsorption capacity for commonly studied HMs (such as Pb, Cd, Cu, and Cr), which can be primarily attributed to the presence of C=O and N-H groups. In contrast, polyvinyl chloride (PVC) demonstrated a lower adsorption capacity, but the strongest adsorption strength resulting from the halogen atom on its surface. In terms of HMs, metal cations were more readily adsorbed by MPs compared with metalloids and metal oxyanions, with Pb (ES = -0.78) exhibiting the most significant adsorption. As the pH and temperature increased, the adsorption of HMs initially increased and subsequently decreased. Using a random forest model, we accurately predicted the adsorption capacity of MPs based on MP/HM properties and experimental conditions. The main factors affecting HM adsorption onto MPs were HM and MP concentrations, specific surface area of MP, and pH. Additionally, surface complexation and electrostatic interaction were the predominant mechanisms in the adsorption of Pb and Cd, with surface functional groups being the primary factors affecting the mechanism of MPs. These findings provide a quantitative summary of the interactions between MPs and HMs, contributing to our understanding of the environmental behavior and ecological risks associated with their correlation.

HBV-miR-3 is closely related to HBV replication and strongly predictive of HBeAg seroconversion in PegIFN-α treated patients.

HBV-miR-3 is encoded by HBV and takes part in pathogenesis of HBV-related liver disease. Whether HBV-miR-3 has a relationship with HBV replication and is predictive of PegIFN-α treatment response is still unknown. HBV-miR-3 quantification is based on qRT-PCR. The relationship of HBV-miR-3 and HBV replication, and predictive value of HBV-miR-3 were evaluated in a cohort of 650 HBeAg positive patients from a multi-center, randomized phase III clinical trial for the study of PegIFN-a2b. HBV-miR-3 is significantly positively related to HBVDNA, HBVpgRNA, HBeAg and HBsAg at baseline and at all the different time points during PegIFN-α treatment. Both univariate regression analyses and multivariate logistic regression analyses showed HBV-miR-3 is a predictor of HBeAg seroconversion in the patients treated with PegIFN-α at weeks of 0, 12, and 24. 70.0% of patients with HBV-miR-3 < 3log at week 12 achieved HBeAg seroconversion, otherwise, with HBV-miR-3 > 6log at week 12 no patient obtained HBeAg seroconversion. Conbination of HBV-miR-3 and HBeAg is more strongly predictive of HBeAg seroconversion (83.64%) at week 12. HBV-miR-3 is new biomarker for HBV replication and positively correlated to HBV replication. HBV-miR-3 is also an early predictor of HBeAg seroconversion in the patients treated with PegIFN-α.

MicroRNA-195 liposomes for therapy of Alzheimer's disease.

The complex etiologies and mechanisms of Alzheimer's disease (AD) underscore the importance for devising multitarget drugs to achieve effective therapy. MicroRNAs (miRNAs) are capable of concurrently regulating the expression of multiple proteins by selectively targeting disease- associated genes in a sequence-specific fashion. Nonetheless, as RNA-based drugs, their stability in the circulation and capacity of traversing the blood-brain barrier (BBB) is largely compromised, thereby limiting their potential clinical applications. In this study, we formulated the nanoliposomes encapsulating polyethyleneimine (PEI)/miR-195 complex (DPMT@PEI/miR-195) that was engineered through dual modifications to contain P-aminophenyl-alpha-d-mannopyranoside (MAN) and cationic cell-penetrating peptide (TAT). DPMT@PEI/miR-195 exhibited the enhanced BBB- and cell membrane penetrating capability. As expected, we observed that DPMT@PEI/miR-195 administered through intravenous tail injection of produced greater effectiveness than donepezil and the same range of effect as aducanumab in alleviating the cognitive decline in 7-month-old APP/PS1 mice. Moreover, the combination treatment with DPMT@PEI/miR-195 and donepezil effectively ameliorated the deterioration of cognition in 16-month-old APP/PS1 mice, with enhanced effects than either DPMT@PEI/miR-195 or donepezil alone. Furthermore, DPMT@PEI/miR-195 effectively attenuated the positive signals of Aß, AT8, and CD68 in APP/PS1 mice without notable side effects. Our findings indicate DPMT@PEI/miR-195 as a promising potentially new agent or approach for the prophylaxis and treatment of early and advanced stages of Alzheimer's disease.

Effect of Percutaneous Endoscopic Gastrostomy on Quality of Life after Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma: A Cross-Sectional Study.

(1) Background: Prophylactic percutaneous endoscopic gastrostomy (PEG) maintained nutritional status and improved survival of patients with locally advanced nasopharyngeal carcinoma (LA-NPC). However, the role of PEG in patients' quality of life (QoL) is still controversial. We aimed to investigate the effect of PEG on the QoL of patients with LA-NPC without progression. (2) Methods: Patients with LA-NPC between 1 June 2010 and 30 June 2014 in Fujian Cancer Hospital were divided into PEG and non-PEG groups. The QoL Questionnaire core 30 (QLQ-C30), incidence of adverse effects, weight, and xerostomia recovery were compared between the two groups of patients without progression as of 30 June 2020. (3) Results: No statistically significant difference in the scores of each QLQ-C30 scale between the two groups (p > 0.05). The incidence of xerostomia was higher in the PEG group than in the non-PEG group (p = 0.044), but the association was not seen after adjusting for gender, age, T, and N stage (OR: 0.902, 95%CI: 0.485−1.680). No significant difference in the incidence of other adverse effects as well as in weight and dry mouth recovery (p > 0.05). (4) Conclusion: PEG seems not to have a detrimental effect on long-term Qol, including the self-reported swallowing function of NPC patients without progressive disease.

Aero-Engine Blade Cryogenic Cooling Milling Deformation Simulation and Process Parameter Optimization.

For the machining of aero-engine blades, factors such as machining residual stress, milling force, and heat deformation can result in poor blade profile accuracy. To address this issue, simulations of blade milling were completed using DEFORM11.0 and ABAQUS2020 software to analyze blade deformation under heat-force fields. Process parameters such as spindle speed, feed per tooth, depth of cut, and jet temperature are used to design both a single-factor control and BBD test scheme to study the influence of jet temperature and multiple changes in process parameters on blade deformation. The multiple quadratic regression method was applied to establish a mathematical model correlating blade deformation with process parameters, and a preferred set of process parameters was obtained through the particle swarm algorithm. Results from the single-factor test indicated that blade deformation rates were reduced by more than 31.36% in low-temperature milling (-190 °C to -10 °C) compared with dry milling (10 °C to 20 °C). However, the margin of the blade profile exceeded the permissible range (±50 µm); therefore, the particle swarm optimization algorithm was used to optimize machining process parameters, resulting in a maximum deformation of 0.0396 mm when the blade temperature was -160 °C~-180 °C, meeting the allowable blade profile deformation error.

Downstream processing of biotechnological produced succinic acid.

Succinic acid is a promising chemical which has a wide range of applications and can be biologically produced. The separation of succinic acid from fermentation broth makes more than 50 % of the total costs in their microbial production. This review summarizes the present state of methods studied for the recovery and purification of biologically produced succinate. Previous studies on the separation of succinic acid primarily include direct crystallization, precipitation, membrane separation, extraction, chromatography, and in situ separation. No single method has proved to be simple and efficient, and improvements are especially needed with regard to yield, purity, and energy consumption. It is argued that separation technologies coupled with upstream technology, in situ product removal, and biorefining strategy deserve more attentions in the future.

miR-140 inhibits osteogenic differentiation of human periodontal ligament fibroblasts through ras homolog gene family, member A -transcriptional co-activator with PDZ-binding motif pathway.

Osteogenesis induced by mechanical stretch is the main factor affecting the orthodontic treatment. Due to the masticatory force transmitted by tooth, human periodontal ligament fibroblasts (hPDLFs) could enhance osteogenic differentiation, and remolding of periodontal. Therefore, in-depth study of hPDLFs osteogenic differentiation and its regulatory mechanism is helpful in the understanding of periodontal remolding promoted by orthodontic force. In the present study, 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide showed that miR-140 inhibited the viability of hPDLFs cells. Moreover, we provided evidence that miR-140 inhibited alkaline phosphatase (ALP) activity, Alizarin Red S (ARS) activity and the mRNA expression of osteogenesis associated genes, including ALP, runt-related transcription factor 2, collagen 1, and osteocalcin. Besides, double-luciferase reporter result demonstrated that Ras homolog gene family, member A (RhoA) was a downstream target gene of miR-140, and by inhibiting RhoA-transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway, miR-140 suppressed the osteogenesis differentiation of hPDLFs. Furthermore, overexpression of RhoA or TAZ promoted ALP activity, ARS activity and osteogenesis associated genes expression, which was inhibited by miR-140 mimics. Our findings not only provided a possible mechanism of hPDLFs osteogenic differentiation but also proposed the clinical application of miR-140 inhibitor to target RhoA-TAZ for orthodontic treatment.

3D nitrogen-doped carbon nanofoam arrays embedded with PdCu alloy nanoparticles: Assembling on flexible microelectrode for electrochemical detection in cancer cells.

In this work, we developed a novel and facile strategy for the synthesis of a highly active and stable electrocatalyst based on PdCu alloy nanoparticles (PdCu-ANPs) embedded in 3D nitrogen-doped carbon (NC) nanofoam arrays (NFAs), which were assembled on flexible carbon fiber (CF) microelectrode for in situ sensitive electrochemical detection of biomarker H2O2 in cancer cells. Our results showed that NC-NFAs support possessed a unique hierarchically porous architecture by integrating the macrospores in arrays scaffold within mesopores in individual NC nanofoam, which offered exceptionally large surface area for embedding high-density PdCu-ANPs in it as well as facilitated the mass transfer and molecular diffusion during the electrochemical reaction. Taking the advantages of the unique structural merit of NC-NFAs support and excellent electrocatalyitc properties of PdCu-ANPs that embedded in it, the resultant PdCu-ANPs/NC-NFAs modified CF microelectrode exhibited good electrochemical sensing performances towards H2O2 including a wide linear range from 2.0 µM to 3.44 mM, a low detection limit of 500 nM, as well as good reproducibility, stability and anti-interference ability. When used in real-time in situ tracking H2O2 secreted from different types of human colorectal cancer cells, i.e., HCT116, HT29, SW48 and LoVo, it can distinguish the types of cancer cells by measuring the number of extracellular H2O2 molecules released per cell, which demonstrates its great promise in cancer diagnose and management.

Therapeutic potential of dental pulp stem cell transplantation in a rat model of Alzheimer's disease.

Dental pulp stem cells are dental pulp-derived mesenchymal stem cells that originate from the neural crest. They exhibit greater potential for the treatment of nervous system diseases than other types of stem cells because of their neurogenic differentiation capability and their ability to secrete multiple neurotrophic factors. Few studies have reported Alzheimer's disease treatment using dental pulp stem cells. Rat models of Alzheimer's disease were established by injecting amyloid-ß1-42 into the hippocampus. Fourteen days later, 5 × 106 dental pulp stem cells were injected into the hippocampus. Immunohistochemistry and western blot assays showed that dental pulp stem cell transplantation increased the expression of neuron-related doublecortin, NeuN, and neurofilament 200 in the hippocampus, while the expression of amyloid-ß was decreased. Moreover, cognitive and behavioral abilities were improved. These findings indicate that dental pulp stem cell transplantation in rats can improve cognitive function by regulating the secretion of neuron-related proteins, which indicates a potential therapeutic effect for Alzheimer's disease. This study was approved by the Animal Ethics Committee of Harbin Medical University, China (approval No. KY2017-132) on February 21, 2017.

Proteomic analysis of early-response to mechanical stress in neonatal rat mandibular condylar chondrocytes.

The objectives of this study were to investigate the early response to mechanical stress in neonatal rat mandibular chondrocytes by proteomic analysis. To evaluate its molecular mechanism, chondrocytes were isolated and cultured in vitro, then loaded mechanical stress by four-point bending system on different patterns. Morphological observation, flow cytometric analysis, and MTT assays indicated that 4,000 microstrain loading for 60 min was an appropriate mechanical stimulus for the following proteome analysis, which produced a transient but obvious inhibitory effect on the cell cycle. Therefore, we took a proteomic approach to identify significantly differential expression proteins in chondrocytes under this mechanical stress. Using 2-DE and MALDI-TOF, we identified seven differentially expressed proteins including the MAPK pathway inhibitor RKIP, cytoskeleton proteins, actin and vimentin, and other selected proteins. Some differentially expressed proteins were validated by both Western blot analysis and fluorescent staining of cytoskeleton at different loading times. The vimentin and RKIP responsive expression were also proven in vivo in oral orthopedic treatment rats, which was in line with the result in vitro. The histological changes in cartilage also showed the inhibition effect. Furthermore, the expressional level of phosphorylated ERK was increased, which demonstrates the changes in MAPK activity. Taken together, these data indicate that mechanical stress resulted in vimentin expression changes first and then led to the subsequent changes in actin expression, MAPK pathway regulated by RKIP and heat shock protein GRP75. All those changes contributed to the cytoskeleton remolding and cell cycle inhibition, finally led to condylar remodeling.