Population-based heteropolymer design to mimic protein mixtures.

Biological fluids, the most complex blends, have compositions that constantly vary and cannot be molecularly defined1. Despite these uncertainties, proteins fluctuate, fold, function and evolve as programmed2-4. We propose that in addition to the known monomeric sequence requirements, protein sequences encode multi-pair interactions at the segmental level to navigate random encounters5,6; synthetic heteropolymers capable of emulating such interactions can replicate how proteins behave in biological fluids individually and collectively. Here, we extracted the chemical characteristics and sequential arrangement along a protein chain at the segmental level from natural protein libraries and used the information to design heteropolymer ensembles as mixtures of disordered, partially folded and folded proteins. For each heteropolymer ensemble, the level of segmental similarity to that of natural proteins determines its ability to replicate many functions of biological fluids including assisting protein folding during translation, preserving the viability of fetal bovine serum without refrigeration, enhancing the thermal stability of proteins and behaving like synthetic cytosol under biologically relevant conditions. Molecular studies further translated protein sequence information at the segmental level into intermolecular interactions with a defined range, degree of diversity and temporal and spatial availability. This framework provides valuable guiding principles to synthetically realize protein properties, engineer bio/abiotic hybrid materials and, ultimately, realize matter-to-life transformations.

Single-chain heteropolymers transport protons selectively and rapidly.

Precise protein sequencing and folding are believed to generate the structure and chemical diversity of natural channels1,2, both of which are essential to synthetically achieve proton transport performance comparable to that seen in natural systems. Geometrically defined channels have been fabricated using peptides, DNAs, carbon nanotubes, sequence-defined polymers and organic frameworks3-13. However, none of these channels rivals the performance observed in their natural counterparts. Here we show that without forming an atomically structured channel, four-monomer-based random heteropolymers (RHPs)14 can mimic membrane proteins and exhibit selective proton transport across lipid bilayers at a rate similar to those of natural proton channels. Statistical control over the monomer distribution in an RHP leads to segmental heterogeneity in hydrophobicity, which facilitates the insertion of single RHPs into the lipid bilayers. It also results in bilayer-spanning segments containing polar monomers that promote the formation of hydrogen-bonded chains15,16 for proton transport. Our study demonstrates the importance of the adaptability that is enabled by statistical similarity among RHP chains and of the modularity provided by the chemical diversity of monomers, to achieve uniform behaviour in heterogeneous systems. Our results also validate statistical randomness as an unexplored approach to realize protein-like behaviour at the single-polymer-chain level in a predictable manner.

Ultrasonography screening of hepatic cystic echinococcosis in sheep flocks used for evaluating control progress in a remote mountain area of Hejing County, Xinjiang.

BACKGROUND: Although ultrasonography (US) has been widely used in the diagnosis of human diseases to monitor the progress of cystic echinococcosis (CE) control, the screening method for hepatic CE in sheep flocks requires adjustment. In this study, we used a US scanner to screen sheep flocks and evaluated the efficacy of dosing dogs once a year with praziquantel for 7 years from 2014 to 2021. METHODS: All sheep in the three flocks were screened using an ultrasound scanner in 2014 and compared with the prevalence of infection in 2021 in Bayinbuluke, Xinjiang, China. Sheep age was determined using incisor teeth. Cyst activity and calcification were determined using US images. The dogs were dewormed with praziquantel once a year to control echinococcosis in the community. RESULTS: Three flocks had 968 sheep in 2014, with 13.22%, 22.62%, 18.7%, 27.27%, 11.88%, and 6.3% of sheep aged 1, 2, 3, 4, 5, and ≥ 6 years old, respectively. US scanning revealed that the overall CE prevalence was 38.43% (372/968), with active cysts and calcified cysts present in 9.40% (91/968) and 29.02% (281/968) of the sheep, respectively. For the young sheep aged 1 and 2 years, the prevalence of active and calcified cysts was: 1.56% and 0.91%, and 10.94% and 18.72%, respectively. Approximately 15.15% and 16.52% of the 4- and 5-year-old sheep, respectively, harbored active cysts. There was no significant difference in the infection rates of sheep between 2014 and 2021 (P > 0.05). CONCLUSIONS: US is a practical tool for the field screening of CE in sheep flocks. One-third of the sheep population in the flocks was 1-2 years old, and these sheep played a very limited role in CE transmission, as most of the cysts were calcified. Old sheep, especially culled aged sheep, play a key role in the transmission of CE. Dosing dogs once a year did not affect echinococcosis control.

Comparison of case-based and lecture-based learning in dental fluorosis diagnostic ability with visual analog scale assessment.

OBJECTIVE: This study aimed to compare the impact of case-based learning (CBL) versus lecture-based learning (LBL) on dental students' clinical decision-making regarding DF severity using Visual Analog Scale (VAS) scoring. METHODS: Eighty first-year graduate dental students were randomly assigned to either the CBL (n = 38) or LBL (n = 42) groups. Both groups received instruction on DF diagnosis, with CBL involving small group sessions analyzing real cases and LBL involving traditional lectures. Effectiveness was assessed by presenting 32 dental fluorosis cases with Thylstrup-Fejerskov Index (TSIF) scores ranging from 0 to 7 through slide presentations to both groups for VAS assessment. Five evaluators of each group randomly selected were asked to repeat the rating 2 weeks later. Statistical analysis included two-way ANOVA for group and gender differences, intra-class correlation coefficient (ICC) for reliability, and Spearman correlation coefficients for validity. RESULTS: Variations in VAS scores were observed between CBL and LBL groups, with no significant gender impact. Excellent inter- and intra-evaluator agreement was found for VAS scoring in both groups, indicating its reliability. Validation against established indices (such as DI and TSIF) demonstrated strong correlations, with CBL students exhibiting higher correlations. CONCLUSIONS: CBL enhances students' clinical decision-making and proficiency in DF diagnosis, as evidenced by more consistent and accurate VAS scoring compared to LBL. These findings highlight the importance of innovative educational strategies in dental curricula, with implications for improving training quality and clinical outcomes. TRIAL REGISTRATION: The study was registered at the Clinical Research Center, Hospital of Stomatology, Wuhan University (Registration code: HGGC-036).

Ultraportable Flow Cytometer Based on an All-Glass Microfluidic Chip.

The flow cytometer has become a powerful and widely accepted measurement device in both biological studies and clinical diagnostics. The application of the flow cytometer in emerging point-of-care scenarios, such as instant detection in remote areas and emergency diagnosis, requires a significant reduction in physical dimension, cost, and power consumption. This requirement promotes studies to develop portable flow cytometers, mostly based on the utilization of polymer microfluidic chips. However, due to the relatively poor optical performance of polymer materials, existing microfluidic flow cytometers are incapable of accurate blood analysis, such as the four-part leukocyte differential count, which is necessary to monitor the immune system and to assess the risk of allergic inflammation or viral infection. To address this issue, an ultraportable flow cytometer based on an all-glass microfluidic chip (AG-UFCM) has been developed in this study. Compared with that of a typical commercial flow cytometer (BD FACSAria III), the volume of the AG-UFCM was reduced by 90 times (from 720 to 8 L). A two-step laser processing was employed to fabricate an all-glass microfluidic chip with a surface roughness of less than 1 nm, significantly improving the optical performance of on-chip micro-lens. The signal-to-noise ratio was enhanced by 3 dB, compared with that of polymer materials. For the first time, a four-part leukocyte differential count based on single fluorescence staining was realized using a miniaturized flow cytometer, laying a foundation for the point-of-care testing of miniaturized flow cytometers.

Biocompatible Conductive Hydrogels: Applications in the Field of Biomedicine.

The impact of COVID-19 has rendered medical technology an important factor to maintain social stability and economic increase, where biomedicine has experienced rapid development and played a crucial part in fighting off the pandemic. Conductive hydrogels (CHs) are three-dimensional (3D) structured gels with excellent electrical conductivity and biocompatibility, which are very suitable for biomedical applications. CHs can mimic innate tissue's physical, chemical, and biological properties, which allows them to provide environmental conditions and structural stability for cell growth and serve as efficient delivery substrates for bioactive molecules. The customizability of CHs also allows additional functionality to be designed for different requirements in biomedical applications. This review introduces the basic functional characteristics and materials for preparing CHs and elaborates on their synthetic techniques. The development and applications of CHs in the field of biomedicine are highlighted, including regenerative medicine, artificial organs, biosensors, drug delivery systems, and some other application scenarios. Finally, this review discusses the future applications of CHs in the field of biomedicine. In summary, the current design and development of CHs extend their prospects for functioning as an intelligent and complex system in diverse biomedical applications.

Efficacy and safety of bone substitutes in lumbar spinal fusion: a systematic review and network meta-analysis of randomized controlled trials.

PURPOSE: A variety of alternative grafts to autologous iliac crest bone (ICBG) have been developed for lumbar spondylodesis, due to frequent complications following ICBG harvest. The optimal alternative graft to ICBG, however, remains elusive till now. The purpose of this study was to compare the efficacy and safety of fusion materials in lumbar degeneration diseases and to provide a ranking spectrum of the grafts. METHODS: Randomized controlled trials (RCTs) comparing different bone grafts in lumbar arthrodesis were eligible for inclusion. A network meta-analysis was performed for endpoints including fusion rate and incidence of adverse events. RESULTS: Twenty-seven RCTs involving 2488 patients and 13 available interventions were included. rhBMP-2 provided the highest fusion rate, being significantly superior to that of ICBG (OR = 0.21, p < 0.001), autograft local bone (ALB) (OR = 0.18, p = 0.022), rhBMP-7 (OR = 0.15, p < 0.001), allograft (OR = 0.13, p = 0.009), and DBM + ALB (OR = 0.07, p = 0.048). The treatment efficacy of allograft could be significantly enhanced by bone marrow concentrate (BMC) supplying (OR = 0.16, p = 0.010). ICBG ranks second on the frequency of complications, which is significantly higher than that of allograft (OR = 0.14, p = 0.041) and ALB (OR = 0.14, p = 0.030). All of the other comparisons showed similar efficacy and safety profiles between groups. CONCLUSION: Ranking spectrums of the efficacy and safety for various bone grafts were provided graphically. Though rhBMP-2 was of the highest success rate, the application should be taken with proper caution because of the widely proposed life-threatening adverse events. ALB, ALB plus synthetic ceramic materials and allograft mixed with BMC were also proved to be potentially effective alternative graft to ICBG. These slides can be retrieved under Electronic Supplementary Material.

One-pot bottom-up fabrication of biocompatible PEGylated WS2 nanoparticles for CT-guided photothermal therapy of tumors in vivo.

BACKGROUND: Tungsten disulfide (WS2), which enjoyed a good potential to be a promising clinical theranostic agent for cancer treatment, is still subject to the tedious synthesis procedure. METHODS: Here, we reported a one-pot 'bottom-up' hydrothermal strategy for the fabrication of PEGylated WS2 nanoparticles (NPs). The WS2-PEG nanoparticles were characterized systematically. The CT imaging and photothermal therapy against tumor as well as biosafety in vitro and in vivo were also investigated. RESULTS: The obtained WS2-PEG NPs enjoyed obvious merits of good solubility and favorable photothermal performance. WS2-PEG NPs exhibited desirable photothermal ablation ability against cancer cells and cancer cell-bearing mice in vitro and in vivo. MTT assay and histological analysis demonstrated the low cytotoxicity and biotoxicity of WS2-PEG NPs, providing a valid biosafety guarantee for the coming biomedical applications. In addition, thanks to the obvious X-ray attenuation of W atom, the WS2-PEG NPs can also be served as a favorable contrast agent for CT imaging of tumors. CONCLUSION: WS2-PEG NPs has enjoyed a good potential to be a promising clinical CT-guided photothermal therapeutic agent against cancers.

Dye-Anchored MnO Nanoparticles Targeting Tumor and Inducing Enhanced Phototherapy Effect via Mitochondria-Mediated Pathway.

Phototherapy is a promising treatment method for cancer therapy. However, the various factors have greatly restricted phototherapy development, including the poor accumulation of photosensitizer in tumor, hypoxia in solid tumor tissue and systemic phototoxicity. Herein, a mitochondrial-targeted multifunctional dye-anchored manganese oxide nanoparticle (IR808@MnO NP) is developed for enhancing phototherapy of cancer. In this nanoplatform, IR808 as a small molecule dye acts as a tumor targeting ligand to make IR808@MnO NPs with capacity to actively target tumor cells and relocate finally in the mitochondria. Meanwhile, continuous production of oxygen (O2 ) and regulation of pH induced by the high reactivity and specificity of MnO NPs toward mitochondrial endogenous hydrogen peroxide (H2 O2 ) could effectively modulate tumor hypoxia and lessen the tumor subacid environment. Large amounts of reactive oxide species (ROS) are generated during the reaction process between H2 O2 and MnO NPs. Furthermore, under laser irradiation, IR808 in IR808@MnO NPs turns O2 into a highly toxic singlet oxygen (1 O2 ) and generates hyperthermia. The results indicate that IR808@MnO NPs have the high efficiency of specific targeting of tumors, relieving tumor subacid environment, improving the tumor hypoxia environment, and generating large amounts of ROS to kill tumor cells. It is expected to have a wide application in treating cancer.

Advanced Anti-Fouling Membranes for Osmotic Power Generation from Wastewater via Pressure Retarded Osmosis (PRO).

A facile and versatile approach was demonstrated for the fabrication of low-fouling pressure retarded osmosis (PRO) membranes for osmotic power generation from highly polluted wastewater. A water-soluble zwitterionic random copolymer with superior hydrophilicity and unique chemistry was molecularly designed and synthesized via a single-step free-radical polymerization between 2-methacryloyloxyethyl phosphorylcholine (MPC) and 2-aminoethyl methacrylate hydrochloride (AEMA). The P[MPC- co-AEMA] copolymer was then chemically grafted onto the surface of PES/Torlon hollow fibers via amino groups coupling of poly(AEMA) with the polyimide structures of Torlon, leaving the zwitterions of poly(MPC) in the feed solution. Because of the outstanding hydrophilicity, unique cationic and anionic groups, and electrical neutrality of the zwitterionic brush, the newly developed membrane showed great resistances to both inorganic scaling and organic fouling in PRO operations. When using a real wastewater brine comprising multifoulants as the feed, the P[MPC- co-AEMA] modified membrane exhibits a much lower flux decline of 37% at Δ P = 0 bar after 24-h tests and a smaller power density decrease of 28% at Δ P = 15 bar within 12-h tests, compared to 61% and 42% respectively for the unmodified one. In addition to the low fouling tendency, the modified membrane shows outstanding performance stability and fouling reversibility, where the flux is almost fully recovered by physical backwash of water at 15 bar for 0.5 h. This study provides valuable insights and strategies for the design and fabrication of effective antifouling materials and membranes for PRO osmotic power generation.

Development of Targeted Nanoscale Drug Delivery System for Osteoarthritic Cartilage Tissue.

Osteoarthritis is a severe and debilitating joint disease, which is characterized as results from damage and degeneration of the articular cartilage of the joint surfaces. The incidence of osteoarthritis is growing increasingly high while current treatment methods remain suboptimal. The major issue for current osteoarthritic medications is that patients frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. The treatment processes could be made more effective, safe, and comfortable if it were possible to deliver the drugs specifically to cartilage tissue. Therefore, developing site-specific and controlled drug release delivery systems is needed for overcoming the aforementioned issues. We have developed a poly(lactic-co-glycolic acid) (PLGA)-based nanoscale drug delivery system based on a short cartilage-targeting peptide sequence: WYRGRL. Nanoparticles (NPs) made of methoxy-poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged WYRGRL peptide was then linked to the surface of the nanoparticles through the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the C═C double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged WYRGRL peptide to PLGA NPs was confirmed by NMR technique. We further demonstrated that the novel delivery system binds very specifically to cartilage tissue in vitro and ex vivo. Given that biodegradable PLGA-based NPs have shown promise for drug delivery, they could be used for a positive advancement for treatments of osteoarthritic patients by creating a more effective treatment process that achieves healing results faster and with fewer deleterious side effects. Taken together, these promising results indicated that this nanoscale targeting drug delivery system was able to bind to cartilage tissue and might have a great potential for treating osteoarthritis.

Structurally Ordered Nanowire Formation from Co-Assembly of DNA Origami and Collagen-Mimetic Peptides.

We describe the co-assembly of two different building units: collagen-mimetic peptides and DNA origami. Two peptides CP++ and sCP++ are designed with a sequence comprising a central block (Pro-Hyp-Gly) and two positively charged domains (Pro-Arg-Gly) at both N- and C-termini. Co-assembly of peptides and DNA origami two-layer (TL) nanosheets affords the formation of one-dimensional nanowires with repeating periodicity of ∼10 nm. Structural analyses suggest a face-to-face stacking of DNA nanosheets with peptides aligned perpendicularly to the sheet surfaces. We demonstrate the potential of selective peptide-DNA association between face-to-face and edge-to-edge packing by tailoring the size of DNA nanostructures. This study presents an attractive strategy to create hybrid biomolecular assemblies from peptide- and DNA-based building blocks that takes advantage of the intrinsic chemical and physical properties of the respective components to encode structural and, potentially, functional complexity within readily accessible biomimetic materials.

Evaluation of the effectiveness of micro-Raman spectroscopy in monitoring the mineral contents change of human enamel in vitro.

The purpose of this in vitro study was to investigate the efficacy of micro-Raman spectroscopy on detecting mineral content change during the demineralization and de/remineralization cycling process. The enamel samples (n = 55) were randomly divided into three groups and separately treated with demineralization solution (n = 20), de/remineralization cycling solution (n = 30), and distilled water (n = 5). Micro-Raman spectroscopy, microhardness (MHS), and the released calcium ions concentration were performed before and after treatment, respectively. A one-way analysis of variance (ANOVA) with a post hoc Tukey test was used to analyze the results. The Spearman correlation coefficients among the parameters of Raman relative intensity decrease (RRID%), the percentage of MHS loss (PML), and the released calcium ions concentration were also analyzed. In demineralization group, RRID%, PML, and released calcium ions concentration were highly correlated with each other (r = 0.979, p < 0.001; r = 0.984, p < 0.001; and r = 0.983, p < 0.001, respectively). While for the de/remineralization cycling group, there also existed a high correlation between RRID% and PML (r = 0.987, p < 0.001). In conclusion, micro-Raman spectroscopy could effectively monitor the mineral content change, and its efficacy was validated by the measurement of released calcium ions concentration and MHS.

Development of mediastinal lymphoma after radiotherapy for concurrent medulloblastoma and PNET in a patient with Gorlin syndrome.

BACKGROUND: Very young children with Gorlin syndrome are at risk for developing medulloblastoma. Patients with Gorlin syndrome may have multiple system abnormalities, including basal cell carcinomas, jaw cysts, desmoplastic medulloblastoma, palmar/plantar pits, rib abnormalities, and intracranial falx calcification. The early diagnosis of Gorlin syndrome in desmoplastic medulloblastoma patients is very important because these patients should receive chemotherapy as a first-line treatment and should avoid radiotherapy as much as possible. CASE PRESENTATION: In the present study, a 5-year-old male patient had a concurrent cerebellar desmoplastic medulloblastoma and temporal primitive neuroectodermal tumor. Examinations of this patient revealed multiple café-au-lait spots, a jaw cyst, and a bifid rib. A molecular classification analysis revealed that the patient's cerebellar tumor was of the sonic hedgehog subtype. Twenty-seven months after tumor resection and cerebrospinal irradiation were performed, mediastinal lymphoma was found in the patient. The patient ultimately died of lymphoma. To the best of our knowledge, this is the first report of a concurrent medulloblastoma and primitive neuroectodermal tumor and the fourth report of multiple café-au-lait spots in a patient with Gorlin syndrome. This report is also the first account of the development of mediastinal lymphoma after spinal irradiation in a patient with Gorlin syndrome. CONCLUSIONS: Chemotherapy should be the first-line treatment for medulloblastoma patients with Gorlin syndrome. Young patients with medulloblastoma of the desmoplastic subtype and multiple café-au-lait spots should be thoroughly examined for Gorlin syndrome.

[Research of Determining Complete Degradation Time in Vitro Based on Cellulose Absorbable Hemostatic Products].

To develop a method for determining complete degradation time of solublehemostatic products in vitro with accuracy, high speed and effectiveness, the current weight loss method originated from GB/T 16886 serial standards was optimized by using dialysis bag combined with assay of reducing sugar. The degradation was carried out with 3% hydrogen peroxide solution, at 37℃, 150 rpm. The dialysis bags were taken out in the 3rd, 6th, 8th, 10th and 14th day, vacuum drying folowed by percentage of weight loss testing. Cumulative content of reducing sugar in degradation solution out of dialysis bag was determined simultaneously. The correlation analysis was performed by SPSS 22.0 equipped with Pearson Correlation Coeffi cient. The correlation coeffi cient between percentage of weight loss and cumulative content of reducing sugar was 0.957, which ilustrated high correlation with each other. Hence dialysis bag combined with assay of reducing sugar is capable of evaluating the degradation endpoint of soluble hemostatic products in vitro. The method also provides a way for the evaluation of degradation of other degradable biomaterials in vitro.

Combinatorial Approach of Antigen Delivery Using M Cell-Homing Peptide and Mucoadhesive Vehicle to Enhance the Efficacy of Oral Vaccine.

Orally ingested pathogens or antigens are taken up by microfold cells (M cells) in Peyer's patches of intestine to initiate protective immunity against infections. However, the uptake of orally delivered protein antigens through M cells is very low due to lack of specificity of proteins toward M cells and degradation of proteins in the harsh environment of gastrointestinal (GI) tract. To overcome these limitations, here we developed a pH-sensitive and mucoadhesive vehicle of thiolated eudragit (TE) microparticles to transport an M cell-targeting peptide-fused model protein antigen. Particularly, TE prolonged the particles transit time through the GI tract and predominantly released the proteins in ileum where M cells are abundant. Thus, oral delivery of TE microparticulate antigens exhibited high transcytosis of antigens through M cells resulting in strong protective sIgA as well as systemic IgG antibody responses. Importantly, the delivery system not only induced CD4(+) T cell immune responses but also generated strong CD8(+) T cell responses with enhanced production of IFN-γ in spleen. Given that M cells are considered a promising target for oral vaccination, this study could provide a new combinatorial method for the development of M-cell-targeted mucosal vaccines.

Controllable hierarchical microstructures self-assembled from multiblock copolymers confined in thin films.

Hierarchical microstructures self-assembled from A(BC)n multiblock copolymers confined between two solid surfaces were explored by dissipative particle dynamics simulations. The strategy using confinement allows us to generate hierarchical microstructures with various numbers and different orientations of small-length-scale lamellae. Except for the hierarchical lamellar microstructures with parallel or perpendicular arrangements of small-length-scale lamellae, the coexistence of two different hierarchical lamellae was also discovered by varying the film thickness. The dynamics of hierarchical microstructure formation was further examined. It was found that the formation of the hierarchical microstructures exhibits a stepwise manner where the formation of small-length-scale structures lags behind that of large-length-scale structures. The present work could provide guidance for controllable manufacture of hierarchical microstructures.

Release and Cytokine Production of BmpB from BmpB-Loaded pH-Sensitive and Mucoadhesive Thiolated Eudragit Microspheres.

Swine dysentery is a contagious mucohaemorrhagic colitis of pigs that is caused by anaerobic intestinal spirochaete Brachyspira hyodysenteriae. Recently, an outer membrane lipoprotein of B. hyodysenteriae (BmpB) has been identified, and the mice or pigs immunized with a recombinant BmpB generated antibodies recognizing the native BmpB of B. hyodysenteriae. In this study, we cloned, expressed and purified BmpB protein from E. coli and used it as a vaccine candidate for oral delivery. The BmpB was encapsulated into the pH-sensitive and thiolated Eudragit microspheres (TEMS). The sizes of the microspheres ranged from 5-20 µ. About 22-34% of BmpB were released from the BmpB-loaded TEMS within 24 h at stomach pH 2.0 whereas the release of BmpB from the BmpB-loaded TEMS was 35% in the first one hour and reached 81% within 24 h at intestinal pH 7.2. These data revealed that the BmpB could be protected in the harsh gastric condition. Mucoadhesive experiment in vitro showed that TEMS have high binding affinity with the mucin glycoproteins of porcine intestine. Finally, in vitro production of cytokines from immune cells treated with the BmpB-loaded TEMS suggested that the TEMS would be a promising approach for oral delivery of BmpB as vaccine candidate.

The dentin tubule occlusion effects of desensitizing agents and the stability against acids and brushing challenges.

PURPOSE: To investigate the effects of desensitizing agents on dentin tubule occlusion, acid and tooth brushing challenge, and microhardness change of human dentin. METHODS: Partially demineralized dentin slabs were divided into four groups (n = 30): (1) Control, (2) Non-desensitizing toothpaste, (3) Pro-Argin toothpaste, (4) CPP-ACP paste. The specimens were treated with these dentifrices for 2 minutes/day and soaked in artificial saliva (AS) for 24-hour remineralization. Then the dentin discs were divided into three subgroups for removal resistance tests: acid challenge, mechanical brushing challenge and blank control. Changes in dentin morphology were observed using scanning electron microscopy (SEM). Vickers microhardness measurements were performed at baseline and after 24-hour remineralization for all groups. RESULTS: A surface layer and intra-tubular crystals were observed in SEM imaging of Pro-Argin toothpaste and CPP-ACP paste groups, which occluded most of the dentin tubules for those specimens. But the dentin tubules were opened after the acid challenge again. Moreover, the dentin microhardness showed a slight increase after 24-hour AS immersion. The percentage microhardness gain (PMG) values of these two groups were 5.4% and 5.1% respectively, which were significantly higher than the other groups (P < 0.05).

Small molecule delivery through nanofibrous scaffolds for musculoskeletal regenerative engineering.

Musculoskeletal regenerative engineering approach using small bioactive molecules in conjunction with advanced materials has emerged as a highly promising strategy for musculoskeletal repair and regeneration. Advanced biomaterials technologies have revealed nanofiber-based scaffolds for musculoskeletal tissue engineering as vehicles for the controlled delivery of small molecule drugs. This review article highlights recent advances in nanofiber-based delivery of small molecules for musculoskeletal regenerative engineering. The article concludes with perspectives on the challenges and future directions. FROM THE CLINICAL EDITOR: In this review, advances in nanofiber-based delivery of small molecules are discussed from the standpoint of their potential role in musculoskeletal regenerative engineering, highlighting both future directions and current challenges.