Design of "Off-On-Off" fluorescence sensors for Heparin detection by precise modulation of molecular structure.

In this strategy, the fluorescence sensor Nap-Co-T1 employing the fluorescence resonance energy transfer (FRET) mechanism was designed and synthesized to have an efficient response to Heparin, and the FRET mechanism was explored for different excitation-emission wavelengths with different distances between the energy acceptor and the energy donor (comparing with fluorescence sensor Nap-TPA-T2). Upon the addition of Heparin, the fluorescence emission of Nap-Co-T1 was turned on at 565 nm, and the fluorescence color changed of the solution from colorless to bright yellow. The limit of detection (LOD) was as low as 0.04 µg/mL. With the addition of antagonistic protamine (PRTM) to the sensor complex with Heparin, the fluorescence emission was turned off to a certain extent, and the reversibility of the "off-on-off" system was maintained for five cycles or more. In addition, Nap-Co-T1 provides rapid and sensitive detection of Heparin in human serum albumin solution and artificial urine and is highly sensitive to environmental viscosity.

Single-cell transcriptomic sequencing identifies subcutaneous patient-derived xenograft recapitulated medulloblastoma.

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant brain tumors that mainly affect children. Various approaches have been used to model MB to facilitate investigating tumorigenesis. This study aims to compare the recapitulation of MB between subcutaneous patient-derived xenograft (sPDX), intracranial patient-derived xenograft (iPDX), and genetically engineered mouse models (GEMM) at the single-cell level. METHODS: We obtained primary human sonic hedgehog (SHH) and group 3 (G3) MB samples from six patients. For each patient specimen, we developed two sPDX and iPDX models, respectively. Three Patch+/- GEMM models were also included for sequencing. Single-cell RNA sequencing was performed to compare gene expression profiles, cellular composition, and functional pathway enrichment. Bulk RNA-seq deconvolution was performed to compare cellular composition across models and human samples. RESULTS: Our results showed that the sPDX tumor model demonstrated the highest correlation to the overall transcriptomic profiles of primary human tumors at the single-cell level within the SHH and G3 subgroups, followed by the GEMM model and iPDX. The GEMM tumor model was able to recapitulate all subpopulations of tumor microenvironment (TME) cells that can be clustered in human SHH tumors, including a higher proportion of tumor-associated astrocytes and immune cells, and an additional cluster of vascular endothelia when compared to human SHH tumors. CONCLUSIONS: This study was the first to compare experimental models for MB at the single-cell level, providing value insights into model selection for different research purposes. sPDX and iPDX are suitable for drug testing and personalized therapy screenings, whereas GEMM models are valuable for investigating the interaction between tumor and TME cells.

Guided bone regeneration for peri-implant augmentation: A retrospective study comparing two surgical techniques with a mean follow-up of 26 months.

OBJECTIVES: To introduce a modified guided bone regeneration (GBR) technique using intact periosteum and deproteinized bovine bone mineral (DBBM) for peri-implant augmentation and compare the clinical outcomes with those of conventional GBR. MATERIALS AND METHODS: Patients who received peri-implant augmentation in posterior sites between 2015 and 2021 were reviewed in this study. Group A was treated with a modified GBR technique, and Group B was treated with conventional GBR. For group comparison, propensity score matching was performed with a sensitivity analysis. The implant survival rate, dimensional changes in hard tissue, marginal bone loss (MBL), and peri-implant parameters were evaluated. RESULTS: In total, 114 implants from 98 patients were included. The implant survival rates were 95.74% in Group A and 95.00% in Group B during the follow-up period. At 6 months, the median horizontal thickness was recorded at 0.87 mm (IQ1-IQ3 = 0.00-1.75 mm) in Group A, exhibiting a relatively lower value compared to the corresponding measurement of 0.98 mm (IQ1-IQ3 = 0.00-1.89 mm) in Group B (p = .937). Vertical height displayed no statistically significant intergroup difference between the two groups (p = .758). The mean follow-up period was 25.83 ± 12.93 months after loading in Group A and 27.47 ± 21.29 months in Group B (p = .761). MBL and peri-implant parameters were comparable between the two groups. CONCLUSIONS: Within the limitations of this study, the modified GBR technique using intact periosteum and DBBM grafting might be a viable alternative to correct bone defects around implants in molar and premolar sites.

Along the microbiota-gut-brain axis: Use of plant polysaccharides to improve mental disorders.

With the development of gut microbiota-specific interventions for mental disorders, the interactions between plant polysaccharides and microbiota in the intestinal and their consequent effects are becoming increasingly important. In this review, we discussed the role of plant polysaccharides in improving various mental disorders via the microbiota-gut-brain axis. The chemical and structural characteristics and metabolites of these plant polysaccharides were summarised. Plant polysaccharides and their metabolites have great potential for reshaping gut microbiota profiles through gut microbiota-dependent fermentation. Along the microbiota-gut-brain axis, the consequent pharmacological processes that lead to the elimination of the symptoms of mental disorders include 1) regulation of the central monoamine neurotransmitters, amino acid transmitters and cholinergic signalling system; 2) alleviation of central and peripheral inflammation mainly through the NLRP3/NF-κB-related signalling pathway; 3) inhibition of neuronal apoptosis; and 4) enhancement of antioxidant activities. According to this review, monosaccharide glucose and structure -4-α-Glcp-(1→ are the most potent compositions of the most reported plant polysaccharides. However, the causal structure-activity relationship remains to be extensively explored. Moreover, mechanistic elucidation, safety verification, and additional rigorous human studies are expected to advance plant polysaccharide-based product development targeting the microbiota-gut-brain axis for people with mental disorders.

Identification of functional biomarkers of Peganum harmala and Hypericum perforatum using PCA-constructed secondary metabolite maps.

Peganum harmala L. (P. harmala), also known as Espand, Harmel, or Syrian rue, and Hypericum perforatum L. (H. perforatum), commonly known as St. John's wort, are two of the widely cultivated industrial crops and used worldwide in antihepatoma-related products. However, their main functional substances are still not clear, thus impeding the efficacy evaluations and quality controls of relative products around the world. In this work, the anti-hepatoma biomarkers of P. harmala and H. perforatum were clarified through the development of principal components analysis (PCA)-HPLC secondary metabolite mapping models. The chemical fingerprints of plant extracts were profiled by HPLC and then mapped to produce the secondary metabolite models using PCA. The models correlated the chemical information with the anti-hepatoma activities of plant extracts, thus indicating the functional inhibitors of P. harmala and H. perforatum against hepatoma cells. The activities of the identified compounds were validated by cytotoxic and apoptotic assays. The major inhibitors of P. harmala and H. perforatum against human hepatoma were determined to be harmine and quercetin, respectively. The IC50 values and the induced apoptotic rate of harmine on HepG2 cells were 20.7 ± 2.8 µM and 46.7 ± 3.5 %, respectively. The IC50 values and the induced apoptotic rate of quercetin on HepG2 cells were 49.5 ± 6.6 µM and 38.7 ± 2.6 %, respectively. In conclusion, the results significantly expanded the understanding of the biochemical foundations of P. harmala and H. perforatum, thus evidently supporting their current applications around the world. Moreover, harmine and quercetin could be used as biomarkers to evaluate the efficacy and quality of related products of industrial crops in therapeutic and health-improving applications.

Influence of rainfall pattern and infiltration capacity on the spatial and temporal inundation characteristics of urban waterlogging.

The rapid development of the city leads to the continuous updating of the land use allocation ratio, particularly during the flood season, which will exacerbate the significant changes in the spatial and temporal patterns of urban flooding, increasing the difficulty of urban flood forecasting and early warning. In this study, the spatial and temporal evolution of flooding in a high-density urban area was analyzed based on the Mike Flood model, and the influence mechanisms of different rainfall peak locations and infiltration rate scenarios on the spatial and temporal characteristics of urban waterlogging were explored. The results revealed that under the same return period, the larger the rainfall peak coefficient, the larger the peak value of inundation volume and inundation area. When the rainfall peak coefficient is small, the higher the return period is, and the larger the peak lag time of the inundation volume is, in which P = 50a, r = 0.2, the peak lag time of the inundation volume reached 32 min and 45 min for the inundation depths H > 0.03 m and H > 0.15 m, respectively. There are also significant differences in the peak lag time of waterlogging inundation volume for different inundation depths. The greater the inundation depth, the longer the peak lag time of the inundation volume, and the higher the return period, the more significant the effect of lag time prolongation. It is worth noting that the increase in infiltration rate may lead to an advance in the peak time of inundation volume and inundation area, and the peak time of the inundation area is overall more obvious than that of inundation volume. The effect of infiltration rate on the peak time of inundation volume for larger inundation depths was relatively large; the peak times of inundation volume and inundation area were advanced by 4-6 min and 4-8 min for H > 0.03 m and H > 0.15 m, respectively, after the increase in infiltration rate, and the higher the rainfall return period, the longer the advance time. The spatial and temporal characteristics of waterlogging under different peak rainfall locations and infiltration capacities obtained in this study can help provide a new perspective for temporal forecasting and warning of urban waterlogging.

A nomogram prediction of implant apical non-coverage on bone-added transcrestal sinus floor elevation: A retrospective cohort study.

OBJECTIVES: To identify the risk indicators and develop and validate a nomogram prediction model of implant apical non-coverage by comprehensively analyzing clinical and radiographic factors in bone-added transcrestal sinus floor elevation (TSFE). MATERIAL AND METHODS: A total of 260 implants in 195 patients receiving bone-added TSFE were included in the study. The population was divided into a development (180 implants) and a validation (80 implants) cohort. According to 6 months post-surgery radiographic images, implants were categorized as "apical non-coverage" or "apical covered." The association of risk factors including clinical and radiographic parameters with implant apical non-coverage was assessed using regression analyses. A nomogram prediction model was developed, and its validation and discriminatory ability were analyzed. RESULTS: The nomogram predicting bone-added TSFE's simultaneously placed implant's apex non-coverage after 6 months. This study revealed that sinus angle, endo-sinus bone gain, implant protrusion length, graft contact walls, and distal angle were predictors of implant apical non-coverage. The generated nomogram showed a strong predictive capability (area under the curve [AUC] = 0.845), confirmed by internal validation using 10-fold cross-validation (Median AUC of 0.870) and temporal validation (AUC = 0.854). The calibration curve and decision curve analysis demonstrated good performance and high net benefit of the nomogram, respectively. CONCLUSIONS: The clinical implementation of the present nomogram is suitable for predicting the apex non-coverage of implants placed simultaneously with bone-added TSFE after 6 months.

Metallic CrP2 monolayer: potential applications in energy storage and conversion.

Phosphorus-rich compounds have emerged as a promising class of energy storage and conversion materials due to their interesting structures and electrochemical properties. Herein, we propose that a metallic CrP2 monolayer, isomorphic to 1H-phase MoS2, is a good prospect as an anode for K-ion batteries and a catalyst for hydrogen evolution through first-principles calculations. The CrP2 monolayer demonstrates not only a desirable high K storage capacity (940 mA h g-1) but also a low K-ion diffusion barrier (0.10 eV) and average open circuit voltage (0.40 V). On the other hand, its Gibbs free energy (0.02 eV)/active site density is superior/comparable to that of commercial Pt, resulting from the contribution of the lone pair electrons of the P atom. Its high structural stability and intrinsic metallicity can ensure high safety and performance during the cyclic process. These interesting properties make the CrP2 monolayer a promising multifunctional material for energy storage and conversion devices.

Berberine and aspirin prevent traumatic heterotopic ossification by inhibition of BMP signalling pathway and osteogenic differentiation.

Heterotopic ossification (HO) is a pathological process that often occurs in soft tissues following severe trauma. There is no effective therapy for HO. The BMP signalling pathway plays an essential role in the pathogenesis of HO. Our previous study showed that AMPK negatively regulates the BMP signalling pathway and osteogenic differentiation. The present study aims to study the effect of two AMPK activators berberine and aspirin on osteogenic differentiation and HO induced by traumatic injury. The effects of two AMPK activators, berberine and aspirin, on BMP signalling and osteogenic differentiation were measured by western blot, ALP and Alizarin red S staining in C3H10T1/2 cells. A mouse model with Achilles tenotomy was employed to assess the effects of berberine and aspirin on HO using µCT and histological analysis. First, our study showed that berberine and aspirin inhibited phosphorylation of Smad1/5 induced by BMP6 and the inhibition was attributed to the down-regulation of ALK2 expression. Second, the combination of berberine and aspirin yielded more potent effects on BMP signalling. Third, we further found that there was an additive effect of berberine and aspirin combination on osteogenic differentiation. Finally, we found that berberine and aspirin blocked trauma-induced ectopic bone formation in mice, which may be through suppression of phosphorylation of Smad1/5 in injured tissues. Collectively, these findings indicate that berberine and aspirin inhibit osteogenic differentiation in C3H10T1/2 cells and traumatic HO in mice, possibly through the down-regulation of the BMP signalling pathway. Our study sheds a light on prevention and treatment of traumatic HO using AMPK pharmacological activators berberine and aspirin.

Effectiveness and complications of transcrestal sinus floor elevation using the cushioned grind-out technique: A retrospective cohort study with up to 7 years of follow-up.

AIM: To evaluate the effectiveness and complications of the cushioned grind-out technique. The primary outcome was endo-sinus bone gain (ESBG), while secondary outcomes included the Schneiderian membrane perforation rate and mid- to long-term implant survival. MATERIALS AND METHODS: In this retrospective study, we compared the cushioned grind-out technique with the classic osteotome technique, establishing statistical models to assess ESBG, membrane perforation rate and implant survival rate. RESULTS: A total of 259 patients and 340 implants were included. The mean ESBG was 5.31 mm for the cushioned grind-out group and 4.64 mm for the osteotome group. Multivariable regression analysis revealed that the cushioned grind-out technique significantly facilitated ESBG (p = .028). Nineteen preparation sites experienced membrane perforation, with rates of 5.5% and 6.4% for the cushioned grind-out and osteotome groups, respectively. However, the difference was not statistically significant (p = .920). Additionally, the cumulative survival rate of the implants for 7 years was 95.2% and 91.4%, respectively, with the surgical technique not significantly influencing the results. CONCLUSIONS: With 6 months to 7 years of post-prosthetic restoration review data, our findings show that the cushioned grind-out technique facilitates a higher ESBG, with no significant difference in membrane perforation or implant failure rate.