Non-invasive screening and subtyping for breast cancer by serum SERS combined with LGB-DNN algorithms.

Early detection of breast cancer and its molecular subtyping is crucial for guiding clinical treatment and improving survival rate. Current diagnostic methods for breast cancer are invasive, time consuming and complicated. In this work, an optical detection method integrating surface-enhanced Raman spectroscopy (SERS) technology with feature selection and deep learning algorithm was developed for identifying serum components and building diagnostic model, with the aim of efficient and accurate noninvasive screening of breast cancer. First, the high quality of serum SERS spectra from breast cancer (BC), breast benign disease (BBD) patients and healthy controls (HC) were obtained. Chi-square tests were conducted to exclude confounding factors, enhancing the reliability of the study. Then, LightGBM (LGB) algorithm was used as the base model to retain useful features to significantly improve classification performance. The DNN algorithm was trained through backpropagation, adjusting the weights and biases between neurons to improve the network's predictive ability. In comparison to traditional machine learning algorithms, this method provided more accurate information for breast cancer classification, with classification accuracies of 91.38 % for BC and BBD, and 96.40 % for BC, BBD, and HC. Furthermore, the accuracies of 90.11 % for HR+/HR- and 88.89 % for HER2+/HER2- can be reached when evaluating BC patients' molecular subtypes. These results demonstrate that serum SERS combined with powerful LGB-DNN algorithm would provide a supplementary method for clinical breast cancer screening.

A Bioactive Degradable Composite Bone Cement Based on Calcium Sulfate and Magnesium Polyphosphate.

Calcium sulfate bone cement (CSC) is extensively used as a bone repair material due to its ability to self-solidify, degradability, and osteogenic ability. However, the fast degradation, low mechanical strength, and insufficient biological activity limit its application. This study used magnesium polyphosphate (MPP) and constructed a composite bone cement composed of calcium sulfate (CS), MPP, tricalcium silicate (C3S), and plasticizer hydroxypropyl methylcellulose (HPMC). The optimized CS/MPP/C3S composite bone cement has a suitable setting time of approximately 15.0 min, a compressive strength of 26.6 MPa, and an injectability of about 93%. The CS/MPP/C3S composite bone cement has excellent biocompatibility and osteogenic capabilities; our results showed that cell proliferation is up to 114% compared with the control after 5 days. After 14 days, the expression levels of osteogenic-related genes, including Runx2, BMP2, OCN, OPN, and COL-1, are about 1.8, 2.8, 2.5, 2.2, and 2.2 times higher than those of the control, respectively, while the alkaline phosphatase activity is about 1.7 times higher. Therefore, the CS/MPP/C3S composite bone cement overcomes the limitations of CSC and has more effective potential in bone repair.

Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

An outlier removal method based on PCA-DBSCAN for blood-SERS data analysis.

Surface-enhanced Raman spectroscopy (SERS) has shown promising potential in cancer screening. In practical applications, Raman spectra are often affected by deviations from the spectrometer, changes in measurement environments, and anomalies in spectrum characteristic peak intensities due to improper sample storage. Previous research has overlooked the presence of outliers in categorical data, leading to significant impacts on model learning outcomes. In this study, we propose a novel method, called Principal Component Analysis and Density Based Spatial Clustering of Applications with Noise (PCA-DBSCAN) to effectively remove outliers. This method employs dimensionality reduction and spectral data clustering to identify and remove outliers. The PCA-DBSCAN method introduces adjustable parameters (Eps and MinPts) to control the clustering effect. The effectiveness of the proposed PCA-DBSCAN method is verified through modeling on outlier-removed datasets. Further refinement of the machine learning model and PCA-DBSCAN parameters resulted in the best cancer screening model, achieving 97.41% macro-average recall and 97.74% macro-average F1-score. This paper introduces a new outlier removal method that significantly improves the performance of the SERS cancer screening model. Moreover, the proposed method serves as inspiration for outlier detection in other fields, such as biomedical research, environmental monitoring, manufacturing, quality control, and hazard prediction.

Effects of ATP on the Physicochemical Properties and Cytocompatibility of Calcium Sulfate/Calcium Citrate Composite Cement.

Adenosine triphosphate (ATP), acting as a source of energy, has effects on cellular activities, such as adhesion, proliferation, and differentiation. In this study, ATP-loaded calcium sulfate hemihydrate/calcium citrate tetrahydrate cement (ATP/CSH/CCT) was successfully prepared for the first time. The effect of different contents of ATP on the structure and physicochemical properties of ATP/CSH/CCT was also studied in detail. The results indicated that incorporating ATP into the cement did not significantly alter their structures. However, the addition ratio of ATP directly impacted the mechanical properties and in vitro degradation properties of the composite bone cement. The compressive strength of ATP/CSH/CCT gradually decreased with an increasing ATP content. The degradation rate of ATP/CSH/CCT did not significantly change at low concentrations of ATP, but it increased with a higher ATP content. The composite cement induced the deposition of a Ca-P layer in a phosphate buffer solution (PBS, pH = 7.4). Additionally, the release of ATP from the composite cement was controlled. The ATP was controlled releasing at the 0.5% and 1% ATP in cement by the diffusion of ATP and the degradation of the cement, whereas it was controlled by the diffusion process merely at the 0.1% ATP in cement. Furthermore, ATP/CSH/CCT demonstrated good cytoactivity with the addition of ATP and is expected to be used for the repair and regeneration of bone tissue.

Laser tweezer Raman spectroscopy combined with deep neural networks for identification of liver cancer cells.

Rapid identification of cancer cells is crucial for clinical treatment guidance. Laser tweezer Raman spectroscopy (LTRS) that provides biochemical characteristics of cells can be used to identify cell phenotypes through classification models in a non-invasive and label-free manner. However, traditional classification methods require extensive reference databases and clinical experience, which is challenging when sampling at inaccessible locations. Here, we describe a classification method combing LTRS with deep neural network (DNN) for differential and discriminative analysis of multiple liver cancer (LC) cells. By using LTRS, we obtained high-quality single-cell Raman spectra of normal hepatocytes (HL-7702) and liver cancer cell lines (SMMC-7721, Hep3B, HepG2, SK-Hep1 and Huh7). The tentative assignment of Raman peaks indicated that arginine content was elevated and phenylalanine, glutathione and glutamate content was decreased in liver cancer cells. Subsequently, we randomly selected 300 spectra from each cell line for DNN model analysis, achieving a mean accuracy of 99.2%, a mean sensitivity of 99.2% and a mean specificity of 99.8% for the identification and classification of multiple LC cells and hepatocyte cells. These results demonstrate the combination of LTRS and DNN is a promising method for rapid and accurate cancer cell identification at single cell level.

The MyD88 inhibitor, ST2825, induces cell cycle arrest and apoptosis by suppressing the activation of the NF­κB/AKT1/p21 pathway in pancreatic cancer.

NF­κB activation occurs in the majority patients with pancreatic ductal adenocarcinoma (PDAC); however, directly targeting NF­κB has proven unsuccessful, and recent studies have demonstrated a certain effect of the indirect inhibition of NF­κB. Myeloid differentiation factor 88 (MyD88) is a common intermediate messenger for NF­κB activation by inducers. In the present study, the level of MyD88 in PDAC was detected using a public database and a tissue chip. A specific inhibitor (ST2825) of MyD88 was used on PDAC cell lines. Flow cytometry was used to examine apoptosis and cell cycle progression. Transcriptome sequencing was used for ST2825­treated PANC­1 cells compared with untreated PANC­1 cells. The levels of related factors were measured using reverse transcription­quantitative PCR and western blot analysis. Chromatin immunoprecipitation, co­immunoprecipitation, transcription factor assay and an NF­κB phospho­antibody array were performed to identify the detailed underlying mechanisms. Animal experiments were performed to verify the effects of ST2825 on PDAC, which were found in the in vitro experiments. MyD88 was found to be overexpressed in PDAC. ST2825 induced the G2/M phase cell cycle arrest and apoptosis of PDAC cells. ST2825 inhibited MyD88 dimerization to inactivate the NF­κB pathway. ST2825 inhibited AKT1 expression and induced p21 overexpression to induce G2/M phase cell cycle arrest and apoptosis by inhibiting NF­κB transcriptional activity. NF­κB activation, AKT1 overexpression or p21 knockdown partially reversed the effects of ST2825 in PDAC. On the whole, the findings of the present study demonstrate that ST2825 induces G2/M cell cycle arrest and apoptosis via the MyD88/NF­κB/AKT1/p21 pathway in PDAC. MyD88 may thus serve as a potential therapeutic target in PDAC. ST2825 may serve as a novel agent for the targeted therapy of PDAC in the future.

Targeting STAT3-VISTA axis to suppress tumor aggression and burden in acute myeloid leukemia.

The acute myeloid leukemia (AML) patients obtain limited benefits from current immune checkpoint blockades (ICBs), although immunotherapy have achieved encouraging success in numerous cancers. Here, we found that V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint, is highly expressed in primary AML cells and associated with poor prognosis of AML patients. Targeting VISTA by anti-VISTA mAb boosts T cell-mediated cytotoxicity to AML cells. Interestingly, high expression of VISTA is positively associated with hyperactive STAT3 in AML. Further evidence showed that STAT3 functions as a transcriptional regulator to modulate VISTA expression by directly binding to DNA response element of VISTA gene. We further develop a potent and selective STAT3 inhibitor W1046, which significantly suppresses AML proliferation and survival. W1046 remarkably enhances the efficacy of VISTA mAb by activating T cells via inhibition of STAT3 signaling and down-regulation of VISTA. Moreover, combination of W1046 and VISTA mAb achieves a significant anti-AML effect in vitro and in vivo. Overall, our findings confirm that VISTA is a potential target for AML therapy which transcriptionally regulated by STAT3 and provide a promising therapeutic strategy for immunotherapy of AML.

Fabricating biodegradable calcium phosphate/calcium sulfate cement reinforced with cellulose: in vitro and in vivo studies.

Osteoporosis is a growing public health concern worldwide. To avoid extra surgeries, developing biodegradable bone cement is critical for the treatment of osteoporosis. Herein, we designed calcium phosphate/calcium sulfate cement reinforced with sodium carboxymethyl cellulose (CMC/OPC). It presents an appropriate physicochemical performance for clinical handling. Meanwhile, CMC/OPC bone cement promotes osteogenic differentiation in vitro. Results of the immune response in vitro and in vivo confirmed that increasing the cellulose content triggered macrophage switching into the M2 phenotype and CMC/OPC exhibited significant anti-inflammation. Furthermore, in vitro and in vivo degradation demonstrated that cellulose tailors the degradation rate of composite bone cement, which achieved a linear degradation process and could degrade by more than 90% for 12 weeks. In summary, the composite bone cement CMC/OPC is a promising candidate for bone repair applications.

Double-network composites based on inorganic fillers reinforced dextran-based hydrogel with high strength.

The biodegradable hydrogels with a 3D network structure have potential applications in bone tissue engineering. Here, inspired by natural bone, the novel organic-inorganic composites (GelMPC-x) with high compressive strength are designed via adding magnesium oxide/calcium dihydrogen phosphate (MPC) powders into the oxidized dextran/gelatin (OD/Gel) hydrogel. GelMPC-x composites can trigger the gelation of OD/Gel hydrogel through an acid-alkaline reaction between magnesium oxide and calcium dihydrogen phosphate, thus forming an organic-inorganic double network. The cross-linked network between oxidized dextran and gelatin, and the multiple weak interactions between OD/Gel hydrogel and MPC enable the composites to have remarkable compressive strength (77-652 kPa) at the strain of 44 %. More importantly, the composites with appropriate MPC content possess superior injectability, high porosity, and excellent cytocompatibility. This work provides guidelines for the preparation of oxidized dextran-based composite hydrogels with enhanced mechanical performance.

Discovery of Novel Benzo[4,5]imidazo[1,2-a]pyrazin-1-amine-3-amide-one Derivatives as Anticancer Human A2A Adenosine Receptor Antagonists.

The blockade of A2A adenosine receptor (A2AAR) activates immunostimulatory response through regulating signaling in tumor microenvironment. Thus, A2AAR has been proposed as a promising target for cancer immunotherapy. In this work, we designed a new series of benzo[4,5]imidazo[1,2-a]pyrazin-1-amine derivatives bearing an amide substitution at 3-position to obtain potent antitumor antagonist in vivo. The structure-activity relationship studies were performed by molecular modeling and radioactive assay. The in vitro anticancer activities were evaluated by 3',5'-cyclic adenosine monophosphate (cAMP) functional and T cell activation assay. The most potent compound 12o·2HCl showed much higher affinity toward A2AAR (Ki = 0.08 nM) and exhibited more significant in vitro immunostimulatory anticancer activity than clinical antagonist AZD4635. More importantly, 12o·2HCl significantly inhibited the growth of triple-negative breast cancer by reversing immunosuppressive tumor microenvironment in the xenograft mouse model without severe toxicity at the testing dose. These results make 12o·2HCl a promising immunotherapy anticancer drug candidate.

The Double-Edged Sword of SIRT3 in Cancer and Its Therapeutic Applications.

Reprogramming of cellular energy metabolism is considered an emerging feature of cancer. Mitochondrial metabolism plays a crucial role in cancer cell proliferation, survival, and metastasis. As a major mitochondrial NAD+-dependent deacetylase, sirtuin3 (SIRT3) deacetylates and regulates the enzymes involved in regulating mitochondrial energy metabolism, including fatty acid oxidation, the Krebs cycle, and the respiratory chain to maintain metabolic homeostasis. In this article, we review the multiple roles of SIRT3 in various cancers, and systematically summarize the recent advances in the discovery of its activators and inhibitors. The roles of SIRT3 vary in different cancers and have cell- and tumor-type specificity. SIRT3 plays a unique function by mediating interactions between mitochondria and intracellular signaling. The critical functions of SIRT3 have renewed interest in the development of small molecule modulators that regulate its activity. Delineation of the underlying mechanism of SIRT3 as a critical regulator of cell metabolism and further characterization of the mitochondrial substrates of SIRT3 will deepen our understanding of the role of SIRT3 in tumorigenesis and progression and may provide novel therapeutic strategies for cancer targeting SIRT3.

Arg-Gly-Asp peptide functionalized poly-amino acid/ poly (p-benzamide) copolymer with enhanced mechanical properties and osteogenicity.

Poly-amino acid (PAA) is a promising biomaterial in biomedical engineering due to its similar amide bond structure to collagen and excellent biocompatibility, but the lack of osteogenic activity and inferior mechanical strength limit its long-term application in orthopedics. In this study, a poly-amino acid/poly (p-benzamide) (PAA-PBA) copolymer with high mechanical strength was designed and fabricated by the method of solution polymerization. The chain structures, thermal properties and mechanical properties of these polymers were evaluated and results showed that PBA greatly promoted the mechanical properties of PAA, and the copolymer performed the maximum mechanical strengths with compressive strength, bending strength and tensile strength of 123 MPa, 107 MPa and, 95 MPa, respectively. To increase the bioactivity of surface, a bioactive coating that consists of poly-(dopamine) (PDA) nanolayers and tripeptide Arginine-Glycine-Aspartic acid (RGD) on sulfonated PAA-PBA copolymer was created. A porous structure appeared on the surface after modification, the surface roughness and hydrophilicity of copolymer has been improved obviously after introducing PDA and RGD peptide coating. The in vitro bioactivity evaluation demonstrated that the RGD-functionalized sample showed a significantly improved ability to promote bone apatite mineralization, cell adhesion, proliferation and osteogenic differentiation. In a word, such a strategy of material synthesis and surface modification method shows a great potential for broadening the use of PAA in the application of load-bearing bone substitute biomaterials.

Study on the interaction between 2,6-dihydroxybenzoic acid nicotine salt and human serum albumin by multi-spectroscopy and molecular dynamics simulation.

As a new form of nicotine introduction for novel tobacco products, the interaction of nicotine salt with biological macromolecules may differ from that of free nicotine and thus affect its transport and distribution in vivo. Hence, the mechanism underlying the interaction between 2,6-dihydroxybenzoic acid nicotine salt (DBN) and human serum albumin (HSA) was investigated by multi-spectroscopy, molecular docking, and dynamic simulation. Experiments on steady-state fluorescence and fluorescence lifetime revealed that the quenching mechanism of DBN and HSA was dynamic quenching, and binding constant was in the order of 10^4 L mol-1. Thermodynamic parameters exhibited that the binding was a spontaneous process with hydrophobic forces as the main driving force. Fluorescence competition experiments revealed that DBN bound to site I of HSA IIA subdomain. According to the results of synchronous fluorescence, 3D fluorescence, FT-IR spectroscopy, circular dichroism (CD) spectroscopy, and molecular dynamics (MD) simulation, DBN did not affect the basic skeleton structure of HSA but changed the microenvironment around the amino acid residues. Computer simulations positively corroborated the experimental results. Moreover, DBN decreased the surface hydrophobicity and weakened the esterase-like activity of HSA, leading to the impaired function of the latter. This work provides important information for studying the interaction between DBN as a nicotine substitute and biological macromolecules and contributes to the further development and application of DBN.

Oxidation and polymer degradation characteristics of high viscosity modified asphalts under various aging environments.

High viscosity modified asphalt (HVMA) was the core material to build ecological permeable pavement, while it was prone to aging, which limited its applications for urban sustainability. This study focused on the oxidation and polymer degradation characteristics of the high-content styrene-butadiene-styrene modified asphalt, high-viscosity composite particle modified asphalt and high-elastic modified asphalt under the simulated aging environments of thermal oxidation and weather. Gel permeation chromatography results showed that the increase percent of large molecular size percent and the decrease percent of polymer weight could characterize the oxidation degree and polymer degradation degree, respectively. The degrees of oxidation and polymer degradation in all HVMAs increased synchronously with aging, and reached the highest after the weather aging. The polymer molecular distribution of HVMA would become more uniform with aging from the proposed ratio of polymer weight to polymer content. Dynamic shear rheometer tests reflected that there existed the dual effects of coupling and parallelism during aging of HVMA, i.e. the oxidation-induced hardening effect and degradation-induced softening effect. Furthermore, the change percent of rheological indicators was proposed as the net aging degree. Considering the rheological properties of aged HVMA were the coupling results of dual effects, the net aging degree could represent the oxidation dominance degree or polymer degradation dominance degree of HVMA. Due to the differences of dual effects and polymer molecular distribution, various HVMAs showed the totally different net aging degree ranking, depending on the aging states and rheological indicators. Notably, the high-elastic modified asphalt showed the greatest aging resistance at all aging states as a result of its weak dual effects and most uniform polymer molecular distribution.

Lenvatinib Plus PD-1 Inhibitors as First-Line Treatment in Patients With Unresectable Biliary Tract Cancer: A Single-Arm, Open-Label, Phase II Study.

OBJECTIVE: We investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC). METHODS: In this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg; <60 kg, 8 mg) daily and PD-1 inhibitors (pembrolizumab/tislelizumab/sintilimab/camrelizumab 200 mg or toripalimab 240 mg) every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included surgical conversion rate, disease control rate (DCR), event-free survival (EFS), overall survival (OS) and tumor biomarkers. RESULTS: Among 38 enrolled patients, the ORR was 42.1% and the DCR was 76.3%. Thirteen (34.2%) patients achieved downstaging and underwent surgery, six of whom (46.2%) achieved a major pathologic response (n=2) or partial pathologic response (n=4) in the primary tumor. In total, 84.2% of patients experienced ≥1 treatment-related adverse event (TRAE), 34.2% experienced a Grade ≥3 TRAE and no treatment-related deaths occurred. After a median follow-up of 13.7 months the median EFS was 8.0 months (95% CI: 4.6-11.4) and the median OS was 17.7 months (95% CI: not estimable). CONCLUSIONS: Lenvatinib plus PD-1 inhibitors showed promising anti-tumor efficacy in patients with initially unresectable BTC and was generally well tolerated. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, ChiCTR2100044476.

Effects of pullulan on the biomechanical and anti-collapse properties of dicalcium phosphate dihydrate bone cement.

In this work, a modified dicalcium phosphate dihydrate (DCPD) bone cement with unique biodegradable ability in a calcium phosphate cement system was prepared by the hydration reaction of monocalcium phosphate monohydrate and calcium oxide and integration with pullulan (Pul), a non-toxic, biocompatible, viscous, and water-soluble polysaccharide that has been successfully used to improve defects in DCPD bone cement, especially its rapid solidification, fragile mechanical properties, and easy collapse. The effect of different contents of Pul on the structure and properties of DCPD were also studied in detail. The modified cement was characterised by X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, ultraviolet-visible absorption, X-ray photoelectron spectroscopy analysis, and rheological property measurements. The results indicated that Pul promoted the hydration formation of DCPD, and interface bonding occurred between Pul and DCPD. With increasing content of Pul, the setting time of the DCPD bone cement increased from 2.6 min to 42.3 min, the compressive strength increased from 0 MPa to 20.4 MPa, and the anti-collapse ability also improved owing to the strong interface bonding, implying that the DCPD bone cement improved by Pul has better potential for application in the field of non-loading bone regenerative medicine compared to unmodified DCPD bone cement.

A novel degradable tricalcium silicate/calcium polyphosphate/polyvinyl alcohol organic-inorganic composite cement for bone filling.

In this study, tricalcium silicate (C3S) calcium/polyphosphate/polyvinyl alcohol organic-inorganic self-setting composites were successfully designed. A variety of tests were conducted to characterize their self-setting properties, mechanical properties, degradation properties, and related biological properties. The composite bone cements showed a short setting time (5.5-37.5 min) with a 5:5-6:4 ratio of C3S/CPP to maintain a stable compressive strength (28 MPa). In addition, PVA effectively reduced the brittleness of the inorganic phase. Degradation experiments confirmed the sustainable surface degradation of bone cement. A maximum degradation rate of 49% was reached within 56 days, and the structure remained intact without collapse. Culturing MC3T3 cells with bone cement extracts revealed that the composite bone cements had excellent biological properties in vitro. The original extract showed a proliferation promotion effect on cells, whereas most of the other original extracts of degradable bone cements were toxic to the cells. Meanwhile, extracellular matrix mineralization and alkaline phosphatase expression showed remarkable effects on cell differentiation. In addition, a good level of adhesion of cells to the surfaces of materials was observed. Taken together, these results indicate that C3S/CPP/PVA composite bone cements have great potential in bone defect filling for fast curing.

Dynamic Behavior of a Precast and Partial Steel Joint under Various Shear Span-to-Depth Ratios.

The dynamic behavior of a PPSRC beam-column joint is related to constraint effect, strength deterioration and strain rate effect. Then, it can be assessed by bearing capacity, stiffness degradation, displacement ductility and energy consumption. The results show that the increased strain rate causes growth in ring stiffness, bearing capacity and energy consumption of PPSRC beam-column joints. However, the influence of shear span-to-depth ratio on dynamic mechanical properties of PPSRC beam-column joints is more obvious than that of strain rate. Regardless of strain rate, the bearing capacity, initial stiffness, ring stiffness and energy consumption of PPSRC beam-column joints decrease as the shear span-to-depth ratio increases. Moreover, the ring stiffness under reverse direction is smaller than that the under forward direction at each displacement level. However, the stiffness degradation under a lower shear span-to-depth ratio is more obvious than that under a higher shear span-to-depth ratio. Moreover, the displacement ductility with a higher shear span-to-depth ratio is better than that with a lower shear span-to-depth ratio. Finally, the mechanical properties of PPSRC beam-column joints are affected by the extension length of partial steel plate, and the reasonable extension length of the partial steel plate in the column is affected by the shear span-to-depth ratio.

Developing a biodegradable tricalcium silicate/glucono-delta-lactone/calcium sulfate dihydrate composite cement with high preliminary mechanical property for bone filling.

Bone cements with the feature of easily shaping could ideally match the defect site and prevent the ingrowth of fibrous tissue. In this manuscript, a biodegradable tricalcium silicate (C3S)/glucono-delta-lactone (GDL)/calcium sulfate dihydrate (CSD) organic-inorganic composite cement was fabricated with shorter setting time (less than 15 min) and high preliminary mechanical property (5.27 MPa in the first hour). Many methods were applied to study the physicochemical and biological properties of the cement in vitro. The weight loss in PBS can reach 58% after 12 weeks soaking indicating the better biodegradability. The excellent bioactivity in vitro was emerging after the cement was soaked in the simulated body fluid. The cell experiments showed that suitable concentration of the extract liquid of cement was conducive to the proliferation, differentiation and extracellular matrix calcification of the mouse bone marrow stromal cells. Briefly, the C3S/GDL/CSD composite cement would have the bright capacity for bone filling.