Optimizing the Strength and Toughness of V/Mo-Modified 0.22C-5.24Mn Steel by Short-Time Partial Austenitization Process.

In order to obtain the good match between yield strength and low-temperature toughness, the short-time partial austenitization (SPA) process was employed for V/Mo-bearing 0.22C-5.24Mn steel. The initial microstructure after intercritical tempering was dual-phase ferrite and reversed austenite (RA), while the final microstructure consisted of ferrite, RA, and secondary martensite (SM) after being subjected to the SPA process. (V, Mo)C with disclike morphology mainly precipitated during intercritical tempering, and the aspect ratio of particles decreased, leading to the appearance of near-spherical morphology. After being subjected to SPA process, the resultant multiphase hierarchical microstructure (three layers: outer layer of ferrite, interlayer of SM, and inner layer of RA) enabled a high yield strength of 1097 MPa, a total elongation of 14%, and an impressive impact energy of 33.3 J at -20 °C. The strengthening contribution of (V, Mo)C precipitation was estimated to be about 108 MPa.

Oncolytic mineralized bacteria as potent locally administered immunotherapeutics.

Oncolytic bacteria can trigger innate immune activity. However, the antitumour efficacy of inactivated bacteria is poor, and attenuated live bacteria pose substantial safety risks. Here we show that intratumourally injected paraformaldehyde-fixed bacteria coated with manganese dioxide potently activate innate immune activity, modulate the immunosuppressive tumour microenvironment and trigger tumour-specific immune responses and abscopal antitumour responses. A single intratumoural administration of mineralized Salmonella typhimurium suppressed the growth of multiple types of subcutaneous and orthotopic tumours in mice, rabbits and tree shrews and protected the cured animals against tumour rechallenge. We also show that mineralized bacteria can be administered via arterial embolization to treat orthotopic liver cancer in rabbits. Our findings support the further translational testing of oncolytic mineralized bacteria as potent and safe antitumour immunotherapeutics.

Research progress of nanovaccine in anti-tumor immunotherapy.

Tumor vaccines aim to activate dormant or unresponsive tumor-specific T lymphocytes by using tumor-specific or tumor-associated antigens, thus enhancing the body's natural defense against cancer. However, the effectiveness of tumor vaccines is limited by the presence of tumor heterogeneity, low immunogenicity, and immune evasion mechanisms. Fortunately, multifunctional nanoparticles offer a unique chance to address these issues. With the advantages of their small size, high stability, efficient drug delivery, and controlled surface chemistry, nanomaterials can precisely target tumor sites, improve the delivery of tumor antigens and immune adjuvants, reshape the immunosuppressive tumor microenvironment, and enhance the body's anti-tumor immune response, resulting in improved efficacy and reduced side effects. Nanovaccine, a type of vaccine that uses nanotechnology to deliver antigens and adjuvants to immune cells, has emerged as a promising strategy for cancer immunotherapy due to its ability to stimulate immune responses and induce tumor-specific immunity. In this review, we discussed the compositions and types of nanovaccine, and the mechanisms behind their anti-tumor effects based on the latest research. We hope that this will provide a more scientific basis for designing tumor vaccines and enhancing the effectiveness of tumor immunotherapy.

Nucleic acid aptamer-based biosensors and their application in thrombin analysis.

Thrombin is a multifunctional serine protease that plays an important role in coagulation and anticoagulation processes. Aptamers have been widely applied in biosensors due to their high specificity, low cost and good biocompatibility. This review summarizes recent advances in thrombin quantification using aptamer-based biosensors. The primary focus is optical sensors and electrochemical sensors, along with their applications in thrombin analysis and disease diagnosis.

Study of Oncolytic Virus Preservation and Formulation.

In recent years, oncolytic viruses (OVs) have emerged as an effective means of treating cancer. OVs have multiple oncotherapeutic functions including specifically infecting and lysing tumor cells, initiating immune cell death, attacking and destroying tumor angiogenesis and triggering a broad bystander effect. Oncolytic viruses have been used in clinical trials and clinical treatment as drugs for cancer therapy, and as a result, oncolytic viruses are required to have long-term storage stability for clinical use. In the clinical application of oncolytic viruses, formulation design plays a decisive role in the stability of the virus. Therefore, this paper reviews the degradation factors and their degradation mechanisms (pH, thermal stress, freeze-thaw damage, surface adsorption, oxidation, etc.) faced by oncolytic viruses during storage, and it discusses how to rationally add excipients for the degradation mechanisms to achieve the purpose of maintaining the long-term stability of oncolytic viral activity. Finally, the formulation strategies for the long-term formulation stability of oncolytic viruses are discussed in terms of buffers, permeation agents, cryoprotectants, surfactants, free radical scavengers, and bulking agent based on virus degradation mechanisms.

Signal Amplification-Based Biosensors and Application in RNA Tumor Markers.

Tumor markers are important substances for assessing cancer development. In recent years, RNA tumor markers have attracted significant attention, and studies have shown that their abnormal expression of post-transcriptional regulatory genes is associated with tumor progression. Therefore, RNA tumor markers are considered as potential targets in clinical diagnosis and prognosis. Many studies show that biosensors have good application prospects in the field of medical diagnosis. The application of biosensors in RNA tumor markers is developing rapidly. These sensors have the advantages of high sensitivity, excellent selectivity, and convenience. However, the detection abundance of RNA tumor markers is low. In order to improve the detection sensitivity, researchers have developed a variety of signal amplification strategies to enhance the detection signal. In this review, after a brief introduction of the sensing principles and designs of different biosensing platforms, we will summarize the latest research progress of electrochemical, photoelectrochemical, and fluorescent biosensors based on signal amplification strategies for detecting RNA tumor markers. This review provides a high sensitivity and good selectivity sensing platform for early-stage cancer research. It provides a new idea for the development of accurate, sensitive, and convenient biological analysis in the future, which can be used for the early diagnosis and monitoring of cancer and contribute to the reduction in the mortality rate.

Electrochemical Sensor Based on Nanomaterials and Its Application in the Detection of Alpha Fetoprotein.

Hepatocellular carcinoma development and many other tumors are closely related to alpha-fetoprotein (AFP), its determination can be used as a positive test for tumors. It is mainly used clinically as a serum marker to diagnose and monitor the efficacy of primary hepatocellular carcinoma. Therefore, a variety of biosensors have been developed to detect AFP. Electrochemical sensors integrate a variety of detection methods. They have inherent advantages over other types of sensors, they are fast, portable, simple, and highly sensitive. Some meaningful electrochemical biosensors work with nanomaterials acting as signal amplification elements or as signal amplification catalysts. This review introduced the field of biosensors and discuss about the use of nanomaterials in electrochemical sensing, specificity electrochemical biosensing of AFP. The study ends with a discussion about the prospects for nanomaterial-based signal amplification and future research directions.

Effect of Mn Content on the Toughness and Plasticity of Hot-Rolled High-Carbon Medium Manganese Steel.

The tensile and impact deformation behavior of three different Mn content test steels, xMn-1.0C-0.25V-1.5Cr-0.3Mo (5, 8 and 13 wt%), were investigated using mechanical properties testing, SEM-EBSD and TEM. The elongation and -20 °C impact energy of the three types of Mn content test steels increased as the Mn content increased. The room temperature tensile elongation was 9%, 23% and 81%, and the -20 °C impact energy was 9 J, 99 J and 241 J, respectively. The fracture morphologies of 5 Mn and 8 Mn were found to be cleavage fractures with secondary cracks and micro-voids. The 13 Mn fracture morphology was a plastic fracture with many coarse dimples. Transverse cracks perpendicular to the tensile direction occurred on the surface of the gauge area of 5 Mn and 8 Mn tensile specimens, reducing plasticity dramatically. This was mainly related to the martensitic transformation produced by stress. We characterized the martensite near the tensile fracture and speculated the main mode of crack propagation. Furthermore, a little amount of sharp-shaped BCC phase was found in the 5 Mn, which was determined to be a hard phase relative to the austenite matrix by nanoindentation test. These steels have stacking fault energies ranging from ~15 to ~29 mJ/m2 with increasing Mn content 13 Mn has high stacking fault energy (SFE) and austenite stability. Twin-induced plasticity (TWIP) was the deformation mechanism.

Superior Comprehensive Mechanical Properties of a Low-Carbon Medium Manganese Steel for Replacing AISI 4330 Steel in the Oil and Gas Industry.

A low-carbon medium manganese steel (0.12C-3.13Mn) containing Cr, Ni, Mo, V, and Cu elements was designed to replace the AISI 4330 steel applied in the oil and gas industry. The mechanical properties, microstructures, and fatigue crack growth rate were comparatively analyzed using uniaxial tension tests, microstructure characterization, and compact tension with fatigue crack growth characterization. The results showed that the ductility and -40 °C impact energy of 0.12C-3.13Mn steel were better than AISI 4330 steel (from 115 J to 179 J), while the yield strength of 957 MPa of the former was lower than the latter of 1060 MPa after being subjected to the same tempering process. The microstructure of 0.12C-3.13Mn steel was composed of a mixture of tempered martensite, reversed austenite, and nanosized precipitation particles, while the microstructure of S4330 steel contained ferrite and large-size Fe3C with lath and near-spherical morphologies. Compared to Cr-rich Fe3C, (V, Mo)C and Cu-rich particles have smaller sizes and, thus, provide more strengthening increment, leading to a higher yield ratio. The impressive fatigue-resistance property was obtained in 0.12C-3.13Mn steel because the threshold value was 5.23 MPa*m1/2 compared to the value of 4.88 MPa*m1/2 for S4330 steel. Even if the fatigue crack grew, the stress intensity factor range of 0.12C-3.13Mn steel was obviously wider than that of AISI 4330 steel due to the presence of reversed austenite and secondary cracks. Overall, the AISI 4330 steel could be replaced with the designed 0.12C-3.13Mn steel due to the similar strength and better ductility, low-temperature toughness, and fatigue-resistance property.

Fluorescent "turn-on" aptamer sensor for sensitive and reliable detection of Golgi glycoprotein 73 based on nitrogen-doped graphene quantum dots and molybdenum disulfide nanosheets.

The sensitivity and specificity of Golgi glycoprotein 73 (GP73) are very important for early diagnosis of hepatocellular carcinoma. Herein, we constructed a new-fashioned fluorescent aptamer sensor for GP73 determination based on nitrogen-doped graphene quantum dots (N-GQDS) and molybdenum disulfide (MoS2) nanosheets. N-GQDs with high fluorescence intensity and good stability were screened out, and GP73 aptamer (GP73Apt) is labeled with N-GQDs to form the N-GQDs-GP73Apt fluorescence probe. MoS2 nanosheets can quench the fluorescence of N-GQDs-GP73Apt owing to fluorescence resonance energy transfer mechanisms. After introducing GP73 into the biosensing system, the N-GQDs-GP73Apt specifically bound with GP73 to form the deployable structures, making N-GQDs-GP73Apt far away from MoS2, blocking the fluorescence energy transfer process, and restoring the fluorescence of N-GQDs-GP73Apt. When the GP73 concentration was in the extent of 2.5 ng/mL∼100 ng/mL, the relative fluorescence recovery is linearly relevant to the concentration of GP73, and the limit of detection (LOD) was 1.29 ng/mL (S/N = 3). Moreover in the application of actual serum sample detection, the recovery was range 98.85∼100.55 %. The fluorescent aptamer sensor can rapidly detect and analyze the serum marker GP73 with the characteristics of low-cost, high sensitivity, good specificity and recovery.

Oncolytic viral vectors in the era of diversified cancer therapy: from preclinical to clinical

With the in-depth research and wide application of immunotherapy recently, new therapies based on oncolytic viruses are expected to create new prospects for cancer treatment via eliminating the suppression of the immune system by tumors. Currently, an increasing number of viruses are developed and engineered, and various virus vectors based on effectively stimulating human immune system to kill tumor cells have been approved for clinical treatment. Although the virus can retard the proliferation of tumor cells, the choice of oncolytic viruses in biological cancer therapy is equally critical given their therapeutic efficacy, safety and adverse effects. Moreover, previously known oncolytic viruses have not been systematically classified. Therefore, in this review, we summarized and distinguished the characteristics of several common types of oncolytic viruses: herpes simplex virus, adenovirus, measles virus, Newcastle disease virus, reovirus and respiratory syncytial virus. Subsequently, we outlined that these oncolytic viral vectors have been transformed from preclinical studies in combination with immunotherapy, radiotherapy, chemotherapy, and nanoparticles into clinical therapeutic strategies for various advanced solid malignancies or circulatory system cancers. (AU)

Oncolytic viral vectors in the era of diversified cancer therapy: from preclinical to clinical.

With the in-depth research and wide application of immunotherapy recently, new therapies based on oncolytic viruses are expected to create new prospects for cancer treatment via eliminating the suppression of the immune system by tumors. Currently, an increasing number of viruses are developed and engineered, and various virus vectors based on effectively stimulating human immune system to kill tumor cells have been approved for clinical treatment. Although the virus can retard the proliferation of tumor cells, the choice of oncolytic viruses in biological cancer therapy is equally critical given their therapeutic efficacy, safety and adverse effects. Moreover, previously known oncolytic viruses have not been systematically classified. Therefore, in this review, we summarized and distinguished the characteristics of several common types of oncolytic viruses: herpes simplex virus, adenovirus, measles virus, Newcastle disease virus, reovirus and respiratory syncytial virus. Subsequently, we outlined that these oncolytic viral vectors have been transformed from preclinical studies in combination with immunotherapy, radiotherapy, chemotherapy, and nanoparticles into clinical therapeutic strategies for various advanced solid malignancies or circulatory system cancers.

Aptamer-based biosensors and application in tumor theranostics.

An aptamer is a short oligonucleotide chain that can specifically recognize targeting analytes. Due to its high specificity, low cost, and good biocompatibility, aptamers as the targeting elements of biosensors have been applied widely in non-invasive tumor imaging and treatment in situ to replace traditional methods. In this review, we will summarize recent advances in using aptamer-based biosensors in tumor diagnosis. After a brief introduction of the advantage of aptamers compared with enzyme sensors and immune sensors, the different sensing designs and mechanisms based on 3 signal transduction modes will be reviewed to cover different kinds of analytical methods, including: electrochemistry analysis, colorimetry analysis, and fluorescence analysis. Finally, the prospective advantages of aptamer-based biosensors in tumor theranostics and post-treatment monitoring are also evaluated in this review.

Protective Effect of Curcumin on Bone Trauma in a Rat Model via Expansion of Myeloid Derived Suppressor Cells.

BACKGROUND Bone fracture, a common injury to bones leads to various biophysiological changes and pathological responses in the body. The current study investigated curcumin for treatment of bone fracture in a rat model of bone trauma, and evaluated the related mechanism. MATERIAL AND METHODS The rats were separated randomly into 3 groups; sham, model, and curcumin treatment groups. The fracture rat model was established by transverse osteotomy in the right femur bone at the mid-shaft. The osteoblast count was determined using hematoxylin and eosin staining. Vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) expression were measured by western blotting. RESULTS The rpS6-phosphorylation was suppressed and light chain 3 (LC3II) expression elevated in the curcumin treated group of the fracture rat model. In the curcumin-treated group, mineralization of fracture calluses was markedly higher on day 14 of fracture. The formation of osteoblasts was observed at a greater rate in the curcumin treated group compared to the model rat group. Treatment of rats with curcumin significantly (P<0.05) promoted expression of PCNA and VEGF. The decrease in CD11b+/Gr-1+ cell expansion in rats with bone trauma was alleviated significantly by curcumin treatment. A marked increase in arginase-1 expression in rats with bone trauma was caused by curcumin treatment. CONCLUSIONS In summary, curcumin activates autophagy and inhibits mTOR activation in bone tissues of rats with trauma. The curcumin promoted myeloid-derived suppressor cell (MDSC) proliferation and increased expansion of MDSCs in a rat model of trauma. Therefore, curcumin may have beneficial effect in patients with bone trauma and should be evaluated further for development of treatment.

Short-term curative effect and safety of propranolol combined with laser in the treatment of infantile hemangiomas.

Short-term curative effect and safety of propranolol combined with laser in the treatment of infantile hemangiomas was studied, so as to provide reference for clinical treatment. A total of 100 cases of infantile hemangiomas admitted to the Affiliated Hospital of Jining Medical University from October 2014 to June 2016 were selected into this study. According to the random number table method, they were divided into the control group and the observation group, with 50 cases in each group. The infant patients in the control group were treated with laser alone, and the infant patients in the observation group were treated with propranolol combined with laser. The healing time, the number of times of laser therapy, the short-term curative effect, the changes in serum inflammatory factors before and after treatment and the incidence of adverse reactions were compared between the two groups of infant patients. The healing time and the times of laser therapy of the infant patients in the observation group were less than those of the infant patients in the control group, and the differences were statistically significant (p<0.05). The short-term curative effect of the observation group (98%) was higher than that of the control group (82%), and the difference was statistically significant (p<0.05). The levels of serum inflammatory factors interleukin (IL)-2, IL-6 and IL-10 in the two groups of infant patients after treatment were lower than those before treatment, and the levels in the observation group were lower than those in the control group, and the differences were statistically significant (p<0.05). Propranolol combined with laser in the treatment of infantile hemangiomas has remarkable short-term curative effects. It can effectively reduce the levels of inflammatory factors, shorten the healing time and reduce the number of times of laser therapy. It is safe and worthy of clinical promotion.

Profile of psychiatric symptoms in methamphetamine users in China: Greater risk of psychiatric symptoms with a longer duration of use.

Chronic methamphetamine (MA) use is associated with psychiatric symptoms. This study explored pattern of co-occurring psychiatric symptoms in MA users and their relationship to duration of MA use. A cross-sectional study was conducted among MA users at the Shenzhen Compulsory Drug Detoxification Center from April 2012 to October 2015. The Positive and Negative Syndrome Scale, Hamilton Anxiety Scale, and Beck Depression Inventory were used to assess psychiatric symptoms. Among 1277 MA users, 57.6% participants had any type of psychiatric symptoms including depressive, anxiety and psychotic symptoms. A dose-response relationship was found between duration of MA use and risk of psychiatric symptoms. The odds ratios (OR) of depressive symptoms increased with the duration of MA use (1-5 years vs. < 1 year: 1.74 [95% CI, 1.24-2.42]; ≥ 5 years vs. < 1 year: 2.07 [1.19-3.61]), so did the ORs of co-occurring anxiety and depressive symptoms (1-5 years: 1.74 [1.20-2.51]; ≥ 5 years: 3.09 [1.76-5.40]). Methamphetamine-dependent individuals were four-times more likely to experience any type of psychiatric symptoms than non-dependent users. The prevalence of psychiatric symptoms was high in chronic MA users and increased with MA use duration. Early prevention and treatment strategies targeting both MA use and associated psychiatric symptoms are needed.

Allogeneic adipose-derived stem cells with low immunogenicity constructing tissue-engineered bone for repairing bone defects in pigs.

The ideal cells for tissue engineering should have the following characteristics: easy obtainment, safety, immune privilege, the capability of self-renewal, and multipotency. Adipose-derived stem cells (ADSCs) are a promising candidate. However, the immunogenicity of allogeneic mesenchymal stem cells limits their long-term benefits. In this study, we introduced human cytomegalovirus US2/US3 gene into the ADSCs to decrease the expression of MHC I protein of ADSCs and reduce the activation of T-cells of the recipient animals. Moreover, the biosafety and biological characteristics of ADSCs transfected with the US2/US3 genes (ADSCs-US2/US3) were similar to normal ADSCs. Then we took ADSCs-US2/US3 to construct a tissue-engineered bone for repairing bone defects in pigs and found that there were no great differences in repair effects or healing time between the allogeneic ADSCs-US2/US3 group and the autologous ADSC group. These results suggest that allogeneic ADSCs-US2/US3 have the advantages of biological safety, low immunogenicity, and effective osteogenesis. Such barely immunogenic ADSCs will be crucial for the success of future tissue-regenerative approaches.

Biomimetic construction of large engineered bone using hemoperfusion and cyto-capture in traumatic bone defect.

Due to lack of blood vessel systems, only a few tissues, such as skin, cartilage, and cornea, have been successfully constructed in vivo. Anticoagulative scaffolds have been used in drug-eluting stent systems both in animal studies and clinical therapies, as in the medicinal leech therapy used to salvage venous-congested microvascular free flaps improved perfusion inspired us to tackle this hurdle in bone tissue engineering. We hypothesize that a combination of bone marrow as the blood supply and a heparin/chitosan-coated acellular bone matrix that acts like hirudin, together with a vacuum-assisted closure therapy system, would provide blood perfusion to the scaffold. Using these methods, a biomimetically engineered bone construct would facilitate clinical translation in bone tissue engineering and offer new therapeutic strategies for reconstructing large bone defects if the hypothesis proves to be practical.

Heparin-chitosan-coated acellular bone matrix enhances perfusion of blood and vascularization in bone tissue engineering scaffolds.

Currently, the main hurdle in the tissue engineering field is how to provide sufficient blood supply to grafted tissue substitutes in the early post-transplanted period. For three-dimensional, cell-dense, thick tissues to survive after transplantation, treatments are required for hypoxia, nutrient insufficiency, and the accumulation of waste products. In this study, a biomacromolecular layer-by-layer coating process of chitosan/heparin onto a decellularized extracellular bone matrix was designed to accelerate the blood perfusion and re-endothelialization process. The results of in vitro measurements of the activated partial thromboplastin time supported the theory that the combination of chitosan and heparin could bring both anticoagulation and hemocompatibility to the scaffold. A rabbit bone defect model was established for further evaluation of the application of this kind of surface-modified scaffold in vivo. The final results of computed tomography (CT) perfusion imaging and histological examination proved that this facile coating approach could significantly promote blood perfusion and re-endothelialization in the early post-transplanted period compared with an acellular bone matrix due to its much-improved anticoagulation property.

Adipose-derived stem cells modified genetically in vivo promote reconstruction of bone defects.

AIMS: Bone defects induced by different causes are difficult to replace and repair. We sought to repair bone defects by transplantation of genetically modified adipose-derived stem cells (ADSC) and acellular bone matrix (ACBM). METHODS: We constructed the biologic material of ACBM and evaluated its mechanical properties, general biocompatibility and biosafety. ADSC isolated from minipigs were cultured in vitro and then transfected by recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human vascular endothelial growth factor (rhVEGF) plasmids, respectively. Subsequently, the compounds of ACBM/ADSC/rhBMP-2/rhVEGF were used to repair bone defects of the ulna in minipigs. X-ray examination, radionuclide bone imaging and single photon emission computerized tomography (SPECT) were employed to monitor the therapeutic effects 2, 4, 8 and 12 weeks after operation. Histologic experiments were carried out 12 weeks after operation. RESULTS: ACBM had no or weak antigenicity and the natural mechanical properties of ACBM were preserved. In vitro, ADSC transfected by rhBMP-2 and rhVEGF, respectively, could release rhBMP-2 or rhVEGF for at least 4 weeks. The X-ray, radionuclide bone imaging and SPECT examinations indicated that the compound of ACBM/ADSC/rhBMP-2/rhVEGF had better treatment effects on bone defects compared with the controls. CONCLUSIONS: Scaffolds, seed cells and bioactive factors are key points in tissue engineering. This research indicates that ACBM is a good biologic material for tissue repair, and ACBM/ADSC/rhBMP-2/rhVEGF can accelerate bone formation significantly.