Objective: To investigate the barrier membrane fixation performance and enhanced guided bone regeneration (GBR) capability of a thermosensitive adhesive containing bioactive glass nanoparticles in order to provide a novel solution for membrane fixation during GBR procedures. Methods: M2NP@BGN (methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle), a thermosensitive adhesive, was synthesized via free radical polymerization by compositing methoxyethyl acrylate, N-isopropylacrylamide, and protocatechuic acid into a basic adhesive that was modified with bioactive glass nanoparticle (BGN). The successful fabrication of basic adhesive M2NP was characterized by attenuated total reflection-Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The thermosensitive adhesive M2NP@BGN (BGN concentration of 1 mg/mL) was characterized by scanning electron microscopy and a rheometer. By adjusting the BGN concentration (0.1 mg/mL, 0.5 mg/mL, 1 mg/mL, and 2 mg/mL), the adhesive and mechanical strengths were investigated with a universal testing machine. Biocompatibility was evaluated with a cell counting kit-8 assay and hemolysis test to identify the optimal formulation. The optimal material’s extract was co-cultured with mouse bone marrow mesenchymal stem cells, and its osteogenic activity was examined in vitro by quantitative real-time PCR, alkaline phosphatase, and alizarin red S staining. The rat mandibular defect model was established, filled with bone graft, and divided into 3 groups based on membrane fixation method: M2NP@BGN (BGN concentration of 1 mg/mL) fixation group (M2NP@BGN), titanium nail fixation group (Nail), and unfixed control group (Negative). Bone regeneration was analyzed after 8 weeks by micro computed tomography and histological staining. Results: M2NP@BGN (BGN concentration of 1 mg/mL) was successfully synthesized and demonstrated rapid gelation under warm, humid conditions. The adhesive with a BGN concentration of 1 mg/mL exhibited the highest adhesive strength (P < 0.001) and significantly enhanced mechanical strength (P < 0.001) under 37℃ wet conditions. All formulations showed excellent biocompatibility, with cell viability > 80% and hemolysis ratio < 5%. M2NP@BGN (BGN concentration of 1 mg/mL) significantly upregulated the expression of Runx2 and Col I (P < 0.001) and enhanced the activity of osteogenic differentiation markers (P < 0.05). In the animal model, the M2NP@BGN group (BGN concentration of 1 mg/mL) achieved significantly higher bone volume fraction and better bone maturity compared to the negative and nail groups (P < 0.05). Conclusion M2NP@BGN (BGN concentration of 1 mg/mL) combines excellent wet adhesion with potent osteogenic activity, enhances the bone augmentation efficacy of membranes, and presents a novel fixation strategy with significant clinical translation potential for GBR therapy.

This study was aimed at investigating the effects and mechanisms of Toxoplasma gondii type Ⅰ(RH strain)ROP16 protein on proliferation and the cell cycle in mouse alveolar macrophage MH-S cells.We constructed a Toxoplasma gondii type Ⅰ(RH)ROP16 overexpression lentivirus,transduced MH-S cells,and then screened cells with puromycin to obtain a cell line stably overexpressing ROP16Ⅰ.RT-qPCR and western blotting were used to verify expression effects,CCK-8 assays were used to detect cell proliferation activity,and flow cytometry was used to detect cell cycle changes.Western blotting and RT-qPCR were used to detect the expression levels of p53,p21,CDK6,Cyclin D1,STAT3,p-STAT3(Y705),and JAK1 proteins or genes,and immunofluorescence was used to detect the expression levels of ROP16Ⅰ and p-STAT3(Y705)and their subcellular co-localization in MH-S cells.ROP16Ⅰ protein and gene expression were detected in MH-S cells transduced with lentivirus for ROP16Ⅰ overexpression.CCK-8 assays revealed that ROP16Ⅰ promoted the proliferation of MH-S cells(P＜0.01)and enhanced cell viability.Flow cytometry revealed that ROP16Ⅰ overexpression decreased the G0/G1 phase and elevated the G2 and S phases of the cell cycle in MH-S cells(P＜0.01 or P＜0.05).Compared with the MH-S cell group and MH-S-empty vector group,the MH-S-ROP16 cell group showed lower expression of p53 and p21 proteins;higher expression of CDK6,Cyclin D1,p-STAT3(Y705),and JAK1 proteins;lower expression of p53 and p21 mRNAs;and higher expression of CDK6 and Cyclin D1 mRNAs(all P＜0.01).Immunofluorescence revealed that ROP16Ⅰ co-localized with p-STAT3(Y705)in the nucleus and surrounding cytoplasm.Therefore,Toxoplasma gondii type Ⅰ(RH)ROP16Ⅰ protein activates the JAK-STAT3 pathway;shortens the G0/G1 phase and lengthens the G2/S phase of the cell cycle;and promotes cell proliferation.These findings provide a theoretical basis for revealing the mechanism of immune evasion of Toxoplasma gondii,and lay a foundation for research on the prevention and treatment of Toxoplasma gondii pneumonia.

In the canonical model of gene transcription,transcription factors regulate the transcription of target genes by binding to double-stranded DNA(dsDNA)containing its specific consensus motifs.In contrast to dsDNA,G-quadruplexes are atypical nucleic acid secondary structures formed by guanine-rich sequences.G-quadruplex structures are involved in regulating various biological processes,including gene transcription,and have emerged as a significant research topic in the field of molecular biology.Re-cently,many research groups,including us,have revealed that G-quadruplex structures recruit transcrip-tion factors to bind to the promoters more efficiently than dsDNA,thereby enhancing target gene expres-sion.However,there is currently a lack of comprehensive summaries and discussions regarding this atypi-cal model of gene transcription regulation.In this review,we first elucidate the characteristics of G-quad-ruplex structures and the techniques used to identify these structures.G-quadruplexes can be classified into intramolecular and intermolecular types;intramolecular G-quadruplexes are further divided into par-allel,antiparallel and hybrid types.The G-quadruplex structures can be determined using techniques such as circular dichroism,nuclear magnetic resonance spectroscopy and gel migration,among others.Then,we discuss the regulatory role of G-quadruplex in gene transcription.G-quadruplexes are mainly highly enriched in gene promoter.Early studies revealed that G-quadruplexes can inhibit gene transcrip-tion.However,lots of studies have recently proven that this structure has a new function of recruiting transcription factors to activate gene transcription.Finally,we summarize the classification of transcrip-tion factors with G-quadruplex binding activity,including transcription factors with C2H2 zinc fingers,forked head/winged helices,and p53 domains.The DNA-binding domain determines the interaction be-tween transcription factors and G-quadruplex.Moreover,we propose future research directions in the field of G-quadruplex and transcription factors in regulating gene transcription.In conclusion,this review can provide important guidance for understanding the concept of G-quadruplex as a cis-acting element for transcriptional activation.

In the canonical model of gene transcription,transcription factors regulate the transcription of target genes by binding to double-stranded DNA(dsDNA)containing its specific consensus motifs.In contrast to dsDNA,G-quadruplexes are atypical nucleic acid secondary structures formed by guanine-rich sequences.G-quadruplex structures are involved in regulating various biological processes,including gene transcription,and have emerged as a significant research topic in the field of molecular biology.Re-cently,many research groups,including us,have revealed that G-quadruplex structures recruit transcrip-tion factors to bind to the promoters more efficiently than dsDNA,thereby enhancing target gene expres-sion.However,there is currently a lack of comprehensive summaries and discussions regarding this atypi-cal model of gene transcription regulation.In this review,we first elucidate the characteristics of G-quad-ruplex structures and the techniques used to identify these structures.G-quadruplexes can be classified into intramolecular and intermolecular types;intramolecular G-quadruplexes are further divided into par-allel,antiparallel and hybrid types.The G-quadruplex structures can be determined using techniques such as circular dichroism,nuclear magnetic resonance spectroscopy and gel migration,among others.Then,we discuss the regulatory role of G-quadruplex in gene transcription.G-quadruplexes are mainly highly enriched in gene promoter.Early studies revealed that G-quadruplexes can inhibit gene transcrip-tion.However,lots of studies have recently proven that this structure has a new function of recruiting transcription factors to activate gene transcription.Finally,we summarize the classification of transcrip-tion factors with G-quadruplex binding activity,including transcription factors with C2H2 zinc fingers,forked head/winged helices,and p53 domains.The DNA-binding domain determines the interaction be-tween transcription factors and G-quadruplex.Moreover,we propose future research directions in the field of G-quadruplex and transcription factors in regulating gene transcription.In conclusion,this review can provide important guidance for understanding the concept of G-quadruplex as a cis-acting element for transcriptional activation.

Objective To explore the value of support vector machine(SVM)model based on gray matter volume(GMV)for identifying amyotrophic lateral sclerosis(ALS),also to analyze the relevant brain regions.Methods MR 3D T1WI data of 60 ALS patients(ALS group)and 60 healthy volunteers(control group)were retrospectively analyzed.Taken GMV of each brain region obtained by voxel-based morphometry as the input features.F-score analysis was used to select feature with the highest classification accuracy to construct SVM model.Receiver operating characteristic curve was drawn to evaluate the efficacy of SVM model for identifying ALS,and top 10％was used as the weight threshold to obtain gray matter brain regions contributed the most to this model.Results SVM model constructed based on the top 40％GMV features had the highest classification accuracy(82.50％),with sensitivity,specificity and area under the curve(AUG)of 85.05％,80.40％and 0.890,respectively.The left precentral gyrus,left anterior cingulate gyrus and paracingulate gyrus,right middle temporal gyrus,opercular part of left inferior frontal gyrus,right dorsolateral superior frontal gyrus,left temporal pole:middle temporal gyrus,right superior occipital gyrus,orbital part of right middle frontal gyrus,right calcarine fissure and surrounding cortex,right fusiform gyrus were the top 1-10 gray matter brain regions contributed to this model.Conclusion ALS had specific GMV change pattern.SVM model based on GMV could be used to effectively identify ALS,while the left precentral gyrus was the most contributive brain region to this model.

This study was aimed at investigating the effects and mechanisms of Toxoplasma gondii type Ⅰ(RH strain)ROP16 protein on proliferation and the cell cycle in mouse alveolar macrophage MH-S cells.We constructed a Toxoplasma gondii type Ⅰ(RH)ROP16 overexpression lentivirus,transduced MH-S cells,and then screened cells with puromycin to obtain a cell line stably overexpressing ROP16Ⅰ.RT-qPCR and western blotting were used to verify expression effects,CCK-8 assays were used to detect cell proliferation activity,and flow cytometry was used to detect cell cycle changes.Western blotting and RT-qPCR were used to detect the expression levels of p53,p21,CDK6,Cyclin D1,STAT3,p-STAT3(Y705),and JAK1 proteins or genes,and immunofluorescence was used to detect the expression levels of ROP16Ⅰ and p-STAT3(Y705)and their subcellular co-localization in MH-S cells.ROP16Ⅰ protein and gene expression were detected in MH-S cells transduced with lentivirus for ROP16Ⅰ overexpression.CCK-8 assays revealed that ROP16Ⅰ promoted the proliferation of MH-S cells(P＜0.01)and enhanced cell viability.Flow cytometry revealed that ROP16Ⅰ overexpression decreased the G0/G1 phase and elevated the G2 and S phases of the cell cycle in MH-S cells(P＜0.01 or P＜0.05).Compared with the MH-S cell group and MH-S-empty vector group,the MH-S-ROP16 cell group showed lower expression of p53 and p21 proteins;higher expression of CDK6,Cyclin D1,p-STAT3(Y705),and JAK1 proteins;lower expression of p53 and p21 mRNAs;and higher expression of CDK6 and Cyclin D1 mRNAs(all P＜0.01).Immunofluorescence revealed that ROP16Ⅰ co-localized with p-STAT3(Y705)in the nucleus and surrounding cytoplasm.Therefore,Toxoplasma gondii type Ⅰ(RH)ROP16Ⅰ protein activates the JAK-STAT3 pathway;shortens the G0/G1 phase and lengthens the G2/S phase of the cell cycle;and promotes cell proliferation.These findings provide a theoretical basis for revealing the mechanism of immune evasion of Toxoplasma gondii,and lay a foundation for research on the prevention and treatment of Toxoplasma gondii pneumonia.

Objective To explore the value of support vector machine(SVM)model based on gray matter volume(GMV)for identifying amyotrophic lateral sclerosis(ALS),also to analyze the relevant brain regions.Methods MR 3D T1WI data of 60 ALS patients(ALS group)and 60 healthy volunteers(control group)were retrospectively analyzed.Taken GMV of each brain region obtained by voxel-based morphometry as the input features.F-score analysis was used to select feature with the highest classification accuracy to construct SVM model.Receiver operating characteristic curve was drawn to evaluate the efficacy of SVM model for identifying ALS,and top 10％was used as the weight threshold to obtain gray matter brain regions contributed the most to this model.Results SVM model constructed based on the top 40％GMV features had the highest classification accuracy(82.50％),with sensitivity,specificity and area under the curve(AUG)of 85.05％,80.40％and 0.890,respectively.The left precentral gyrus,left anterior cingulate gyrus and paracingulate gyrus,right middle temporal gyrus,opercular part of left inferior frontal gyrus,right dorsolateral superior frontal gyrus,left temporal pole:middle temporal gyrus,right superior occipital gyrus,orbital part of right middle frontal gyrus,right calcarine fissure and surrounding cortex,right fusiform gyrus were the top 1-10 gray matter brain regions contributed to this model.Conclusion ALS had specific GMV change pattern.SVM model based on GMV could be used to effectively identify ALS,while the left precentral gyrus was the most contributive brain region to this model.

ObjectiveExisting artificial vision devices can be divided into two types: implanted devices and extracorporeal devices, both of which have some disadvantages. The former requires surgical implantation, which may lead to irreversible trauma, while the latter has some defects such as relatively simple instructions, limited application scenarios and relying too much on the judgment of artificial intelligence (AI) to provide enough security. Here we propose a system that has voice interaction and can convert surrounding environment information into tactile commands on head and neck. Compared with existing extracorporeal devices, our device can provide a larger capacity of information and has advantages such as lower cost, lower risk, suitable for a variety of life and work scenarios. MethodsWith the latest remote wireless communication and chip technologies, microelectronic devices, cameras and sensors worn by the user, as well as the huge database and computing power in the cloud, the backend staff can get a full insight into the scenario, environmental parameters and status of the user remotely (for example, across the city) in real time. In the meanwhile, by comparing the cloud database and in-memory database and with the help of AI-assisted recognition and manual analysis, they can quickly develop the most reasonable action plan and send instructions to the user. In addition, the backend staff can provide humanistic care and emotional sustenance through voice dialogs. ResultsThis study originally proposes the concept of “remote virtual companion” and demonstrates the related hardware and software as well as test results. The system can not only achieve basic guide functions, for example, helping a person with visual impairment to shop in supermarkets, find seats at cafes, walk on the streets, construct complex puzzles, and play cards, but also can meet the demand for fast-paced daily tasks such as cycling. ConclusionExperimental results show that this “remote virtual companion” is applicable for various scenarios and demands. It can help blind people with their travels, shopping and entertainment, or accompany the elderlies with their trips, wilderness explorations, and travels.

ObjectiveTo explore the scientific connotation of fried charcoal survivability of Lonicerae Japonicae Flos（LJF） by analyzing the correlation between the color change and the intrinsic components during the processing of LJF Carbonisata（LJFC）， and taking pH， charcoal adsorption and microscopic characteristics as indexes. MethodLJFC samples with different degrees of processing were prepared according to the stir-frying time of 0.0， 1.5， 3.0， 4.5， 6.0， 7.5， 9.0， 10.5 min（numbered S1-S8）， and the contents of gallic acid， chlorogenic acid， cryptochlorogenic acid， rutin， luteoloside， isochlorogenic acid A and isochlorogenic acid C were determined by high performance liquid chromatography（HPLC）， and the L^*（brightness）， a^*（red-greenness） and b^*（yellow-blueness） of LJFC samples with different degrees of processing were determined by spectrophotometer， and the correlation analysis and principal component analysis（PCA） between the contents of seven representative components and the color of the samples were carried out by SPSS 26. 0 and SIMCA-P 14.1. Then pH， adsorption force and characteristic structure of different samples of LJFC were detected and the processing pattern of LJFC was analyzed. ResultThe results of quantitative analysis revealed that the contents of luteoloside， rutin， chlorogenic acid and isochlorogenic acid A gradually decreased， and the contents of cryptochlorogenic acid， isochlorogenic acid C and gallic acid firstly increased and then decreased. The L^* and b^* of the sample powders decreased， and a^* showed a trend of increasing and then decreasing. The L^* and b^* were positively correlated with the contents of chlorogenic acid， rutin， luteoloside， isochlorogenic acid A， b^* was positively correlated with the content of gallic acid， and a^* was positively correlated with the contents of cryptochlorogenic acid and isochlorogenic acid C. PCA revealed that samples could be clearly divided into 3 groups， S1-S2 as one group， S3-S5 as one group， and S6-S8 as one group， with S3 having the highest score. The results of regression analysis showed that only isochlorogenic acid C could be used to predict the contents of components by colorimetric values combined with regression equations. Physicochemical analysis showed that pH of LJFC increased with the increase of degree of charcoal stir-frying， while adsorption force showed a tendency of increasing and then decreasing， with the highest adsorption force in the S5 sample， and the non-glandular hairs， calcium oxalate clusters and pollen grains had a varying degree of decreasing with the deepening of processing degree， and the microstructures of S6-S8 samples were obviously charred with pollen grains almost invisible. ConclusionThe changes in chemical composition and color characteristics of LJFC during the processing have certain correlations， combined with the changes in physicochemical properties， S5 sample is found to be the optimal processed products， which can provide a reference for the processing standardization and quality evaluation of LJFC， and enrich the scientific connotation of fried charcoal survivability of LJF.

Radioactive contamination can occur during nuclear accidents, loss of radioactive sources and the use of radiation for photography, disinfection and detection. When the human body is accidentally contaminated by radionuclides, radionuclides can cause harm to the human body through inhalation, ingestion, direct transdermal absorption and contaminated wounds into body tissues and organs. In the treatment of radionuclide contamination in vivo, the main way is decorporation therapy, which mainly uses specific decorporation agents to selectively bind radionuclides to form stable non-toxic complexes, thereby preventing their deposition in the body, accelerating excretion, and reducing the total accumulation of radionuclides in human tissues. At present, internal radionuclide decorporation agents promote the release of radionuclides from the body mainly by stopping the entry of radionuclides into the body, ion exchange, chelation, and binding of exportants to carriers. But recent studies have found that lysosomal exocytosis, the natural clearing function of activated cells, also has a significant exportation effect. In this paper, we first introduced and analyzed the mechanism and research status of radionuclide decorporation agents that have been used in clinical practice, such as the blocking effect of potassium iodide, the ion exchange effect of Prussian blue, the chelation effect of DTPA, and the urine alkalinization effect of sodium bicarbonate. The second part introduces the mechanism and research status of promising radionuclide decorporation agents. Among them, 3,4,3-LI (1,2-HOPO) and 5-LIO (Me-3,2-HOPO) are the most promising ones and have been approved for phase I clinical trials. Others such as catecholamines, polyethyleneimine and fullerenes are also being studied with great potential. Polyethyleneimine, as a biological macromolecular chelator, has more chelating sites and stronger targeting effects than small molecule chelators, and has achieved a real breakthrough in decorporation. Fullerenes are known as “free radical sponges” with good free radical scavenging ability and antioxidant properties. In recent years, biomaterials have been widely used in the field of radionuclide decorporation, which has greatly improved the decorporation efficiency. Chitosan and pectin have shown great advantages in promoting radionuclide decorporation, chitosan can adsorb metal ions through electrostatic interaction and chelation, and can also react with free radicals to remove free radicals generated after radionuclides enter the body. Pectin can promote uranium efflux, but the exact mechanism remains unclear. Liposomes and nanomaterials as carriers enhance the intracellular drug delivery, prolong the retention time of drugs in the body, reduce adverse reactions, and make the traditional efflux enhancers glow with new vitality and have good development prospects. The last part summarizes and looks forward to the future research direction of radionuclide decorporation agents. At present, the research on decorporation agents at home and abroad is mostly stuck in the stage of drug development and drug synthesis, and few have actually entered the clinical trial stage. Therefore, the optimization of existing decorporation agents and the development of new ligands are critical. The targeting, biological safety, oral availability, and treatment needs of large-scale contamination scenarios are still the focus of attention. In addition, from the point of view of the mechanism itself, it is a new idea to promote the emission of radionuclides by activating potential channels, which can be continuously explored.