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The incorporation of trinitrophenyl-modified 1,3,4-oxadiazole fragments is commonly observed in high-energy molecules with heat-resistant properties. This study explores the strategy of developing heat-resistant energetic materials by incorporating trinitrophenyl and an azo group into 1,3,4-oxadiazole, which involved the synthesis and characterization of (E)-1,2-bis(5-(2,4,6-trinitrophenyl)-1,3,4-oxadiazol-2-yl)diazene (2), N-(5-(2,4,6-trinitrophenyl)-1,3,4-oxadiazol-2-yl)nitramide (3), and the energetic salts of 3. Characterization techniques employed included 1H and 13C NMR, IR and elemental analysis. Additionally, the structures of 2 and 3 were validated using single crystal X-ray analysis. To further understand the physical and chemical characteristics of these novel energetic compounds, various calculations and measurements were performed. Compound 2 exhibits excellent thermostability (Td = 294 °C), which is comparable to that of traditional heat-resistant explosive HNS (Td = 318 °C). But 2 is insensitive towards impact (>40 J) and friction (>360 N), surpassing HNS (5 J, 240 N), suggesting that compound 2 deserves further investigation as a potential heat-resistant explosive.
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Two-dimensional materials with ultrahigh in-plane thermal conductivity are ideal for heat spreader applications but cause significant thermal contact resistance in complex interfaces, limiting their use as thermal interface materials. In this study, we present an interfacial phonon bridge strategy to reduce the thermal contact resistance of boron nitride nanosheets-based composites. By using a low-molecular-weight polymer, we are able to manipulate the alignment of boron nitride nanosheets through sequential stacking and cutting, ultimately achieving flexible thin films with a layer of arc-like structure superimposed on perpendicularly aligned ones. Our results suggest that arc-like structure can act as a phonon bridge to lower the contact resistance by 70% through reducing phonon back-reflection and enhancing phonon coupling efficiency at the boundary. The resulting composites exhibit ultralow thermal contact resistance of 0.059 in2 KW-1, demonstrating effective cooling of fast-charging batteries at a thickness 2-5 times thinner than commercial products.
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Polythioamide is a unique type of sulfur-containing polymer with advanced functionalities. Nonetheless, the elemental sulfur commonly used in their synthesis tends to react readily with unsaturated functional groups, thereby limiting the scope of eligible substrates. Inspired by the highly efficient sulfur-fluoride exchange (SuFEx) polymerization through discrete hubs, we present herein a pioneering and versatile approach to the synthesis of polythioamides from diboronic acids, secondary diamines, and thiocarbonyl fluoride as the central connective hub. Well-defined structures, including previously inaccessible unsaturated substrates, were realized. These newly devised polythioamides can efficiently and selectively bind to metal ions and were applied in precious-metal recovery. Further development resulted in PdII -crosslinked single-chain nanoparticles serving as recyclable homogeneous catalysts, thus demonstrating the vast potential of these unprecedented polythioamides. We anticipate that thiocarbonyl fluoride could emerge as a potent hub for facilitating the intricate synthesis of sulfur-containing polymers.
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OBJECTIVES: Biofilm formed by cariogenic microbes is the direct cause of dental caries, therefore, prevention of dental caries should be anti-biofilm-based. Previously, we found the amyloid hexapeptides efficiently inhibited biofilm formation by aggregating into amyloid fibrils agglutinating microbes. This study aimed to select the most stable amyloid hexapeptide GIDLKI (GI6) and study its anti-caries effect. METHODS: Biofilms of multi-species bacteria, derived from mixed saliva, were cultured to evaluate the anti-biofilm formation effect of GI6. And then, the primary cariogenic bacterium Streptococcus mutans (S.mutans) was cultured in BHI with various pH, gradient concentrations of sucrose, glucose, and calcium ions to evaluate the anti-biofilm formation effects of GI6. Then models of human enamel block caries and twenty male SPF-SD rat caries induced by S. mutans biofilm were constructed, and confocal laser scanning microscopy, scanning electron microscopy, and micro-computed tomography were applied to investigate the anti-biofilm formation, anti-caries effects and use safety of GI6. RESULTS: GI6 could inhibit the multi-species bacteria biofilm formation and remained effective in anti-biofilm activity against S. mutans in environments closely related to caries. GI6 suppressed S. mutans biofilm formation and thus prevented or alleviated the development of caries in human tooth blocks and rat teeth. GI6 did not affect the intestinal flora, serum biochemical parameters, and the pathological changes of various organs. CONCLUSIONS: Amyloid hexapeptides, including but not limited to GI6, are novel effective anti-caries agents that can be used to prevent dental caries safely. CLINICAL SIGNIFICANCE: This study explored the anti-biofilm formation and anti-caries effect of GI6 in vitro, highlighting the anti-biofilm formation therapy for dental caries and setting a foundation for the practical application of GI6 for the treatment of dental caries.
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Caries Dental , Animales , Ratas , Masculino , Humanos , Caries Dental/prevención & control , Caries Dental/microbiología , Amiloide/farmacología , Cariostáticos/farmacología , Microtomografía por Rayos X , Ratas Sprague-Dawley , Streptococcus mutans , BiopelículasRESUMEN
Molecules featuring fluorine-containing functional groups exhibit outstanding properties with high density, low sensitivity, excellent thermal stability, and good energetic performance due to the strong electron-withdrawing ability and high density of fluorine. Hence, they play a pivotal role in the field of energetic materials. In light of current theoretical and experimental reports, this review systematically focuses on three types of energetic materials possessing fluorine-containing functional groups F- and NF2 - substituted trinitromethyl groups (C(NO2 )2 F, C(NO2 )2 NF2 ), trifluoromethyl group (CF3 ), and difluoroamino and pentafluorosulfone groups (NF2 , SF5 ) and investigates the synthetic methods, physicochemical parameters, and energetic properties of each. The incorporation of fluorine-containing functional moieties is critical for the development of novel high energy density materials, and is rapidly being adopted in the design of energetic materials.
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Microbe (including bacteria, fungi, and virus) infection in brains is associated with amyloid fibril deposit and neurodegeneration. Increasing findings suggest that amyloid proteins, like Abeta (Aß), are important innate immune effectors in preventing infections. In some previous studies, amyloid peptides have been linked to antimicrobial peptides due to their common mechanisms in membrane-disruption ability, while the other mechanisms of bactericidal protein aggregation and protein function knockdown are less discussed. Besides, another important function of amyloid peptides in pathogen agglutination is rarely illustrated. In this review, we summarized and divided the different roles and mechanisms of amyloid peptides against microbes in antimicrobial activity and microbe agglutination activity. Besides, the range of amyloids' antimicrobial spectrum, the effectiveness of amyloid peptide states (monomers, oligomers, and fibrils), and cytotoxicity are discussed. The good properties of amyloid peptides against microbes might provide implications for the development of novel antimicrobial drug. KEY POINTS: ⢠Antimicrobial and/or microbial agglutination is a characteristic of amyloid peptides. ⢠Various mechanisms of amyloid peptides against microbes are discovered recently. ⢠Amyloid peptides might be developed into novel antimicrobial drugs.
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Amiloide , Antiinfecciosos , Amiloide/química , Amiloide/metabolismo , Péptidos beta-Amiloides/química , Péptidos beta-Amiloides/metabolismo , Antiinfecciosos/farmacología , Proteínas Amiloidogénicas , Antibacterianos , AglutinaciónRESUMEN
Objective@# To explore the feasibility of curettage combined with fenestration for jaw classic ameloblastoma treatment and to provide a basis for improving the treatment of classic ameloblastoma. @*Methods@# Twenty-two patients with jaw classic ameloblastoma admitted to Liuzhou People’s Hospital from 2016 to 2019 were selected. They were treated by curettage combined with fenestration. Monthly follow-up visits were conducted after surgery, and orthopantomography was performed for reexamination to observe the recovery of bone and whether there was recurrence. @*Results @#Tumors were completely scraped off in 22 patients, no pathological fracture occurred, and no wound infection occurred after surgery. After 1 to 3 years of follow-up, 19 patients showed excellent bone recovery in the original tumor area, and no recurrence was observed. Three patients relapsed and underwent a second curettage combined with fenestration, and the bone at the original tumor site recovered well. During the 12-month follow-up, no tumor recurrence was observed. After the second curettage combined with open surgery, the bone at the original tumor site recovered well. Eight patients underwent dental implants to repair dentition defects one year after surgery.@*Conclusion@#Curettage combined with fenestration is a convenient and effective treatment for jaw classic ameloblastoma.
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Systemic lupus erythematosus (SLE) is an autoimmune disease that is mainly caused by excessive accumulation of autoantibodies that target autoantibodies such as nucleic acids. T helper (Th) cell have been associated with the development of SLE. Typically, different subsets of Th cells secrete various cytokines to regulate the disease progression. IL-12 and IL-23 participate in the differentiation and activation of multiple Th cell subsets, including Th1, Th2, Th9, Th17, regulatory T (Treg) and follicular helper T (Tfh) cells. Because of the signature p40 subunit shared by IL-12 and IL-23, blocking IL-12/IL-23 signaling may interfere the differentiation of Th cell and directly inhibit the secretion of proinflammatory cytokines. In this study, we examined the effects of anti-IL-12/23 p40 antibody on chronic graft-versus-host disease with lupus nephritis, and found that the therapeutic effectiveness was mediated through the inhibition of Tfh cell in mice. Moreover, anti-IL-12/23 p40 antibody inhibited human Tfh cell differentiation in vitro. These results strongly suggest that Tfh cell contribute to the pathogenesis of SLE, and the neutralization of IL-12/IL-23 signaling during Tfh cell differentiation may be critical for the treatment of SLE.
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Anticuerpos/farmacología , Diferenciación Celular/efectos de los fármacos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Subunidad p40 de la Interleucina-12/antagonistas & inhibidores , Riñón/efectos de los fármacos , Nefritis Lúpica/tratamiento farmacológico , Células T Auxiliares Foliculares/efectos de los fármacos , Animales , Anticuerpos Antinucleares/sangre , Células Cultivadas , Enfermedad Crónica , Modelos Animales de Enfermedad , Femenino , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/metabolismo , Enfermedad Injerto contra Huésped/patología , Humanos , Subunidad p40 de la Interleucina-12/inmunología , Subunidad p40 de la Interleucina-12/metabolismo , Riñón/inmunología , Riñón/metabolismo , Riñón/patología , Nefritis Lúpica/inmunología , Nefritis Lúpica/metabolismo , Nefritis Lúpica/patología , Ratones Endogámicos DBA , Proteínas Proto-Oncogénicas c-bcl-6/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Transducción de Señal , Células T Auxiliares Foliculares/inmunología , Células T Auxiliares Foliculares/metabolismoRESUMEN
INTRODUCTION: ephrinA1 plays important roles in tumor angiogenesis. Matrix metalloproteases (MMPs) can cleave ephrinA1 from the cell membrane into extracellular environment. However, how soluble ephrinA1 is modulated by hypoxia and whether MMPs participate in this hypoxic process remains to be investigated in detail. METHODS: Thirty-seven patients with oral squamous cell carcinoma (OSCC) were included in the present study for HIF-1α, MMP-2, MMP-9 and ephrinA1 detection by immunohistochemistry. Serum samples from 35 patients were collected both preoperatively and postoperatively to confirm the existence of soluble ephrinA1 by ELISA. Block assay and Western blot analysis were further carried out to elucidate the proteolysis mechanism of ephrinA1 under hypoxic condition in vitro. RESULTS: Our data demonstrated that HIF-1α, MMP-2, MMP-9 and ephrinA1 expressed positively, and correlated with microvessel density in OSCCs, except for MMP-9. The serum expression level of ephrinA1 in OSCC patients decreased significantly after surgical removal of the solid tumors. In vitro experiments indicated that GM6001, a MMP-specific inhibitor, could reduce hypoxia-induced soluble ephrinA1 secretion from SCC cells. Further Western blot analysis confirmed that both HIF-1α and MMP-2 were up-regulated by hypoxia in a similar time-dependent manner, with the MMP-9 expression unchanged during this course. CONCLUSION: These results suggested a possible novel mechanism that ephrinA1 secretion is mediated by HIF-1α/MMP-2 signaling cascade which may play pivotal roles in OSCC neovascularization in a paracrine manner.
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OBJECTIVE: To observe the clinical outcomes of a combined unilateral intraoral and extraoral reduction approach in the treatment of anterior temporomandibular joint (TMJ) dislocation. METHODS: Postural muscular chains were utilized in the biomechanical analysis of stomatognathic systems for improving TMJ repositioning approaches. A total of 87 patients with anterior TMJ dislocation were included in the present study. A combined unilateral intraoral and extraoral reduction approach was applied, and the clinical effects were evaluated. RESULTS: Biomechanical analysis reveal that reflexive contrac-tion of the maxillary muscle group was blocked sufficiently during the combined unilateral intraoral and extraoral reduction process. All dislocated TMJs were set successfully and efficiently with few complications. CONCLUSIONS: Combined unilateral intraoral and extraoral reduction approach is an effective, convenient, and minimally invasive way to treat anterior TMJ dislo-cations.
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Luxaciones Articulares , Procedimientos de Cirugía Plástica , Trastornos de la Articulación Temporomandibular , Humanos , Articulación Temporomandibular , Trastornos de la Articulación Temporomandibular/cirugíaRESUMEN
Objective@#The purpose of this study was to a new operative approach for sagittal condylar fractures via a preauricular small incision-based technique and to examine the effectiveness of this approach. @*Methods@#Fifteen patients (19 sides) with sagittal condylar fractures were included in the study. The incision length was approximately 4 cm through the tragus, exposing the superficial temporal vessels, which was then pulled forward. Next, the deep temporal superficial fascia was cut, and the surface of the zygomatic arch and the articular capsule of the temporomandibular joint were exposed. Joint capsule incision was performed, with mandibular condylar fracture fixation under direct vision. We followed up with the patients postoperatively for 6 months with clinical and radiographic examinations. @*Results @#All patients had 1 week postoperation before being discharged, during which 2 cases of mild facial paralysis (with lateral temporal level Ⅱ facial paralysis, with lateral temporal branch level Ⅲ facial paralysis and level Ⅱ zygomatic branch of facial nerve paralysis after treatment) were observed, after given nerve nutrition agents, 2 cases returned to normal within 3 months. No patient exhibited a postoperative delayed fistula infection or other serious complications. Intraoperative occlusion relationships recovered well, and postoperative CTs suggested that the fracture ends and condyles were in good condition. The occlusion relationship was normal for 3 months after surgery, with a degree of opening greater than 30 mm, no play in the joints and no oblique openings being observed, and reexamination 6 months after the surgery revealed no obvious scars.@*Conclusion@#This surgical method involves a small incision and clear anatomic structures and avoids damage to the facial nerve. This method provides better surgical vision for treatment of sagittal condylar fractures, is safe and convenient, and deserves clinical recommendation.
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Craniofacial registration is used to establish the point-to-point correspondence in a unified coordinate system among human craniofacial models. It is the foundation of craniofacial reconstruction and other craniofacial statistical analysis research. In this paper, a non-rigid 3D craniofacial registration method using thin-plate spline transform and cylindrical surface projection is proposed. First, the gradient descent optimization is utilized to improve a cylindrical surface fitting (CSF) for the reference craniofacial model. Second, the thin-plate spline transform (TPST) is applied to deform a target craniofacial model to the reference model. Finally, the cylindrical surface projection (CSP) is used to derive the point correspondence between the reference and deformed target models. To accelerate the procedure, the iterative closest point ICP algorithm is used to obtain a rough correspondence, which can provide a possible intersection area of the CSP. Finally, the inverse TPST is used to map the obtained corresponding points from the deformed target craniofacial model to the original model, and it can be realized directly by the correspondence between the original target model and the deformed target model. Three types of registration, namely, reflexive, involutive and transitive registration, are carried out to verify the effectiveness of the proposed craniofacial registration algorithm. Comparison with the methods in the literature shows that the proposed method is more accurate.
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Cara/anatomía & histología , Imagenología Tridimensional , Cráneo/anatomía & histología , Algoritmos , HumanosRESUMEN
IL-23/STAT3 signaling pathway is a key process in Th17 cell differentiation, and Th17 cells are closely related to the development of autoimmune diseases. We previously designed and prepared rhIL23R-CHR protein to antagonize endogenous IL-23, showing effectiveness in the treatment of experimental autoimmune encephalomyelitis (EAE) in mice. To further elucidate the mechanism of action, mouse lncRNA microarray was used to screen expression profiles of lncRNAs, and a particular lncRNA, 1700040D17Rik was found to down-regulate in EAE model and its expression was significantly increased after the treatment by rhIL23R-CHR. The function of 1700040D17Rik was revealed to associate with the differentiation of Th17 cells through the regulation of the key transcription factor RORγt. Together, regulation of Th17 cells through lncRNA is responsible for the effects of rhIL23R-CHR to balance the immune responses, and 1700040D17Rik has the potential to serve as a therapeutic target or a biomarker for autoimmune diseases.
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Encefalomielitis Autoinmune Experimental/genética , Interleucina-23/metabolismo , Esclerosis Múltiple/inmunología , ARN Largo no Codificante/genética , Células Th17/inmunología , Animales , Diferenciación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Regulación hacia Abajo , Encefalomielitis Autoinmune Experimental/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Ratones , Ratones Endogámicos C57BL , Glicoproteína Mielina-Oligodendrócito/inmunología , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fragmentos de Péptidos/inmunología , Factor de Transcripción STAT3/metabolismo , Transducción de SeñalRESUMEN
IL-23 is an important cytokine to regulate Th17 cell differentiation and promote the proliferation of inflammatory cells in Th17-mediated autoimmune diseases. The collagen-induced arthritis (CIA) in rat is a model of rheumatoid arthritis characterized by pronounced inflammatory auto-responses from B and T cells, especially Th17 cells in lesions. In the present study, we used rhIL23R-CHR to block the IL-23 signaling pathway to probe the importance of IL-23 in misbalancing the ratio of Th17/Th9/Treg cells in CIA rats. After treatments with rhIL23R-CHR, the CIA rats showed a significant decrease of secretions of IL-17 and IL-9, whereas FoxP3 was activated in the process, indicating that IL-23 can manipulate the balance of Th17/Th9/Treg cells. Similar to the animal model, IL-23 also possessed remarkable proinflammatory effects on human fibroblast-like synoviocyte cells (HFLS), showing synergetic outcomes with TNF-α. Together, IL-23 could act as a modulator to imbalance the ratio of Th17/Th9/Treg cells, and rhIL23R-CHR could serve as a potential therapeutic agent for RA patients.
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Antiinflamatorios/administración & dosificación , Artritis Experimental/prevención & control , Colágeno Tipo II , Fragmentos de Péptidos/administración & dosificación , Receptores de Interleucina/administración & dosificación , Células Th17/efectos de los fármacos , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/inmunología , Artritis Experimental/metabolismo , Células Cultivadas , Relación Dosis-Respuesta a Droga , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Interleucina-17/metabolismo , Interleucina-23/metabolismo , Interleucina-9/metabolismo , Fenotipo , Dominios y Motivos de Interacción de Proteínas , Ratas Wistar , Proteínas Recombinantes/administración & dosificación , Transducción de Señal/efectos de los fármacos , Sinoviocitos/efectos de los fármacos , Sinoviocitos/inmunología , Sinoviocitos/metabolismo , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Factores de TiempoRESUMEN
Interleukin (IL)-12 and IL-23 respectively driving polarization of T helper (Th) 1 and Th17 cells has been strongly implicated in the pathogenesis of both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). In this study, we first constructed, expressed and purified a novel human truncated IL12rß1-Fc fusion protein (tIL12rß1/Fc) binding multiple forms of the p40 subunit of human IL-12 and IL-23. tIL12rß1/Fc was found to effectively ameliorate MOG35-55-induced EAE through reducing the production of Th1- and Th17-polarized pro-inflammatory cytokines and suppressing inflammation and demyelination in the focused parts. Moreover, tIL12rß1/Fc suppressed Th1 (IFN-γ(+) alone) and IFN-γ(+) IL-17(+) as well as the population of classic Th17 (IL-17(+) alone) cells in vivo. Furthermore, tIL12rß1/Fc ameliorated EAE at the peak of disease via the inhibition of STAT pathway, thereby causing a prominent reduction of RORγt (Th17) and T-bet (Th1) expression. Notably, tIL12rß1/Fc could increase the relative number of CD4(+) Foxp3(+) regulatory T cells. These findings indicates that tIL12rß1/Fc is a novel fusion protein for specific binding multiple forms of p40 subunit to exert potent anti-inflammatory effects and provides a valuable approach for the treatment of MS and other autoimmune diseases.