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OBJECTIVES: B10 and B10pro cells suppress immune responses via secreting interleukin (IL)-10. However, their regulators and underlying mechanisms, especially in human autoimmune diseases, are elusive. This study aimed to address these questions in rheumatoid arthritis (RA), one of the most common highly disabling autoimmune diseases. METHODS: The frequencies and functions of B10 and B10pro cells in healthy individuals and patients with RA were first analysed. The effects of proinflammatory cytokines, particularly tumour necrosis factor (TNF)-α on the quantity, stability and pathogenic phenotype of these cells, were then assessed in patients with RA before and after anti-TNF therapy. The underlying mechanisms were further investigated by scRNA-seq database reanalysis, transcriptome sequencing, TNF-α-/- and B cell-specific SHIP-1-/- mouse disease model studies. RESULTS: TNF-α was a key determinant for B10 cells. TNF-α elicited the proinflammatory feature of B10 and B10pro cells by downregulating IL-10, and upregulating interferon-γ and IL-17A. In patients with RA, B10 and B10pro cells were impaired with exacerbated proinflammatory phenotype, while anti-TNF therapy potently restored their frequencies and immunosuppressive functions, consistent with the increased B10 cells in TNF-α-/- mice. Mechanistically, TNF-α diminished B10 and B10pro cells by inhibiting their glycolysis and proliferation. TNF-α also regulated the phosphatidylinositol phosphate signalling of B10 and B10pro cells and dampened the expression of SHIP-1, a dominant phosphatidylinositol phosphatase regulator of these cells. CONCLUSIONS: TNF-α provoked the proinflammatory phenotype of B10 and B10pro cells by disturbing SHIP-1 in RA, contributing to the disease development. Reinstating the immunosuppressive property of B10 and B10pro cells might represent novel therapeutic approaches for RA.
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Artritis Reumatoide , Enfermedades Autoinmunes , Linfocitos B Reguladores , Factor de Necrosis Tumoral alfa , Animales , Humanos , Ratones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Enfermedades Autoinmunes/metabolismo , Linfocitos B Reguladores/metabolismo , Fenotipo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/genética , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatasas/metabolismo , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
D-Glucose-to-L-sorbose isomerization on Lewis acidic zeolite is a highly attractive avenue for sorbose production. But the L-sorbose yield is limited by the competing D-glucose-to-D-fructose isomerization and reaction equilibrium. In this work, it is suggested that ethanol directs the glucose conformation for selective D-glucose-to-L-sorbose isomerization. It also reacts with the produced L-sorbose to form ethyl-sorboside, which allows the D-glucose-to-L-sorbose isomerization to proceed beyond the thermodynamic equilibrium limit. It is shown that a bifunctional zeolite Beta containing framework titanium (Ti) and boron (B) is a selective catalyst for this tandem reaction: Lewis acidic framework Ti catalyzes the D-glucose-to-L-sorbose isomerization via an intramolecular 5,1-hydride shift process as confirmed by isotopic tracing experiments followed by 13C-NMR, while weak Brønsted acid framework B selectively promotes the sorbose ketalization with ethanol. A remarkably high yield of L-sorbose with a high fraction of sugar (>95%: 27% unreacted glucose, 11.4% fructose, 57% sorbose) was obtained after the mixture produced in ethanol was hydrolyzed.
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SAPO-37 molecular sieve, characterized by its three-dimensional 12-membered-ring FAU structure, has drawn wide attention due to its unique properties and catalytic potential. However, its susceptibility to framework collapse under low-temperature and humid conditions hinders practical applications, affecting both the reaction performance and sample storage. To tackle this, we utilized aluminum phosphate as a precursor for synthesizing SAPO-37, aiming to modify Si incorporation mechanisms and improve P and Al environments. Solid NMR spectroscopy combined with other techniques proves that the resulting SAPO-37-AP has enriched silicon islands, leading to reduced water adsorption, more reversible structural change, and significantly enhanced stability after low-temperature vapor treatment compared to conventional SAPO-37. Remarkably, SAPO-37-AP, after water vapor treatment, still exhibits superior performance in the liquid-phase Beckmann rearrangement reaction. This approach enhances stability, reduces templating agent amounts, and improves the solid product yield, offering promising practical applications.
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OBJECTIVE: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. METHODS: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. RESULTS: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. CONCLUSION: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.
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Hidroxicloroquina , Lupus Eritematoso Sistémico , Humanos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
Small-pore Lewis acid zeolites have been showing increasing potential in shape-selective reactions regarding small-molecule conversion. In this study, Sn-CHA with tunable framework Sn contents was facilely prepared via a fluoride-free, seed-assisted interzeolite conversion (IZC) pathway. Commercially available dealuminated USY functioned as the parent sample, and seeding played a vital role in accelerating the transformation process, promoting the target zeolite yield, and guiding the attached-growth pathway. Notably, a proto-zeolite phase with a semi-constructed pore structure was captured during the IZC process, which represents a crucial intermediate stage for developing the complete CHA structure and ensuring a well-defined Sn status. The detailed synthesis mechanism was explored in multiscale by a series of techniques. The obtained Sn-CHA and proto-Sn-CHA exhibited excellent catalytic performance in converting 1,3-dihydroxyacetone to methyl lactate. Proto-Sn-CHA was proven to be a highly effective glucose isomerization catalyst owing to its larger pore size and Lewis acidic nature.
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Selectively anchoring active centers on the external surface for forming highly exposed acid sites is a highly desirable but challenging task in zeolite catalyst synthesis. Herein, a defect-guided etching-regrowth strategy is rationally designed for facilely positioning Sn Lewis acid sites on the outer surface of the Sn-B-Beta while fabricating a bifunctional hierarchical structure. The synthesis was conducted by hydrothermal treatment of the as-made B-Beta (uncalcined), which has intrinsic defects of the BEA structure, with Sn source and basic organic structure directing agent (SDA). Under a moderate SDA concentration, with blocked micropore channels, such SDA-triggered etching-regrowth will proceed along the defect defined pathway, which ensures Sn selectively anchored on the external surface. Moreover, this methodology has exclusively introduced tetrahedrally coordinated framework Sn with open Sn sites as the predominated species. Mono- and disaccharide isomerizations in ethanol over different Sn-Beta catalysts proved the prominent advantages of the hierarchical structure with highly exposed and synergetic acid sites.
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Phosphorus-modified siliceous zeolites, or P-zeosils, catalyze the selective dehydration of biomass derivatives to platform chemicals such as p-xylene and 1,3-butadiene. Water generated during these reactions is a critical factor in catalytic activity, but the effects of hydrolysis on the structure, acidity, and distribution of the active sites are largely unknown. In this study, the P-sites in an all-silica self-pillared pentasil (P-SPP) with a low P-loading (Si/P = 27) were identified by solid-state 31P NMR using frequency-selective detection. This technique resolves overlapping signals for P-sites that are covalently bound to the solid phase, as well as oligomers confined in the zeolite but not attached to the zeolite. Dynamic Nuclear Polarization provides the sensitivity necessary to conduct 29Si-filtered 31P detection and 31P-31P correlation experiments. The aforementioned techniques allow us to distinguish sites with P-O-Si linkages from those with P-O-P linkages. The spectra reveal a previously unappreciated diversity of P-sites, including evidence for surface-bound oligomers. In the dry P-zeosil, essentially all P-sites are anchored to the solid phase, including mononuclear sites and dinuclear sites containing the [Si-O-P-O-P-O-Si] motif. The fully-condensed sites evolve rapidly when exposed to humidity, even at room temperature. Partially hydrolyzed species have a wide range of acidities, inferred from their calculated LUMO energies. Initial cleavage of some P-O-Si linkages results in an evolving mixture of surface-bound mono- and oligonuclear P-sites with increased acidity. Subsequent P-O-P cleavage leads to a decrease in acidity as the P-sites are eventually converted to H3PO4. The ability to identify acidic sites in P-zeosils and to describe their structure and stability will play an important role in controlling the activity of microporous catalysts by regulating their water content.
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OBJECTIVES: IgG4-related disease (IgG4-RD) is recently recognized as a fibro-inflammatory condition featured by tumefactive lesions in multiple organs, and the retroperitoneum is one of the common involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with retroperitoneum lesion (IgG4-RD RPF+) and retroperitoneum free IgG4-RD (IgG4-RD RPF-) in a large cohort. METHODS: We carried out a retrospective review of the medical records of 407 cases of IgG4-RD diagnosed at Peking University People's Hospital between March 2009 and May 2019. RESULTS: Among 407 patients, 58 had retroperitoneum affected. As compared with IgG4-RD RPF- patients, IgG4-RD RPF+ patients showed older age at disease onset and diagnosis. IgG4-RD RPF+ group involved more male patients. In terms of organ involvement, IgG4-RD RPF+ group was more frequently presented with kidney involvement, while salivary gland, lacrimal gland and pancreas were more prominent in the IgG4-RD RPF- group. In addition, the CRP, ESR level and creatinine level were significantly higher in IgG4-RD RPF+ patients, and hypocomplementemia were more common in this group. CONCLUSION: We have revealed demographic, clinical and laboratory differences between IgG4-RD RPF+ and RPF- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.
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Autoinmunidad , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Inmunoglobulina G/inmunología , Fibrosis Retroperitoneal/diagnóstico , Glándulas Salivales/diagnóstico por imagen , Femenino , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/inmunología , Masculino , Persona de Mediana Edad , Fibrosis Retroperitoneal/inmunología , Estudios Retrospectivos , Glándulas Salivales/metabolismo , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Primary Sjögren's syndrome (SS) is a lymphoproliferative disease with a chronic autoimmune disorder characterized by mononuclear cell (MNC) infiltration of notably the lacrimal and salivary glands. As mesenchymal stem cells (MSCs) regulate series of immunological responses partially by regulating proportion of CD4+ T cells and inducing an immunosuppressive local milieu, umbilical cord MSCs (UC-MSCs) are being considered as a novel source for cell-based therapies against primary SS. This study aimed to investigate the feasibility of UC-MSCs in treatment of SS and to explore the possible mechanism(s) with the special emphasis on regulatory T cells (Tregs). METHODS: Potent immunosuppressive effects of human UC-MSCs on SS were explored in vivo and in vitro. To study the effects of human UC-MSCs on the development and progression of SS, human UC-MSCs were administered before disease onset (preventive protocol) and after disease occurrence (therapeutic protocol) in non-obese diabetic (NOD) mice. In human study, the effect of human UC-MSCs on T cells from SS patients was studied. RESULTS: In both protocols, the histopathology of submandibular and sublingual salivary glands showed decreased inflammatory infiltrates. In vitro, human UC-MSCs exhibited potent suppressive effects on responses of MNCs in NOD mice and T cells in SS patients. Such inhibitory effects were coupled with decreased production of proinflammtory cytokines interferon-γ, interleukin (IL)-6, tumor necrosis factor-α and increased production of IL-10 (n = 10, p < .01). The frequency of CD4+Foxp3+T cells in the spleen of NOD recipients was elevated (n = 6, p < .05). CONCLUSION: Human UC-MSCs are capable of inducing CD4+Foxp3+ T cells in both NOD mice and human in vitro. Human UC-MSCs effectively interfere with the autoimmune attack in the course of SS by inducing an in vivo state of T cell unresponsiveness and the upregulation of Tregs.
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Trasplante de Células Madre Mesenquimatosas/métodos , Síndrome de Sjögren/terapia , Linfocitos T Reguladores/inmunología , Animales , Células Cultivadas , Citocinas/inmunología , Humanos , Células Madre Mesenquimatosas/inmunología , Ratones , Ratones Endogámicos NOD , Glándulas Salivales/inmunología , Síndrome de Sjögren/inmunología , Cordón Umbilical/citologíaRESUMEN
OBJECTIVES: IgG4-related disease (IgG4-RD) has recently been recognized as a fibro-inflammatory condition featuring tumefactive lesions in multiple organs, and the salivary gland is one of the most commonly involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with salivary gland lesions (IgG4-RD SG+) and salivary-gland-free IgG4-RD (IgG4-RD SG-) in a large cohort. METHODS: We carried out a retrospective review of the medical records of 428 cases of IgG4-RD diagnosed at Peking University People's Hospital between March 2006 and May 2018. RESULTS: Among 428 patients, 249 had salivary glands that were affected. IgG4-RD SG+ patients showed younger age at disease onset and diagnosis, and a longer interval between symptom onset and diagnosis. The IgG4-RD SG+ group involved more female patients, and allergic diseases were more common in this group. In terms of organ involvement, the IgG4-RD SG+ group were more frequently presented with lacrimal gland involvement, while lymph node, retroperitoneal fibrosis, pancreas, biliary system, kidney and aorta were more prominent in the IgG4-RD SG- group. In addition, the serum IgG4 level, IgG4/IgG ratio and IgE level were significantly higher in IgG4-RD SG+ patients. Patients with eosinophilia were more common in the IgG4-RD SG+ group, while elevated ESR, CRP and positive ANA were more common in the IgG4-RD SG- group. CONCLUSION: We have revealed demographic, clinical and laboratory differences between IgG4-RD SG+ and SG- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.
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Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Inmunoglobulina G/sangre , Glándulas Salivales/patología , Adulto , Anciano , Femenino , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/sangre , Enfermedad Relacionada con Inmunoglobulina G4/patología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The conventional magnetoelastic resonant sensor suffers from a low detecting sensitivity problem. In this study, an hourglass-shaped magnetoelastic resonant sensor was proposed, analyzed, fabricated, and tested. The hourglass-shaped magnetoelastic resonant sensor was composed of an hourglass and a narrow ribbon in the middle. The hourglass and the narrow ribbon increased the detection sensitivity by reducing the connecting stress. The resonant frequency of the sensor was investigated by the finite element method. The proposed sensor was fabricated and experiments were carried out. The tested resonance frequency agreed well with the simulated one. The maximum trust sensitivity of the proposed sensor was 37,100 Hz/strain. The power supply and signal transmission of the proposed sensor were fulfilled via magnetic field in a wireless and passive way due to the magnetostrictive effect. Parametric studies were carried out to investigate the influence of the hourglass shape on the resonant frequency and the output voltage. The hourglass-shaped magnetoelastic resonant sensor shows advantages of high sensitivity, a simple structure, easy fabrication, passiveness, remoteness, and low cost.
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OBJECTIVE: To assess the advantage of using the sEMG signal for establishing the mathematical model of lower limb movement and evaluating the improvement in the jumping ability of basketball players as the ultimate target strength. Also, to evaluate its use it in the training of lower limb strengthening of basketball players. METHODS: In this study conducted from March 1, 2019 to June 1, 2019, 30 professional male basketball players were selected as the subjects, gait analysis was carried out when they finished the three-step layup in 15 minutes. Acquisition and noise reduction process of the collected sEMG signals were first filtered by band-pass filter to eliminate the noise outside the frequency, then suppressed by the spectral interpolation method, and finally subjected to wavelet transformation. RESULTS: The lower limb muscle group was activated once in a cycle. The anterior and posterior thigh muscle groups, and anterior Tibial muscles were activated in the early stage, increased to the maximum value and then decreased gradually; the long and short muscles attached to the fibula were activated in the middle stage, and decreased rapidly. CONCLUSIONS: The research results of sEMG signal showed that the torque intensity of the front and back thigh muscles is greater than that of other muscle groups. Strengthening the training is helpful to enhance the jumping ability of basketball players.
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Baloncesto , Músculos Isquiosurales , Electromiografía , Masculino , Músculo Esquelético , Muslo , TorqueRESUMEN
A new two-dimensional wireless and passive stress sensor using the inverse magnetostrictive effect is proposed, designed, analyzed, fabricated, and tested in this work. Three pieces of magnetostrictive material are bonded on the surface of a smart elastomer structure base to form the sensor. Using the external load, an amplitude change in the higher-order harmonic signal of the magnetic material is detected (as a result of the passive variation of the magnetic permeability wirelessly). The finite element method (FEM) is used to accomplish the design and analysis process. The strain-sensitive regions of the tension and torque are distributed at different locations, following the FEM analysis. After the fabrication of a sensor prototype, the mechanical output performance is measured. The effective measurement range is 0â»40 N and 0â»4 N·M under tension and torque, respectively. Finally, the error of the sensor after calibration and decoupling for Fx is 3.4% and for Tx is 4.2% under a compound test load (35 N and 3.5 N·M). The proposed sensor exhibits the merits of being passive and wireless, and has an ingenious structure. This passive and wireless sensor is useful for the long-term detection of mechanical loading within a moving object, and can even potentially be used for tracing dangerous overloads and for preventing implant failures by monitoring the deformation of implants in the human body.
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Técnicas Biosensibles/instrumentación , Monitoreo Fisiológico/instrumentación , Ajuste de Prótesis/instrumentación , Estrés Mecánico , Tecnología Inalámbrica , Calibración , Diseño de Equipo , Análisis de Elementos Finitos , Humanos , Magnetismo/instrumentación , Torque , Soporte de PesoRESUMEN
A magnetoelastic-based (MB) sensor was employed as a novel method to monitor and assess the degradation rate of magnesium-based artificial bone (MBAB) in vitro, which can be used as an implant to repair a bone defect, providing a quantitative method to depict the degradation rate of MBAB. MBABs were fabricated by the Pro/Engineering software and a precision machine tool using high-purity (HP) magnesium. The MB sensor was embedded in the neutral surface of MBAB by an unharmful quick adhesive, forming the MB sensor-embedded MBAB (EMBAB). The modified simulated body fluid (MSBF) media (PH = 7.4), mimicking the human internal environment, and the NaOH media (PH = 12), accelerating EMBAB's degradation, were used to immerse the EMBAB for 15 days at 37 °C. The EMBAB was then tested daily on a self-developed experimental platform to monitor the relative output power under a 100 N external force. The results showed that the relative output power of the sensing coil gradually increased with the EMBAB's degradation. The degradation rate of the EMBAB could be calculated on the basis of the changes of the relative output power caused by the MB sensor and of the degradation time. With the EMBAB's degradation, an increasing strain directly worked on the MB sensor, significantly changing the value of the relative output power, which means that the EMBAB was characterized by a quick degradation rate. During the 15 days of the experiment, the degradation rates on the 7th and 15th days were 0.005 dbm/day and 0.02 dbm/day, and 0.02 dbm/day and 0.04 dbm/day in MSBF and alkaline media, respectively. Therefore, the MB sensor provides a wireless and passive method to monitor and assess the degradation rate of bone implants in vitro.
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Órganos Artificiales , Huesos , Magnesio/química , Magnetismo , Ensayo de Materiales/instrumentación , Prótesis e Implantes , Tecnología Inalámbrica/instrumentación , Adhesivos , Líquidos Corporales/química , Elasticidad , Humanos , Técnicas In VitroRESUMEN
BACKGROUND: We aimed to investigate the relationship between quality of life and the factors that may influence it in an elderly community-dwelling population in Shanghai. METHODS: From August to October 2014, elderly individuals were enrolled from three randomly selected communities in Shanghai. Participant information was collected from responses to a general questionnaire and to the Lubben Social Network Scale-6, Cumulative Illness Rating Scale for Geriatrics, Patient Health Questionnaire, and the 12-item Short Form Health Survey. The factors influencing quality of life were explored in a multivariate stepwise linear regression model. RESULTS: Physical and mental component summary scores for the elderly in Shanghai communities were 50.1 ± 10.1 and 47.3 ± 7.9, respectively. Physical component summary scores in the rural area were higher than those in the urban-rural intersection area (a place where urban and rural transitions are taking place) (52.32 ± 9.81 vs 49.63 ± 9.33, P < 0.05) and the urban area (52.32 ± 9.81 vs 47.34 ± 10.18, P < 0.05). Additionally, mental component summary scores in the rural area were higher than those in the urban-rural intersection area (52.63 ± 9.28 vs 48.43 ± 9.42, P < 0.05) and the urban area (52.63 ± 9.28 vs 48.13 ± 10.69, P < 0.05). CONCLUSIONS: Depression, self-care ability, and medical care burden were found to be significantly associated with the quality of life of elderly individuals in Shanghai, China. Therefore, more attention should be paid to the mental health of this elderly population.
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Depresión/epidemiología , Vida Independiente/psicología , Salud Mental , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Femenino , Estado de Salud , Encuestas Epidemiológicas , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Población Rural/estadística & datos numéricos , Encuestas y Cuestionarios , Población Urbana/estadística & datos numéricosRESUMEN
A metal-organic framework (MOF)-based catalyst, chromium hydroxide/MIL-101(Cr), was prepared by a one-pot synthesis method. The combination of chromium hydroxide particles on and within Lewis acidic MIL-101 accomplishes highly selective conversion of glucose to fructose in the presence of ethanol, matching the performance of optimized Sn-containing Lewis acidic zeolites. Differently from zeolites, NMR spectroscopy studies with isotopically labeled molecules demonstrate that isomerization of glucose to fructose on this catalyst, proceeds predominantly via a proton transfer mechanism.
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Amorphous zeolitic imidazolate frameworks (ZIFs) offer promising applications as novel functional materials. Herein, amorphization of ZIF-L through scanning-electron-beam exposure is demonstrated, based on amorphization of individual ZIF-L crystals. The amorphized ZIF product has drastically increased stability against dissolution in water. An electron dose that allows for complete preservation of amorphous particles after immersion in water is established, resulting in new shapes of amorphous ZIF-L with spatial control at the sub-micrometer length scale. Changed water stability as a consequence of scanning-electron-beam exposure is demonstrated for three additional metal-organic frameworks (ZIF-8, Zn(BeIm)OAc, MIL-101), highlighting the potential use of an electron beam for top-down MOF patterning. Lastly, recrystallization of ZIF-L in the presence of linker is studied and shows distinct differences for crystalline and amorphized material.
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Regulatory B10 cells were functionally impaired in rheumatoid arthritis (RA), yet the mechanisms were unclear. B cells are recently recognized as important participants in osteoclastogenesis by producing RANKL. In this study, we investigated whether regulatory B10 cells could convert into RANKL-producing cells, thus impairing their immunosuppressive functions in RA and exacerbating the disease progression. Our results showed that human regulatory B10 cells could ectopically express RANKL. Under RA circumstance, RANKL-producing B10 cells expanded dramatically, partially induced by TNF-α. The frequencies of these cells were positively correlated with RA patient disease activities and tender joint counts, but negatively correlated with the frequencies of regulatory B10 cells. Strikingly, RANKL-producing B10 cells from RA patients, but not healthy individuals significantly promoted osteoclast differentiation and bone erosion in a paracrine and cell-cell contact-dependent manner. Moreover, these pathogenic RANKL-producing B10 cells declined while regulatory IL-10-producing B10 cells increased in RA patients with disease remission after therapy. Collectively, these results showed that in RA, regulatory B10 cells demonstrated the potential of converting into RANKL-producing cells, thus exacerbating osteoclast formation, bone destruction and disease progression. Modulating the status of B10 cells might provide novel therapeutic strategies for RA.
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Artritis Reumatoide/etiología , Artritis Reumatoide/metabolismo , Linfocitos B Reguladores/citología , Linfocitos B Reguladores/metabolismo , Transdiferenciación Celular , Osteoclastos/citología , Osteoclastos/metabolismo , Artritis Reumatoide/patología , Artritis Reumatoide/terapia , Autoanticuerpos/inmunología , Linfocitos B Reguladores/inmunología , Biomarcadores , Estudios de Casos y Controles , Transdiferenciación Celular/inmunología , Expresión Génica Ectópica , Humanos , Inmunofenotipificación , Fenotipo , Ligando RANK/genética , Ligando RANK/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This paper reports on a sensor for monitoring bone plate strain in real time. The detected bone plate strain could be used for judging the healing state of fractures in patients. The sensor consists of a magnetoelastic material, which can be wirelessly connected and passively embedded. In order to verify the effectiveness of the sensor, a tibia-bone plate-screw (TBS) model was established using the finite element analysis method. A variation of the bone plate strain was obtained via this model. A goat hindquarter tibia was selected as the bone fracture model in the experiment. The tibia was fixed on a high precision load platform and an external force was applied. Bone plate strain variation during the bone fracture healing process was acquired with sensing coils. Simulation results indicated that bone plate strain decreases as the bone gradually heals, which is consistent with the finite element analysis results. This validated the soundness of the sensor reported here. This sensor has wireless connections, no in vivo battery requirement, and long-term embedding. These results can be used not only for clinical practices of bone fracture healing, but also for bone fracture treatment and rehabilitation equipment design.
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Metal-organic frameworks (MOFs) provide convenient systems for organizing high concentrations of single catalytic sites derived from metallic or oxo-metallic nodes. However, high-temperature processes cause agglomeration of these nodes, so that the single-site character and catalytic activity are lost. In this work, we present a simple nanocasting approach to provide a thermally stable secondary scaffold for MOF-based catalytic single sites, preventing their aggregation even after exposure to air at 600 °C. We describe the nanocasting of NU-1000, a MOF with 3 nm channels and Lewis-acidic oxozirconium clusters, with silica. By condensing tetramethylorthosilicate within the NU-1000 pores via a vapor-phase HCl treatment, a silica layer is created on the inner walls of NU-1000. This silica layer provides anchoring sites for the oxozirconium clusters in NU-1000 after the organic linkers are removed at high temperatures. Differential pair distribution functions obtained from synchrotron X-ray scattering confirmed that isolated oxozirconium clusters are maintained in the heated nanocast materials. Pyridine adsorption experiments and a glucose isomerization reaction demonstrate that the clusters remain accessible to reagents and maintain their acidic character and catalytic activity even after the nanocast materials have been heated to 500-600 °C in air. Density functional theory calculations show a correlation between the Lewis acidity of the oxozirconium clusters and their catalytic activity. The ability to produce MOF-derived materials that retain their catalytic properties after exposure to high temperatures makes nanocasting a useful technique for obtaining single-site catalysts suitable for high-temperature reactions.