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1.
Proc Natl Acad Sci U S A ; 121(7): e2316320121, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38319966

RESUMEN

Stinger-like structures in living organisms evolved convergently across taxa for both defensive and offensive purposes, with the main goal being penetration and damage. Our observations over a broad range of taxa and sizes, from microscopic radiolarians to narwhals, reveal a self-similar geometry of the stinger extremity: the diameter (d) increases along the distance from the tip (x) following a power law [Formula: see text] , with the tapering exponent varying universally between 2 and 3. We demonstrate, through analytical and experimental mechanics involving three-dimensional (3D) printing, that this geometry optimizes the stinger's performance; it represents a trade-off between the propensity to buckle, for n smaller than 2, and increased penetration force, for n greater than 3. Moreover, we find that this optimal tapering exponent does not depend on stinger size and aspect ratio (base diameter over length). We conclude that for Nature's stingers, composed of biological materials with moduli ranging from hundreds of megapascals to ten gigapascals, the necessity for a power-law contour increases with sharpness to ensure sufficient stability for penetration of skin-like tissues. Our results offer a solution to the puzzle underlying this universal geometric trait of biological stingers and may provide a new strategy to design needle-like structures for engineering or medical applications.


Asunto(s)
Agujas , Piel , Extremidades
2.
Proc Natl Acad Sci U S A ; 119(1)2022 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-34983853

RESUMEN

Solid-solid phase transformations can affect energy transduction and change material properties (e.g., superelasticity in shape memory alloys and soft elasticity in liquid crystal elastomers). Traditionally, phase-transforming materials are based on atomic- or molecular-level thermodynamic and kinetic mechanisms. Here, we develop elasto-magnetic metamaterials that display phase transformation behaviors due to nonlinear interactions between internal elastic structures and embedded, macroscale magnetic domains. These phase transitions, similar to those in shape memory alloys and liquid crystal elastomers, have beneficial changes in strain state and mechanical properties that can drive actuations and manage overall energy transduction. The constitutive response of the elasto-magnetic metamaterial changes as the phase transitions occur, resulting in a nonmonotonic stress-strain relation that can be harnessed to enhance or mitigate energy storage and release under high-strain-rate events, such as impulsive recoil and impact. Using a Landau free energy-based predictive model, we develop a quantitative phase map that relates the geometry and magnetic interactions to the phase transformation. Our work demonstrates how controllable phase transitions in metamaterials offer performance capabilities in energy management and programmable material properties for high-rate applications.

3.
Arch Gynecol Obstet ; 308(5): 1641-1647, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37430177

RESUMEN

PURPOSE: This study aimed to compare the distribution and drainage pathway of sentinel lymph nodes between high- and low-risk endometrial cancers. METHODS: In total, 429 patients with endometrial cancer who underwent sentinel lymph node biopsy in Peking University People's Hospital from July 2015 to April 2022 were retrospectively enrolled. There were 148 patients in the high-risk group and 281 patients in the low-risk group. RESULTS: The unilateral and bilateral detection rates of sentinel lymph nodes were 86.5% and 55.9%, respectively. The highest detection rate was achieved in the subgroup with a combined use of indocyanine green (ICG) and carbon nanoparticles (CNP) (94.4% for unilateral detection and 66.7% for bilateral detection). The upper paracervical pathway (UPP) was detected in 93.3% of cases in the high-risk group and 96.0% of cases in the low-risk group (p = 0.261). The lower paracervical pathway (LPP) was detected in 10.0% of cases in the high-risk group and 17.9% of cases in the low-risk group (p = 0.048). Remarkably increased detection rates of SLN in the common iliac (7.5%) and para-aortic or precaval areas (2.9%) were observed in the high-risk group. In contrast, a markedly decreased detection rate of SLN in the internal iliac area (1.9%) was observed in the high-risk group. CONCLUSION: The highest detection rate of SLN was observed in the subgroup with a combined use of ICG and CNP. The detection of UPP is important for both high-risk and low-risk cases, while LPP detection plays a more important role in the low-risk group. Lymphadenectomy in the common iliac and para-aortic or precaval areas is essential for patients with high-risk EC. Removal of internal iliac lymph nodes is essential for patients with low-risk EC, in case of ineffective SLN mapping.


Asunto(s)
Neoplasias Endometriales , Ganglio Linfático Centinela , Femenino , Humanos , Ganglio Linfático Centinela/cirugía , Metástasis Linfática/patología , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Neoplasias Endometriales/patología , Escisión del Ganglio Linfático , Verde de Indocianina
4.
Mycopathologia ; 188(1-2): 99-109, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36378354

RESUMEN

BACKGROUND: Vulvovaginal candidiasis (VVC) is a public health issue worldwide. Little is known of the optimal treatment of recurrent VVC (RVVC) has not been established. OBJECTIVE: Through the in vitro antifungal susceptibility profiling of VVC isolates, we hope to foster significant improvements in the control and treatment of this disease. METHODS: Candida isolates from VVC patients were collected from 12 hospitals in 10 cities across China. Species were identified by phenotype analysis and DNA sequencing. Species were identified by phenotype analysis and DNA sequencing. Susceptibilities to 11 drugs were determined by Clinical and Laboratory Standards Institute broth microdilution. RESULTS: 543 strains were isolated from those VVC patients enrolled in this study, of which, 15.7% were from RVVC. The most commonly identified species was C. albicans (460, 84.71%), and the most commonly non-albicans Candida spp. (NAC) was C. glabrata (47, 8.66%). NAC also included C. Krusei, Meyerozyma Guillermondii, Meyerozyma Caribbica, C. Tropicalis, C. Parapsilosis, and C. Nivariensis. Most C. albicans isolates were susceptible to caspofungin (99.8%), followed by fluconazole (92%) and voriconazole (82.6%). The proportion of C. albicans strains with wild type (WT) MICs that were susceptible to amphotericin B and caspofungin were 98%, followed by posaconazole at 95%, itraconazole at 86%, fluconazole at 74% and voriconazole at 54%. The fluconazole MICs for C. albicans were lower than those for NAC (P < 0.05), while the itraconazole MICs showing no significant difference (P > 0.05). The susceptible rate of uncomplicated VVC to fluconazole was 92%. The proportion of WT strains to fluconazole in RVVC was much lower than that in other types of VVC (67 vs. 77%, P < 0.05). However, the proportions of WT strains to itraconazole in RVVC was over 85%, which was much higher than that to fluconazole (87 vs. 67%, P < 0.05). CONCLUSIONS: C. albicans was still the predominant pathogen for VVC in China, while C. glabrata was the main species in NAC. Fluconazole could still be used as an empirical treatment for uncomplicated VVC. However, fluconazole may not be the first choice for the therapy of RVVC. In such cases, itraconazole appears to be the more appropriate treatment. As for VVC caused by NAC, nonfluconazole drugs, such as itraconazole, may be a good choice.


Asunto(s)
Antifúngicos , Candidiasis Vulvovaginal , Humanos , Femenino , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/microbiología , Fluconazol/uso terapéutico , Azoles/farmacología , Azoles/uso terapéutico , Itraconazol/uso terapéutico , Voriconazol/uso terapéutico , Caspofungina , Candida , Candida albicans , Candida glabrata
5.
Environ Sci Technol ; 56(9): 5390-5397, 2022 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-35442649

RESUMEN

Urban greening has often been proposed as a cost-effective solution to improve environmental comfort, but may also deteriorate air quality. Quantifying these two opposing effects of urban greening is necessary to develop successful environmental policies for specific mega-city clusters. In this study, a high-resolution regional climate and air quality model (WRF-Chem, v4.0.3) was employed to test three scenarios aimed at quantifying the impact of land-use change and biogenic emissions from urban greening on regional climate and air quality. It was found that urban greening could effectively decrease the near-surface temperature by up to 0.45 °C, but the increased biogenic volatile organic compound (BVOC) emissions offset some of this cooling effect (by up to 65%). Land-use change due to urban greening dominated the improvement in human comfort but worsened diffusion conditions to result in the convergence of fine particulate matter in specific areas. The selection of low-emission tree species may be imperative, although increased emissions from urban greening will not change the sensitivity of ozone to precursors under the current scenario of anthropogenic emissions. This is because BVOC emissions due to urban greening will become a more important source of pollution with the development of clean energy and the popularity of low-carbon lifestyles.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Compuestos Orgánicos Volátiles , Contaminación del Aire/prevención & control , Monitoreo del Ambiente , Política Ambiental , Contaminación Ambiental , Humanos , Material Particulado
6.
J Obstet Gynaecol Res ; 48(7): 1888-1896, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35384146

RESUMEN

OBJECTIVE: To discuss the impact of chemoradiotherapy (CRT) on the survival of patients with stage III endometrial cancer (EC) compared with chemotherapy (CT) alone. METHODS: Articles involving adjuvant CRT versus CT on survival in stage III EC were retrieved from PubMed and EMBASE. Hazard ratios (HRs) of overall survival (OS) and relapse-free survival (RFS) were collected and pooled, and publication bias was measured by Begg's and Egger's test. Quality of researches was measured by the Newcastle-Ottawa scale and the modified Jadad scale. RESULTS: Eleven were included in the statistical analysis. A significant advantage of CRT over CT on OS was shown (HR 0.59, 95% CI 0.49-0.70). Further subgroup analysis suggested the advantage was mostly associated with stage IIIC (HR 0.63, 95% CI 0.52, 0.76]). A similar result favoring CRT was also reached on RFS (HR 0.66, 95% CI 0.47-0.93). No significant publication bias was observed. CONCLUSION: CRT was associated with a better OS and RFS than CT alone in stage III EC patients.


Asunto(s)
Quimioradioterapia Adyuvante , Neoplasias Endometriales , Quimioradioterapia , Quimioterapia Adyuvante , Neoplasias Endometriales/tratamiento farmacológico , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Radioterapia Adyuvante
7.
Ren Fail ; 44(1): 81-93, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35164633

RESUMEN

BACKGROUND: The diagnostic value of procalcitonin (PCT) in patients undergoing hemodialysis (HD) remains unclear. METHODS: We searched multiple databases (PubMed, EMBASE, and Cochrane Library) for studies published through August 2021 that evaluated the diagnostic performance of PCT in patients undergoing HD and having suspected bacterial infections. The bivariate fixed effects model was used to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and summary receiver operating characteristic (SROC) curves. RESULTS: We identified a total of 1799 studies, of which seven diagnostic studies comprised 1444 patients and 430 bacterial infection episodes. Bivariate pooled sensitivity and specificity for PCT were 0.90 (95% CI: 0.85-0.94) and 0.83 (95% CI: 0.56-0.95), respectively. Furthermore, pooled DOR, PLR, NLR, and area under the curve (AUC) were 47 (95% CI: 11-209), 5.4 (95% CI: 1.7-16.9), 0.12 (95% CI: 0.07-0.20), and 0.92 (95% CI: 0.90-0.94), respectively. We also compared the diagnostic accuracy of PCT and C-reactive protein (CRP), and our results showed that the diagnostic accuracy parameters for PCT were significantly higher than those for CRP. CONCLUSIONS: PCT is a useful marker for diagnosis of bacterial infections in patients undergoing HD at a cutoff value of 1.5 ng/ml.


Asunto(s)
Infecciones Bacterianas/sangre , Proteína C-Reactiva/análisis , Polipéptido alfa Relacionado con Calcitonina/sangre , Diálisis Renal , Infecciones Bacterianas/diagnóstico , Biomarcadores/sangre , Humanos , Sensibilidad y Especificidad
8.
J Surg Oncol ; 124(3): 411-419, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34086291

RESUMEN

OBJECTIVE: To evaluate the feasibility and clinical value of the combination of carbon nanoparticles (CNPs) and indocyanine green (ICG) for identifying sentinel lymph nodes (SLNs) in endometrial cancer. MATERIALS AND METHODS: About 153 patients with endometrial cancer were recruited from July 2015 to May 2019. All patients underwent SLN biopsy according to the SLN algorithm for surgical staging with ICG and/or CNPs. The detection rate, factors associated with the detection rate, sensitivity, and negative predictive value (NPV) of SLNs were analyzed. RESULTS: The detection rates of SLNs with the combined method were the highest among the different methods. As calculated per hemipelvis, the sensitivity and NPV with ICG alone or with ICG plus CNPs were 100%. With CNP, tumor Grade 3 and laparoscopy were related to unsuccessful overall SLN mapping while tumor diameter greater than 2 cm and laparoscopy were statistically associated with failed bilateral mapping. With ICG, a higher body mass index was significantly associated with unsuccessful bilateral detection of SLN. CONCLUSION: SLN assessment in endometrial cancer is feasible and safe with high sensitivity and high NPV when ICG and CNPs are combined and in low-risk patients. It is a superior option to use CNPs in laparotomy for patients with endometrial cancer.


Asunto(s)
Carbono/química , Neoplasias Endometriales/diagnóstico por imagen , Verde de Indocianina/química , Nanopartículas/química , Biopsia del Ganglio Linfático Centinela/métodos , Ganglio Linfático Centinela/diagnóstico por imagen , Colorantes/química , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Retrospectivos , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía
9.
Ren Fail ; 43(1): 968-979, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34157937

RESUMEN

AIM: Podocyte injury plays an important role in diabetic nephropathy (DN), yet the underlying molecular mechanisms of podocyte injury in DN is not clear. Here, we investigated the role of activating transcription factor 4 (ATF4) and HO-1 in DN-induced podocyte injury. METHODS: Protein expression was measured by western blotting (WB) and immunofluorescence. Cellular apoptosis was quantified by flow cytometry. ATF4 siRNA knockdown and HO-1 overexpression in podocyte were employed to evaluate the role of ER stress in DN-induced apoptosis and autophagy response. Urinary protein levels, nephrin expression, serum creatinine and BUN were evaluated and glomerulosclerosis was quantified by Periodic Acid-Schiff staining. RESULTS: Expression of ATF4 was increased in podocytes exposed to serum from DN mice. ATF4 knockdown enhanced DN-induced podocyte apoptosis. HO-1 overexpression reduced the decline of DN-induced podocyte autophagy and inhibited apoptosis and the beneficial effects of HO-1 overexpression in DN were blocked by ATF4 knockdown. The diabetic mice were significantly ameliorated by HO-1 agonist hemin treatment. CONCLUSIONS: ATF4 induces autophagy by enhancing the expression of HO-1, and inhibits podocyte apoptosis in DN. Treatment with the HO-1 agonist reduced proteinuria, apoptosis, and enhanced autophagy response, and thus improved renal function in DN mice.


Asunto(s)
Factor de Transcripción Activador 4/metabolismo , Autofagia/efectos de los fármacos , Glucosa/farmacología , Hemo-Oxigenasa 1/metabolismo , Podocitos/patología , Factor de Transcripción Activador 4/genética , Animales , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/metabolismo , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/genética , Masculino , Ratones , Podocitos/efectos de los fármacos , Podocitos/enzimología , Proteinuria/tratamiento farmacológico , ARN Interferente Pequeño/genética , Transducción de Señal/efectos de los fármacos
10.
Phys Rev Lett ; 125(10): 108002, 2020 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-32955335

RESUMEN

Impulsive deformation is widely observed in biological systems to generate movement with high acceleration and velocity. By storing elastic energy in a quasistatic loading and releasing it through an impulsive elastic recoil, organisms circumvent the intrinsic trade-off between force and velocity and achieve power amplified motion. However, such asymmetry in strain rate in loading and unloading often results in reduced efficiency in converting elastic energy to kinetic energy for homogeneous materials. Here, we demonstrate that specific internal structural designs can offer the ability to tune quasistatic and high-speed recoil independently to control energy storage and conversion processes. Experimental demonstrations with mechanical metamaterials reveal that certain internal structures optimize energy conversion far beyond unstructured materials under the same conditions. Our results provide the first quantitative model and experimental demonstration for tuning energy conversion processes through internal structures of metamaterials.

11.
Nephrology (Carlton) ; 25(9): 723-729, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31999031

RESUMEN

AIM: Evaluate the relationship between anti-Xa activity and anticoagulant effect, and ascertain whether accumulation of low-molecular-weight heparins (LMWH) occurs during haemodialysis. METHODS: There was an observational, single-centre study among participants who received the LMWH dalteparin, enoxaparin or nadroparin. A standard haemodialysis session lasted 4 hours. All included participants had anti-Xa activity measures at 0.5 and 4 hours. Extracorporeal circuit (ECC) clotting was evaluated by visual inspection of the haemodialyser and bubble trap after each haemodialysis session. The same person was tested at three consecutive haemodialysis sessions. RESULTS: Overall, 90 participants were enrolled and 259 haemodialysis sessions assessed. There was no significant difference in the mean anti-Xa activity at 0.5 and 4 hours for three consecutive sessions, so LMWH accumulation did not occur. There were 69 (26.6%) sessions in which, ECC clotting was visible. Compared with the group where circuit clotting did not occur, the LMWH dose and anti-Xa activity in the group where circuit clotting occurred were significantly lower. At 0.5 hour, anti-Xa <0.88 IU/mL had significantly higher odds of ECC clotting than that at ≥0.88 IU/mL. At 4 hours, anti-Xa <0.35 IU/mL had significantly higher odds of ECC clotting than that at ≥0.35 IU/mL. CONCLUSION: We found that over three haemodialysis sessions, no significant accumulation of LMWH was evident in subjects receiving a LMWH dose of between 2000 and 5000 IU for regular. Anti-Xa activity measurement can be used to adjust the dosage of LMWH and predict the anticoagulant effect during haemodialysis.


Asunto(s)
Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Deficiencia del Factor X , Heparina de Bajo-Peso-Molecular/farmacología , Fallo Renal Crónico , Diálisis Renal , China/epidemiología , Cálculo de Dosificación de Drogas , Deficiencia del Factor X/inducido químicamente , Deficiencia del Factor X/diagnóstico , Factor Xa/metabolismo , Femenino , Heparina de Bajo-Peso-Molecular/clasificación , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Diálisis Renal/efectos adversos , Diálisis Renal/métodos
12.
BMC Nephrol ; 21(1): 252, 2020 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-32616008

RESUMEN

BACKGROUND: According to the "lipid nephrotoxicity hypothesis", there is now significant research being conducted in this area. By studying the role of hyperlipidemia in chronic kidney disease in the general Zhejiang population, we aimed to explore the correlation between changes in blood lipid levels and chronic kidney disease. METHODS: We collected and analyzed clinical data from ordinary residents who participated in the annual comprehensive physical examination with no overt kidney disease in Zhejiang Provincial People's Hospital, China from January 2011 to December 2016. According to triglyceride, total cholesterol and low-density lipoprotein levels, participants were respectively divided into 4 groups. Statistical methods were used to evaluate the correlation between different blood lipid profiles and chronic kidney disease. RESULTS: Five thousand one hundred eighty-three participants were included in our study. During the six-year follow-up period, 227 participants (4.4%) developed chronic kidney disease. The odds ratio for incident chronic kidney disease was 3.14 (95%CI: 1.53-6.43) in Q3, 3.84 (95%CI: 1.90-7.76) in Q4 according to the total cholesterol group and 1.17 (95%CI: 1.04-1.32) in Q3, 1.40 (95%CI: 1.11-2.48) in Q4 according to the low-density lipoprotein group, respectively, after multivariable-adjusted analyses. According to the triglyceride grouping, the odds ratio for incident chronic kidney disease was 2.88 (95%CI: 1.29-6.43) in Q2, 2.92 (95%CI: 1.44-6.57) in Q3 and 3.08 (95%CI: 1.11-6.69) in Q4, after multivariable-adjusted analyses. CONCLUSION: Increased triglycerides and high levels of total cholesterol and low-density lipoprotein were independently associated with an increased likelihood of estimated glomerular filtration rate (eGFR) decline and development of incident chronic kidney disease in the general Zhejiang population.


Asunto(s)
Dislipidemias/epidemiología , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica/epidemiología , Adulto , Anciano , China/epidemiología , Colesterol/sangre , Dislipidemias/sangre , Femenino , Humanos , Hipertensión/epidemiología , Incidencia , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Estudios Retrospectivos , Triglicéridos/sangre , Adulto Joven
13.
BMC Infect Dis ; 19(1): 940, 2019 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-31699037

RESUMEN

BACKGROUND: Bacillus anthracis causes a highly lethal infectious disease primarily due to toxin-mediated injury. Antibiotics are no longer effective to treat the accumulation of anthrax toxin, thereby new strategies of antibody treatment are essential. Two anti- anthrax protective antigen (PA) antibodies, hmPA6 and PA21, have been reported by our lab previously. METHODS: The mechanisms of the two antibodies were elucidated by Electrophoresis, Competitive Enzyme-linked immune sorbent assay, Western blot analysis and immunoprecipitation test, and in vitro, in vivo (F344 rats) treatment test. The epitopes of the two antibodies were proved by Western blot and Enzyme-linked immune sorbent assay with different domains of PA. RESULTS: In this study, we compared affinity and neutralization of these two antibodies. PA21 was better in protecting cells and rats, whereas hmPA6 had higher affinity. Furthermore, the neutralization mechanisms of the two antibodies and their recognition domains of PA were studied. The results showed that hmPA6 recognized domain IV, thus PA could not bind to cell receptors. Conversely, PA21 recognized domain II, thereby limiting heptamer oligomerization of PA63 in cells. CONCLUSIONS: Our studies elucidated the mechanisms and epitopes of hmPA6 and PA21. The present investigation can advance future use of the two antibodies in anthrax treatment or prophylaxis, and potentially as a combination treatment as the antibodies target different epitopes.


Asunto(s)
Anticuerpos Antibacterianos/metabolismo , Anticuerpos Neutralizantes/metabolismo , Bacillus anthracis/inmunología , Animales , Carbunco/inmunología , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/farmacología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/farmacología , Antígenos Bacterianos/toxicidad , Toxinas Bacterianas/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Electroforesis , Epítopos/análisis , Epítopos/inmunología , Inmunoensayo , Ratas , Ratas Endogámicas F344
14.
BMC Infect Dis ; 18(1): 640, 2018 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-30526504

RESUMEN

BACKGROUND: Disease caused by Bacillus anthracis is often accompanied by high mortality primarily due to toxin-mediated injury. In the early disease course, anthrax toxins are secreted; thus, antibiotic use is limited to the early stage. In this regard, antibodies against the toxin component, protective antigen (PA), play an important role in protecting against anthrax. Therefore, we developed PA21, a fully human anti-PA immunoglobulin G monoclonal antibody. METHODS: Combining human Fab was screened from a phage library with human heavy constant regions. Enzyme-linked immune sorbent assay, Western blot analysis and immunoprecipitation test evaluated the binding ability of PA21. Moreover, the affinity and neutralizing activity of the antibody was detected in vitro while the protective effectiveness in 60 rats was also examined in vivo. RESULTS: The Fischer 344 rats challenged with the lethal toxin can be protected by PA21 at a concentration of 0.067 mg/kg. All six rats remained alive although PA21 was injected 24 h before the toxin challenge. PA21 did not influence the binding of PA to cell receptors and that of a lethal factor to PA. CONCLUSION: The PA21 monoclonal antibody against PA can be used for emergency prophylaxis and anthrax treatment.


Asunto(s)
Carbunco/prevención & control , Anticuerpos Antibacterianos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Antígenos Bacterianos/inmunología , Bacillus anthracis/inmunología , Toxinas Bacterianas/inmunología , Profilaxis Posexposición/métodos , Animales , Carbunco/inmunología , Anticuerpos Antibacterianos/inmunología , Células Cultivadas , Exotoxinas/inmunología , Femenino , Humanos , Ratones , Ratas , Ratas Endogámicas F344
15.
Soft Matter ; 12(37): 7726-7730, 2016 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-27722731

RESUMEN

A cylindrical elastomer tube can stay in an everted state without any external forces. If the thickness of the tube is small, the everted tube, except for the regions close to the free ends of the tube, maintains a cylindrical shape, and if the thickness is larger than a critical value, the cross-section of the everted tube becomes noncircular, which is caused by mechanical instability. Although eversion-induced instability in an elastomer tube has been reported several decades ago, a satisfying explanation of the phenomenon is still unavailable. In all previous studies, linear analyses have been adopted to predict the critical thickness of the tube for eversion-induced instability. The discrepancy between prediction and experiment is significant. In this communication, based on experiments and theoretical analyses, we show that crease formation on the inner surface of an everted tube is the mechanical instability mode, which cannot be captured by linear stability analyses. Instead, a combination of energetic analyses and numerical simulations of finite deformation in an everted tube enables us to correctly predict both the critical tube thickness for the onset of creases and the profile of the noncircular cross-section of an everted tube.

16.
Proc Natl Acad Sci U S A ; 108(23): 9466-71, 2011 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-21593411

RESUMEN

The mechanism by which ECM elasticity induces lineage specification of stem cells has not been clearly understood. Integrins are well-documented mechanosensors that are positioned at the beginning of the sensing pathway. By using an antibody specifically recognizing the active conformation of ß1 integrin, we observed that ß1 integrin activation in bone marrow mesenchymal stem cells (BMMSCs) was induced by soft substrate to a significantly greater degree than by stiff substrate. In contrast, however, the level of cell surface integrin on soft substrate was significantly lower than that on stiff substrate. Soft substrate markedly enhanced the internalization of integrin, and this internalization was mediated mainly through caveolae/raft-dependent endocytosis. The inhibition of integrin internalization blocked the neural lineage specification of BMMSCs on soft substrate. Furthermore, soft substrate also repressed the bone morphogenetic protein (BMP)/Smad pathway at least partially through integrin-regulated BMP receptor endocytosis. A theoretical analysis based on atomic force microscopy (AFM) data indicated that integrin-ligand complexes are more easily ruptured on soft substrate; this outcome may contribute to the enhancement of integrin internalization on soft substrate. Taken together, our results suggest that ECM elasticity affects integrin activity and trafficking to modulate integrin BMP receptor internalization, thus contributing to stem cell lineage specification.


Asunto(s)
Diferenciación Celular , Endocitosis , Matriz Extracelular/metabolismo , Integrina beta1/metabolismo , Células Madre/metabolismo , Animales , Western Blotting , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/metabolismo , Caveolas/metabolismo , Caveolina 1/genética , Caveolina 1/metabolismo , Células Cultivadas , Elasticidad , Citometría de Flujo , Inmunohistoquímica , Microdominios de Membrana/metabolismo , Microscopía de Fuerza Atómica , Interferencia de ARN , Ratas , Ratas Sprague-Dawley , Células Madre/citología
17.
Diabetes Ther ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38776037

RESUMEN

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have attracted much attention because of their significant hypoglycemic and weight-loss effects. Previous preparations can only be subcutaneously injected. Oral administration of GLP-1RAs semaglutide helps to broaden treatment options, but its safety in the real world still needs to be observed. This study is based on FDA adverse event reporting system (FAERS) database to mine adverse drug events (ADE) of oral semaglutide, and provide references for the clinical safe use of this drug. METHODS: To analyze the signal quality of oral semaglutide, which is a drug used in the FAERS database from the third quarter of 2019 to the third quarter of 2023, we collected ADE data and performed data mining by using disproportionate analysis. Then, we standardized the data and used a variety of signal-quantification techniques, including reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian belief propagation neural network (BCPNN), and multiple empirical Bayesian gamma Poisson contractions (MGPS), for further analysis. RESULTS: We screened 2398 reports on the use of semaglutide tablets, involving a total of 5653 ADE. These reports were mainly submitted by consumers, and the reporting country was mainly the United States. A total of 23 system organ classes (SOC) and 93 preferred terms (PT) were mined for the signals of semaglutide tablets. The three most common SOC were gastrointestinal disorders, general disorders and administration site conditions, and investigations. At the PT level, metabolism and nutrition disorders exhibit the highest number of signals, with the top three being thyroid cyst, acute cholecystitis, and ketosis. Gastrointestinal disorders rank second, primarily involving eructation, pancreatitis, impaired gastric emptying, and regurgitation. In addition, vith nerve paralysis occurs and the signal intensity is high. CONCLUSIONS: Our study provides a deeper and broader understanding of the safety of oral semaglutide. The results of the ROR, PRR, BCPNN, and MGPS algorithms exhibit high consistency, with metabolism and nutrition-related disorders having the highest number of signals. The conclusions align with the technical specifications of the product. Notably, other unexpected effects are reported, including acute cholecystitis, paralysis of the abducens nerve, and positional vertigo.

18.
Front Med (Lausanne) ; 11: 1380464, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903808

RESUMEN

Background: Metabolic syndrome (MetS) is a global health concern, and it is particularly harmful to middle-aged and elderly individuals. Life Element Eight (LE8), a measure to improve cardiovascular health, may offer benefits for MetS. Herein, we examined the relationship between LE8 and MetS among middle-aged and elderly individuals, and elucidated the role of biological aging and inflammation in this process. Methods: We obtained the LE8 scores of 2,901 Americans, along with their biological aging indicators (Biological age, Phenotypic age, Serum Klotho), and computed their inflammatory indicators SII, DII. Using logistic regression model, we assessed the association among inflammatory markers, Biological aging, LE8 and MetS. Additionally, we generated restricted cubic spline (RCS) plots to display trends in significant variables in logistic regression. Using parallel mediation analysis, we evaluated the possible mediating role of various factors in the risk relationship between LE8 and MetS. Results: Our examination revealed that higher LE8 scores were associated with a lower incidence of MetS in a fully adjusted model. The high LE8 subgroup had a 79.73% reduction in the risk of MetS compared to the low subgroup with an OR = 0.2027 (95% Cl 0.0871, 0.4714), with similar correlations between health factor scores and MetS risk. Biological aging mediated the associations between LE8, health behaviors and health factor scores and MetS risk. Conclusion: A rise in the LE8 score among middle-aged and elderly individuals is a protective factor for MetS, and this association may be partially mediated by biological aging, suggesting that LE8 may reduce the risk of MetS by ameliorating aging.

19.
Adv Sci (Weinh) ; : e2402940, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767181

RESUMEN

Structural materials such as ceramics, metals, and carbon fiber-reinforced plastics (CFRP) are frequently threatened by large compressive and impact forces. Energy absorption layers, i.e., polyurethane and silicone foams with excellent damping properties, are applied on the surfaces of different substrates to absorb energy. However, the amount of energy dissipation and penetration resistance are limited in commercial polyurethane foams. Herein, a distinctive nacre-like architecture design strategy is proposed by integrating hard porous ceramic frameworks and flexible polyurethane buffers to improve energy absorption and impact resistance. Experimental investigations reveal the bioinspired designs exhibit optimized hardness, strength, and modulus compared to that of polyurethane. Due to the multiscale energy dissipation mechanisms, the resulting normalized absorbed energy (≈8.557 MJ m-3) is ≈20 times higher than polyurethane foams under 50% quasi-static compression. The bioinspired composites provide superior protection for structural materials (CFRP, glass, and steel), surpassing polyurethane films under impact loadings. It is shown CFRP coated with the designed materials can withstand more than ten impact loadings (in energy of 10 J) without obvious damage, which otherwise delaminates after a single impact. This biomimetic design strategy holds the potential to offer valuable insights for the development of lightweight, energy-absorbent, and impact-resistant materials.

20.
Phys Rev E ; 107(3-2): 035002, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37072976

RESUMEN

Soft layered systems buckling to form surface patterns has been widely studied under quasistatic loading. Here, we study the dynamic formation of wrinkles in a stiff-film-on-viscoelastic-substrate system as a function of impact velocity. We observe a spatiotemporally varying range of wavelengths, which display impactor velocity dependence and exceed the range exhibited under quasistatic loading. Simulations suggest the importance of both inertial and viscoelastic effects. Film damage is also examined, and we find that it can tailor dynamic buckling behavior. We expect our work to have applications to soft elastoelectronic and optic systems and open routes for nanofabrication.

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