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Non-obstructive azoospermia (NOA), the most severe form of male infertility, could be treated with intracytoplasmic sperm injection, providing spermatozoa were retrieved with the microdissection testicular sperm extraction (mTESE). We hypothesized that testis-specific and germ cell-specific proteins would facilitate flow cytometry-assisted identification of rare spermatozoa in semen cell pellets of NOA patients, thus enabling non-invasive diagnostics prior to mTESE. Data mining, targeted proteomics, and immunofluorescent microscopy identified and verified a panel of highly testis-specific proteins expressed at the continuum of germ cell differentiation. Late germ cell-specific proteins AKAP4_HUMAN and ASPX_HUMAN (ACRV1 gene) revealed exclusive localization in spermatozoa tails and acrosomes, respectively. A multiplex imaging flow cytometry assay facilitated fast and unambiguous identification of rare but morphologically intact AKAP4+/ASPX+/Hoechst+ spermatozoa within debris-laden semen pellets of NOA patients. While the previously suggested markers for spermatozoa retrieval suffered from low diagnostic specificity, the multistep gating strategy and visualization of AKAP4+/ASPX+/Hoechst+ cells with elongated tails and acrosome-capped nuclei facilitated fast and unambiguous identification of the mature intact spermatozoa. AKAP4+/ASPX+/Hoechst+ assay may emerge as a noninvasive test to predict retrieval of morphologically intact spermatozoa by mTESE, thus improving diagnostics and treatment of severe forms of male infertility.
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Azoospermia , Infertilidad Masculina , Masculino , Humanos , Azoospermia/genética , Azoospermia/metabolismo , Azoospermia/terapia , Semen/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo , Infertilidad Masculina/metabolismo , Estudios Retrospectivos , Proteínas de Anclaje a la Quinasa A/metabolismoRESUMEN
Global population growth and industrialization have exacerbated the nonrenewable energy crises and environmental issues, thereby stimulating an enormous demand for producing environmentally friendly materials. Typically, biomass-based aerogels (BAs), which are mainly composed of biomass materials, show great application prospects in various fields because of their exceptional properties such as biocompatibility, degradability, and renewability. To improve the performance of BAs to meet the usage requirements of different scenarios, a large number of innovative works in the past few decades have emphasized the importance of micro-structural design in regulating macroscopic functions. Inspired by the ubiquitous random or regularly arranged structures of materials in nature ranging from micro to meso and macro scales, constructing different microstructures often corresponds to completely different functions even with similar biomolecular compositions. This review focuses on the preparation process, design concepts, regulation methods, and the synergistic combination of chemical compositions and microstructures of BAs with different porous structures from the perspective of gel skeleton and pore structure. It not only comprehensively introduces the effect of various microstructures on the physical properties of BAs, but also analyzes their potential applications in the corresponding fields of thermal management, water treatment, atmospheric water harvesting, CO2 absorption, energy storage and conversion, electromagnetic interference (EMI) shielding, biological applications, etc. Finally, we provide our perspectives regarding the challenges and future opportunities of BAs. Overall, our goal is to provide researchers with a thorough understanding of the relationship between the microstructures and properties of BAs, supported by a comprehensive analysis of the available data.
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Single-site copper-based catalysts have shown remarkable activity and selectivity for a variety of reactions. However, deactivation by sintering in high-temperature reducing environments remains a challenge and often limits their use due to irreversible structural changes to the catalyst. Here, we report zeolite-based copper catalysts in which copper oxide agglomerates formed after reaction can be repeatedly redispersed back to single sites using an oxidative treatment in air at 550 °C. Under different environments, single-site copper in Cu-Zn-Y/deAlBeta undergoes dynamic changes in structure and oxidation state that can be tuned to promote the formation of key active sites while minimizing deactivation through Cu sintering. For example, single-site Cu2+ reduces to Cu1+ after catalyst pretreatment (270 °C, 101 kPa H2) and further to Cu0 nanoparticles under reaction conditions (270-350 °C, 7 kPa EtOH, 94 kPa H2) or accelerated aging (400-450 °C, 101 kPa H2). After regeneration at 550 °C in air, agglomerated CuO was dispersed back to single sites in the presence and absence of Zn and Y, which was verified by imaging, in situ spectroscopy, and catalytic rate measurements. Ab initio molecular dynamics simulations show that solvation of CuO monomers by water facilitates their transport through the zeolite pore, and condensation of the CuO monomer with a fully protonated silanol nest entraps copper and reforms the single-site structure. The capability of silanol nests to trap and stabilize copper single sites under oxidizing conditions could extend the use of single-site copper catalysts to a wider variety of reactions and allows for a simple regeneration strategy for copper single-site catalysts.
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Nasopharyngeal Carcinoma (NC) refers to the malignant tumor that occurs at the top and side walls of the nasopharyngeal cavity. The NC incidence rate always dominates the first among the malignant tumors of the ear, nose and throat, and mainly occurs in Asia. NC cases are mainly concentrated in southern provinces in China, with about 4 million existing NC. With the pollution of environment and pickled diet, and the increase of life pressure, the domestic NC incidence rate has reached 4.5-6.5/100000 and is increasing year by year. It was reported that the known main causes of NC include hereditary factor, genetic mutations, and EB virus infection, common clinical symptoms of NC include nasal congestion, bloody mucus, etc. About 90% of NC is highly sensitive to radiotherapy which is regard as the preferred treatment method; However, for NC with lower differentiation, larger volume, and recurrence after treatment, surgical resection and local protons and heavy ions therapy are also indispensable means. According to reports, the subtle heterogeneity and diversity exists in some NC, with about 80% of NC undergone radiotherapy and about 25% experienced recurrence and death within five years after radiotherapy in China. Therefore, screening the NC population with suspected recurrence after concurrent chemoradiotherapy may improve survival rates in current clinical decision-making.
NC is one of the prevalent malignancies of the head and neck region with poor prognosis. The aim of this study is to establish a predictive model for assessing NC prognosis using clinical and MR radiomics data.
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Quimioradioterapia , Neoplasias Nasofaríngeas , Recurrencia Local de Neoplasia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , China/epidemiología , Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo/patología , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/diagnóstico por imagen , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Radiómica , Estudios RetrospectivosRESUMEN
BACKGROUND: A lower adherence rate existed in patients receiving allergen-specific immunotherapy due to its lengthy period and adverse effects even though it is the only curative treatment for IgE-mediated allergies. Therefore, exploring innovative allergen-specific immunotherapy routes is necessary. OBJECTIVE: To explore the efficacy and safety of the intratonsillar injection of house dust mite (HDM) extract in patients with HDM-induced allergic rhinitis (AR). METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 80 patients with HDM-induced AR were randomized to receive 6 intratonsillar injections with HDM extract or placebo in 3 months. The total nasal symptom score (TNSS), visual analogue scale of nasal symptoms, combined symptom and medication score, mini rhinoconjunctivitis quality of life questionnaire, and serum allergen-specific IgG4 to Dermatophagoides pteronyssinus were all monitored at baseline and 3 months, 6 months, and 12 months after the treatment was finished. The intent-to-treat and per-protocol set (PPS) are both analyzed. RESULTS: The primary end points TNSS and ΔTNSS were improved significantly at 3 months after the patients with AR finished a 3-month 6-injection intratonsillar immunotherapy compared with those in the placebo treatment in both intent-to-treat and PPS. Results of visual analogue scale, combined symptom and medication score, and mini rhinoconjunctivitis quality of life questionnaire were also improved significantly at 3 months after the treatment in PPS. However, the improvement effect of intratonsillar immunotherapy at 6 and 12 months was limited and uncertain based on the data. The increase of serum Der p IgG4 in the active group was significantly higher than that in the placebo group at 3, 6, and 12 months after the treatment was finished. Adverse events were monitored, and no systemic adverse reactions were observed. CONCLUSION: The clinical trial revealed that intratonsillar injection with HDM extract was safe and effective in patients with AR. Optimizing the protocol and allergen formulations is expected to increase and maintain the efficacy of this novel approach. TRIAL REGISTRATION: https://www.chictr.org.cn/index.html, identifier: ChiCTR-TRC-13003600.
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Conjuntivitis , Rinitis Alérgica Perenne , Rinitis Alérgica , Inmunoterapia Sublingual , Animales , Humanos , Calidad de Vida , Pyroglyphidae , Inmunoterapia Sublingual/métodos , Resultado del Tratamiento , Antígenos Dermatofagoides , Alérgenos , Rinitis Alérgica Perenne/tratamiento farmacológico , Método Doble Ciego , Conjuntivitis/etiología , Inmunoglobulina GRESUMEN
Recent years have seen ticagrelor, a potent P2Y12 inhibitor, emerge as a significant advancement in the peri-thrombolytic management of patients with ST-segment elevation myocardial infarction (STEMI), offering a promising alternative to traditional antiplatelet drugs like clopidogrel. This review critically examines the efficacy and safety of ticagrelor during the peri-thrombolytic phase in STEMI patients, drawing on evidence from key clinical trials such as TREAT and MIRTOS, as well as other relevant studies. These investigations underscore ticagrelor's superior platelet inhibition capabilities, which are crucial for minimizing thrombotic complications post-thrombolysis without increasing bleeding risks. Despite its potential, clopidogrel remains the guideline-recommended choice for such patients, leaving the appropriateness of ticagrelor in this context open to debate. By summarizing the current evidence and identifying gaps in our understanding, this study advocates for targeted research to clarify the long-term benefits and optimal deployment of ticagrelor, highlighting its evolving significance in cardiovascular care.
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BACKGROUND: There are no clear recommendations for optimal transfusion thresholds for patients with coronary artery disease who undergo noncardiac surgery. By comparing restrictive and liberal transfusion strategies for coronary artery disease combined with hip surgery, this study hopes to provide recommendations for transfusion strategies in this special population. METHODS: A total of 805 patients from the FOCUS trial (Transfusion Trigger Trial for Functional Outcomes in Cardiovascular Patients Undergoing Surgical Hip Fracture Repair) with coronary artery disease combined with hip surgery were divided into two groups based on transfusion thresholds: restricted transfusion (a hemoglobin level of 8 g/deciliter) and liberal transfusion (a hemoglobin threshold of 10 g/deciliter). The primary outcome of this study was a composite endpoint including in-hospital death, myocardial infarction, unstable angina, and acute heart failure. The secondary endpoints included other in-hospital adverse events and 30- and 60-day follow-up events. Analyses were performed by intention to treat. RESULTS: Except for the proportion of congestive heart failure patients, the baseline levels of the two groups were comparable. The median number of transfusion units in the liberal transfusion group was 2 units, and the median transfusion volume in the restricted transfusion group was 0 units. The primary outcome was not significantly different between the two groups (9.2% vs. 9.4%, p = 0.91). The incidence of in-hospital myocardial infarction events was lower in the liberal transfusion group than in the restricted transfusion group (3.2% vs. 6.2%) (OR = 0.51, P = 0.048). The remaining in-hospital endpoint events, except for myocardial infarction, were not significantly different between the two groups. The 30-day and 60-day endpoints of death and inability to walk independently were not significantly different between the two groups, with ORs (95% CI) of 1.00 (0.75-1.31) and 1.06 (0.80-1.41), respectively. We also found no interaction between transfusion strategies and factors such as age, sex, or multiple underlying comorbidities at the 60-day follow-up. CONCLUSIONS: There was no significant difference in the in-hospital, 30-day or 60-day outcome endpoints between the two groups. However, this study demonstrated that a liberal transfusion strategy tends to reduce the incidence of in-hospital myocardial infarction events in patients with coronary artery disease combined with hip surgery compared to a restrictive transfusion strategy. More high-quality studies should be designed to investigate the optimal transfusion threshold in patients with coronary artery disease treated without cardiac surgery.
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Transfusión Sanguínea , Enfermedad de la Arteria Coronaria , Hemoglobinas , Fracturas de Cadera , Mortalidad Hospitalaria , Humanos , Femenino , Masculino , Anciano , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/terapia , Resultado del Tratamiento , Factores de Tiempo , Fracturas de Cadera/cirugía , Fracturas de Cadera/mortalidad , Factores de Riesgo , Hemoglobinas/metabolismo , Hemoglobinas/análisis , Anciano de 80 o más Años , Biomarcadores/sangre , Medición de Riesgo , Persona de Mediana Edad , Fijación de Fractura/efectos adversos , Fijación de Fractura/mortalidad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/etiologíaRESUMEN
To examine the prevalence of comorbidities in Chinese urticaria patients and assess medication use patterns across different ages (6-11 years, 12-17 years, above 18 years), a retrospective cohort study was performed in 192,647 urticaria patients within the Health Database. After 1:1 propensity score matching, 166,921 people were divided into the urticaria group and the control group, and the follow-up data were collected within 2 years. During the 12-month and 24-month follow-up period, significant comorbidities identified included allergic rhinitis and asthma, with distinct patterns observed across age groups. Chronic urticaria patients often have complications, such as allergic rhinitis, upper respiratory infection, oropharyngeal infection, and dental caries. The study underscores the need for age-specific treatment strategies in urticaria management.
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Urticaria Crónica , Comorbilidad , Humanos , Estudios Retrospectivos , Niño , Masculino , Adolescente , Femenino , China/epidemiología , Prevalencia , Factores de Edad , Adulto Joven , Urticaria Crónica/epidemiología , Urticaria Crónica/tratamiento farmacológico , Adulto , Rinitis Alérgica/epidemiología , Factores de Tiempo , Urticaria/epidemiología , Urticaria/diagnóstico , Factores de Riesgo , Puntaje de Propensión , Persona de Mediana Edad , Bases de Datos Factuales , Asma/epidemiología , Asma/tratamiento farmacológico , Asma/diagnóstico , Pueblos del Este de AsiaRESUMEN
Objective: To construct a nomogram model for predicting the occurrence of the laparoscopic appendectomy surgical site infection (LASSI) and explore prevention strategies. Methods: A total of 995 patients who underwent laparoscopic appendectomy in Shanxi Bethune Hospital from October 2017 to August 2022 were selected. According to whether there was incision infection within 30 days after operation, the patients were divided into the LASSI (97 cases) and non-LASSI (898 cases) group. The following clinicopathological data from these two groups of patients were collected: gender, age, body mass index, ect. The subjects were randomly divided into training group and verification group according to the 7:3 ratio. Univariate and multivariate analysis was used to screen the related influencing factors and construct a nomogram model to predict the occurrence of LASSI. Rreceiver operating characteristic (ROC) curves and the calibration curve were used to evaluate the predictive value of the model. For patients with LASSI, a more effective preventive measure was explored. Results: Multivariate logistic regression analysis showed that operation time >1h (OR: 1.891; 95% CI: 1.07 to 3.36; P = .029), perforated and gangrenous appendix (OR: 4.078; 95% CI: 1.84 to 9.86; P = .001), free intraperitoneal fluid (OR: 2.836; 95% CI: 1.57 to 5.35; P = .001), BMI>30 kg/m2 (OR: 2.828; 95% CI:1.54 to 5.12; P = .001), diabetes mellitus (DM) (OR: 2.795; 95% CI: 1.54 to 5.28; P = .001) were the independent prognostic factors of LASSI. The prediction nomogram model showed satisfactory performance in predicting the occurrence of LASSI, ROC curve area value of the training and verification groups were respectively 0.753 (95 % CI: 0.688 ~ 0.818) and 0.772 (95 % CI: 0.691-0.852). In the event of LASSI, we took out appendix specimens in sections and sterilized surgical site, which effectively prevented it. Conclusion: This study evaluated the risk factors related to the occurrence of LASSI and established a prediction model for LASSI. The prediction model provides a convenient and fast risk assessment tool for clinicians to predict the occurrence of LASSI. Combined with the newly discovered prevention strategy of segmental removal of appendix and incision disinfection, it can effectively avoid the occurrence of LASSI and potentially reduce the hospitalization time and costs.
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Apendicectomía , Laparoscopía , Nomogramas , Infección de la Herida Quirúrgica , Humanos , Apendicectomía/efectos adversos , Apendicectomía/métodos , Masculino , Femenino , Infección de la Herida Quirúrgica/prevención & control , Laparoscopía/métodos , Adulto , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
Friction control and technological advancement are intimately intertwined. Concomitantly, two-dimensional materials occupy a unique position for realizing quasi-frictionless contacts. However, the question arises of how to tune superlubric sliding. Drawing inspiration from twistronics, we propose to control superlubricity via moiré patterning. Friction force microscopy and molecular dynamics simulations unequivocally demonstrate a transition from a superlubric to dissipative sliding regime for different twist angles of graphene moirés on a Pt(111) surface triggered by the normal force. This follows from a novel mechanism at superlattice level where, beyond a critical load, moiré tiles are manipulated in a highly dissipative shear process connected to the twist angle. Importantly, the atomic detail of the dissipation associated with the moiré tile manipulationâi.e., enduring forced registry beyond a critical normal loadâallows the bridging of disparate sliding regimes in a reversible manner, thus paving the road for a subtly intrinsic control of superlubricity.
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BACKGROUND: The nursing profession is characterized by high intensity and significant stress. Nurses must not only manage heavy workloads but also address diverse patient needs, engage in emotional labor, and cope with occupational exposure risks. These factors collectively contribute to substantial work-related stress for nurses. Currently, there is limited research on identifying distinct categories of nurse stress profiles and their influencing factors. OBJECTIVES: This study aimed to explore the potential categories of perceived stress among nurses using Latent profile analysis (LPA) and to analyze the influence of sociodemographic factors, effort-reward imbalance, and perceived organizational support on perceived stress categories. DESIGN: Cross-sectional study METHODS: Data were collected via electronic surveys from 696 nurses in Shanxi Province, China, from February 18 to 28, 2023. The survey parameters included sociodemographic characteristics, nurse job stressors scale, effort-reward imbalance scale, and perceived organizational support scale. Latent profile analysis (LPA) was used to classify the perceived stress levels of nurses, and disordered multi-classification logistic regression was used to identify the influencing factors. RESULTS: The most suitable model was a three-profile model, comprising the "low perceived stress" group (10.5%), "moderate perceived stress" group (66.7%), and "high perceived stress" group (22.8%). Multi-classification logistic regression analysis showed that average working hours per day (OR = 3.022, p = 0.026), extrinsic effort (C2 vs. C1, OR = 1.589, p < 0.001; C3 vs. C1, OR = 2.515, p < 0.001), and perceived organizational support (C2 vs. C1, OR = 0.853, p < 0.001; C3 vs. C1, OR = 0.753, p < 0.001) were the factors influencing the classification of nurses' perceived stress. CONCLUSIONS: Latent profile analysis revealed that nurses' perceived stress exhibits distinct characteristics. It is recommended that clinical administrators should identify these characteristics and the influencing factors of different nurse categories, and adopt targeted intervention strategies to reduce the levels of perceived stress.
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The solid-state conversion of amorphous carbon into graphene is extremely difficult, but it can be achieved in the friction experiments that induce macroscale superlubricity. However, the underlying conversion mechanisms remain elusive. Here, the friction experiments with Cu nanoparticles and (non-hydrogen (H) or H) a-C in vacuum, show the H-induced conversion of mechanical to chemical wear, resulting in the a-C's tribosoftening and nanofragmentating that produce hydrocarbon nanoclusters or molecules. It is such exactly hydrocarbon species that yield graphene at hydrogen-rich a-C friction interface, through reaction of them with Cu nanoparticles. In comparison, graphene isn't formed at Cu/non-H a-C friction interface. Atomistic simulations reveal the hydrogen-enhanced tribochemical decomposition of a-C and demonstrate the energetically favorable graphitization transformation of hydrocarbons on Cu substrates. The findings are of importance to achieve solid-state transformation between different carbon allotropes and provide a good strategy to synthesize other graphitic encapsulated catalysts with doped elements.
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Infections caused by antimicrobial resistance are a serious problem in the world. Currently, commercial devices for antimicrobial susceptibility testing and resistant bacteria identification are time-consuming. There is an urgent need to develop fast and accurate methods, especially in the process of sample pretreatment. Electrokinetic (EK) is a family of electric-field-based kinetic phenomena of fluid or embedded objects, and EK applications have been found in various fields. In this paper, EK bacteria manipulation, including enrichment and separation, is reviewed. Focus is given to the rapid electric-based minimum inhibitory concentration measurement. The future directions and major challenges in this field are also outlined.
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Antibacterianos , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Electricidad , Cinética , BacteriasRESUMEN
At present, there is still limited report on the electrokinetic (EK) behavior of bioparticles at the interface of an aqueous two-phase system. In this paper, the EK motion and viability assessment of live algae mixed with the NaClO treated dead algae were carried out at the interface formed by polyethylene glycol (PEG)-rich phase and dextran (DEX)-rich phase in a straight microchannel. The experimental results show that both the live and dead algae at the PEG-DEX interface migrate from the negative electrode to the positive electrode, and the EK velocity of live algae at the interface is slightly larger than that of the dead ones with similar diameters. For either live or dead algae, the EK velocity at the interface decreases with the increase in diameter. A size-velocity curve was used to evaluate the viability of the algae. As most of the microorganisms in ballast water are algae, the method in this paper provides a promising way to detect and evaluate the live microorganism in treated ballast water of a ship.
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Dextranos , Polietilenglicoles , Agua , Movimiento (Física) , NavíosRESUMEN
Percutaneous coronary intervention (PCI) is a widely used reperfusion strategy for coronary artery disease, with millions of procedures performed annually. Attention has recently been drawn to a unique population, known as "bi-risk" patients, who have high ischemic and high bleeding risks and undergo PCI. However, there is currently no established definition or optimal antithrombotic therapy for this group. Genotype-guided antithrombotic therapy, which uses cytochrome P450 (CYP) 2C19 gene testing, may offer a more personalized and precise approach. Nevertheless, recent research has shown that routine genetic testing to guide treatment in the PCI population does not improve patient outcomes, preventing it from being routinely recommended in guidelines. This review proposes, for the first time, the definition of the bi-risk population and the concept of TAILOR-BIRISK for their treatment strategies. TAILOR-BIRISK emphasizes de-escalating antithrombotic treatment and suggests that a short course of dual antiplatelet therapy (DAPT) followed by monotherapy by either clopidogrel or ticagrelor 60 mg BID (BID, twice daily) could be a reasonable option for this population. Additionally, the use of CYP2C19 gene testing to guide P2Y 12 inhibitor selection can help better individualize and customize the antithrombotic regimen. However, more large-sample randomized control studies should be conducted to further explore the optimal antithrombotic strategy for the bi-risk population.
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BACKGROUND: Spinal astrocytes contribute to chronic itch via sensitization of itch-specific neurons expressing gastrin-releasing peptide receptor (GRPR). However, whether microglia-neuron interactions contribute to itch remains unclear. In this study, we aimed to explore how microglia interact with GRPR+ neurons and promote chronic itch. METHODS: RNA sequencing, quantitative real-time PCR, western blot, immunohistochemistry, RNAscope ISH, pharmacologic and genetic approaches were performed to examine the roles of spinal NLRP3 (The NOD-like receptor family, pyrin-containing domain 3) inflammasome activation and IL-1ß-IL1R1 signaling in chronic itch. Grpr-eGFP and Grpr KO mice were used to investigate microglia-GRPR+ neuron interactions. RESULTS: We observed NLRP3 inflammasome activation and IL-1ß production in spinal microglia under chronic itch conditions. Blockade of microglial activation and the NLRP3/caspase-1/IL-1ß axis attenuated chronic itch and neuronal activation. Type 1 IL-1 receptor (IL-1R1) was expressed in GRPR+ neurons, which are essential for the development of chronic itch. Our studies also find that IL-1ß+ microglia are localized in close proximity to GRPR+ neurons. Consistently, intrathecal injection of IL1R1 antagonist or exogenous IL-1ß indicate that the IL-1ß-IL-1R1 signaling pathway enhanced the activation of GRPR+ neurons. Furthermore, our results demonstrate that the microglial NLRP3/caspase-1/IL-1ß axis contributes to several different chronic itches triggered by small molecules and protein allergens from the environment and drugs. CONCLUSION: Our findings reveal a previously unknown mechanism in which microglia enhances the activation of GRPR+ neurons through the NLRP3/caspase-1/IL-1ß/IL1R1 axis. These results will provide new insights into the pathophysiology of pruritus and novel therapeutic strategies for patients with chronic itch.
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Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Microglía/metabolismo , Receptores de Bombesina/metabolismo , Prurito/genética , Prurito/metabolismo , Enfermedad Crónica , Interleucina-1beta/metabolismo , Neuronas/metabolismo , Caspasas , Ratones Endogámicos C57BLRESUMEN
Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.
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Genoma Humano/genética , Genómica , Mutación , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Cromotripsis , Variaciones en el Número de Copia de ADN , Metilación de ADN , Exoma/genética , Humanos , Masculino , Metástasis de la Neoplasia/genética , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , RecurrenciaRESUMEN
PURPOSE OF REVIEW: In this review, we aim to summarize the current understanding of high bleeding risk (HBR) patients in coronary artery disease (CAD) and provide a comprehensive evaluation of the available antithrombotic strategies for both percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) procedures. RECENT FINDINGS: CAD is a major cause of mortality among cardiovascular diseases, resulting from insufficient blood flow in the coronary artery due to atherosclerosis. Antithrombotic therapy is a crucial component of drug therapy for CAD and multiple studies had been focusing on the optimal antithrombotic strategies of different CAD populations. However, there is no fully harmonized definition of the model of bleeding, and the optimal antithrombotic strategy for such patients at HBR is inconclusive. In this review, we summarize bleeding risk stratification models for CAD patients and discuss the de-escalation of antithrombotic strategies among HBR patients. Furthermore, we realize that for certain subgroups of CAD-HBR patients, more individualized and precise antithrombotic strategy development is needed. So, we highlight special populations, such as CAD patients combined with valvular diseases, with both high ischemia and bleeding risks, and those proceeding surgical treatment, which requires greater research attention. We note that de-escalating therapy for CAD-HBR patients is an emerging trend in managing this population, but the optimal antithrombotic strategies should be re-considered according to the patient's baseline characteristics.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Fibrinolíticos/efectos adversos , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo , Puente de Arteria Coronaria , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Resultado del TratamientoRESUMEN
Salmonella is a primary cause of foodborne diseases, and the increasing prevalence of mcr-1-carrying plasmids, which confer colistin resistance to Salmonella, poses significant global health concerns. As the frequency of occurrence of the mcr-1 gene is increasing globally, we studied the prevalence of mcr-1 in clinical Salmonella isolates by analyzing 195 clinical strains isolated in 2020. Of the 195 Salmonella isolates, 41 isolates were resistant to colistin. We found mcr-1 in two strains (Salmonella Typhimurium ZJJX20006 and Salmonella Kentucky ZJJX20014), which we analyzed in detail via whole-genome sequencing and antibiotic susceptibility testing. Two strains displayed resistance to ampicillin, ampicillin-sulbactam, tetracycline, chloramphenicol, and cotrimoxazole, while ZJJX20006 displayed resistance to colistin and ZJJX20014 was sensitive. Genomic analysis revealed that these strains had plasmid-encoded mcr-1 in IncHI2 plasmids, which were not similar to the mcr-1-IncX4 identified in 2016. These two strains also harbored other drug resistance genes, including blaOXA-1 and blaCTX-M-14. Our findings may help clarify the molecular mechanisms of mcr-1 dissemination among Salmonella strains in Jiaxing City and offer insights into the evolution of mcr-1 in Salmonella.
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Ferrofluids (FFs) can adapt their shape to a magnetic field. However, they cannot maintain their shape when the magnetic field is removed. Here, with a magneto-responsive and reconfigurable interfacial self-assembly (MRRIS) process, we show that FFs can be structured by a magnetic field and maintain their shape, like solids, after removing the magnetic field. The competing self-assembly of magnetic and nonmagnetic nanoparticles at the liquid interface endow FFs with both reconfigurability and structural stability. By manipulating the external magnetic field, we show that it is possible to "write" and "erase" the shape of the FFs remotely and repeatedly. To gain an in-depth understanding of the effect of MRRIS on the structure of FFs, we systematically study the shape variation of these liquids under both the static and dynamic magnetic fields. Our study provides a simple yet novel way of manipulating FFs and opens opportunities for the fabrication of all-liquid devices.