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Social groups in various social species are organized with hierarchical structures that shape group dynamics and the nature of within-group interactions. In-group social bonding, exemplified by grooming behaviors among animals and collective rituals and team-building activities in human societies, is recognized as a practical adaptive strategy to foster group harmony and stabilize hierarchical structures in both human and nonhuman animal groups. However, the neurocognitive mechanisms underlying the effects of social bonding on hierarchical groups remain largely unexplored. Here, we conducted simultaneous neural recordings on human participants engaged in-group communications within small hierarchical groups (n = 528, organized into 176 three-person groups) to investigate how social bonding influenced hierarchical interactions and neural synchronizations. We differentiated interpersonal interactions between individuals of different (inter-status) or same (intra-status) social status and observed distinct effects of social bonding on inter-status and intra-status interactions. Specifically, social bonding selectively increased frequent and rapid information exchange and prefrontal neural synchronization for inter-status dyads but not intra-status dyads. Furthermore, social bonding facilitated unidirectional neural alignment from group leader to followers, enabling group leaders to predictively align their prefrontal activity with that of followers. These findings provide insights into how social bonding influences hierarchical dynamics and neural synchronization while highlighting the role of social status in shaping the strength and nature of social bonding experiences in human groups.
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Encéfalo , Relaciones Interpersonales , Animales , HumanosRESUMEN
Hydrogen peroxide (H2O2) is a major reactive oxygen species in unicellular and multicellular organisms, and is produced extracellularly in response to external stresses and internal cues1-4. H2O2 enters cells through aquaporin membrane proteins and covalently modifies cytoplasmic proteins to regulate signalling and cellular processes. However, whether sensors for H2O2 also exist on the cell surface remains unknown. In plant cells, H2O2 triggers an influx of Ca2+ ions, which is thought to be involved in H2O2 sensing and signalling. Here, by using forward genetic screens based on Ca2+ imaging, we isolated hydrogen-peroxide-induced Ca2+ increases (hpca) mutants in Arabidopsis, and identified HPCA1 as a leucine-rich-repeat receptor kinase belonging to a previously uncharacterized subfamily that features two extra pairs of cysteine residues in the extracellular domain. HPCA1 is localized to the plasma membrane and is activated by H2O2 via covalent modification of extracellular cysteine residues, which leads to autophosphorylation of HPCA1. HPCA1 mediates H2O2-induced activation of Ca2+ channels in guard cells and is required for stomatal closure. Our findings help to identify how the perception of extracellular H2O2 is integrated with responses to various external stresses and internal cues in plants, and have implications for the design of crops with enhanced fitness.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , Peróxido de Hidrógeno/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Calcio/metabolismo , Canales de Calcio/metabolismo , Señalización del Calcio , Cisteína/química , Cisteína/metabolismo , Activación Enzimática , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Mutación , Oxidación-Reducción , Células Vegetales/metabolismo , Dominios Proteicos , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
Dendritic cells (DC) play important roles in balancing immunity and tolerance, in which ß-catenin signaling plays an important role, yet the underlying mechanisms remain elusive. In this study, we investigated the functions of the tumor suppressor adenomatous polyposis coli (APC), also a key component of the ß-catenin upstream destruction complex in DC. APC depletion in DC does not alter DC and T cell homeostasis under resting conditions. However, APC deficiency in DC leads to attenuated antitumor immunity in mice, which exhibit fewer CD8+ T cells and more Foxp3+ regulatory T cells in tumor and draining lymph nodes. Loss of APC in DC does not affect the expression levels of costimulatory molecules. However, APC-deficient DC produce more IL-10 and exhibit a higher ability of inducing regulatory T cells but a lower ability of priming CD8+ T cells, both of which can be reversed by IL-10 inhibition. Lastly, ß-catenin depletion in APC-deficient DC rescues their antitumor immunity and reverses elevated IL-10 production. Taken together, our results identify that APC drives DC tolerance via the ß-catenin/IL-10 axis.
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Poliposis Adenomatosa del Colon , beta Catenina , Ratones , Animales , beta Catenina/metabolismo , Cateninas , Interleucina-10 , Poliposis Adenomatosa del Colon/metabolismo , Células Dendríticas , Proteína de la Poliposis Adenomatosa del Colon/metabolismoRESUMEN
BACKGROUND: Cerebral small vessel disease (CSVD) is a group of neurological disorders that affect the small blood vessels within the brain, for which no effective treatments are currently available. We conducted a Mendelian randomization (MR) study to identify candidate therapeutic genes for CSVD. METHODS: We retrieved genome-wide association study data from 6 recently conducted, extensive investigations focusing on CSVD magnetic resonance imaging markers and performed a 2-sample MR analysis to assess the potential causal effects of gene expression and protein level within druggable genes on CSVD in blood and brain tissues. Colocalization analyses and repeat studies were undertaken to verify the relationship. Additionally, mediation analysis was conducted to explore the potential mechanisms involving druggable genes and known risk factors for CSVD. Finally, phenome-wide MR analyses were applied to evaluate the potential adverse effects related to the identified druggable genes for CSVD treatment. RESULTS: Overall, 5 druggable genes consistently showed associations with CSVD in MR analyses across both the discovery and validation cohorts. Notably, the ALDH2 and KLHL24 genes were identified as associated with CSVD in both blood and brain tissues, whereas the genes ADRB1, BTN3A2, and EFEMP1 were exclusively detected in brain tissue. Moreover, mediation analysis elucidated the proportion of the total effects mediated by CSVD risk factors through candidate druggable genes, which ranged from 5.5% to 18.5%, and offered potential explanations for the observed results. A comprehensive phenome-wide MR analysis further emphasized both the therapeutic benefits and potential side effects of targeting these candidate druggable genes. CONCLUSIONS: This study provides genetic evidence supporting the potential therapeutic benefits of targeting druggable genes for treating CSVD, which will be useful for prioritizing CSVD drug development.
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BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.
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Carcinoma Hepatocelular , Células Estrelladas Hepáticas , Interleucina-17 , Neoplasias Hepáticas , Animales , Humanos , Masculino , Ratas , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Endopeptidasas/metabolismo , Endopeptidasas/genética , Regulación Neoplásica de la Expresión Génica , Células Estrelladas Hepáticas/metabolismo , Interleucina-17/metabolismo , Interleucina-17/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Ratas Sprague-Dawley , Microambiente TumoralRESUMEN
Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.
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Imagen de Difusión por Resonancia Magnética , Sistema Glinfático , Humanos , Masculino , Femenino , Sistema Glinfático/diagnóstico por imagen , Sistema Glinfático/patología , Sistema Glinfático/fisiopatología , Persona de Mediana Edad , Estudios Transversales , Anciano , Imagen de Difusión por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Procesamiento de Imagen Asistido por Computador/métodos , Adulto , Estudios de CohortesRESUMEN
The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.
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Hipertrofia , Núcleo Olivar , Estimulación Transcraneal de Corriente Directa , Humanos , Masculino , Persona de Mediana Edad , Núcleo Olivar/patología , Núcleo Olivar/diagnóstico por imagen , Estimulación Transcraneal de Corriente Directa/métodos , Terapia por Ejercicio/métodos , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Enfermedades Neurodegenerativas/terapia , Degeneración OlivarRESUMEN
Obtaining compounds with large nonlinear-optical (NLO) coefficients and wide band gaps is challenging due to their competitive requirements for chemical bonds. Herein, the first member with mixed cations on the A site in the A-M3-Q5 or A-Ag-M6-Q10 (A = alkali metal; M = Ga, In; Q = S, Se, Te) family, viz. Na0.45Ag0.55Ga3Se5 (NAGSe), was obtained by a solid-state reaction. Its structure features [GaSe4] tetrahedra built three-dimensional {[Ga3Se5]-}∞ network, with Na and Na/Ag cations located at the octahedral cavities. Noncentrosymmetric (R32) NAGSe can also be transformed from centrosymmetric RbGa3S5 (P21/c) via multiple-site cosubstitution. NAGSe exhibits the highest NLO response (1.9 × AGS) in the A-Ag-M-Q family. Crystal structure analysis and theoretical calculations suggest that the NLO response is mainly contributed by the regularly arranged [GaSe4] units. This work enriches the exploration of the undeveloped A-M3-Q5 or A-Ag-M6-Q10 family as potential infrared NLO materials.
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BACKGROUND: Exposure to a high-altitude environment is a risk factor for cerebral venous thrombosis (CVT) probably due to hypercoagulability. The study aims to explore the unique characteristics of CVT patients in high-altitude areas of China by comparing them with those in plain areas. METHODS: We retrospectively included consecutive patients with CVT admitted to Tibet Autonomous Region People's Hospital (altitude 3650 m) and Peking Union Medical College Hospital (altitude 43.5 m) between January 2015 and December 2023. Patients from the plateau and the plain were considered two independent groups in this study. The risk factors, clinical and radiological presentations, treatment, and outcomes were analyzed and compared between the two groups. RESULTS: A total of 169 patients with CVT were included in the study, 48 patients from plateau and 121 patients from plain. The median age was 27 and 34 years old, and women accounted for 66.7% and 54.5% respectively. Headache (91.7% vs. 71.1%, P = 0.004), altered consciousness (31.3% vs. 16.5%, P = 0.033), hemorrhage (41.7% vs. 19.0%, P = 0.002), and venous infarction (50.0% vs. 25.6%, P = 0.002) on imaging were more common in patients from plateau than those from plain. Pregnancy or puerperium was significantly more common in highland patients (25% vs. 5.8%, P < 0.001). The levels of D-Dimer (1.7 vs. 0.8 mg/L FEU, P = 0.01), fibrinogen (3.7 vs. 3.0 g/L, P < 0.001), hemoglobin (157 vs. 129 g/L, P = 0.01), white blood cells (9.6 vs. 7.5*1012/L, P < 0.001) and highly sensitive C-reactive protein (20.2 vs. 3.2 mg/L, P = 0.005) were remarkably higher in highland patients. The percentage of receiving anticoagulant therapy was lower in high-altitude patients (70.8% vs. 93.4%, P < 0.001). Favorable outcome at follow-up was observed in 81.4% of highland patients and 90.7% of lowland patients, with a median follow-up time of 330 days and 703 days respectively. CONCLUSIONS: The more severe clinical and imaging manifestations along with prominent inflammatory and hypercoagulable states were observed in plateau CVT patients, probably due to exposure to the hypoxic environment at high altitude. Pregnancy or puerperium were more common in highland patients. The overall prognosis of CVT patients from both groups were favorable.
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Fluorite materials have received particular attention in electron optics due to their favorable optical properties. However, further exploration of these materials in the thermoelectric (TE) field is hampered by the lack of studies on their lattice thermal transport properties. In this work, we use first-principles calculations, combined with self-consistent phonon theory, compressive sensing lattice dynamics and the Boltzmann transport equation, to study the microscopic mechanism of lattice thermal transport properties in AF2 (A = Ca, Sr, Ba) with a fluorite structure. We investigate the effects of three-phonon and four-phonon scattering and quartic anharmonic renormalization of phonon frequencies on this system. The results show that the bonding strength of atoms A (Ca, Sr, and Ba) plays an important role in the thermal transport process, and the third-order anharmonicity also plays an important role in this system. Meanwhile, the role of the quartic anharmonicity cannot be ignored. Our findings not only fill in the gaps in the study of lattice thermal transport of fluorite materials, but also deepen the comprehensive understanding of the high κL value of fluorite materials.
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Based on first-principles calculations, the current study deeply explores the thermoelectric properties of the Zintl compound SrPdTe. We found that the anharmonic vibration of Pd atoms plays an important role in the quartic anharmonic effect and the temperature dependence of the thermal conductivity. In the crystalline structure, Sr atoms form octahedra with eight surrounding Te atoms, while Pd atoms are located in the gaps between the octahedra. This structure makes the strong atomic mean square displacement of Pd atoms the main factor leading to the ultralow thermal conductivity. The study also reveals the effects of phonon frequency renormalization and four-phonon scattering on heat transfer performance. Even considering the spin-orbit coupling effect, multiple secondary valence band tops maintain the power factor of the material at high temperatures, providing a potential opportunity for achieving excellent thermoelectric performance.
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BACKGROUND AND PURPOSE: Testing for antiphospholipid antibodies (aPL) is useful to determine the cause of ischemic stroke in young and female patients. However, the clinical relevance of aPL in older patients with ischemic stroke remains unclear. We aimed to explore the status and diagnostic value of initial aPL testing in all patients with acute ischemic stroke. METHODS: We retrospectively analyzed patients with acute ischemic stroke who were consecutively hospitalized in our hospital between June 2012 and January 2022 and investigated the factors associated with performing aPL screening in real-world clinical practice. Furthermore, factors associated with initial aPL positivity were evaluated by comparing the demographic, etiological, and therapeutic characteristics. RESULTS: Of 1209 patients, 287 (23.7%) were tested for aPL and 58 (20.2%) tested positive. Physicians tended to conduct aPL testing on female patients (P<0.001), younger patients (P<0.001), patients with fewer vascular risk factors (P<0.001), and multiple infarctions in the multivascular blood supply area (P<0.001). Multivariate logistic regression analysis showed that only stroke of other determined etiology type was a significant influencing factor for positive aPL results (OR 2.97, 95% CI 1.137, 7.774, P=0.026), adjusting for sex, age, and causes of stroke, etc. CONCLUSION: Approximately one-quarter of the patients with acute ischemic stroke were tested for aPL. Age, sex, number of vascular risk factors, and neuroimaging features affected the discretion in performing aPL testing. aPL testing may be appropriate in older patients with no identified cause of ischemic stroke and may provide additional diagnostic opportunities for acute ischemic stroke.
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Síndrome Antifosfolípido , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Anticuerpos Antifosfolípidos/uso terapéutico , Estudios Retrospectivos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiologíaRESUMEN
Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis of breast cancer. Thiostrepton exerts anti-tumor activities against several cancers including TNBC. Herein we discussed the new molecular mechanisms of thiostrepton in TNBC. Thiostrepton inhibited MDA-MB-231 cell viability, accompanied by a decrease of c-FLIP and p-SMAD2/3. c-FLIP overexpression reduced the sensitivity of MDA-MB-231 cells to thiostrepton, while SMAD2/3 knockdown increased the sensitivity of MDA-MB-231 cells to thiostrepton. Moreover, c-FLIP overexpression significantly increased the expression and phosphorylation of SMAD2/3 proteins and vice versa. In conclusion, our study reveals c-FLIP/SMAD2/3 signaling pathway as a novel mechanism of antitumor activity of thiostrepton.
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Transducción de Señal , Proteína Smad2 , Proteína smad3 , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Proteína smad3/metabolismo , Proteína Smad2/metabolismo , Femenino , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Línea Celular Tumoral , Estructura Molecular , Regulación hacia Abajo/efectos de los fármacos , Supervivencia Celular/efectos de los fármacosRESUMEN
Although nano SiO2 exhibits excellent application potential in the field of oil and gas exploration and development, such as drilling fluid, enhanced oil/gas recovery, etc., it is prone to agglomeration and loses its effectiveness due to the action of cations in saline environments of oil and gas reservoirs. Therefore, it is crucial to study the mechanism of the change in energy between nano SiO2 and cations for its industrial application. In this paper, the effect of cations (Na+, K+, Ca2+, and Mg2+) on the surface energy of nano SiO2 particles is investigated from the perspective of molecular motion and electronic change by density functional theory. The results are as follows: Due to the electrostatic interactions, cations can migrate towards the surface of nano SiO2 particles. During the migration process, monovalent cations are almost unaffected by water molecules, and they can be directly adsorbed on the surface by nano SiO2 particles. However, when divalent cations migrate from a distance to the surface of nano SiO2 particles, they can combine with water molecules to create an energy barrier, which can prevent them from moving forward. When divalent cations break through the energy barrier, the electronic kinetic energy between them and nano SiO2 particles changes more strongly, and the electrons carried by them are more likely to break through the edge of the atomic nucleus and undergo charge exchange with nano SiO2 particles. The change in interaction energy is more intense, which can further disrupt the configuration stability of nano SiO2. The interaction energy between cations and nano SiO2 particles mainly comes from electrostatic energy, followed by Van der Waals energy. From the degree of influence of four cations on nano SiO2 particles, the order from small to large is as follows: K+ < Na+ < Mg2+ < Ca2+. The research results can provide a theoretical understanding of the interaction between nano SiO2 particles and cations during the application of nano SiO2 in the field of oil and gas exploration and development.
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ACC007 is a new-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with favorable pharmacokinetic and safety profiles. NNRTIs are typically administered in combination with two nucleoside reverse transcriptase inhibitors as first-line recommended regimens in several guidelines. Therefore, this open-label, randomized, single-period, parallel-cohort study aimed to assess the drug-drug interactions (DDIs) and safety profiles of ACC007 in combination with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) in healthy subjects. All 24 screened subjects were randomly assigned to group A or B. On days 1 to 17, 3TC at 300 mg and TDF at 300 mg were taken orally by group A, and ACC007 at 300 mg was coadministered on days 8 to 17. On days 1 to 17, 300 mg of ACC007 was taken orally by group B, and 300 mg 3TC and 300 mg TDF were coadministered on days 8 to 17. When we compared 3TC-TDF versus 3TC-TDF-ACC007 DDIs, the geometric mean ratios (GMRs, with 90% confidence intervals [CIs] in parentheses) of the maximum concentration at steady state (Cmax,ss) and area under the concentration-time curve from 0 h to infinity (i.e., at steady state; AUCss) values for TDF were 108.14% (95.68 to 122.22%) and 89.90% (82.67 to 97.76%) (P = 0.344); for 3TC, these values were 113.48% (91.45 to 140.82%) and 95.33% (83.61 to 108.7%) (P = 0.629). When ACC007 alone was compared to the combination 3TC-TDF-ACC007, the GMRs (90% CIs) of the Cmax,ss and AUCss values for ACC007 were 89.00% (76.35 to 103.74%) and 82.57% (73.27 to 93.05%) (P = 0.375). The coadministration of 3TC-TDF-ACC007 did not significantly affect the time to maximum concentration of any of the drugs in terms of P values. ACC007 combined with 3TC-TDF was generally well tolerated during daily dosing for 17 days with no serious adverse events. Overall, ACC007 and 3TC-TDF had no significant or meaningful interactions and a favorable safety profile, which supports the use of the combination regimen.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Tenofovir/efectos adversos , Lamivudine/efectos adversos , Fármacos Anti-VIH/efectos adversos , Estudios de Cohortes , Infecciones por VIH/tratamiento farmacológico , Interacciones FarmacológicasRESUMEN
Synthetic light-driven consortia composed of phototrophs and heterotrophs have attracted increasing attention owing to their potential to be used in sustainable biotechnology. In recent years, synthetic phototrophic consortia have been used to produce bulk chemicals, biofuels, and other valuable bioproducts. In addition, autotrophic-heterotrophic symbiosis systems have potential applications in wastewater treatment, bioremediation, and as a method for phytoplankton bloom control. Here, we discuss progress made on the biosynthesis of phototrophic microbial consortia. In addition, strategies for optimizing the synthetic light-driven consortia are summarized. Moreover, we highlight current challenges and future research directions for the development of robust and controllable synthetic light-driven consortia.
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Biotecnología , Consorcios Microbianos , Biotecnología/métodos , Biodegradación Ambiental , Simbiosis , Biología Sintética/métodosRESUMEN
HH-120, an IgM-like angiotensin converting enzyme 2 (ACE2) fusion protein, has been developed as a nasal spray against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently undergoing human trials. HH-120 nasal spray was assessed for postexposure prophylaxis (PEP) in two investigator-initiated (NS01 and NS02) trials with different risk levels of SARS-CoV-2 exposure. NS01 enrolled family caregiver participants who had continuous contacts with laboratory-confirmed index cases; NS02 enrolled participants who had general contacts (Part 1) or close contacts (Part 2) with index cases. The primary endpoints were safety and laboratory-confirmed and/or symptomatic SARS-CoV-2 infection. In NS01 trial (14 participants), the SARS-CoV-2 infection rates were 25% in the HH-120 group and 83.3% in the external control group (relative risk reduction [RRR]: 70.0%). In NS02-Part 1 (193 participants), the infection rates were 4% (HH-120) versus 11.3% (placebo), symptomatic infection rates were 0.8% versus 3.5%, hence with a RRR of 64.6% and 77.1%, respectively. In Part 2 (76 participants), the infection rates were 17.1% (HH-120) versus 30.4% (placebo), symptomatic infection rates were 7.5% versus 27.3%, with a RRR of 43.8% and 72.5%, respectively. No HH-120-related serious adverse effects were observed. The HH-120 nasal spray used as PEP was safe and effective in preventing laboratory-confirmed and symptomatic SARS-CoV-2 infection.
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Enzima Convertidora de Angiotensina 2 , COVID-19 , Proteínas Recombinantes de Fusión , Humanos , Enzima Convertidora de Angiotensina 2/uso terapéutico , COVID-19/prevención & control , Inmunoglobulina M , Rociadores Nasales , SARS-CoV-2 , Proteínas Recombinantes de Fusión/uso terapéutico , Profilaxis PosexposiciónRESUMEN
Ataxia-ocular apraxia 2 (AOA2) is a rare neurodegenerative autosomal recessive disorder with no effective treatment. In this study, we present the case of a patient diagnosed with AOA2, who experienced walking instability and uncoordinated movement. The patient underwent transcranial alternating current stimulation (tACS) treatment for 4 weeks with follow-up after 1 month. The effectiveness of the treatment was evaluated using the International Cooperative Ataxia Rating Scale (ICARS), the Scale for the Assessment and Rating of Ataxia (SARA), the 9-Hole Peg Test (9HPT), and functional near-infrared spectroscopy (fNIRS). Following treatment, the patient's ataxia symptoms showed significant improvement and continued to be alleviated during the follow-up period, suggesting a lasting effect of tACS treatment. Our findings from this case study provide compelling evidence for the potential of tACS as a treatment option for AOA2.
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BACKGROUND AND PURPOSE: Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke in China, but the prevalence and prognosis of asymptomatic ICAD detected using high-resolution magnetic resonance imaging (HR-MRI) is largely unknown. The aim of this study was to investigate the prevalence and prognosis in order to guide neurologists in interpreting ICAD detected on HR-MRI. METHODS: We included stroke-free participants from a community-based prospective cohort (Shunyi study participants) who underwent HR-MRI between July 2014 and April 2016. The participants were divided into two groups: those with or without ICAD (ICAD+ and ICAD- , respectively). ICAD included intracranial artery stenosis and non-stenotic plaque. The primary outcome was ischemic stroke. Cox proportional hazard models were used to evaluate the association between ICAD and event outcomes. RESULTS: A total of 1060 stroke-free participants evaluated by HR-MRI were included from the Shunyi study. The median age at HR-MRI was 56 years and 64.7% were female. The ICAD prevalence was 36.3% (n = 385). The ICAD+ group was older and had more cerebrovascular risk factors. The rates of ischemic stroke in the ICAD- and ICAD+ groups were 1.3% (n = 9) and 5.2% (n = 20), respectively, with a median follow-up time of 54 months. ICAD was associated with an increased risk of ischemic stroke in the unadjusted and adjusted Cox models, with hazard ratios of 4.12 (95% confidence interval [CI] 1.87-9.05) and 2.50 (95% CI 1.05-5.94), respectively. The greatest risk of an event outcome was observed in participants with ≥70% stenosis or occlusion. The features of high-risk plaques were also identified. CONCLUSIONS: We found that ICAD detected using HR-MRI increases the long-term risk of a first-ever ischemic stroke in a stroke-free population, suggesting that the current primary prevention protocol of stroke awaits further optimization.
Asunto(s)
Arteriosclerosis Intracraneal , Accidente Cerebrovascular Isquémico , Placa Aterosclerótica , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Constricción Patológica/patología , Prevalencia , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Pronóstico , Placa Aterosclerótica/complicaciones , Accidente Cerebrovascular Isquémico/complicaciones , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW configurations in the general population. We explored this relationship in a community-based Chinese sample. METHODS: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. RESULTS: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004-4.270) and CMB presence (OR = 1.542; 95% CI, 1.012-2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069-3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064-2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346-0.915). CONCLUSIONS: COW configuration was significantly related to various covert vascular brain injuries.