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Stroke is a multiphasic process in which initial cerebral ischemia is followed by secondary injury from immune responses to ischemic brain components. Here we demonstrate that peripheral CD11b+CD45+ myeloid cells magnify stroke injury via activation of triggering receptor expressed on myeloid cells 1 (TREM1), an amplifier of proinflammatory innate immune responses. TREM1 was induced within hours after stroke peripherally in CD11b+CD45+ cells trafficking to ischemic brain. TREM1 inhibition genetically or pharmacologically improved outcome via protective antioxidant and anti-inflammatory mechanisms. Positron electron tomography imaging using radiolabeled antibody recognizing TREM1 revealed elevated TREM1 expression in spleen and, unexpectedly, in intestine. In the lamina propria, noradrenergic-dependent increases in gut permeability induced TREM1 on inflammatory Ly6C+MHCII+ macrophages, further increasing epithelial permeability and facilitating bacterial translocation across the gut barrier. Thus, following stroke, peripheral TREM1 induction amplifies proinflammatory responses to both brain-derived and intestinal-derived immunogenic components. Critically, targeting this specific innate immune pathway reduces cerebral injury.
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Encéfalo/imunologia , Mucosa Intestinal/imunologia , Macrófagos/imunologia , Neutrófilos/imunologia , Acidente Vascular Cerebral/patologia , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Animais , Encéfalo/citologia , Linhagem Celular , Imunidade Inata/imunologia , Inflamação/patologia , Mucosa Intestinal/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células RAW 264.7RESUMO
Lysine lactylation (Kla) is a newly discovered posttranslational modification that is involved in important life activities, such as glycolysis-related cell function, macrophage polarization and nervous system regulation, and has received widespread attention due to the Warburg effect in tumor cells. In this work, we first design a natural language processing method to automatically extract the 3D structural features of Kla sites, avoiding potential biases caused by manually designed structural features. Then, we establish two Kla prediction frameworks, Attention-based feature fusion Kla model (ABFF-Kla) and EBFF-Kla, to integrate the sequence features and the structure features based on the attention layer and embedding layer, respectively. The results indicate that ABFF-Kla and Embedding-based feature fusion Kla model (EBFF-Kla), which fuse features from protein sequences and spatial structures, have better predictive performance than that of models that use only sequence features. Our work provides an approach for the automatic extraction of protein structural features, as well as a flexible framework for Kla prediction. The source code and the training data of the ABFF-Kla and the EBFF-Kla are publicly deposited at: https://github.com/ispotato/Lactylation_model.
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Lisina , Processamento de Linguagem Natural , Sequência de Aminoácidos , Domínios Proteicos , Processamento de Proteína Pós-TraducionalRESUMO
Bacteriophages and bacteria are engaged in a constant arms race, continually evolving new molecular tools to survive one another. To protect their genomic DNA from restriction enzymes, the most common bacterial defence systems, double-stranded DNA phages have evolved complex modifications that affect all four bases. This study focuses on modifications at position 7 of guanines. Eight derivatives of 7-deazaguanines were identified, including four previously unknown ones: 2'-deoxy-7-(methylamino)methyl-7-deazaguanine (mdPreQ1), 2'-deoxy-7-(formylamino)methyl-7-deazaguanine (fdPreQ1), 2'-deoxy-7-deazaguanine (dDG) and 2'-deoxy-7-carboxy-7-deazaguanine (dCDG). These modifications are inserted in DNA by a guanine transglycosylase named DpdA. Three subfamilies of DpdA had been previously characterized: bDpdA, DpdA1, and DpdA2. Two additional subfamilies were identified in this work: DpdA3, which allows for complete replacement of the guanines, and DpdA4, which is specific to archaeal viruses. Transglycosylases have now been identified in all phages and viruses carrying 7-deazaguanine modifications, indicating that the insertion of these modifications is a post-replication event. Three enzymes were predicted to be involved in the biosynthesis of these newly identified DNA modifications: 7-carboxy-7-deazaguanine decarboxylase (DpdL), dPreQ1 formyltransferase (DpdN) and dPreQ1 methyltransferase (DpdM), which was experimentally validated and harbors a unique fold not previously observed for nucleic acid methylases.
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Bacteriófagos , Guanina , Bactérias/genética , Bacteriófagos/genética , DNA/genética , Guanina/análogos & derivadosRESUMO
Lactylation, as a novel posttranslational modification, is essential for studying the functions and regulation of proteins in physiological and pathological processes, as well as for gaining in-depth knowledge on the occurrence and development of many diseases, including tumors. However, few studies have examined the protein lactylation of one whole organism. Thus, we studied the lactylation of global proteins in Caenorhabditis elegans to obtain an in vivo lactylome. Using an MS-based platform, we identified 1836 Class I (localization probabilities > 0.75) lactylated sites in 487 proteins. Bioinformatics analysis showed that lactylated proteins were mainly located in the cytoplasm and involved in the tricarboxylic acid cycle (TCA cycle) and other metabolic pathways. Then, we evaluated the conservation of lactylation in different organisms. In total, 41 C. elegans proteins were lactylated and homologous to lactylated proteins in humans and rats. Moreover, lactylation on H4K80 was conserved in three species. An additional 238 lactylated proteins were identified in C. elegans for the first time. This study establishes the first lactylome database in C. elegans and provides a basis for studying the role of lactylation.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Humanos , Animais , Ratos , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Ciclo do Ácido Cítrico , Redes e Vias Metabólicas , Proteoma/metabolismoRESUMO
This study aimed to investigate the role of bone marrow stromal cell antigen-1 (Bst1; also known as CD157) in acute kidney injury (AKI). Bst1 is a cell surface molecule with various enzymatic activities and downstream intracellular signaling pathways that modulate the immune response. Previous research has linked Bst1 to diseases such as ovarian cancer, Parkinson's disease, and rheumatoid arthritis. We used bilateral ischemia-reperfusion injury (IRI) as an AKI model and created bone marrow chimeric mice to evaluate the role of Bst1 in bone marrow-derived cells. We also used flow cytometry to identify Bst1/CD157 expression in hematopoietic cells and evaluate immune cell dynamics in the kidney. The findings showed that Bst1-deficient (Bst1-/-) mice were protected against renal bilateral IRI. Bone marrow chimera experiments revealed that Bst1 expression on hematopoietic cells, but not parenchymal cells, induced renal IRI. Bst1 was mainly found in B cells and neutrophils by flow cytometry of the spleen and bone marrow. In vitro, migration of neutrophils from Bst1-/- mice was suppressed, and adoptive transfer of neutrophils from wild-type Bst1+/+ mice abolished the renal protective effect in Bst1 knockout mice. In conclusion, the study demonstrated that Bst1-/- mice are protected against renal IRI and that Bst1 expression in neutrophils plays a crucial role in inducing renal IRI. These findings suggest that targeting Bst1 in neutrophils could be a potential therapeutic strategy for AKI.NEW & NOTEWORTHY Acute kidney injury (AKI), a serious disease for which there is no effective Federal Drug Administration-approved treatment, is associated with high mortality rates. Bone marrow stromal cell antigen-1 (Bst1) is a cell surface molecule that can cause kidney fibrosis, but its role in AKI is largely unknown. Our study showed that Bst1-/- mice revealed a protective effect against renal bilateral ischemia-reperfusion injury (IRI). Adoptive transfer studies confirmed that Bst1 expression in hematopoietic cells, especially neutrophils, contributed to renal bilateral IRI.
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Injúria Renal Aguda , Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Camundongos , Animais , Injúria Renal Aguda/genética , Injúria Renal Aguda/prevenção & controle , Rim/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Neutrófilos/metabolismo , Camundongos Knockout , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.
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Imunidade Adaptativa , Imunidade Inata , Ativação de Macrófagos , Macrófagos , Psoríase , Receptor A2A de Adenosina , Psoríase/imunologia , Animais , Camundongos , Imunidade Inata/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Receptor A2A de Adenosina/metabolismo , Receptor A2A de Adenosina/genética , Ativação de Macrófagos/efeitos dos fármacos , Ativação de Macrófagos/imunologia , Imunidade Adaptativa/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Quimiocina CXCL10/genética , Quimiocina CXCL10/metabolismo , Quimiocina CXCL10/imunologia , Humanos , Camundongos Knockout , Fenetilaminas/farmacologia , Adenosina/análogos & derivados , Adenosina/farmacologia , Imiquimode/farmacologia , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Agonistas do Receptor A2 de Adenosina/farmacologia , Queratinócitos/imunologia , Queratinócitos/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
Multispectral/hyperspectral technologies can easily detect man-made objects in vegetation by subtle spectral differences between the object and vegetation, and powerful reconnaissance increases the demand for camouflage materials closely resembling vegetation spectra. However, previous biomimetic materials have only presented static colors that cannot change color, and camouflage in multiple bands is difficult to achieve. To address this challenge, inspiration is drawn from the color change of foliage, and a color-change model is proposed with active and static pigments embedded in a matrix medium. The color of a composite material is dominated by the colored active pigment, which conceals the color of the static pigments and the color is revealed when the active pigment fades. A color-changing biomimetic material (CCBM) is developed with a solution casting method by adopting microcapsuled thermochromic pigments and chrome titanate yellow pigments as fillers in a base film with polyvinyl alcohol and lithium chloride. A Kubelka-Munk four-flux model is constructed to optimize the component proportions of the CCBM. The material has a reversible color change, closely resembles the foliage spectrum in UV-vis-NIR ranges, and imitates the thermal behavior of natural foliage in the mid-infrared regime. These results provide a novel approach to multispectral and hyperspectral camouflage.
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PURPOSE: The purpose of our study was to evaluate the association of baseline MRI Prostate Imaging Reporting and Data System (PI-RADS) score with biopsy reclassification in a multicenter active surveillance (AS) cohort. MATERIALS AND METHODS: We identified men in the Michigan Urological Surgery Improvement Collaborative registry (46 hospital-based/academic/private practice urology groups) with National Comprehensive Cancer Network (NCCN) low-risk and favorable intermediate-risk prostate cancer who underwent MRI within 6 months before or after initial biopsy and enrolled in AS from June 2016 to January 2021. The primary objective was to determine the association of baseline MRI PI-RADS score (≥4 lesion) with reclassification to high-grade prostate cancer (≥grade group 3) on surveillance biopsy. Multivariable Cox proportional hazards regression models were constructed and adjusted for pathologic, MRI, and clinical/biopsy factors, with landmark time of 6 months from diagnostic biopsy. We included an interaction term between PI-RADS score and NCCN group in the Cox model. RESULTS: A total of 1491 men were included with median age 64 years (IQR: 59-69) with median follow-up 11.0 months (IQR: 6.0-23.0) after landmark. Baseline PI-RADS ≥ 4 lesion was associated with an increased hazard of biopsy reclassification (HR: 2.3 [95% CI: 1.6-3.2], P < .001), along with grade group 2 vs 1 (HR: 2.5 [95% CI: 1.7-3.7], P < .001), and increasing age (per 10 years; HR: 1.8 [95% CI: 1.4-2.4], P < .001). The interaction between NCCN risk group with MRI findings was not significant (P = .7). CONCLUSIONS: In this multicenter cohort study of real-world data, baseline MRI PI-RADS score was significantly associated with early biopsy reclassification in men undergoing AS with NCCN low- or favorable intermediate-risk prostate cancer.
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Cat-state qubits formed by photonic cat states have a biased noise channel, i.e., one type of error dominates over all the others. We demonstrate that such biased-noise qubits are also promising for error-tolerant simulations of the quantum Rabi model (and its varieties) by coupling a cat-state qubit to an optical cavity. Using the cat-state qubit can effectively enhance the counterrotating coupling, allowing us to explore several fascinating quantum phenomena relying on the counterrotating interaction. Moreover, another benefit from biased-noise cat qubits is that the two main error channels (frequency and amplitude mismatches) are both exponentially suppressed. Therefore, the simulation protocols are robust against parameter errors of the parametric drive that determines the projection subspace. We analyze three examples: (i) collapse and revivals of quantum states; (ii) hidden symmetry and tunneling dynamics; and (iii) pair-cat-code computation.
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OBJECTIVE: The objective of this retrospective cohort study is to investigate the impact of monitoring serum estradiol (E2) levels before progesterone administration within hormone replacement therapy (HRT) on pregnancy outcomes in women undergoing frozen-thawed embryo transfer (FET). METHODS: Analyzed HRT-FET cycles conducted at a reproductive center from 2017 to 2022. Serum E2 levels were measured prior to progesterone administration. Multivariate stratified and logistic regression analyses were performed on 26,194 patients grouped according to terciles of serum E2 levels before progesterone administration. RESULTS: The clinical pregnancy rate (CPR) and live birth rate (LBR) exhibited a gradual decline with increasing serum E2 levels across the three E2 groups. Even after controlling for potential confounders, including female age, body mass index, infertility diagnosis, cycle category, number of embryos transferred, fertilization method, indication for infertility, and endometrial thickness, both CPR and LBR persistently showed a gradual decrease as serum E2 levels increased within the three E2 groups. The same results were obtained by multivariate logistic regression analysis. CONCLUSIONS: This large retrospective study indicates that elevated serum E2 levels before progesterone administration during HRT-FET cycles are associated with reduced CPR and LBR post-embryo transfer. Therefore, it is advisable to monitor serum E2 levels and adjust treatment strategies accordingly to maximize patient outcomes.
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Criopreservação , Transferência Embrionária , Estradiol , Terapia de Reposição Hormonal , Resultado da Gravidez , Taxa de Gravidez , Progesterona , Humanos , Feminino , Gravidez , Transferência Embrionária/métodos , Estradiol/sangue , Progesterona/sangue , Estudos Retrospectivos , Adulto , Terapia de Reposição Hormonal/métodos , Resultado da Gravidez/epidemiologia , Fertilização in vitro/métodos , Nascido Vivo/epidemiologiaRESUMO
BACKGROUND: The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. RESULTS: In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-ß1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. CONCLUSIONS: Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.
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Bleomicina , Senescência Celular , Ritmo Circadiano , Fibrose Pulmonar , Animais , Humanos , Masculino , Camundongos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Ritmo Circadiano/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/patologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
The thermal management of electronics has gained significant attention, with loop heat pipes (LHPs) emerging as an attractive solution for heat dissipation. The heat transfer performance of LHPs is influenced by the heat and mass transfer processes within the wick. However, designing the pore diameter of the wick is challenging due to the different requirements of flow resistance and capillary force. Specifically, the working fluid needs large pores to reduce resistance, while the liquid suction requires small pores to provide a large capillary force. To address this issue, we drew inspiration from the stomatal array of natural leaves used for transpiration and developed an alumina ceramic bionic wick with finger-like pores using the phase-inversion tape casting method. The finger-like pores in the wick resemble the straight hole structure of stomata, which increases the gas-liquid interface area within the wick. This design allows for timely discharge of water vapor generated by boiling, thereby reducing mass transfer resistance. Additionally, numerous micrometer-sized small pores surrounding the finger-like pores provide sufficient capillary force to replenish liquid for the gas-liquid evaporation interface. Experimental results demonstrate that the introduction of finger-like pores in the wick increases gas and water permeabilities by 2.4 and 5.2 times, respectively. Furthermore, the superior heat and mass transfer performance of the bionic wick was demonstrated with an LHP. This work effectively addresses the conflicting demands of capillary force and flow resistance, enhancing the heat transfer performance of LHPs, which holds great promise for addressing heat dissipation challenges in high power density electronic chips and has potential applications in aviation, aerospace, and microelectronics for efficient thermal management.
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BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1â2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.
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The adsorption of CO on the surface of MgO has long been a model problem in surface chemistry. Here, we report periodic Gaussian-based calculations for this problem using second-order perturbation theory (MP2) and coupled-cluster theory with single and double excitations (CCSD) and perturbative triple excitations [CCSD(T)], with the latter two performed using a recently developed extension of the local natural orbital approximation to problems with periodic boundary conditions. The low cost of periodic local correlation calculations allows us to calculate the full CCSD(T) binding curve of CO approaching the surface of MgO (and thus the adsorption energy) and the two-dimensional potential energy surface (PES) as a function of the distance from the surface and the CO stretching coordinate. From the PES, we obtain the fundamental vibrational frequency of CO on MgO, whose shift from the gas phase value is a common experimental probe of surface adsorption. We find that CCSD(T) correctly predicts a positive frequency shift upon adsorption of +14.7 cm-1, in excellent agreement with the experimental shift of +14.3 cm-1. We use our CCSD(T) results to assess the accuracy of MP2, CCSD, and several density functional theory (DFT) approximations, including exchange correlation functionals and dispersion corrections. We find that MP2 and CCSD yield reasonable binding energies and frequency shifts, whereas many DFT calculations overestimate the magnitude of the adsorption energy by 5-15 kJ mol-1 and predict a negative frequency shift of about -20 cm-1, which we attribute to self-interaction-induced delocalization errors that are mildly ameliorated with hybrid functionals. Our findings highlight the accuracy and computational efficiency of the periodic local correlation for the simulation of surface chemistry with accurate wavefunction methods.
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PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.
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BACKGROUND: COVID-19 is a new infectious disease. To investigate whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the adverse reactions of subcutaneous specific immunotherapy (SCIT) in children. METHODS: This study was conducted by collecting relevant data from children who underwent house dust mite SCIT from April 3, 2021, to March 18, 2023, including information on the time of COVID-19 infection, symptoms, and adverse reactions after each allergen injection. A mixed effects model was used to analyze the changes in adverse reactions before and after the COVID-19 infection. RESULTS: Among the records of adverse reactions from 2658 injections in 123 children who underwent SCIT, the overall adverse reaction rate before COVID-19 infection was 39.8% and 30.0% after COVID-19 infection. Compared with pre-infection with COVID-19, the risks of overall adverse reactions, local adverse reactions, and systemic adverse reactions of immunotherapy after COVID-19 infection were reduced (odds ratio [OR] = 0.24, 0.31, and 0.28, all P < 0.05). Among the local adverse reactions, the incidence of the unvaccinated group was the highest (15.3% vs. 7.1%). The incidence of overall and local adverse reactions to SCIT decreased in 2-vaccinated COVID-19 recipients (OR = 0.29-0.31, P < 0.05). CONCLUSIONS: In children, SARS-CoV-2 infection does not increase the incidence of adverse reactions to SCIT. This finding can provide a basis for the implementation of allergen-specific immunotherapy (AIT) during the COVID-19 pandemic.
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COVID-19 , Dessensibilização Imunológica , SARS-CoV-2 , Humanos , COVID-19/terapia , COVID-19/imunologia , Criança , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , SARS-CoV-2/imunologia , Injeções Subcutâneas , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Adolescente , Animais , Pyroglyphidae/imunologia , Alérgenos/imunologia , Alérgenos/efeitos adversos , Alérgenos/administração & dosagem , LactenteRESUMO
Ozone pollution is increasingly recognized as a serious environmental threat that exacerbates dementia risks, including Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI). Amid rapid industrialization, China faces significant air quality challenges. However, there has been a scarcity of detailed studies assessing the health and economic impacts of ozone pollution on these conditions. This study aims to address this gap by utilizing the BenMap-CE tool and incorporating parameters obtained from systematic reviews of epidemiological studies, official statistics, and weighted averages, to accurately quantify the effects of ozone exposure in China. This research evaluated the health and economic burdens at both national and provincial levels, focusing on the additional impacts attributed to increased ozone levels. The results reveal that in 2023, compared to 2015, ozone pollution contributed to approximately 110,000 new cases (5.6 per 10,000) of AD and 1.6 million new cases (81.7 per 10,000) of MCI, imposing significant economic costs of about US $1200 million for AD and US $18,000 million for MCI, based on 2015 dollar values. Additionally, our projections indicate that reducing the 2023 ozone concentrations to 70 µg/m3 could significantly curb these conditions, potentially preventing over 210,000 new AD cases (10.7 per 10,000) and 2.9 million (148.1 per 10,000) MCI cases. Such reductions are projected to yield substantial economic benefits, estimated at US $2200 million for AD and US $34,000 million for MCI (2015 dollar values). These findings underscore the profound implications of ozone pollution on public health and the economy in China, highlighting the urgent need for effective ozone management strategies to mitigate these impacts.
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In this work, we introduce a differentiable implementation of the local natural orbital coupled cluster (LNO-CC) method within the automatic differentiation framework of the PySCFAD package. The implementation is comprehensively tuned for enhanced performance, which enables the calculation of first-order static response properties on medium-sized molecular systems using coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)]. We evaluate the accuracy of our method by benchmarking it against the canonical CCSD(T) reference for nuclear gradients, dipole moments, and geometry optimizations. In addition, we demonstrate the possibility of property calculations for chemically interesting systems through the computation of bond orders and Mössbauer spectroscopy parameters for a [NiFe]-hydrogenase active site model, along with the simulation of infrared spectra via ab initio LNO-CC molecular dynamics for a protonated water hexamer.
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BACKGROUND: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes. METHODS: This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses. SETTING: Single reproductive medical center. SUBJECTS: All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included. EXPOSURE: Next-generation sequencing platforms for chromosomal analysis. MAIN OUTCOME MEASURES: Blastocyst formation and euploid blastocyst rates. RESULTS: In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy. CONCLUSION: In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates.
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BACKGROUND: Quality of life, social support, and loneliness are common problems among older adults in China , but the relationships among these issues have not been clearly identified. OBJECTIVES: The present study aimed to determine the relationships among Quality of life, social support, and loneliness. METHODS: A total of 560 older adults were randomly selected , the social support rating scale (SSRS), University of California at Los Angeles (UCLA) loneliness scale, and Short-Form 12 (SF-12) were employed to measure their degree of social support, level of loneliness, and quality of life. RESULTS: The average physical component summary (PCS) score was 49.97±16.33, and the average mental component summary (MCS) score was 47.26±11.49. Loneliness plays a partial mediating role between social support and quality of life. CONCLUSION: Loneliness and a lack of social support will affect the quality of life of the older adults. Thus, we need to urgently strengthen the care and support for the older adults and alleviate the loneliness of the older adults in the community.