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1.
J Agric Food Chem ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38759097

RESUMEN

Thirty-four new pyrido[4,3-d]pyrimidine analogs were designed, synthesized, and characterized. The crystal structures for compounds 2c and 4f were measured by means of X-ray diffraction of single crystals. The bioassay results showed that most target compounds exhibited good fungicidal activities against Pyricularia oryzae, Rhizoctonia cerealis, Sclerotinia sclerotiorum, Botrytis cinerea, and Penicillium italicum at 16 µg/mL. Compounds 2l, 2m, 4f, and 4g possessed better fungicidal activities than the commercial fungicide epoxiconazole against B. cinerea. Their half maximal effective concentration (EC50) values were 0.191, 0.487, 0.369, 0.586, and 0.670 µg/mL, respectively. Furthermore, the inhibitory activities of the bioactive compounds were determined against sterol 14α-demethylase (CYP51). The results displayed that they had prominent activities. Compounds 2l, 2m, 4f, and 4g also showed better inhibitory activities than epoxiconazole against CYP51. Their half maximal inhibitory concentration (IC50) values were 0.219, 0.602, 0.422, 0.726, and 0.802 µg/mL, respectively. The results of molecular dynamics (MD) simulations exhibited that compounds 2l and 4f possessed a stronger affinity to CYP51 than epoxiconazole.

2.
J Med Chem ; 67(10): 7954-7972, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38703119

RESUMEN

To discover potential sterol 14α-demethylase (CYP51) inhibitors, thirty-four unreported 4H-pyrano[3,2-c]pyridine derivatives were designed and synthesized. The assay results indicated that most compounds displayed significant fungicidal activity against Sclerotinia sclerotiorum, Colletotrichum lagenarium, Botrytis cinerea, Penicillium digitatum, and Fusarium oxysporum at 16 µg/mL. The half maximal effective concentration (EC50) values of compounds 7a, 7b, and 7f against B. cinerea were 0.326, 0.530, and 0.610, respectively. Namely, they had better antifungal activity than epoxiconazole (EC50 = 0.670 µg/mL). Meanwhile, their half maximal inhibitory concentration (IC50) values against CYP51 were 0.377, 0.611, and 0.748 µg/mL, respectively, representing that they also possessed better inhibitory activities than epoxiconazole (IC50 = 0.802 µg/mL). The fluorescent quenching tests of proteins showed that 7a and 7b had similar quenching patterns to epoxiconazole. The molecular dynamics simulations indicated that the binding free energy of 7a and epoxiconazole to CYP51 was -35.4 and -27.6 kcal/mol, respectively.


Asunto(s)
Inhibidores de 14 alfa Desmetilasa , Antifúngicos , Diseño de Fármacos , Simulación de Dinámica Molecular , Piridinas , Esterol 14-Desmetilasa , Inhibidores de 14 alfa Desmetilasa/farmacología , Inhibidores de 14 alfa Desmetilasa/síntesis química , Inhibidores de 14 alfa Desmetilasa/química , Antifúngicos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Piridinas/farmacología , Piridinas/síntesis química , Piridinas/química , Esterol 14-Desmetilasa/metabolismo , Esterol 14-Desmetilasa/química , Relación Estructura-Actividad , Pruebas de Sensibilidad Microbiana , Fusarium/efectos de los fármacos , Penicillium , Ascomicetos/efectos de los fármacos , Colletotrichum/efectos de los fármacos , Botrytis/efectos de los fármacos , Estructura Molecular , Simulación del Acoplamiento Molecular
3.
Ann Hematol ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38805037

RESUMEN

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

4.
BMC Microbiol ; 24(1): 179, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789934

RESUMEN

BACKGROUND: Ticks are blood-feeding significant arthropods that can harbour various microorganisms, including pathogens that pose health risks to humans and animals. Tick-symbiont microorganisms are believed to influence tick development, but the intricate interactions between these microbes and the relationships between different tick-borne microorganisms remain largely unexplored. RESULTS: Based on 111 tick pool samples presenting questing and engorged statuses including 752 questing tick and 1083 engorged tick from cattle and goats, which were collected in two types of geographic landscape (semi-desert and alpine meadow). We observed significant variations in the composition of tick-borne microorganisms across different environments and blood-engorgement statuses, with a pronounced divergence in symbionts compared to environmental bacteria. Metabolic predictions revealed over 90 differential pathways for tick-borne microorganisms in distinct environments and more than 80 metabolic variations in response to varying blood engorgement statuses. Interestingly, nine pathways were identified, particularly related to chorismate synthesis and carbohydrate metabolism. Moreover, microbial network relationships within tick-borne microorganism groups were highly distinct across different environments and blood-engorgement statuses. The microbial network relationships of symbionts involve some pathogenic and environmental microorganisms. Regression modelling highlighted positive correlations between the Coxiella symbiont and related pathogens, while some environmental bacteria showed strong negative correlations with Coxiella abundance. We also identified commensal bacteria/pathogens in bacterial cooccurrence patterns. Furthermore, we tested pathogenic microorganisms of each tick sample analysis revealed that 86.36% (1601/1855) of the tick samples carried one or more pathogenic microorganisms, The total carrier rate of bacterial pathogens was 43.77% ((812/1855). Most blood samples carried at least one pathogenic microorganism. The pathogens carried by the ticks have both genus and species diversity, and Rickettsia species are the most abundant pathogens among all pathogens. CONCLUSION: Our findings underscore that the bacterial pattern of ticks is dynamic and unstable, which is influenced by the environment factors and tick developmental characteristics.


Asunto(s)
Bacterias , Cabras , Simbiosis , Animales , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Bovinos , Coxiella/aislamiento & purificación , Coxiella/genética , Coxiella/clasificación
5.
Materials (Basel) ; 17(10)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38793268

RESUMEN

Commercial oxygen-free copper sheets were cold-rolled with reduction rates ranging from 20% to 87% and annealed at 400, 500 and 600 °C. The microstructure and texture evolution during the cold-rolling and annealing processes were studied using optical microscopy (OM), scanning electron microscopy (SEM) and electron back-scattered diffraction (EBSD). The results show that the deformation textures of {123}<634> (S), {112}<111> (Copper) and {110}<112> (Brass) were continuously enhanced with the increase in cold-rolling reduction. The orientations along the α-oriented fiber converged towards Brass, and the orientation density of ß fiber obviously increased when the rolling reduction exceeded 60%. The recrystallization texture was significantly affected by the cold-rolling reduction. After 60% cold-rolling reduction, Copper and S texture components gradually decreased, and the {011}<511> recrystallization texture component formed with the increase in annealing temperature. After 87% cold-rolling reduction, a strong Cube texture formed, and other textures were inhibited with the increase in annealing temperature. The strong Brass and S deformation texture was conducive to the formation of a strong Cube annealing texture. The density of the annealing twin boundary decreased with the increase in annealing temperature, and more annealing twin boundaries formed in the oxygen-free copper sheets with the increase in cold-rolling reduction.

6.
Biotechnol Biofuels Bioprod ; 17(1): 68, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802837

RESUMEN

BACKGROUND: Bacterial nanocellulose (BNC), a natural polymer material, gained significant popularity among researchers and industry. It has great potential in areas, such as textile manufacturing, fiber-based paper, and packaging products, food industry, biomedical materials, and advanced functional bionanocomposites. The main current fermentation methods for BNC involved static culture, as the agitated culture methods had lower raw material conversion rates and resulted in non-uniform product formation. Currently, studies have shown that the production of BNC can be enhanced by incorporating specific additives into the culture medium. These additives included organic acids or polysaccharides. γ-Polyglutamic acid (γ-PGA), known for its high polymerization, excellent biodegradability, and environmental friendliness, has found extensive application in various industries including daily chemicals, medicine, food, and agriculture. RESULTS: In this particular study, 0.15 g/L of γ-PGA was incorporated as a medium additive to cultivate BNC under agitated culture conditions of 120 rpm and 30 â„ƒ. The BNC production increased remarkably by 209% in the medium with 0.15 g/L γ-PGA and initial pH of 5.0 compared to that in the standard medium, and BNC production increased by 7.3% in the medium with 0.06 g/L γ-PGA. The addition of γ-PGA as a medium additive resulted in significant improvements in BNC production. Similarly, at initial pH levels of 4.0 and 6.0, the BNC production also increased by 39.3% and 102.3%, respectively. To assess the characteristics of the BNC products, scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis were used. The average diameter of BNC fibers, which was prepared from the medium adding 0.15 g/L γ-PGA, was twice thicker than that of BNC fibers prepared from the control culture medium. That might be because that polyglutamic acid relieved the BNC synthesis from the shear stress from the agitation. CONCLUSIONS: This experiment held great significance as it explored the use of a novel medium additive, γ-PGA, to improve the production and the glucose conversion rate in BNC fermentation. And the BNC fibers became thicker, with better thermal stability, higher crystallinity, and higher degree of polymerization (DPv). These findings lay a solid foundation for future large-scale fermentation production of BNC using bioreactors.

7.
Angew Chem Int Ed Engl ; : e202406153, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730419

RESUMEN

Innovative molecule design strategy holds promise for the development of next-generation acceptor materials for efficient organic solar cells with low non-radiative energy loss (ΔEnr). In this study, we designed and prepared three novel acceptors, namely BTP-Biso, BTP-Bme and BTP-B, with sterically structured triisopropylbenzene, trimethylbenzene and benzene as side chains inserted into the shoulder of the central core. The progressively enlarged steric hindrance from BTP-B to BTP-Bme and BTP-Biso induces suppressed intramolecular rotation and altered the molecule packing mode in their aggregation states, leading to significant changes in absorption spectra and energy levels. By regulating the intermolecular π-π interactions, BTP-Bme possesses relatively reduced non-radiative recombination rate and extended exciton diffusion lengths. The binary device based on PB2:BTP-Bme exhibits an impressive power conversion efficiency (PCE) of 18.5% with a low ΔEnr of 0.19 eV. Furthermore, the ternary device comprising PB2:PBDB-TF:BTP-Bme achieves an outstanding PCE of 19.3%. The molecule design strategy in this study proposed new perspectives for developing high-performance acceptors with low ΔEnr in OSCs.

8.
Biosens Bioelectron ; 257: 116345, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38692247

RESUMEN

Nitrite (NO2-) is present in a variety of foods, but the excessive intake of NO2- can indirectly lead to carcinogenic, teratogenic, mutagenicity and other risks to the human body. Therefore, the detection of NO2- is crucial for maintaining human health. In this study, an integrated array sensor for NO2- detection is developed based on molybdenum single atom material (IMSMo-SAC) using high-resolution electrohydrodynamic (EHD) printing technology. The sensor comprises three components: a printed electrode array, multichannels designed on polydimethylsiloxane (PDMS) and an electronic signal process device with bluetooth. By utilizing Mo-SAC to facilitate electron transfer during the redox reaction, rapid and efficient detection of NO2- can be achieved. The sensor has a wide linear range of 0.1 µM-107.8 mM, a low detection limit of 33 nM and a high sensitivity of 0.637 mA-1mM-1 cm-2. Furthermore, employing this portable array sensor allows simultaneously measurements of NO2- concentrations in six different foods samples with acceptable recovery rates. This array sensor holds great potential for detecting of small molecules in various fields.


Asunto(s)
Técnicas Biosensibles , Diseño de Equipo , Análisis de los Alimentos , Límite de Detección , Molibdeno , Nitritos , Molibdeno/química , Técnicas Biosensibles/instrumentación , Nitritos/análisis , Análisis de los Alimentos/instrumentación , Humanos , Dimetilpolisiloxanos/química , Electrodos , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Contaminación de Alimentos/análisis
9.
Zhongguo Zhong Yao Za Zhi ; 49(4): 884-893, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621895

RESUMEN

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.


Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Medicamentos Herbarios Chinos , Sepsis , Humanos , Medicina Tradicional China , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Apoptosis , Transducción de Señal , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología
10.
Artículo en Inglés | MEDLINE | ID: mdl-38570431

RESUMEN

The impact of biogas residual biochar (BRB) on the humification and carbon balance process of co-composting of hog slurry (HGS) and wheat straw (WTS) was examined. The 50-day humification process was significantly enhanced by the addition of BRB, particular of 5% BRB, as indicated by the relatively higher humic acid content (67.28 g/kg) and humification ratio (2.31) than other treatments. The carbon balance calculation indicated that although BRB addition increased 22.16-46.77% of C lost in form of CO2-C, but the 5% BRB treatment showed relatively higher C fixation and lower C loss than other treatments. In addition, the BRB addition reshaped the bacterial community structure during composting, resulting in increased abundances of Proteobacteria (25.50%) during the thermophilic phase and Bacteroidetes (33.55%) during the maturation phase. Combined these results with biological mechanism analysis, 5% of BRB was likely an optimal addition for promoting compost humification and carbon fixation in practice.

11.
Front Vet Sci ; 11: 1269530, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577545

RESUMEN

This paper examines the role of the World Organisation for Animal Health (WOAH) in the global surveillance and management of pathogens. Since the creation of WOAH, one of its missions has been to ensure transparency of the global animal health situation. WOAH established a Working Group on Wildlife in 1994 to inform and advise WOAH Members, leadership, and technical teams on issues relating to wildlife health. In 2020 it conducted a consultation with its Members before developing a Wildlife Health Framework to improve global health and wildlife conservation. WOAH Members report diseases in wildlife, but detections are dependent on the surveillance systems in place. As an example of data collected in the most recent years (2019-2023), 154 countries have reported 68,862,973 cases, through alert messages and weekly updates, for 84 diseases. One-hundred and fifty countries have reported 68,672,115 cases in domestic animals and 95 countries have reported 190,858 cases in wild animals. These figures illustrate the performance of the organization in collecting data on wildlife, and provide an indication of the difference in completeness of data collected in domestic animals and wildlife. There are several challenges to wildlife disease surveillance and real figures remain unknown; they depend on the existence, quality and sensitivity of national surveillance. A WOAH-led One Health approach with cross-sectoral collaboration is needed to improve surveillance sensitivity, address the challenges and help safeguard wildlife population health and biodiversity conservation.

12.
Int J Med Sci ; 21(5): 914-920, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38617012

RESUMEN

Background: We aimed to compare the prevention of hypoxemia using High-flow nasal oxygen (HFNO) or regular nasal tubing (CNC) in elderly patients undergoing gastroscopy with sedation. Methods: This study was a prospective, randomized, controlled trial conducted at a single center. We included elective patients aged 65 and above who were undergoing gastroscopy with sedation. In the intervention group (HFNO), we set the oxygen flow rate to 60 liters per minute with an oxygen fraction (FiO2) of 0.6, while in the control group (CNC), it was 6 liters per minute. The primary outcome was the occurrence of hypoxemia (defined as Spo2 < 90%). Results: A total of 125 participants were enrolled (HFNO group: n = 63; CNC group: n = 62). The occurrence of hypoxemia was found to be significantly lower in the HFNO group compared to the CNC group (3.2% vs. 22.6%, p = 0.001). Additionally, a significantly shorter duration of low oxygen levels was observed in the HFNO group [0.0 seconds (0.0-13.0)] compared to the CNC group [0.0 seconds (0.0-124.0), p<0.001]. Moreover, a higher minimum Spo2 value was achieved in the HFNO group [99.0% (98.0-100.0) vs. 96.5% (91.0-99.0), p < 0.001], and a shorter recovery time was recorded [0.5 minutes (0.0-0.5) vs. 0.5 minutes (0.0-1.0), p = 0.016] in comparison to the CNC group. There were no differences in terms of comfort level [0 (0-4) vs. 0 (0-5), p = 0.268] between the two groups. Conclusions: The HFNO system was determined to be a safe and highly effective method for oxygen delivery, leading to a reduction in the occurrence of hypoxemia in elderly patients undergoing gastroscopy with sedation. It is recommended that HFNO be considered as the standard approach for management in this population.


Asunto(s)
Gastroscopía , Oxígeno , Anciano , Humanos , Gastroscopía/efectos adversos , Cánula , Estudios Prospectivos , Hipoxia/etiología , Hipoxia/prevención & control
13.
J Neuroinflammation ; 21(1): 88, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600569

RESUMEN

BACKGROUND: Mechanical softening of the glial scar region regulates axonal regeneration to impede neurological recovery in central nervous system (CNS) injury. Microglia, a crucial cellular component of the glial scar, facilitate neuronal survival and neurological recovery after spinal cord injury (SCI). However, the critical mechanical characterization of injured spinal cord that harmonizes neuroprotective function of microglia remains poorly understood. METHODS: Spinal cord tissue stiffness was assessed using atomic force microscopy (AFM) in a mouse model of crush injury. Pharmacological depletion of microglia using PLX5622 was used to explore the effect of microglia on mechanical characterization. Conditional knockout of Fascin-1 in microglia (Fascin-1 CKO) alone or in combination with inhibition of myosin activity was performed to delve into relevant mechanisms of microglia regulating mechanical signal. Immunofluorescence staining was performed to evaluate the related protein levels, inflammatory cells, and neuron survival after SCI. The Basso mouse scale score was calculated to assess functional recovery. RESULTS: Spinal cord tissue significantly softens after SCI. Microglia depletion or Fascin-1 knockout in microglia limits tissue softening and alters mechanical characterization, which leads to increased tissue pathology and impaired functional recovery. Mechanistically, Fascin-1 inhibits myosin activation to promote microglial migration and control mechanical characterization after SCI. CONCLUSIONS: We reveal that Fascin-1 limits myosin activity to regulate mechanical characterization after SCI, and this mechanical signal should be considered in future approaches for the treatment of CNS diseases.


Asunto(s)
Proteínas de Microfilamentos , Microglía , Traumatismos de la Médula Espinal , Animales , Ratones , Proteínas Portadoras , Gliosis/metabolismo , Proteínas de Microfilamentos/metabolismo , Microglía/metabolismo , Médula Espinal/patología , Traumatismos de la Médula Espinal/patología
14.
Small ; : e2312083, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38644686

RESUMEN

Due to the ubiquitous and inexhaustible solar source, photothermal materials have gained considerable attention for their potential in heating and de-icing. Nevertheless, traditional photothermal materials, exemplified by graphene, frequently encounter challenges emanating from their elevated reflectance. Inspired by ocular structures, this study uses the Fresnel equation to enhance the photo-thermal conversion efficiency of graphene by introducing a polydimethylsiloxane (PDMS)/silicon dioxide (SiO2) coating, which reduces the light reflectance (≈20%) through destructive interference. The designed coating achieves an equilibrium temperature of ≈77 °C at one sun and a quick de-icing in ≈65 s, all with a thickness of 5 µm. Simulations demonstrate that applying this coating to high-rise buildings results in energy savings of ≈31% in winter heating. Furthermore, the combination of PDMS/SiO2 and graphene confers a notable enhancement in thermal stability through a synergistic flame-retardant mechanism, effectively safeguarding polyurethane against high temperatures and conflagrations, leading to marked reduction of 58% and 28% in heat release rate and total heat release. This innovative design enhances the photo-thermal conversion, de-icing function, and flame retardancy of graphene, thereby advancing its applications in outdoor equipment, high-rise buildings, and aerospace vessels.

15.
Front Psychol ; 15: 1352094, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38686090

RESUMEN

Objectives: Explore the relationship between adult attachment and depression among college students, and the mechanism of perfectionism. Study design: Questionnaire survey. Methods: A questionnaire survey was conducted nationwide, totally 313 valid questionnaires were received. The survey collected information such as adult attachment (Adult Attachment Scale, AAS), depression (The Center for Epidemiologic Studies Depression Scale, CESD), and perfectionism (The Frost Multidimensional Perfectionism Scale, FMPS). Then used SPSS26.0 to analyze the collected data. Results: There were significant differences in perfectionism and depression between secure attachment and insecure attachment in college students. Perfectionism plays a partial mediating role in the relationship between the close-depend composite dimension, anxiety dimension of attachment and depression. Conclusion: The closeness-dependence dimension of attachment significantly and negatively predicted perfectionism and depression; the anxiety dimension of attachment significantly and positively predicted perfectionism and depression; and perfectionism partially mediated the effect of both the closeness-dependence dimension of attachment on depression and the anxiety dimension of attachment on depression. Attachment can directly affect college students' depression, but also indirectly through perfectionism.

16.
J Clin Pharmacol ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38686508

RESUMEN

Proline henagliflozin, a novel selective inhibitor of sodium glucose cotransporter 2, is a treatment for type 2 diabetes mellitus. We designed a parallel-group, open-label, and multicenter study to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety profiles of henagliflozin in Chinese subjects with varying degrees of liver dysfunction. Thirty-two subjects were enrolled and divided into four groups based on liver function (normal liver function, mild, moderate, or severe liver dysfunction). The area under the plasma concentration from time zero to infinity of henagliflozin in subjects with mild liver dysfunction, moderate liver dysfunction, and severe liver dysfunction compared with normal liver function was increased by 137%, 197%, and 204%, respectively. The maximum plasma concentration was also increased by 123%, 129%, and 139%, respectively. PK parameters of three metabolites varied to different degrees in the liver dysfunction groups than in the normal liver function group. The mean accumulative excretion amounts and fraction of dose excreted in urine expressed as a percentage were all increased with the decrease of liver function. The PD parameters were significantly higher in liver dysfunction groups than those in the normal liver function group. However, the urine creatinine (UCr) was not significantly different among the groups. No notable adverse events or adverse drug reactions were observed. Due to the higher exposures in subjects with liver dysfunction, the benefit: risk ratio should be individually assessed because the long-term safety profile and efficacy have not been specifically studied in this population.

17.
Nucleic Acids Res ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38686791

RESUMEN

In plant chloroplasts, certain ribosomal proteins (RPs) and ribosome biogenesis factors (RBFs) are present in nucleoids, implying an association between nucleoids and ribosome biogenesis. In Arabidopsis, the YqeH-type GTPase Brassinazole-Insensitive Pale Green2 (BPG2) is a chloroplast nucleoid-associated RBF. Here, we investigated the relationship between nucleoids and BPG2-involved ribosome biogenesis steps by exploring how BPG2 targets ribosomes. Our findings demonstrate that BPG2 interacts with an essential plastid RP, uS10c, in chloroplast nucleoids in a ribosomal RNA (rRNA)-independent manner. We also discovered that uS10c is a haploinsufficient gene, as the heterozygous deletion of this gene leads to variegated shoots and chlorophyll aggregation. uS10c is integrated into 30S ribosomal particles when rRNA is relatively exposed and also exists in polysome fractions. In contrast, BPG2 exclusively associates with 30S ribosomal particles. Notably, the interaction between BPG2 and 30S particles is influenced by the absence of uS10c, resulting in BPG2 diffusing in chloroplasts instead of targeting nucleoids. Further, our results reveal that the loss of BPG2 function and the heterozygous deletion of uS10c impair the processing of 16S and 23S-4.5S rRNAs, reduce plastid protein accumulation, and trigger the plastid signaling response. Together, these findings indicate that the uS10c-BPG2 module mediates ribosome biogenesis in chloroplast nucleoids.

18.
Angew Chem Int Ed Engl ; : e202402827, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602019

RESUMEN

Lithium-ion batteries have found extensive applications due to their high energy density and low self-discharge rates, spanning from compact consumer electronics to large-scale energy storage facilities. Despite their widespread use, challenges such as inherent capacity degradation and the potential for thermal runaway hinder sustainable development. In this study, we introduce a unique approach to synthesize anode materials for lithium-ion batteries, specifically imidazole-intercalated cobalt hydroxide. This innovative material significantly enhances the Li+ desolvation/diffusion reaction and flame-retardant dynamics through complexing and catalytic synergetic effects. The lithium-ion batteries incorporating these materials demonstrate exceptional performance, boasting an impressive capacity retention of 997.91 mAh g-1 after 500 cycles. This achievement can be attributed to the optimization of the solid electrolyte interphase (SEI) interface engineering, effectively mitigating anode degradation and minimizing electrolyte consumption. Experimental and theoretical calculations validate these improvements. Importantly, imidazole intercalated Co(OH)2 (MI-Co(OH)2) exhibits a remarkable catalytic effect on electrolyte carbonization and the conversion of CO to CO2. This dual action suppresses smoke and reduces toxicity significantly. The presented work introduces a novel approach to realizing high-performance and safe lithium-ion batteries, addressing key challenges in the pursuit of sustainable energy solutions.

19.
Front Oncol ; 14: 1388564, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38634054

RESUMEN

Objective: To assess the impact of different treatment strategies and risk factors on the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL) in a single medical center. Methods and analysis: The clinical features of 266 patients with ENKTL were retrospectively analyzed, among whom those in stages I and II received sandwich therapy, while those in stages III and IV underwent chemotherapy plus autologous hematopoietic stem cell transplantation. The Kaplan-Meier curves, univariate and multivariate Cox regression analyses were employed for survival and prognosis analysis. Statistical significance was set at P<0.05. Results: Following treatment, the post-intervention outcomes demonstrated a complete remission (CR) rate of 71.05% and a partial remission (PR) rate of 3.76%. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 70.4% and 70.9%, respectively. In addition, the PFS for patients in stage I/II was 79.8%, with an OS of 81.1%, whereas for those in stage III/IV, the PFS was 41.7% and the OS was 40.9%. Notably, the achievement of CR immediately after treatment was an independent prognostic factor (P<0.001). Patients in stage I/II depicted a favorable 5-year OS rate, while those in stage III/IV manifested a less favorable prognosis. Conclusion: Stages of the disease and whether CR was achieved following treatment are important factors determining the survival and prognosis of patients with ENKTL. Further researches focusing on disease onset and mechanisms of drug resistance will contribute to better management of ENKTL.

20.
Neurol Res ; : 1-8, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38661091

RESUMEN

OBJECTIVES: To evaluate the effect of external diaphragmatic pacing (EDP) combined with inspiratory muscle training on respiratory function in post-stroke patients. METHODS: Patients with stroke were enrolled from the First Affiliated Hospital of Soochow University in China between 2021 and 2022. The patients were randomized into an EDP treatment group (control group) or an EDP treatment plus inspiratory muscle training group (experimental group). Each therapy was administered once a day for 6 days per week. The peak inspiratory flow (PIF), maximal inspiratory pressure (MIP), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% ratio, and diaphragm thickness and mobility were measured and compared between the two groups after 4 weeks. RESULTS: After 4 weeks of intervention, respiratory muscle function indicators including PIF (95% CI: 0.21-1.28, p = 0.008) and MIP (95% CI: 6.92-25.44, p = 0.001) significantly improved in the experimental group. Diaphragmatic thickness also significantly increased in the experimental group (p < 0.05), while diaphragmatic excursion showed no significant difference between the two groups. Additionally, FVC (95% CI: 0.14-1.14, p = 0.013) and FEV1 (95% CI: 0.20-1.06, p = 0.005) demonstrated a significant increase in the experimental group, whereas FEV1/FVC% (95% CI: -0.84 to 9.36, p = 0.099) exhibited no significant group difference. CONCLUSION: EDP combined with inspiratory muscle training in individuals with stroke provides greater benefits than EDP alone in terms of respiratory function recovery, except for the parameters of diaphragmatic excursion and FEV1/FVC%.

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