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1.
Inquiry ; 61: 469580241249425, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38727154

RESUMEN

Quality improvement is an international priority, and quality education and training are important parts of hospital quality management. The aim of this study was to understand the knowledge, attitudes and practices (KAP) and its influencing factors related to quality training in medical staff. A questionnaire survey was conducted by convenience sampling to assess the KAP of quality training in Taizhou Enze Medical Center. Principal component analysis was used to extract factors from the questionnaire. Descriptive statistics (frequency, median, mean), Kendall grade correlation analysis, and Mann-Whitney U tests were used to analyze the data. A total of 205 staff members participated in the questionnaire survey. For the 5 factors of the KAP scale, the highest score was factor F4, recognition and support for quality training (mean = 90.55, median = 100), followed by factor F3, perceived benefits (mean = 84.46, median = 85.65). Relatively lower scores were found for factor F2, quality knowledge learning and mastery (mean = 63.09, median = 63.89), and F5, quality management practices and sharing (mean = 82.07, median = 75.00). There was a correlation between the 5 factors. The scores of F2 (quality knowledge learning and mastery) for staff with senior professional titles were higher than those for staff with intermediate professional titles or below. The score of F3 (perceived benefits of quality training) in medical technicians and nurses was higher than in doctors and administrative personnel. Our findings showed that the respondents' attitude toward quality training was positive, but their knowledge mastery and practice behaviors should be further improved. Occupational category and professional title were the influencing factors of the quality training KAP. Therefore, hospital should conduct quality management training at a wider scope according to the competency requirements of different groups, and further optimize the improvement and innovation system.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Hospitales Generales , Centros de Atención Terciaria , Humanos , Estudios Transversales , Masculino , Femenino , Adulto , Encuestas y Cuestionarios , Mejoramiento de la Calidad , Persona de Mediana Edad , Actitud del Personal de Salud , Cuerpo Médico de Hospitales , China
2.
Front Microbiol ; 15: 1379484, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38680920

RESUMEN

Purpose: This study aims to investigate the effects of frozen storage on the stability of traditional dough starters in China. Methods: The microbial community structure and abundance of related metabolic genes in different fermented sourdough prepared by Jiaozi (JZ) and Laomian (LM) starters before and after frozen storage at -20°C for half a year were analyzed using the shotgun metagenomic sequencing method, and differences in characteristics of texture in steamed bread were also compared by formal methods. Results: The fermentation ability (FA) and metabolic activities of yeast in the JZH sourdough (started by JZ which was stored at -20°C for half a year) were better than those of LMH sourdough (started by LM which was stored at -20°C for half a year). The dominant genera of Acetobacter were found to be increased in the JZH0 sourdough (started by JZH and fermented for 0 h) and those of Lactobacillus were found to be decreased. Lactobacillus (98.72%), Pediococcus (0.37%), Saccharomyces (0.27%), and Acetobacter (0.01%), were dominant in sourdough LMH0 (started by LMH and fermented for 0 h). The abundances of "oxidative phosphorylation-related enzymes" and the "biosynthesis of glutamate"-related enzymes and genes related to "biosynthesis of glutamate" and "unsaturated fatty acid" were higher in JZH0 than in the JZ0 sourdough (started by JZ without being frozen and fermented for 0 h). The good FA of yeast, the acid production capacity of bacteria in the sourdough, and the quality of the JZH steamed bread (made by the JZH starter) indicated the better freezing tolerance of the microorganisms in JZ than in LM. Conclusion: The conclusion of this study suggests the better application potential of the JZ as the fermentation starter in actual production.

3.
Lancet Oncol ; 25(4): 463-473, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38467131

RESUMEN

BACKGROUND: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. METHODS: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. FINDINGS: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. INTERPRETATION: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. FUNDING: AbbVie.


Asunto(s)
Antineoplásicos , Leucemia Linfocítica Crónica de Células B , Adulto , Humanos , Masculino , Femenino , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Antineoplásicos/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Sulfonamidas/efectos adversos , Respuesta Patológica Completa , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
4.
Arch Virol ; 169(4): 80, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38519825

RESUMEN

Here, we report a novel wheat-infecting marafivirus, tentatively named "Triticum aestivum marafivirus" (TaMRV). The full-length genome sequence of TaMRV comprises 6,437 nucleotides, excluding the poly(A) tail. Pairwise sequence comparisons and phylogenetic analysis revealed that TaMRV may represent a novel species within the genus Marafivirus in the family Tymoviridae. We also observed a mass of isometric particles with a diameter of about 30 nm in ultrathin sections of infected wheat leaf tissue. In addition, the leafhopper Psammotettix alienus was identified as a vector for this virus. This is the first report of the occurrence of a wheat-infecting marafivirus.


Asunto(s)
Hemípteros , Tymoviridae , Animales , Tymoviridae/genética , Triticum , ARN Viral/genética , Filogenia , Genoma Viral , Genómica
5.
Biochem Pharmacol ; 222: 116050, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38354960

RESUMEN

The side effects of high-dose dexamethasone in anti-infection include increased ROS production and immune cell apoptosis. Dexamethasone effectively activates serum/glucocorticoid-regulated kinase 1 (SGK1), which upregulates various ion channels by activating store-operated calcium entry (SOCE), leading to Ca2+ oscillations. PIEZO1 plays a crucial role in macrophages' immune activity and function, but whether dexamethasone can regulate PIEZO1 by enhancing SOCE via SGK1 activation remains unclear. The effects of dexamethasone were assessed in a mouse model of sepsis, and primary BMDMs and the RAW264.7 were treated with overexpression plasmids, siRNAs, or specific activators or inhibitors to examine the relationships between SGK1, SOCE, and PIEZO1. The functional and phenotypic changes of mouse and macrophage models were detected. The results indicate that high-dose dexamethasone upregulated SGK1 by activating the macrophage glucocorticoid receptor, which enhanced SOCE and subsequently activated PIEZO1. Activation of PIEZO1 resulted in Ca2+ influx and cytoskeletal remodelling. The increase in intracellular Ca2+ mediated by PIEZO1 further increased the activation of SGK1 and ORAI1/STIM1, leading to intracellular Ca2+ peaks. In the context of inflammation, activation of PIEZO1 suppressed the activation of TLR4/NFκB p65 in macrophages. In RAW264.7 cells, PIEZO1 continuous activation inhibited the change in mitochondrial membrane potential, accelerated ROS accumulation, and induced autophagic damage and cell apoptosis in the late stage. CaMK2α was identified as a downstream mediator of TLR4 and PIEZO1, facilitating high-dose dexamethasone-induced macrophage immunosuppression and apoptosis. PIEZO1 is a new glucocorticoid target to regulate macrophage function and activity. This study provides a theoretical basis for the rational use of dexamethasone.


Asunto(s)
Glucocorticoides , Proteínas Serina-Treonina Quinasas , Humanos , Glucocorticoides/farmacología , Especies Reactivas de Oxígeno/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Toll-Like 4/metabolismo , Macrófagos/metabolismo , Apoptosis , Inflamación , Dexametasona/farmacología , Calcio/metabolismo , Proteína ORAI1/metabolismo , Molécula de Interacción Estromal 1/metabolismo , Canales Iónicos/genética
6.
Cell Rep ; 43(2): 113821, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38368611

RESUMEN

The titer of viruses that persist and propagate in their insect vector must be high enough for transmission yet not harm the insect, but the mechanism of this dynamic balance is unclear. Here, expression of inosine monophosphate dehydrogenase (LsIMPDH), a rate-limiting enzyme for guanosine triphosphate (GTP) synthesis, is shown to be downregulated by increased levels of N6-methyladenosine (m6A) on LsIMPDH mRNA in rice stripe virus (RSV)-infected small brown planthoppers (SBPHs; Laodelphax striatellus), the RSV vector, which decreases GTP content, thus limiting viral proliferation. Moreover, planthopper methyltransferase-like protein 3 (LsMETTL3) and m6A reader protein LsYTHDF3 are found to catalyze and recognize the m6A on LsIMPDH mRNA, respectively, and cooperate in destabilizing LsIMPDH transcripts. Co-silencing assays show that negative regulation of viral proliferation by both LsMETTL3 and LsYTHDF3 is partially dependent on LsIMPDH. This distinct mechanism limits virus replication in an insect vector, providing a potential gene target to block viral transmission.


Asunto(s)
Adenosina/análogos & derivados , Insectos Vectores , Animales , Guanosina Trifosfato , ARN Mensajero/genética , Proliferación Celular
7.
Blood Adv ; 8(8): 1992-2004, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38290108

RESUMEN

ABSTRACT: Chromosome 17p deletion (del[17p]) is associated with poor prognosis in patients with chronic lymphocytic leukemia (CLL). Venetoclax is approved for treatment of previously untreated and relapsed/refractory (R/R) CLL, including patients with del(17p), based on the open-label, multicenter, phase 2 M13-982 trial (NCT01889186). Here, we detail the 6-year follow-up analysis for M13-982. A total of 158 patients with previously untreated (n = 5) or R/R (n = 153) del(17p) CLL received 400 mg venetoclax daily after initial ramp-up until progressive disease. After a median follow-up of 70 months, the best objective response rate (ORR) was 77% (21% complete remission [CR] and 49% partial remission [PR]), with a median duration of response (DOR) of 39.3 months (95% confidence interval [CI], 31.1-50.5). The median progression-free survival (PFS) was 28.2 months (95% CI, 23.4-37.6), and median overall survival (OS) was 62.5 months (95% CI, 51.7-not reached), with 16% of patients remaining on treatment after 6 years. Multivariable analysis did not identify statistically significant correlation between patient subgroups defined by clinical or laboratory variables and ORR or PFS. The most common grade ≥3 adverse events were neutropenia (42%), infections (33%), anemia (16%), and thrombocytopenia (16%). Post hoc comparative analyses of PFS and OS from treatment initiation, from a 24-month landmark, and by minimal residual disease status were performed between patients with del(17p) in the M13-982 and MURANO studies in the interest of understanding these data in another context. These long-term data show the continued benefits of venetoclax in patients with del(17p) CLL. The trial was registered at www.clinicaltrials.gov as #NCT01889186.


Asunto(s)
Leucemia Linfocítica Crónica de Células B , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Estudios de Seguimiento , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Sulfonamidas/efectos adversos , Recurrencia , Deleción Cromosómica
8.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38243850

RESUMEN

Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.


Asunto(s)
Lagartos , Melaninas , Animales , Melaninas/genética , Lagartos/genética , Pez Cebra , Regulación de la Temperatura Corporal/genética , Pigmentación de la Piel/genética , Color
9.
Plant Biotechnol J ; 22(3): 572-586, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37855813

RESUMEN

Barley yellow dwarf viruses (BYDVs) cause widespread damage to global cereal crops. Here we report a novel strategy for elevating resistance to BYDV infection. The 17K protein, a potent virulence factor conserved in BYDVs, interacted with barley IMP-α1 and -α2 proteins that are nuclear transport receptors. Consistently, a nuclear localization signal was predicted in 17K, which was found essential for 17K to be transported into the nucleus and to interact with IMP-α1 and -α2. Reducing HvIMP-α1 and -α2 expression by gene silencing attenuated BYDV-elicited dwarfism, accompanied by a lowered nuclear accumulation of 17K. Among the eight common wheat CRISPR mutants with two to four TaIMP-α1 and -α2 genes mutated, the triple mutant α1aaBBDD /α2AAbbdd and the tetra-mutant α1aabbdd /α2AAbbDD displayed strong BYDV resistance without negative effects on plant growth under field conditions. The BYDV resistance exhibited by α1aaBBDD /α2AAbbdd and α1aabbdd /α2AAbbDD was correlated with decreased nuclear accumulation of 17K and lowered viral proliferation in infected plants. Our work uncovers the function of host IMP-α proteins in BYDV pathogenesis and generates the germplasm valuable for breeding BYDV-resistant wheat. Appropriate reduction of IMP-α gene expression may be broadly useful for enhancing antiviral resistance in agricultural crops and other economically important organisms.


Asunto(s)
Luteovirus , Triticum , Triticum/genética , alfa Carioferinas/genética , Resistencia a la Enfermedad/genética , Fitomejoramiento , Luteovirus/genética , Productos Agrícolas/genética , Expresión Génica , Enfermedades de las Plantas/genética
10.
Aging Dis ; 15(2): 480-502, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37548933

RESUMEN

The gut-brain axis is a communication channel that mediates a complex interplay of intestinal flora with the neural, endocrine, and immune systems, linking gut and brain functions. Gut metabolites, a group of small molecules produced or consumed by biochemical processes in the gut, are involved in central nervous system regulation via the highly interconnected gut-brain axis affecting microglia indirectly by influencing the structure of the gut-brain axis or directly affecting microglia function and activity. Accordingly, pathological changes in the central nervous system are connected with changes in intestinal metabolite levels as well as altered microglia function and activity, which may contribute to the pathological process of each neuroinflammatory condition. Here, we discuss the mechanisms by which gut metabolites, for instance, the bile acids, short-chain fatty acids, and tryptophan metabolites, regulate the structure of each component of the gut-brain axis, and explore the important roles of gut metabolites in the central nervous system from the perspective of microglia. At the same time, we highlight the roles of gut metabolites affecting microglia in the pathogenesis of neurodegenerative diseases and neurodevelopmental disorders. Understanding the relationship between microglia, gut microbiota, neuroinflammation, and neurodevelopmental disorders will help us identify new strategies for treating neuropsychiatric disorders.


Asunto(s)
Microbioma Gastrointestinal , Enfermedades Neurodegenerativas , Humanos , Eje Cerebro-Intestino , Microglía , Encéfalo/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Microbioma Gastrointestinal/fisiología
11.
Sci Total Environ ; 912: 168992, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38052387

RESUMEN

Climate warming is expected to affect the vulnerability of sympatric species differentially due to their divergent traits, but the underlying physiological mechanisms of those impacts are poorly understood. We conducted field warming experiments (present climate vs. warm climate) using open-top chambers to determine the effects of climate warming on active body temperature, oxidative damage, immune competence, growth and survival in two sympatric desert-dwelling lizards, Eremias multiocellata and Eremias argus from May 2019 to September 2020. Our climate warming treatment did not affect survival of the two species, but it did increase active body temperatures and growth rate in E. multiocellata compared to E. argus. Climate warming also induced greater oxidative damage (higher malondialdehyde content and catalase activity) in E. multiocellata, but not in E. argus. Further, climate warming increased immune competence in E. multiocellata, but decreased immune competence in E. argus, with regards to white blood cell counts, bacteria killing ability and relative expression of immunoglobulin M. Our results suggest that climate warming enhances body temperature, and thereby oxidative stress, immune competence and growth in E. multiocellata, but decreases immune competence of E. argus, perhaps as a cost of thermoregulation to maintain body temperatures under climate warming. The divergent physiological effects of climate warming on sympatric species may have profound ecological consequences if it eventually leads to changes in reproductive activities, population dynamics and community structure. Our study highlights the importance of considering interspecific differences in physiological traits when we evaluate the impact of climate warming on organisms, even for those closely-related species coexisting within the same geographical area.


Asunto(s)
Lagartos , Animales , Lagartos/fisiología , Simpatría , Clima , Temperatura Corporal , Regulación de la Temperatura Corporal , Cambio Climático , Temperatura
12.
ACS Med Chem Lett ; 14(12): 1647-1655, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38116441

RESUMEN

iNKT cells are a type of T lymphocyte that recognizes glycolipid antigens presented by CD1d protein. αGC is an agonistic glycolipid that activates iNKT cells and triggers immune modulatory cytokine responses, making it a promising vaccine adjuvant. To find more potent immunostimulating glycolipids, we prepared 4,6-O-galactosyl conformationally restricted analogues of αGC. Mice vaccinated with the SARS-CoV-2 RBD-Fc vaccine adjuvanted with these newly developed glycolipids produced robust anti-RBD antibody responses, comparable to those achieved with αGC. Importantly, we also found that omitting αGC, α-C-GalCer (Th1-type agonist), or C20:2 (Th2-type agonist) from the booster vaccine had negligible impact on antibody and cellular responses, potentially reducing the frequency of adjuvant use required to maintain potent immune responses.

13.
Mol Neurobiol ; 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37940779

RESUMEN

Alzheimer's disease (AD) is a major cause of age-related dementia, which is becoming a global health crisis. However, the pathogenesis and etiology of AD are still not fully understood. And there are no valid treatment methods or precise diagnostic tools for AD. There is increasing evidence that P2X7R expression is upregulated in AD and is involved in multiple related pathological processes such as Aß plaques, neurogenic fiber tangles, oxidative stress, and chronic neuroinflammation. This suggests that P2X7R may be a key player in the development of AD. P2X7R is a member of the ligand-gated purinergic receptor (P2X) family. It has received attention in neuroscience due to its role in a wide range of aging and age-related neurological disorders. In this review, we summarize current information on the roles of P2X7R in AD and suggest potential pharmacological interventions to slow down AD progression.

14.
Front Neurol ; 14: 1258216, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37900599

RESUMEN

Background: Frequent digital monitoring of cognition is a promising approach for assessing endpoints in prevention and treatment trials of Alzheimer's disease and related dementias (ADRD). This study evaluated the feasibility of the MIND GamePack© for recurrent semi-passive assessment of cognition across a longitudinal interval. Methods: The MIND GamePack consists of four iPad-based games selected to be both familiar and enjoyable: Word Scramble, Block Drop, FreeCell, and Memory Match. Participants were asked to play 20 min/day for 5 days (100 min) for 4 months. Feasibility of use by older adults was assessed by measuring gameplay time and game performance. We also evaluated compliance through semi-structured surveys. A linear generalized estimating equation (GEE) model was used to analyze changes in gameplay time, and a regression tree model was employed to estimate the days it took for game performance to plateau. Subjective and environmental factors associated with gameplay time and performance were examined, including daily self-reported questions of memory and thinking ability, mood, sleep, energy, current location, and distractions prior to gameplay. Results: Twenty-six cognitively-unimpaired older adults participated (mean age ± SD = 71.9 ± 8.6; 73% female). Gameplay time remained stable throughout the 4-months, with an average compliance rate of 91% ± 11% (1946 days of data across all participants) and weekly average playtime of 210 ± 132 min per participant. We observed an initial learning curve of improving game performance which on average, plateaued after 22-39 days, depending on the game. Higher levels of self-reported memory and thinking ability were associated with more gameplay time and sessions. Conclusion: MIND GamePack is a feasible and well-designed semi-passive cognitive assessment platform which may provide complementary data to traditional neuropsychological testing in research on aging and dementia.

15.
Proc Biol Sci ; 290(2009): 20231768, 2023 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-37876201

RESUMEN

Climate change often includes increases in the occurrence of extreme environmental events. Among these, heatwaves affect the pace of life and performance of wildlife, particularly ectothermic animals, owing to their low thermoregulatory abilities. However, the underlying mechanisms by which this occurs remain unclear. Evidence shows that heatwaves alter the redox balance of ectotherms, and oxidative stress is a major mediator of life-history trade-offs. Therefore, oxidative stress may mediate the effect of extreme thermal conditions on the life histories of ectotherms. To test this hypothesis, a 2 × 2 experiment was conducted to manipulate the redox balance (through a mitochondrial uncoupler that alleviates oxidative stress) of the desert toad-headed agama (Phrynocephalus przewalskii) exposed to heatwave conditions. We recorded lizard growth and survival rates and quantified their redox and immune statuses. In control lizards (unmanipulated redox balance), heatwave conditions decreased growth and survival and induced oxidative damage and immune responses. By contrast, lizards with alleviated oxidative stress showed close-to-normal growth, survival, and immune status when challenged with heatwaves. These results provide mechanistic insight into the role of oxidative stress in mediating the effects of extreme temperatures on ectothermic vertebrates, which may have major eco-evolutionary implications.


Asunto(s)
Lagartos , Animales , Lagartos/fisiología , Calor , Cambio Climático , Regulación de la Temperatura Corporal , Estrés Oxidativo
16.
medRxiv ; 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37693466

RESUMEN

Genes on the X-chromosome are extensively expressed in the human brain, resulting in substantial influences on brain development, intellectual disability, and other brain-related disorders. To comprehensively investigate the X-chromosome's impact on the cerebral cortex, white matter tract microstructures, and intrinsic and extrinsic brain functions, we examined 2,822 complex brain imaging traits obtained from n=34,000 subjects in the UK Biobank. We unveiled potential autosome-X-chromosome interaction, while proposing an atlas of dosage compensation (DC) for each set of traits. We observed a pronounced X-chromosome impact on the corticospinal tract and the functional amplitude and connectivity of visual networks. In association studies, we identified 50 genome-wide significant trait-locus pairs enriched in Xq28, 22 of which replicated in independent datasets (n=4,900). Notably, 13 newly identified pairs were in the X-chromosome's non-pseudo-autosomal regions (NPR). The volume of the right ventral diencephalon shared genetic architecture with schizophrenia and educational attainment in a locus indexed by rs2361468 (located ~3kb upstream of PJA1, a conserved and ubiquitously expressed gene implicated in multiple psychiatric disorders). No significant associations were identified in the pseudo-autosomal regions (PAR) or the Y-chromosome. Finally, we explored sex-specific associations on the X-chromosome and compared differing genetic effects between sexes. We found much more associations can be identified in males (33 versus 9) given a similar sample size. In conclusion, our research provides invaluable insights into the X-chromosome's role in the human brain, contributing to the observed sex differences in brain structure and function.

17.
Heliyon ; 9(8): e18543, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37600369

RESUMEN

Acute ischemic stroke (AIS) is the second leading cause of death worldwide. This study aims at assessing platelet morphology, ultrastructure and function changes of platelets in acute ischemic stroke (AIS) patients by the technique of Structured Illumination Microscopy (SIM). This assay collected platelet-rich plasma (PRP) from 11 AIS patients and 12 healthy controls. Each PRP sample was divided into 7 groups:1) rest group; 2) Thrombin-treated 5 min group; 3) Thrombin plus 2MeSAMP-treated 5 min group; 4) Thrombin plus Aspirin-treated 5 min group; 5) Thrombin-treated 1 h group; 6) Thrombin plus 2MeSAMP-treated 1 h group; 7) Thrombin plus Aspirin-treated 1 h group. SIM was applied to observe dense granules and α-granules morphology changes of platelet in AIS patients. FIJI was used to quantify the image data. We finally observed 1448 images of platelets within the 7 groups. In rest group, 7162 platelets were calculated platelet diameter, CD63 dots, average CD63-positive dots area, CD63-positive area per platelet, CD63-positive area Fov, VWF dots, average VWF-positive dots area, VWF-positive area per platelet and VWF-positive area Fov. ELISA was used to detect release of platelet factor 4 (PF4) of α-granules. The results showed that AIS patients had lower number and smaller area of platelet granules. Platelet α-granules of AIS patients concentrated to parenchymal-like fluorescent blocks in Thrombin-treated 1 h group. Antiplatelet drug treatment could reverse the concentration of platelets α-granules, and 2MeSAMP was more powerful than Aspirin in vitro. This study complemented detail information of platelet ultrastructure of AIS patients, provided a new perspective on the pathogenesis of AIS and the mechanism of antiplatelet drugs based on SIM and provided a reference for future related studies. SIM-based analysis of platelet ultrastructure may be useful for detecting antiplatelet drugs and AIS in the future.

18.
Braz J Microbiol ; 54(3): 1935-1942, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37581711

RESUMEN

A new Lysinibacillus fusiformis strain with abundant laccase activity was isolated from soil under forest rotted leaf and identified as L. fusiformis W11 based on its 16S rRNA gene sequence and physiological characteristics. The laccase LfuLac was purified and characterized. The optimum temperature and pH of LfuLac on guaiacol were 45 °C and pH 9, respectively. LfuLac kept 78%, 88%, 92%, 74%, and 47% of activity at pH 7-11, respectively, suggesting the alkali resistance of the enzyme. The effects of various metal ions on LfuLac showed that Cu2+, Mg2+, and Na+ were beneficial to laccase activity and 10 mM Cu2+ increased the activity of LfuLac to 216%. LfuLac showed about 90% activity at 5% organic solvents and more than 60% activity at 20%, indicating its resistance to organic solvents. In addition, LfuLac decolorized different kinds of dyes. This study enriched our knowledge about laccase from L. fusiformis W11 and its potential industrial applications.


Asunto(s)
Bacillaceae , Colorantes , Lacasa , Álcalis , Colorantes/química , Concentración de Iones de Hidrógeno , Lacasa/química , Lacasa/genética , Lacasa/aislamiento & purificación , ARN Ribosómico 16S/genética , Solventes , Temperatura , Bacillaceae/enzimología
19.
Trends Microbiol ; 31(12): 1251-1261, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37453843

RESUMEN

Plant reoviruses, transmitted only by insect vectors, seriously threaten global cereal production. Understanding how insect vectors efficiently transmit the viruses is key to controlling the viral diseases. Autophagy commonly plays important roles in plant host defense against virus infection, but recent studies have shown that plant reoviruses can hijack the autophagy pathway in insect cells to enable their persistence in the insect and continued transmission to plants. Here, we summarize and discuss new insights on viral activation, evasion, regulation, and manipulation of autophagy within the insect vectors and the role of autophagy in virus survival in insect vectors. Deeper knowledge of the functions of autophagy in vectors may lead to novel strategies for blocking transmission of insect-borne plant viruses.


Asunto(s)
Enfermedades de las Plantas , Reoviridae , Animales , Insectos Vectores , Insectos , Reoviridae/fisiología , Plantas , Autofagia
20.
Virology ; 585: 61-71, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37295338

RESUMEN

China is the leading country for pumpkin production in the world. As other cucurbits, diseases caused by viruses are among the serious threats to pumpkin production, but our knowledge on the virus species infecting pumpkin plants is fragmentary. To understand the occurrence of viral diseases on pumpkin, we determined the geographical distribution characteristics, relative abundance and evolutionary relationship of pumpkin infected viruses by meta-transcriptome sequencing (RNA-seq) and viromic analysis of 159 samples exhibited typical viral symptoms collected across China in this study. Totally, 11 known and 3 new viruses were identified. Interestingly, 3 new viruses identified in this study should be positive-sense single-stranded RNA virus whose hosts are prokaryotes. The viruses identified in different sampling locations exhibit significant variations in term of virus species and relative abundance. Here, the results provide valuable information for understanding the virus species and their diversity in cultivated pumpkin across major growing regions of China.


Asunto(s)
Cucurbita , Virus , Filogenia , China
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