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1.
Sci Total Environ ; 932: 173047, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38723957

RESUMEN

This research was designed to estimate the contributions of phosphorus (P) in different factions from an upstream plain river network to algal growth in a downstream shallow eutrophic lake, Taihu Lake, in China. During three flow regimes, the P fractions in multiple phases (particulate, colloidal and dissolved phases) and their algal availabilities were assessed via bioassays with Dolichospermum flos-aquae as the test organism. The P partitioning patterns among multiple phases were strongly affected by the concentration of total suspended solids (TSS) that changed with the river flow regime, with stronger disturbance of sediments at lower water levels (low flow) and weaker disturbance of sediments at higher water levels (high flow) in the plain river network. The median TSS concentration across the river network decreased from 157.4 mg/L during low flow to 31.8 mg/L during high flow, and the median particulate P concentration decreased from 0.132 mg/L to 0.093 mg/L. The particulate P contributed equally to the amount of algal available P (AAP) as did the water-mobilizable P (colloidal plus dissolved phase) in the rivers flowing into Taihu Lake. The annual average concentrations of particulate algal available P (P-AAP), colloidal algal available P (C-AAP) and dissolved algal available P (D-AAP) were estimated to be 0.032 mg/L, 0.012 mg/L and 0.019 mg/L, respectively, during 2012-2018, accounting for 50.8 %, 19.0 % and 30.2 %, respectively, of the total AAP. At the watershed scale, controlling P drainage from downstream urbanized areas should be emphasized. Additionally, controlling sediment resuspension or reducing the TSS concentration in the inflowing rivers is important for decreasing the particulate P flux to downstream lakes.

2.
Nat Commun ; 15(1): 3946, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38729950

RESUMEN

Disease modeling with isogenic Induced Pluripotent Stem Cell (iPSC)-differentiated organoids serves as a powerful technique for studying disease mechanisms. Multiplexed coculture is crucial to mitigate batch effects when studying the genetic effects of disease-causing variants in differentiated iPSCs or organoids, and demultiplexing at the single-cell level can be conveniently achieved by assessing natural genetic barcodes. Here, to enable cost-efficient time-series experimental designs via multiplexed bulk and single-cell RNA-seq of hybrids, we introduce a computational method in our Vireo Suite, Vireo-bulk, to effectively deconvolve pooled bulk RNA-seq data by genotype reference, and thereby quantify donor abundance over the course of differentiation and identify differentially expressed genes among donors. Furthermore, with multiplexed scRNA-seq and bulk RNA-seq, we demonstrate the usefulness and necessity of a pooled design to reveal donor iPSC line heterogeneity during macrophage cell differentiation and to model rare WT1 mutation-driven kidney disease with chimeric organoids. Our work provides an experimental and analytic pipeline for dissecting disease mechanisms with chimeric organoids.


Asunto(s)
Diferenciación Celular , Células Madre Pluripotentes Inducidas , Organoides , RNA-Seq , Análisis de la Célula Individual , Organoides/metabolismo , Análisis de la Célula Individual/métodos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Humanos , Diferenciación Celular/genética , RNA-Seq/métodos , Análisis de Secuencia de ARN/métodos , Macrófagos/metabolismo , Macrófagos/citología , Animales , Análisis de Expresión Génica de una Sola Célula
3.
Int J Mol Sci ; 25(9)2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38731915

RESUMEN

The mammalian pituitary gland drives highly conserved physiological processes such as somatic cell growth, pubertal transformation, fertility, and metabolism by secreting a variety of hormones. Recently, single-cell transcriptomics techniques have been used in pituitary gland research. However, more studies have focused on adult pituitary gland tissues from different species or different sexes, and no research has yet resolved cellular differences in pituitary gland tissue before and after sexual maturation. Here, we identified a total of 15 cell clusters and constructed single-cell transcriptional profiles of rats before and after sexual maturation. Furthermore, focusing on the gonadotrope cluster, 106 genes were found to be differentially expressed before and after sexual maturation. It was verified that Spp1, which is specifically expressed in gonadotrope cells, could serve as a novel marker for this cell cluster and has a promotional effect on the synthesis and secretion of follicle-stimulating hormone. The results provide a new resource for further resolving the regulatory mechanism of pituitary gland development and pituitary hormone synthesis and secretion.


Asunto(s)
Gonadotrofos , Hipófisis , Maduración Sexual , Análisis de la Célula Individual , Animales , Ratas , Maduración Sexual/genética , Hipófisis/metabolismo , Gonadotrofos/metabolismo , Análisis de la Célula Individual/métodos , Masculino , Femenino , Biomarcadores/metabolismo , Transcriptoma , Perfilación de la Expresión Génica , Hormona Folículo Estimulante/metabolismo
4.
Int Immunopharmacol ; 134: 112141, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38733819

RESUMEN

BACKGROUND: Novel coronaviruses constitute a significant health threat, prompting the adoption of vaccination as the primary preventive measure. However, current evaluations of immune response and vaccine efficacy are deemed inadequate. OBJECTIVES: The study sought to explore the evolving dynamics of immune response at various vaccination time points and during breakthrough infections. It aimed to elucidate the synergistic effects of epidemiological factors, humoral immunity, and cellular immunity. Additionally, regression curves were used to determine the correlation between the protective efficacy of the vaccine and the stimulated immune response. METHODS: Employing LASSO for high-dimensional data analysis, the study utilised four machine learning algorithms-logistical regression, random forest, LGBM classifier, and AdaBoost classifier-to comprehensively assess the immune response following booster vaccination. RESULTS: Neutralising antibody levels exhibited a rapid surge post-booster, escalating to 102.38 AU/mL at one week and peaking at 298.02 AU/mL at two weeks. Influential factors such as sex, age, disease history, and smoking status significantly impacted post-booster antibody levels. The study further constructed regression curves for neutralising antibodies, non-switched memory B cells, CD4+T cells, and CD8+T cells using LASSO combined with the random forest algorithm. CONCLUSION: The establishment of an artificial intelligence evaluation system emerges as pivotal for predicting breakthrough infection prognosis after the COVID-19 booster vaccination. This research underscores the intricate interplay between various components of immunity and external factors, elucidating key insights to enhance vaccine effectiveness. 3D modelling discerned distinctive interactions between humoral and cellular immunity within prognostic groups (Class 0-2). This underscores the critical role of the synergistic effect of humoral immunity, cellular immunity, and epidemiological factors in determining the protective efficacy of COVID-19 vaccines post-booster administration.

5.
Heliyon ; 10(9): e30378, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707441

RESUMEN

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P < 0.05), and hemodynamics and SpO2 were more stable during sedation (P < 0.05). Conclusion: There was no significant difference between propofol and ciprofol in terms of euphoria experienced by patients after sedation in patients undergoing gastroscopy. Ciprofol has demonstrated addictive potential similar to that of propofol, warranting careful attention to its addictive potential during clinical application.

6.
Biochem Biophys Res Commun ; 716: 150038, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38704891

RESUMEN

Hyperuricemia (HUA) is caused by increased synthesis and/or insufficient excretion of uric acid (UA). Long-lasting HUA may lead to a number of diseases including gout and kidney injury. Harpagoside (Harp) is a bioactive compound with potent anti-inflammatory activity from the roots of Scrophularia ningpoensis. Nevertheless, its potential effect on HUA was not reported. The anti-HUA and nephroprotective effects of Harp on HUA mice were assessed by biochemical and histological analysis. The proteins responsible for UA production and transportation were investigated to figure out its anti-HUA mechanism, while proteins related to NF-κB/NLRP3 pathway were evaluated to reveal its nephroprotective mechanism. The safety was evaluated by testing its effect on body weight and organ coefficients. The results showed that Harp significantly reduced the SUA level and protected the kidney against HUA-induced injury but had no negative effect on safety. Mechanistically, Harp significantly reduced UA production by acting as inhibitors of xanthine oxidase (XOD) and adenosine deaminase (ADA) and decreased UA excretion by acting as activators of ABCG2, OAT1 and inhibitors of GLUT9 and URAT1. Moreover, Harp markedly reduced infiltration of inflammatory cells and down-regulated expressions of TNF-α, NF-κB, NLRP3 and IL-1ß in the kidney. Harp was a promising anti-HUA agent.

8.
Alzheimers Res Ther ; 16(1): 95, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693554

RESUMEN

BACKGROUND: Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology of Alzheimer's disease (AD). The natural psychedelic N, N-dimethyltryptamine (DMT) is a Sig-1r agonist that may have the anti-AD potential through protecting neuronal ER-mitochondrial interplay. METHODS: 3×TG-AD transgenic mice were administered with chronic DMT (2 mg/kg) for 3 weeks and then performed water maze test. The Aß accumulation in the mice brain were determined. The Sig-1r level upon DMT treatment was tested. The effect of DMT on the ER-mitochondrial contacts site and multiple mitochondria-associated membrane (MAM)-associated proteins were examined. The effect of DMT on calcium transport between ER and mitochondria and the mitochondrial function were also evaluated. RESULTS: chronic DMT (2 mg/kg) markedly alleviated cognitive impairment of 3×TG-AD mice. In parallel, it largely diminished Aß accumulation in the hippocampus and prefrontal cortex. DMT restored the decreased Sig-1r levels of 3×TG-AD transgenic mice. The hallucinogen reinstated the expression of multiple MAM-associated proteins in the brain of 3×TG-AD mice. DMT also prevented physical contact and calcium dynamic between the two organelles in in vitro and in vivo pathological circumstances. DMT modulated oxidative phosphorylation (OXPHOS) and ATP synthase in the in vitro model of AD. CONCLUSION: The anti-AD effects of DMT are associated with its protection of neuronal ER-mitochondria crosstalk via the activation of Sig-1r. DMT has the potential to serve as a novel preventive and therapeutic agent against AD.


Asunto(s)
Enfermedad de Alzheimer , Retículo Endoplásmico , Alucinógenos , Ratones Transgénicos , Mitocondrias , N,N-Dimetiltriptamina , Receptores sigma , Receptor Sigma-1 , Animales , Receptores sigma/metabolismo , Receptores sigma/agonistas , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ratones , Alucinógenos/farmacología , N,N-Dimetiltriptamina/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Masculino
9.
J Cell Mol Med ; 28(9): e18350, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38700030

RESUMEN

Mechanical force induces hypoxia in the pulpal area by compressing the apical blood vessels of the pulp, triggering pulpal inflammation during orthodontic tooth movement. However, this inflammation tends to be restorable. Macrophages are recognized as pivotal immunoreactive cells in the dental pulp. Whether they are involved in the resolution of pulpal inflammation in orthodontic teeth remains unclear. In this study, we investigated macrophage polarization and its effects during orthodontic tooth movement. It was demonstrated that macrophages within the dental pulp polarized to M2 type and actively participated in the process of pulpal inflammation resolution. Inflammatory reactions were generated and vascularization occurred in the pulp during orthodontic tooth movement. Macrophages in orthodontic pulp show a tendency to polarize towards M2 type as a result of pulpal hypoxia. Furthermore, by blocking M2 polarization, we found that macrophage M2 polarization inhibits dental pulp-secreting inflammatory factors and enhances VEGF production. In conclusion, our findings suggest that macrophages promote pulpal inflammation resolution by enhancing M2 polarization and maintaining dental health during orthodontic tooth movement.


Asunto(s)
Pulpa Dental , Inflamación , Macrófagos , Técnicas de Movimiento Dental , Pulpa Dental/metabolismo , Pulpa Dental/patología , Animales , Macrófagos/metabolismo , Inflamación/patología , Inflamación/metabolismo , Ratones , Polaridad Celular , Masculino , Factor A de Crecimiento Endotelial Vascular/metabolismo , Pulpitis/patología , Pulpitis/metabolismo , Activación de Macrófagos
10.
J Chem Inf Model ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743449

RESUMEN

Antifungal peptides (AFPs) are emerging as promising candidates for advanced antifungal therapies because of their broad-spectrum efficacy and reduced resistance development. In silico design of AFPs, however, remains challenging, due to the lack of an efficient and well-validated quantitative assessment of antifungal activity. This study introduced an AFP design approach that leverages an innovative quantitative metric, named the antifungal index (AFI), through a three-step process, i.e., segmentation, single-point mutation, and global multipoint optimization. An exhaustive search of 100 putative AFP sequences indicated that random modifications without guidance only have a 5.97-20.24% chance of enhancing antifungal activity. Analysis of the search results revealed that (1) N-terminus truncation is more effective in enhancing antifungal activity than the modifications at the C-terminus or both ends, (2) introducing the amino acids within the 10-60% sequence region that enhance aromaticity and hydrophobicity are more effective in increasing antifungal efficacy, and (3) incorporating alanine, cysteine, and phenylalanine during multiple point mutations has a synergistic effect on enhancing antifungal activity. Subsequently, 28 designed peptides were synthesized and tested against four typical fungal strains. The success rate for developing promising AFPs, with a minimal inhibitory concentration of ≤5.00 µM, was an impressive 82.14%. The predictive and design tool is accessible at https://antifungipept.chemoinfolab.com.

11.
ACS Nano ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38743777

RESUMEN

Chiral materials possess broken inversion and mirror symmetry and show great potential in the application of next-generation optic, electronic, and spintronic devices. Two-dimensional (2D) chiral crystals have planar chirality, which is nonsuperimposable on their 2D enantiomers by any rotation about the axis perpendicular to the substrate. The degree of freedom to construct vertical stacking of 2D monolayer enantiomers offers the possibility of chiral manipulation for designed properties by creating multilayers with either a racemic or enantiomerically pure stacking order. However, the rapid recognition of the relative proportion of two enantiomers becomes demanding due to the complexity of stacking orders of 2D chiral crystals. Here, we report the unambiguous identification of racemic and enantiomerically pure stackings for layered ReSe2 and ReS2 using circular polarized Raman spectroscopy. The chiral Raman response is successfully manipulated by the enantiomer proportion, and the stacking orders of multilayer ReSe2 and ReS2 can be completely clarified with the help of second harmonic generation and scanning transmission electron microscopy measurements. Finally, we trained an artificial intelligent Spectra Classification Assistant to predict the chirality and the complete crystallographic structures of multilayer ReSe2 from a single circular polarized Raman spectrum with the accuracy reaching 0.9417 ± 0.0059.

12.
Signal Transduct Target Ther ; 9(1): 133, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38744811

RESUMEN

Sirtuin 3 (SIRT3) is well known as a conserved nicotinamide adenine dinucleotide+ (NAD+)-dependent deacetylase located in the mitochondria that may regulate oxidative stress, catabolism and ATP production. Accumulating evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis, myocardial fibrosis and even heart failure (HF), through its deacetylation modifications. Accordingly, discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently needed. Herein, we identified a new small-molecule activator of SIRT3 (named 2-APQC) by the structure-based drug designing strategy. 2-APQC was shown to alleviate isoproterenol (ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat models. Importantly, in SIRT3 knockout mice, 2-APQC could not relieve HF, suggesting that 2-APQC is dependent on SIRT3 for its protective role. Mechanically, 2-APQC was found to inhibit the mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (p70S6K), c-jun N-terminal kinase (JNK) and transforming growth factor-ß (TGF-ß)/ small mother against decapentaplegic 3 (Smad3) pathways to improve ISO-induced cardiac hypertrophy and myocardial fibrosis. Based upon RNA-seq analyses, we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1 (PYCR1) axis was closely assoiated with HF. By activating PYCR1, 2-APQC was shown to enhance mitochondrial proline metabolism, inhibited reactive oxygen species (ROS)-p38 mitogen activated protein kinase (p38MAPK) pathway and thereby protecting against ISO-induced mitochondrialoxidative damage. Moreover, activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase (AMPK)-Parkin axis to inhibit ISO-induced necrosis. Together, our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis, which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.


Asunto(s)
Cardiomegalia , Fibrosis , Sirtuina 3 , Animales , Sirtuina 3/genética , Sirtuina 3/metabolismo , Cardiomegalia/genética , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/patología , Cardiomegalia/inducido químicamente , Cardiomegalia/metabolismo , Fibrosis/genética , Ratas , Ratones , Isoproterenol , Humanos , Ratones Noqueados , Homeostasis/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/genética , Mitocondrias/patología , Mitocondrias/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/genética , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Miocardio/patología , Miocardio/metabolismo , Masculino
13.
IEEE Trans Cybern ; PP2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713576

RESUMEN

This article is concerned with the prescribed performance tracking control problem for the strict-feedback systems with unknown nonlinearities and unmatched disturbances. The challenge lies in the realization of a complete performance specification for trajectory tracking in the sense of quantitatively regulating the peak value, overshoot, settling time, and accuracy while ensuring that the initial condition holds naturally. To this end, an error transformation, equipped with a shifting function, is introduced and incorporated with a new-type barrier function. Then, a class of performance functions is exploited to quantify the settling times and steady-state bounds of the intermediate errors. Moreover, to improve the flexibility of formulating performance specifications for the tracking error, a pair of asymmetric performance boundaries are further designed. With their combination, a novel robust prescribed performance control (PPC) approach is proposed in this article. It not only achieves the quantitative performance guarantees but also preserves the unique simplicity of PPC, evading the needs for function approximation, parameter identification, disturbance estimation, derivative calculation, or command filtering. The above theoretical findings are confirmed via three simulation studies.

14.
Int J Nanomedicine ; 19: 3773-3804, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38708181

RESUMEN

Geriatric diseases are a group of diseases with unique characteristics related to senility. With the rising trend of global aging, senile diseases now mainly include endocrine, cardiovascular, neurodegenerative, skeletal, and muscular diseases and cancer. Compared with younger populations, the structure and function of various cells, tissues and organs in the body of the elderly undergo a decline as they age, rendering them more susceptible to external factors and diseases, leading to serious tissue damage. Tissue damage presents a significant obstacle to the overall health and well-being of older adults, exerting a profound impact on their quality of life. Moreover, this phenomenon places an immense burden on families, society, and the healthcare system.In recent years, stem cell-derived exosomes have become a hot topic in tissue repair research. The combination of these exosomes with biomaterials allows for the preservation of their biological activity, leading to a significant improvement in their therapeutic efficacy. Among the numerous biomaterial options available, hydrogels stand out as promising candidates for loading exosomes, owing to their exceptional properties. Due to the lack of a comprehensive review on the subject matter, this review comprehensively summarizes the application and progress of combining stem cell-derived exosomes and hydrogels in promoting tissue damage repair in geriatric diseases. In addition, the challenges encountered in the field and potential prospects are presented for future advancements.


Asunto(s)
Exosomas , Hidrogeles , Células Madre , Exosomas/química , Humanos , Hidrogeles/química , Anciano , Envejecimiento/fisiología , Animales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Geriatría
15.
PhytoKeys ; 241: 177-189, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721011

RESUMEN

Angiopterisnodosipetiolata Ting Wang tris, H.F.Chen & Y.H.Yan, a new fern of Marattiaceae, is described and illustrated. Morphologically, A.nodosipetiolata is similar to A.chingii with more than one naked pulvinus on the stipe and numerous jointed hairs on the undersides of the mature pinnae. However, the pinnae of A.nodosipetiolata are lanceolate and can reach up to 4-6 pairs, whereas they are elliptic and occur in 2-3 pairs in A.chingii. Phylogenetic and genetic distance analysis, based on the plastid genomes, also indicates that A.nodosipetiolata is not closely related to A.chingii. Currently, there are ca. 500 mature individuals in Gulinqing Nature Reserve and we suggest A.nodosipetiolata should be categorised as an Endangered (EN) species according to the criteria of IUCN.

16.
Sci Total Environ ; 931: 172938, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38703850

RESUMEN

Cadmium (Cd) is a widely distributed typical environmental pollutant and one of the most toxic heavy metals. It is well-known that environmental Cd causes testicular damage by inducing classic types of cell death such as cell apoptosis and necrosis. However, as a new type of cell death, the role and mechanism of pyroptosis in Cd-induced testicular injury remain unclear. In the current study, we used environmental Cd to generate a murine model with testicular injury and AIM2-dependent pyroptosis. Based on the model, we found that increased cytoplasmic mitochondrial DNA (mtDNA), activated mitochondrial proteostasis stress occurred in Cd-exposed testes. We used ethidium bromide to generate mtDNA-deficient testicular germ cells and further confirmed that increased cytoplasmic mtDNA promoted AIM2-dependent pyroptosis in Cd-exposed cells. Uracil-DNA glycosylase UNG1 overexpression indicated that environmental Cd blocked UNG-dependent repairment of damaged mtDNA to drive the process in which mtDNA releases to cytoplasm in the cells. Interestingly, we found that environmental Cd activated mitochondrial proteostasis stress by up-regulating protein expression of LONP1 in testes. Testicular specific LONP1-knockdown significantly reversed Cd-induced UNG1 protein degradation and AIM2-dependent pyroptosis in mouse testes. In addition, environmental Cd significantly enhanced the m6A modification of Lonp1 mRNA and its stability in testicular germ cells. Knockdown of IGF2BP1, a reader of m6A modification, reversed Cd-induced upregulation of LONP1 protein expression and pyroptosis activation in testicular germ cells. Collectively, environmental Cd induces m6A modification of Lonp1 mRNA to activate mitochondrial proteostasis stress, increase cytoplasmic mtDNA content, and trigger AIM2-dependent pyroptosis in mouse testes. These findings suggest that mitochondrial proteostasis stress is a potential target for the prevention of testicular injury.

17.
J Phys Chem Lett ; : 5177-5182, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38717311

RESUMEN

Exciton dynamics of perovskite nanoclusters has been investigated for the first time using femtosecond transient absorption (TA) and time-resolved photoluminescence (TRPL) spectroscopy. The TA results show two photoinduced absorption signals at 420 and 461 nm and a photoinduced bleach (PB) signal at 448 nm. The analysis of the PB recovery kinetic decay and kinetic model uncovered multiple processes contributing to electron-hole recombination. The fast component (∼8 ps) is attributed to vibrational relaxation within the initial excited state, and the medium component (∼60 ps) is attributed to shallow carrier trapping. The slow component is attributed to deep carrier trapping from the initial conduction band edge (∼666 ps) and the shallow trap state (∼40 ps). The TRPL reveals longer time dynamics, with modeled lifetimes of 6.6 and 93 ns attributed to recombination through the deep trap state and direct band edge recombination, respectively. The significant role of exciton trapping processes in the dynamics indicates that these highly confined nanoclusters have defect-rich surfaces.

18.
Nat Med ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693247

RESUMEN

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.

19.
Sci Data ; 11(1): 438, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698068

RESUMEN

The Bethylidae are the most diverse of Hymenoptera chrysidoid families. As external parasitoids, the bethylids have been widely adopted as biocontrol agents to control insect pests worldwide. Thus far, the genomic information of the family Bethylidae has not been reported yet. In this study, we crystallized into a high-quality chromosome-level genome of ant-like bethylid wasps Sclerodermus sp. 'alternatusi' (Hymenoptera: Bethylidae) using PacBio sequencing as well as Hi-C technology. The assembled S. alternatusi genome was 162.30 Mb in size with a contig N50 size of 3.83 Mb and scaffold N50 size of 11.10 Mb. Totally, 92.85% assembled sequences anchored to 15 pseudo-chromosomes. A total of 10,204 protein-coding genes were annotated, and 23.01 Mb repetitive sequences occupying 14.17% of genome were pinpointed. The BUSCO results showed that 97.9% of the complete core Insecta genes were identified in the genome, while 97.1% in the gene sets. The high-quality genome of S. alternatusi will not only provide valuable genomic information, but also show insights into parasitoid wasp evolution and bio-control application in future studies.


Asunto(s)
Genoma de los Insectos , Avispas , Animales , Avispas/genética , Cromosomas de Insectos/genética
20.
Artículo en Inglés | MEDLINE | ID: mdl-38709610

RESUMEN

The Transformer has been successfully used in medical image segmentation due to its excellent long-range modeling capabilities. However, patch segmentation is necessary when building a Transformer class model. This process ignores the tissue structure features within patch, resulting in the loss of shallow representation information. In this study, we propose a Heterogeneous Swin Transformer with Multi-Receptive Field (HST-MRF) model that fuses patch information from different receptive fields to solve the problem of loss of feature information caused by patch segmentation. The heterogeneous Swin Transformer (HST) is the core module, which achieves the interaction of multi-receptive field patch information through heterogeneous attention and passes it to the next stage for progressive learning, thus complementing the patch structure information. We also designed a two-stage fusion module, multimodal bilinear pooling (MBP), to assist HST in further fusing multi-receptive field information and combining low-level and high-level semantic information for accurate localization of lesion regions. In addition, we developed adaptive patch embedding (APE) and soft channel attention (SCA) modules to retain more valuable information when acquiring patch embedding and filtering channel features, respectively, thereby improving model segmentation quality. We evaluated HST-MRF on multiple datasets for polyp, skin lesion and breast ultrasound segmentation tasks. Experimental results show that our proposed method outperforms state-of-the-art models and can achieve superior performance. Furthermore, we verified the effectiveness of each module and the benefits of multi-receptive field segmentation in reducing the loss of structural information through ablation experiments and qualitative analysis.

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