RESUMEN

A novel electrocatalytic dimerization of o-aminphenols and a hydrogen borrowing-like cascade for synthesizing N-monoalkylated aminophenoxazinones have been developed. This electrocatalytic reaction uses a constant current mode in an undivided cell and is free of metal catalysis, open to the air, and eco-friendly. In particular, this protocol exhibits a wide substrate range and provides versatile N-monoalkylated aminophenoxazinones in medium to good yields. The results of our mechanistic research reveal that this protocol involves a cascade of electrochemical cyclocondensation of o-aminphenols and the hydrogen transfer process via paired electrolysis.

RESUMEN

Bioenergy decline occurs with reperfusion following acute ischemic stroke. However, the molecular mechanisms that limit energy metabolism and their impact on post-stroke cognitive and emotional complications are still unclear. In the present study, we demonstrate that the p53 transcriptional response is responsible for neuronal adenosine triphosphate (ATP) deficiency and progressively neuropsychiatric disturbances, involving the downregulation of mitochondrial voltage-dependent anion channels (VDACs). Neuronal p53 transactivated the promoter of microRNA-183 (miR-183) cluster, thereby upregulating biogenesis of miR-183-5p (miR-183), miR-96-5p (miR-96), and miR-182-5p. Both miR-183 and miR-96 directly targeted and post-transcriptionally suppressed VDACs. Neuronal ablation of p53 protected against ATP deficiency and neurological deficits, whereas post-stroke rescue of miR-183/VDAC signaling reversed these benefits. Interestingly, cyclin-dependent kinase 9 (CDK9) was found to be enriched in cortical neurons and upregulated the p53-induced transcription of the miR-183 cluster in neurons after ischemia. Post-treatment with the CDK9 inhibitor oroxylin A promoted neuronal ATP production mainly through suppressing the miR-183 cluster/VDAC axis, further improved long-term sensorimotor abilities and spatial memory, and alleviated depressive-like behaviors in mice following stroke. Our findings reveal an intrinsic CDK9/p53/VDAC pathway that drives neuronal bioenergy decline and underlies post-stroke cognitive impairment and depression, thus highlighting the therapeutic potential of oroxylin A for better outcomes.

Asunto(s)

RESUMEN

OBJECTIVES: To investigate the therapeutic effect and mechanism of Danggui Buxue Tang in the treatment of biceps longus tendon lesions, and to preliminarily explore the relevant factors affecting this injury. METHODS: Using network pharmacology analysis methods, the potential mechanism of Danggui Buxue Tang in treating key lesions of the long head of the biceps brachii muscle was studied. RESULTS: Model analysis revealed 44 protein-protein interactions associated with long head binding. The distribution of 19 strongly correlated targets is Pharmaper>SEA>Stitch>Swiss. Further discovery revealed 17 immune system and inflammation related KEGG pathways with P values less than 0.01. The TNF and sphingolipid signaling pathways are associated with inflammation, while the MAPK signaling pathway is associated with immunity. Finally, it was found that the FoxO and HIF-1 signaling pathways are directly associated with long head restraint injury in the biceps brachii muscle. CONCLUSION: Danggui Buxue Tang inhibits related pathways, regulates the immune system, reduces inflammation, and alleviates disease progression. Danggui Buxue Tang can be an effective choice for treating combined lesions of the long head of the biceps brachii muscle.

Asunto(s)

RESUMEN

Age-related osteoporosis manifests as a complex pathology that disrupts bone homeostasis and elevates fracture risk, yet the mechanisms facilitating age-related shifts in bone marrow macrophages/osteoclasts (BMMs/OCs) lineage are not fully understood. To decipher these mechanisms, we conducted an investigation into the determinants controlling BMMs/OCs differentiation. We performed single-cell multi-omics profiling on bone marrow samples from mice of different ages (1, 6, and 20 months) to gain a holistic understanding of cellular changes across time. Our analysis revealed that aging significantly instigates OC differentiation. Importantly, we identified Cebpd as a vital gene for osteoclastogenesis and bone resorption during the aging process. Counterbalancing the effects of Cebpd, we found Irf8, Sox4, and Klf4 to play crucial roles. By thoroughly examining the cellular dynamics underpinning bone aging, our study unveils novel insights into the mechanisms of age-related osteoporosis and presents potential therapeutic targets for future exploration.

RESUMEN

The dehydro-Diels-Alder (DDA) reaction is a powerful method for the construction of aromatic compounds. However, the enantioselective DDA reaction has been rarely developed, probably due to the competitive thermal reaction. Herein, we report a copper-catalyzed enantioselective DDA reaction through vinyl cation pathway. The reaction leads to the atom-economical synthesis of axially chiral phenyl and indolyl carbazoles in generally excellent yields with good to excellent atroposelectivities. This methodology represents the first example of non-noble metal-catalyzed enantioselective DDA reaction. Notably, new chiral ligand and organocatalyst derived from the constructed axially chiral carbazole are demonstrated to be useful in asymmetric catalysis.

RESUMEN

Wetlands are one of the ecosystems most easily and severely invaded by alien species. Biological invasions can have significant impacts on local plant communities and ecosystem functioning. While numerous studies have assessed the impacts of biological invasions on wetlands, relatively few have been conducted in protected areas such as national wetland parks. We conducted a field survey to investigate the effects of the invasive herb Alternanthera philoxeroides (alligator weed) on the productivity and structure of plant communities and soil microbial communities in the Lishui Jiulong National Wetland Park in Zhejiang, China. We also examined the potential influence of the distance to the river edge on the impact of the alligator weed invasion. The alligator weed invasion significantly altered the plant community structure. It reduced the coverage of co-occurring plant species, including native (-31.2 %), invasive (-70.1 %), and non-invasive alien plants (-58.4 %). However, it increased species richness by 50 %, Pielou's evenness by 20 %, and Simpson's diversity index by 29.1 % for the overall plant community. Furthermore, within the community not invaded by alligator weed, increasing the distance to the river edge decreased the number of native plants by 57.0 % and the aboveground biomass of other invasive plants by 78.6 %. Contrary to expectations, no effects of the alligator weed invasion were observed on soil fungal and bacterial communities. Therefore, the impacts of the alligator weed invasion varied with spatial context and plant category, emphasizing the need to consider multiple scales and environmental factors when assessing the effects of invasive species on plant biodiversity. These insights enhance our understanding of plant invasions in wetlands and can guide the development of effective management strategies for these important ecosystems.

RESUMEN

This study aims to establish phantom-solution systems suitable for estimating doses in boron neutron capture therapy (BNCT). The phantom containing three typical solutions, H3BO3, LiOH, and Gd(NO3)3·6H2O with different concentrations and nuclide abundances have been studied since the nuclides 10B, 6Li, and 157Gd are capable of absorbing thermal neutrons. The results indicate that all three phantom-solution systems, with suitable concentrations and nuclide abundances, effectively distinguish between the nitrogen dose and the hydrogen dose for dose measurement in BNCT.

RESUMEN

Human spermatogonial stem cells (SSCs) have significant applications in reproductive medicine and regenerative medicine because of their great plasticity. Nevertheless, it remains unknown about the functions and mechanisms of long non-coding RNA (LncRNA) in regulating the fate determinations of human SSCs. Here we have demonstrated that LncRNA ACVR2B-as1 (activin A receptor type 2B antisense RNA 1) controls the self-renewal and apoptosis of human SSCs by interaction with ALDOA via glycolysis activity. LncRNA ACVR2B-as1 is highly expressed in human SSCs. LncRNA ACVR2B-as1 silencing suppresses the proliferation and DNA synthesis and enhances the apoptosis of human SSCs. Mechanistically, our ChIRP-MS and RIP assays revealed that ACVR2B-as1 interacted with ALDOA in human SSCs. High expression of ACVR2B-as1 enhanced the proliferation, DNA synthesis, and glycolysis of human SSCs but inhibited their apoptosis through up-regulation of ALDOA. Importantly, overexpression of ALDOA counteracted the effect of ACVR2B-as1 knockdown on the aforementioned biological processes. Collectively, these results indicate that ACVR2B-as1 interacts with ALDOA to control the self-renewal and apoptosis of human SSCs by enhancing glycolysis activity. This study is of great significance because it sheds a novel insight into molecular mechanisms underlying the fate decisions of human SSCs and it may offer innovative approaches to address the etiology of male infertility.

Asunto(s)

RESUMEN

BACKGROUND: Calcium-dependent protein kinase (CDPK) plays a key role in cotton tolerance to abiotic stress. However, its role in cotton heat stress tolerance is not well understood. Here, we characterize the GhCDPK gene family and their expression profiles with the aim of identifying CDPK genes associated with heat stress tolerance. RESULTS: This study revealed 48 GhCDPK members in the cotton genome, distributed on 18 chromosomes. Tree phylogenetic analysis showed three main clustering groups of the GhCDPKs. Cis-elements revealed many abiotic stress and phytohormone pathways conserved promoter regions. Similarly, analysis of the transcription factor binding sites (TFBDS) in the GhCDPK genes showed many stress and hormone related sites. The expression analysis based on qRT-PCR showed that GhCDPK16 was highly responsive to high-temperature stress. Subsequent protein-protein interactions of GhCDPK16 revealed predictable interaction with ROS generating, calcium binding, and ABA signaling proteins. Overexpression of GhCDPK16 in cotton and Arabidopsis improved thermotolerance by lowering ROS compound buildup. Under heat stress, GhCDPK16 transgenic lines upregulated heat-inducible genes GhHSP70, GHSP17.3, and GhGR1, as demonstrated by qRT-PCR analysis. Contrarily, GhCDPK16 knockout lines in cotton exhibited an increase in ROS accumulation. Furthermore, antioxidant enzyme activity was dramatically boosted in the GhCDPK16-ox transgenic lines. CONCLUSIONS: The collective findings demonstrated that GhCDPK16 could be a viable gene to enhance thermotolerance in cotton and, therefore, a potential candidate gene for improving heat tolerance in cotton.

Asunto(s)

RESUMEN

The in situ dimeric coordination of two chiral ligands bearing quinoline-2-carboxylic acid units and substituted BINOL backbones with a copper ion generates a new chiral catalyst for oxidative homo- and cross-coupling of various 2-naphthols, enabling enantioselective synthesis of a broad range of highly useful diversely substituted C2- and C1-symmetric BINOLs in up to 96% yield with good to excellent enantioselectivities (up to 98:2 e.r.).

RESUMEN

Biological ion channels usually conduct the high-flux transport of 107 ~ 108 ions·s-1; however, the underlying mechanism is still lacking. Here, by applying the KcsA potassium channel as a typical example, and performing multitimescale molecular dynamics simulations, we demonstrate that there is coherence of the K+ ions confined in biological channels, which determines transport. The coherent oscillation state of confined K+ ions with a nanosecond-level lifetime in the channel dominates each transport event, serving as the physical basis for the high flux of ~108 ions∙s-1. The coherent transfer of confined K+ ions only takes several picoseconds and has no perturbation effect on the ion coherence, acting as the directional key of transport. Such ion coherence is allowed by quantum mechanics. An increase in the coherence can significantly enhance the ion conductance. These findings provide a potential explanation from the perspective of coherence for the high-flux ion transport with ultralow energy consumption of biological channels.

Asunto(s)

RESUMEN

BACKGROUND: Hydrogen sulfide (H2S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H2S alleviates skeletal muscle ageing by regulating autophagy has not been reported. METHODS: Mice were administered 150 mg/kg/day of D-galactose ( D-gal), and C2C12 myotubes were cultured in 20 g/L D-gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H2S was quantified by the 7-azido-4-methylcoumarin fluorescence probe. The proteins involved in the ubiquitin-mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (Co-IP). S-sulfhydration of USP5 was tested by a biotin-switch assay. Associated proteins were analysed by western blot. RESULTS: NaHS was found to effectively restore the H2S content in both ageing gastrocnemius (+91.89%, P < 0.001) and C2C12 myotubes (+27.55%, P < 0.001). In comparison to the D-gal group, NaHS was observed to increase the mean cross-sectional area of muscle fibres (+44.91%, P < 0.001), to decrease the collagen volume fraction of gastrocnemius (-81.32%, P = 0.001) and to reduce the ß-galactosidase-positive area of C2C12 myotubes (-28.74%, P < 0.001). NaHS was also found to reverse the expression of muscle atrophy F box protein (MAFbx), muscle-specific RING finger protein 1 (MuRF1), Cyclin D1 and p21 in the ageing gastrocnemius tissue (MAFbx: -31.73%, P = 0.008; MuRF1: -32.37%, P = 0.003; Cyclin D1: +45.34%, P = 0.010; p21: -25.53%, P = 0.022) and C2C12 myotubes (MAFbx: -16.38%, P < 0.001; MuRF1: -16.45%, P = 0.003; Cyclin D1: +40.23%, P < 0.001; p21: -35.85%, P = 0.026). The AMPKα1-ULK1 pathway was activated and autophagy was up-regulated in NaHS-treated gastrocnemius tissue (p-AMPKα1: +61.61%, P = 0.018; AMPKα1: +30.64%, P = 0.010; p-ULK1/ULK1: +85.87%, P = 0.005; p62: -29.07%, P < 0.001; Beclin1: +24.75%, P = 0.007; light chain 3 II/I [LC3 II/I]: +55.78%, P = 0.004) and C2C12 myotubes (p-AMPKα1: +77.49%, P = 0.018; AMPKα1: +26.18%, P = 0.022; p-ULK1/ULK1: +38.34%, P = 0.012; p62: -9.02%, P = 0.014; Beclin1: +13.36%, P < 0.001; LC3 II/I: +79.38%, P = 0.017; autophagy flux: +24.88%, P = 0.034) compared with the D-gal group. The effects of NaHS on autophagy were comparable to those of acadesine and LYN-1604, and chloroquine could reverse its effects on ageing. LC-MS/MS and Co-IP experiments demonstrated that USP5 is a deubiquitinating enzyme of AMPKα1. Following the knockdown of USP5, the activation of AMPKα1 was decreased (p-AMPKα1: -42.10%, P < 0.001; AMPKα1: -43.93%, P < 0.001), autophagy was inhibited (p-ULK1/ULK1: -27.51, P = 0.001; p62: +36.00, P < 0.001; Beclin1: -22.15%, P < 0.001) and NaHS lost its ability to up-regulate autophagy. NaHS was observed to restore the expression (gastrocnemius: +62.17%, P < 0.001; C2C12 myotubes: +37.51%, P = 0.003) and S-sulfhydration (+53.07%, P = 0.009) of USP5 and reduce the ubiquitination of AMPKα1. CONCLUSIONS: H2S promotes the deubiquitination of AMPKα1 by increasing the expression and S-sulfhydration of USP5, thereby up-regulating autophagy and alleviating skeletal muscle ageing.

RESUMEN

There is growing evidence that the KDM5 family of histone demethylases plays a causal role in human cancer. However, few studies have been reported on the KDM5 family in endometrial carcinoma (EC). Moreover, it was found that there was some correlation between the KDM5 family and FOXO1 in EC. The current study was performed to explore the expressions of KDM5A, KDM5B, and FOXO1 in endometrioid adenocarcinoma detected by immunohistochemistry; paracancer endometrium, simple hyperplastic endometrium, and normal endometrium were used as control groups to explore the possible diagnostic value of KDM5A and KDM5B expression in endometrioid adenocarcinoma, with the aim of evaluating the potential of this marker in predicting the prognosis of endometrioid adenocarcinoma.

Asunto(s)

RESUMEN

The meat of local livestock breeds often has unique qualities and flavors. In this study, three Shanghai native pig breeds (MSZ, SWT, and SHB) exhibited better meat quality traits than globalized commercial pig breeds (DLY). Subsequently, metabolomic and lipidomic differences in the longissimus dorsi (L) and gluteus (T) muscles of the Shanghai native pig breeds and DLY pig breed were compared using liquid chromatography-mass spectrometry (LC-MS). The results demonstrated that the metabolites mainly consisted of (28.16%) lipids and lipid-like molecules, and (25.87%) organic acids and their derivatives were the two most dominant groups. Hundreds of differential expression metabolites were identified in every compared group, respectively. One-way ANOVA was applied to test the significance between multiple groups. Among the 20 most abundant differential metabolites, L-carnitine was significantly different in the muscles of the four pig breeds (p-value = 7.322 × 10-11). It was significantly higher in the L and T muscles of the two indigenous black pig breeds (MSZ and SWT) than in the DLY pigs (p-value < 0.001). Similarly, lipidomic analysis revealed the PA (18:0/18:2) was significantly more abundant in the muscle of these two black breeds than that in the DLY breed (p-value < 0.001). These specific metabolites and lipids might influence the meat quality and taste properties and lead to customer preferences. Therefore, this study provided insights into the characterization of meat metabolites and lipids in Shanghai native pig breeds.

RESUMEN

The recent advent of in-context learning (ICL) capabilities in large pre-trained models has yielded significant advancements in the generalization of segmentation models. By supplying domain-specific image-mask pairs, the ICL model can be effectively guided to produce optimal segmentation outcomes, eliminating the necessity for model fine-tuning or interactive prompting. However, current existing ICL-based segmentation models exhibit significant limitations when applied to medical segmentation datasets with substantial diversity. To address this issue, we propose a dual similarity checkup approach to guarantee the effectiveness of selected in-context samples so that their guidance can be maximally leveraged during inference. We first employ large pre-trained vision models for extracting strong semantic representations from input images and constructing a feature embedding memory bank for semantic similarity checkup during inference. Assuring the similarity in the input semantic space, we then minimize the discrepancy in the mask appearance distribution between the support set and the estimated mask appearance prior through similarity-weighted sampling and augmentation. We validate our proposed dual similarity checkup approach on eight publicly available medical segmentation datasets, and extensive experimental results demonstrate that our proposed method significantly improves the performance metrics of existing ICL-based segmentation models, particularly when applied to medical image datasets characterized by substantial diversity.

RESUMEN

Recently, large pretrained vision foundation models based on masked image modeling (MIM) have attracted unprecedented attention and achieved remarkable performance across various tasks. However, the study of MIM for ultrasound imaging remains relatively unexplored, and most importantly, current MIM approaches fail to account for the gap between natural images and ultrasound, as well as the intrinsic imaging characteristics of the ultrasound modality, such as the high noise-to-signal ratio. In this paper, motivated by the unique high noise-to-signal ratio property in ultrasound, we propose a deblurring MIM approach specialized to ultrasound, which incorporates a deblurring task into the pretraining proxy task. The incorporation of deblurring facilitates the pretraining to better recover the subtle details within ultrasound images that are vital for subsequent downstream analysis. Furthermore, we employ a multi-scale hierarchical encoder to extract both local and global contextual cues for improved performance, especially on pixel-wise tasks such as segmentation. We conduct extensive experiments involving 280,000 ultrasound images for the pretraining and evaluate the downstream transfer performance of the pretrained model on various disease diagnoses (nodule, Hashimoto's thyroiditis) and task types (classification, segmentation). The experimental results demonstrate the efficacy of the proposed deblurring MIM, achieving state-of-the-art performance across a wide range of downstream tasks and datasets. Overall, our work highlights the potential of deblurring MIM for ultrasound image analysis, presenting an ultrasound-specific vision foundation model.

Asunto(s)

RESUMEN

Lumbar spine disorders often cause lower back pain, lower limb radiating pain, restricted movement, and neurological dysfunction, which seriously affect the quality of life of middle-aged and older people. It has been found that pathological changes in the spine often cause changes in the morphology and function of the paraspinal muscles (PSMs). Fatty infiltration (FI) in PSMs is closely associated with disc degeneration and Modic changes. And FI causes inflammatory responses that exacerbate the progression of lumbar spine disease and disrupt postoperative recovery. Magnetic resonance imaging can better distinguish between fat and muscle tissue with the threshold technique. Three-dimensional magnetic resonance imaging multi-echo imaging techniques such as water-fat separation and proton density are currently popular for studying FI. Muscle fat content obtained based on these imaging sequences has greater accuracy, visualization, acquisition speed, and utility. The proton density fat fraction calculated from these techniques has been shown to evaluate more subtle changes in PSMs. Magnetic resonance spectroscopy can accurately reflect the relationship between FI and the degeneration of PSMs by measuring intracellular and extracellular lipid values to quantify muscle fat. We have pooled and analyzed published studies and found that patients with spinal disorders often exhibit FI in PSMs. Some studies suggest an association between FI and adverse surgical outcomes, although conflicting results exist. These suggest that clinicians should consider FI when assessing surgical risks and outcomes. Future studies should focus on understanding the biological mechanisms underlying FI and its predictive value in spinal surgery, providing valuable insights for clinical decision-making.

RESUMEN

OBJECTIVE: Imaging parameters of Chiari malformation type I (CMI) development are not well established. This study aimed to collect evidence of general or specific imaging measurements in patients with CMI, analyze indicators that may assist in determining the severity of CMI, and guide its diagnosis and treatment. METHODS: A comprehensive search was conducted across various databases including the Cochrane Library, PubMed, MEDLINE, Scopus, and Embase, covering the period from January 2002 to October 2023, following predefined inclusion criteria. Meta-analyses were performed using RevMan (ver. 5.4). We performed a quantitative summary and systematic analysis of the included studies. This study was registered in the PROSPERO (International Prospective Register of Systematic Reviews) prior to initiation (CRD42023415454). RESULTS: Thirty-three studies met our inclusion criteria. The findings indicated that out of the 14 parameters examined, 6 (clivus length, basal angle, Boogard's angle, supraocciput lengths, posterior cranial fossa [PCF] height, and volume) exhibited significant differences between the CMI group and the control group. Furthermore, apart from certain anatomical parameters that hold prognostic value for CMI, functional parameters like tonsillar movement, obex displacement, and cerebrospinal fluid dynamics serve as valuable indicators for guiding the clinical management of the disease. CONCLUSION: We collated and established a set of linear, angular, and area measurements deemed essential for diagnosing CMI. However, more indicators can only be analyzed descriptively for various reasons, particularly in prognostic prediction. We posit that the systematic assessment of patients' PCF morphology, volume, and other parameters at a 3-dimensional level holds promising clinical application prospects.

RESUMEN

Alloparenting refers to the practice of caring for the young by individuals other than their biological parents. The relationship between the dynamic changes in psychological functions underlying alloparenting and the development of specific neuroreceptors remains unclear. Using a classic 10-day pup sensitization procedure, together with a pup preference and pup retrieval test on the EPM (elevated plus maze), we showed that both male and female adolescent rats (24 days old) had significantly shorter latency than adult rats (65 days old) to be alloparental, and their motivation levels for pups and objects were also significantly higher. In contrast, adult rats retrieved more pups than adolescent rats even though they appeared to be more anxious on the EPM. Analysis of mRNA expression using real-time-PCR revealed a higher dopamine D2 receptor (DRD2) receptor expression in adult hippocampus, amygdala, and ventral striatum, along with higher dopamine D1 receptor (DRD1) receptor expression in ventral striatum compared to adolescent rats. Adult rats also showed significantly higher levels of 5-hydroxytryptamine receptor 2A (HTR2A) receptor expression in the medial prefrontal cortex, amygdala, ventral striatum, and hypothalamus. These results suggest that the faster onset of alloparenting in adolescent rats compared to adult rats, along with the psychological functions involved, may be mediated by varying levels of dopamine DRD1, DRD2, and HTR2A in different forebrain regions.

Asunto(s)