Autophagy is a degradative pathway that delivers cellular components to the lysosome for degradation. The role of autophagy in cell differentiation is poorly understood. Here we show that CaMKII can ...directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. Meanwhile, CaMKII can also promote K63-linked ubiquitination of inhibitor of differentiation 1/2 (Id-1/2) by catalyzing phosphorylation of Id proteins and recruiting TRAF-6. Ubiquitinated Id-1/Id-2 can then bind to p62 and be transported to autolysosomes for degradation. Id degradation promotes the differentiation of neuroblastoma cells and reduces the proportion of stem-like cells. Our study proposes a mechanism by which autophagic degradation of Id proteins can regulate cell differentiation. This suggests that targeting of CaMKII and the regulation of autophagic degradation of Id may be an effective therapeutic strategy to induce cell differentiation in neuroblastoma.
The challenges of developing neuromorphic vision systems inspired by the human eye come not only from how to recreate the flexibility, sophistication, and adaptability of animal systems, but also how ...to do so with computational efficiency and elegance. Similar to biological systems, these neuromorphic circuits integrate functions of image sensing, memory and processing into the device, and process continuous analog brightness signal in real-time. High-integration, flexibility and ultra-sensitivity are essential for practical artificial vision systems that attempt to emulate biological processing. Here, we present a flexible optoelectronic sensor array of 1024 pixels using a combination of carbon nanotubes and perovskite quantum dots as active materials for an efficient neuromorphic vision system. The device has an extraordinary sensitivity to light with a responsivity of 5.1 × 10
A/W and a specific detectivity of 2 × 10
Jones, and demonstrates neuromorphic reinforcement learning by training the sensor array with a weak light pulse of 1 μW/cm
.
Verticillium dahliae isolates are most virulent on the host from which they were originally isolated. Mechanisms underlying these dominant host adaptations are currently unknown. We sequenced the ...genome of V. dahliae Vd991, which is highly virulent on its original host, cotton, and performed comparisons with the reference genomes of JR2 (from tomato) and VdLs.17 (from lettuce).
Pathogenicity-related factor prediction, orthology and multigene family classification, transcriptome analyses, phylogenetic analyses, and pathogenicity experiments were performed.
The Vd991 genome harbored several exclusive, lineage-specific (LS) genes within LS regions (LSRs). Deletion mutants of the seven genes within one LSR (G-LSR2) in Vd991 were less virulent only on cotton. Integration of G-LSR2 genes individually into JR2 and VdLs.17 resulted in significantly enhanced virulence on cotton but did not affect virulence on tomato or lettuce. Transcription levels of the seven LS genes in Vd991 were higher during the early stages of cotton infection, as compared with other hosts. Phylogenetic analyses suggested that G-LSR2 was acquired from Fusarium oxysporum f. sp. vasinfectum through horizontal gene transfer.
Our results provide evidence that horizontal gene transfer from Fusarium to Vd991 contributed significantly to its adaptation to cotton and may represent a significant mechanism in the evolution of an asexual plant pathogen.
The integration of heterometallic units and nanostructures into metal–organic frameworks (MOFs) used for the oxygen evolution reaction (OER) can enhance the electrocatalytic performance and help ...elucidate underlying mechanisms. We have synthesized a series of stable MOFs (CTGU‐10a1–d1) based on trinuclear metal carboxylate clusters and a hexadentate carboxylate ligand with a (6,6)‐connected nia net. We also present a strategy to synthesize hierarchical bimetallic MOF nanostructures (CTGU‐10a2–d2). Among these, CTGU‐10c2 is the best material for the OER, with an overpotential of 240 mV at a current density of 10 mA cm−2 and a Tafel slope of 58 mV dec−1. This is superior to RuO2 and confirms CTGU‐10c2 as one of the few known high‐performing pure‐phase MOF‐OER electrocatalysts. Notably, bimetallic CTGU‐10b2 and c2 show an improved OER activity over monometallic CTGU‐10a2 and d2. Both DFT and experiments show that the remarkable OER performance of CTGU‐10c2 is due to the presence of unsaturated metal sites, a hierarchical nanobelt architecture, and the Ni–Co coupling effect.
Finding the right balance: The integration of heterometallic clusters and nanostructures into stable hierarchical nanosheet‐based bimetal–organic frameworks allows to increase the oxygen evolution reaction performance of electrocatalysts. The ideal ratio between Co and Ni leads to one of the best performances of pure‐phase MOF–OER electrocatalysts.
Secreted small cysteine‐rich proteins (SCPs) play a critical role in modulating host immunity in plant–pathogen interactions. Bioinformatic analyses showed that the fungal pathogen Verticillium ...dahliae encodes more than 100 VdSCPs, but their roles in host–pathogen interactions have not been fully characterized. Transient expression of 123 VdSCP‐encoding genes in Nicotiana benthamiana identified three candidate genes involved in host–pathogen interactions. The expression of these three proteins, VdSCP27, VdSCP113, and VdSCP126, in N. benthamiana resulted in cell death accompanied by a reactive oxygen species burst, callose deposition, and induction of defence genes. The three VdSCPs mainly localized to the periphery of the cell. BAK1 and SOBIR1 (associated with receptor‐like protein) were required for the immunity triggered by these three VdSCPs in N. benthamiana. Site‐directed mutagenesis showed that cysteine residues that form disulphide bonds are essential for the functioning of VdSCP126, but not VdSCP27 and VdSCP113. VdSCP27, VdSCP113, and VdSCP126 individually are not essential for V. dahliae infection of N. benthamiana and Gossypium hirsutum, although there was a significant reduction of virulence on N. benthamiana and G. hirsutum when inoculated with the VdSCP27/VdSCP126 double deletion strain. These results illustrate that the SCPs play a critical role in the V. dahliae–plant interaction via an intrinsic virulence function and suppress immunity following infection.
Small cysteine‐rich proteins secreted by Verticillium dahliae play critical roles in interactions with hosts via an intrinsic virulence function and can suppress immunity following infection.
Objective
To review of our hospital's experiences in transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and challenges we encountered in performance of the procedure, so as to ...provide help to medical institutions who are preparing to carry out vNOTES.
Methods
We retrospectively analyzed the data of all patients receiving vNOTES in our hospital from April 2018 to May 2021. Data we collected cover the general characteristics, perioperative outcomes, and complications of the patients.
Results
A total of 1147 patients underwent vNOTES in the past 3 years at our hospital. The total numbers of adnexal surgery, myomectomy, hysterectomy, pelvic floor reconstruction surgery, and malignant tumor surgery performed via vNOTES were 902, 98, 82, 51, and 14, respectively. Eighteen patients were converted to transabdominal laparoscopic surgery. A total of 38 patients had complications according to Clavien‐Dindo classification, and the total complication rate was 3.31%. Among these cases of complications, 27 were Grade I, 4 were Grade II, and 7 were Grade III. No complications of Grade IV or V were reported.
Conclusion
The application of vNOTES is safe and feasible for most gynecological surgeries. Moreover, hospitals with traditional laparoscopic equipment are advised to try this technique as there is no need to purchase additional expensive equipment. However, since vNOTES represents a novel approach, the long‐term complications and efficacy associated with this technique are pending to be verified through large‐scale prospective multicenter randomized controlled studies.
There is clear evidence that high sodium intake is associated with many health issues including hypertension and cardiovascular diseases (CVDs). Several national and worldwide studies have estimated ...deaths from CVDs attributable to high sodium. But how to evaluate the impact of high sodium intake on diseases using regional routine monitoring and investigation data is necessary and important. Our study aimed to quantitatively evaluate the high sodium intake attributed to CVDs deaths based on the routine monitoring data from China National Nutrition and Health Survey (CNNHS) in Tianjin, China. The population attributable fractions (PAF) were calculated by comparing the observed systolic blood pressure (SBP) distribution with the theoretical minimum or counterfactual distribution by sex and age groups. The results showed that CVDs deaths due to elevated SBP were 22728 (95% uncertainty intervals: 22679‐23050), accounting for 62.8% of total CVDs deaths. According to sodium intake recommended by World Health Organization (WHO), PAF of CVDs deaths attributable to high sodium diet in our study was 14.6% of total CVDs deaths, accounting for 5228 (95% UI: 5005–5998) cases. The dietary sodium intake of residents is nearly three times than sodium intake recommended by WHO. If sodium intake was reduced to reference level, the potential avoidable CVD deaths attributable to the SBP‐raising effect were more than 5200 among adults 25 aged and over in Tianjin. This evaluation method can be extended to other cities.
Verticillium dahliae is a broad host-range pathogen that causes vascular wilts in plants. Interactions between three hosts and specific V. dahliae genotypes result in severe defoliation. The ...underlying mechanisms of defoliation are unresolved.
Genome resequencing, gene deletion and complementation, gene expression analysis, sequence divergence, defoliating phenotype identification, virulence analysis, and quantification of V. dahliae secondary metabolites were performed.
Population genomics previously revealed that G-LSR2 was horizontally transferred from the fungus Fusarium oxysporum f. sp. vasinfectum to V. dahliae and is exclusively found in the genomes of defoliating (D) strains. Deletion of seven genes within G-LSR2, designated as VdDf genes, produced the nondefoliation phenotype on cotton, olive, and okra but complementation of two genes restored the defoliation phenotype. Genes VdDf5 and VdDf6 associated with defoliation shared homology with polyketide synthases involved in secondary metabolism, whereas VdDf7 shared homology with proteins involved in the biosynthesis of N-lauroylethanolamine (N-acylethanolamine (NAE) 12:0), a compound that induces defoliation. NAE overbiosynthesis by D strains also appears to disrupt NAE metabolism in cotton by inducing overexpression of fatty acid amide hydrolase.
The VdDfs modulate the synthesis and overproduction of secondary metabolites, such as NAE 12:0, that cause defoliation either by altering abscisic acid sensitivity, hormone disruption, or sensitivity to the pathogen.
DNA hypermethylation and the silencing of tumor suppressor genes caused by DNA hypermethylation is considered as a molecular hallmark of many kinds of cancers. Procaine, a local anesthetic, has been ...shown as a potential DNA methylation inhibitor in some types of cancers. However, the influence of procaine on DNA methylation regulation as well as the biological function in gastric cancer is still unknown. We report here that procaine represses the DNA‐methylation level and promotes the proliferation arrest and apoptosis of gastric cancer cells. Global DNA methylation measurement demonstrates that procaine significantly reduces the global DNA methylation level. Analyses of the DNMTs expression and activity show procaine represses the activity, but not the expression, of DNMT1/DNMT3A. Further evidence on specific genes shows that procaine reduces the DNA methylation level in the promoter regions of CDKN2A and RARβ genes through abrogating the binding of DNMT1/DNMT3A toward these regions. This repression would not be reversed by the overexpression of DNMT1/DNMT3A. Moreover, RT‐qPCR and luciferase report assays demonstrate that procaine leads to the upregulation of CDKN2A and RARβ due to the activation of the promoter of these genes. In the end, we test the function of procaine toward gastric cancer cells and find that procaine has the growth inhibitory and apoptosis inducement effect toward gastric cancer cells. Collectively, our data not only uncovers the regulation mechanisms of procaine to DNA methylation but also suggests an anti‐tumor potential of procaine specific to the gastric carcinoma and provides a new therapeutic strategy for gastric carcinoma.
In this study, we investigated the influence of procaine on DNA methylation as well as on cell proliferation and apoptosis of gastric cancer cells. We found that procaine repressed the activity but not the expression of DNMT1 and DNMT3A. Further evidence showed that procaine increased the expression of CDKN2A and RARβ through activating the promoter activity of those genes, which is determined by the DNA methylation level. Functionally, procaine inhibited the proliferation and induced the apoptosis of gastric cancer cells. Our results describe a critical role of procaine in the expression of DNMT1 and some critical target genes and suggest the procaine treatment might be a new therapeutic strategy for gastric cancer.
Summary
Improving genetic resistance is a preferred method to manage Verticillium wilt of cotton and other hosts. Identifying host resistance is difficult because of the dearth of resistance genes ...against this pathogen. Previously, a novel candidate gene involved in Verticillium wilt resistance was identified by a genome‐wide association study using a panel of Gossypium hirsutum accessions. In this study, we cloned the candidate resistance gene from cotton that encodes a protein sharing homology with the TIR‐NBS‐LRR receptor‐like defence protein DSC1 in Arabidopsis thaliana (hereafter named GhDSC1). GhDSC1 expressed at higher levels in response to Verticillium wilt and jasmonic acid (JA) treatment in resistant cotton cultivars as compared to susceptible cultivars and its product was localized to nucleus. The transfer of GhDSC1 to Arabidopsis conferred Verticillium resistance in an A. thaliana dsc1 mutant. This resistance response was associated with reactive oxygen species (ROS) accumulation and increased expression of JA‐signalling‐related genes. Furthermore, the expression of GhDSC1 in response to Verticillium wilt and JA signalling in A. thaliana displayed expression patterns similar to GhCAMTA3 in cotton under identical conditions, suggesting a coordinated DSC1 and CAMTA3 response in A. thaliana to Verticillium wilt. Analyses of GhDSC1 sequence polymorphism revealed a single nucleotide polymorphism (SNP) difference between resistant and susceptible cotton accessions, within the P‐loop motif encoded by GhDSC1. This SNP difference causes ineffective activation of defence response in susceptible cultivars. These results demonstrated that GhDSC1 confers Verticillium resistance in the model plant system of A. thaliana, and therefore represents a suitable candidate for the genetic engineering of Verticillium wilt resistance in cotton.
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