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Pseudoprogression (PSP) is a related reaction of glioblastoma treatment, and misdiagnosis can lead to unnecessary intervention. Magnetic resonance imaging (MRI) provides cross-modality images for PSP prediction studies. However, how to effectively use the complementary information between the cross-modality MRI to improve PSP prediction is still a challenging task. To address this challenge, we propose a cross-modality feature interaction network for PSP prediction. Firstly, we propose a triple-branch multi-scale module to extract low-order feature representations and a skip-connection multi-scale module to extract high-order feature representations. Then, a cross-modality interaction module based on attention mechanism is designed to make the complementary information between cross-modality MRI fully interact. Finally, the high-order cross-modality interaction information is fed into a multi-layer perceptron to achieve the PSP prediction task. We evaluate the proposed network on a private dataset with 52 subjects from Hunan Cancer Hospital and validate it on a private dataset with 30 subjects from Xiangya Hospital. The accuracy of our proposed network on the datasets is 0.954 and 0.929, respectively, which is better than most typical convolutional neural network and interaction methods.
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Background: Cervical cancer (CC) remains the second leading cause of cancer-related death in women, and the ability to accurately anticipate the presence or absence of lymphovascular space invasion (LVSI) is critical to maintaining optimal patient outcomes. The objective of this study was to establish and verify an MRI radiomics-based model to predict the status of LVSI in patients with operable CC. Methods: The current study performed a retrospective analysis, with 86 patients in the training cohort and 38 patients in the testing group, specifically focusing on patients with CC. The radiomics feature extraction process included ADC, T2WI-SPAIR, and T2WI sequences. The training group data were used for the initial radionics-based model building, and the model predictive performance was subsequently validated using data from patients recruited in the experimental group. Results: The development of the radiomics scoring model has been completed with 17 selected features. The study found several risk factors associated with LVSI. These risk factors included moderate tumor differentiation (P = 0.005), poor tumor differentiation (P = 0.001), and elevated combined sequence-based radiomics scores (P = 0.001). Radiomics scores based on predictive model, combined sequences, ADC, T2WI-SPAIR, and T2WI exhibited AUCs of 0.897, 0.839, 0.815, 0.698, and 0.739 in the training cohort, respectively, with corresponding testing cohort values of 0.833, 0.833, 0.683, 0.692, and 0.725. Excellent consistency was shown by the calibration curve analysis, which showed a higher degree of agreement between the actual and anticipated LVSI status. Moreover, the decision curve analysis outcomes demonstrated the medical application of this prediction model. Conclusion: This investigation indicated that the MRI radiomics model was successfully developed and validated to predict operable CC patient LVSI status, attaining high overall diagnostic accuracy. However, further external validation and more deeper analysis on a larger sample size are still needed.
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An unprecedented chemodivergent strategy for parallel kinetic resolution (PKR) is disclosed through which two planar chiral products bearing different structures were simultaneously afforded with opposite stereoselectivities. Two achiral esters are activated by one single chiral N-heterocyclic carbene (NHC) catalyst to react with the different enantiomers of the racemic imine substrate in a parallel fashion. Two products bearing distinct structures and opposite stereoselectivities are respectively afforded from the same reaction system in good to excellent yields, enantio- and diastereoselectivities. Control experiments and kinetic studies are carried out to probe the kinetic and dynamic properties during the reaction progress. The planar chiral pyridine and lactam products show interesting applications in both asymmetric synthesis and pesticide development.
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Introduction: In patients with pulmonary nodules (PNs), computed tomography (CT)-guided localization is commonly performed prior to the resection of these nodules through video-assisted thoracic surgery (VATS). Aim: To evaluate the relative clinical efficacy of coil and anchored needle (AN) insertion as approaches to preoperative CT-guided PN localization. Material and methods: This single-center, prospective, open-label, randomized controlled trial (registration number: NCT05183945) enrolled consecutive patients from January 2022 to July 2022, assigning these patients at random to undergo either coil or AN localization prior to VATS. Efficacy and safety outcomes in these two groups were then compared. Results: This study enrolled in total 100 patients with 120 PNs who were assigned at random to the coil (patients = 50; PNs = 60) and AN (patients = 50; PNs = 60) localization groups. The respective technical success rates for coil and AN localization were 98.3% (59/60) and 100% (60/60), with no significant difference between the groups (p = 1.000). The coil group had a significantly longer median duration of localization relative to the AN group (16.0 min vs. 8.0 min, p < 0.001). Similar rates of localization-related pneumothorax (8.3% vs. 5.0%, p = 0.715) and pulmonary hemorrhage (5.0% vs. 13.3%, p = 0.110) were observed in both groups. In addition, the VATS resection procedures achieved 100% technical success rates in both of these localization groups. Conclusions: Both coil- and AN-based localization approaches can be successfully employed to localize PNs prior to VATS resection, with the AN localization procedure requiring less time to complete on average as compared to the coil-based approach.
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Background: Ensuring the survival of the distal end of a random flap during hypoperfusion (ischaemia) is difficult in clinical practice. Effective prevention of programmed cell death is a potential strategy for inhibiting ischaemic flap necrosis. The activation of stimulator of interferon genes (STING) pathway promotes inflammation and leads to cell death. The epidermal growth factor family member neuregulin-1 (NRG1) reduces cell death by activating the protein kinase B (AKT) signalling pathway. Moreover, AKT signalling negatively regulates STING activity. We aimed to verify the efficacy of NRG1 injection in protecting against flap necrosis. Additionally, we investigated whether NRG1 effectively enhances ischemic flap survival by inhibiting pyroptosis and necroptosis through STING suppression. Methods: A random-pattern skin flap model was generated on the backs of C57BL/6 mice. The skin flap survival area was determined. The blood supply and vascular network of the flap was assessed by laser Doppler blood flow analysis. Cluster of differentiation 34 immunohistochemistry (IHC) and haematoxylin and eosin (H&E) staining of the flap sections revealed microvessels. Transcriptome sequencing analysis revealed the mechanism by which NRG1 promotes the survival of ischaemic flaps. The levels of angiogenesis, oxidative stress, necroptosis, pyroptosis and indicators associated with signalling pathways in flaps were examined by IHC, immunofluorescence and Western blotting. Packaging adeno-associated virus (AAV) was used to activate STING in flaps. Results: NRG1 promoted the survival of ischaemic flaps. An increased subcutaneous vascular network and neovascularization were found in ischaemic flaps after the application of NRG1. Transcriptomic gene ontology enrichment analysis and protein level detection indicated that necroptosis, pyroptosis and STING activity were reduced in the NRG1 group. The phosphorylation of AKT and forkhead box O3a (FOXO3a) were increased after NRG1 treatment. The increased expression of STING in flaps induced by AAV reversed the therapeutic effect of NRG1. The ability of NRG1 to phosphorylate AKT-FOXO3a, inhibit STING and promote flap survival was abolished after the application of the AKT inhibitor MK2206. Conclusions: NRG1 inhibits pyroptosis and necroptosis by activating the AKT-FOXO3a signalling pathway to suppress STING activation and promote ischaemic flap survival.
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Stochastic and deterministic processes are the major themes governing microbial community assembly; however, their roles in bioreactors are poorly understood. Herein, the mechanisms underlying microbial assembly and the effect of rare taxa were studied in biofilters. Phylogenetic tree analysis revealed differences in microbial communities at various stages. Null model analysis showed that stochastic processes shaped the community assembly, and deterministic processes emerged only in the inoculated activated sludge after domestication. This finding indicates the dominant role of stochastic factors (biofilm formation, accumulation, and aging). The Sloan neutral model corroborated the advantages of stochastic processes and mainly attributed these advantages to rare taxa. Cooccurrence networks revealed the importance of rare taxa, which accounted for more than 85% of the keystones. Overall, these results provide good foundations for understanding community assembly, especially the role of rare taxa, and offer theoretical support for future community design and reactor regulation.
Subject(s)
Bioreactors , Phylogeny , Stochastic Processes , Bioreactors/microbiology , Filtration , Sewage/microbiology , Bacteria/metabolism , Bacteria/genetics , Biofilms , Microbiota , RNA, Ribosomal, 16S/geneticsABSTRACT
BACKGROUND: Potato virus Y (PVY) is a prominent representative of plant viruses. It can inflict severe damage upon Solanaceae plants, leading to global dissemination and substantial economic losses. To discover new antiviral agents, a class of planar chiral thiourea molecules through the key step of N-heterocyclic carbene-catalyzed nitrile formation reaction was synthesized with excellent optical purities for antiviral evaluations against plant virus PVY. RESULTS: The absolute configurations of the planar chiral compounds exhibited obvious distinctions in the anti-PVY activities. Notability, compound (S)-4u exhibited remarkable curative activities against PVY, with a half maximal effective concentration (EC50) of 349.3 µg mL-1, which was lower than that of the ningnanmycin (NNM) (EC50 = 400.8 µg mL-1). Additionally, The EC50 value for the protective effects of (S)-4u was 146.2 µg mL-1, which was superior to that of NNM (276.4 µg mL-1). Furthermore, the mechanism-of-action of enantiomers of planar chiral compound 4u was investigated through molecular docking, defensive enzyme activity tests and chlorophyll content tests. CONCLUSION: Biological mechanism studies have demonstrated that the configuration of planar chiral target compounds plays a crucial role in the molecular interaction with PVY-CP, enhancing the activity of defense enzymes and affecting chlorophyll content. The current study has provided significant insights into the roles played by planar chiralities in plant protection against viruses. This paves the way for the development of novel green pesticides bearing planar chiralities with excellent optical purities. © 2024 Society of Chemical Industry.
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Antiviral Agents , Potyvirus , Thiourea , Thiourea/pharmacology , Thiourea/analogs & derivatives , Thiourea/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/chemistry , Potyvirus/drug effects , Molecular Docking Simulation , Drug Design , StereoisomerismABSTRACT
Ecdysone-induced protein 93 (E93), known as the 'adult-specifier' transcription factor in insects, triggers metamorphosis in both hemimetabolous and holometabolous insects. Although E93 is conserved in ametabolous insects, its spatiotemporal expression and physiological function remain poorly understood. In this study, we first discover that, in the ametabolous firebrat Thermobia domestica, the previtellogenic ovary exhibits cyclically high E93 expression, and E93 mRNA is broadly distributed in previtellogenic ovarioles. E93 homozygous mutant females of T. domestica exhibit severe fecundity deficiency due to impaired previtellogenic development of the ovarian follicles, likely because E93 induces the expression of genes involved in ECM (extracellular matrix)-receptor interactions during previtellogenesis. Moreover, we reveal that in the hemimetabolous cockroach Blattella germanica, E93 similarly promotes previtellogenic ovarian development. In addition, E93 is also essential for vitellogenesis that is necessary to guarantee ovarian maturation and promotes the vitellogenesis-previtellogenesis switch in the fat body of adult female cockroaches. Our findings deepen the understanding of the roles of E93 in controlling reproduction in insects, and of E93 expression and functional evolution, which are proposed to have made crucial contributions to the origin of insect metamorphosis.
Subject(s)
Metamorphosis, Biological , Ovary , Reproduction , Animals , Female , Reproduction/genetics , Metamorphosis, Biological/genetics , Ovary/metabolism , Gene Expression Regulation, Developmental , Vitellogenesis/genetics , Insect Proteins/metabolism , Insect Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Drosophila Proteins/metabolism , Drosophila Proteins/geneticsABSTRACT
An approach utilizing N-heterocyclic carbene for nitrile formation and desymmetrization reaction is developed. The process involves kinetic resolution, with the axially chiral aryl monoaldehydes obtained in moderate yields with excellent optical purities. These axially chiral aryl monoaldehydes can be conveniently transformed into functionalized molecules, showing great potential as catalysts in organic chemistry.
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Given the challenge of multidrug resistance in antibiotics, non-antibiotic-dependent antibacterial strategies show promise for anti-infective therapy. V2C MXene-based nanomaterials have demonstrated strong biocompatibility and photothermal conversion efficiency (PCE) for photothermal therapy (PTT). However, the limitation of V2C MXene's laser irradiation to the near-infrared region I (NIR-I) restricts tissue penetration, making it difficult to achieve complete bacterial eradication with single-effect therapeutic strategies. To address this, Pt nanoparticles (Pt NPs) are attached to V2C, forming artificial nanoplatforms (Pt@V2C). Pt@V2C exhibits enhanced PCE (59.6%) and a longer irradiation laser (NIR-II) due to the surface plasmon resonance effect of Pt NPs and V2C. Notably, Pt@V2C displays dual enzyme-like activity with chemodynamic therapy (CDT) and NIR-II enhanced dual enzyme-like activity. The biocatalytic mechanism of Pt@V2C is elucidated using density functional theory. In an in vivo animal model, Pt@V2C effectively eliminates methicillin-resistant Staphylococcus aureus from deep-seated tissues in subcutaneous abscesses and bacterial keratitis environments, accelerating abscess resolution and promoting wound and cornea healing through the synergistic effects of PTT/CDT. Transcriptomic analysis reveals that Pt@V2C targets inflammatory pathways, providing insight into its therapeutic mechanism. This study presents a promising therapeutic approach involving hyperthermia-amplified biocatalysis with Pt NPs and MXene nanocomposites.
Subject(s)
Anti-Bacterial Agents , Metal Nanoparticles , Methicillin-Resistant Staphylococcus aureus , Photothermal Therapy , Platinum , Platinum/chemistry , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Animals , Methicillin-Resistant Staphylococcus aureus/drug effects , Mice , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Infrared Rays , Staphylococcal Infections/drug therapyABSTRACT
We have developed a catalytic method using chiral N-heterocyclic carbene (NHC) as the sole organic catalyst to synthesize planar chiral carbonitriles asymmetrically, resulting in optically pure, multifunctional compounds. The method demonstrates remarkable tolerance toward diverse substituents and substitution patterns through kinetic resolution (KR) or desymmetrization processes. The resulting optically pure planar chiral products hold significant potential for applications in asymmetric synthesis and antibacterial pesticide development.
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Sulfur-containing gases are main sources of landfill odors, which has become a big issue for pollution to environment and human health. Biocover is promising for treating landfill odors, with advantages of durability and environmental friendliness. In this study, charcoal sludge compost was utilized as the main effective component of a novel alternative landfill cover and the in situ control of sulfur-containing odors from municipal solid waste landfilling process was simulated under nine different operating conditions. Results showed that five sulfur-containing odors (hydrogen sulfide, H2S; methyl mercaptan, CH3SH; dimethyl sulfide, CH3SCH3; ethylmercaptan, CH3CH2SH; carbon disulfide, CS2) were monitored and removed by the biocover, with the highest removal efficiencies of 77.18% for H2S, 87.36% for CH3SH, and 92.19% for CH3SCH3 in reactor 8#, and 95.94% for CH3CH2SH and 94.44% for CS2 in reactor 3#. The orthogonal experiment showed that the factors influencing the removal efficiencies of sulfur-containing odors were ranked from high to low as follows: temperature > weight ratio > humidity content. The combination of parameters of 20% weight ratio, 25°C temperature, and 30% water content was more recommended based on the consideration of the removal efficiencies and economic benefits. The mechanisms of sulfur conversion inside biocover were analyzed. Most organic sulfur was firstly degraded to reduced sulfides or element sulfur, and then oxidized to sulfate which could be stable in the layer as the final state. In this process, sulfur-oxidizing bacteria play a great role, and the distribution of them in reactor 1#, 5#, and 8# was specifically monitored. Bradyrhizobiaceae and Rhodospirillaceae were the dominant species which can utilize sulfide as substance to produce sulfate and element sulfur, respectively. Based on the results of OUTs, the biodiversity of these sulfur-oxidizing bacteria, these microorganisms, was demonstrated to be affected by the different parameters. These results indicate that the novel alternative landfill cover modified with bamboo charcoal compost is effective in removing sulfur odors from landfills. Meanwhile, the findings have direct implications for addressing landfill odor problems through parameter adjustment.
Subject(s)
Hydrogen Sulfide , Odorants , Humans , Charcoal/metabolism , Hydrogen Sulfide/metabolism , Sulfur/metabolism , Waste Disposal Facilities , Sulfur Oxides , Bacteria/metabolism , Sulfates/metabolismABSTRACT
We generated PUMCi005-A, an induced pluripotent stem cell (iPSC) line, from dermal fibroblasts of a 32-year-old female Perrault syndrome patient with double heterozygous (794 G > A and 1181 G > A) mutations in the TWNK gene using Sendai viral delivery of OCT4, SOX2, KLF4, and c-MYC. The PUMCi005-A iPSC line carried the TWNK mutations, displayed typical iPSC morphology, expressed pluripotent stem cell markers, did not have integration of Sendai virus, and exhibited a normal karyotype and differentiation into three germ layers.
Subject(s)
Gonadal Dysgenesis, 46,XX , Hearing Loss, Sensorineural , Induced Pluripotent Stem Cells , Female , Humans , Adult , Induced Pluripotent Stem Cells/metabolism , Kruppel-Like Factor 4 , Hearing Loss, Sensorineural/metabolism , Gonadal Dysgenesis, 46,XX/metabolism , Cell Differentiation/genetics , Sendai virus/genetics , Mutation/genetics , Fibroblasts/metabolismABSTRACT
Starvation disturbance due to nutrient limitation is a common problem in bioreactors. However, an understanding of how microbial systems respond to starvation remains in its infancy. Here the metabolic response mechanism of a biofilm community to starvation was investigated using a well-controlled gaseous toluene treatment biofilter through interruption of its operation. It was found that metabolic characteristics showed significant differences before and after starvation. The dominant carbon source utilization type shifted from amino acids and carboxylic acids to esters and carbohydrates after starvation, which is more conducive to improving energy production. Metagenomic sequencing analysis supported that the changes in the dominant metabolic substrate, enhanced metabolic stability, and flexibility in the mode of energy metabolism could be the main ways to guarantee functional resilience in ecosystems after starvation. The results highlight the microbial metabolic response to starvation, which would be beneficial to the understanding of functional resilience and bioreactor stability.
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Ecosystem , Resilience, Psychological , Gases , Metagenome , Carbon , BioreactorsABSTRACT
OBJECTIVE: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. METHODS: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. RESULTS: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. CONCLUSION: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.
Subject(s)
Breast Neoplasms , Designed Ankyrin Repeat Proteins , Humans , Mice , Animals , Female , Epithelial Cell Adhesion Molecule/genetics , Epithelial Cell Adhesion Molecule/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Gene Transfer Techniques , Genetic Therapy/methods , Genetic Vectors/genetics , Dependovirus/genetics , Dependovirus/metabolismABSTRACT
We present a new reaction between carboxylic acids and allene ketones mediated by N-heterocyclic carbene (NHC) catalysts, which exhibit, in principle, nearly perfect atom economy. In this new approach, allene ketones act as both an activating reagent and a reactant. All atoms in the substrates end up in the product without the need for coupling reagents. The present study aims to encourage further explorations of NHC catalytic reactions with alternative activation strategies and better atom economy.
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Single-atom catalysts (SACs) have been one of the frontiers in the field of catalysis in recent years owing to their high atomic utilization and unique electronic structure. To facilitate the practical application of single-atom, it is vital to develop a sustainable, facile single-atom preparation method with mass production potential. Herein, a universal one-step electrochemical synthesis strategy is proposed, and various metal-organic framework-supported SACs (including Pt, Au, Ir, Pd, Ru, Mo, Rh, and W) are straightforwardly obtained by simply replacing the guest metal precursors. As a proof-of-concept, the electrosynthetic Pt-based catalysts exhibit outstanding activity and stability in the electrocatalytic hydrogen evolution reaction (HER). This study not only enriches the single-atom synthesis methodology, but also extends the scenario of electrochemical synthesis, opening up new avenues for the design of advanced electro-synthesized catalysts.
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Introduction: Default mode network (DMN) is the most involved network in the study of brain development and brain diseases. Resting-state functional connectivity (rsFC) is the most used method to study DMN, but different studies are inconsistent in the selection of seed. To evaluate the effect of different seed selection on rsFC, we conducted an image-based meta-analysis (IBMA). Methods: We identified 59 coordinates of seed regions of interest (ROIs) within the default mode network (DMN) from 11 studies (retrieved from Web of Science and Pubmed) to calculate the functional connectivity; then, the uncorrected t maps were obtained from the statistical analyses. The IBMA was performed with the t maps. Results: We demonstrate that the overlap of meta-analytic maps across different seeds' ROIs within DMN is relatively low, which cautions us to be cautious with seeds' selection. Discussion: Future studies using the seed-based functional connectivity method should take the reproducibility of different seeds into account. The choice of seed may significantly affect the connectivity results.
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Herein we aimed at exploring mitochondrial energy metabolism status in patients with repeated implantation failure (RIF) and whether key regulatory factor PGC-1α of energy metabolism is involved in the decidualization of endometrial stromal cells. Mitochondrial oxidative phosphorylation level and ATP synthesis were compared in primary endometrial stromal cells from RIF and control group. At the same time, as one of key transcription regulators of mitochondrial energy metabolism, the expression level and acetylation level of PGC-1α were compared with two groups. Then, we downregulated the acetylation levels of PGC-1α, and the expression of decidual markers (PRL and IGFBP1) was observed further. Mitochondrial energy metabolism, showing by mitochondrial oxidative phosphorylation level and ATP synthesis, was decreased in the endometrial stromal cells of the RIF group (RIF-hEnSCs). Meanwhile, PGC-1α acetylation levels were significantly higher in RIF-hEnSCs. When we reduced the acetylation levels of PGC-1α in RIF-hEnSCs, the basal O2 consumption rate and maximal respiration were increased, and also the PRL and IGFBP1. Overall, our data indicated that the endometrial stromal cells of the RIF patients had low level of mitochondrial energy metabolism. Reducing acetylation level of key energy metabolism regulator PGC-1α can increase the decidualization level of RIF-hEnSCs. These findings may inspire new ideas about the treatment of RIF.