The role of hydrogen-rich water in delaying the pulp breakdown of litchi fruit during postharvest storage.

Previous studies have indicated that hydrogen-rich water (HW) treatment can delay fruit ripening and senescence. However, little is known about the HW-delaying pulp breakdown. In this study, eight physiological characteristics revealed that HW treatment delayed both pericarp browning and pulp breakdown of litchi fruit. To gain a comprehensive understanding of the changes in litchi pulp, a combination of multiple metabolomics and gene expression analyses was conducted, assessing 67 primary metabolites, 103 volatiles, 31 amino acids, and 13 crucial metabolite-related genes. Results showed that HW treatment promoted starch degradation, decelerated cell wall degradation and glycolysis, and maintained the flavor and quality of litchi fruit. Furthermore, HW treatment stimulated the production of volatile alcohols, aldehydes, ketones, olefins, and amino acids, which might play a vital role in HW-delaying pulp breakdown. This study sheds light on the mechanism by which HW delayed pulp breakdown by investigating small molecule metabolites and metabolic pathways.

Parvalbumin Regulates GAD Expression through Calcium Ion Concentration to Affect the Balance of Glu-GABA and Improve KA-Induced Status Epilepticus in PV-Cre Transgenic Mice.

Aims: the study aimed to (i) use adeno-associated virus technology to modulate parvalbumin (PV) gene expression, both through overexpression and silencing, within the hippocampus of male mice and (ii) assess the impact of PV on the metabolic pathway of glutamate and γ-aminobutyric acid (GABA). Methods: a status epilepticus (SE) mouse model was established by injecting kainic acid into the hippocampus of transgenic mice. When the seizures of mice reached SE, the mice were killed at that time point and 30 min after the onset of SE. Hippocampal tissues were extracted and the mRNA and protein levels of PV and the 65 kDa (GAD65) and 67 kDa (GAD67) isoforms of glutamate decarboxylase were assessed using real-time quantitative polymerase chain reaction and Western blot, respectively. The concentrations of glutamate and GABA were detected with high-performance liquid chromatography (HPLC), and the intracellular calcium concentration was detected using flow cytometry. Results: we demonstrate that the expression of PV is associated with GAD65 and GAD67 and that PV regulates the levels of GAD65 and GAD67. PV was correlated with calcium concentration and GAD expression. Interestingly, PV overexpression resulted in a reduction in calcium ion concentration, upregulation of GAD65 and GAD67, elevation of GABA concentration, reduction in glutamate concentration, and an extension of seizure latency. Conversely, PV silencing induced the opposite effects. Conclusion: parvalbumin may affect the expression of GAD65 and GAD67 by regulating calcium ion concentration, thereby affecting the metabolic pathways associated with glutamate and GABA. In turn, this contributes to the regulation of seizure activity.

Reproductive and fetal outcomes in women with epilepsy: a systematic review and meta-analysis.

OBJECTIVE: Although early evidence shows that epilepsy can increase the risks of adverse pregnancy, some outcomes are still debatable. We performed a systematic review and meta-analysis to explore the effects of maternal and fetal adverse outcomes in pregnant women with epilepsy. METHODS: PubMed, Embase, Cochrane, and Web of Science were employed to collect studies that investigated the potential risk of obstetric complications during the antenatal, intrapartum, or postnatal period, as well as any neonatal complications. The search was conducted from inception to November 16, 2022. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included original studies. The odds ratio (OR) values were extracted after adjusting for confounders to measure the relationship between pregnant women with epilepsy and adverse maternal or fetal outcomes. The protocol for this systematic review is registered with PROSPERO ID CRD42023391539. RESULTS: Of 35 articles identified, there were 142,577 mothers with epilepsy and 34,381,373 mothers without epilepsy. Our study revealed a significant association between pregnant women with epilepsy (PWWE) and the incidence of cesarean section, preeclampsia/eclampsia, gestational hypertension, induction of labor, gestational diabetes and postpartum hemorrhage compared with those without epilepsy. Regarding newborns outcomes, PWWE versus those without epilepsy had increased odds of preterm birth, small for gestational age, low birth weight (<2500 g), and congenital malformations, fetal distress. The odds of operative vaginal delivery, newborn mortality, and Apgar (≤ 7) were similar between PWWE and healthy women. CONCLUSION: Pregnant women affected by epilepsy encounter a higher risk of adverse obstetric outcomes and fetal complications. Therefore, it is crucial to develop appropriate prevention and intervention strategies prior to or during pregnancy to minimize the negative impacts of epilepsy on maternal and fetal health.

Laponite-activated AIE supramolecular assembly with modulating multicolor luminescence for logic digital encryption and perfluorinated pollutant detection.

Recently, the non-covalently activated supramolecular scaffold method has become a prominent research area in the field of intelligent materials. Here, the inorganic clay (LP) promoted the AIE properties of 4,4',4″,4‴-(ethene-1,1,2,2-tetrayltetrakis(benzene-4,1-diyl))tetrakis(1-ethylpyridin-1-ium) (P-TPE), showing an astonishing 42-fold enhancement of the emission intensity of the yellow-green luminescence and a 34-fold increase of the quantum yield via organic-inorganic supramolecular strategy as well as the efficient light-harvesting properties (energy transfer efficiency up to 33 %) after doping with the dye receptor Rhodamine B. Furthermore, the full-color spectral regulation, including white light, was achieved by adjusting the ratio of the donor to the acceptor component and co-assembling with the carbon dots (CD). Interestingly, this TPE-based non-covalently activated full-color supramolecular light-harvesting system (LHS) could be achieved not only in aqueous media but also in the hydrogel and the solid state. More importantly, this panchromatic tunable supramolecular LHS exhibited the multi-mode and quadruple digital logic encryption property as well as the specific detection ability towards the perfluorobutyric acid and the perfluorobutanesulfonic acid, which are harmful to human health in drinking water. This result develops a simple, convenient and effective approach for the intelligent anti-counterfeiting and the pollutant sensing.

The detoxification ability of sex-role reversed seahorses determines the sexual dimorphism in immune responses to benzo[a]pyrene exposure.

Sexual dimorphism in immune responses is an essential factor in environmental adaptation. However, the mechanisms involved remain obscure owing to the scarcity of data from sex-role-reversed species in stressed conditions. Benzo[a]pyrene (BaP) is one of the most pervasive and carcinogenic organic pollutants in coastal environments. In this study, we evaluated the potential effects on renal immunotoxicity of the sex-role-reversed lined seahorse (Hippocampus erectus) toward environmental concentrations BaP exposure. Our results discovered the presence of different energy-immunity trade-off strategies adopted by female and male seahorses during BaP exposure. BaP induced more severe renal damage in female seahorses in a concentration-dependent manner. BaP biotransformation and detoxification in seahorses resemble those in mammals. Benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide (BPDE) and 9-hydroxybenzo[a]pyrene (9-OH-BaP) formed DNA adducts and disrupted Ca2+ homeostasis may together attribute the renal immunotoxicity. Sexual dimorphisms in detoxification of both BPDE and 9-OH-BaP, and in regulation of Ca2+, autophagy and inflammation, mainly determined the extent of renal damage. Moreover, the mechanism of sex hormones regulated sexual dimorphism in immune responses needs to be further elucidated. Collectively, these findings contribute to the understanding of sexual dimorphism in the immunotoxicity induced by BaP exposure in seahorses, which may attribute to the dramatic decline in the biodiversity of the genus.

Regulatory mechanism and expression level of PRPS2 in lung cancer.

BACKGROUND: Lung cancer, with high morbidity and mortality, is the commonest respiratory system neoplasm, which seriously endangers the life safety of patients. In this study, the effect of PRPS2 on cell progression was preliminarily investigated. METHODS: Immunohistochemical staining, western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were performed to verify the expression level of PRPS2 in lung cancer. Lung cancer cell lines with stable downregulation of PRPS2 were constructed in A549 cells and NCIH460 cells. The function of PRPS2 silencing on the proliferation ability was verified by the EdU and cell colony formation experiment. Scratch and transwell tests were conducted to verify the role of PRPS2 silencing on the migratory and invasive ability of cells. The impact of PRPS2 silencing on cell apoptosis and cell cycle was verified by flow cytometry test. The effects of PRPS2 silencing on apoptosis-associated proteins were assessed by western blot assay. The function of PRPS2 silencing on tumor growth in vivo was studied through xenograft tumor experiment. RESULTS: In comparison with normal tissues, PRPS2 was upregulated in lung cancer tissues. PRPS2 knockdown notably hindered the migratory ability, invasive ability and proliferation, but accelerated cell apoptosis. In vivo experiments confirmed that PRPS2 silencing blocked the growth of transplanted tumors. CONCLUSION: In lung cancer, PRPS2 silencing suppressed the malignant progression, indicating that PRPS2 might be a novel biomarker for lung cancer treatment and diagnosis.

Acibenzolar-S-methyl promotes wound healing of harvested sweet potatoes (Ipomoea batatas) by regulation of reactive oxygen species metabolism and phenylpropanoid pathway.

Rapid wound healing is crucial in protecting sweet potatoes (Ipomoea batatas ) against infection, water loss and quality deterioration during storage. The current study investigated how acibenzolar-S-methyl (ASM) treatment influenced wound healing in harvested sweet potatoes by investigating the underlying mechanism. It was found that ASM treatment of wounded sweet potatoes induced a significant accumulation of lignin at the wound sites, which effectively suppressed weight loss. After 4days of healing, the lignin content of ASM-treated sweet potatoes was 41.8% higher than that of untreated ones, and the weight loss rate was 20.4% lower. Moreover, ASM treatment increased the ability of sweet potatoes to defend against wounding stress through enhancing processes such as increased production of reactive oxygen species (ROS), activation of enzymes involved in the ROS metabolism (peroxidase, superoxide dismutase and catalase) and phenylpropanoid pathway (phenylalanine ammonia lyase, cinnamate-4-hydroxylase, 4-coumarate-CoA ligase and cinnamyl alcohol dehydrogenase), and intensive synthesis of phenolics and flavonoids. These results suggest that treating harvested sweet potatoes with ASM promotes wound healing through the activation of the ROS metabolism and phenylpropanoid pathway.

An Ionic Assisted Enhancement Strategy Enabled High Performance Flexible Pressure-Temperature Dual Sensor.

Flexible pressure sensors with a broad range and high sensitivity are greatly desired yet challenging to build. Herein, we have successfully fabricated a pressure-temperature dual sensor via an ionic assisted charge enhancement strategy. Benefiting from the immobilization effect for [EMIM+] [TFSI-] ion pairs and charge transfer between ionic liquid (IL) and HFMO (H10Fe3Mo21O51), the formed IL-HFMO-TPU pressure sensor shows a high sensitivity of 25.35 kPa-1 and broad sensing range (∼10 MPa), respectively. Furthermore, the sensor device exhibits high durability and stability (5000 cycles@1 MPa). The IL-HFMO-TPU sensor also shows the merit of good temperature sensing properties. Attributed to these superior properties, the proposed sensor device could detect pressure in an ultrawide sensing range (from Pa to MPa), including breathe and biophysical signal monitoring etc. The proposed ionic assisted enhancement approach is a generic strategy for constructing high performance flexible pressure-temperature dual sensor.

Self-Healable Multifunctional Fibers via Thermal Drawing.

The development of soft electronics and soft fiber devices has significantly advanced flexible and wearable technology. However, they still face the risk of damage when exposed to sharp objects in real-life applications. Taking inspiration from nature, self-healable materials that can restore their physical properties after external damage offer a solution to this problem. Nevertheless, large-scale production of self-healable fibers is currently constrained. To address this limitation, this study leverages the thermal drawing technique to create elastic and stretchable self-healable thermoplastic polyurethane (STPU) fibers, enabling cost-effective mass production of such functional fibers. Furthermore, despite substantial research into the mechanisms of self-healable materials, quantifying their healing speed and time poses a persistent challenge. Thus, transmission spectra are employed as a monitoring tool to observe the real-time self-healing process, facilitating an in-depth investigation into the healing kinetics and efficiency. The versatility of the fabricated self-healable fiber extends to its ability to be doped with a wide range of functional materials, including dye molecules and magnetic microparticles, which enables modular assembly to develop distributed strain sensors and soft actuators. These achievements highlight the potential applications of self-healable fibers that seamlessly integrate with daily lives and open up new possibilities in various industries.

Ultrastrong exciton-plasmon couplings in WS2 multilayers synthesized with a random multi-singular metasurface at room temperature.

Van der Waals semiconductors exemplified by two-dimensional transition-metal dichalcogenides have promised next-generation atomically thin optoelectronics. Boosting their interaction with light is vital for practical applications, especially in the quantum regime where ultrastrong coupling is highly demanded but not yet realized. Here we report ultrastrong exciton-plasmon coupling at room temperature in tungsten disulfide (WS2) layers loaded with a random multi-singular plasmonic metasurface deposited on a flexible polymer substrate. Different from seeking perfect metals or high-quality resonators, we create a unique type of metasurface with a dense array of singularities that can support nanometre-sized plasmonic hotspots to which several WS2 excitons coherently interact. The associated normalized coupling strength is 0.12 for monolayer WS2 and can be up to 0.164 for quadrilayers, showcasing the ultrastrong exciton-plasmon coupling that is important for practical optoelectronic devices based on low-dimensional semiconductors.

Evaluating Urine Cytology Slide Digitization Efficiency: A Comparative Study Using an Artificial Intelligence-Based Heuristic Scanning Simulation and Multiple-Z-Plane Scanning.

INTRODUCTION: Digitizing cytology slides presents challenges because of their three-dimensional features and uneven cell distribution. While multi-Z-plane scan is a prevalent solution, its adoption in clinical digital cytopathology is hindered by prolonged scanning times, increased image file sizes, and the requirement for cytopathologists to review multiple Z-plane images. METHODS: This study presents heuristic scan as a novel solution, using an artificial intelligence (AI)-based approach specifically designed for cytology slide scanning as an alternative to the multi-Z-plane scan. Both the 21 Z-plane scan and the heuristic scan simulation methods were used on 52 urine cytology slides from three distinct cytopreparations (Cytospin, ThinPrep, and BD CytoRich™ (SurePath)), generating whole-slide images (WSIs) via the Leica Aperio AT2 digital scanner. The AI algorithm inferred the WSI from 21 Z-planes to quantitate the total number of suspicious for high-grade urothelial carcinoma or more severe cells (SHGUC+) cells. The heuristic scan simulation calculated the total numbers of SHGUC+ cells from the 21 Z-plane scan data. Performance metrics including SHGUC+ cell coverage rates (calculated by dividing the number of SHGUC+ cells identified in multiple Z-planes or heuristic scan simulation by the total SHGUC+ cells in the 21 Z-planes for each WSI), scanning time, and file size were analyzed to compare the performance of each scanning method. The heuristic scan's metrics were linearly estimated from the 21 Z-plane scan data. Additionally, AI-aided interpretations of WSIs with scant SHGUC+ cells followed The Paris System guidelines and were compared with original diagnoses. RESULTS: The heuristic scan achieved median SHGUC+ cell coverage rates similar to 5 Z-plane scans across three cytopreparations (0.78-0.91 vs. 0.75-0.88, P=0.451-0.578). Notably, it substantially reduced both scanning time (137.2-635.0 seconds vs. 332.6-1278.8 seconds, P<0.05) and image file size (0.51-2.10 GB vs. 1.16-3.10 GB, P<0.05). Importantly, the heuristic scan yielded higher rates of accurate AI-aided interpretations compared to the single Z-plane scan (62.5% vs. 37.5%). CONCLUSION: We demonstrated that the heuristic scan offers a cost-effective alternative to the conventional multi-Z-plane scan in digital cytopathology. It achieves comparable SHGUC+ cell capture rates while reducing both scanning time and image file size, promising to aid digital urine cytology interpretations with a higher accuracy rate compared to the conventional single (optimal) plane scan. Further studies are needed to assess the integration of this new technology into compatible digital scanners for practical cytology slide scanning.

The interpositional bypass with a parietal branch of superficial temporal artery graft for symptomatic atherosclerotic anterior cerebral artery stenosis or occlusion.

Background: For nonmoyamoya patients with anterior cerebral artery (ACA) stenosis or occlusion, whether direct revascularization of the ACA territory can prevent stroke is still unclear. The objective of this study was to investigate the efficacy and safety of a parietal branch of superficial temporal artery-interposed superficial temporal artery-to-ACA bypass (PISAB) for preventing stroke in patients with symptomatic atherosclerotic ACA stenosis or occlusion (SAASO). Methods: We retrospectively analyzed the data from patients with SAASO who had undergone PISAB in our center between April 2016 and November 2021. The rates of patency, satisfaction (revascularization grades A and B) of bypass, perioperative complications, recurrence of ischemic stroke, changes in bypass flow, and improvements in cerebral blood perfusion were analyzed. Results: A total of 19 SAASO patients were involved in this study. Sixteen out of 19 (84.2%) patients were free from any cerebral ischemic events after surgery. Only 3 patients (15.8%) had recurrent stroke postoperatively. Two (10.5%) surgery-related complications occurred, including hyperperfusion syndrome and minor stroke. No skin ischemic complications occurred. The average follow-up period was 50.6 ± 18.3 months. The flow rate of the bypass was significantly increased half a year after surgery (56.2 ± 8.0 mL/min vs. 44.3 ± 5.3 mL/min, p < 0.001). The ratio of ipsilateral/contralateral mean transit time in the superior frontal gyrus was decreased significantly after bypass (1.08 ± 0.07 vs. 1.23 ± 0.05, p < 0.001) and continued to decrease 6 months after surgery (1.05 ± 0.04 vs. 1.08 ± 0.07, p = 0.002). The patency rate of PISAB was 94.7% (18/19) 2 years after surgery. The satisfaction rate of bypass was 89.5% (17/19). Conclusion: The results of this study indicate that PISAB, as a safe superficial bypass, can effectively reduce the risk of stroke in SAASO patients. More precise conclusions will require randomized control studies.

Benchmarking multi-omics integration algorithms across single-cell RNA and ATAC data.

Recent advancements in single-cell sequencing technologies have generated extensive omics data in various modalities and revolutionized cell research, especially in the single-cell RNA and ATAC data. The joint analysis across scRNA-seq data and scATAC-seq data has paved the way to comprehending the cellular heterogeneity and complex cellular regulatory networks. Multi-omics integration is gaining attention as an important step in joint analysis, and the number of computational tools in this field is growing rapidly. In this paper, we benchmarked 12 multi-omics integration methods on three integration tasks via qualitative visualization and quantitative metrics, considering six main aspects that matter in multi-omics data analysis. Overall, we found that different methods have their own advantages on different aspects, while some methods outperformed other methods in most aspects. We therefore provided guidelines for selecting appropriate methods for specific scenarios and tasks to help obtain meaningful insights from multi-omics data integration.

Encoding ordered structural complexity to covalent organic frameworks.

Installing different chemical entities onto crystalline frameworks with well-defined spatial distributions represents a viable approach to achieve ordered and complex synthetic materials. Herein, a covalent organic framework (COF-305) is constructed from tetrakis(4-aminophenyl)methane and 2,3-dimethoxyterephthalaldehyde, which has the largest unit cell and asymmetric unit among known COFs. The ordered complexity of COF-305 is embodied by nine different stereoisomers of its constituents showing specific sequences on topologically equivalent sites, which can be attributed to its building blocks deviating from their intrinsically preferred simple packing geometries in their molecular crystals to adapt to the framework formation. The insight provided by COF-305 supplements the principle of covalent reticular design from the perspective of non-covalent interactions and opens opportunities for pursuing complex chemical sequences in molecular frameworks.

Pressure-Induced Defects and Reduced Size Endow TiO2 with High Capacity over 20 000 Cycles and Excellent Fast-Charging Performance in Sodium Ion Batteries.

Anatase TiO2 as sodium-ion-battery anode has attracted increased attention because of its low volume change and good safety. However, low capacity and poor rate performance caused by low electrical conductivity and slow ion diffusion greatly impede its practical applications. Here, a bi-solvent enhanced pressure strategy that induces defects (oxygen vacancies) into TiO2 via N doping and reduces its size by using mutual-solvent ethanol and dopant dimethylformamide as pressure-increased reagent of tetrabutyl orthotitanate tetramer is proposed to fabricate N-doped TiO2 /C nanocomposites. The induced defects can increase ion storage sites, improve electrical conductivity, and decrease bandgap and ion diffuse energy barrier of TiO2 . The size reduction increases contact interfaces between TiO2 and C and shortens ion diffuse distance, thus increasing extra ion storage sites and boosting ion diffusion rate of TiO2 . The N-doped TiO2 possesses highly stable crystal structure with a slightly increase of 0.86% in crystal lattice spacing and 3.2% in particle size after fully sodiation. Consequently, as a sodium-ion battery anode, the nanocomposite delivers high capacity and superior rate capability along with ultralong cycling life. This work proposes a novel pressure-induced synthesis strategy that provides unique guidance for designing TiO2 -based anode materials with high capacity and excellent fast-charging capability.

ROCK1 deficiency preserves caveolar compartmentalization of signaling molecules and cell membrane integrity.

In this study, we investigated the roles of ROCK1 in regulating structural and functional features of caveolae located at the cell membrane of cardiomyocytes, adipocytes, and mouse embryonic fibroblasts (MEFs) as well as related physiopathological effects. Caveolae are small bulb-shaped cell membrane invaginations, and their roles have been associated with disease conditions. One of the unique features of caveolae is that they are physically linked to the actin cytoskeleton that is well known to be regulated by RhoA/ROCKs pathway. In cardiomyocytes, we observed that ROCK1 deficiency is coincident with an increased caveolar density, clusters, and caveolar proteins including caveolin-1 and -3. In the mouse cardiomyopathy model with transgenic overexpressing Gαq in myocardium, we demonstrated the reduced caveolar density at cell membrane and reduced caveolar protein contents. Interestingly, coexisting ROCK1 deficiency in cardiomyocytes can rescue these defects and preserve caveolar compartmentalization of ß-adrenergic signaling molecules including ß1-adrenergic receptor and type V/VI adenylyl cyclase. In cardiomyocytes and adipocytes, we detected that ROCK1 deficiency increased insulin signaling with increased insulin receptor activation in caveolae. In MEFs, we identified that ROCK1 deficiency increased caveolar and total levels of caveolin-1 and cell membrane repair ability after mechanical or chemical disruptions. Together, these results demonstrate that ROCK1 can regulate caveolae plasticity and multiple functions including compartmentalization of signaling molecules and cell membrane repair following membrane disruption by mechanical force and oxidative damage. These findings provide possible molecular insights into the beneficial effects of ROCK1 deletion/inhibition in cardiomyocytes, adipocytes, and MEFs under certain diseased conditions.

Frameshift mutations in peripheral blood as a biomarker for surveillance of lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes, which lead to high microsatellite instability (MSI-H) and frameshift mutations (FSMs) at coding mononucleotide repeats (cMNRs) in the genome. Recurrent FSMs in these regions are thought to play a central role in the increased risk of various cancers. However, there are no biomarkers currently available for the surveillance of MSI-H-associated cancers. METHODS: An FSM-based biomarker panel was developed and validated by targeted next generation sequencing of supernatant DNA from cultured MSI-H colorectal cancer cells. This supported selection of 122-FSM targets as potential biomarkers. This biomarker panel was then tested using matched tumor, adjacent normal tissue, and buffy coat (53 samples), and blood-derived cell-free DNA (cfDNA; 38 samples) obtained from 45 cases of MSI-H/MMR deficient (MMRd) patients/carriers. cfDNA from 84 healthy individuals was also sequenced to assess background noise. RESULTS: Recurrent FSMs at cMNRs were detectable not only in tumors, but also in cfDNA from MSI-H/MMRd cases including a LS carrier with a varying range of target detection (up to 85.2%), whereas they were virtually undetectable in healthy individuals. ROC analysis showed high sensitivity and specificity (AUC = 0.94) of the investigated panel. CONCLUSIONS: We demonstrated that FSMs can be detected in cfDNA from MSI-H/MMRd cases and asymptomatic carriers. The 122-target FSM panel described here has promise as a tool for improved surveillance of MSI-H/MMRd carriers with the potential to reduce the frequency of invasive screening methods for this high-cancer-risk cohort.

METTL3 orchestrates glycolysis by stabilizing the c-Myc/WDR5 complex in triple-negative breast cancer.

BACKGROUND: The carcinogenic transcription factor c-Myc is the most aggressive oncogene, which drive malignant transformation and dissemination of triple-negative breast cancer (TNBC). Recruitment of many cofactors, especially WDR5, a protein that nucleates H3K4me chromatin modifying complexes, play a pivotal role in regulating c-Myc-dependent gene transcription, a critical process for c-Myc signaling to function in a variety of biological and pathological contexts. For this reason, interrupting the interaction between c-Myc and the transcription cofactor WDR5 may become the most promising new strategy for treating c-Myc driven TNBC. METHODS: Immunoprecipitation and mass spectrometry (IP-MS) is used to screen proteins that bind c-Myc/WDR5 interactions. The interaction of METTL3 with c-Myc/WDR5 in breast cancer tissues and TNBC cells was detected by Co-IP and immunofluorescence. Subsequently, we further analyzed the influence of METTL3 expression on c-Myc/WDR5 protein expression and its interaction stability by Western blot and Co-IP. The correlation between METTL3 and c-Myc pathway was analyzed by ChIP-seq sequencing and METTL3 knockdown transcriptome data. The effect of METTL3 expression on c-Myc transcriptional activity was detected by ChIP-qPCR and Dual Luciferase Reporter. At the same time, the overexpression vector METTL3-MUT (m6A) was constructed, which mutated the methyltransferase active site (Aa395-398, DPPW/APPA), and further explored whether the interaction between METTL3 and c-Myc/WDR5 was independent of methyltransferase activity. In addition, we also detected the changes of METTL3 expression on TNBC's sensitivity to small molecule inhibitors such as JQ1 and OICR9429 by CCK8, Transwell and clonal formation assays. Finally, we further verified our conclusions in spontaneous tumor formation mouse MMTV-PyMT and nude mouse orthotopic transplantation tumor models. RESULTS: METTL3 was found to bind mainly to c-Myc/WDR5 protein in the nucleus. It enhances the stability of c-Myc/WDR5 interaction through its methyltransferase independent mechanism, thereby enhancing the transcriptional activity of c-Myc on downstream glucose metabolism genes. Notably, the study also confirmed that METTL3 can directly participate in the transcription of glucose metabolism genes as a transcription factor, and knockdown METTL3 enhances the drug sensitivity of breast cancer cells to small molecule inhibitors JQ1 and OICR9429. The study was further confirmed by spontaneous tumor formation mouse MMTV-PyMT and nude mouse orthotopic transplantation tumor models. CONCLUSION: METTL3 binds to the c-Myc/WDR5 protein complex and promotes glycolysis, which plays a powerful role in promoting TNBC progression. Our findings further broaden our understanding of the role and mechanism of action of METTL3, and may open up new therapeutic avenues for effective treatment of TNBC with high c-Myc expression.

Effects of ambient UVB light on Pacific oyster Crassostrea gigas mantle tissue based on multivariate data.

Ambient ultraviolet radiation (UVB) from solar and artificial light presents serious environmental risks to aquatic ecosystems. The Pacific oyster, Crassostrea gigas, perceives changes in the external environment primarily through its mantle tissue, which contains many nerve fibers and tentacles. Changes within the mantles can typically illustrate the injury of ambient UVB. In this study, a comprehensive analysis of phenotypic, behavioral, and physiological changes demonstrated that extreme UVB radiation (10 W/m²) directly suppressed the behavioral activities of C. gigas. Conversely, under ambient UVB radiation (5 W/m²), various physiological processes exhibited significant alterations in C. gigas, despite the behavior remaining relatively unaffected. Using mathematical model analysis, the integrated analysis of the full-length transcriptome, proteome, and metabolome showed that ambient UVB significantly affected the metabolic processes (saccharide, lipid, and protein metabolism) and cellular biology processes (autophagy, apoptosis, oxidative stress) of the C. gigas mantle. Subsequently, using Procrustes analysis and Pearson correlation analysis, the association between multi-omics data and physiological changes, as well as their biomarkers, revealed the effect of UVB on three crucial biological processes: activation of autophagy signaling (key factors: Ca2+, LC3B, BECN1, caspase-7), response to oxidative stress (reactive oxygen species, heat shock 70, cytochrome c oxidase), and recalibration of energy metabolism (saccharide, succinic acid, translation initiation factor IF-2). These findings offer a fresh perspective on the integration of multi-data from non-model animals in ambient UVB risk assessment.