Radiomics-based machine learning models for differentiating pathological subtypes in cervical cancer: a multicenter study.

Purpose: This study was designed to determine the diagnostic performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) radiomics-based machine learning (ML) in the classification of cervical adenocarcinoma (AC) and squamous cell carcinoma (SCC). Methods: Pretreatment 18F-FDG PET/CT data were retrospectively collected from patients who were diagnosed with locally advanced cervical cancer at two centers. Radiomics features were extracted and selected by the Pearson correlation coefficient and least absolute shrinkage and selection operator regression analysis. Six ML algorithms were then applied to establish models, and the best-performing classifier was selected based on accuracy, sensitivity, specificity, and area under the curve (AUC). The performance of different model was assessed and compared using the DeLong test. Results: A total of 227 patients with locally advanced cervical cancer were enrolled in this study (N=136 for the training cohort, N=59 for the internal validation cohort, and N=32 for the external validation cohort). The PET radiomics model constructed based on the lightGBM algorithm had an accuracy of 0.915 and an AUC of 0.851 (95% confidence interval [CI], 0.715-0.986) in the internal validation cohort, which were higher than those of the CT radiomics model (accuracy: 0.661; AUC: 0.513 [95% CI, 0.339-0.688]). The DeLong test revealed no significant difference in AUC between the combined radiomics model and the PET radiomics model in either the training cohort (z=0.940, P=0.347) or the internal validation cohort (z=0.285, P=0.776). In the external validation cohort, the lightGBM-based PET radiomics model achieved good discrimination between SCC and AC (AUC = 0.730). Conclusions: The lightGBM-based PET radiomics model had great potential to predict the fine histological subtypes of locally advanced cervical cancer and might serve as a promising noninvasive approach for the diagnosis and management of locally advanced cervical cancer.

Inhibition of neuroinflammation and neuronal damage by the selective non-steroidal ERß agonist AC-186.

BACKGROUND: AC-186 (4-[4-4-Difluoro-1-(2-fluorophenyl) cyclohexyl] phenol) is a neuroprotective non-steroidal selective oestrogen receptor modulator. This study investigated whether inhibition of neuroinflammation contributed to neuroprotective activity of this compound. METHODS: BV-2 microglia were treated with AC-186 (0.65-5 µM) prior to stimulation with LPS (100 ng/mL). Levels of pro-inflammatory mediators and proteins were then evaluated. RESULTS: Treatment of LPS-activated BV-2 microglia with AC-186 resulted in significant (p < 0.05) reduction in TNFα, IL-6, NO, PGE2, iNOS and COX-2. Further investigations showed that AC-186 decreased LPS-induced elevated levels of phospho-p65, phospho-IκBα and acetyl-p65 proteins, while blocking DNA binding and luciferase activity of NF-κB. AC-186 induced significant (p < 0.05) increase in protein expression of ERß, while enhancing ERE luciferase activity in BV-2 cells. Effects of the compound on oestrogen signalling in the microglia was confirmed in knockdown experiments which revealed a loss of anti-inflammatory activity following transfection with ERß siRNA. In vitro neuroprotective activity of AC-186 was demonstrated by inhibition of activated microglia-mediated damage to HT-22 neurons. CONCLUSIONS: This study established that AC-186 produces NF-κB-mediated anti-inflammatory activity, which is proposed as a contributory mechanism involved in its neuroprotective actions. It is suggested that the anti-inflammatory activity of this compound is linked to its agonist effect on ERß.

Selenium Improves Arsenic-Induced Male Reproductive Dysfunction by Regulating H3K14ac Level.

Arsenic exposure has been known to be associated with male reproduction injury. Exploring the antidote of arsenic and ascertaining proper dose of antidote are important for detoxifying the male reproductive toxicity of arsenic. Selenium, which is essential for the male reproduction and spermatogenesis, can alleviate the toxicity of many environmental toxins, such as metals, and fluoride (F). Selenium relieves arsenic-induced reductions in spermatogenesis index and testicular function marker enzymes via promoting the antioxidative ability of rats. Our previous study has found that arsenic can induce male reproductive toxicity by affecting the level of H3K14ac in the testis, so we further investigate whether selenium can antagonize arsenic-induced male reproductive toxicity through the H3K14ac pathway and ascertain the appropriate dose of selenium. The results show that selenium intervention reduces the accumulation of arsenic in rat testis probably attributing to promote the excretion of arsenic from rat, then improves the testis injury induced by arsenic. Selenium intervention enhances sperm quality, testosterone level, and expression of steroidogenic genes by regulating H3K14ac level and expression of its associated enzymes (KAT2A, BAZ2A, and HDAC6), and thus alleviates the male reproductive toxicity of arsenic, and the proper dose of Se for mitigating arsenic male reproductive toxicity is 1 mg/kg.

Genome-Wide Profiling of H3K27ac Identifies TDO2 as a Pivotal Therapeutic Target in Metabolic Associated Steatohepatitis Liver Disease.

H3K27ac has been widely recognized as a representative epigenetic marker of active enhancer, while its regulatory mechanisms in pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive. Here, a genome-wide comparative study on H3K27ac activities and transcriptome profiling in high fat diet (HFD)-induced MASLD model is performed. A significantly enhanced H3K27ac density with abundant alterations of regulatory transcriptome is observed in MASLD rats. Based on integrative analysis of ChIP-Seq and RNA-Seq, TDO2 is identified as a critical contributor for abnormal lipid accumulation, transcriptionally activated by YY1-promoted H3K27ac. Furthermore, TDO2 depletion effectively protects against hepatic steatosis. In terms of mechanisms, TDO2 activates NF-κB pathway to promote macrophages M1 polarization, representing a crucial event in MASLD progression. A bovine serum albumin nanoparticle is fabricated to provide sustained release of Allopurinol (NPs-Allo) for TDO2 inhibition, possessing excellent biocompatibility and desired targeting capacity. Venous injection of NPs-Allo robustly alleviates HFD-induced metabolic disorders. This study reveals the pivotal role of TDO2 and its underlying mechanisms in pathogenesis of MASLD epigenetically and genetically. Targeting H3K27ac-TDO2-NF-κB axis may provide new insights into the pathogenesis of abnormal lipid accumulation and pave the way for developing novel strategies for MASLD prevention and treatment.

NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction.

BACKGROUND: N4-Acetylcytidine (ac4C), a highly conserved post-transcriptional mechanism, plays a pivotal role in RNA modification and tumor progression. However, the molecular mechanism by which ac4C modification mediates tumor immunosuppression remains elusive in triple-negative breast cancer (TNBC). METHODS: NAT10 expression was analyzed in TNBC samples in the level of mRNA and protein, and compared with the corresponding normal tissues. ac4C modification levels also measured in the TNBC samples. The effects of NAT10 on immune microenvironment and tumor metabolism were investigated. NAT10-mediated ac4C and its downstream regulatory mechanisms were determined in vitro and in vivo. The combination therapy of targeting NAT10 in TNBC was further explored. RESULTS: The results revealed that the loss of NAT10 inhibited TNBC development and promoted T cell activation. Mechanistically, NAT10 upregulated JunB expression by increasing ac4C modification levels on its mRNA. Moreover, JunB further up-regulated LDHA expression and facilitated glycolysis. By deeply digging, remodelin, a NAT10 inhibitor, elevated the surface expression of CTLA-4 on T cells. The combination of remodelin and CTLA-4 mAb can further activate T cells and inhibite tumor progression. CONCLUSION: Taken together, our study demonstrated that the NAT10-ac4C-JunB-LDHA pathway increases glycolysis levels and creates an immunosuppressive tumor microenvironment (TME). Consequently, targeting this pathway may assist in the identification of novel therapeutic strategies to improve the efficacy of cancer immunotherapy.

KDELR2 is necessary for chronic obstructive pulmonary disease airway Mucin5AC hypersecretion via an IRE1α/XBP-1s-dependent mechanism.

Airway mucus hypersecretion, a crucial pathological feature of chronic obstructive pulmonary disease (COPD), contributes to the initiation, progression, and exacerbation of this disease. As a macromolecular mucin, the secretory behaviour of Mucin5AC (MUC5AC) is highly dependent on a series of modifying and folding processes that occur in the endoplasmic reticulum (ER). In this study, we focused on the ER quality control protein KDEL receptor (KDELR) and demonstrated that KDELR2 and MUC5AC were colocalized in the airway epithelium of COPD patients and COPD model rats. In addition, knockdown of KDELR2 markedly reduced the expression of MUC5AC both in vivo and in vitro and knockdown of ATF6 further decreased the levels of KDELR2. Furthermore, pretreatment with 4µ8C, an IRE1α inhibitor, led to a partial reduction in the expression of KDELR2 and MUC5AC both in vivo and in vitro, which indicated the involvement of IRE1α/XBP-1s in the upstream signalling cascade. Our study revealed that KDELR2 plays a crucial role in airway MUC5AC hypersecretion in COPD, which might be dependent on ATF6 and IRE1α/XBP-1s upstream signalling.

Assessment of homogeneous electro-Fenton process coupled with microbial fuel cell utilizing Serratia sp. AC-11 for glyphosate degradation in aqueous phase.

Glyphosate (GLY), a globally-used organophosphate herbicide, is frequently detected in various environmental matrices, including water, prompting significant attention due to its persistence and potential ecological impacts. In light of this environmental concern, innovative remediation strategies are warranted. This study utilized Serratia sp. AC-11 isolated from a tropical peatland as a biocatalyst in a microbial fuel cell (MFC) coupled with a homogeneous electron-Fenton (EF) process to degrade glyphosate in aqueous medium. After coupling the processes with a resistance of 100 Ω, an output voltage value of 0.64 V was obtained and maintained stable throughout the experiment. A bacterial biofilm of Serratia sp. AC-11 was formed on the carbon felt electrode, confirmed by attenuated total reflectance-Fourier transformed infrared (ATR-FTIR) and scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS). In the anodic chamber, the GLY biodegradation rate was 100% after 48 h of experimentation, with aminomethylphosphonic acid (AMPA) remaining in the solution. In the cathodic chamber, the GLY degradation rate for the EF process was 69.5% after 48 h experimentation, with almost all of the AMPA degraded by the in situ generated hydroxyl radicals. In conclusion, the results demonstrated that Serratia sp. AC-11 not only catalyzed the biodegradation of glyphosate but also facilitated the generation of electrons for subsequent transfer to initiate the EF reaction to degrade glyphosate. This dual functionality emphasizes the unique capabilities of Serratia sp. AC-11, it as an electrogenic microorganism with application in innovative bioelectrochemical processes, and highlighting its role in sustainable strategies for environmental remediation.

Therapeutic efficacy of Genistein in activation of neuronal AC/cAMP/CREB/PKA and mitochondrial ETC-Complex pathways in experimental model of autism: Evidence from CSF, blood plasma and brain analysis.

Autism is a complex neurodevelopmental condition characterized by repetitive behaviors, impaired social communication, and various associated conditions such as depression and anxiety. Its multifactorial etiology includes genetic, environmental, dietary, and gastrointestinal contributions. Pathologically, Autism is linked to mitochondrial dysfunction, oxidative stress, neuroinflammation, and neurotransmitter imbalances involving GABA, glutamate, dopamine, and oxytocin. Propionic acid (PRPA) is a short-chain fatty acid produced by gut bacteria, influencing central nervous system functions. Elevated PRPA levels can exacerbate Autism-related symptoms by disrupting metabolic processes and crossing the blood-brain barrier. Our research investigates the neuroprotective potential of Genistein (GNT), an isoflavone compound with known benefits in neuropsychiatric and neurodegenerative disorders, through modulation of the AC/cAMP/CREB/PKA signaling pathway and mitochondrial ETC complex (I-IV) function. In silico analyses revealed GNT's high affinity for these targets. Subsequent in vitro and in vivo experiments using a PRPA-induced rat model of autism demonstrated that GNT (40 and 80 mg/kg., orally) significantly improves locomotion, neuromuscular coordination, and cognitive functions in PRPA-treated rodents. Behavioral assessments showed reduced immobility in the forced swim test, enhanced Morris water maze performance, and restored regular locomotor activity. On a molecular level, GNT restored levels of key signaling molecules (AC, cAMP, CREB, PKA) and mitochondrial complexes (I-V), disrupted by PRPA exposure. Additionally, GNT reduced neuroinflammation and apoptosis, normalized neurotransmitter levels, and improved the complete blood count profile. Histopathological analyses confirmed that GNT ameliorated PRPA-induced brain injuries, restored normal brain morphology, reduced demyelination, and promoted neurogenesis. The study supports GNT's potential in autism treatment by modulating neural pathways, reducing inflammation, and restoring neurotransmitter balance.

Loss of NAT10 Reduces the Translation of Kmt5a mRNA Through ac4C Modification in Cardiomyocytes and Induces Heart Failure.

BACKGROUND: In the past decade, the biological functions of various RNA modifications in mammals have been uncovered. N4-acetylcytidine (ac4C), a highly conserved RNA modification, has been implicated in human diseases. Despite this, the involvement of RNA ac4C modification in cardiac physiology and pathology remains incompletely understood. NAT10 (N-acetyltransferase 10) stands as the sole acetyltransferase known to catalyze RNA ac4C modification. This study aims to explore the role of NAT10 and ac4C modification in cardiac physiology and pathology. METHODS AND RESULTS: Cardiac-specific knockout of NAT10, leading to reduced RNA ac4C modification, during both neonatal and adult stages resulted in severe heart failure. NAT10 deficiency induced cardiomyocyte apoptosis, a crucial step in heart failure pathogenesis, supported by in vitro data. Activation of the p53 signaling pathway was closely associated with enhanced apoptosis in NAT10-deficient cardiomyocytes. As ac4C modification on mRNA influences translational efficiency, we employed ribosome footprints coupled with RNA sequencing to explore genome-wide translational efficiency changes caused by NAT10 deficiency. We identified and validated that the translational efficiency of Kmt5a was suppressed in NAT10 knockout hearts due to reduced ac4C modification on its mRNA. This finding was consistent with the observation that Kmt5a protein levels were reduced in heart failure despite unchanged mRNA expression. Knockdown of Kmt5a in cardiomyocytes recapitulated the phenotype of NAT10 deficiency, including increased cardiomyocyte apoptosis and activated p53 signaling. Finally, overexpression of Kmt5a rescued cardiomyocyte apoptosis and p53 activation induced by NAT10 inhibition. CONCLUSIONS: Our study highlights the significance of NAT10 in cardiomyocyte physiology, demonstrating that NAT10 loss is sufficient to induce cardiomyocyte apoptosis and heart failure. NAT10 regulates the translational efficiency of Kmt5a, a key mediator, through mRNA ac4C modification during heart failure.

Transcriptome-Wide Profiling of Nascent RNA in Neurons with Enriched H3K27ac Signal Elevates eRNA Identification Efficiency.

Growing evidence suggests that activity-dependent gene expression is crucial for neuronal plasticity and behavioral experience. Enhancer RNAs (eRNAs), a class of long noncoding RNAs, play a key role in these processes. However, eRNAs are highly dynamic and are often present at lower levels than their corresponding mRNAs, making them difficult to detect using total RNA-seq techniques. Nascent RNA sequencing, which separates nascent RNAs from the steady-state RNA population, has been shown to increase the ability to detect activity-induced eRNAs with a higher signal-to-noise ratio. However, there is a lack of bioinformatic tools or pipelines for detecting eRNAs utilizing nascent RNA-seq and other multiomics data sets. In this study, we addressed this gap by developing a novel bioinformatic framework, e-finder, for finding eRNAs and have made it available to the scientific community. Additionally, we reanalyzed our previous nascent RNA sequencing data and compared them with total RNA-seq data to identify activity-regulated RNAs in neuronal cell populations. Using H3K27 acetylome data, we characterized activity-dependent eRNAs that drive the transcriptional activity of the target genes. Our analysis identified a subset of eRNAs involved in mediating synapse organization, which showed increased activity-dependent transcription after the potassium chloride stimulation. Notably, our data suggest that nascent RNA-seq with an enriched H3K27ac signal exhibits high resolution to identify potential eRNAs in response to membrane depolarization. Our findings uncover the role of the eRNA-mediated gene activation network in neuronal systems, providing new insights into the molecular processes characterizing neurological diseases.

Preclinical Evaluation of 226Ac as a Theranostic Agent: Imaging, Dosimetry, and Therapy.

226Ac (t½ = 29.37 h) has been proposed as a theranostic radioisotope leveraging both its diagnostic γ-emissions and therapeutic α-emissions. 226Ac emits 158 and 230 keV γ-photons ideal for quantitative SPECT imaging and acts as an in vivo generator of 4 high-energy α-particles. Because of these nuclear decay properties, 226Ac has potential to act as a standalone theranostic isotope. In this proof-of-concept study, we evaluated a preclinical 226Ac-radiopharmaceutical for its theranostic efficacy and present the first 226Ac-targeted α-therapy study. Methods: 226Ac was produced at TRIUMF and labeled with the chelator-peptide bioconjugate crown-TATE. [226Ac]Ac-crown-TATE was selected to target neuroendocrine tumors in male NRG mice bearing AR42J tumor xenografts for SPECT imaging, biodistribution, and therapy studies. A preclinical SPECT/CT scanner acquired quantitative images reconstructed from both the 158 and the 230 keV emissions. Mice in the biodistribution study were euthanized at 1, 3, 5, 24, and 48 h after injection, and internal radiation dosimetry was derived for the tumor and organs of interest to establish appropriate therapeutic activity levels. Mice in the therapy study were administered 125, 250, or 375 kBq treatments and were monitored for tumor size and body condition. Results: We present quantitative SPECT images of the in vivo biodistribution of [226Ac]Ac-crown-TATE, which showed agreement with ex vivo measurements. Biodistribution studies demonstrated high uptake (>30%IA/g at 5 h after injection) and retention in the tumor, with an estimated mean absorbed dose coefficient of 222 mGy/kBq. [226Ac]Ac-crown-TATE treatments significantly extended the median survival from 7 d in the control groups to 16, 24, and 27 d in the 125, 250, and 375 kBq treatment groups, respectively. Survival was prolonged by slowing tumor growth, and no weight loss or toxicities were observed. Conclusion: This study highlights the theranostic potential of 226Ac as a standalone therapeutic isotope in addition to its demonstrated diagnostic capabilities to assess dosimetry in matched 225Ac-radiopharmaceuticals. Future studies will investigate maximum dose and toxicity to further explore the therapeutic potential of 226Ac-radiopharmaceuticals.

Drought-responsive dynamics of H3K9ac-marked 3D chromatin interactions are integrated by OsbZIP23-associated super-enhancer-like promoter regions in rice.

BACKGROUND: In response to drought stress (DS), plants undergo complex processes that entail significant transcriptome reprogramming. However, the intricate relationship between the dynamic alterations in the three-dimensional (3D) genome and the modulation of gene co-expression in drought responses remains a relatively unexplored area. RESULTS: In this study, we reconstruct high-resolution 3D genome maps based on genomic regions marked by H3K9ac, an active histone modification that dynamically responds to soil water variations in rice. We discover a genome-wide disconnection of 3D genome contact upon DS with over 10,000 chromatin loops lost, which are partially recovered in the subsequent re-watering. Loops integrating promoter-promoter interactions (PPI) contribute to gene expression in addition to basal H3K9ac modifications. Moreover, H3K9ac-marked promoter regions with high affinities in mediating PPIs, termed as super-promoter regions (SPRs), integrate spatially clustered PPIs in a super-enhancer-like manner. Interestingly, the knockout mutation of OsbZIP23, a well-defined DS-responsive transcription factor, leads to the disassociation of over 80% DS-specific PPIs and decreased expression of the corresponding genes under DS. As a case study, we show how OsbZIP23 integrates the PPI cluster formation and the co-expression of four dehydrin genes, RAB16A-D, through targeting the RAB16C SPR in a stress signaling-dependent manner. CONCLUSIONS: Our high-resolution 3D genome maps unveil the principles and details of dynamic genome folding in response to water supply variations and illustrate OsbZIP23 as an indispensable integrator of the yet unique 3D genome organization that is essential for gene co-expression under DS in rice.

AC Loss Measurement in Nb3Sn Coil for a New Fast Switching-field MR Concept Magnet.

The ability to perform magnetic resonance (MR) imaging or spectroscopy at significantly different magnetic field strengths during scanning holds great potential for expanding the range of contrast parameter options and obtaining high "superthermal" spin polarization for increased signal-to-noise ratio (SNR) or measuring certain spins at what would otherwise be impractically high RF frequencies. Enabling measurements at multiple field strengths heretofore has required either rapidly altering the strength of a resistive magnet with pulsed currents or shuttling the specimen between two field regions. We propose a novel approach to switching-field MR that we expect to be practical for live animal and ultimately human imaging. In this paper we propose the design of a liquid-helium-free fast switching-field MR magnet that can change the field very quickly in time (≤ 1 s) between significantly different field strengths. For this magnet, two types of Nb3Sn wire are selected, and AC loss is measured by electrical method, and characteristics are analyzed.

Privacy-preserving distributed frequency control for AC microgrids with constrained communication.

Distributed control of AC microgrids is one of the most popular methods in the islanded operation mode. Whereas, most of the existing studies either do not consider the potential threat of privacy security or rely on the assumption of ideal communication networks. To this end, this paper presents a novel privacy-preserving distributed secondary frequency control strategy for the privacy protection problem of an islanded AC microgrid with constrained communication. The key contributions of this paper are threefold. (1) Different from the existing privacy-preserving approaches used in AC microgrids, a time-varying function is introduced to mask interactive information such that the frequency cannot be reconstructed by malicious attackers. (2) An event-triggered communication scheme is employed to cope with the constrained communication environment. (3) A privacy-preserving distributed event-triggered control strategy with communication delay is developed such that the frequency restoration and active power sharing of the microgrid are guaranteed. Moreover, the maximum communication delay that the proposed control can withstand is analyzed. Simulation results show the properties of the privacy preservation, the decrease of communication load, and the bounded communication delay allowed in the proposed control strategy.

The Faithless Analyst.

In this lecture, I wish to speak about the faithless analyst. This is an analyst without fixed religious notions, without specific preferences with regard to religious faith and practice, without religious commitments or attachments of the kind that would influence the course of the analysis. Is this possible? Analysts like everyone else grow up in specific cultures that are deeply entangled with religious traditions. Can analysts shed this formation when they enter the consulting room? Should they? Values come with religious faith and practice. Should the analyst shed such religiously based values for the sake of absolute neutrality? I want to think about such faithlessness as an impossible ideal for analytical practice and how to work with failures to remain faithless in the presence of different faiths or the absence of faith among patients.

Dans cette conférence, je souhaite parler de l'analyste sans foi. Il s'agit d'un analyste sans notions religieuses fixes, sans préférences spécifiques en ce qui concerne la foi et la pratique religieuses, sans engagements religieux ou attachements du type de ceux qui influenceraient le cours de l'analyse. Est­ce possible? Les analystes, comme tout le monde, grandissent dans des cultures spécifiques qui sont profondément enchevêtrées avec des traditions religieuses. Les analystes peuvent­ils se débarrasser de cela lorsqu'ils entrent dans la salle de consultation? Devraient­ils le faire? Les valeurs viennent avec la foi et la pratique religieuses. L'analyste devrait­il se débarrasser de telles valeurs fondées sur la religion au nom d'une neutralité absolue? Je veux réfléchir à une telle absence de foi religieuse comme un idéal impossible pour la pratique analytique, et à la façon de travailler avec les situations où l'on ne parvient pas à rester sans foi en présence de fois différentes ou de l'absence de foi chez les patients.

En esta conferencia quiero hablar del analista sin fe. Se trata de un analista sin nociones religiosas fijas, sin preferencias específicas con respecto a la fe y la práctica religiosas, sin compromisos religiosos ni apegos del tipo que influirían en el curso del análisis. ¿Es esto posible? Los analistas, como todo el mundo, crecen en culturas específicas profundamente vinculadas a tradiciones religiosas. ¿Pueden los analistas desprenderse de esta formación cuando entran en la consulta? ¿Deberían hacerlo? Los valores vienen con la fe y la práctica religiosas. ¿Debería el analista desprenderse de esos valores basados en la religión en búsqueda de una neutralidad absoluta? Quiero reflexionar sobre esta falta de fe como un ideal imposible para la práctica analítica y sobre cómo trabajar con los fracasos para permanecer sin fe en presencia de diferentes credos o de la ausencia de fe entre los pacientes.

AC Electric Conductivity of High Pressure and High Temperature Formed NaFePO4 Glassy Nanocomposite.

Olivine-like NaFePO4 glasses and nanocomposites are promising materials for cathodes in sodium batteries. Our previous studies focused on the preparation of NaFePO4 glass, transforming it into a nanocomposite using high-pressure-high-temperature treatment, and comparing both materials' structural, thermal, and DC electric conductivity. This work focuses on specific features of AC electric conductivity, containing messages on the dynamics of translational processes. Conductivity spectra measured at various temperatures are scaled by apparent DC conductivity and plotted against frequency scaled by DC conductivity and temperature in a so-called master curve representation. Both glass and nanocomposite conductivity spectra are used to test the (effective) exponent using Jonscher's scaling law. In both materials, the values of exponent range from 0.3 to 0.9, with different relation to temperature. It corresponds to the electronic conduction mechanism change from low-temperature Mott's variable range hopping (between Fe2+/Fe3+ centers) to phonon-assisted hopping, which was suggested by previous DC measurements. Following the pressure treatment, AC conductivity activation energies were reduced from EAC≈0.40 eV for glass to EAC≈0.18 eV for nanocomposite and are lower than their DC counterpart, following a typical empirical relation with the value of the exponent. While pressure treatment leads to a 2-3-orders-of-magnitude rise in the AC and apparent DC conductivity due to the reduced distance between the hopping centers, a nonmonotonic relation of AC power exponent and temperature is observed. It occurs due to the disturbance of polaron interactions with Na+ mobile ions.

The AC010247.2/miR-125b-5p axis triggers the malignant progression of acute myelocytic leukemia by IL-6R.

AML is a malignant tumor derived from the hematopoietic system, which has a poor prognosis and its incidence is increasing recent years. LncRNAs bind to miRNAs as competitive endogenous RNAs to regulate the occurrence and progression of AML， with IL-6R playing a crucial role in hematological malignancies. However, the mechanism by which noncoding RNAs regulate IL6R expression in AML remains unclear. This study found that the AC010247.2/miR-125b-5p axis promotes AML progression by regulating IL-6R expression. Specifically, knocking down or inhibiting AC010247.2 and miR-125b-5p affected IL6R and its downstream genes. Mechanistically, AC010247.2 acts as a ceRNA for miR-125b-5p, influencing IL-6R expression. Additionally, AC010247.2's regulation of AML progression partially depends on miR-125b-5p. Notably, the AC010247.2/miR-125b-5p/IL6R axis serves as a better polygenic diagnostic marker for AML. Our study identifies a key ceRNA regulatory axis that modulates IL6R expression in AML, providing a reliable multigene diagnostic method and potential therapeutic target.

Analysis of neuraminidase activity of human parainfluenza viruses using enzyme-linked lectin assay and BTP3-Neu5Ac assay.

Human parainfluenza viruses (hPIVs) are causative agents of upper and lower respiratory tract infections and they have four serotypes. The virion surface displays hemagglutinin-neuraminidase (HN), having hemagglutinating (HA) and neuraminidase (NA) activities in a single molecule. The HA activity binds the virion to sialic acid on the viral receptor on host cells and the NA releases the progeny viruses from the cell surface. There are several methods for assaying viral NA activity, such as the thiobarbituric acid assay, 4-methylumbelliferyl-N-acetyl-α-d-neuraminic acid assay, NA-Star assay, and enzyme-linked lectin assay (ELLA). However, these are mainly used for influenza viruses and not for hPIVs. A fluorescent-based cytochemical NA assay using BTP3-Neu5Ac as the substrate was recently developed and used for orthomyxo- and paramyxoviruses, including types 1 and 3 hPIVs. In this study, we used the ELLA, and BTP-Neu5Ac assay for 14 field isolate strains of hPIVs including all four serotypes. The reaction in ELLA at pH 6.5 using peanut agglutinin (PNA) as a lectin was very low for all tested viruses except a type 3 virus strain with the maximum reaction at pH 6.5 and the acidic conditions did not enhance the reaction. ELLA with another lectin, Erythrina cristagalli agglutinin exhibited significant and stronger reactions than with PNA in some strains of types 1 and 3 viruses. The BTP3-Neu5Ac assay showed a fluorescent signal on cells infected with all the viruses except the hPIV1/Sendai/713/2018 strain in LLC-MK2 and/or MNT-1. The signal was detected in cell-free virus, as well, in all the viruses except the hPIV4a/Sendai/3935/2003 strain. The strength of the signal varied among viral strains but it was stronger in the reaction at pH 4.0 than pH 7.0 and strongest in type 2 hPIVs.

Resistance of Bt and Non-Bt Soybean Cultivars Adapted to Novel Growing Regions of Brazil to Chrysodeixis includens and Spodoptera frugiperda.

Soybean is a highly valuable commodity crop for Brazil's economy. However, it faces significant threats from the attack of a complex of lepidopteran pests, particularly Chrysodeixis includens (Walker) and Spodoptera frugiperda (J. E. Smith). These pests have been managed primarily using transgenic Bt soybeans, but limited knowledge exists about the resistance levels of Bt and non-Bt cultivars adapted to novel soybean-growing areas in Brazil, such as the Minas Gerais state. This study evaluated the resistance levels of Bt and non-Bt soybean cultivars to C. includens and S. frugiperda, and whether the Bt cultivars can differentially affect these pests across larval stages. No-choice bioassays were conducted using Bt (NS6010 IPRO and P97R50 IPRO) and non-Bt soybeans (UFLA 6301 RR, P96R90 RR, and ANsc 80111 RR) at V4-stage in the laboratory with neonate (24 h) and third-instar larvae. Larvae were fed leaf discs in Petri dishes, recording the mortality, leaf consumption, and weight gain after 7 days. There was high mortality of C. includens neonates on the Bt cultivars, but this trend was not observed for older larvae. For S. frugiperda neonates, there was high mortality on the Bt cultivar NS 6010 IPRO and non-Bt cultivar UFLA 6301 RR, but only the former was effective for older larvae. Although the Bt cultivars did not kill the third instars, antinutritional effects were found, such that leaf tissue consumed was not converted to larval weight gain. These findings are important for defining regional strategies of integrated and resistance management of C. includens and S. frugiperda in expanding regions of soybean cultivation in Brazil.

A numerical study of the effects of lateral flow and retention in open tubular vortex chromatography.

Axial dispersion in chromatographic columns is responsible for a reduced separation efficiency. In the present research macrotransport theory is used to predict the phenomenological constants related to axial dispersion. We evaluate the efficacy of lateral flow induced by alternating current (AC) in the presence of retaining walls on the separation resolution. Results show that lateral flows induced by laterally applied potentials as low as 0.3 V reduce C-term dispersion by a factor of 5.0 for unretained conditions (k = 0) and 2.7 for retained (k = 5) conditions, with a diffusion coefficient (Dm) of 10-11m2/s. The present paper further contributes to the understanding of the use of secondary lateral flows for dispersion reduction and offers practical guidance for designing future vortex chromatographic columns. It appears that a maximal performance gain is attained at low aspect ratios (AR=1), with the gain reduced from a factor of 5 to 1.6 for AR=4 for unretained conditions, and from 2.7 to 1.4 for retained conditions (k = 5).