Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir.

Nirmatrelvir is a specific antiviral targeting the main protease (Mpro) of SARS-CoV-2, and has been approved to treat COVID-191,2. As an RNA virus characterized by high mutation rates, whether SARS-CoV-2 will develop resistance to nirmatrelvir is a concern. Our previous studies have shown that several mutational pathways confer resistance to nirmatrelvir but some result in a loss of viral replicative fitness, which in turn are compensated by additional mutations3. The molecular mechanisms for this observed resistance are yet unknown. Here we combined biochemical and structural methods to demonstrate that mutations at the substrate binding pocket of the Mpro can allow SARS-CoV-2 to develop resistance to nirmatrelvir in two distinct ways. Comprehensive studies of 14 complex structures of Mpro mutants with drugs or substrate revealed that mutations at the S1 and S4 subsites significantly decreased inhibitor binding, while mutations at the S2 and S4' subsites unexpectedly increased protease activity. Both mechanisms contributed to nirmatrelvir resistance, whereas the latter compensated for the loss in enzymatic activity of the former, which in turn accounted for the restoration of viral replicative fitness as we have observed previously3. Such a profile was also observed for ensitrelvir, another clinically relevant Mpro inhibitor. These results shed light on the mechanisms by which SARS-CoV-2 evolves to develop resistance to the current generation of protease inhibitors and provide the basis for the design of next-generation Mpro inhibitors.

SPSI: A Novel Composite Index for Estimating Panicle Number in Winter Wheat before Heading from UAV Multispectral Imagery.

Rapid and accurate estimation of panicle number per unit ground area (PNPA) in winter wheat before heading is crucial to evaluate yield potential and regulate crop growth for increasing the final yield. The accuracies of existing methods were low for estimating PNPA with remotely sensed data acquired before heading since the spectral saturation and background effects were ignored. This study proposed a spectral-textural PNPA sensitive index (SPSI) from unmanned aerial vehicle (UAV) multispectral imagery for reducing the spectral saturation and improving PNPA estimation in winter wheat before heading. The effect of background materials on PNPA estimated by textural indices (TIs) was examined, and the composite index SPSI was constructed by integrating the optimal spectral index (SI) and TI. Subsequently, the performance of SPSI was evaluated in comparison with other indices (SI and TIs). The results demonstrated that green-pixel TIs yielded better performances than all-pixel TIs apart from TI[HOM], TI[ENT], and TI[SEM] among all indices from 8 types of textural features. SPSI, which was calculated by the formula DATT[850,730,675] + NDTICOR[850,730], exhibited the highest overall accuracies for any date in any dataset in comparison with DATT[850,730,675], TINDRE[MEA], and NDTICOR[850,730]. For the unified models assembling 2 experimental datasets, the RV2 values of SPSI increased by 0.11 to 0.23, and both RMSE and RRMSE decreased by 16.43% to 38.79% as compared to the suboptimal index on each date. These findings indicated that the SPSI is valuable in reducing the spectral saturation and has great potential to better estimate PNPA using high-resolution satellite imagery.

DataDTA: a multi-feature and dual-interaction aggregation framework for drug-target binding affinity prediction.

MOTIVATION: Accurate prediction of drug-target binding affinity (DTA) is crucial for drug discovery. The increase in the publication of large-scale DTA datasets enables the development of various computational methods for DTA prediction. Numerous deep learning-based methods have been proposed to predict affinities, some of which only utilize original sequence information or complex structures, but the effective combination of various information and protein-binding pockets have not been fully mined. Therefore, a new method that integrates available key information is urgently needed to predict DTA and accelerate the drug discovery process. RESULTS: In this study, we propose a novel deep learning-based predictor termed DataDTA to estimate the affinities of drug-target pairs. DataDTA utilizes descriptors of predicted pockets and sequences of proteins, as well as low-dimensional molecular features and SMILES strings of compounds as inputs. Specifically, the pockets were predicted from the three-dimensional structure of proteins and their descriptors were extracted as the partial input features for DTA prediction. The molecular representation of compounds based on algebraic graph features was collected to supplement the input information of targets. Furthermore, to ensure effective learning of multiscale interaction features, a dual-interaction aggregation neural network strategy was developed. DataDTA was compared with state-of-the-art methods on different datasets, and the results showed that DataDTA is a reliable prediction tool for affinities estimation. Specifically, the CI of DataDTA is 0.806 and the R value is 0.814 on the test dataset, which is higher than other methods. AVAILABILITY AND IMPLEMENTATION: The codes of DataDTA are available at https://github.com/YanZhu06/DataDTA. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sodium Layered/Tunnel Intergrowth Oxide Cathodes: Formation Process, Interlocking Chemistry, and Electrochemical Performance.

Manganese-based layered oxides are prospective cathode materials for sodium-ion batteries (SIBs) due to their low cost and high theoretical capacities. The biphasic intergrowth structure of layered cathode materials is essential for improving the sodium storage performance, which is attributed to the synergistic effect between the two phases. However, the in-depth formation mechanism of biphasic intergrowth materials remains unclear. Herein, the layered/tunnel intergrowth Na0.6MnO2 (LT-NaMO) as a model material was successfully prepared, and their formation processes and electrochemical performance were systematically investigated. In situ high-temperature X-ray diffraction displays the detailed evolution process and excellent thermal stability of the layered/tunnel intergrowth structure. Furthermore, severe structural strain and large lattice volume changes are significantly mitigated by the interlocking effect between the phase interfaces, which further enhances the structural stability of the cathode materials during the charging/discharging process. Consequently, the LT-NaMO cathode displays fast Na+ transport kinetics with a remarkable capacity retention of ∼70.5% over 300 cycles at 5C, and its assembled full cell with hard carbon also exhibits high energy density. These findings highlight the superior electrochemical performance of intergrowth materials due to interlocking effects between layered and tunnel structures and also provide unique insights into the construction of intergrowth cathode materials for SIBs.

Glioblastoma cellular MAP4K1 facilitates tumor growth and disrupts T effector cell infiltration.

MAP4K1 has been identified as a cancer immunotherapy target. Whether and how cancer cell-intrinsic MAP4K1 contributes to glioblastoma multiforme (GBM) progression remains unclear. We found that MAP4K1 was highly expressed in the glioma cells of human GBM specimens. High levels of MAP4K1 mRNA were prevalent in IDH-WT and 1p/19q non-codeletion gliomas and correlated with poor prognosis of patients. MAP4K1 silencing inhibited GBM cell proliferation and glioma growth. Transcriptome analysis of GBM cells and patient samples showed that MAP4K1 modulated cytokine‒cytokine receptor interactions and chemokine signaling pathway, including IL-18R and IL-6R Importantly, MAP4K1 loss down-regulated membrane-bound IL-18R/IL-6R by inhibiting the PI3K-AKT pathway, whereas MAP4K1 restoration rescued this phenotype and therefore GBM cell proliferation. MAP4K1 deficiency abolished GBM cell pro-proliferation responses to IL-18, suggesting an oncogenic role of MAP4K1 via the intrinsic IL-18/IL-18R pathway. In addition, GBM cell-derived MAP4K1 impaired T-cell migration and reduced CD8+ T-cell infiltration in mouse glioma models. Together, our findings provide novel insight into the pathological significance of GBM cell-intrinsic MAP4K1 in driving tumor growth and immune evasion by remodeling cytokine-chemokine networks.

A protocol for measuring the sexual receptivity of female Drosophila.

Female receptivity in mating is crucial for successful copulation, but protocols for quantifying female behaviors reflecting receptivity are scarce compared to the analysis of male behaviors. Here, we present a protocol for assessing the sexual receptivity of female Drosophila that considers behaviors from both sexes. We describe steps for preparing and loading flies into a courtship chamber, video recording the behaviors of the pairs, and analyzing their behavioral displays. This protocol includes behavior recognition criteria suitable for typical laboratory settings. For complete details on the use and execution of this protocol, please refer to Yang et al. (2023).1.

Effect of auricular acupressure combined with acupuncture for juvenile pseudomyopia.

This retrospective study investigated the effect of auricular acupressure combined with acupuncture for juvenile pseudomyopia (JPM). In this retrospective study, we collected and analyzed a total of 66 eligible records of subjects with JPM. They were allocated into a treatment group (n = 33) and a control group (n = 33). All participants in both groups received auricular acupressure. Additionally, children in the treatment group also underwent acupuncture. The primary outcome was naked visual acuity (VA). It was performed using a standard E visual acuity chart. The secondary outcome was visual fatigue symptoms, as assessed by the College of Optometrists in Vision Development Quality of Life (COVD-QoL) questionnaire. All outcomes were analyzed before and after treatment. There were no significant differences regarding the naked VA and COVD-QoL scores before and after treatment between the 2 groups. However, there were significant differences regarding on naked VA (P < .01) and COVD-QoL scores (P < .01) within 2 groups compared before and after treatment. The findings of this study showed that both APP plus acupuncture and APP alone benefit children with JPM.

Highly Stretchable, Biodegradable, and Recyclable Green Electronic Substrates.

As a steady stream of electronic devices being discarded, a vast amount of electronic substrate waste of petroleum-based nondegradable polymers is generated, raising endless concerns about resource depletion and environmental pollution. With coupled reagent (CR)-grafted artificial marble waste (AMW@CR) as functional fillers, polylactic acid (PLA)-based highly stretchable biodegradable green composite (AMW@CR-SBGC) is prepared, with elongation at break up to more than 250%. The degradation mechanism of AMW@CR-SBGC is deeply revealed. AMW@CR not only contributed to the photodegradation of AMW@CR-SBGC but also significantly promoted the water degradation of AMW@CR-SBGC. More importantly, AMW@CR-SBGC showed great potential as sustainable green electronic substrates and AMW@CR-SBGC-based electronic skin can simulate the perception of human skin to strain signals. The outstanding programmable degradability, recyclability, and reusability of AMW@CR-SBGC enabled its application in transient electronics. As the first demonstration of artificial marble waste in electronic substrates, AMW@CR-SBGC killed three birds with one stone in terms of waste resourcing, e-waste reduction, and saving nonrenewable petroleum resources, opening up vast new opportunities for green electronics applications in areas such as health monitoring, artificial intelligence, and security.

[Effects of Combined Application of Different Nitrogen Fertilizers and Biochar on Cadmium Uptake by Pakchoi (Brassica chinensis L.) in Cadmium Contaminated Soil].

Nitrogen is an essential nutrient element for crop growth, and biochar is a good material for soil remediation. In this study, a pakchoi (Brassica chinensis L.) pot experiment was conducted to investigate the effects of the combined application of three nitrogen fertilizers, including urea, ammonium sulfate, calcium nitrate, and biochar on pakchoi growth and cadmium (Cd) uptake from cropland soil contaminated by Cd. The results showed that the application of nitrogen fertilizers and biochar prompted pakchoi growth, and the biomass of pakchoi in the treatments of single applications of urea, ammonium sulfate, calcium nitrate, and biochar were significantly increased by 5.02%-32.9%, as compared with that in the control treatment without nitrogen fertilizer application. The biomass of pakchoi in the treatments of the combined application of nitrogen fertilizers and biochar were significantly increased by 8.84%-50.8%, as compared with that in the treatment of the single application of nitrogen fertilizer. Compared with that under the control treatment without nitrogen fertilizer application, the single application of urea significantly reduced soil pH by 0.27 and significantly increased the content of soil available Cd by 30.0%. The single application of ammonium sulfate significantly reduced soil pH by 0.33 and significantly increased Cd content in pakchoi by 29.2%, as compared with that in the control treatment. The single application of calcium nitrate had no significant effect on soil pH or Cd content in pakchoi, whereas the single application of biochar significantly increased soil pH by 0.35 and significantly decreased the content of soil available Cd and content of Cd in pakchoi by 57.4% and 53.7%, respectively, as compared with that in the control treatment. Soil pH in the treatments of the combined application of nitrogen fertilizers and biochar was significantly increased by 0.14-0.28, the contents of soil available Cd were decreased by 16.5%-30.1%, and the contents of Cd in pakchoi were reduced by 15.3%-28.6%, as compared with that in the treatment of single application of nitrogen fertilizers. In general, the application of biochar could adjust the effects of different nitrogen fertilizers on Cd availability in the contaminated soil. During the remediation process of heavy metal-contaminated cropland, nitrogen fertilizer should be selected and applied reasonably to obtain the maximum economic and environmental benefits.

The associations between dietary flavonoid intake and the prevalence of diabetes mellitus: Data from the National Health and Nutrition Examination Survey 2007-2010 and 2017-2018.

Background: Diabetes mellitus (DM) is a prominent health concern worldwide, leading to the high incidence of disability and mortality and bringing in heavy healthcare and social burden. Plant-based diets are reported associated with a reduction of DM risk. Plant-based diets are rich in flavonoids, which possess properties such as scavenging free radicals and exerting both anti-inflammatory and antioxidant effects. Purpose: However, whether dietary flavonoids are associated with the prevalence of DM remains controversial. The potential reasons for contradictory epidemiological outcomes on the association between dietary flavonoids and DM prevalence have not been determined. Methods: To address these limitations, we employed data from 22,481 participants in the National Health and Nutrition Examination Survey to explore the association between the intake of flavonoids and DM prevalence by weighted Logistic regression and weighted restricted cubic splines. Results: We found that the prevalence of DM was inversely associated with the intake of total flavonoids in the second quartile [Odds Ratio (OR) 0.78 95% confidence interval (CI) (0.63, 0.97), p = 0.028], in the third quartile [0.76 (0.60, 0.97), p = 0.031], and in the fourth quartile [0.80 (0.65, 0.97), p = 0.027]. However, the p for trend was not significant [0.94 (0.88, 1.01), p = 0.096]. Moreover, the association between DM prevalence and the intake of total flavonoids was significantly influenced by race (p for interaction = 0.006). In Mexican Americans, there was a significant positive association between DM prevalence and total flavonoid intake within the third quartile [1.04 (1.02, 1.07), p = 0.003]. Total flavan-3-ol and subtotal catechin intake exhibited a non-linear U-shaped association with DM prevalence (p for non-linearity < 0.0001 and p for non-linearity < 0.0001, respectively). Compared to the first quartile of corresponding intakes, consumption within the third quartile of subtotal catechins [0.70 (0.55, 0.89), p = 0.005] and total flavan-3-ols [0.65 (0.50, 0.84), p = 0.002] was associated with a lower prevalence of DM. Conclusion: Taken together, our study may provide preliminary research evidence for personalized improvement of dietary habits to reduce the prevalence of diabetes.

Phosphate ester functionalized fluorene-benzothiadiazole alternating copolymer/hydroxylated g-C3N4 heterojunctions for efficient hydrogen evolution under visible-light irradiation.

It is highly desirable to explore functionalized polymer semiconductor/g-C3N4 heterojunction photocatalysts with the tight interfacial connection for promoting the photogenerated electron-hole pair separation, improving the hydrophilicity, extending the visible light response and achieving the efficient visible light-driven H2 evolution. Herein, we synthesized novel poly[9,9-bis(3-ethyl phosphate propyl)fluorene-alt-benzothiadiazole] (PPFBT) with a phosphate ester on every repeating unit by the Suzuki polymerization and then fabricated PPFBT/hydroxylated g-C3N4 (PPFBT/CN-OH) heterojunctions via a surface hydroxyl-induced assembly process. The ratio-optimized 5PPFBT/CN-OH shows the hydrogen evolution activity of 2662.4 µmol·g-1·h-1, an 11.1-time enhancement compared to CN-OH. The improved photocatalytic activity is mainly attributed to the enhanced electron-hole pair separation due to the tight interfacial connection by hydrogen bond (P=O…H-O) and N…S interactions between PPFBT and CN-OH. It is verified that abundant phosphate ester groups of PPFBT improve the hydrophilicity and form coordination bonds with platinum (P=O:Pt) as a cocatalyst to facilitate water splitting for H2 evolution. It is also confirmed that the enhanced electron-hole pair separation is mainly dependent on the excited high-energy level electron transfer from CN-OH to PPFBT. This work provides a rational molecular design strategy for constructing efficient functionalized polymer semiconductor/g-C3N4 heterojunctions for sunlight-driven H2 evolution.

Isolation of ACE2-dependent and -independent sarbecoviruses from Chinese horseshoe bats.

While the spike proteins from severe acute respiratory syndrome coronaviruses-1 and 2 (SARS-CoV and SARS-CoV-2) bind to host angiotensin-converting enzyme 2 (ACE2) to infect cells, the majority of bat sarbecoviruses cannot use ACE2 from any species. Despite their discovery almost 20 years ago, ACE2-independent sarbecoviruses have never been isolated from field samples, leading to the assumption these viruses pose little risk to humans. We have previously shown how spike proteins from a small group of ACE2-independent bat sarbecoviruses may possess the ability to infect human cells in the presence of exogenous trypsin. Here, we adapted our earlier findings into a virus isolation protocol and recovered two new ACE2-dependent viruses, RsYN2012 and RsYN2016A, as well as an ACE2-independent virus, RsHuB2019A. Although our stocks of RsHuB2019A rapidly acquired a tissue-culture adaption that rendered the spike protein resistant to trypsin, trypsin was still required for viral entry, suggesting limitations on the exogenous entry factors that support bat sarbecoviruses. Electron microscopy revealed that ACE2-independent sarbecoviruses have a prominent spike corona and share similar morphology to other coronaviruses. Our findings demonstrate a broader zoonotic threat posed by sarbecoviruses and shed light on the intricacies of coronavirus isolation and propagation in vitro. IMPORTANCE Several coronaviruses have been transmitted from animals to people, and 20 years of virus discovery studies have uncovered thousands of new coronavirus sequences in nature. Most of the animal-derived sarbecoviruses have never been isolated in culture due to cell incompatibilities and a poor understanding of the in vitro requirements for their propagation. Here, we built on our growing body of work characterizing viral entry mechanisms of bat sarbecoviruses in human cells and have developed a virus isolation protocol that allows for the exploration of these understudied viruses. Our protocol is robust and practical, leading to successful isolation of more sarbecoviruses than previous approaches and from field samples that had been collected over a 10-year longitudinal study.

Transcriptomics analysis and fed-batch regulation of high astaxanthin-producing Phaffia rhodozyma/Xanthophyllomyces dendrorhous obtained through adaptive laboratory evolution.

Astaxanthin has high utilization value in functional food because of its strong antioxidant capacity. However, the astaxanthin content of Phaffia rhodozyma is relatively low. Adaptive laboratory evolution is an excellent method to obtain high-yield strains. TiO2 is a good inducer of oxidative stress. In this study, different concentrations of TiO2 were used to domesticate P. rhodozyma, and at a concentration of 1000 mg/L of TiO2 for 105 days, the optimal strain JMU-ALE105 for astaxanthin production was obtained. After fermentation, the astaxanthin content reached 6.50 mg/g, which was 41.61% higher than that of the original strain. The ALE105 strain was fermented by batch and fed-batch, and the astaxanthin content reached 6.81 mg/g. Transcriptomics analysis showed that the astaxanthin synthesis pathway, and fatty acid, pyruvate, and nitrogen metabolism pathway of the ALE105 strain were significantly upregulated. Based on the nitrogen metabolism pathway, the nitrogen source was adjusted by ammonium sulphate fed-batch fermentation, which increased the astaxanthin content, reaching 8.36 mg/g. This study provides a technical basis and theoretical research for promoting industrialization of astaxanthin production of P. rhodozyma. ONE-SENTENCE SUMMARY: A high-yield astaxanthin strain (ALE105) was obtained through TiO2 domestication, and its metabolic mechanism was analysed by transcriptomics, which combined with nitrogen source regulation to further improve astaxanthin yield.

Enhancement of Terahertz Emission by Silver Nanoparticles in a Liquid Medium.

Due to higher molecular density, lower ionization potential, and a better self-healing property compared with gases, liquid targets have been used for laser-induced terahertz generation for many years. In this work, a liquid target used for terahertz radiation is embedded with silver nanoparticles (Ag NPs), which makes the material have both the fluidity of liquids and conductivity of metals. Meanwhile, the experimental setup is easier to implement than that of liquid metals. Polyvinyl alcohol (PVA) is used as a stabilizing agent to avoid precipitation formation. It is observed that the power of 0.5 THz radiation from the Ag NP suspension is five times stronger than that from liquid water in identical experimental conditions. In addition, the reusability of the material is investigated using multiple excitations. UV-visible spectroscopy and TEM imaging are carried out to analyze the target material after each excitation. As a result, quasispherical Ag NP suspensions show good reusability for several excitations and only a decrease in particle concentration is observed. By contrast, the chain-like Ag NP suspension shows poor stability due to PVA damage caused by intense laser pulses, so it cannot be used in a recyclable manner.

Polyamidoamine Dendrimers Functionalized Water-Stable Metal-Organic Frameworks for Sensitive Fluorescent Detection of Heavy Metal Ions in Aqueous Solution.

In this work, polyamidoamine (PAMAM)-functionalized water-stable Al-based metal-organic frameworks (MIL-53(Al)-NH2) were proposed with enhanced fluorescence intensity, and used for the sensitive detection of heavy metal ions in aqueous solution. The size and morphology of MIL-53(Al)-NH2 were effectively optimized by regulating the component of the reaction solvents. PAMAM dendrimers were subsequently grafted onto the surface with glutaraldehyde as a cross-linking agent. It was found that the size and morphology of MIL-53(Al)-NH2 have great influence on their fluorescence properties, and PAMAM grafting could distinctly further improve their fluorescence intensity. With higher fluorescence intensity, the PAMAM-grafted MIL-53(Al)-NH2 showed good linearity (R2 = 0.9925-0.9990) and satisfactory sensitivity (LOD = 1.1-8.6 µmol) in heavy metal ions determination. Fluorescence enhancement and heavy metal ions detection mechanisms were discussed following the experimental results. Furthermore, analogous water-stable Materials of Institute Lavoisier (MIL) metal-organic frameworks such as MIL-53(Fe)-NH2 were also proved to have similar fluorescence enhancement performance after PAMAM modification, which demonstrates the universality of the method and the great application prospects in the design of PAMAM-functionalized high-sensitivity fluorescence sensors.

Automatic Modulation Classification Based on CNN-Transformer Graph Neural Network.

In recent years, neural network algorithms have demonstrated tremendous potential for modulation classification. Deep learning methods typically take raw signals or convert signals into time-frequency images as inputs to convolutional neural networks (CNNs) or recurrent neural networks (RNNs). However, with the advancement of graph neural networks (GNNs), a new approach has been introduced involving transforming time series data into graph structures. In this study, we propose a CNN-transformer graph neural network (CTGNet) for modulation classification, to uncover complex representations in signal data. First, we apply sliding window processing to the original signals, obtaining signal subsequences and reorganizing them into a signal subsequence matrix. Subsequently, we employ CTGNet, which adaptively maps the preprocessed signal matrices into graph structures, and utilize a graph neural network based on GraphSAGE and DMoNPool for classification. Extensive experiments demonstrated that our method outperformed advanced deep learning techniques, achieving the highest recognition accuracy. This underscores CTGNet's significant advantage in capturing key features in signal data and providing an effective solution for modulation classification tasks.

Exploratory study of a multifrequency EIT-based method for detecting intracranial abnormalities.

Objective: The purpose of this paper is to compare the differences in the features of multifrequency electrical impedance tomography (MFEIT) images of human heads between healthy subjects and patients with brain diseases and to explore the possibility of applying MFEIT to intracranial abnormality detection. Methods: Sixteen healthy volunteers and 8 patients with brain diseases were recruited as subjects, and the cerebral MFEIT data of 9 frequencies in the range of 21 kHz - 100 kHz of all subjects were acquired with an MFEIT system. MFEIT image sequences were obtained according to certain imaging algorithms, and the area ratio of the ROI (AR_ROI) and the mean value of the reconstructed resistivity change of the ROI (MVRRC_ROI) on both the left and right sides of these images were extracted. The geometric asymmetry index (GAI) and intensity asymmetry index (IAI) were further proposed to characterize the symmetry of MFEIT images based on the extracted indices and to statistically compare and analyze the differences between the two groups of subjects on MFEIT images. Results: There were no significant differences in either the AR_ROI or the MVRRC_ROI between the two sides of the brains of healthy volunteers (p > 0.05); some of the MFEIT images mainly in the range of 30 kHz - 60 kHz of patients with brain diseases showed stronger resistivity distributions (larger area or stronger signal) that were approximately symmetric with the location of the lesions. However, statistical analysis showed that the AR_ROI and the MVRRC_ROI on the healthy sides of MFEIT images of patients with unilateral brain disease were not significantly different from those on the affected side (p > 0.05). The GAI and IAI were higher in all patients with brain diseases than in healthy volunteers except for 80 kHz (p < 0.05). Conclusion: There were significant differences in the geometric symmetry and the signal intensity symmetry of the reconstructed targets in the MFEIT images between healthy volunteers and patients with brain diseases, and the above findings provide a reference for the rapid detection of intracranial abnormalities using MFEIT images and may provide a basis for further exploration of MFEIT for the detection of brain diseases.

The CTBP2-PCIF1 complex regulates m6Am modification of mRNA in head and neck squamous cell carcinoma.

PCIF1 can mediate the methylation of N6,2'-O-dimethyladenosine (m6Am) in mRNA. Yet, the detailed interplay between PCIF1 and the potential cofactors and its pathological significance remains elusive. Here, we demonstrated that PCIF1-mediated cap mRNA m6Am modification promoted head and neck squamous cell carcinoma (HNSCC) progression both in vitro and in vivo. CTBP2 was identified as a cofactor of PCIF1 to catalyze m6Am deposition on mRNA. CLIP-seq data demonstrated CTBP2 bound to similar mRNAs as PCIF1. We then utilized m6Am-seq method to profile mRNA m6Am site at single-base resolution and found mRNA of TET2, a well-known tumor suppressor, was a major target substrate of PCIF1-CTBP2 complex. Mechanistically, knockout of CTBP2 reduced PCIF1 occupancy on TET2 mRNA and PCIF1-CTBP2 complex negatively regulated the translation of TET2 mRNA. Collectively, our study demonstrated the oncogenic function of the epitranscriptome regulator PCIF1-CTBP2 complex, highlighting the importance of the m6Am modification in tumor progression.

Effects of pre-anthesis low-temperature stress on the mineral components in wheat grains.

Introduction: The nutritional value of wheat is important to human health. Despite minerals being essential nutrients for the human body, they are often neglected in consideration of the nutritional quality of cereal grains. Extreme low-temperature events have become more frequent due to the current environmental unpredictability, and it is yet unknown how the mineral components in grains are affected by low temperature. Methods: To provide valuable information for enhancing the nutritional quality of wheat under potential climatic conditions, we treated different cold-sensitive wheat cultivars at four low-temperature levels during the individual and combined stages of jointing and booting in controlled-environment phytotrons. Results and Discussion: In general, the contents of P, K, Ca, and Zn in the cold-sensitive cultivar (Yangmai16) and K in the cold-tolerant cultivar (Xumai30) were enhanced by low temperature. However, the accumulation of minerals in mature grains was reduced under low-temperature treatment, except for P, Ca, and Zn in Yangmai16. In addition, the mineral content and accumulation in Yangmai16 (except for Fe) were more susceptible to low temperature during the combined stages, while the mineral content and accumulation of K, Fe, and Zn in Xumai30 were more susceptible to low temperature during the booting stage. Moreover, Yangmai16 under extremely low temperatures (T3 and T4) during booting and Xumai30 under all low-temperature treatments during the combined stages had lower comprehensive evaluation values. These findings offer a crucial reference for enhancing the nutritional quality of wheat grains under climate change.

A Universal Strategy Based on Bridging Microstructure Engineering and Local Electronic Structure Manipulation for High-Performance Sodium Layered Oxide Cathodes.

Due to their high capacity and sufficient Na+ storage, O3-NaNi0.5Mn0.5O2 has attracted much attention as a viable cathode material for sodium-ion batteries (SIBs). However, the challenges of complicated irreversible multiphase transitions, poor structural stability, low operating voltage, and an unstable oxygen redox reaction still limit its practical application. Herein, using O3-NaNi0.5Mn0.5-xSnxO2 cathode materials as the research model, a universal strategy based on bridging microstructure engineering and local electronic structure manipulation is proposed. The strategy can modulate the physical and chemical properties of electrode materials, so as to restrain the unfavorable and irreversible multiphase transformation, improve structural stability, manipulate redox potential, and stabilize the anion redox reaction. The effect of Sn substitution on the intrinsic local electronic structure of the material is articulated by density functional theory calculations. Meanwhile, the universal strategy is also validated by Ti substitution, which could be further extrapolated to other systems and guide the design of cathode materials in the field of SIBs.