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Abstract The myeloid transcription factor CEBPA is recurrently biallelically mutated (i.e., double mutated; CEBPA DM) in acute myeloid leukemia (AML) with a combination of hypermorphic N-terminal mutations (CEBPA NT), promoting expression of the leukemia-associated p30 isoform, and amorphic C-terminal mutations. The most frequently co-mutated genes in CEBPA DM AML are GATA2 and TET2, however the molecular mechanisms underlying this co-mutational spectrum are incomplete. By combining transcriptomic and epigenomic analyses of CEBPA-TET2 co-mutated patients with models thereof, we identify GATA2 as a conserved target of the CEBPA-TET2 mutational axis, providing a rationale for the mutational spectra in CEBPA DM AML. Elevated CEBPA levels, driven by CEBPA NT, mediate recruitment of TET2 to the Gata2 distal hematopoietic enhancer thereby increasing Gata2 expression. Concurrent loss of TET2 in CEBPA DM AML induces a competitive advantage by increasing Gata2 promoter methylation, thereby rebalancing GATA2 levels. Of clinical relevance, demethylating treatment of Cebpa-Tet2 co-mutated AML restores Gata2 levels and prolongs disease latency.

Abstract Single-cell resolution analysis of complex biological tissues is fundamental to capture cell-state heterogeneity and distinct cellular signaling patterns that remain obscured with population-based techniques. The limited amount of material encapsulated in a single cell however, raises significant technical challenges to molecular profiling. Due to extensive optimization efforts, single-cell proteomics by Mass Spectrometry (scp-MS) has emerged as a powerful tool to facilitate proteome profiling from ultra-low amounts of input, although further development is needed to realize its full potential. To this end, we carry out comprehensive analysis of orbitrap-based data-independent acquisition (DIA) for limited material proteomics. Notably, we find a fundamental difference between optimal DIA methods for high- and low-load samples. We further improve our low-input DIA method by relying on high-resolution MS1 quantification, thus enhancing sensitivity by more efficiently utilizing available mass analyzer time. With our ultra-low input tailored DIA method, we are able to accommodate long injection times and high resolution, while keeping the scan cycle time low enough to ensure robust quantification. Finally, we demonstrate the capability of our approach by profiling mouse embryonic stem cell culture conditions, showcasing heterogeneity in global proteomes and highlighting distinct differences in key metabolic enzyme expression in distinct cell subclusters.

Here the authors show that differentiation of haematopoietic stem cells into mature blood cells is primed by cell type-specific transcription factors at the enhancer level during early differentiation, before they confere promoter-driven growth arrest, and activate post-mitotic terminal differentiation.

Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

Single-cell proteomics can provide insights into the molecular basis for cellular heterogeneity. Here, the authors develop a multiplexed single-cell proteomics and computational workflow, and show that their strategy captures the cellular hierarchies in an Acute Myeloid Leukemia culture model.

Testosterone deficiency is associated with autoimmunity and increased B cell numbers, but the underlying mechanism is unclear. Here the authors show that testosterone may modulate the production of B cell survival factor BAFF by fibroblastic reticular cells via regulation of splenic neurotransmitter levels.

Ageing and cancer is often associated with altered T cell distributions and this phenomenon has been suggested to be the main driver in the development of immunosenescence. Memory phenotype PD-1+ CD4+ T cells accumulate with age and during leukemic development, and they might account for the attenuated T cell response in elderly or diseased individuals. The transcription factor C/EBPα has been suggested to be responsible for the accumulation as well as for the senescent features of these cells including impaired TCR signaling and decreased proliferation. Thus modulating the activity of C/EBPα could potentially target PD-1+ CD4+ T cells and consequently, impede the development of immunosenescence. To exploit this possibility we tested the importance of C/EBPα for the development of age-dependent PD-1+ CD4+ T cells as well as its role in the accumulation of PD-1+ CD4+ T cells during leukemic progression. In contrast to earlier suggestions, we find that loss of C/EBPα expression in the lymphoid compartment led to an increase of PD-1+ CD4+ T cells specifically in old mice, suggesting that C/EBPα repress the accumulation of these cells in elderly by inhibiting their proliferation. Furthermore, C/EBPα-deficiency in the lymphoid compartment had no effect on leukemic development and did not affect the accumulation of PD-1+ CD4+ T cells. Thus, in addition to contradict earlier suggestions of a role for C/EBPα in immunosenescence, these findings efficiently discard the potential of using C/EBPα as a target for the alleviation of ageing/cancer-associated immunosenescence.

BackgroundTranscription factors play a key role in lineage commitment and differentiation of stem cells into distinct mature cells. In hematopoiesis, they regulate lineage-specific gene expression in a stage-specific manner through various physical and functional interactions with regulatory proteins that are simultanously recruited and activated to ensure timely gene expression. The transcription factor CCAAT/enhancer binding protein α (C/EBPα) is such a factor and is essential for the development of granulocytic/monocytic cells. The activity of C/EBPα is regulated on several levels including gene expression, alternative translation, protein interactions and posttranslational modifications, such as phosphorylation. In particular, the phosphorylation of serine 248 of the transactivation domain has been shown to be of crucial importance for granulocytic differentiation of 32Dcl3 cells in vitro.Methodology/principal findingsHere, we use mouse genetics to investigate the significance of C/EBPα serine 248 in vivo through the construction and analysis of Cebpa(S248A/S248A) knock-in mice. Surprisingly, 8-week old Cebpa(S248A/S248A) mice display normal steady-state hematopoiesis including unaltered development of mature myeloid cells. However, over time some of the animals develop a hematopoietic disorder with accumulation of multipotent, megakaryocytic and erythroid progenitor cells and a mild impairment of differentiation along the granulocytic-monocytic lineage. Furthermore, BM cells from Cebpa(S248A/S248A) animals display a competitive advantage compared to wild type cells in a transplantation assay.Conclusions/significanceTaken together, our data shows that the substitution of C/EBPα serine 248 to alanine favors the selection of the megakaryocytic/erythroid lineage over the monocytic/granulocytic compartment in old mice and suggests that S248 phosphorylation may be required to maintain proper hematopoietic homeostasis in response to changes in the wiring of cellular signalling networks. More broadly, the marked differences between the phenotype of the S248A variant in vivo and in vitro highlight the need to exert caution when extending in vitro phenotypes to the more appropriate in vivo context.

BackgroundNonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA surveillance process that facilitates the recognition and destruction of mRNAs bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs may arise from different processes, including erroneous processing and expression of pseudogenes, but also from more regulated events such as alternative splicing coupled NMD (AS-NMD). Thus, the NMD pathway serves both as a silencer of genomic noise and a regulator of gene expression. Given the early embryonic lethality in NMD deficient mice, uncovering the full regulatory potential of the NMD pathway in mammals will require the functional assessment of NMD in different tissues.Methodology/principal findingsHere we use mouse genetics to address the role of UPF2, a core NMD component, in the development, function and regeneration of the liver. We find that loss of NMD during fetal liver development is incompatible with postnatal life due to failure of terminal differentiation. Moreover, deletion of Upf2 in the adult liver results in hepatosteatosis and disruption of liver homeostasis. Finally, NMD was found to be absolutely required for liver regeneration.Conclusion/significanceCollectively, our data demonstrate the critical role of the NMD pathway in liver development, function and regeneration and highlights the importance of NMD for mammalian biology.

Abstract Ultraflat metal foils are essential for semiconductor nanoelectronics applications and nanomaterial epitaxial growth. Numerous efforts have been devoted to metal surface engineering studies in the past decades. However, various challenges persist, including size limitations, polishing non-uniformities, and undesired contaminants. Thus, further exploration of advanced metal surface treatment techniques is essential. Here, we report a physical strategy that utilizes surface acoustic wave assisted annealing to flatten metal foils by eliminating the surface steps, eventually transforming commercial rough metal foils into ultraflat substrates. Large-area, high-quality, smooth 2D materials, including graphene and hexagonal boron nitride (hBN), were successfully grown on the resulting flat metal substrates. Further investigation into the oxidation of 2D-material-coated metal foils, both rough and flat, revealed that the hBN-coated flat metal foil exhibits enhanced anti-corrosion properties. Molecular dynamics simulations and density functional theory validate our experimental observations.

Abstract Rejection seriously affects the success of kidney transplantations. However, the molecular mechanisms underlying this rejection remain unclear. The GSE21374 and GSE36059 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Next, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to infer the proportions of 22 immune cells. Moreover, infiltrating immune cell-related genes were identified using weighted gene co-expression network analysis (WGCNA), and enrichment analysis was conducted to observe their biological functions. Extreme Gradient Boosting (XGBoost) and Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression algorithms were used to screen hub genes. Quantitative real-time PCR was conducted to verify the number of immune cells and hub gene expression levels. The rejection and non-rejection groups showed significantly different distributions (P

Abstract Hexagonal boron nitride (hBN), as one of the few two-dimensional insulators, holds strategic importance for advancing post-silicon electronic devices and circuits. Achieving wafer-scale, high-quality monolayer hBN is essential for its integration into the semiconductor industry. However, the physical mechanisms behind the chemical vapor deposition (CVD) synthesis of hBN are not yet well understood. Investigating morphology engineering is critical for developing scalable synthetic techniques for the large-scale production of high-quality hBN. In this study, we explored the underlying mechanisms of the CVD growth process of hBN and found that the involvement of a small amount of oxygen effectively modulates the shape of the single-crystal hBN islands. By tuning the oxygen content in the CVD system, we synthesized well-aligned hexagonal hBN islands and achieved a continuous, high-quality single-crystal monolayer hBN film through the merging of these hexagonal islands on conventional single-crystal metal-foil substrates. Density functional theory was used to study the edges of hBN monolayers grown in an oxygen-assisted environment, providing insights into the formation mechanism. This study opens new pathways for controlling the island shape of 2D materials and establishes a foundation for the industrial-scale production of high-quality, large-area, single-crystal hBN.

Abstract Controversy still exists regarding how much the inflow arterial percutaneous transluminal angioplasty (PTA) contributed to maintaining fistula function for hemodialysis. We aimed to analyze patency and risk factors after inflow arterial PTA. Hemodialysis patients with inflow arterial primary stenosis who were admitted to our institution from January 2017 to December 2022 were examined. One group had arterial-venous fistula with inflow artery stenosis alone (AVF + iAS) and another group had AVF with inflow artery stenosis and any vein stenosis (AVF + iAS + VS). The characteristics of patients, stenotic lesions, and PTA procedures were recorded. Kaplan–Meier analysis was used to compare primary patency, assisted primary patency, and secondary patency in the two groups. Cox proportional hazard analysis was used to identify risk factors associated with patency. We examined 213 patients, 53 in the AVF + iAS group (51 radial arterial stenosis and 2 ulnar arterial stenosis) and 160 in the AVF + iAS + VS group (159 radial arterial stenosis and 1 ulnar arterial stenosis). Kaplan–Meier analysis indicated the AVF + iAS group had better primary patency and assisted primary patency (both P

Abstract Bacterial testicular inflammation is one of the important causes of male infertility. Using plant-derived compounds to overcome the side effects of antibiotics is an alternative treatment strategy for many diseases. Schizandrin B (SchB) is a bioactive compound of herbal medicine Schisandra chinensis which has multiple pharmacological effects. However its effect and the mechanism against testicular inflammation are unknown. Here we tackled these questions using models of lipopolysaccharide (LPS)-induced mice and -Sertoli cells (SCs). Histologically, SchB ameliorated the LPS-induced damages of the seminiferous epithelium and blood-testicular barrier, and reduced the production of pro-inflammatory mediators in mouse testes. Furthermore, SchB decreased the levels of pro-inflammatory mediators and inhibited the nuclear factor kB (NF-κB) and MAPK (especially JNK) signaling pathway phosphorylation in LPS-induced mSCs. The bioinformatics analysis based on receptor prediction and the molecular docking was further conducted. We targeted androgen receptor (AR) and illustrated that AR might bind with SchB in its function. Further experiments indicate that the AR expression was upregulated by LPS stimulation, while SchB treatment reversed this phenomenon; similarly, the expression of the JNK-related proteins and apoptotic-related protein were also reversed after AR activator treatment. Together, SchB mitigates LPS-induced inflammation and apoptosis by inhibiting the AR-JNK pathway.

Abstract Electrocatalytic H2 production from seawater, recognized as a promising technology utilizing offshore renewables, faces challenges from chloride-induced reactions and corrosion. Here, We introduce a catalytic surface where OH– dominates over Cl– in adsorption and activation, which is crucial for O2 production. Our NiFe-based anode, enhanced by nearby Cr sites, achieves low overpotentials and selective alkaline seawater oxidation. It outperforms the RuO2 counterpart in terms of lifespan in scaled-up stacks, maintaining stability for over 2500 h in three-electrode tests. Ex situ/in situ analyses reveal that Cr(III) sites enrich OH–, while Cl– is repelled by Cr(VI) sites, both of which are well-dispersed and close to NiFe, enhancing charge transfer and overall electrode performance. Such multiple effects fundamentally boost the activity, selectively, and chemical stability of the NiFe-based electrode. This development marks a significant advance in creating durable, noble-metal-free electrodes for alkaline seawater electrolysis, highlighting the importance of well-distributed catalytic sites.

Abstract It is vital to explore effective ways for prolonging electrode lifespans under harsh electrolysis conditions, such as high current densities, acid environment, and impure water source. Here we report alternating electrolysis approaches that realize promptly and regularly repair/maintenance and concurrent bubble evolution. Electrode lifespans are improved by co-action of Fe group elemental ions and alkali metal cations, especially a unique Co2+-Na+ combo. A commercial Ni foam sustains ampere-level current densities alternatingly during continuous electrolysis for 93.8 h in an acidic solution, whereas such a Ni foam is completely dissolved in ~2 h for conventional electrolysis conditions. The work not only explores an alternating electrolysis-based system, alkali metal cation-based catalytic systems, and alkali metal cation-based electrodeposition techniques, and beyond, but demonstrates the possibility of prolonged electrolysis by repeated deposition-dissolution processes. With enough adjustable experimental variables, the upper improvement limit in the electrode lifespan would be high.

Abstract In enzymatic catalysis, the redox site and Lewis acid are the two main roles played by metal to assist amino acids. However, the reported enzyme mimics only focus on the redox-active metal as redox site, while the redox-inert metal as Lewis acid has, to the best of our knowledge, not been studied, presenting a bottleneck of enzyme mimics construction. Based on this, a series of highly efficient MxV2O5·nH2O peroxidase mimics with vanadium as redox site and alkaline-earth metal ion (M2+) as Lewis acid are reported. Experimental results and theoretical calculations indicate the peroxidase-mimicking activity of MxV2O5·nH2O show a periodic change with the Lewis acidity (ion potential) of M2+, revealing the mechanism of redox-inert M2+ regulating electron transfer of V-O through non-covalent polarization and thus promoting H2O2 adsorbate dissociation. The biomimetic synergetic effect of redox site and Lewis acid is expected to provide an inspiration for design of enzyme mimics.

Abstract Solar photovoltaic (PV) power generation is susceptible to environmental factors, and redundant features can disrupt prediction accuracy. To achieve rapid and accurate online prediction, we propose a method that combines Principal Component Analysis (PCA) with a multi-strategy improved Squirrel Search Algorithm (SSA) to optimize Support Vector Machine (MISSA-SVM) for prediction. Initially, to mitigate the impact of redundant features on prediction accuracy, KPCA is employed for feature dimensionality reduction. Subsequently, SVM is suggested as the foundational algorithm for constructing the prediction model. Furthermore, to address the influence of hyperparameter selection on model performance, SSA is introduced for optimizing SVM hyperparameters, with the aim of establishing the optimal prediction model. Moreover, to enhance solution efficiency and accuracy, a multi-strategy approach termed MISSA is proposed, which integrates Population Initialization based on the Tent map, Nonlinear Predator Presence Probability, Chaotic-based Dynamic Opposition-based Learning, and Selection Strategy, to refine SSA. Finally, through case studies, the performance of MISSA optimization is assessed using challenging CEC2021 test functions, demonstrating its high optimization performance, stability, and significance. Subsequently, the performance of the prediction model is validated using two datasets, showcasing that the proposed prediction method achieves high accuracy and robust prediction stability.

Abstract Thermal comfort studies are usually employed to find subjective thermal responses [indicated by neutral temperature (NT), i.e. the temperature with no thermal stress] of residents from a region towards thermal environments. According to the recently published works in the literature, NTs are affected by many factors, such as geographical location and microenvironments. To elucidate the origins of these effects, the impact of microenvironment elements around a water surface on pedestrians’ thermal perceptions was systematically investigated in this work. The Fujiang River (FJR) in Mianyang City was taken as the sample site. The municipal meteorology station is located next to the site by around 2.5 km. By performing meteorology measurements combining questionnaires, it was found that the riverside NT (indicated by physiologically equivalent temperature, PET) of Mianyang in the summer of 2023 was 21.4 °C. The relationship between the distance from the water (DFW) and NT was quadratic linear. The same phenomenon took place by using either PET or Universal Thermal Climate Index (UTCI) indexes. Meanwhile, the meteorological contexts also affected NTs, including relative humidity (RH) and air velocity (Va). Regarding RH, the NPET increased from 15.2 °C (RH = 50%) to 26.9 °C (RH = 90%). In contrast, the NPET dropped from 23.0 to − 50.6 °C when the Va increased from 0.2 to 2.5 m/s, respectively. From our analysis, it was demonstrated that human thermal responses are significantly affected by both the microenvironmental and meteorological backgrounds around the water surface. Our work provides valuable insights for the proper use of water surfaces in urban design for adjusting thermal comfort.

Abstract The semiconductors industry has put its eyes on two-dimensional (2D) materials produced by chemical vapour deposition (CVD) because they can be grown at the wafer level with small thickness fluctuations, which is necessary to build electronic devices and circuits. However, CVD-grown 2D materials can contain significant amounts of lattice distortions, which degrades the performance at the device level and increases device-to-device variability. Here we statistically analyse the quality of commercially available CVD-grown hexagonal boron nitride (h-BN) from the most popular suppliers. h-BN is of strategic importance because it is one of the few insulating 2D materials, and can be used as anti-scattering substrate and gate dielectric. We find that the leakage current and electrical homogeneity of all commercially available CVD h-BN samples are significantly worse than those of mechanically exfoliated h-BN of similar thickness. Moreover, in most cases the properties of the CVD h-BN samples analysed don’t match the technical specifications given by the suppliers, and the sample-to-sample variability is unsuitable for the reproducible fabrication of capacitors, transistors or memristors in different batches. In the short term, suppliers should try to provide accurate sample specifications matching the properties of the commercialized materials, and researchers should keep such inaccuracies in mind; and in the middle term suppliers should try to reduce the density of defects to enable the fabrication of high-performance devices with high reliability and reproducibility.

Abstract The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation.

Abstract The edible fungus industry is one of the pillar industries in the Yunnan–Guizhou Plateau, China. The expansion of the planting scale has led to the release of various mushroom residues, such as mushroom feet, and other wastes, which are not treated adequately, resulting in environmental pollution. This study investigated the ability of black soldier fly (Hermetia illucens L.) larvae (BSFL) to degrade mushroom waste. Moreover, this study analyzed changes in the intestinal bacterial community and gene expression of BSFL after feeding on mushroom waste. Under identical feeding conditions, the remaining amount of mushroom waste in Pleurotus ostreatus treatment group was reduced by 18.66%, whereas that in Flammulina velutipes treatment group was increased by 31.08%. Regarding gut microbial diversity, compared with wheat bran-treated control group, Dysgonomonas, Providencia, Enterococcus, Pseudochrobactrum, Actinomyces, Morganella, Ochrobactrum, Raoultella, and Ignatzschineria were the most abundant bacteria in the midgut of BSFL in F. velutipes treatment group. Furthermore, Dysgonomonas, Campylobacter, Providencia, Ignatzschineria, Actinomyces, Enterococcus, Morganella, Raoultella, and Pseudochrobactrum were the most abundant bacteria in the midgut of BSFL in P. ostreatus treatment group. Compared with wheat bran-treated control group, 501 upregulated and 285 downregulated genes were identified in F. velutipes treatment group, whereas 211 upregulated and 43 downregulated genes were identified in P. ostreatus treatment group. Using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we identified 14 differentially expressed genes (DEGs) related to amino sugar and nucleotide sugar metabolism in F. velutipes treatment group, followed by 12 DEGs related to protein digestion and absorption. Moreover, in P. ostreatus treatment group, two DEGs were detected for fructose and mannose metabolism, and two were noted for fatty acid metabolism. These results indicate that feeding on edible mushroom waste can alter the intestinal microbial community structure of BSFL; moreover, the larval intestine can generate a corresponding feedback. These changes contribute to the degradation of edible mushroom waste by BSFL and provide a reference for treating edible mushroom waste using BSFL.

Abstract This study presents a case of weakly consolidated strata developed in Dananhu No.7 coal mine. Using a combination of numerical simulation, field measurement comparison, and the critical hydraulic gradient criterion, we investigate the overburden failure and the risk possibility of water–sand mixture inrush during excavation. The following are the principal findings: (1) Weakly consolidated rocks have poor physical characteristics, particularly when they are mudded and disintegrated after encountering water, which may become a favorable source of water–sand inrush; (2) The water-conducting zone develops to a height of 160.5 m with a crack-mining ratio of 15.29 times, extending upward to Toutunhe Formation aquifer. The predictions are consistent with measurements in adjacent mines with similar geological conditions; (3) Cracks without larger subsidence are developed at the front edge of the mining direction, and some parallel stepped cracks behind the goaf could be easily observed. Ground subsidence along the goaf center finally displays a symmetrically wide-gentle U shape; (4) The critical hydraulic gradient of Toutunhe Formation aquifer, aquifer above 3# coal seam, and aquifer of 3#–7# coal seam in Xishanyao Formation is 1.314, 1.351, and 1.380, the actual value is 0.692, 2.089, and 7.418 accordingly. It is inferred water–sand mixture outburst will not occur in Toutunhe Formation aquifer, while the potential risk exists in the aquifers of Xishanyao Formation. Through drainage and depressurization projects, a water–sand mixture outburst accident does not occur during excavation. This study reveals the overburden failure characteristics and the initiation mechanism of water–sand inrush in weakly cemented strata, as well as the internal relationship between them, which provides new research ideas for safe operation in other mining areas with similar geological conditions. The research work has certain practical guiding significance.

Abstract Seawater electroreduction is attractive for future H2 production and intermittent energy storage, which has been hindered by aggressive Mg2+/Ca2+ precipitation at cathodes and consequent poor stability. Here we present a vital microscopic bubble/precipitate traffic system (MBPTS) by constructing honeycomb-type 3D cathodes for robust anti-precipitation seawater reduction (SR), which massively/uniformly release small-sized H2 bubbles to almost every corner of the cathode to repel Mg2+/Ca2+ precipitates without a break. Noticeably, the optimal cathode with built-in MBPTS not only enables state-of-the-art alkaline SR performance (1000-h stable operation at –1 A cm−2) but also is highly specialized in catalytically splitting natural seawater into H2 with the greatest anti-precipitation ability. Low precipitation amounts after prolonged tests under large current densities reflect genuine efficacy by our MBPTS. Additionally, a flow-type electrolyzer based on our optimal cathode stably functions at industrially-relevant 500 mA cm−2 for 150 h in natural seawater while unwaveringly sustaining near-100% H2 Faradic efficiency. Note that the estimated price (~1.8 US$/kgH2) is even cheaper than the US Department of Energy’s goal price (2 US$/kgH2).

Abstract Membranes with precise Li+/Na+ and Li+/K+ separations are imperative for lithium extraction from brine to address the lithium supply shortage. However, achieving this goal remains a daunting challenge due to the similar valence, chemical properties, and subtle atomic‐scale distinctions among these monovalent cations. Herein, inspired by the strict size‐sieving effect of biological ion channels, a membrane is presented based on nonporous crystalline materials featuring structurally rigid, dimensionally confined, and long‐range ordered ion channels that exclusively permeate naked Li+ but block Na+ and K+. This naked‐Li+‐sieving behavior not only enables unprecedented Li+/Na+ and Li+/K+ selectivities up to 2707.4 and 5109.8, respectively, even surpassing the state‐of‐the‐art membranes by at least two orders of magnitude, but also demonstrates impressive Li+/Mg2+ and Li+/Ca2+ separation capabilities. Moreover, this bioinspired membrane has to be utilized for creating a one‐step lithium extraction strategy from natural brines rich in Na+, K+, and Mg2+ without utilizing chemicals or creating solid waste, and it simultaneously produces hydrogen. This research has proposed a new type of ion‐sieving membrane and also provides an envisioning of the design paradigm and development of advanced membranes, ion separation, and lithium extraction.

Abstract Direct seawater splitting (DSS) offers an aspirational route toward green hydrogen (H2) production but remains challenging when operating in a practically continuous manner, mainly due to the difficulty in establishing the water supply–consumption balance under the interference from impurity ions. A DSS system is reported for continuous ampere‐level H2 production by coupling a dual‐cation exchange membrane (CEM) three‐compartment architecture with a circulatory electrolyte design. Monovalent‐selective CEMs decouple the transmembrane water migration from interferences of Mg2+, Ca2+, and Cl− ions while maintaining ionic neutrality during electrolysis; the self‐loop concentrated alkaline electrolyte ensures the constant gradient of water chemical potential, allowing a specific water supply–consumption balance relationship in a seawater–electrolyte–H2 sequence to be built among an expanded current range. Even paired with commercialized Ni foams, this electrolyzer (model size: 2 × 2 cm2) continuously produces H2 from flowing seawater with a rate of 7.5 mL min−1 at an industrially relevant current of 1.0 A over 100 h. More importantly, the energy consumption can be further reduced by coupling more efficient NiMo/NiFe foams (≈6.2 kWh Nm−3 H2 at 1.0 A), demonstrating the potential to further optimize the continuous DSS electrolyzer for practical applications.

Abstract Monolithic integration of novel materials without modifying the existing photonic component library is crucial to advancing heterogeneous silicon photonic integrated circuits. Here we show the introduction of a silicon nitride etch stop layer at select areas, coupled with low-loss oxide trench, enabling incorporation of functional materials without compromising foundry-verified device reliability. As an illustration, two distinct chalcogenide phase change materials (PCMs) with remarkable nonvolatile modulation capabilities, namely Sb2Se3 and Ge2Sb2Se4Te1, were monolithic back-end-of-line integrated, offering compact phase and intensity tuning units with zero-static power consumption. By employing these building blocks, the phase error of a push-pull Mach–Zehnder interferometer optical switch could be reduced with a 48% peak power consumption reduction. Mirco-ring filters with >5-bit wavelength selective intensity modulation and waveguide-based >7-bit intensity-modulation broadband attenuators could also be achieved. This foundry-compatible platform could open up the possibility of integrating other excellent optoelectronic materials into future silicon photonic process design kits.

Abstract Reactive uptake of dinitrogen pentaoxide (N2O5) into aqueous aerosols is a major loss channel for NOx in the troposphere; however, a quantitative understanding of the uptake mechanism is lacking. Herein, a computational chemistry strategy is developed employing high-level quantum chemical methods; the method offers detailed molecular insight into the hydrolysis and ammonolysis mechanisms of N2O5 in microdroplets. Specifically, our calculations estimate the bulk and interfacial hydrolysis rates to be (2.3 ± 1.6) × 10−3 and (6.3 ± 4.2) × 10−7 ns−1, respectively, and ammonolysis competes with hydrolysis at NH3 concentrations above 1.9 × 10−4 mol L−1. The slow interfacial hydrolysis rate suggests that interfacial processes have negligible effect on the hydrolysis of N2O5 in liquid water. In contrast, N2O5 ammonolysis in liquid water is dominated by interfacial processes due to the high interfacial ammonolysis rate. Our findings and strategy are applicable to high-chemical complexity microdroplets.

Abstract The electromagnetic force used in electromagnetic forming is mainly divided into attraction and repulsion. Dual-coil attractive electromagnetic forming can be used in the field of sheet pit repair. However, the magnetic field and eddy current generated by the two coils compete with each other, and the energy utilization rate is low. Therefore, a compensation coil is introduced, and an electromagnetic forming scheme of a three-coil dual-power sheet based on mixed force is proposed and verified by simulation. It is found that the three-coil mixed force can effectively improve the competition between the magnetic field and eddy current. The loading of the mixing force is not a simple superposition of attraction and repulsion, but the mutual promotion of the two. The forming displacement of the three-coil mixed force forming scheme is 582% higher than that of the dual-coil attraction forming scheme, and 89% higher than that of the attract first and then repel forming scheme. The forming effect of the three-coil mixing force is related to the number of turns of the compensation coil. The research results can improve the energy utilization rate of electromagnetic forming and provide a new idea for the loading scheme of electromagnetic forming force field.

Abstract Roundabout guidance receptor 2 (Robo2) is closely related to malignant tumors such as pancreatic cancer and liver fibrosis, but there is no relevant research on the role of Robo2 in HCC. The study will further explore the function and mechanism of Robo2 and its downstream target genes in HCC. Firstly, Robo2 protein levels in human HCC tissues and paired adjacent normal liver tissues were detected. Then we established HepG2 and Huh7 hepatoma cell lines with knock-down Robo2 by transfection with lentiviral vectors, and examined the occurrence of EMT, proliferation and apoptosis abilities in HCC cells by western blot, flow cytometry, wound healing assay and TUNEL staining. Then we verified the interaction between Robo2 and its target gene by Co-IP and immunofluorescence co-staining, and further explored the mechanism of Robo2 and YB-1 by rescue study. The protein expression level of Robo2 in HCC was considerably higher than that in the normal liver tissues. After successfully constructing hepatoma cells with knock-down Robo2, it was confirmed that down-regulated Robo2 suppressed EMT and proliferation of hepatoma cells, and accelerated the cell apoptosis. High-throughput sequencing and validation experiments verified that YB-1 was the downstream target gene of Robo2, and over-expression of YB-1 could reverse the apoptosis induced by Robo2 down-regulation and its inhibitory effect on EMT and proliferation. Robo2 deficiency inhibits EMT and proliferation of hepatoma cells and augments the cell apoptosis by regulating YB-1, thus inhibits the occurrence of HCC and provides a new strategy for the treatment of HCC.

Abstract To a certain extent, the development and vaccination of COVID-19 vaccine have reduced the alarming rate of transmission speed and mortality rate. At present, vaccine coverage is quite high in countries around the world. Since individual differences are unavoidable, it is necessary to assess the efficacy of the vaccine in each vaccinated person in order to reflect the protective effect of the vaccine in different populations. In this study, we developed a novel COVID-19 neutralizing antibody detection kit combining lateral flow immunochromatography and novel quantum dot technology with 85.23% sensitivity, 92.50% specificity. The novel QD-ICA could achieve an accurate detection of SARS-CoV-2 neutralizing antibodies with 10 minutes, two steps, small equipment size, and broad testing application, suggesting its capability to assess vaccine effectiveness on a large scale in areas of world that currently affected by the pandemic.

Abstract Optical neural networks (ONNs) herald a new era in information and communication technologies and have implemented various intelligent applications. In an ONN, the activation function (AF) is a crucial component determining the network performances and on-chip AF devices are still in development. Here, we first demonstrate on-chip reconfigurable AF devices with phase activation fulfilled by dual-functional graphene/silicon (Gra/Si) heterojunctions. With optical modulation and detection in one device, time delays are shorter, energy consumption is lower, reconfigurability is higher and the device footprint is smaller than other on-chip AF strategies. The experimental modulation voltage (power) of our Gra/Si heterojunction achieves as low as 1 V (0.5 mW), superior to many pure silicon counterparts. In the photodetection aspect, a high responsivity of over 200 mA/W is realized. Special nonlinear functions generated are fed into a complex-valued ONN to challenge handwritten letters and image recognition tasks, showing improved accuracy and potential of high-efficient, all-component-integration on-chip ONN. Our results offer new insights for on-chip ONN devices and pave the way to high-performance integrated optoelectronic computing circuits.

Abstract Improving diabetes self-management (DSM) is facing real-world challenges among people with type 2 diabetes mellitus (T2DM) who have a low education level in resource-limited areas. This study aimed to investigate whether diabetes knowledge could predict glycemic levels in people with T2DM in rural China. This analytical cross-sectional study recruited 321 people with T2DM from eight villages by purposive sampling at baseline. After 10 months, 206 patients completed the follow-up survey and HbA1c tests, with a response rate of 64.17% (206/321). Multiple regression analysis was employed to explore the correlation between diabetes knowledge and HbA1c levels. The patient's diabetes knowledge was significantly negatively correlated with HbA1c levels before and after controlling for covariates in both hierarchical multiple regression and multiple logistic regression (p

Abstract Bidirectional signal transduction between tumor epithelial cells and tumor microenvironment (TME) is important for tumor development. Here we show that Lin28b/let-7 pathway is indispensable for modulating the expression of Wnt5a in tumor epithelium, which could be secreted and then up-regulates Lin28b in cancer-associated fibroblasts (CAFs). Moreover, we demonstrate that Lin28b in CAFs promoted growth of PDAC by inducing cytokine PCSK9’s production. Using an orthotopic mouse model of PDAC, we find that depletion of Lin28b in CAFs reduced tumor weight, highlighting the importance of Lin28b in PDAC stroma. Thus, our study shows that the Lin28b-Wnt5a axis plays a critical role in bidirectional crosstalk between pancreatic tumor epithelium and TME and results in a pro-‍tumorigenic contexture.

Abstract Considering the high fatality of hepatocellular carcinoma (HCC), current prognostic systems are insufficient to accurately forecast HCC patients' outcomes. In our study, nine anoikis‑related genes (PTRH2, ITGAV, ANXA5, BIRC5, BDNF, BSG, DAP3, SKP2, and EGF) were determined to establish a risk scoring model using LASSO regression, which could be validated in ICGC dataset. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis confirmed the risk score possessed an accurate predictive value for the prognosis of HCC patients. The high-risk group showed a higher infiltration of aDCs, macrophages, T-follicular helper cells, and Th2 cells. Besides, PD-L1 was significantly higher in the high-risk group compared to the low-risk group. Several anoikis‑related genes, such as ANX5, ITGAV, BDNF and SKP2, were associated with drug sensitivity in HCC. Finally, we identified BIRC5 and SKP2 as hub genes among the nine model genes using WGCNA analysis. BIRC5 and SKP2 were over-expressed in HCC tissues, and their over-expression was associated with poor prognosis, no matter in our cohort by immunohistochemical staining or in the TCGA cohort by mRNA-Seq. In our cohort, BIRC5 expression was highly associated with the T stage, pathologic stage, histologic grade and AFP of HCC patients. In general, our anoikis-related risk model can enhance the ability to predict the survival outcomes of HCC patients and provide a feasible therapeutic strategy for immunotherapy and drug resistance in HCC. BIRC5 and SKP2 are hub genes of anoikis‑related genes in HCC.

Summary: The efficacy of COVID-19 vaccination relies on the induction of neutralizing antibodies, which can vary among vaccine recipients. In this study, we investigated the potential factors affecting the neutralizing antibody response by combining plasma and urine proteomics and gut microbiota analysis. We found that activation of the LXR/FXR pathway in plasma was associated with the production of ACE2-RBD-inhibiting antibodies, while urine proteins related to complement system, acute phase response signaling, LXR/FXR, and STAT3 pathways were correlated with neutralizing antibody production. Moreover, we observed a correlation between the gut microbiota and plasma and urine proteins, as well as the vaccination response. Based on the above data, we built a predictive model for vaccination response (AUC = 0.85). Our study provides insights into characteristic plasma and urine proteins and gut microbiota associated with the ACE2-RBD-inhibiting antibodies, which could benefit our understanding of the host response to COVID-19 vaccination.

Summary: Herein, a hierarchical NiTe@NiFe-LDH core-shell array on Ni foam (NiTe@NiFe-LDH/NF) demonstrates its effectiveness for oxygen evolution reaction (OER) in alkaline seawater electrolyte. This NiTe@NiFe-LDH/NF array showcases remarkably low overpotentials of 277 mV and 359 mV for achieving current densities of 100 and 500 mA cm−2, respectively. Also, it shows a low Tafel slope of 68.66 mV dec−1. Notably, the electrocatalyst maintains robust stability over continuous electrolysis for at least 50 h at 100 mA cm−2. The remarkable performance and hierarchical structure advantages of NiTe@NiFe-LDH/NF offer innovative insights for designing efficient seawater oxidation electrocatalysts.

Summary: High-purity hydrogen produced by water electrolysis has become a sustainable energy carrier. Due to the corrosive environments and strong oxidizing working conditions, the main challenge faced by acidic water oxidation is the decrease in the activity and stability of anodic electrocatalysts. To address this issue, efficient strategies have been developed to design electrocatalysts toward acidic OER with excellent intrinsic performance. Electronic structure modification achieved through defect engineering, doping, alloying, atomic arrangement, surface reconstruction, and constructing metal-support interactions provides an effective means to boost OER. Based on introducing OER mechanism commonly present in acidic environments, this review comprehensively summarizes the effective strategies for regulating the electronic structure to boost the activity and stability of catalytic materials. Finally, several promising research directions are discussed to inspire the design and synthesis of high-performance acidic OER electrocatalysts.

Abstract The serine/threonine kinase AKT is a central node in cell signaling. While aberrant AKT activation underlies the development of a variety of human diseases, how different patterns of AKT-dependent phosphorylation dictate downstream signaling and phenotypic outcomes remains largely enigmatic. Herein, we perform a systems-level analysis that integrates methodological advances in optogenetics, mass spectrometry-based phosphoproteomics, and bioinformatics to elucidate how different intensity, duration, and pattern of Akt1 stimulation lead to distinct temporal phosphorylation profiles in vascular endothelial cells. Through the analysis of ~35,000 phosphorylation sites across multiple conditions precisely controlled by light stimulation, we identify a series of signaling circuits activated downstream of Akt1 and interrogate how Akt1 signaling integrates with growth factor signaling in endothelial cells. Furthermore, our results categorize kinase substrates that are preferably activated by oscillating, transient, and sustained Akt1 signals. We validate a list of phosphorylation sites that covaried with Akt1 phosphorylation across experimental conditions as potential Akt1 substrates. Our resulting dataset provides a rich resource for future studies on AKT signaling and dynamics.

Abstract As one member of fatty acid binding proteins (FABPs), FABP5 makes a contribution in the occurrence and development of several tumor types, but existing analysis about FABP5 and FABP5-related molecular mechanism remains limited. Meanwhile, some tumor patients showed limited response rates to current immunotherapy, and more potential targets need to be explored for the improvement of immunotherapy. In this study, we made a pan-cancer analysis of FABP5 based on the clinical data from The Cancer Genome Atlas database for the first time. FABP5 overexpression was observed in many tumor types, and was statistically associated with poor prognosis of several tumor types. Additionally, we further explored FABP5-related miRNAs and corresponding lncRNAs. Then, miR-577-FABP5 regulatory network in kidney renal clear cell carcinoma as well as CD27-AS1/GUSBP11/SNHG16/TTC28-AS1-miR-22-3p-FABP5 competing endogenous RNA regulatory network in liver hepatocellular carcinoma were constructed. Meanwhile, Western Blot and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis were used to verify miR-22-3p-FABP5 relationship in LIHC cell lines. Moreover, the potential relationships of FABP5 with immune infiltration and six immune checkpoints (CD274, CTLA4, HAVCR2, LAG3, PDCD1 and TIGIT) were discovered. Our work not only deepens the understanding of FABP5’s functions in multiple tumors and supplements existing FABP5-related mechanisms, but also provides more possibilities for immunotherapy.

Intrahepatic cholestasis of pregnancy (ICP) is a liver disease that sometimes develops during pregnancy and is characterized by increased serum bile acid levels. Here the authors report that the gut microbiome species B. fragilis is enriched in patients with ICP and promotes ICP development in mice via inhibition of signalling though the bile acid receptor FXR.

Nonalcoholic steatohepatitis (NASH) has been linked with the gut-liver axis. Here, the authors show that disulfiram (DSF) reduces Clostridium-mediated 7α-dehydroxylation activity to suppress secondary bile acid biosynthesis and ameliorate NASH in mice, and validate DSF regulation of the gut-liver axis in healthy men in a self-controlled clinical trial.

Abstract The traditional construction monitoring methods of suspended pole-mounted decomposed towers are mostly manual monitoring. The monitoring personnel has multiple blind spots, and the possibility of misjudgment based on personal experience is relatively large. It is difficult to ensure the construction safety of the suspended pole decomposing tower. For this reason, combined with the current power Internet of Things technology, this paper develops an intelligent monitoring system for suspended pole-mounted decomposing towers. According to the construction technology and its safety requirements of inner suspension derrick for transmission tower erection in sections, this system is classified into intellisense layer, wireless transport layer and information integration layer. According to the physical characteristics of the seven major risk points of the inner suspension pole group tower, the intellisense layer developed corresponding sensing equipment to obtain risk information. In the wireless transport layer, the ZigBee and 4G communication technologies are selected to interconnect self-constituted LAN and 4G wide area networks, to complete on-site data interaction and long-distance transmission. In the information integration layer, the force of cable, the inclination and height of derrick, and the distance between derrick and tower are determined. The system has been verified by the 500 kV delivery project of Fujian Zhouning Pumped Storage Power Station. The average error of critical monitoring point data is 4.14%, and the average data transmission delays in the far and near fields of the system are 18 ms and 176 ms.

Conservation tillage has been promoted as an effective practice to preserve soil health and enhance agroecosystem services. Changes in tillage intensity have a profound impact on soil nitrogen cycling, yet their influence on nitrate losses at large spatiotemporal scales remains uncertain. This study examined the effects of tillage intensity on soil nitrate losses in the US Midwest from 1979–2018 using field data synthesis and process-based agroecosystem modeling approaches. Our results revealed that no-tillage (NT) or reduced tillage intensity (RTI) decreased nitrate runoff but increased nitrate leaching compared to conventional tillage. These trade-offs were largely caused by altered water fluxes, which elevated total nitrate losses. The structural equation model suggested that precipitation had more pronounced effects on nitrate leaching and runoff than soil properties (i.e. texture, pH, and bulk density). Reduction in nitrate runoff under NT or RTI was negatively correlated with precipitation, and the increased nitrate leaching was positively associated with soil bulk density. We further explored the combined effects of NT or RTI and winter cover crops and found that incorporating winter cover crops into NT systems effectively reduced nitrate runoff but did not significantly affect nitrate leaching. Our findings underscore the precautions of implementing NT or RTI to promote sustainable agriculture under changing climate conditions. This study provides valuable insights into the complex relationship between tillage intensity and nitrate loss pathways, contributing to informed decision-making in climate-smart agriculture.

Abstract Characterization and categorization of quantum correlations are both fundamentally and practically important in quantum information science. Although quantum correlations such as non-separability, steerability, and non-locality can be characterized by different theoretical models in different scenarios with either known (trusted) or unknown (untrusted) knowledge of the associated systems, such characterization sometimes lacks unambiguous to experimentalist. In this work, we propose the physical interpretation of nonlocal quantum correlation between two systems. In the absence of complete local description of one of the subsystems quantified by the local uncertainty relation, the correlation between subsystems becomes nonlocal. Remarkably, different nonlocal quantum correlations can be discriminated from a single uncertainty relation derived under local hidden state (LHS)–LHS model only. We experimentally characterize the two-qubit Werner state in different scenarios.

NK cells can be affected by tumour cells and this difference could be utilised as a cancer diagnostic. Here the authors use a nickel based plasmonic spectroscopy system to measure metabolic differences in NK cells that have been exposed to cancer cells as a method of cancer detection.