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Abstract Histone lysine crotonylation, an evolutionarily conserved modification differing from acetylation, exerts pivotal control over diverse biological processes. Among these are gene transcriptional regulation, spermatogenesis, and cell cycle processes. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. Here, we show that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 results in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrate that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful progression of embryo development up to the blastocyst stage. Moreover, the modification of histone H3 lysine 18 crotonylation (H3K18cr) is primarily localized to active promoter regions. This modification serves as a distinctive epigenetic indicator of crucial transcriptional regulators, facilitating the activation of gene transcription. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.

Abstract Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables—ferroelectric polarization and magnetization—we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.

Abstract Background Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal tumor that mostly involves the pleura and infrequently involves extra-pleural sites. De novo SFT of the kidney is uncommon, and malignant SFT is extremely rare. Case presentation We report a case of a 51-year-old man with a large malignant SFT in the left kidney. Pathological examination confirmed the diagnosis of SFT based on typical morphology, nuclear STAT6 expression, and NAB2-STAT6 gene fusion. The malignant subtype was determined by a large tumor size (≥ 15 cm) and high mitotic counts (8/10 high-power fields). KRAS mutation was identified by DNA sequencing. Insulin-like growth factor 2 (IGF2) was diffusely and strongly expressed in tumor cells, however, hypoglycemia was not observed. Hyperglycemia and high adrenocorticotropic hormone (ACTH) concentration were observed one month after surgery. Hormone measurements revealed normal blood cortisol and aldosterone levels, and increased urinary free cortisol level. A pituitary microadenoma was identified using brain magnetic resonance imaging, which may be responsible for the promotion of hyperglycemia. Conclusions We report a case of renal malignant SFT with a KRAS mutation, which was previously unreported in SFT and may be associated with its malignant behavior. Additionally, we emphasize that malignant SFT commonly causes severe hypoglycemia due to the production of IGF2. However, this effect may be masked by the presence of other lesions that promote hyperglycemia. Therefore, when encountering a malignant SFT with diffuse and strong IGF2 expression and without hypoglycemia, other lesions promoting hyperglycemia need to be ruled out.

Abstract Background Colorectal cancer, which originates from the human colon or rectum, is one of the leading causes of death worldwide. Timely diagnosis and interventional therapy can significantly improve the prognostic survival of colorectal cancer patients, making regular screening and early detection essential. Aim To investigate the regulatory function of lncRNA CTBP1-DT (CTBP1-DT) on colorectal cancer cells and to assess its diagnostic significance. Methods A total of 102 patients with colorectal cancer and 92 healthy individuals were selected. The levels of CTBP1-DT and microRNA-30a-5p (miR-30a-5p) in serum and cell samples of the above subjects were compared by RT-qPCR. The effects of CTBP1-DT and miR-30a-5p dysregulation on the biological functions of colorectal cancer cells were analyzed via CCK-8, flow cytometry and Transwell assays. In addition, the ability of CTBP1-DT and miR-30a-5p to early identify colorectal cancer patients was determined through ROC curve. Results Serum CTBP1-DT was elevated in patients with colorectal cancer, which was obviously higher than in healthy controls. The expression of serum miR-30a-5p was downregulated in colorectal cancer. Both CTBP1-DT and miR-30a-5p have the value of distinguishing colorectal cancer, and the combined diagnostic ability is higher. Knockdown of CTBP1-DT directly targeted miR-30a-5p to repress cell activity and metastatic ability, whereas deregulation of miR-30a-5p eliminated the above inhibitory effects. Conclusion Overexpression of CTBP1-DT has a certain application potential in the diagnosis of colorectal cancer and may be a therapeutic target for colorectal cancer.

This study aimed to investigate the impact of different strains of Lactiplantibacillus plantarum on malolactic fermentation (MLF), antioxidant activity, and aroma of ciders. A commercial strain of Saccharomyces cerevisiae and six indigenous L. plantarum strains were co-inoculated into apple juice to induce simultaneous alcoholic fermentation (AF) and MLF. The findings indicated that despite belonging to the same species, the different L. plantarum strains significantly differed (p

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. Methods The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT–PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. Results The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. Conclusions Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.

Background: Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins are protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins and CVDs, yet the exact causal relationship remains to be elucidated. To address this, we propose using Mendelian randomization (MR) to explore the causal relationships between cathepsins and CVDs.Methods: We obtained single nucleotide polymorphism (SNP) data for cathepsins from the INTERVAL study, a publicly accessible genome-wide association study (GWAS) dataset. Outcome SNP data were sourced from seven distinct GWAS datasets, ensuring a comprehensive analysis across multiple cardiovascular outcomes. For MR analysis, we primarily employed the inverse variance weighted (IVW) method, known for its efficiency when all SNPs are valid instruments. This was supplemented by the weighted median and MR-Egger methods to provide robustness against potential violations of MR assumptions, such as pleiotropy. The IVW method offers precision and efficiency, the weighted median method adds robustness against invalid instruments, and the MR-Egger method helps identify and correct for pleiotropic biases. Cochran’s Q test was utilized to assess heterogeneity, and sensitivity analyses were conducted using MR-PRESSO and the leave-one-out approach.Results: The strength of the associations between exposure and outcome was measured using odds ratios (ORs), and results were presented with 95% confidence intervals (CIs). The cathepsin E increases the risk of myocardial infarction (MI) (OR = 1.053%, 95% CI: 1.007–1.101, p = 0.024) and ischemic stroke (IS) (OR = 1.06%, 95% CI: 1.019–1.103, p = 0.004). Conversely, cathepsin L2 decreases the risk of chronic heart failure (CHF) (OR = 0.922%, 95% CI: 0.859–0.99, p = 0.025) and atrial fibrillation (AF) (OR = 0.956%, 95% CI: 0.918–0.996, p = 0.033). Cathepsin O was associated with an increased risk of IS (OR = 1.054%, 95% CI: 1.008–1.102, p = 0.021) and AF (OR = 1.058%, 95% CI: 1.02–1.098, p = 0.002).Conclusion: Our MR analysis reveals that cathepsin E is a risk factor for MI and IS, cathepsin L2 offers protective effects against CHF and AF, and cathepsin O increases the risk for IS and AF.

Background and aimsPatients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure.MethodsThis retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab).ResultsA total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p

Abstract Background In December 2022, a large‐scale epidemic occurred in China due to Omicron variant of SARS‐CoV‐2. This study explored risk factors for Omicron infection in transplant recipients at our institution and investigated the factors influencing the severity of SARS‐CoV‐2 Omicron infection among recipients of allo‐HSCT. Methods This single‐center study investigated totally 63 allogeneic hematopoietic stem cell transplant patients infected with Omicron variant at the Beijing GoBroad Boren Hospital Transplant Center during December 2022 and analyzed their risk factors. Results The study included 63 allogeneic hematopoietic stem cell transplant patients who developed Omicron infection. There were 34 mild and 29 moderate to severe cases. Their median age was 22 years (range, 1–65 years), with the male‐to‐female ratio being 1:1.1. Acute myeloid leukemia (53.97%), acute lymphoblastic leukemia (42.86%), and non‐Hodgkin lymphoma (3.17%) were underlying diseases. The median time between HCT and Omicron infection was 8.45 months. Significant predictive factors for moderate to severe Omicron infection included older age (p

The use of anti-inflammatory peptides (AIPs) as an alternative therapeutic approach for inflammatory diseases holds great research significance. Due to the high cost and difficulty in identifying AIPs with experimental methods, the discovery and design of peptides by computational methods before the experimental stage have become promising technology. In this study, we present BertAIP, a bidirectional encoder representation from transformers (BERT)-based method for predicting AIPs directly from their amino acid sequence without using any other information. BertAIP implements a BERT model to extract features of a protein, and uses a fully connected feed-forward network for AIP classification. It was constructed and evaluated using the AIP datasets that were reconstructed from the latest Immune Epitope Database. The experimental results showed that BertAIP achieved an accuracy of 0.751 and a Matthews correlation coefficient of 0.451, which were higher than other commonly used methods. The results of the independent test suggested that BertAIP outperformed the existing AIP predictors. In addition, to enhance the interpretability of BertAIP, we explored and visualized the amino acids that the model considered important for AIP prediction. We believe that the BertAIP proposed herein will be a useful tool for large-scale screening and identifying novel AIPs for drug development and therapeutic research related to inflammatory diseases.

Abstract Magnetic skyrmions have great potential for developing novel spintronic devices. The electrical manipulation of skyrmions has mainly relied on current-induced spin-orbit torques. Recently, it was suggested that the skyrmions could be more efficiently manipulated by surface acoustic waves (SAWs), an elastic wave that can couple with magnetic moment via the magnetoelastic effect. Here, by designing on-chip piezoelectric transducers that produce propagating SAW pulses, we experimentally demonstrate the directional motion of Néel-type skyrmions in Ta/CoFeB/MgO/Ta multilayers. We find that the shear horizontal wave effectively drives the motion of skyrmions, whereas the elastic wave with longitudinal and shear vertical displacements (Rayleigh wave) cannot produce the motion of skyrmions. A longitudinal motion along the SAW propagation direction and a transverse motion due to topological charge are simultaneously observed and further confirmed by our micromagnetic simulations. This work demonstrates that acoustic waves could be another promising approach for manipulating skyrmions, which could offer new opportunities for ultra-low power skyrmionics.

Abstract The poor dispersibility of layered double hydroxides (LDHs) is considered to be the main drawback limiting their application in anti-corrosive coatings. In this work, the problem is solved by combining LDHs with graphene (Gr). A facile electrochemically assisted deposition technique (EAT) is developed to prepare Gr/LDH micro/nano-containers. The high-barrier Gr and LDHs synergistically build a ‘labyrinth effect’ to lengthen the diffusion path of corrosive mediums. Moreover, corrosion inhibitors can be released from the interlayer galleries of LDHs and impede corrosion of metal substrate by substituting the aggressive ions. Therefore, the polyvinyl butyral (PVB) coatings doped with Gr/LDH micro/nano-containers pre-loaded with inhibitors 2-Mercaptobenzothiazole (MBT) have both passive and active corrosion protection properties and provide excellent protection to copper substrate.

In response to the challenge of mitigating flight delays, this study introduces an innovative solution that encompasses the prediction of delay durations for existing flights and the subsequent optimization of ground service processes based on these predictions. The indirect forecasting of flight delays is achieved through the construction of a random forest model, exhibiting a remarkable 100% accuracy when considering a 15-minute standard for flight delays. In light of the delay prediction outcomes, distinct delay coefficients are assigned to individual flights, facilitating the development of a ground service optimization model through the application of a genetic algorithm. Within the genetic algorithm optimization framework, significant enhancements have been implemented in the gene encoding of the initial population, incorporating a segmented encoding approach. Employing this refined model to optimize the service sequence and duration of ground service vehicles for all flights culminates in the notable accomplishment of achieving zero delays for the entire set of flights.

As a high energy density cathode material, further development of high working voltage spinel LiNi0.5Mn1.5O4 has hindered by its rapid capacity degradation. To address this, a hetero-valent substitution of magnesium for manganese was used to synthesize spinel LiNi0.5MgxMn1.5−xO4 (x = 0, 0.03, 0.05) via a microwave sol-gel method. XRD and refined results indicate that such strategy leads to the modification of the 16c interstitial sites. The electrical performance demonstrates that a modest substitution (x = 0.03) significantly improves both rate performance (113.1 mAh/g, charge and discharge at 5 C) and cycling stability (85% capacity retention after 500 cycles at 1 C). A higher substitution level (x = 0.05) markedly improves high-rate cycling performance, achieving 96% capacity retention after 500 cycles at 5 C. It offers tailored solutions for various application needs, including capacity-focused and high-current-rate applications. Furthermore, the stable LiNi0.5Mg0.05Mn1.45O4 sample could also serve as an effective coating layer for other electrode materials to enhance their cycling stability.

In this work, TiO2 was firmly attached on freestanding graphene (Gr, rather than graphene oxide or reduced graphene oxide) nanosheets (Gr@e-TiO2) by a novel electrodeposition method. The morphology, crystal structure, band gap characteristics, optical properties and photoelectric properties were systematically investigated. It is indicated that the absorption of visible light increased and the recombination of photogenerated electron-hole pairs decreased for the as-obtained Gr@e-TiO2. Compared with pure TiO2 as well as GO (graphene oxide)@h-TiO2 prepared by conventional hydrothermal method, Gr@e-TiO2 exhibited a more negative open circuit potential and higher photocurrent density for 304SS protection. The enhanced photocathodic protection performance of Gr@e-TiO2 can be attributed to the large specific surface area and good charge transport efficiency of graphene.

In order to design and prepare water-based cutting fluid for 2A12 aluminum alloy to ensure no rust on the surface after machining，addition amounts of triethanolamine (TEA)， dodecanedioic acid (DC12) and ethylenediaminetetraacetic acid (EDTA) in the formula were optimized by response surface methodology.The synergistic corrosion inhibition effect on 2A12 aluminum alloy was investigated，and the amidemodified vegetable oil (AMV-1) and self-emulsifying ester (SEE) were utilized to improve the anti-corrosive effect of the formula， and the surfactants were added to enhance the wetting performance of the formula system.At last， combined with infrared spectroscopy and molecular structure analysis， the structure-activity relationship of AMV-1 and SEE corrosion inhibition performance was clarified.Results showed that TEA， DC12 and EDTA were the significant factors affecting the corrosion of 2A12 aluminum alloy， and there was an interaction between TEA and DC12.The optimal addition amounts (mass fraction， the same below) were 11.10%， 1.70% and 0.44%， respectively.Adding 8.0%(mass fraction) AMV-1 and 2.0%(mass fraction) SEE could make the aluminum alloy surface free from corrosion and discoloration.Meanwhile， polyether L44 could improve the wetting performance of the formula， and the surface static contact angle decreased from 49.732° to 36.451° with the addition of 2.0%(mass fraction).AMV-1 and SEE formed a coordination compound protective film and a hydrophobic film on the surface of aluminum alloy， respectively， to achieve corrosion inhibition effect.

Abstract Current induced spin-orbit torque (SOT) holds great promise for next generation magnetic-memory technology. Field-free SOT switching of perpendicular magnetization requires the breaking of in-plane symmetry, which can be artificially introduced by external magnetic field, exchange coupling or device asymmetry. Recently it has been shown that the exploitation of inherent crystal symmetry offers a simple and potentially efficient route towards field-free switching. However, applying this approach to the benchmark SOT materials such as ferromagnets and heavy metals is challenging. Here, we present a strategy to break the in-plane symmetry of Pt/Co heterostructures by designing the orientation of Burgers vectors of dislocations. We show that the lattice of Pt/Co is tilted by about 1.2° when the Burgers vector has an out-of-plane component. Consequently, a tilted magnetic easy axis is induced and can be tuned from nearly in-plane to out-of-plane, enabling the field-free SOT switching of perpendicular magnetization components at room temperature with a relatively low current density (~1011 A/m2) and excellent stability (> 104 cycles). This strategy is expected to be applicable to engineer a wide range of symmetry-related functionalities for future electronic and magnetic devices.

In the current context of fossil energy depletion and the requirement for low carbon emissions, the efficient use of energy and a diversified energy mix have become increasingly important. The use of cleaner and low-carbon alternative fuels is rapidly growing. However, corrosion remains a key issue limiting the large-scale application of alternative fuels. This paper describes the corrosion characteristics of different alternative fuels. Also, the mechanisms of fuel corrosion, corrosion measurement methods, and the future of corrosion inhibitor applications are discussed. Corrosion causes changes in material weight and surface morphology and generates electrical signals as it progresses. Although there are well-established methods to characterize corrosion by recognizing these changes, there is still a need to identify a universal standard signal for their detailed description. For the foreseeable future, corrosion in fuels will continue to be mitigated by the addition of corrosion inhibitors. The research on corrosion inhibitors focuses on green corrosion inhibitors and multifunctional corrosion inhibitors. However, further analysis is needed to understand the active ingredients in green corrosion inhibitors, and the mechanism of corrosion inhibition for different types of corrosion inhibitors needs further research.

The n-butanol/low-carbon alcohol/diesel microemulsion system is a good alternative fuel to diesel. In this study, the microemulsions were formulated in four ways: ultrasonication, vortex oscillation, shaker mixing and spontaneous formation. The results reveal that the ultrasonication method is significantly influenced by temperature. Specifically, at 45 °C, the quantity of cosolvent added during the ultrasonic process can be reduced by a maximum of 25% compared to that at 25 °C. However, while the amount of cosolvent required is the lowest at 45 °C, the stability of the emulsion is the poorest. In all cases of this study, the stability of the microemulsion increases when the volume ratio of the lower carbon alcohol exceeds 60%. The lowest amount of co-solvent and high stability were achieved using the shaker mixing method at both 25 °C and 35 °C. Although the quantity of cosolvent required at 45 °C is second only to the lowest, its stability surpasses that of the ultrasonication method. Therefore, it is more effective to choose the shaker mixing method that provides uniform and ordered forces for the preparation of microemulsion liquids.

Abstract Background Drug resistance limits the treatment effect of cisplatin-based chemotherapy in head and neck squamous cell carcinoma (HNSCC), and the underlying mechanism is not fully understood. The aim of this study was to explore the cause of cisplatin resistance in HNSCC. Methods We performed survival and gene set variation analyses based on HNSCC cohorts and identified the critical role of tumor necrosis factor alpha-induced protein 2 (TNFAIP2) in cisplatin-based chemotherapy resistance. Half-maximal inhibitory concentration (IC50) examination, colony formation assays and flow cytometry assays were conducted to examine the role of TNFAIP2 in vitro, while xenograft models in nude mice and 4-nitroquinoline N-oxide (4NQO)-induced HNSCC models in C57BL/6 mice were adopted to verify the effect of TNFAIP2 in vivo. Gene set enrichment analysis (GSEA) and coimmunoprecipitation coupled with mass spectrometry (Co-IP/MS) were performed to determine the mechanism by which TNFAIP2 promotes cisplatin resistance. Results High expression of TNFAIP2 is associated with a poor prognosis, cisplatin resistance, and low reactive oxygen species (ROS) levels in HNSCC. Specifically, it protects cancer cells from cisplatin-induced apoptosis by inhibiting ROS-mediated c-JUN N-terminal kinase (JNK) phosphorylation. Mechanistically, the DLG motif contained in TNFAIP2 competes with nuclear factor-erythroid 2-related factor 2 (NRF2) by directly binding to the Kelch domain of Kelch-like ECH-associated protein 1 (KEAP1), which prevents NRF2 from undergoing ubiquitin proteasome-mediated degradation. This results in the accumulation of NRF2 and confers cisplatin resistance. Positive correlations between TNFAIP2 protein levels and NRF2 as well as its downstream target genes were validated in HNSCC specimens. Moreover, the small interfering RNA (siRNA) targeting TNFAIP2 significantly enhanced the cisplatin treatment effect in a 4NQO-induced HNSCC mouse model. Conclusions Our results reveal the antioxidant and cisplatin resistance-regulating roles of the TNFAIP2/KEAP1/NRF2/JNK axis in HNSCC, suggesting that TNFAIP2 might be a potential target in improving the cisplatin treatment effect, particularly for patients with cisplatin resistance.

The greater yam (Dioscorea alata), a widely cultivated and nutritious food crop, suffers from widespread yield reduction due to anthracnose caused by Colletotrichum gloeosporioides. Latent infection often occurs before anthracnose phenotypes can be detected, making early prevention difficult and causing significant harm to agricultural production. Through comparative genomic analysis of 60 genomes of 38 species from the Colletotrichum genus, this study identified 17 orthologous gene groups (orthogroups) that were shared by all investigated C. gloeosporioides strains but absent from all other Colletotrichum species. Four of the 17 C. gloeosporioides-specific orthogroups were used as molecular markers for PCR primer designation and C. gloeosporioides detection. All of them can specifically detect C. gloeosporioides out of microbes within and beyond the Colletotrichum genus with different sensitivities. To establish a rapid, portable, and operable anthracnose diagnostic method suitable for field use, specific recombinase polymerase amplification (RPA) primer probe combinations were designed, and a lateral flow (LF)-RPA detection kit for C. gloeosporioides was developed, with the sensitivity reaching the picogram (pg) level. In conclusion, this study identified C. gloeosporioides-specific molecular markers and developed an efficient method for C. gloeosporioides detection, which can be applied to the prevention and control of yam anthracnose as well as anthracnose caused by C. gloeosporioides in other crops. The strategy adopted by this study also serves as a reference for the identification of molecular markers and diagnosis of other plant pathogens.

In recent years, the detection of offshore pile foundations has received wide attention in engineering. Compared with traditional methods, the O-cell test has unique advantages in offshore pile foundation detection. To study the load transfer characteristics of the O-cell method for pile testing in coastal soft soil foundation, this paper established the pile–soil numerical model to simulate the O-cell and traditional testing processes. The finite element method and equal displacement method are combined to calculate the conversion coefficient and ultimate bearing capacity, and the distribution forms of axial force, side friction resistance, and tip resistance are discussed. The research results show that the O-cell test method and the traditional method have different load transfer forms. By introducing the equal displacement method into the O-cell pile–soil model, the error between the equivalent conversion ultimate bearing capacity and the calculation result of the surcharge method is less than 0.5%, and the O-cell conversion coefficient can be accurately calculated.

microRNA-331-3p (miR-331-3p) has been displayed as an oncogene in pancreatic cancer (PC). The current research set out to elucidate how miR-331-3p in carcinoma-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) facilitated the tumorigenesis in PC. First, a dual-luciferase reporter assay was adopted to investigate the relationship between miR-331-3p and SCARA5. In addition, EVs were isolated normal fibroblasts and CAFs, and these isolated EVs were co-cultured with PC cells. Cell proliferative and migrating/invasive potentials were further evaluated with the help of a CCK-8 and Transwell assays, respectively. Gain- and loss-of-function assays were also implemented to assess the role of miR-331-3p, SCARA5, and FAK pathway in PC cells. Lastly, xenograft nude mice were established to investigate the role of miR-331-3p in vivo. miR-331-3p negatively targeted SCARA5 and was highly expressed in CAFs-derived EVs, which accelerated the proliferative, migrating, and invasive potentials of PC cells. Meanwhile, over-expression of miR-331-3p enhanced the proliferative, migrating, and invasive properties of PC cells and promoted tumor growth in vivo by manipulating SCARA5/FAK axis, whereas SCARA5 countered the oncogenic effects of miR-331-3p. Overall, miR-331-3p in CAFs-derived EVs inhibits SCARA5 expression and activates the FAK pathway, thereby augmenting the progression of PC. Our study provides a potential therapeutic target for the treatment of PC.

Abstract Identification, sorting, and sequencing of individual cells directly from in situ samples have great potential for in‐depth analysis of the structure and function of microbiomes. In this work, based on an artificial intelligence (AI)‐assisted object detection model for cell phenotype screening and a cross‐interface contact method for single‐cell exporting, we developed an automatic and index‐based system called EasySort AUTO, where individual microbial cells are sorted and then packaged in a microdroplet and automatically exported in a precisely indexed, “One‐Cell‐One‐Tube” manner. The target cell is automatically identified based on an AI‐assisted object detection model and then mobilized via an optical tweezer for sorting. Then, a cross‐interface contact microfluidic printing method that we developed enables the automated transfer of cells from the chip to the tube, which leads to coupling with subsequent single‐cell culture or sequencing. The efficiency of the system for single‐cell printing is >93%. The throughput of the system for single‐cell printing is ~120 cells/h. Moreover, >80% of single cells of both yeast and Escherichia coli are culturable, suggesting the superior preservation of cell viability during sorting. Finally, AI‐assisted object detection supports automated sorting of target cells with high accuracy from mixed yeast samples, which was validated by downstream single‐cell proliferation assays. The automation, index maintenance, and vitality preservation of EasySort AUTO suggest its excellent application potential for single‐cell sorting.

Abstract Background Bloodstream infection (BSI) is a significant cause of mortality among patients with fever of unknown origin (FUO). Inappropriate empiric antimicrobial therapy increases difficulty in BSI diagnosis and treatment. Knowing the risk of BSI at early stage may help improve clinical outcomes and reduce antibiotic overuse. Methods We constructed a multivariate prediction model based on clinical features and serum inflammatory markers using a cohort of FUO patients over a 5-year period by Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression. Results Among 712 FUO patients, BSI was confirmed in 55 patients. Five independent predictors available within 24 h after admission for BSI were identified: presence of diabetes mellitus, chills, C-reactive protein level of 50–100 mg/L, procalcitonin > 0.3 ng/mL, neutrophil percentage > 75%. A predictive score incorporating these 5 variables has adequate concordance with an area under the curve of 0.85. The model showed low positive predictive value (22.6%), but excellent negative predictive value (97.4%) for predicting the risk of BSI. The risk of BSI reduced to 2.0% in FUO patients if score

Abstract Due to the challenges in detecting in situ activity and cultivating the not-yet-cultured, functional assessment and mining of living microbes from nature has typically followed a ‘culture-first’ paradigm. Here, employing phosphate-solubilizing microbes (PSM) as model, we introduce a ‘screen-first’ strategy that is underpinned by a precisely one-cell-resolution, complete workflow of single-cell Raman-activated Sorting and Cultivation (scRACS-Culture). Directly from domestic sewage, individual cells were screened for in-situ organic-phosphate-solubilizing activity via D2O intake rate, sorted by the function via Raman-activated Gravity-driven Encapsulation (RAGE), and then cultivated from precisely one cell. By scRACS-Culture, pure cultures of strong organic PSM including Comamonas spp., Acinetobacter spp., Enterobacter spp. and Citrobacter spp., were derived, whose phosphate-solubilizing activities in situ are 90–200% higher than in pure culture, underscoring the importance of ‘screen-first’ strategy. Moreover, employing scRACS-Seq for post-RACS cells that remain uncultured, we discovered a previously unknown, low-abundance, strong organic-PSM of Cutibacterium spp. that employs secretary metallophosphoesterase (MPP), cell-wall-anchored 5′-nucleotidase (encoded by ushA) and periplasmic-membrane located PstSCAB-PhoU transporter system for efficient solubilization and scavenging of extracellular phosphate in sewage. Therefore, scRACS-Culture and scRACS-Seq provide an in situ function-based, ‘screen-first’ approach for assessing and mining microbes directly from the environment.

Abstract Rapid expansion of the probiotics industry demands fast, sensitive, comprehensive, and low‐cost strategies for quality assessment. Here, we introduce a culture‐free, one‐cell‐resolution, phenome‐genome‐combined strategy called Single‐Cell Identification, Viability and Vitality tests, and Source‐tracking (SCIVVS). For each cell directly extracted from the product, the fingerprint region of D2O‐probed single‐cell Raman spectrum (SCRS) enables species‐level identification with 93% accuracy, based on a reference SCRS database from 21 statutory probiotic species, whereas the C–D band accurately quantifies viability, metabolic vitality plus their intercellular heterogeneity. For source‐tracking, single‐cell Raman‐activated Cell Sorting and Sequencing can proceed, producing indexed, precisely one‐cell‐based genome assemblies that can reach ~99.40% genome‐wide coverage. Finally, we validated an integrated SCIVVS workflow with automated SCRS acquisition where the whole process except sequencing takes just 5 h. As it is >20‐fold faster, >10‐time cheaper, vitality‐revealing, heterogeneity‐resolving, and automation‐prone, SCIVVS is a new technological and data framework for quality assessment of live‐cell products.

Electrical switching of topological antiferromagnetic states in Mn3Sn thin films has been a subject of active investigation. However, dependences of switching behaviors on the film thickness, external field, and crystal orientation remain to be fully explored, which motivate the present study. In this work, (112̄0)-orientated Mn3Sn thin films are fabricated on sapphire substrates, in which a large anomalous Hall effect over a wide temperature range (270–400 K) can be identified. The current-induced spin–orbit torques (SOTs) are utilized to electrically manipulate the topological antiferromagnetic states in Mn3Sn/Pt bilayers. The robust SOT switching can be realized in Mn3Sn films with thicknesses up to 100 nm and with in-plane fields up to 1200 mT. Furthermore, SOT switching behaviors that are independent of the choice of crystal orientations are clearly revealed. Our results could be useful for implementing Mn3Sn films for efficient and stable antiferromagnetic spintronics.

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case–control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

Background: Rapid and reliable diagnostic methods for Aspergillus fumigatus infection are urgently needed. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 13a (Cas13a) has high sensitivity and specificity in the diagnosis of viral infection. However, its potential use in detecting A. fumigatus remains unexplored. A highly sensitive and specific method using the CRISPR/Cas13a system was developed for the reliable and rapid detection of A. fumigatus. Methods: The conserved internal transcribed spacer (ITS) region of A. fumigatus was used to design CRISPR-derived RNA (crRNA) and the corresponding recombinase polymerase amplification (RPA) primer sequence with the T7 promoter for the CRISPR assay. Twenty-five clinical isolates and 43 bronchoalveolar lavage fluid (BALF) remaining from routine examinations of patients with confirmed pulmonary aspergillosis were collected to further validate the CRISPR assay. Results: No amplification signal was observed when genomic DNA from closely clinically related Aspergillus species, such as Aspergillus flavus, Aspergillus niger, and Aspergillus terreus, as well as Monascus purpureus Went and Escherichia coli, was tested by this assay, and the detection limit for A. fumigatus was 3 copies in a single reaction system. Validation experiments using the 25 clinical isolates demonstrated 91.7% specificity for the A. fumigatus section, and the sensitivity was 100% when first-generation sequencing was used as the standard. There was no significant difference between the PCR and CRISPR methods (P = 1.0), and the diagnosis results of the two methods were consistent (Kappa = 0.459, P = 0.003). Conclusion: The study offers a new validated CRISPR/Cas13a technique for A. fumigatus detection, providing a simple, rapid and affordable test that is ready for application in the diagnosis of A. fumigatus infection.

Polyphenols, as an important category of natural organics, are ubiquitous in plants and structurally diverse. Batch experiments were conducted to investigate the role of natural polyphenol, such as gallic acid (GA) and tannic acid (TA), in the biochemical behavior of Cr(VI) in soil media. GA and TA can effectively convert Cr(VI) to Cr(III) under neutral conditions (pH 7.0). However, there are significant differences in the transport, leaching toxicity, and bioavailability of reduced Cr(III) between the two systems. UV–vis spectra, chromium (Cr) mass balance, speciation distribution, and X-ray photoelectron spectroscopy were used to explore the intrinsic mechanisms of Cr(VI) reduction and (im)mobilization in the presence of GA or TA. Results showed that the reduction of Cr(VI) by GA was accompanied by poor immobilization of reduced Cr(III), especially at high GA concentrations (4–10 g/L), which was associated with the formation of soluble Cr(III) complexes. After treatment with 4 g/L GA, 51.49 ± 3.04% of the Cr in GA system was mobilized as complexes into aqueous phase. In contrast, the reduction of Cr(VI) and the subsequent precipitation of reduced Cr(III) was dominant in the TA system. After treatment with 4 g/L TA, 97.24 ± 0.31% of the total Cr in the TA system was immobilized into soil phase and transformed into more stable fractions. Our findings provide new insights into how natural organics shape the fate and transport of Cr in soils, which also have substantial implications for the development of Cr sequestration technology.

BackgroundThe emergence of highly drug-resistant K. pneumoniae, has become a major public health challenge. In this work, we aim to investigate the diversity of species and sequence types (STs) of clinical Klebsiella isolates and to characterize the prevalence and structure of class 1 integrons.MethodsBased on the whole genome sequencing, species identification was performed by 16S rRNA gene homology and average nucleotide identity (ANI) analysis. STs were determined in accordance with the international MLST schemes for K. pneumoniae and K. variicola. Integron characterization and comparative genomic analysis were performed using various bioinformatic tools.ResultsSpecies identification showed that the 167 isolates belonged to four species: K. pneumoniae, K. variicola subsp. variicola, K. quasipneumoniae and K. aerogenes. Thirty-six known and 5 novel STs were identified in K. pneumoniae, and 10 novel STs were identified in K. variicola subsp. variicola. Class 1 integrons were found in 57.49% (96/167) of the isolates, and a total of 169 resistance gene cassettes encoding 19 types of resistance genes, including carbapenem resistance gene (blaIPM-4) and class D β-lactamases gene (blaOXA-1 and blaOXA-10), were identified. Among the 17 complete genomes, 29 class 1 integrons from 12 groups were found, only 1 group was encoded on chromosomes. Interestingly, one plasmid (pKP167-261) carrying two copies of approximately 19-kb IS26-Int1 complex resistance region that contains an integron and a multidrug resistance gene fragment.ConclusionThe results of this work demonstrated that the species and STs of the clinical Klebsiella isolates were more complex by the whole genome sequence analysis than by the traditional laboratory methods. Finding of the new structure of MGEs related to the resistance genes indicates the great importance of deeply exploring the molecular mechanisms of bacterial multidrug resistance.

Abstract Background Long noncoding RNAs (lncRNAs) exert crucial biological functions by regulating miRNAs, which are implicated in cancer progression and tumorigenesis. A previous study has indicated that lncRNA linc02544 expression is upregulated in lung adenocarcinoma, whereas, the role of linc02544 in LUSC is elusive. Methods The differential linc02544 expression in LUSC tissues and adjacent non-tumor tissues were evaluated with RT-qPCR. Kaplan-Meier curve was conducted to evaluate the clinical prognostic significance of linc02544. Then cellular experiments were performed to assess the influence of linc02544 in LUSC proliferation, invasion, and migration, and a western blot assay was used to measure the metastasis-related protein levels. The downstream miRNAs were verified using the LncBase Experimental v.2 database and dual-luciferase reporter assay. Results Linc02544 was overexpressed in LUSC tissues from positive lymph node metastasis-positive and TNM high-stage patients. Low linc02544 expression was associated with a longer survival rate. Downregulation of linc02544 by si-linc02544 restrained cell growth capacities, migration, and invasion abilities. Expression of MMP-2, MMP-9, and vimentin was decreased while E-cadherin was increased in si-linc02544 cells compared with that in untreated cells. Mechanistically, we identified that linc02544 acted as a sponge of miR-138-5p, which expression had a negative correlation. E2F3 was a potential target of miR-138-5p, Conclusions Notably, high linc02544 expression was associated with severe clinical parameters and was a putative prognostic predictor for patients with LUSC. Downregulation of linc02544 may weaken the LUSC cell proliferation, migration, and invasion by regulating miR-138-5p/E2F3, which maybe serve as a biomarker for the prognosis and target treatment of LUSC.

Abstract Background Etiological diagnosis is a key step in the treatment of patients with rare pulmonary mycosis, and the lack of understanding of this disease and lack of specific markers for the detection of rare species, such as Exophiala dermatitidis, add to the difficulty in diagnosing the condition. Therefore, improving the diagnostic strategies for this disease is very important. Case presentation A 52-year-old man presented with cough, sputum production and hemoptysis; chest computed tomography (CT) revealed multiple bilateral lesions. The pathogen was unable to be identified after three biopsies. Subsequently, we performed combined tissue metagenomic next-generation sequencing (mNGS). The results of mNGS and a good therapeutic response helped to identify the causative pathogen as Exophiala dermatitidis. Finally, the patient was diagnosed with Exophiala dermatitidis pneumonia. Conclusions Combining molecular techniques, such as mNGS, with clinical microbiological tests will improve the rate of positivity in the diagnosis of rare fungal infections, and the importance of follow-up should be emphasized.

Severely cold weather reduces the willingness of residents to open windows while cooking. This results in an insufficient replenishment of makeup air and a reduction in the range hood discharge capacity. For an effective trade-off between indoor air temperature maintenance and air quality aggravation in winter, a new makeup air supply method (ceiling makeup air) was proposed and established both experimentally and numerically. The improvements in the kitchen air environment during cooking were studied through experimental tests and CFD simulations, considering different makeup air arrangements. The results reveal that the ceiling makeup air scheme can significantly reduce the concentration of PM2.5 compared with the cracks makeup air scheme (wherein the kitchen window and door are closed). Moreover, it increased the indoor temperature by over 11.9 °C compared with the open window makeup air scheme. The average relative error between the experimental and simulated data was within 6.1%. Among the considered factors, the size of the air inlet had the largest impact. This was followed by the layout, size, and shape of the ceiling inlets. The ceiling makeup air scheme demonstrated the potential for improving residential kitchen air environments in severely cold regions. [ABSTRACT FROM AUTHOR]

For the construction of dam substations in coastal or mountainous areas, inclined soft soil foundations are very common. The unique engineering characteristics of inclined soft soil foundations can bring great difficulties to the construction of dam substations. In this paper, a pile foundation reinforcement dam slope model on an inclined soft soil foundation is established; the influence of different pile spacings, the pile length, and the soft soil foundation angle on the slope safety factor is studied; and the failure mechanism and stability of pile-supported dam slope foundation are analyzed. The research results indicate that pile foundation reinforcement can reduce the deformation of the dam slope foundation and improve stability. The pile layout has an important impact on stability, but a change in the pile spacing has little effect on the settlement surface at the bottom of the dam slope. The pile length has a significant impact on the safety of the slope within a certain range. The main stress area of the pile is 0–2 m above the pile, and its main deformation is the lateral deformation of the upper part of the pile. The research results of this article can provide parameter support and theoretical guidance for the construction of dam substations.