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Abstract Background Circulating microRNAs (miRNAs) are recently a rapidly increasing of interest as non-invasive biomarkers for diagnosis and prognosis of acute myocardial infarction (AMI). Previous studies revealed that several miRNAs exhibited the capacity for diagnosis and prognosis of AMI, the reasons why these circulating miRNAs are concerned as targets for investigation are quite cryptogenic, presumably due to the lack of clues provided by global surveillance at the transcriptome level, and the current data for some miRNAs are controversial and inconsistent among independent studies. Methods To comprehensively profiling the potential miRNAs for diagnosis and prognosis of AMI, we reported transcriptomes of circulating miRNAs in the plasma of 27 healthy controls, 64 AMI patients (37 STEMI and 27 NSTEMI) and 20 AMI patients who were subjected to reperfusion therapy. Meanwhile, the cTnI of AMI patients was parallel determined. Differentially-circulated miRNAs were analyzed between each group. All detected circulating miRNAs were examined by ROC analysis and then LASSO dimension reduction to obtain an optimal panel for diagnosis of AMI. A five-year period follow-up towards the AMI and reperfusion patients was performed, and the prognostic value of circulating miRNAs in these patients was estimated by using the Cox regression model, ROC and Kaplan-Meier curves. Results Comprehensive global differences of miRNAs transcriptome among AMI, reperfusion patients and healthy controls were identified. A total of 40 miRNAs, called high diagnostic performance miRNAs, including several previous well-studied miRNAs with AUC greater than 0.85 were shown to discriminate AMI with healthy controls. In addition, 29 miRNAs were analyzed to be strongly correlated with the plasma cTnI level, of which 20 overlapped with high diagnostic performance miRNAs. These overlapped miRNAs are over-represented in the pathways which actually reflect the pathological cause of myocardial infarction, as well as the regulation of gene expression and energetic pathway of cellular response to hypoxia. Finally, two miRNAs were analyzed to be significantly correlated to all-cause mortality. Conclusion This is the first time to survey plasma miRNAs for the development of AMI diagnostic and prognostic biomarkers at the transcriptome level. A subset of miRNAs exhibited potential diagnostic and prognostic merits for AMI.

The inconsistent findings concerning the effects of vitamin D supplementation on cardiometabolic risk factors and the large heterogeneity in the published literature call for further research to identify sources of heterogeneity and potential effect modifiers. We performed a meta-analysis of randomized controlled trials (RCTs) published until March 2024 that reported estimates for the effects of vitamin D supplementation on cardiometabolic factors and relevant baseline covariates of RCT participants. A total of 17 656 participants from 99 RCTs were analyzed, and weighted mean differences (95% confidence intervals (CI)) for the intervention status were derived using random-effects modeling. Overall, compared with the placebo, vitamin D supplementation (median dose: 3320 international unit (IU)·day−1; range 40–120 000 IU·day−1) had favorable effects on systolic blood pressure (SBP; −2.04 (95% CI, −3.50, −0.59) mmHg; 1 mmHg = 0.133 kPa), diastolic blood pressure (DBP; −3.00 (95% CI, −3.61, −2.39) mmHg), total cholesterol (TC; −0.12 (95% CI, −0.21, −0.03) mmol·L−1), fasting blood glucose (FBG; −0.13 (95% CI, −0.20, −0.05) mmol·L−1), hemoglobin A1C (A1C; −0.09% (95% CI, −0.13%, −0.05%)), and fasting blood insulin (FBI: −7.61 (95% CI, −11.93, −3.30) pmol·L−1). The benefits of vitamin D were most evident in trials performed in non-Westerners, participants with baseline 25-hydroxyvitamin D (25[OH]D) lower than 15.0 ng·mL−1, non-obese (body mass index (BMI) < 30 kg·m−2), and older (age ≥ 50 years). The findings of this study underscore the need for personalized vitamin D intervention strategies that comprehensively account for individual patient characteristics (such as ethnocultural background, age, BMI, and circulating 25[OH]D level), intervention dosage, and intervention duration to optimize cardiometabolic health outcomes.

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.

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 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.

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.

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.

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.

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 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.

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.

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 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.

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.

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.

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.

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.

The seismic reflectivity and quality factor Q play an important role in seismic processing and interpretation, such as improving the resolution of seismic data and enhancing the reservoir identification. Most methods estimate seismic reflectivity and Q separately. However, the error of Q model has a negative impact on the reflectivity estimation and the interference of reflectivity makes Q estimates less reliable. In this paper, we propose a new method for concurrent estimation of seismic reflectivity and Q by using optimal dictionary learning. This new method first constructs a complete dictionary based on the non-stationary convolution model, then computes the reflectivity series under different dictionary matrices with the corresponding referencing Q values, and finally selects the optimal dictionary matrix by comprehensively analyzing the residual and reflectivity sparsity so as to obtain seismic reflectivity and Q simultaneously. The results of synthetic and real data examples test confirm the effectiveness of the proposed method. The proposed method provides accurate estimation of seismic reflectivity and Q, improves the vertical resolution without losing weak events and offers more accurate information concerning stratigraphic features in great details.

BackgroundPatients with refractory/relapsed (r/r) acute B lymphocytic leukemia (B-ALL) can achieve complete response (CR) after chimeric antigen receptor T-cell (CAR-T) therapy, but recurrence occurs in the short term. To reduce recurrence and improve survival, CAR-T therapy followed by transplantation is a feasible option. We analyzed the long-term follow-up outcomes and the risk factors for allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR by CAR-T therapy in this study.MethodsA total of 144 patients who underwent allo-HSCT after CAR-T therapy in our hospital were enrolled in this study. Target gene analysis was performed in 137 r/r B-ALL patients receiving allo-HSCT after CR by CAR-T therapy. Among the 137 patients, 87 were evaluated for germline predisposition gene mutations, and 92 were evaluated for tumor somatic gene mutations using NGS. The clinical factors, germline predisposition gene and somatic gene mutations associated with the prognosis of patients receiving transplantation after CAR-T therapy were analyzed using univariate Cox regression. Factors related to disease-free survival (DFS) and overall survival (OS) were analyzed using multivariate Cox regression analysis.ResultsIn 137 r/r B-ALL patients, the 2-year cumulative incidence of recurrence (CIR), OS and DFS in patients receiving allo-HSCT after CAR-T therapy was 31.5%, 71.4%, and 60.5%, respectively. The 2-year OS and DFS in MRD-negative patients were 80.9% and 69.3%, respectively. Univariate Cox analysis showed that pretransplant MRD positivity, fungal infection, germline EP300 mutation and somatic TP53 mutation were associated with a poor prognosis after transplantation; a TBI-based regimen was a protective factor for survival and recurrence after transplantation. Multivariate Cox regression analysis showed that the TBI-based regimen was an independent protective factor for DFS, fungal infection and MRD positivity were independent risk factors for DFS, and tumor somatic TP53 mutation and germline EP300 mutation were independent risk factors for DFS and OS.ConclusionGermline EP300 mutation and tumor somatic TP53 mutation are poor prognostic factors for posttransplant recurrence and survival in r/r B-ALL patients achieving CR after CAR-T therapy. The prognostic risk factors should be considered in adjusting treatment strategies to improve the efficacy of clinical diagnosis and treatment.

Abstract Background Accumulating studies have revealed that aberrant expression of circular RNAs (circRNAs) is widely involved in the tumorigenesis and progression of malignant cancers, including colorectal cancer (CRC). Nevertheless, the clinical significance, levels, features, biological function, and molecular mechanisms of novel circRNAs in CRC remain largely unexplored. Methods CRC-related circRNAs were identified through bioinformatics analysis and verified in clinical specimens by qRT–PCR and in situ hybridization (ISH). Then, in vitro and in vivo experiments were performed to determine the clinical significance of, functional roles of, and clinical characteristics associated with circIL4R in CRC specimens and cells. Mechanistically, RNA pull-down, fluorescence in situ hybridization (FISH), luciferase reporter, and ubiquitination assays were performed to confirm the underlying mechanism of circIL4R. Results CircIL4R was upregulated in CRC cell lines and in sera and tissues from CRC patients and was positively correlated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that circIL4R promotes CRC cell proliferation, migration, and invasion via the PI3K/AKT signaling pathway. Mechanistically, circIL4R was regulated by TFAP2C and competitively interacted with miR-761 to enhance the expression of TRIM29, thereby targeting PHLPP1 for ubiquitin-mediated degradation to activate the PI3K/AKT signaling pathway and consequently facilitate CRC progression. Conclusions Our findings demonstrate that upregulation of circIL4R plays an oncogenic role in CRC progression and may serve as a promising diagnostic and prognostic biomarker for CRC detection and as a potential therapeutic target for CRC treatment.

Abstract Background Eukaryotic translation initiation factor 6 (eIF6), also known as integrin β4 binding protein, is involved in ribosome formation and mRNA translation, acting as an anti-association factor. It is also essential for the growth and reproduction of cells, including tumor cells. Yet, its role in oral squamous cell carcinoma (OSCC) remains unclear. Methods The expression characteristics of eIF6 in 233 samples were comprehensively analyzed by immunohistochemical staining (IHC). Effects of eIF6 over-expression and knockdown on cell proliferation, migration and invasion were determined by CCK-8, wound healing and Transwell assays. Western blot, immunofluorescence (IF) and co-immunoprecipitation (co-IP) were performed for mechanical verification. Results We found that cytoplasmic eIF6 was abnormally highly expressed in OSCC tissues, and its expression was associated with tumor size and the clinical grade. Amplification of eIF6 promoted the growth, migration and invasion capabilities of OSCC cell lines in vitro and tumor growth in vivo. Through Western blot analysis, we further discovered that eIF6 significantly promotes epithelial-mesenchymal transformation (EMT) in OSCC cells, while depletion of eIF6 can reverse this process. Mechanistically, eIF6 promoted tumor progression by activating the AKT signaling pathway. By performing co-immunoprecipitation, we discovered a direct interaction between endogenous eIF6 and AKT protein in the cytoplasm. Conclusion These results demonstrated that eIF6 could be a new therapeutic target in OSCC, thus providing a new basis for the prognosis of OSCC patients in the future. Video abstract

In this study, we identified and characterized a novel chromosomally-encoded class B metallo-β-lactamase (MBL) gene designated blaWUS-1 in a carbapenem-resistant isolate Myroides albus P34 isolated from sewage discharged from an animal farm. Comparative analysis of the deduced amino acid sequence revealed that WUS-1 shares the highest amino acid similarities with the function-characterized MBLs MUS-1 (AAN63647.1; 70.73%) and TUS-1 (AAN63648.1; 70.32%). The recombinant carrying blaWUS-1 exhibited increased MICs levels against a number of β-lactam antimicrobials such as carbenicillin, ampicillin and imipenem, and β-lactamase inhibitors (clavulanic acid and tazobactam). The metallo-β-lactamase WUS-1 could also hydrolyze these antimicrobials and the hydrolytic activities could be inhibited by EDTA. Genetic context analysis of blaWUS-1 revealed that no mobile genetic element was found in its surrounding region. The plasmid pMA84474 of Myroides albus P34 harbored 6 resistance genes (blaOXA-347, aadS, blaMYO-1, ereD, sul2 and ermF) within an approximately 17 kb multidrug resistance (MDR) region. These genes, however, were all related to mobile genetic elements.

Xylitol production from lignocellulose hydrolysate is a sustainable and environment-friendly process. In this study, a systematic process of converting corncob waste into xylitol is described. First, the corncobs are hydrolyzed with acid to a hydrolysate. Second, Kluyveromyces marxianus YZJQ016 derived from K. marxianus YZJ074, constructed by overexpressing ScGAL2-N376F from Saccharomyces cerevisiae, CtXYL1 from Candida tropicalis, and KmZWF1 from K. marxianus, produces xylitol from the hydrolysate. A total of ten xylose reductase genes were evaluated, and CtXYL1 proved best by showing the highest catalytic activity under the control of the KmGAPDH promoter. A 5 L fermenter at 42°C produced 105.22 g/L xylitol using K. marxianus YZJQ016—the highest production reported to date from corncob hydrolysate. Finally, for crystallization of the xylitol, the best conditions were 50% (v/v) methanol as an antisolvent, at 25°C, with purity and yield of 99%–100% and 74%, respectively—the highest yield reported to date.

Background: There is a significant gender difference in the prevalence of depression. Recent studies have shown that estrogen plays a crucial role in depression. Therefore, studying the specific mechanism of estrogen’s role in depression can provide new ideas to address the treatment of depression. Chaigui granule has been shown to have exact antidepressant efficacy, and the contents of saikosaponin (a, b1, b2, d) and paeoniflorin in Chaigui granule are about 0.737% and 0.641%, respectively. Some studies have found that they can improve depression-induced decrease in testosterone (T) levels (∼36.99% decrease compared to control). However, whether Chaigui granule can exert antidepressant efficacy by regulating estrogen is still unclear. This study aimed to elucidate the regulation of estrogen levels by Chaigui granule and the underlying mechanism of its anti-depressant effect.Methods: Eighty-four male Sprague-Dawley (SD) rats were modeled using a chronic unpredictable mild stress (CUMS) procedure. The administration method was traditional oral gavage administration, and behavioral indicators were used to evaluate the anti-depressant effect of Chaigui granule. Enzyme-linked immunosorbent assay (ELISA) was adopted to assess the modulating impact of Chaigui granule on sex hormones. Then, reverse transcription-quantitative PCR (RT-qPCR), and Western blot (WB) techniques were employed to detect extracellular regulated protein kinases (ERK) signaling-related molecules downstream of estradiol in the hippocampus tissue.Results: The administration of Chaigui granule significantly alleviated the desperate behavior of CUMS-induced depressed rats. According to the results, we found that Chaigui granule could upregulate the level of estradiol (E2) in the serum (∼46.56% increase compared to model) and hippocampus (∼26.03% increase compared to model) of CUMS rats and increase the levels of CYP19A1 gene and protein, which was the key enzyme regulating the synthesis of T into E2 in the hippocampus. Chaigui granule was also found to have a significant back-regulatory effect on the gene and protein levels of ERβ, ERK1, and ERK2.Conclusion: Chaigui granule can increase the synthesis of E2 in the hippocampus of CUMS-induced depressed rats and further exert antidepressant effects by activating the CYP19A1-E2-ERKs signaling pathway.

The use of zero-carbon and carbon-neutral fuels reduces emissions of conventional pollutants, but their emissions can be toxic and have various adverse effects on human health. This article reviews the possible combustion products of zero-carbon and carbon-neutral fuels, as well as their cytotoxic effects and potential health risks. At the same time, the review outlines biological models and toxicity detection methods commonly used in pollutant toxicity studies. Metals, nitrogen oxides (NOX), and ammonia (NH3) emitted from the combustion of metal fuels, hydrogen fuels, and ammonia fuels in zero-carbon fuels are harmful to human health. Exhaust emissions from carbon-neutral fuels, particularly biodiesel, and their blends with gasoline/diesel are cytotoxic, leading to severe cellular damage, such as oxidative damage, inflammatory responses, DNA damage, cell death, or apoptosis. Moreover, the normal function of the human body’s respiratory, cardiovascular, immune, digestive, urinary, and nervous systems may also be impacted by these fuel emissions according to cytotoxic research. Cytotoxicity of fuel combustion products is usually related to the fuel type, time, dose, and cell line used in the experiment. This review provides some ideas for the exhaust emission management of zero-carbon and carbon-neutral fuels and human health assessment. It also presents a theoretical and experimental basis for further research, including in vivo experiments.

Vertical transmission of group B Streptococcus (GBS) is among the leading causes of neonatal illness and death. Colonization with GBS usually is screened weeks before delivery during pregnancy, on the basis of which preventive measures, such as antibiotic prophylaxis, were taken. However, the accuracy of such an antenatal screening strategy has been questionable because of the intermittent nature of GBS carriage. We developed a simple-to-use, rapid, CRISPR-based assay for GBS detection. We conducted studies in a prospective cohort of 412 pregnant women and a retrospective validation cohort to evaluate its diagnostic performance. We demonstrated that CRISPR-GBS is highly sensitive and offered shorter turnaround times and lower instrument demands than PCR-based assays. This novel GBS test exhibited an overall improved diagnostic performance over culture and PCR-based assays and represents a novel diagnostic for potential rapid, point-of-care GBS screening.

Florfenicol is widely used for the treatment of bacterial infections in domestic animals. The aim of this study was to analyze the molecular mechanisms of florfenicol and oxazolidinone resistance in Enterococcus isolates from anal feces of domestic animals. The minimum inhibitory concentration (MIC) levels were determined by the agar dilution method. Polymerase chain reaction (PCR) was performed to analyze the distribution of the resistance genes. Whole-genome sequencing and comparative plasmid analysis was conducted to analyze the resistance gene environment. A total of 351 non-duplicated enteric strains were obtained. Among these isolates, 22 Enterococcus isolates, including 19 Enterococcus. faecium and 3 Enterococcus. faecalis, were further studied. 31 florfenicol resistance genes (13 fexA, 3 fexB, 12 optrA, and 3 poxtA genes) were identified in 15 of the 19 E. faecium isolates, and no florfenicol or oxazolidinone resistance genes were identified in 3 E. faecalis isolates. Whole-genome sequencing of E. faecium P47, which had all four florfenicol and oxazolidinone resistance genes and high MIC levels for both florfenicol (256 mg/L) and linezolid (8 mg/L), revealed that it contained a chromosome and 3 plasmids (pP47-27, pP47-61, and pP47-180). The four florfenicol and oxazolidinone resistance genes were all related to the insertion sequences IS1216 and located on two smaller plasmids. The genes fexB and poxtA encoded in pP47-27, while fexA and optrA encoded in the conjugative plasmid pP47-61. Comparative analysis of homologous plasmids revealed that the sequences with high identities were plasmid sequences from various Enterococcus species except for the Tn6349 sequence from a Staphylococcus aureus chromosome (MH746818.1). The current study revealed that florfenicol and oxazolidinone resistance genes (fexA, fexB, poxtA, and optrA) were widely distributed in Enterococcus isolates from animal in China. The mobile genetic elements, including the insertion sequences and conjugative plasmid, played an important role in the horizontal transfer of florfenicol and oxazolidinone resistance.

Abstract Background Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease’s complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques. Results We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes. Conclusions Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP. Trial registration Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628 .

The finite-difference (FD) method is one of the most commonly used numerical methods for elastic wave modeling. However, due to the difference approximation of the derivative, the time dispersion phenomenon cannot be avoided. This paper proposes the use of pix2pix algorithm based on a conditional generative adversarial network (cGAN) for removing time dispersion from elastic FD modeling. Firstly, we analyze the time dispersion of elastic wave FD modeling. Then, we discuss the pix2pix algorithm based on cGAN, improve the loss function of the pix2pix algorithm by introducing a Sobel operator, and analyze the parameter selection of the network model for the pix2pix algorithm. Finally, we verify the feasibility and effectiveness of the pix2pix algorithm in removing time dispersion from elastic wave FD modeling through testing some model simulation data.

The rapid development of neural networks has come at the cost of increased computational complexity. Neural networks are both computationally intensive and memory intensive; as such, the minimal energy and computing power of satellites pose a challenge for automatic target recognition (ATR). Knowledge distillation (KD) can distill knowledge from a cumbersome teacher network to a lightweight student network, transferring the essential information learned by the teacher network. Thus, the concept of KD can be used to improve the accuracy of student networks. Even when learning from a teacher network, there is still redundancy in the student network. Traditional networks fix the structure before training, such that training does not improve the situation. This paper proposes a distillation sparsity training (DST) algorithm based on KD and network pruning to address the above limitations. We first improve the accuracy of the student network through KD, and then through network pruning, allowing the student network to learn which connections are essential. DST allows the teacher network to teach the pruned student network directly. The proposed algorithm was tested on the CIFAR-100, MSTAR, and FUSAR-Ship data sets, with a 50% sparsity setting. First, a new loss function for the teacher-pruned student was proposed, and the pruned student network showed a performance close to that of the teacher network. Second, a new sparsity model (uniformity half-pruning UHP) was designed to solve the problem that unstructured pruning does not facilitate the implementation of general-purpose hardware acceleration and storage. Compared with traditional unstructured pruning, UHP can double the speed of neural networks.

Abstract Background With the wide use of florfenicol to prevent and treat the bacterial infection of domestic animals, the emergence of the florfenicol resistance bacteria is increasingly serious. It is very important to elucidate the molecular mechanism of the bacteria’s resistance to florfenicol. Methods The minimum inhibitory concentration (MIC) levels were determined by the agar dilution method, and polymerase chain reaction was conducted to analyze the distribution of florfenicol resistance genes in 39 CoNS strains isolated from poultry and livestock animals and seafood. The whole genome sequence of one multidrug resistant strain, Staphylococcus lentus H29, was characterized, and comparative genomics analysis of the resistance gene-related sequences was also performed. Results As a result, the isolates from the animals showed a higher resistance rate (23/28, 82.1%) and much higher MIC levels to florfenicol than those from seafood. Twenty-seven animal isolates carried 37 florfenicol resistance genes (including 26 fexA, 6 cfr and 5 fexB genes) with one carrying a cfr gene, 16 each harboring a fexA gene, 5 with both a fexA gene and a fexB gene and the other 5 with both a fexA gene and a cfr gene. On the other hand, all 11 isolates from seafood were sensitive to florfenicol, and only 3 carried a fexA gene each. The whole genome sequence of S. lentus H29 was composed of a chromosome and two plasmids (pH29-46, pH29-26) and harbored 11 resistance genes, including 6 genes [cfr, fexA, ant(6)-Ia, aacA-aphD, mecA and mph(C)] encoded on the chromosome, 4 genes [cfr, fexA, aacA-aphD and tcaA] on pH29-46 and 1 gene (fosD) on pH29-26. We found that the S. lentus H29 genome carried two identical copies of the gene arrays of radC-tnpABC-hp-fexA (5671 bp) and IS256-cfr (2690 bp), of which one copy of the two gene arrays was encoded on plasmid pH29-46, while the other was encoded on the chromosome. Conclusions The current study revealed the wide distribution of florfenicol resistance genes (cfr, fexA and fexB) in animal bacteria, and to the best of our knowledge, this is the first report that one S. lentus strain carried two identical copies of florfenicol resistance-related gene arrays.

Research on resistance against polymyxins induced by the mcr-1 gene is gaining interest. In this study, using agar dilution method, polymerase chain reaction, and comparative genomic analysis, we investigated the colistin resistance mechanism of clinical E. coli isolates. The minimum inhibitory concentration (MIC) analysis results revealed that of the 515 isolates tested, bacteria with significantly increased MIC levels against colistin were isolated in 2019. Approximately one-fifth (17.14% to 19.65%) of the isolates showed MIC values ≥1 mg/L against colistin in 2015, 2016, and 2017. However, in 2019, up to three-quarters (74.11%, 146/197) of the isolates showed MIC values ≥1 mg/L against colistin indicating an increase in colistin resistance. Six isolates (EC7518, EC4968, EC3769, EC16, EC117, EC195, 1.13%, 6/515) were found to carry the mcr-1 gene and a novel mcr-1 variant with Met2Ile mutation was identified in EC3769. All six strains showed higher MIC levels (MIC=4 mg/L) than any mcr-1-negative strains (MIC ≤ 2 mg/L). Whole-genome sequencing of the six mcr-1-positive isolates revealed that EC195 carried the highest number of resistance genes (n = 28), nearly a half more than those of the following EC117 (n = 19). Thus, EC195 showed a wider resistance spectrum and higher MIC levels against the antimicrobials tested than the other five isolates. Multi-locus sequence typing demonstrated that these mcr-1-positive strains belonged to six different sequence types. The six mcr-1 genes were located in three different incompatibility group plasmids (IncI2, IncHI2 and IncX4). The genetic context of mcr-1 was related to a sequence derived from Tn6330 (ISApl1-mcr-1-pap2-ISApl1). Investigations into the colistin resistance mechanism and characterization of the molecular background of the mcr genes may help trace the development and spread of colistin resistance in clinical settings.