A lightweight network architecture for traffic sign recognition based on enhanced LeNet-5 network.

As an important part of the unmanned driving system, the detection and recognition of traffic sign need to have the characteristics of excellent recognition accuracy, fast execution speed and easy deployment. Researchers have applied the techniques of machine learning, deep learning and image processing to traffic sign recognition successfully. Considering the hardware conditions of the terminal equipment in the unmanned driving system, in this research work, the goal was to achieve a convolutional neural network (CNN) architecture that is lightweight and easily implemented for an embedded application and with excellent recognition accuracy and execution speed. As a classical CNN architecture, LeNet-5 network model was chosen to be improved, including image preprocessing, improving spatial pool convolutional neural network, optimizing neurons, optimizing activation function, etc. The test experiment of the improved network architecture was carried out on German Traffic Sign Recognition Benchmark (GTSRB) database. The experimental results show that the improved network architecture can obtain higher recognition accuracy in a short interference time, and the algorithm loss is significantly reduced with the progress of training. At the same time, compared with other lightweight network models, this network architecture gives a good recognition result, with a recognition accuracy of 97.53%. The network structure is simple, the algorithm complexity is low, and it is suitable for all kinds of terminal equipment, which can have a wider application in unmanned driving system.

Single-cell analysis of the survival mechanisms of fratricidal CAR-T targeting of T cell malignancies.

Chimeric antigen receptor T (CAR-T) cell therapy targeting T cell tumors still faces many challenges, one of which is its fratricide due to the target gene expressed on CAR-T cells. Despite this, these CAR-T cells can be expanded in vitro by extending the culture time and effectively eliminating malignant T cells. However, the mechanisms underlying CAR-T cell survival in cell subpopulations, the molecules involved, and their regulation are still unknown. We performed single-cell transcriptome profiling to investigate the fratricidal CAR-T products (CD26 CAR-Ts and CD44v6 CAR-Ts) targeting T cells, taking CD19 CAR-Ts targeting B cells from the same donor as a control. Compared with CD19 CAR-Ts, fratricidal CAR-T cells exhibit no unique cell subpopulation, but have more exhausted T cells, fewer cytotoxic T cells, and more T cell receptor (TCR) clonal amplification. Furthermore, we observed that fratricidal CAR-T cell survival was accompanied by target gene expression. Gene expression results suggest that fratricidal CAR-T cells may downregulate their human leukocyte antigen (HLA) molecules to evade T cell recognition. Single-cell regulatory network analysis and suppression experiments revealed that exhaustion mediated by critical regulatory factors may contribute to fratricidal CAR-T cell survival. Together, these data provide valuable and first-time insights into the survival of fratricidal CAR-T cells.

Lethal pulmonary thromboembolism in mice induced by intravenous human umbilical cord mesenchymal stem cell-derived large extracellular vesicles in a dose- and tissue factor-dependent manner.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 µg/g body weight) in 100 µL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 µg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.

Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study.

BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

MsWRKY44 regulates Mg-K homeostasis of shoots and promotes alfalfa sensitivities to acid and Al stresses.

Mg-K homeostasis is essential for plant response to abiotic stress, but its regulation remains largely unknown. MsWRKY44 cloned from alfalfa was highly expressed in leaves and petioles. Overexpression of it inhibited alfalfa growth, and promoted leaf senescence and alfalfa sensitivities to acid and Al stresses. The leaf tips, margins and interveins of old leaves occurred yellow spots in MsWRKY44-OE plants under pH4.5 and pH4.5 +Al conditions. Meanwhile, Mg-K homeostasis was substantially changed with reduction of K accumulation and increases of Mg as well as Al accumulation in shoots of MsWRKY44-OE plants. Further, MsWRKY44 was found to directly bind to the promoters of MsMGT7 and MsCIPK23, and positively activated their expression. Transiently overexpressed MsMGT7 and MsCIPK23 in tobacco leaves increased the Mg and Al accumulations but decreased K accumulation. These results revealed a novel regulatory module MsWRKY44-MsMGT7/MsCIPK23, which affects the transport and accumulation of Mg and K in shoots, and promotes alfalfa sensitivities to acid and Al stresses.

Rock pressure evaluation in coal face based on multi-factor decision-making theory.

The behavior of rock pressure is a natural and inevitable phenomenon during coal seam mining, resulting in numerous casualties and equipment damage annually. The ability to predict and assess the strength of rock pressure in the coal face beforehand has become crucial in preventing rock pressure accidents. This paper took the prediction of rock pressure strength in coal face as the research object, and based on the multi-factor decision-making theory, proposed a new method for the evaluation of rock pressure strength in coal face-"dual-dimension rock pressure strength evaluation method". Initially, the rock pressure strength index IA was obtained through the application of the law of sedimentary pressure control and microseismic monitoring data. The drilling data at the exploration scale served as references. Then, based on the rock pressure control mechanism, the rock pressure strength index IB was obtained by utilizing a type of Euclidean distance formula at the coal face scale. Finally, in order to mutually correct the two rock pressure strength indices, the rock pressure strength grade matrix was employed to acquire the rock pressure strength grade of the coal face. Applying this evaluation method to the coal face, the prediction outcomes aligned with the actual situation. Therefore, this method can provide a theoretical reference for the prediction of rock pressure strength and the prevention of rock pressure accidents in alternative areas.

A predictive model for premature atherosclerosis in systemic lupus erythematosus based on clinical characteristics.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with a significant risk of atherosclerotic cardiovascular disease, especially in the development of premature atherosclerosis. Specific prediction models for premature atherosclerosis in SLE patients are still limited. The objective of this study was to establish a predictive model for premature atherosclerosis in SLE. METHOD: The study collected clinical and laboratory data from 148 SLE patients under the age of 55, between January 2021 and June 2023. The least absolute shrinkage and selection operator logistic regression model was utilized to identify potentially relevant features. Subsequently, a nomogram was developed using multivariable logistic analysis. The performance of the nomogram was evaluated through a receiver-operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of 148 SLE patients who fulfilled the inclusion criteria were enrolled in the study, of whom 53 patients (35.81%) met the definition of premature atherosclerosis. Hypertension, antiphospholipid syndrome, azathioprine use, duration of glucocorticoid, and age of patients were included in the multivariable regression. The nomogram, based on the non-overfitting multivariable model, was internally validated and demonstrated sufficient clinical utility for assessing the risk of premature atherosclerosis (area under curve: 0.867). CONCLUSIONS: The comprehensive nomogram constructed in this study serves as a useful and convenient tool for evaluating the risk of premature atherosclerosis in SLE patients. It is helpful for clinicians to early identify SLE patients with premature atherosclerosis and facilitates the implementation of more effective preventive measures. Key Points • SLE patients are at a significantly higher risk of developing premature atherosclerosis compared to the general population, and this risk persists even in cases with low disease activity. Traditional models used to evaluate and predict premature atherosclerosis in SLE patients often underestimate the risk. • This study establishes a comprehensive and visually orientated predictive model of premature atherosclerosis in SLE patients, based on clinical characteristics. • The scoring system allows for convenient and effective prediction of individual incidence of premature atherosclerosis, and could provide valuable information for identification and making further intervention decision.

Factors influencing postoperative visual improvement in 208 patients with tuberculum sellae meningiomas.

OBJECTIVE: Tuberculum sellae meningiomas (TSMs) usually compress the optic nerve and optic chiasma, thus affecting vision. Surgery is an effective means to remove tumors and improve visual outcomes. On a larger scale, this study attempted to further explore and confirm the factors related to postoperative visual outcomes to guide the treatment of TSMs. METHODS: Data were obtained from 208 patients with TSMs who underwent surgery at our institution between January 2010 and August 2022. Demographics, ophthalmologic examination results, imaging data, extent of resection, radiotherapy status, and surgical approaches were included in the analysis. Univariate and multivariate logistic regressions were used to assess the factors that could lead to favorable visual outcomes. RESULTS: The median follow-up duration was 63 months, and gross total resection (GTR) was achieved in 174 (83.7%) patients. According to our multivariate logistic regression analysis, age < 60 years (odds ratio [OR] = 0.310; P = 0.007), duration of preoperative visual symptoms (DPVS) < 10 months (OR = 0.495; P = 0.039), tumor size ≤ 27 mm (OR = 0.337; P = 0.002), GTR (OR = 3.834; P = 0.006), and a tumor vertical-to-horizontal dimensional ratio < 1 (OR = 2.593; P = 0.006) were found to be significant independent predictors of favorable visual outcomes. CONCLUSION: Age, DPVS, tumor size, GTR, and the tumor vertical-to-horizontal dimensional ratio were found to be powerful predictors of favorable visual outcomes. This study may help guide decisions regarding the treatment of TSMs.

A method for predicting drugs that can boost the efficacy of immune checkpoint blockade.

Combination therapy is a promising therapeutic strategy to enhance the efficacy of immune checkpoint blockade (ICB); however, predicting drugs for effective combination is challenging. Here we developed a general data-driven method called CM-Drug for screening compounds that can boost ICB treatment efficacy based on core and minor gene sets identified between responsive and nonresponsive samples in ICB therapy. The CM-Drug method was validated using melanoma and lung cancer mouse models, with combined therapeutic efficacy demonstrated in eight of nine predicted compounds. Among these compounds, taltirelin had the strongest synergistic effect. Mechanistic analysis and experimental verification demonstrated that taltirelin can stimulate CD8+ T cells and is mediated by the induction of thyroid-stimulating hormone. This study provides an effective and general method for predicting and evaluating drugs for combination therapy and identifies candidate compounds for future ICB combination therapy.

A Predictive Network-Based Immune Checkpoint Blockade Immunotherapeutic Signature Optimizing Patient Selection and Treatment Strategies.

Immune checkpoint blockade (ICB) therapy has brought significant advancements to the field of oncology. However, the diverse responses among patients highlight the need for more accurate predictive tools. In this study, insights are drawn from tumor-immunology pathways, and a novel network-based ICB immunotherapeutic signature, termed ICBnetIS, is constructed. The signature is derived from advanced biological network-based computational strategies involving co-expression networks and molecular interactions networks. The efficacy of ICBnetIS is established through its association with enhanced patient survival and a robust immune response characterized by diverse immune cell infiltration and active anti-tumor immune pathways. The validation process positions ICBnetIS as an effective tool in predicting responses to ICB therapy, analyzing ICB data from a broad collection of over 700 samples from multiple cancer types of more than 15 datasets. It achieves an aggregated prediction AUC of 0.784, which outperforms the other nine renowned immunotherapeutic signatures, indicating the superior predictive capability of ICBnetIS. To sum up, the findings suggest ICBnetIS as a potent tool in predicting ICB therapy responses, offering significant implications for patient selection and treatment optimization in oncology. The study highlights the role of ICBnetIS in advancing personalized treatment strategies, potentially transforming the clinical landscape of ICB therapy.

Optimization of FFPE preparation and identification of gene attributes associated with RNA degradation.

Formalin-fixed paraffin-embedded (FFPE) tissues are widely available specimens for clinical studies. However, RNA degradation in FFPE tissues often restricts their utility. In this study, we determined optimal FFPE preparation conditions, including tissue ischemia at 4°C (<48 h) or 25°C for a short time (0.5 h), 48-h fixation at 25°C and sampling from FFPE scrolls instead of sections. Notably, we observed an increase in intronic reads and a significant change in gene rank based on expression level in the FFPE as opposed to fresh-frozen (FF) samples. Additionally, we found that more reads were mapped to genes associated with chemical stimulus in FFPE samples. Furthermore, we demonstrated that more degraded genes in FFPE samples were enriched in genes with short transcripts and high free energy. Besides, we found 40 housekeeping genes exhibited stable expression in FF and FFPE samples across various tissues. Moreover, our study showed that FFPE samples yielded comparable results to FF samples in dimensionality reduction and pathway analyses between case and control samples. Our study established the optimal conditions for FFPE preparation and identified gene attributes associated with degradation, which would provide useful clues for the utility of FFPE tissues in clinical practice and research.

Identification of P21 (CDKN1A) Activated Kinase 4 as a Susceptibility Gene for Familial Non-Medullary Thyroid Carcinoma.

Background: Familial non-medullary thyroid carcinoma (FNMTC) is a genetically predisposed disease with unclear genetic mechanisms. This makes research on susceptibility genes important for the diagnosis and treatment options. Methods: This study included a five-member family affected by papillary thyroid carcinoma. The candidate genes were identified through whole-exome sequencing and Sanger sequencing in family members, other FNMTC patients, and sporadic non-medullary thyroid carcinoma patients. The pathogenicity of the mutation was predicted using in silico tools. Cell phenotype experiments in vitro and models of lung distant metastasis in vivo were conducted to confirm the characteristics of the mutation. Transcriptome sequencing and mechanistic validation were employed to compare the disparities between PAK4 wild-type (WT) and PAK4 mutant (MUT) cell lines. Results: This mutation alters the protein structure, potentially increasing instability by affecting hydrophobicity, intra-molecular hydrogen bonding, and phosphorylation sites. It specifically promotes phosphorylated PAK4 nuclear translocation and expression in thyroid tissue and cell lines. Compared with the WT cells line, PAK4 I417T demonstrates enhanced proliferation, invasiveness, accelerated cell division, and inhibition of cell apoptosis in vitro. In addition, it exhibits a significant propensity for metastasis in vivo. It activates tumor necrosis factor signaling through increased phosphorylation of PAK4, JNK, NFκB, and c-Jun, unlike the WT that activates it via the PAK4-NFκ-MMP9 axis. In addition, PAK4 MUT protein interacts with matrix metalloproteinase (MMP)3 and regulates MMP3 promoter activity, which is not observed in the WT. Conclusions: Our study identified PAK4: c.T1250C: p.I417T as a potential susceptibility gene for FNMTC. The study concludes that the mutant form of PAK4 exhibits oncogenic function, suggesting its potential as a novel diagnostic molecular marker for FNMTC.

PECTIN ACETYLESTERASE12 regulates shoot branching via acetic acid and auxin accumulation in alfalfa shoots.

Shoot branching is an important biological trait affecting alfalfa (Medicago sativa L.) production, but its development is complicated and the mechanism is not fully clear. In the present study, pectin acetylesterase 12 (MsPAE12) and NAM/ATAF/CUC-domain transcription factor gene (MsNAC73) were isolated from alfalfa. MsPAE12 was highly expressed in shoot apexes, and MsNAC73 was found to be a key transcriptional repressor of MsPAE12 by directly binding to salicylic acid (SA) and jasmonic acid (JA) elements in the MsPAE12 promoter. The biological functions of MsPAE12 and MsNAC73 were studied through overexpression (OE) and down-expression (RNAi) of the 2 genes in alfalfa. The numbers of shoot branches increased in MsPAE12-OE lines but decreased in MsPAE12-RNAi and MsNAC73-OE plants, which was negatively related to their indole-3-acetic acid (IAA) accumulation in shoot apexes. Furthermore, the contents of acetic acid (AA) in shoot apexes decreased in MsPAE12-OE plants but increased in MsPAE12-RNAi and MsNAC73-OE plants. The changes of AA contents were positively related to the expression of TRYPTOPHAN AMINOTRANSFERASE 1 (MsTAA1), TRYPTOPHAN AMINOTRANSFERASE-RELATED 2 (MsTAR2), and YUCCA flavin monooxygenase (MsYUCC4) and the contents of tryptophan (Trp), indole-3-pyruvic acid (IPA), and IAA in shoot apexes of MsPAE12-OE, MsPAE12-RNAi, and MsNAC73-OE plants. Exogenous application of AA to wild type (WT) and MsPAE12-OE plants increased Trp, IPA, and IAA contents and decreased branch number. Exogenous IAA suppressed shoot branching in MsPAE12-OE plants, but exogenous IAA inhibitors increased shoot branching in MsPAE12-RNAi plants. These results indicate that the MsNAC73-MsPAE12 module regulates auxin-modulated shoot branching via affecting AA accumulation in shoot apexes of alfalfa.

Elucidating the Bioinspired Synthesis Process of Magnetosomes-Like Fe3O4 Nanoparticles.

Iron oxide nanoparticles are a kind of important biomedical nanomaterials. Although their industrial-scale production can be realized by the conventional coprecipitation method, the controllability of their size and morphology remains a huge challenge. In this study, a kind of synthetic polypeptide Mms6-28 which mimics the magnetosome protein Mms6 is used for the bioinspired synthesis of Fe3O4 nanoparticles (NPs). Magnetosomes-like Fe3O4 NPs with uniform size, cubooctahedral shape, and smooth crystal surfaces are synthesized via a partial oxidation process. The Mms6-28 polypeptides play an important role by binding with iron ions and forming nucleation templates and are also preferably attached to the [100] and [111] crystal planes to induce the formation of uniform cubooctahedral Fe3O4 NPs. The continuous release and oxidation of Fe2+ from pre-formed Fe2+-rich precursors within the Mms6-28-based template make the reaction much controllable. The study affords new insights into the bioinspired- and bio-synthesis mechanism of magnetosomes.

SMART-SLE: serology monitoring and repeat testing in systemic lupus erythematosus-an analysis of anti-double-stranded DNA monitoring.

OBJECTIVE: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. METHODS: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. RESULTS: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009). CONCLUSION: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing.

The MsDHN1-MsPIP2;1-MsmMYB module orchestrates the trade-off between growth and survival of alfalfa in response to drought stress.

Dehydrins and aquaporins play crucial roles in plant growth and stress responses by acting as protector and controlling water transport across membranes, respectively. MsDHN1 (dehydrin) and MsPIP2;1 (aquaporin) were demonstrated to interact with a membrane-anchored MYB protein, MsmMYB (as mMYB) in plasma membrane under normal condition. MsDHN1, MsPIP2;1 and MsDHN1-MsPIP2;1 positively regulated alfalfa tolerance to water deficiency. Water deficiency caused phosphorylation of MsPIP2;1 at Ser 272, which led to release C terminus of mMYB (mMYBΔ83) from plasma membrane and translocate to nucleus, where C terminus of MsDHN1 interacted with mMYBΔ83, and promoted mMYBΔ83 transcriptional activity in response to water deficiency. Overexpression of mMYB and mMYBΔ83 down-regulated the expression of MsCESA3, but up-regulated MsCESA7 expression by directly binding to their promoters, and resulted in high drought tolerance in transgenic hairy roots. These results indicate that the MsDHN1-MsPIP2;1-MsMYB module serves as a key regulator in alfalfa against drought stress.

ncRNADrug: a database for validated and predicted ncRNAs associated with drug resistance and targeted by drugs.

Drug resistance is a major barrier in cancer treatment and anticancer drug development. Growing evidence indicates that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), play pivotal roles in cancer progression, therapy, and drug resistance. Furthermore, ncRNAs have been proven to be promising novel therapeutic targets for cancer treatment. Reversing dysregulated ncRNAs by drugs holds significant potential as an effective therapeutic strategy for overcoming drug resistance. Therefore, we developed ncRNADrug, an integrated and comprehensive resource that records manually curated and computationally predicted ncRNAs associated with drug resistance, ncRNAs targeted by drugs, as well as potential drug combinations for the treatment of resistant cancer. Currently, ncRNADrug collects 29 551 experimentally validated entries involving 9195 ncRNAs (2248 miRNAs, 4145 lncRNAs and 2802 circRNAs) associated with the drug resistance of 266 drugs, and 32 969 entries involving 10 480 ncRNAs (4338 miRNAs, 6087 lncRNAs and 55 circRNAs) targeted by 965 drugs. In addition, ncRNADrug also contains associations between ncRNAs and drugs predicted from ncRNA expression profiles by differential expression analysis. Altogether, ncRNADrug surpasses the existing related databases in both data volume and functionality. It will be a useful resource for drug development and cancer treatment. ncRNADrug is available at http://www.jianglab.cn/ncRNADrug.

Relationship between ideal cardiovascular health score and perioperative acute kidney injury: A case-control study.

BACKGROUND: Maintaining ideal cardiovascular health scores (CHS) may indirectly contribute to reducing the risk of perioperative acute kidney injury (AKI), which has never been explored previously. In this study, we aimed to explore the relationship between CHS and AKI and provide new ideas for AKI prevention and treatment. METHODS: We examined the effects of CHS on the occurrence of AKI among 2783 participants from the Kailuan study, who received general anesthesia during noncardiac surgery from 2016 to 2020. The odds ratios (ORs) and 95% confidence intervals (95% CIs) for AKI were calculated by using the logistic regression. RESULTS: Among 2783 participants 187 were diagnosed with perioperative AKI. We found an inverse relationship between the CHS scores and the risk of AKI. Participants with CHS score ≥ 10 had 57% decreased risk of AKI (OR = 0.43, 95% CI = 0.23, 0.79), compared with participants with CHS score ≤ 7, especially in men (OR = 0.39, 95% CI: 0.20, 0.76). In addition, participants who never smoked, exercised frequently, and had normal blood pressure had decreased risk of AKI, with corresponding ORs (95% CIs) of 0.66 (0.47, 0.91), 0.73 (0.60, 0.92), and 0.46 (0.28, 0.75), respectively. CONCLUSIONS: CHS was strongly associated with the risk of perioperative AKI, and higher CHS scores were associated with a lower risk of AKI. Further research is needed to explore the long-term effects of achieving and maintaining an ideal CHS on AKI risk.

In Situ TEM Observation of (Cr, Mn, Fe, Co, and Ni)3O4 High-Entropy Spinel Oxide Formation During Calcination at Atomic Scale.

High-entropy oxides (HEOs) are promising anode materials for lithium-ion batteries (LIBs), owing to their stable crystal structure, superionic conductivity, and high capacity. In this study, the (Cr, Mn, Fe, Co, and Ni)3O4 HEO via solid-state reaction is prepared. To improve the synthetic efficiency, it is necessary to understand the formation mechanism. Therefore, a high-resolution transmission electron microscopy (HRTEM) is used to record information during calcination at increasing temperature. The overall formation process included MnO2 and NiO aggregation at 500 °C, followed by (Mn, and Ni)3O4 combined with Co3O4 at 600 °C to form (Mn, Co, and Ni)3O4. At higher temperatures, Fe2O3 and Cr2O3 sequentially combined with (Mn, Co, and Ni)3O4 and formed the (Cr, Mn, Fe, Co, Ni)3O4 at 900 °C. In addition, the valence-state-changing mechanisms and ion arrangements of (Cr, Mn, Fe, Co, and Ni)3O4 are determined using electron energy loss spectroscopy (EELS) and extended X-ray absorption fine structure (EXAFS). This study successfully revealed the formation of HEO at atomic scale. The results provide valuable insights for improving the manufacturing process of (Cr, Mn, Fe, Co, and Ni)3O4 HEOs, which is expected to play a vital role in the development of anode materials for next-generation LIBs.

Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.

Adhesion molecules play essential roles in the homeostatic regulation and malignant transformation of hematopoietic cells. The dysregulated expression of adhesion molecules in leukemic cells accelerates disease progression and the development of drug resistance. Thus, targeting adhesion molecules represents an attractive anti-leukemic therapeutic strategy. In this study, we investigated the prognostic role and functional significance of cytohesin-1 (CYTH1) in acute myeloid leukemia (AML). Analysis of AML patient data from the GEPIA and BloodSpot databases revealed that CYTH1 was significantly overexpressed in AML and independently correlated with prognosis. Functional assays using AML cell lines and an AML xenograft mouse model confirmed that CYTH1 depletion significantly inhibited the adhesion, migration, homing, and engraftment of leukemic cells, delaying disease progression and prolonging animal survival. The CYTH1 inhibitor SecinH3 exerted in vitro and in vivo anti-leukemic effects by disrupting leukemic adhesion and survival programs. In line with the CYTH1 knockdown results, targeting CYTH1 by SecinH3 suppressed integrin-associated adhesion signaling by reducing ITGB2 expression. SecinH3 treatment efficiently induced the apoptosis and inhibited the growth of a panel of AML cell lines (MOLM-13, MV4-11 and THP-1) with mixed-lineage leukemia gene rearrangement, partly by reducing the expression of the anti-apoptotic protein MCL1. Moreover, we showed that SecinH3 synergized with the BCL2-selective inhibitor ABT-199 (venetoclax) to inhibit the proliferation and promote the apoptosis of ABT-199-resistant leukemic cells. Taken together, our results not only shed light on the role of CYTH1 in cell-adhesion-mediated leukemogenesis but also propose a novel combination treatment strategy for AML.