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Powder Bed Fusion Laser Beam (PBF-LB) is an attractive additive manufacturing technique for fabricating K447A superalloys components. Unfortunately, these as-built parts generally exhibit unsatisfied mechanical properties because they are highly susceptible to internal defects. Herein, we propose different post-treatments, including laser shock peening (LSP), ultrasonic shock peening (USP), laser after ultrasonic shock peening (ULSP), and ultrasonic after laser shock peening (LUSP) for tuning the microstructures and performances of a PBF-LB fabricated K447A superalloys. The microstructural response, residual stress and microhardness redistribution, as well as tensile properties of the K447A superalloys treated by different post-treatments are systematically studied. Results indicate that a gradient heterogeneous structure, which is primarily characterized with gradient variations in grain size, precipitation phase size and dislocation density, is formed on the K447A specimen surface under LUSP treatment. The surface residual stress is completely transformed into compressive state with a maximum amplitude value of −185 MPa, and the peak value of microhardness is improved to 568 HV. The various strengthening mechanisms of gradient heterogeneous structures, as well as dislocation multiplication, grain refinement and precipitated phase strengthening, are responsible for achieving strength-ductility synergy. This work provides promising route and valuable theoretical guidance for optimizing mechanical properties of additively manufactured metastable high γ′ phase fraction superalloys via tuning microstructures.

Abstract Postherpetic neuralgia (PHN) manifests as persistent chronic pain that emerges after a herpes zoster outbreak and greatly diminishes quality of life. Unfortunately, its treatment efficacy has remained elusive, with many therapeutic efforts yielding less than satisfactory results. The research to discern risk factors predicting the onset, trajectory, and prognosis of PHN has been extensive. However, these risk factors often present as nonspecific and diverse, indicating the need for more reliable, measurable, and objective detection methods. The exploration of potential biological markers, including hematological indices, pathological insights, and supportive tests, is increasing. This review highlights potential biomarkers that are instrumental for the diagnosis, management, and prognosis of PHN while also delving deeper into its genesis. Drawing from prior research, aspects such as immune responsiveness, neuronal injury, genetic makeup, cellular metabolism, and pain signal modulation have emerged as prospective biomarkers. The immune spectrum spans various cell subtypes, with an emphasis on T cells, interferons, interleukins, and other related cytokines. Studies on nerve injury are directed toward pain-related proteins and the density and health of epidermal nerve fibers. On the genetic and metabolic fronts, the focus lies in the detection of predisposition genes, atypical protein manifestations, and energy-processing dynamics, with a keen interest in vitamin metabolism. Tools such as functional magnetic resonance imaging, electromyography, and infrared imaging have come to the forefront in the pain signaling domain. This review compiles the evidence, potential clinical implications, and challenges associated with these promising biomarkers, paving the way for innovative strategies for predicting, diagnosing, and addressing PHN.

Abstract Background CFAP65 (cilia and flagella associated protein 65) is a fundamental protein in the development and formation of ciliated flagella, but few studies have focused on its role in cancer. This study aimed to investigate the prognostic significance of CFAP65 in colon cancer. Methods The functionally enriched genes related to CFAP65 were analyzed through the Gene Ontology (GO) database. Subsequently, CFAP65 expression levels in colon cancer were evaluated by reverse transcription and quantitative polymerase chain reaction (RT-qPCR) and immunoblotting in 20 pairs of frozen samples, including tumors and their matched paratumor tissue. Furthermore, protein expression of CFAP65 in 189 colon cancer patients were assessed via immunohistochemical staining. The correlations between CFAP65 expression and clinical features as well as long-term survival were statistically analyzed. Results CFAP65-related genes are significantly enriched on cellular processes of cell motility, ion channels, and GTPase-associated signaling. The expression of CFAP65 was significantly higher in colon cancer tissue compared to paratumor tissue. The proportion of high expression and low expression of CFAP65 in the clinical samples of colon cancer were 61.9% and 38.1%, respectively, and its expression level was not associated with the clinical parameters including gender, age, tumor location, histological differentiation, tumor stage, vascular invasion and mismatch repair deficiency. The five-year disease-free survival rate of the patients with CFAP65 low expression tumors was significantly lower than that those with high expression tumors (56.9% vs. 72.6%, P = 0.03), but the overall survival rate has no significant difference (69% vs. 78.6%, P = 0.171). The cox hazard regression analysis model showed that CFAP65 expression, tumor stage and tumor location were independent prognostic factors. Conclusions In conclusion, we demonstrate CFAP65 is a potential predictive marker for tumor progression in colon cancer.

AbstractCamellia tetracocca H.T. Chang 1981 is an important wild relative of cultivated tea plants. Its leaves are widely used by local people to make tea, showing great economic and breeding values. We here report the complete chloroplast genome of C. tetracocca using Illumina sequencing technology. The complete chloroplast genome of C. tetracocca is 157,026 bp in length, and structurally contains a pair of inverted repeat regions (IRa and IRb, 26,052 bp) separated by a large single-copy region (LSC, 86,669 bp) and a small single-copy region (SSC, 18,253 bp). It is composed of 131 predicted genes, including 86 protein-coding genes, 37 transfer RNA genes, and eight ribosomal RNA genes. The overall GC content is 37.31%. Phylogenetic analysis among four Camellia species and 11 other close species reveals a close relationship between C. tetracocca and C. gymnogyna.

The stimulator of interferon genes (STING) plays a pivotal role in orchestrating innate immunity, and dysregulated activity of STING has been implicated in the pathogenesis of autoimmune diseases. Recent findings suggest that bacterial infection activates STING, relieving ER stress, and triggers non-canonical autophagy by spatially regulating STX17. Despite these insights, the precise mechanism governing the dynamics of autophagosome fusion elicited by STING remains unclear. In this study, we demonstrate that dynamic STING activation guides the autophagy flux, mirroring the trajectory of canonical autophagy adaptors. STING engages in a physical interaction with STX17, and agonist-induced phosphorylation or degradation alleviates STING's inhibitory effects on the assembly of the STX17-SNAP29-VAMP8 complex. Consistent with these findings, degradation-deficient mutants hinder autophagy flux by impeding STX17-mediated autophagosome-lysosome fusion. Moreover, STING mutants associated with lupus disrupt the assembly of the STX17-SNAP29-VAMP8 complex and autophagy process, which lead to persistent STING activation and elevated IFN-β production. Our results highlight that the intracellular trajectory of STING, coupled with autophagy flux, guides the assembly and membrane fusion of the STX17-SNAP29-VAMP8 complex, ensuring the accurate regulation of innate immunity.

Abstract Background and purpose To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P-value

Abstract The proportion of natural sand replaced by steel slag sand affects the volumetric stability of steel slag mortar and steel slag concrete. However, the steel slag substitution rate detection method is inefficient and lacks representative sampling. Therefore, a deep learning-based steel slag sand substitution rate detection method is proposed. The technique adds a squeeze and excitation (SE) attention mechanism to the ConvNeXt model to improve the model's efficiency in extracting the color features of steel slag sand mix. Meanwhile, the model's accuracy is further enhanced by using the migration learning method. The experimental results show that SE can effectively help ConvNeXt acquire images' color features. The model's accuracy in predicting the replacement rate of steel slag sand is 87.99%, which is better than the original ConvNeXt network and other standard convolutional neural networks. After using the migration learning training method, the model predicts the steel slag sand substitution rate with 92.64% accuracy, improving accuracy by 4.65%. The SE attention mechanism and the migration learning training method can help the model acquire the critical features of the image better and effectively improve the model's accuracy. The method proposed in this paper can identify the steel slag sand substitution rate quickly and accurately and can be used for the detection of the steel slag sand substitution rate.

Abstract Objective The optimal blood pressure (BP) targets for acute ischemic stroke are unclear. We aimed to assess the relationship between Mean BP and clinical outcomes during hospitalization. Materials and methods We included 649 patients with Acute ischemic stroke (AIS) from December 2020 to July 2021. BP was measured daily, and mean blood pressure was calculated. Clinical events recorded within 90 days of randomization were: recurrent ischemic stroke, symptomatic intracranial hemorrhage, and death. The modified Rankin Scale (mRS) was used to measure primary outcomes 3 months after AIS. Logistic multiple regression analysis was performed by statistical software R. Result There is a nonlinear U-shaped relationship between SBP and poor outcomes. This means higher SBP and lower SBP will increase the incidence of poor outcomes. The optimal mean SBP during hospitalization was 135-150 mmHg, and patients with SBP 150mmhg OR 2.04 [95% Cl, 1.02 ~ 4.08], p = 0.045 had a higher probability of poor outcomes. Conclusion Our study shows that the optimal SBP of patients with AIS during hospitalization was 135-150 mmHg. The findings suggest that the relationship between mean SBP and 3-month functional outcome after AIS was U-shaped. Both higher SBP and lower SBP lead to poor prognosis in AIS patients.

When using current methods to predict electricity theft behavior, there are problems of large sample data errors before training, high line loss rate, and low prediction effect. To this end, a power-stealing behavior prediction method based on multi-dimensional features and BP neural network is proposed. The method first extracts the abnormal power usage characteristics according to the abnormal features of the user’s power usage behavior. Then the genetic algorithm is used to optimize the BP network, and the optimized network is used to train the abnormal power consumption characteristics. Finally, a prediction model is established based on the training results to achieve the final prediction. The experimental results show that the training error test, line loss rate test and prediction effect test of the method before and after training verify the practicability and effectiveness of the method.

Ethnopharmacological relevanceDanshen preparations are widely used in the treatment of ischaemic cerebrovascular disease. However, the clinical efficacy of such preparations remains unclear. Consequently, Danshen preparations are used to a lesser extent in vascular cognitive impairment (VCI).Aim of the studyIn this study, we aimed to systematically assess the clinical efficacy and safety of Danshen preparations in VCI. To this end, we examined and performed a meta-analysis (MA) of the evidence available from randomised controlled trials (RCTs) of Danshen preparations conducted in patients with VCI.MethodsWe queried the following sources and collected all articles reporting on RCTs of Danshen preparations published prior to December 2021: PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chongqing VIP Database (CQVIP), and China Biology Medicine (CBM) disc databases. The assessment of treatments that were included in references were performed by RevMan 5.2 software based on guidelines from Cochrane Handbook for Systematic Reviews of Interventions.ResultsWe included a total of 12 RCTs that included data on clinical therapeutic effects. The evaluation criteria included the following: National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI), Mini-Mental State Assessment (MMSE), Montreal Cognitive Assessment (MOCA), Activities of Daily Living Scale (ADL), treatment effect index, and incidence of adverse reaction index. In the included studies, the observation groups included 656 cases and the control groups included 660 cases. The results of the MA were as follows: the mean difference (MD) value after combining the effect size for NIHSS was −2.91, with a 95% confidence interval (CI) of −4.22 to −1.59; the combined effect quantity hypothesis test revealed that Z = 4.33 (p

Abstract Background To investigate whether respectively radial extracoporeal shock wave therapy (rESWT) or a combination of rESWT, celecoxib and eperisone (rESWT + C + E) are superior in reducing pain in patients with chronic nonspecific low back pain (cnsLBP) compared to C + E alone (a standard treatment of this condition in China). Methods 140 patients with cnsLBP were randomly allocated to rESWT (n = 47), rESWT + C + E (n = 45) or C + E alone (n = 48) for four weeks between November 2017 and March 2019. Outcome was evaluated using the Pain Self-Efficacy Questionnaire (PSEQ), Numerical Rating Scale (NRS), Oswestry Low Back Pain Disability Questionnaire and Patient Health Questionnaire 9, collected at baseline as well as one week (W1), W2, W3, W4 and W12 after baseline. Results All scores showed a statistically significant improvement over time. The PSEQ and NRS scores showed a significant Time × Treatment effect. Patients treated with rESWT had significantly lower mean NRS values than patients treated with rESWT + C + E at W1 and W3, as well as than patients treated with C + E alone at W3 and W4. No severe adverse events were observed. Conclusions rESWT may not be inferior to respectively rESWT + C + E or C + E alone in reducing pain in patients with cnsLBP. Level of Evidence: Level I, prospective, randomized, active-controlled trial. Trial registration: Clinicaltrials.gov Identifier NCT03337607. Registered November 09, 2017, https://www.clinicaltrials.gov/ct2/show/NCT03337607 . Level of evidence Level I; prospective, randomized, controlled trial.

Many brittle materials, such as single-crystal materials, amorphous materials, and ceramics, are widely used in many industries such as the energy industry, aerospace industry, and biomedical industry. In recent years, there is an increasing demand for high-precision micro-machining of these brittle materials to produce precision functional parts. Traditional ultra-precision micro-machining can lead to workpiece cracking, low machined surface quality, and reduced tool life. To reduce and further solve these problems, a new micro-machining process is needed. As one of the nontraditional machining processes, rotary ultrasonic machining is an effective method to reduce the issues generated by traditional machining processes of brittle materials. Therefore, rotary ultrasonic micro-machining (RUμM) is investigated to conduct the surface micro-machining of brittle materials. Due to the small diameter cutting tool (

ObjectivesVaricella-zoster virus (VZV) can induce herpes zoster (HZ) and postherpetic neuralgia (PHN). Immune cells play an important role in regulating HZ and PHN pathogenesis, but the dynamic immune profiles and molecular mechanisms remain unclear. This study aimed to screen dynamic immune signatures during HZ progression and elucidate the mechanism of VZV-specific T cells in PHN.MethodsWe used cytometry by time-of-flight (CyTOF) to analyze peripheral blood mononuclear cells (PBMC) samples from 45 patients with HZ and eight age-sex-matched healthy controls, eight PHN samples and seven non-PHN samples. Correlations between the immune subsets and clinical pain-related scores were performed. Further, the characteristics of VZV-specific T cells between PHN and non-PHN patients were evaluated by VZV peptide pools stimulation. The expression level of cytokines, including granzyme B, interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was performed via cytometric bead array. Finally, we analyzed the alteration of Ca2+ signals in dorsal root ganglion (DRG)-derived cells after TNF-α stimulation.ResultsWe investigated the dynamic characteristics of the immune landscape of peripheral blood samples of patients with HZ and PHN, and depicted two major dynamic signatures in NK, CD4+ and CD8+ T subsets in patients with HZ, which closely correlated with clinical pain-related scores. The frequency of PD-1+CD4+ T cells, VZV-specific PD-1+CD4+ T cells, and the amount of TNF-α produced by VZV-specific T cells were higher in patients with PHN than without PHN. Furthermore, we showed that TNF-α could induce calcium influx in DRG-derived cells in a dose-dependent manner.ConclusionsOur results profiled the dynamic signatures of immune cells in patients with HZ and highlighted the important role of VZV-specific T cells in the pathogenesis of PHN.

Wearable surface electromyography (sEMG) signal-acquisition devices have considerable potential for medical applications. Signals obtained from sEMG armbands can be used to identify a person’s intentions using machine learning. However, the performance and recognition capabilities of commercially available sEMG armbands are generally limited. This paper presents the design of a wireless high-performance sEMG armband (hereinafter referred to as the α Armband), which has 16 channels and a 16-bit analog-to-digital converter and can reach 2000 samples per second per channel (adjustable) with a bandwidth of 0.1–20 kHz (adjustable). The α Armband can configure parameters and interact with sEMG data through low-power Bluetooth. We collected sEMG data from the forearms of 30 subjects using the α Armband and extracted three different image samples from the time–frequency domain for training and testing convolutional neural networks. The average recognition accuracy for 10 hand gestures was as high as 98.6%, indicating that the α Armband is highly practical and robust, with excellent development potential.

A novel class of polymers and oligomers of chiral folding chirality has been designed and synthesized, showing structurally compacted triple-column/multiple-layer frameworks. Both uniformed and differentiated aromatic chromophoric units were successfully constructed between naphthyl piers of this framework. Screening monomers, catalysts, and catalytic systems led to the success of asymmetric catalytic Suzuki-Miyaura polycouplings. Enantio- and diastereochemistry were unambiguously determined by X-ray structural analysis and concurrently by comparison with a similar asymmetric induction by the same catalyst in the asymmetric synthesis of a chiral three-layered product. The resulting chiral polymers exhibit intense fluorescence activity in a solid form and solution under specific wavelength irradiation.

Abstract Background Color directly affects fruit quality and consumer preference. In fig syconia, the female flower tissue is contained in a receptacle. Anthocyanin pigmentation of this tissue and the peel differs temporally and spatially. A transcriptome study was carried out to elucidate key genes and transcription factors regulating differences in fig coloring. Results Anthocyanins in the female flower tissue were identified mainly as pelargonidin-3-glucoside and cyanidin-3-rutinoside; in the peel, the major anthocyanins were cyanidin 3-O-glucoside and cyanidin-3-rutinoside. Anthocyanin content was significantly higher in the female flower tissue vs. peel before fig ripening, whereas at ripening, the anthocyanin content in the peel was 5.39 times higher than that in the female flower tissue. Light-deprivation treatment strongly inhibited peel, but not female flower tissue, anthocyanin pigmentation. RNA-Seq revealed 522 differentially expressed genes (recruited with criteria log2 ≥ 2 and P

BackgroundAs the incidence of nonalcoholic fatty liver disease (NAFLD) increases globally, nonalcoholic steatohepatitis (NASH) has become the second common cause of liver transplantation for liver diseases. Recent evidence shows that Roux-en-Y gastric bypass (RYGB) surgery obviously alleviates NASH. However, the mechanism underlying RYGB induced NASH improvement is still elusive.MethodsWe obtained datasets, including hepatic gene expression data and histologic NASH status, at baseline and 1 year after RYGB surgery. Differentially expressed genes (DEGs) were identified comparing gene expression before and after RYGB surgery in each dataset. Common DEGs were obtained between both datasets and further subjected to functional and pathway enrichment analysis. Protein–protein interaction (PPI) network was constructed, and key modules and hub genes were also identified.ResultsIn the present study, GSE106737 and GSE83452 datasets were included. One hundred thirty common DEGs (29 up-regulated and 101 down-regulated) were identified between GSE106737 and GSE83452 datasets. KEGG analysis showed that mineral absorption, IL-17 signaling pathway, osteoclast differentiation, and TNF signaling pathway were significantly enriched. Based on the PPI network, IGF1, JUN, FOS, LDLR, TYROBP, DUSP1, CXCR4, ATF3, CXCL2, EGR1, SAA1, CTSS, and PPARA were identified as hub genes, and three functional modules were also extracted.ConclusionThis study identifies the global gene expression change in the liver of NASH patients before and after RYGB surgery in a bioinformatic method. Our findings will contribute to the understanding of molecular biological changes underlying NASH improvement after RYGB surgery.

In this study, the influence of the blending degree between virgin and aged binder on the pavement performance of hot-mix recycled asphalt mixture (HMRAM) with high RAP content is analyzed. The aggregate gradation of AC-16 was selected. The RAP contents were 30, 40, and 50%. HMRAMs with different degrees of blending (DOBs) were prepared by changing the mixing temperature (150, 165, and 180°C) without the occurrence of excessive aging for asphalt binders. An improved Hirsch dynamic modulus prediction model was then used to quantitatively characterize the DOB of HMRAM. Finally, the high-temperature, low-temperature, moisture stability, and fatigue resistance performance of HMRAM were tested and the effect of the DOB between the virgin and aged asphalt binder on the pavement performance was analyzed. The results showed that the DOB between the virgin and aged asphalt binder cannot reach 100% at the three mixing temperatures for HMRAM with 30, 40, and 50% RAP contents, which is inconsistent with the assumption of complete blending in China’s specification. The dynamic stability of the mixture gradually decreases with the increased DOB for HMRAM with a high RAP content, while the moisture stability, low-temperature, and fatigue resistance performance are continuously improved. This means that with the increase in DOB in the stage of open to traffic, meeting high-temperature performance criteria at the design stage may become unsatisfactory for HMRAM. The moisture stability, low-temperature performance, and fatigue resistance performances of HMRAM measured at the design stage were reasonable and conservative. The change in DOB significantly affects the content and properties of total free binder in HMRAM, affecting pavement performance. The content and physical properties of the RAP aggregate also have a significant impact on pavement performance.

Titanium and its alloys exhibit superior properties of high corrosion resistance, an excellent strength to weight ratio and outstanding stiffness among other things. However, their relatively low hardness and wear resistance limit their service life in high-performance applications of structure parts, gears and bearings, for example. The fabrication of a ceramic reinforced titanium matrix composite (TMC) coating could be one of the solutions to enhance the microhardness and wear resistance. Titanium carbide (TiC) is a preferable candidate due to the advantages of self-lubrication, low cost and a similar density and thermal expansion coefficient with titanium. The fabrication of TiC-TMC coatings onto titanium using a laser directed energy deposition (LDED) process has been conducted. The problems of TiC aggregation, low bonding quality and the generation of fabrication defects still exist. Considering ultrasonic vibration could generate acoustic steaming and transient cavitation actions in melted materials, which could homogenize the distribution of reinforcement materials and promote the dissolution of TiC into liquid titanium. In this study, for the first time, we investigate the ultrasonic vibration-assisted LDED of TiC-TMC coatings. The effects of ultrasonic vibration and reinforcement content on the phase compositions, reinforcement aggregation, bonding quality, fabrication defects and mechanical properties (including microhardness and wear resistance) of LDED deposited TiC-TMC coatings have been investigated. With the assistance of ultrasonic vibration, the aggregation of TiC was reduced, the porosity was decreased, the defects in the bonding interface were reduced and the mechanical properties including microhardness and wear resistance were increased. However, the excessive TiC content could significantly increase the TiC aggregation and manufacturing defects, resulting in the reduction of the mechanical properties.

The characterization of residual stress in complicated components is a tough issue. The method of Rayleigh surface wave-based V(z) curve is adopted in this work to evaluate the distribution of residual stresses in aeroengine blades. First, the velocity of Rayleigh surface wave in aeroengine blade was measured by the V(z) curve technique, which can be used to calculate the local residual stress because the change of velocity is thought to be correlated with the contribution from residual stress. Two kinds of plastic-deformed Ti-6Al-4V samples were fabricated by ball-gun shooting to artificially induce distribution of residual stress and then measured by the proposed method. The results indicate that the distribution of the residual stress in both of the samples displays a predictable symmetry. The error of the measured stress is much less than 10% of the yielding stress in Ti-6Al-4V (i.e., about 800 MPa). Finally, the measured residual stresses were verified by X-ray diffraction method, whose results correlate reasonably well with each other. The proposed V(z) curve method and its experimental set-up appear to be a potential in characterizing residual stress at a point-like region, such as in complicated components.

Objective: To determine the efficacy and safety of the Yinmei Kuijie decoction combined with 5-aminosalicylic acid (5-ASA) in treating mildly to moderately active ulcerative colitis (UC) under real-world conditions. Methods: This multicenter, prospective, non-randomized, observational study will be conducted in real-world settings. A total of 204 eligible patients will be consecutively enrolled in the study. Patients in the combination treatment group will receive Yinmei Kuijie decoction in combination with 5-ASA, whereas those in the control group will be treated with 5-ASA alone. The primary endpoint will be a clinical response at week 12, defined as a ≥3 point and ≥30% reduction from baseline in the Mayo total score with ≥1 reduction in rectal bleeding or rectal bleeding score = 0 or 1. Secondary efficacy endpoints at week 12 will include health-related quality of life, mucosal healing, and inflammation indicators. Conclusion: The results of this study may provide evidence of the efficacy and safety of Yinmei Kuijie decoction combined with 5-ASA in treating patients with mildly to moderately active UC under real-world principles. The results will provide a basis for further confirmatory studies on the efficacy of Yinmei Kuijie decoction.

Ferroptosis is a regulated cell death implicated in various diseases, including stroke. We have explored the ferroptosis-related key genes and the underlying association with acute ischemic stroke. Differentially expressed mRNAs and miRNAs in ischemic stroke were screened based on the GSE16561 and GSE95204 datasets, respectively. Ferroptosis-related genes were downloaded from the FerrDb and GeneCards databases. Eleven ferroptosis-related differentially expressed genes were identified. Based on weighted gene co-expression network analysis, three key modules were identified as being closely associated with stroke. Furthermore, two hub genes, lysosomal associated membrane protein 2 and signal transducer and activator of transcription 3, were selected by a support vector machine-based recursive feature elimination algorithm based on machine learning and showed excellent diagnostic accuracy in stroke, with an area under the curve value of 0.939 and 0.875 in the GSE16561 cohort, respectively. Furthermore, the Comparative Toxicogenomic Database predicted 24 potential therapeutic drugs targeting the two hub genes. To sum up, the identification of hub genes associated with ferroptosis and acute ischemic stroke based on bioinformatics analysis may contribute to the exploration of promising diagnostic and therapeutic biomarkers and provide clues for the prediction of therapeutic candidates. [ABSTRACT FROM AUTHOR]

Abstract Background Metastasis is the major cause of colorectal cancer (CRC) mortality. Emerging evidence suggests that long noncoding RNAs (lncRNAs) drive cancer metastasis and that their regulatory pathways could be targeted for preventing metastasis. However, the underlying mechanisms of lncRNAs in CRC metastasis remain poorly understood. Methods Microarray analysis was used to screen for differentially expressed lncRNAs. Transwell assays, fibronectin cell adhesion assays, and mouse metastasis models were utilized to evaluate the metastatic capacities of CRC in vitro and in vivo. Chromatin isolation by RNA purification, chromatin immunoprecipitation and chromosome conformation capture were applied to investigate the underlying mechanism involved. qRT‒PCR and transmission electron microscopy were performed to confirm macrophage polarization and the presence of cancer-derived exosomes. Results The lncRNA RP11-417E7.1 was screened and identified as a novel metastasis-associated lncRNA that was correlated with a poor prognosis. RP11-417E7.1 enhances the metastatic capacity of CRC cells in vivo and in vitro. Mechanistically, RP11-417E7.1 binding with High mobility group A1 (HMGA1) promotes neighboring thrombospondin 2 (THBS2) transcription via chromatin loop formation between its promoter and enhancer, which activates the Wnt/β-catenin signaling pathway and facilitates CRC metastasis. Furthermore, exosomes derived from CRC cells transport THBS2 into macrophages, thereby inducing the M2 polarization of macrophages to sustain the prometastatic microenvironment. Notably, netropsin, a DNA-binding drug, suppresses chromatin loop formation mediated by RP11-417E7.1 at the THBS2 locus and significantly inhibits CRC metastasis in vitro and in vivo. Conclusions This study revealed the novel prometastatic function and mechanism of the lncRNA RP11-417E7.1, which provides a potential prognostic indicator and therapeutic target in CRC.

Within the Tan-Lu Fault Zone, the largest active tectonic belt in eastern China, the Anqiu-Juxian Fault exhibits the most recent activity period, evident surface traces, and highest seismic hazard, making it a Holocene active fault. This study utilized the vertical component continuous data observed by 100 short-period temporary stations from August 1–21, 2023, and extracted 1,944 Rayleigh wave group velocity dispersion curves within the period of 0.2–4 s. Using the direct surface wave tomography method, we calculated a high-resolution 3-D shear-wave velocity structure at depths of 0.2–1.25 km within the study area. Our results are summarized as follows: 1) The development of faults F1, F2, and F5 in the Tan-Lu Fault Zone highly correlated with the shear-wave velocity anomalies at depths >0.8 km. Specifically, fault F5 comprised two boundary faults, F5-1 and F5-2, which together controlled a Cenozoic depression covered by a thick, low-velocity sediment layer. 2) The complex velocity structure characteristics in the Suqian area revealed that the influence of faults on the sedimentary layers in the Suqian area was not expressed as an overall uplift or subsidence of the block but rather as differential subsidence. 3) Near Sankeshu, the F5 fault formed a small pull-apart basin. The latest activity in this pull-apart basin has shifted to the fault in the center of the basin, indicating that the pull-apart basin has entered the extinction stage.