Red Fluorescent Molecule with Aggregation-Induced Emission Based on Dehydroabietic Acid Diarylamine for Bioimaging.

In this paper, molecules with AIE red light properties were designed by coupling dehydroabietic acid diarylamine and 2,3-diphenylfumaronitrile, which were designated 2DTPA-CN and 2TPA-CN. The emission wavelengths were 683 nm and 701 nm, respectively. The 2DTPA-CN and 2TPA-CN showed typical AIE characteristics with large Stokes shifts of 7.4 × 104 cm-1 and 6.7 × 104 cm-1, respectively. The obvious solvatochromism and electron cloud distributions of HOMO/LUMO in the ground and excited states both reveal the intramolecular charge transfer (ICT) effect. The 2DTPA-CN, boasting exceptional biocompatibility, was successfully prepared into nanoparticles (NPs), which were applied to tumor cell imaging, showing good bioimaging effects both in vitro imaging in live cells and in vivo imaging in live mice. The results demonstrated that it possesses significant potential as an effective bioimaging reagent for the detection of tumor cells. Furthermore, the incorporation of 2,3-diphenylfumaronitrile moieties to dehydroabietic acid diarylamine emerged as a proficient approach to broaden the emission wavelengths of rosin-based fluorescent materials.

Multi-omics analysis reveals the unique landscape of DLD in the breast cancer tumor microenvironment and its implications for immune-related prognosis.

Background: Cuproptosis, i.e., copper-induced programmed cell death, has potential implications in cancer therapy. However, the impact of the cuproptosis-related gene (CRG) dihydrolipoyl dehydrogenase (DLD) on breast cancer (BC) prognosis remains underexplored. Methods: We employed real-time quantitative PCR and multiplexed immunostaining techniques to quantify DLD expression in both BC and the adjacent non-cancerous tissues. Immunofluorescence analysis was employed to assess the influence of DLD on immune cells and immunological checkpoints in the BC microenvironment. DLD knockdown experiments were conducted in BC cell lines MDA-MB-468 and SK-BR-3, with knockdown efficiency validated via western blot. Subsequently, we performed the cell counting kit-8 (CCK-8) assay, clone formation assay, Transwell migration assay, and invasion assay. To construct a prognostic model, we employed a Lasso-Cox regression analysis of immune-related genes associated with DLD. Additionally, we established a competing endogenous RNA network based on CRGs to evaluate potential regulatory pathways. Results: Compared to the adjacent tissues, BC tissues exhibited markedly elevated DLD expression levels. In vitro experiments demonstrated that DLD knockdown effectively inhibited BC cell migration, invasion, and proliferation. DLD exhibited positive correlations with CD68+ macrophages and PD-L1 in the tumor, as well as with macrophages and CD4+ T cells in the stroma. Tumor regions with high DLD expression were enriched in PD-L1 and macrophages, while stromal regions with high DLD expression contained CD4+ T cells and macrophages. The AUC values for 1-, 3-, and 5-year overall survival in TCGA-BRCA training set were 0.67, 0.66, and 0.66, respectively. A nomogram with a C-index of 0.715 indicated that risk score, tumor stage, and age could serve as independent prognostic factors for BC. Conclusion: Our findings underscore the significant predictive significance of DLD in BC and its influence on the tumor microenvironment. DLD represents a promising diagnostic and prognostic marker for BC, offering novel avenues for the identification of therapeutic targets and the enhancement of immunotherapy in BC.

A noninvasive method for predicting clinically significant prostate cancer using magnetic resonance imaging combined with PRKY promoter methylation level: a machine learning study.

BACKGROUND: Traditional process for clinically significant prostate cancer (csPCA) diagnosis relies on invasive biopsy and may bring pain and complications. Radiomic features of magnetic resonance imaging MRI and methylation of the PRKY promoter were found to be associated with prostate cancer. METHODS: Fifty-four Patients who underwent prostate biopsy or photoselective vaporization of the prostate (PVP) from 2022 to 2023 were selected for this study, and their clinical data, blood samples and MRI images were obtained before the operation. Methylation level of two PRKY promoter sites, cg05618150 and cg05163709, were tested through bisulfite sequencing PCR (BSP). The PI-RADS score of each patient was estimated and the region of interest (ROI) was delineated by 2 experienced radiologists. After being extracted by a plug-in of 3D-slicer, radiomic features were selected through LASSCO regression and t-test. Selected radiomic features, methylation levels and clinical data were used for model construction through the random forest (RF) algorithm, and the predictive efficiency was analyzed by the area under the receiver operation characteristic (ROC) curve (AUC). RESULTS: Methylation level of the site, cg05618150, was observed to be associated with prostate cancer, for which the AUC was 0.74. The AUC of T2WI in csPCA prediction was 0.84, which was higher than that of the apparent diffusion coefficient ADC (AUC = 0.81). The model combined with T2WI and clinical data reached an AUC of 0.94. The AUC of the T2WI-clinic-methylation-combined model was 0.97, which was greater than that of the model combined with the PI-RADS score, clinical data and PRKY promoter methylation levels (AUC = 0.86). CONCLUSIONS: The model combining with radiomic features, clinical data and PRKY promoter methylation levels based on machine learning had high predictive efficiency in csPCA diagnosis.

Quantitative ultrasound parameters from scattering and propagation may reduce the biopsy rate for breast tumor.

Breast cancer has become the most common cancer worldwide, and early screening improves the patient's survival rate significantly. Although pathology with needle-based biopsy is the gold standard for breast cancer diagnosis, it is invasive, painful, and expensive. Meanwhile it makes patients suffer from misplacement of the needle, resulting in misdiagnosis and further assessment. Ultrasound imaging is non-invasive and real-time, however, benign and malignant tumors are hard to differentiate in grayscale B-mode images. We hypothesis that breast tumors exhibit characteristic properties, which generates distinctive spectral patterns not only in scattering, but also during propagation. In this paper, we propose a breast tumor classification method that evaluates the spectral pattern of the tissues both inside the tumor and beneath it. First, quantitative ultrasonic parameters of these spectral patterns were calculated as the representation of the corresponding tissues. Second, parameters were classified by the K-Nearest Neighbor machine learning model. This method was verified with an open access dataset as a reference, and applied to our own dataset to evaluate the potential for tumors assessment. With both datasets, the proposed method demonstrates accurate classification of the tumors, which potentially makes it unnecessary for certain patients to take the biopsy, reducing the rate of the painful and expensive procedure.

Incidence of Cement Leakage and Potential Risk Factors in Surgery for Spinal Metastasis: A Systematic Review and Meta-Analysis.

OBJECTIVES: The current meta-analysis was performed to gather available evidence regarding the incidence and risk factors of cement leakage (CL) in patients undergoing surgical procedures for spinal metastasis. METHODS: Two authors independently searched the PubMed, Embase, and CENTRAL databases. Clinical studies reporting the incidence or risk factors of CL were included for analysis. The primary outcome analyzed was the incidence of various types of CL. Random-effects or fixed-effects single-proportion meta-analyses were conducted to pool the available evidence, based on the heterogeneity test. Subgroup analyses were conducted based on surgical procedures (percutaneous vertebroplasty, percutaneous kyphoplasty, and others). Risk factors of CL were synthesized narratively to identify the most commonly accepted factors. RESULTS: A total of 26 studies, involving 2551 patients, were included. The number of operated spine segments was reported in 23 studies, accounting for 4101 vertebrae. The pooled incidences of general, intradiscal, paravertebral, spinal canal, and intravascular CLs were 0.18 (95% confidence interval [CI], 0.11-0.28), 0.14 (95% CI, 0.08-0.21), 0.13 (95% CI, 0.06-0.21), 0.11 (95% CI, 0.05-0.19), and 0.12 (95% CI, 0.08-0.17), respectively. Subgroup analyses revealed significantly different incidences of general CL (0.37 vs. 0.06 vs. 0.09, P < 0.01), intradiscal CL (0.22 vs. 0.06 vs. 0.12, P < 0.01), paravertebral CL (0.25 vs. 0.03 vs. 0.06, P < 0.01), and vascular CL (0.14 vs. 0.03 vs. 0.15, P < 0.01) among the three groups. Posterior wall disruption, pathologic fracture, and the number of treated vertebral levels were the most commonly identified independent risk factors for general CL. Posterior wall disruption was determined as a common significant risk factor for spinal canal CL. CONCLUSIONS: This review provides insights into the incidence and risk factors associated with CL in surgical procedures for spinal metastasis. Understanding these risk factors can contribute to the development of tailored strategies aimed at minimizing CL occurrence and optimizing surgical outcomes for patients undergoing spinal metastatic surgery.

Voriconazole plus flucytosine is not superior to amphotericin B deoxycholate plus flucytosine as an induction regimen for cryptococcal meningitis treatment.

BACKGROUND: The efficacy and side effects of voriconazole plus 5-flucytosine (Vori + 5-FC) versus amphotericin B deoxycholate plus 5-flucytosine (AmBd + 5-FC) as an induction treatment for cryptococcal meningitis are unknown. METHODS: Forty-seven patients treated with Vori + 5-FC and 92 patients treated with AmBd + 5-FC were included in the current study after propensity score matching (PSM) at a ratio of 1:2. Two-week laboratory test results and 90-day mortality were compared between the two groups. RESULTS: After 2 weeks of induction treatment, the CSF Cryptococcus sterile culture rate was 57.1% in the Vori + 5-FC group and 76.5% in the AmBd + 5-FC group (p = .026). No difference was found in the normalization of CSF indicators (glucose, total protein, intracranial pressure and India ink sterile rate) between the two groups. Both the Vori + 5FC regimen and AmBd + 5-FC regimen obviously decreased haemoglobin concentrations, platelet counts and serum potassium levels (all p ≤ .010). Notably, the Vori + 5FC regimen did not influence serum creatinine levels (p = .263), while AmBd + 5FC increased serum creatinine levels (p = .019) after 2-week induction treatment. The Vori + 5-FC group and AmBd + 5-FC group had similar 90-day cumulative survival rates (89.9% vs. 87.8%, p = .926). CONCLUSION: The Vori + 5-FC regimen was associated with low 2-week CSF sterile culture and was not superior to AmBd + 5-FC as induction therapy in terms of the 90-day cumulative survival rate of CM patients.

6-Gingerol regulates triglyceride and cholesterol biosynthesis to improve hepatic steatosis in MAFLD by activating the AMPK-SREBPs signaling pathway.

Excessive synthesis of triglycerides and cholesterol accelerates the progression of hepatic steatosis in metabolic-associated fatty liver disease (MAFLD). However, the precise mechanism by which 6-gingerol mitigates hepatic steatosis in MAFLD model mice has yet to be fully understood. The present study observed that 6-gingerol administration exhibited significant protective effects against obesity, insulin resistance, and hepatic steatosis in mice subjected to a high-fat diet (HFD), and mitigated lipid accumulation in HepG2 cells treated with palmitate (PA). Following the hepatic lipidomic analysis, we confirmed that the AMPK-SREBPs signaling pathway as the underlying molecular mechanism by which 6-gingerol inhibited triglyceride and cholesterol biosynthesis, both in vivo and in vitro, through Western blot and immunofluorescence assay. Additionally, the application of an AMPK agonist/inhibitor further validated that 6-gingerol promoted AMPK activation by increasing the phosphorylation level of AMPK in vitro. Notably, the inhibitory effect of 6-gingerol on cholesterol biosynthesis, rather than triglyceride biosynthesis, was significantly diminished after silencing SREBP2 using a lentiviral plasmid shRNA in HepG2 cells. Our study demonstrates that 6-gingerol mitigates hepatic triglyceride and cholesterol biosynthesis to alleviate hepatic steatosis by activating the AMPK-SREBPs signaling pathway, indicating that 6-gingerol may be a potential candidate in the therapy of MAFLD.

Aspartate Aminotransferase/Platelet Ratio Index Upon Admission Predicts 24-Week Mortality in Patients With HIV-Associated Talaromyces marneffei.

Background: A high aspartate aminotransferase/platelet ratio index (APRI) predicts mortality in patients with severe infection. This study aims to assess the potential of APRI as a predictor for mortality in patients with HIV-associated Talaromyces marneffei (HTM). Methods: Associations between APRI and CD4 count, white blood cell count, C-reactive protein (CRP) level, procalcitonin (PCT) level, and cytokines were assessed in 119 patients. Univariate and multivariate Cox regression models were used to predict APRI on 24-week mortality. Results: APRI was positively associated with CRP (r = 0.190, P = .039), PCT (r = 0.220, P = .018), interleukin 6 (r = 0.723, P < .001), interleukin 10 (r = 0.416, P = .006), and tumor necrosis factor α (r = 0.575, P < .001) and negatively associated with CD4 count (r = -0.234, P = .011). In total, 20.2% (24/119) of patients died within the 24-week follow-up. The 24-week survival rate was 88.0% for patients with APRI <5.6% and 61.1% for those with APRI ≥5.6 (log-rank P < .001). After adjustment for sex, age, body mass index, and CD4 count, as well as serum levels of hemoglobin, APRI ≥5.6 (adjusted hazard ratio [95% CI]; 3.0 [1.2-7.1], P = .015), PCT ≥1.7 ng/mL (3.7 [1.5-9.6], P = .006), and non-amphotericin B deoxycholate treatment (2.8 [1.2-6.6], P = .018) were independent risk factors for 24-week mortality. Conclusions: For patients with HTM, APRI is associated with severity and is an independent risk factor for 24-week mortality.

Neo-intline: integrated pipeline enables neoantigen design through the in-silico presentation of T-cell epitope.

Neoantigen vaccines are one of the most effective immunotherapies for personalized tumour treatment. The current immunogen design of neoantigen vaccines is usually based on whole-genome sequencing (WGS) and bioinformatics prediction that focuses on the prediction of binding affinity between peptide and MHC molecules, ignoring other peptide-presenting related steps. This may result in a gap between high prediction accuracy and relatively low clinical effectiveness. In this study, we designed an integrated in-silico pipeline, Neo-intline, which started from the SNPs and indels of the tumour samples to simulate the presentation process of peptides in-vivo through an integrated calculation model. Validation on the benchmark dataset of TESLA and clinically validated neoantigens illustrated that neo-intline could outperform current state-of-the-art tools on both sample level and melanoma level. Furthermore, by taking the mouse melanoma model as an example, we verified the effectiveness of 20 neoantigens, including 10 MHC-I and 10 MHC-II peptides. The in-vitro and in-vivo experiments showed that both peptides predicted by Neo-intline could recruit corresponding CD4+ T cells and CD8+ T cells to induce a T-cell-mediated cellular immune response. Moreover, although the therapeutic effect of neoantigen vaccines alone is not sufficient, combinations with other specific therapies, such as broad-spectrum immune-enhanced adjuvants of granulocyte-macrophage colony-stimulating factor (GM-CSF) and polyinosinic-polycytidylic acid (poly(I:C)), or immune checkpoint inhibitors, such as PD-1/PD-L1 antibodies, can illustrate significant anticancer effects on melanoma. Neo-intline can be used as a benchmark process for the design and screening of immunogenic targets for neoantigen vaccines.

[Effects of Methionine Restriction on Proliferation, Cell Cycle, and Apoptosis of Human Acute Leukemia Cells].

OBJECTIVE: To investigate the effects of methionine restriction on proliferation, cell cycle and apoptosis of human acute leukemia cells. METHODS: Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of methionine restriction on HL-60 and Jurkat cells proliferation. The effect of methionine restriction on cell cycle of HL-60 and Jurkat cells was examined by PI staining. Annexin V-FITC / PI double staining was applied to detect apoptosis of HL-60 and Jurkat cells following methionine restriction. The expression of cell cycle-related proteins cyclin B1, CDC2 and apoptosis-related protein Bcl-2 was evaluated by Western blot assay. RESULTS: Methionine restriction significantly inhibited the proliferation of HL-60 and Jurkat cells in a time-dependent manner (HL-60: r =0.7773, Jurkat: r =0.8725), arrested the cells at G2/M phase (P < 0.001), and significantly induced apoptosis of HL-60 and Jurkat cells (HL-60: P < 0.001; Jurkat: P < 0.05). Furthermore, Western blot analysis demonstrated that methionine restriction significantly reduced the proteins expression of Cyclin B1 (P < 0.05), CDC2 (P < 0.01) and Bcl-2 (P < 0.001) in HL-60 and Jurkat cells. CONCLUSION: Acute leukemia cells HL-60 and Jurkat exhibit methionine dependence. Methionine restriction can significantly inhibit the proliferation, promote cell cycle arrest and induce apoptosis of HL-60 and Jurkat cells, which suggests that methionine restriction may be a potential therapeutic strategy for acute leukemia.

Dual-Recognition Triggered Proximity Ligation Combined with a Rolling Circle Amplification Strategy for Analysis of Exosomal Protein-Specific Glycosylation.

Exosomal surface glycan reveals the biological function and molecular information on the protein, especially in indicating the pathogenesis of certain diseases through monitoring of specific protein glycosylation accurately. However, in situ and nondestructive measurement techniques for certain Exosomal glycoproteins are still lacking. In this work, combined with on-chip purification, we designed a proximity ligation assay-induced rolling circle amplification (RCA) strategy for highly sensitive identification of Exosomal protein-specific glycosylation based on a couple of proximity probes to target Exosomal protein and the protein-specific glycosylation site. Benefiting from efficient separation, scalable dual-recognition, and proximity-triggered RCA amplification, the proposed strategy could convert different protein-specific glycan levels to prominent changes in absorbance signals, resulting in accurate quantification of specific glycosylated Exosomal protein. When detecting the glycosylated PD-L1 on MDA-MB-231 exosomes and glycosylated PTK7 on HepG2 exosomes, the detection limits were calculated to be as low as 1.04 × 104 and 2.759 × 103 particles/mL, respectively. In addition, we further expand the dual-recognition site to investigate the potential correlation of Exosomal glycosylation with polarization of THP-1 cells toward the tumor-suppressive M1 phenotype. Overall, this strategy provides a universal tool for multiple analyses of diverse protein-specific glycosylated exosomes, exhibiting enormous potential to explore exosome function and search for new early diagnosis markers.

NUP62CL as an Immunological and Prognostic Biomarker of Oral Squamous Cell Carcinoma.

Background: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a high mortality rate and poor prognosis. The exploration and understanding of biomarkers will help to further improve the diagnosis and treatment of OSCC. Methods: Tumor tissue samples from 319 OSCC patients were retrospectively collected, along with their clinical information. In combination with bioinformatics tools and multiplex immunohistochemistry (mIHC) analyses, we evaluated NUP62CL protein expression and its relationship to tumor-infiltrating immune cells (TIICs) and immune checkpoints in the tumor microenvironment (TME), as well as its association with clinical features and prognosis of OSCC. Results: We identified high-NUP62CL expression in OSCC tissues, and high-NUP62CL protein expression was associated with large tumor size, advanced clinical stage and poor prognosis. In addition, NUP62CL protein expression was positively associated with the abundance of CD3+CD4+ T cells (P<0.01), CD3+CD8+ T cells (P<0.01), CD56+ NK cells (P<0.05), CD68+CD86+ macrophages (P<0.01) and CD68+CD163+ macrophages (P<0.01), as well as the immune checkpoints, including PD-1 (P<0.001), PD-L1 (P<0.001), and CTLA-4 (P<0.001) protein expression. Conclusion: In conclusion, NUP62CL could be an effective prognostic and immunological biomarker for OSCC patients.

Machine learning- and WGCNA-mediated double analysis based on genes associated with disulfidptosis, cuproptosis and ferroptosis for the construction and validation of the prognostic model for breast cancer.

BACKGROUND: Disulfidptosis, a recently discovered cellular death mechanism, has not been extensively studied in relation to breast cancer (BC). Specifically, no previous research has integrated disulfidptosis-related genes (DRGs), cuproptosis-related genes (CRGs), and ferroptosis-related genes (FRGs) to construct a prognostic signature for BC. METHODS: DRGs, CRGs and FRGs with prognostic potential were identified through Cox regression analysis. A predictive model was constructed by intersecting the core genes obtained from unsupervised cluster analysis and weighted correlation network analysis (WGCNA). Differences in chemotherapy drug sensitivity, immune checkpoint levels were analyzed according to different risk score groups. The expression of the core disulfidptosis gene, SLC7A11, was analyzed using immunofluorescence. RESULTS: Single-cell RNA sequencing analysis revealed differential expression of DRGs in the BC tumor microenvironment. We developed a prognostic model, consisting of six genes, based on machine learning which included unsupervised cluster analysis and Lasso-Cox analysis. An internal training set and a validation set, both derived from the Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database, GSE20685 and GSE42568 as external validation sets all verified the model's validity. The low-risk group exhibited increased sensitivity to paclitaxel. Additionally, the high-risk group demonstrated significantly higher expression of tumor mutation burden and microsatellite instability compared to the low-risk group. A nomogram confirmed that the risk score can be an independent risk factor for BC. Notably, our findings highlighted the impact of SLC7A11 on the BC tumor microenvironment. Immunofluorescence analysis revealed significantly higher expression of SLC7A11 in BC tissues compared to paracancerous tissues. CONCLUSION: Multiplex analysis based on DRGs, CRGs and FRGs correlated strongly with BC, providing new insights for developing clinical prognostic tools and designing immunotherapy regimens for BC patients.

A Crosstalk Between Castration-Resistant Prostate Cancer Cells, M2 Macrophages, and NK Cells: Role of the ATM-PI3K/AKT-PD-L1 Pathway.

Castration-resistant prostate cancer (CRPC) in males is associated with a poor prognosis and a higher risk of treatment-related adverse effects, with high mortality among cancers globally. It is thus imperative to explore novel potential molecules with dual therapeutic and biomarker functions. Based on the recent research findings, the expression levels of ataxia telangiectasia mutant kinase (ATM) in prostate cancer (PC) tissues collected from CRPC patients were higher than hormone-dependent PC patients. Using CRPC cell lines (C4-2 and CWR22Rv1), the transwell chamber experiments revealed ATM promoted macrophage recruitment in CRPC cells in vitro via C-X-C motif chemokine ligand 12 (CXCL12). Further in vitro investigations demonstrated that polarized macrophages prevented NK cell recruitment and reduced the immunocidal activity of NK cells against CRPC cell lines. Moreover, ATM boosted programmed death receptor ligand 1 (PD-L1) expression while inhibiting NK group 2D (NKG2D) ligand expression in selected cell lines via PI3K/AKT signaling pathway. The in vivo investigations revealed ATM induced proliferation of CRPC and macrophage recruitment, while the NK cell recruitment was found to suppress ATM expression and CRPC proliferation. In conclusion, it could be demonstrated that inhibiting ATM increased the susceptibility of CRPC to NK cell inhibitors by dampening the CXCL12 and PI3K/AKT-PD-L1 pathways, thereby offering a novel and individualized treatment protocol for treating CRPC.

Prevalence of sufficient physical activity among general adult population and sub-populations with chronic conditions or disability in the USA.

BACKGROUND: Recently, the World Health Organization (WHO) released an updated global guideline on physical activity and sedentary behavior, including recommendations for sub-populations living with chronic conditions or disabilities. We aimed to examine the prevalence of meeting the WHO recommendations among these sub-populations in the USA. METHODS: We conducted a cross-sectional study using data from the 2017 to 2018 cycle of the National Health and Nutrition Examination Survey (NHANES). RESULTS: We revealed variations in physical activity levels among individuals with chronic conditions and disability. US adults with diabetes, hypertension or disability had a lower prevalence of recommended physical activity levels than the general population. In addition, certain demographic groups such as being female, older and having lower socioeconomic status were associated with a lower likelihood of meeting the WHO recommendations on physical activity. CONCLUSIONS: Our findings underscore the importance of promoting physical activity levels among US adults, especially those with older age, low socioeconomic status, hypertension and disability.

Numerical Modeling of Transient Flow Characteristics on the Top Surface of a Steel Slab Continuous Casting Strand Using a Large Eddy Simulation Combined with Volume of Fluid Model.

In the current study, the transient flow characteristics on the top surface of a steel slab continuous casting strand were numerically investigated using a large eddy simulation combined with volume of fluid (LES + VOF) model. The validation of numerical simulation was verified via nail board measurement in the industrial continuous casting mold. The effects of casting speed on the top surface level profile and the instantaneous distribution of vortex were discussed. The level variation profile migrated after a period of time, moving from one side of the wide face of the mold to the other. The wave height and transient variation degree of the standing wave increased with an increase in the casting speed. The region near the SEN was more likely to promote the formation of vortices. The vortex generation became easier when the vorticity peaks were concentrated on the outer edge of the low-speed confluence area near the submerged entry nozzle. In addition, the effect of surface velocity on the instantaneous level fluctuation was analyzed. The frequency of level fluctuations was highest at 3~4 mm, and the high-frequency range of velocity fluctuation was 20~60 mm/s at 0.9 m/min casting speed for a 1500 mm × 200 mm caster section. The linear relationship between the level fluctuation and surface velocity magnitude was obtained. The present work aimed at evaluating the dynamic problem of the standing wave at the liquid powder-molten steel interface on the top surface of the mold, which is helpful in optimizing the casting parameters for regular casting practice and improving the quality of the steel slabs.

Ultraflexible endovascular probes for brain recording through micrometer-scale vasculature.

Implantable neuroelectronic interfaces have enabled advances in both fundamental research and treatment of neurological diseases but traditional intracranial depth electrodes require invasive surgery to place and can disrupt neural networks during implantation. We developed an ultrasmall and flexible endovascular neural probe that can be implanted into sub-100-micrometer-scale blood vessels in the brains of rodents without damaging the brain or vasculature. In vivo electrophysiology recording of local field potentials and single-unit spikes have been selectively achieved in the cortex and olfactory bulb. Histology analysis of the tissue interface showed minimal immune response and long-term stability. This platform technology can be readily extended as both research tools and medical devices for the detection and intervention of neurological diseases.

FATP2 regulates non-small cell lung cancer by mediating lipid metabolism through ACSL1.

Lipid metabolism is believed to play an important role in cancer. This study aimed to investigate the role and possible mechanism of fatty acid transporter protein 2 (FATP2) in non-small cell lung cancer (NSCLC). FATP2 expression and its relationship with NSCLC prognosis were analyzed using the TCGA database. The si-RNA was used to intervene FATP2 in NSCLC cells, and the effects of si-FATP2 on cell proliferation, apoptosis, lipid deposition, endoplasmic reticulum (ER) morphology, and the proteins expressions of fatty acid metabolism and ER stress were analyzed. In addition, Co-IP analyzed the interaction between FATP2 and ACSL1, and further analyzed the possible mechanism of FATP2 in regulating lipid metabolism using pcDNA-ACSL1. Results found that FATP2 was overexpressed in NSCLC and associated with poor prognosis. Si-FATP2 significantly inhibited the proliferation and lipid metabolism of A549 and HCC827 cells, and induced ER stress to promote apoptosis. Further studies confirmed the protein interaction between FATP2 and ACSL1. Si-FATP2 and pcDNA-ACSL1 co-transfection further inhibit the proliferation and lipid deposition of NSCLS cells, and promote the decomposition of fatty acids. In conclusion, FATP2 promoted the progression of NSCLC by regulating lipid metabolism through ACSL1.

Sexual Dimorphism in Brain Sirtuin-1 and m6A Methylated Sirtuin-1 mRNA, and in Protection with Post-Injury Anti-miR-200c treatment, after Experimental Stroke in Aged Mice.

We previously demonstrated that inhibition of miR-200c was protective against stroke in young adult male mice by augmenting sirtuin-1 (Sirt1). In the present study we assessed the role of miR-200c on injury, Sirt1, and bioenergetic and neuroinflammatory markers in aged male and female mice after experimental stroke. Mice were subjected to 1hr of transient middle cerebral artery occlusion (MCAO) and assessed for post-injury expression of miR-200c, Sirt1 protein and mRNA, N6-methyladenosine (m6A) methylated Sirt1 mRNA, ATP, cytochrome C oxidase activity, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), infarct volume and motor function. MCAO induced a decrease in Sirt1 expression at 1d post-injury only in males. No differences in SIRT1 mRNA were observed between the sexes. Females had greater baseline miR-200c expression and a greater increase in miR-200c in response to stroke, while pre-MCAO levels of m6A SIRT1 was greater in females. Males had lower post-MCAO ATP levels and cytochrome C oxidase activity, and higher TNFα and IL-6. Post-injury intravenous treatment with anti-miR-200c reduced miR-200c expression in both sexes. In males, anti-miR-200c increased Sirt1 protein expression, reduced infarct volume, and improved neurological score. Conversely in females anti-miR-200c had no effect on Sirt1 levels and provided no protection against injury from MCAO. These results provide the first evidence of sexual dimorphism in the role of a microRNA in aged mice after experimental stroke and suggest sex-differences in epigenetic modulation of the transcriptome and downstream effects on miR biological activity may play a role in sexually dimorphic outcomes after stroke in aged brains.