A Low-Complexity Beamformer for Ultrasound Imaging Based on Sub-Beamformer and Multi-Apodization With Cross-Correlation.

OBJECTIVE: This paper proposes an ultrasound imaging algorithm based on sub-beamformer and multi-apodization with cross-correlation (SUB-MAX), aiming to achieve high resolution close to the minimum variance (MV) beamforming with low complexity and to enhance image contrast while maintaining background quality. METHODS: The output of two (N/2)-element DAS beamformers with asymmetric phase centers is subtracted, resulting in a large drop in the main-lobe amplitude, while the sidelobe maintains a relatively high amplitude level. Inspired by this characteristic, the coefficients with opposite trends compared with the subtracted output are obtained and fused with the normalized cross-correlation (NCC) weighting matrix acquired by using multi-pair received apodization, the proposed SUB-MAX obtains a new weighting matrix to weight the output of the DAS beamformer. RESULTS: For ats_wire point targets, the average full-width at half-maximum (FWHM) of SUB-MAX compared with DAS, DMAS, CF, and MAX decreases by 52.7%, 43.5%, 33.3%, and 52.7%, respectively. For geabr_0 cysts, the average contrast ratio (CR) of SUB-MAX compared with DAS, MV, DMAS, and CF increases by 57.7%, 86.8%, 2.5%, and 14.4%, respectively. Experiments on rat_tumor dataset also indicate that SUB-MAX has a superior comprehensive imaging performance. CONCLUSION: The experimental results indicate that the superior comprehensive imaging performance of the proposed SUB-MAX is expected to be suitable for real-time imaging systems due to its non-reliance on covariance matrix inversion.

Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas.

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

Diagnosis of malignant body fluids via cancer-universal methylation in cell-free DNA.

BACKGROUNDDifferentiating malignant from nonmalignant body fluids remains a clinical challenge because of the unsatisfying performance of conventional cytology. We aimed to improve the sensitivity and ubiquity of cancer cell detection by assaying universal cancer-only methylation (UCOM) markers in supernatant cell-free DNA (cfDNA).METHODSAn observational prospective cohort including 1,321 nonmalignant and malignant body fluids of multiple cancers was used to develop and validate a cfDNA UCOM methylation diagnostic assay. All samples were divided into 2 portions for cytology and supernatant cfDNA methylation analysis.RESULTSThe significant hypermethylation of a potentially novel UCOM marker, TAGMe, together with the formerly reported PCDHGB7, was identified in the cfDNA of malignant body fluid samples. The combined model, cell-free cancer-universal methylation (CUE), was developed and validated in a prospective multicancer cohort with markedly elevated sensitivity and specificity, and was further verified in a set containing additional types of malignant body fluids and metastases. In addition, it remained hypersensitive in detecting cancer cells in cytologically negative malignant samples.CONCLUSIONcfDNA methylation markers are robust in detecting tumor cells and are applicable to diverse body fluids and tumor types, providing a feasible complement to current cytology-based diagnostic analyses.TRIAL REGISTRATIONThis study was registered at Chictr.org.cn (ChiCTR2200060532).FUNDINGNational Natural Science Foundation of China (32270645, 31872814, 32000505, 82170088), the National Key R&D Program of Ningxia Hui Autonomous region (2022BEG01003), Shanghai Municipal Key Clinical Specialty (shslczdzk02201), Science and Technology Commission of Shanghai Municipality (20DZ2261200, 20DZ2254400), and Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101).

Carbon doping enhances the fluoride removal performance of aluminum-based adsorbents.

Excessive fluoride presence in water poses significant environmental and public health risks, necessitating the development of effective remediation techniques. Conventional aluminum-based adsorbents face inherent limitations such as limited pH range and low adsorption capacity. To overcome these challenges, we present a facile solvent-thermal method for synthesizing a carbon-doped aluminum-based adsorbent (CDAA). Extensive characterization of CDAA reveals remarkable features including substantial carbon-containing groups, unsaturated aluminum sites, and a high pH at point of zero charge (pHpzc). CDAA demonstrates superior efficiency and selectivity in removing fluoride contaminants, surpassing other adsorbents. It exhibits exceptional adaptability across a broad pH spectrum from 3 to 12, with a maximum adsorption capacity of 637.4 mg/g, more than 110 times higher than alumina. The applicability of the Langmuir isotherm and pseudo-second-order models effectively supports these findings. Notably, CDAA exhibits rapid kinetics, achieving near-equilibrium within just 5 min. Comprehensive analyses utilizing Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) offer detailed insights into the mechanisms involving electrostatic attraction, ion exchange, and ligand exchange. Carbon-based groups play a role in ligand exchange processes, synergistically interacting with the unsaturated aluminum structure to provide a multitude of adsorption sites. The exceptional attributes of CDAA establish its immense potential as a transformative solution for the pressing challenge of fluoride removal from water sources.

Risks and Clinical Predictors of Hepatocellular Carcinoma in Chinese Populations: A Real-World Study of 10,359 Patients in Six Medical Centers.

Purpose: Early detection of hepatocellular carcinoma (HCC) through surveillance could reduce this cancer-associated mortality. We aimed to develop and validate algorithms using panel serum biomarkers to identify HCC in a real-world multi-center study in China. Patients and Methods: A total of 10,359 eligible subjects, including HCCs and benign liver diseases (BLDs), were recruited from six Chinese medical centers. The three nomograms were built using logistic regression and their sensitivities and specificities were carefully assessed in training and validation cohorts. HCC patients after surgical resection were followed to determine the prognostic values of these algorithms. Prospective surveillance performance was assessed in a cohort of chronic hepatitis B patients during 144 weeks follow-up. Results: Independent risk factors such as alpha-fetoprotein (AFP), lens cuinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), albumin (ALB), and total bilirubin (TBIL) obtained from train cohort were used to construct three nomograms (LAD, C-GALAD, and TAGALAD) using logistic regression. In the training and two validation cohorts, their AUCs were all over 0.900, and the higher AUCs appeared in TAGALAD and C-GALAD. Furthermore, the three nomograms could effectively stratify HCC into two groups with different survival and recurrence outcomes in follow-up validation. Notably, TAGALAD could predict HCC up to 48 weeks (AUC: 0.984) and 24 weeks (AUC: 0.900) before clinical diagnosis. Conclusion: The proposed nomograms generated from real-world Chinese populations are effective and easy-to use for HCC surveillance, diagnosis, as well as prognostic evaluation in various clinical scenarios based on data feasibility.

The association of cigarette smoking with DNA methylation and gene expression in human tissue samples.

Cigarette smoking adversely affects many aspects of human health, and epigenetic responses to smoking may reflect mechanisms that mediate or defend against these effects. Prior studies of smoking and DNA methylation (DNAm), typically measured in leukocytes, have identified numerous smoking-associated regions (e.g., AHRR). To identify smoking-associated DNAm features in typically inaccessible tissues, we generated array-based DNAm data for 916 tissue samples from the GTEx (Genotype-Tissue Expression) project representing 9 tissue types (lung, colon, ovary, prostate, blood, breast, testis, kidney, and muscle). We identified 6,350 smoking-associated CpGs in lung tissue (n = 212) and 2,735 in colon tissue (n = 210), most not reported previously. For all 7 other tissue types (sample sizes 38-153), no clear associations were observed (false discovery rate 0.05), but some tissues showed enrichment for smoking-associated CpGs reported previously. For 1,646 loci (in lung) and 22 (in colon), smoking was associated with both DNAm and local gene expression. For loci detected in both lung and colon (e.g., AHRR, CYP1B1, CYP1A1), top CpGs often differed between tissues, but similar clusters of hyper- or hypomethylated CpGs were observed, with hypomethylation at regulatory elements corresponding to increased expression. For lung tissue, 17 hallmark gene sets were enriched for smoking-associated CpGs, including xenobiotic- and cancer-related gene sets. At least four smoking-associated regions in lung were impacted by lung methylation quantitative trait loci (QTLs) that co-localize with genome-wide association study (GWAS) signals for lung function (FEV1/FVC), suggesting epigenetic alterations can mediate the effects of smoking on lung health. Our multi-tissue approach has identified smoking-associated regions in disease-relevant tissues, including effects that are shared across tissue types.

The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men.

BACKGROUND: American men of African ancestry (AA) have higher prostate cancer incidence and mortality rates compared with American men of European ancestry (EA). Differences in genetic susceptibility mechanisms may contribute to this disparity. METHODS: To gain insights into the regulatory mechanisms of prostate cancer susceptibility variants, we tested the association between SNPs and DNA methylation (DNAm) at nearby CpG sites across the genome in benign and cancer prostate tissue from 74 AA and 74 EA men. Genome-wide SNP data (from benign tissue) and DNAm were generated using Illumina arrays. RESULTS: Among AA men, we identified 6,298 and 2,641 cis-methylation QTLs (meQTL; FDR of 0.05) in benign and tumor tissue, respectively, with 6,960 and 1,700 detected in EA men. We leveraged genome-wide association study (GWAS) summary statistics to identify previously reported prostate cancer GWAS signals likely to share a common causal variant with a detected meQTL. We identified nine GWAS-meQTL pairs with strong evidence of colocalization (four in EA benign, three in EA tumor, two in AA benign, and three in AA tumor). Among these colocalized GWAS-meQTL pairs, we identified colocalizing expression quantitative trait loci (eQTL) impacting four eGenes with known roles in tumorigenesis. CONCLUSIONS: These findings highlight epigenetic regulatory mechanisms by which prostate cancer-risk SNPs can modify local DNAm and/or gene expression in prostate tissue. IMPACT: Overall, our findings showed general consistency in the meQTL landscape of AA and EA men, but meQTLs often differ by tissue type (normal vs. cancer). Ancestry-based linkage disequilibrium differences and lack of AA representation in GWAS decrease statistical power to detect colocalization for some regions.

Angong Niuhuang Wan inhibit ferroptosis on ischemic and hemorrhagic stroke by activating PPARγ/AKT/GPX4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Angong Niuhuang Wan (AGNHW) is a prescription from traditional Chinese medicine (TCM) that has been used for centuries to treat ischemic stroke (IS) and hemorrhagic stroke (HS). According to a recent study, targeting ferroptosis might be effective in the management of IS and HS. However, the ferroptosis-related effects and mechanisms of AGNHW have not yet been reported. AIM OF THE STUDY: This research examines the anti-ferroptosis mechanisms of AGNHW in the treatment of IS and HS. MATERIALS AND METHODS: A system pharmacological approach including in vivo experiment, UHPLC-Q-Orbitrap HRMS, network pharmacology, molecular docking, microscale thermophoresis, and in vitro experiment was utilized to study the anti-ferroptosis mechanisms of AGNHW against IS and HS. RESULTS: In vivo experiments indicated that AGNHW enhanced nerve function, decreased cerebral infarct volume, ameliorated histological brain injuries, improved the structural integrity of the blood-brain barrier, ameliorated the mitochondrial dysfunction and morphology disruption, and inhibits ROS, LPO and Fe2+ accumulations in IS and HS rats. Using UHPLC-Q-Orbitrap HRMS, the key ingredients of AGNHW-containing serum were identified as bilirubin, berberine, baicalin, and wogonoside. According to the network pharmacology analyses, AGNHW could inhibit ferroptosis by modulating the PPAR and PI3K/AKT signaling pathways. The core targets are PPARγ, AKT, and GPX4. Molecular docking and microscale thermophoresis experiments further revealed that the key ingredients have strong interactions with ferroptosis-regulating core proteins. Moreover, in vitro experiment results showed that AGNHW alleviated ferroptosis injury induced by erastin in PC12 cells, increased cell viability, reduced the LPO and Fe2+ levels, and up-regulated mRNA expressions of PPARγ, AKT, and GPX4. AGNHW also up-regulated protein expressions of PPARγ, p-AKT/AKT, and GPX4 in IS and HS rats. CONCLUSIONS: AGNHW attenuated ferroptosis in treating IS and HS by targeting the PPARγ/AKT/GPX4 pathway. This work reveals AGNHW's anti-ferroptosis mechanism against IS and HS, but it also develops an integrated approach to demonstrate the common characteristics of drugs in treating different diseases.

The distribution of intestinal flora after hematopoietic stem cell transplantation in children.

BACKGROUND: This prospective study aimed to comprehensively understand the changes in intestinal flora at different stages after hematopoietic stem cell transplantation (HSCT) in pediatric patients and to analyze the effect of intestinal flora on acute graft versus host disease (aGVHD), especially on gastrointestinal graft versus host disease (GI GVHD). METHODS: A total of 32 children with primary diseases of primary immunodeficiency disease (PID) and thalassemia were included. 16S sequencing was used to characterize the microbiota layout at three time points peri-transplant including pre-transplant, Day +3, and Day +30. RESULTS: By comparing the intestinal flora of children with GI GVHD and those without GI GVHD, it suggests that in children with GI GVHD, the distribution of intestinal flora after transplantation was more variable and more chaotic (chao1 index, Friedman test, p = .029). Besides, Veillonella and Ruminococcaceae were more abundant before transplantation, Bifidobacteriaceae and Bacillales were more abundant after transplantation. Comparing children with PID and thalassemia, it was found that the destruction of gut microbiota diversity was more significant in children with thalassemia after transplantation. The comparison of children with 0-I° aGVHD and II-III° aGVHD indicates that children with II-III° aGVHD had more Bilophila before transplantation than children with 0-I° aGVHD. Additionally, exploratory analyses to evaluate correlations between clinical characteristics (medications, immune cell recovery, etc.) and microbiome features were also performed. CONCLUSIONS: This study has synthetically shown the distribution of intestinal flora after allo-HSCT, and some characteristic bacteria at different stages that may serve as potential biomarkers were screened out additionally, perhaps providing clues for the prevention and treatment of the disease.

Development of an autoantibody panel for early detection of lung cancer in the Chinese population.

Introduction: Tumor-associated autoantibodies have been revealed as promising biomarkers for the early detection of lung cancer. This study was designed to develop an autoantibody panel for early detection of lung cancer in the Chinese population. Methods: Recruited prospectively in three clinical centers, the subjects (n = 991) who had a definite diagnosis during follow-up were included in the development of the autoantibody panel. The levels of 14 autoantibody candidates in plasma were detected. Results: A panel of nine autoantibody markers (named as CN9), namely, P53, SOX2, SSX1, HuD, NY-ESO-1, CAGE, MAGE-A4, P62, and CK20, was preferably selected from 14 candidates. The overall specificity, sensitivity, and AUC were 90.5%, 40.8%, and 0.64, respectively. The CN9 panel demonstrated a reasonable detection rate in lung cancer patients at all stages, histological types, sizes of lesions, and risk levels. Its estimated overall accuracy is 85.5% and 90%, with PPV at 0.32 and 0.04, and NPV at 0.93 and 0.99 in the scenario of pulmonary nodules' characterizing and lung cancer screening, respectively. Two risk models were developed within the subgroups of malignant and benign pulmonary nodules in this study. By adding the CN9 result to the Mayo model indicators, it achieved a sensitivity of 41.3% and an AUC of 0.74 at a specificity of 91.3%. By adding the CN9 result to the Brock model indicators, it achieved a sensitivity of 47.7% and an AUC of 0.78 at a specificity of 91.3%. Both were improved compared with either the standalone Mayo or Brock model. Discussion: This multi-center prospective study indicates a panel of nine autoantibody markers that can help in the detection of lung cancer and the classification of pulmonary nodules in the Chinese population.

Regulator of G protein signaling protein 6 alleviates acute lung injury by inhibiting inflammation and promoting cell self-renewal in mice.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a disease with high mortality and morbidity. Regulator of G protein signaling protein 6 (RGS6), identified as a tumor suppressor gene, has received increasing attention owing to its close relationship with oxidative stress and inflammation. However, the association between ARDS and RGS6 has not been reported. METHODS: Congruously regulated G protein-coupled receptor (GPCR)-related genes and differentially expressed genes (DEGs) in an acute lung injury (ALI) model were identified, and functional enrichment analysis was conducted. In an in vivo study, the effects of RGS6 knockout were studied in a mouse model of ALI induced by lipopolysaccharide (LPS). HE staining, ELISA, and immunohistochemistry were used to evaluate pathological changes and the degree of inflammation. In vitro, qRT‒PCR, immunofluorescence staining, and western blotting were used to determine the dynamic changes in RGS6 expression in cells. The RGS6 overexpression plasmid was constructed for transfection. qRT‒PCR was used to assess proinflammatory factors transcription. Western blotting and flow cytometry were used to evaluate apoptosis and reactive oxygen species (ROS) production. Organoid culture was used to assess the stemness and self-renewal capacity of alveolar epithelial type II cells (AEC2s). RESULTS: A total of 110 congruously regulated genes (61 congruously upregulated and 49 congruously downregulated genes) were identified among GPCR-related genes and DEGs in the ALI model. RGS6 was downregulated in vivo and in vitro in the ALI model. RGS6 was expressed in the cytoplasm and accumulated in the nucleus after LPS stimulation. Compared with the control group, we found higher mortality, more pronounced body weight changes, more serious pulmonary edema and pathological damage, and more neutrophil infiltration in the RGS6 knockout group upon LPS stimulation in vivo. Moreover, AEC2s loss was significantly increased upon RGS6 knockout. Organoid culture assays showed slower alveolar organoid formation, fewer alveolar organoids, and impaired development of new structures after passaging upon RGS6 knockout. In addition, RGS6 overexpression decreased ROS production as well as proinflammatory factor transcription in macrophages and decreased apoptosis in epithelial cells. CONCLUSIONS: RGS6 plays a protective role in ALI not only in early inflammatory responses but also in endogenous lung stem cell regeneration.

Genome-wide association study of prostate-specific antigen levels in 392,522 men identifies new loci and improves cross-ancestry prediction.

We conducted a multi-ancestry genome-wide association study of prostate-specific antigen (PSA) levels in 296,754 men (211,342 European ancestry; 58,236 African ancestry; 23,546 Hispanic/Latino; 3,630 Asian ancestry; 96.5% of participants were from the Million Veteran Program). We identified 318 independent genome-wide significant (p≤5e-8) variants, 184 of which were novel. Most demonstrated evidence of replication in an independent cohort (n=95,768). Meta-analyzing discovery and replication (n=392,522) identified 447 variants, of which a further 111 were novel. Out-of-sample variance in PSA explained by our new polygenic risk score reached 16.9% (95% CI=16.1%-17.8%) in European ancestry, 9.5% (95% CI=7.0%-12.2%) in African ancestry, 18.6% (95% CI=15.8%-21.4%) in Hispanic/Latino, and 15.3% (95% CI=12.7%-18.1%) in Asian ancestry, and lower for higher age. Our study highlights how including proportionally more participants from underrepresented populations improves genetic prediction of PSA levels, with potential to personalize prostate cancer screening.

Keratin 15 protects against cigarette smoke-induced epithelial mesenchymal transformation by MMP-9.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease, is a leading cause of morbidity and mortality worldwide. Prolonged cigarette smoking (CS) that causes irreversible airway remodeling and significantly reduces lung function is a major risk factor for COPD. Keratin15+ (Krt15+) cells with the potential of self-renewal and differentiation properties have been implicated in the maintenance, proliferation, and differentiation of airway basal cells; however, the role of Krt15 in COPD is not clear. METHODS: Krt15 knockout (Krt15-/-) and wild-type (WT) mice of C57BL/6 background were exposed to CS for six months to establish COPD models. Krt15-CrePGR;Rosa26-LSL-tdTomato mice were used to trace the fate of the Krt15+ cells. Hematoxylin and eosin (H&E) and Masson stainings were performed to assess histopathology and fibrosis, respectively. Furthermore, lentivirus-delivered short hairpin RNA (shRNA) was used to knock down KRT15 in human bronchial epithelial (HBE) cells stimulated with cigarette smoke extract (CSE). The protein expression was assessed using western blot, immunohistochemistry, and enzyme-linked immunosorbent assay. RESULTS: Krt15-/- CS mice developed severe inflammatory cell infiltration, airway remodeling, and emphysema. Moreover, Krt15 knockout aggravated CS-induced secretion of matrix metalloproteinase-9 (MMP-9) and epithelial-mesenchymal transformation (EMT), which was reversed by SB-3CT, an MMP-9 inhibitor. Consistent with this finding, KRT15 knockdown promoted MMP-9 expression and EMT progression in vitro. Furthermore, Krt15+ cells gradually increased in the bronchial epithelial cells and were transformed into alveolar type II (AT2) cells. CONCLUSION: Krt15 regulates the EMT process by promoting MMP-9 expression and protects the lung tissue from CS-induced injury, inflammatory infiltration, and apoptosis. Furthermore, Krt15+ cells transformed into AT2 cells to protect alveoli. These results suggest Krt15 as a potential therapeutic target for COPD.

[Expression of interleukin-37, vascular endothelial growth factor A, and transforming growth factor-ß1 and their correlation with T cells in children with primary immune thrombocytopenia]. / å„¿ç«¥åŽŸå‘å ç–«æ€§è¡€å°æ¿å‡å°‘ç—‡IL-37、VEGFA、TGF-ß1çš„è¡¨è¾¾åŠå ¶ä¸ŽTç»†èƒžçš„ç›¸å ³æ€§ç ”ç©¶.

OBJECTIVES: To investigate the expression of interleukin-37 (IL-37), vascular endothelial growth factor A (VEGFA), and transforming growth factor-ß1 (TGF-ß1) in children with primary immune thrombocytopenia (ITP) and their correlation with T cells. METHODS: A retrospective analysis was conducted on 45 children with ITP (ITP group) who were admitted to Handan Central Hospital from January 2020 to April 2022, and 30 healthy children who underwent physical examination during the same period were included as the healthy control group. The mRNA expression levels of IL-37, VEGFA, and TGF-ß1 and the levels of regulatory T cells (Treg) and helper T cells 17 (Th17) were measured before and after treatment, and the correlation between the mRNA expression levels of IL-37, VEGFA, and TGF-ß1 and the levels of Treg, Th17, and Treg/Th17 ratio were analyzed. RESULTS: Compared with the healthy control group, the ITP group had a significantly higher mRNA expression level of IL-37 and a significantly higher level of Th17 before and after treatment, as well as significantly lower mRNA expression levels of VEGFA and TGF-ß1 and significantly lower levels of Treg and Treg/Th17 ratio (P<0.05). After treatment, the ITP group had significant reductions in the mRNA expression level of IL-37 and the level of Th17 and significant increases in the mRNA expression levels of VEGFA and TGF-ß1 and the levels of Treg and Treg/Th17 ratio (P<0.05). Correlation analysis showed that in the ITP group, the mRNA expression levels of IL-37 and TGF-ß1 were negatively correlated with the levels of Treg and Treg/Th17 ratio (P<0.05) and were positively correlated with the level of Th17 (P<0.05) before and after treatment; the mRNA expression level of VEGFA was positively correlated with the levels of Treg and Treg/Th17 ratio (P<0.05) and was negatively correlated with the Th17 level (P<0.05) before and after treatment. CONCLUSIONS: Abnormal expression levels of IL-37, VEGFA, and TGF-ß1 may be observed in children with ITP, which is significantly associated with the imbalance of Treg/Th17 ratio. It is speculated that the cytokines such as IL-37, VEGFA, and TGF-ß1 may be involved in the development and progression of ITP or may become important potential targets for the treatment of children with ITP. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(11): 1131-1136.

Multi-apodization with cross-correlation combined with generalized sidelobe canceller applied to ultrasound imaging.

BACKGROUND: Beamforming is vital for medical ultrasound imaging systems. The generalized sidelobe canceller (GSC) beamforming can improve the image quality of lateral resolution, but its performance improvement in contrast and robustness is limited. OBJECTIVE: This paper proposes an improved generalized sidelobe canceller algorithm based on multi-apodization with cross-correlation (MAXB-IGSC), which aims to improve the contrast and robustness of ultrasound imaging while maintaining the high image resolution and background speckle quality of GSC. METHODS: The proposed MAXB-IGSC uses multiple pairs of complementary received apodization functions to process the echo data individually to obtain multiple pairs of data sets. The average of their normalized cross-correlation coefficients is then calculated and utilized to determine the adaptive subarray length of the GSC covariance matrix and weights the output of the improved GSC. RESULTS: The MAXB-IGSC improves the contrast ratio (CR) by 171.18% in anechoic cyst simulation and by 91.23%/130.97%/171.76% in geabr_0 (a dataset from the University of Michigan) experiment compared with GSC, respectively. Furthermore, MAXB-IGSC exhibits significant noise immunity, which greatly improves the robustness of the imaging. The technology also maintains the brightness and uniformity of the background speckle. CONCLUSION: The proposed MAXB-IGSC has potential for obtaining high-quality ultrasound images in clinical applications.

Near-Infrared-Driven Nanorocket for Rapid and Ultrasensitive Detection of MicroRNA.

Herein, by introducing gold nanostars (AuNSs) as fuel core, a near-infrared-driven nanorocket (NIDNR) with pretty fast walking was exploited for ultrasensitive miRNA detection. Compared with traditional nanomaterials-comprised nanomachines (NMs), the NIDNR possesses much better kinetic and thermodynamic performance owing to the extra photothermal driving force from localized surface plasmon (LSP). Impressively, the whole reaction time of NIDNR down to 15 min was realized, which is almost more than 8 times beyond those of conventional DNA-based NMs. This way, the inherent obstacle of traditional NMs, including long reaction time and low efficiency, could be easily addressed. As a proof of concept, the NIDNR was successfully applied to develop an electrochemical biosensing platform for rapid and sensitive detection of miRNA with an LOD down to 2.95 aM and achieved the real-time assay of real biological samples from human hepatocellular carcinoma cells (MHCC97L) and HeLa, thus providing an innovative insight to design more versatile DNA nanomachines for ultimate application in biosensing platform construction and clinical sample detection.

Association between albumin-to-globulin ratio and the risk of overall survival in advanced non-small cell lung cancer patients with anlotinib treatment: a retrospective cohort study.

OBJECTIVE: Researches about the association between serum albumin-to-globulin ratio (AGR) and the prognosis of lung cancer are limited. We aimed to investigate the relationship between AGR and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) treated with anlotinib. METHODS: A retrospective cohort study was conducted on 196 advanced NSCLC patients with anlotinib treatment between June 1, 2018 and June 1, 2021. The exposure was AGR, calculated by baseline serum albumin / (serum total protein - serum albumin). The outcome was OS, defined as the period from the date of initial treatment with anlotinib to death or the last follow-up. The univariate and multivariate linear regression models and generalized additive models (GAM) were used to analyze the relationship between AGR and OS. The Kaplan-Meier method was used to analyze the OS. RESULTS: After adjusting for potential confounders, a non-linear relationship was observed between AGR and OS, which had an inflection point of 1.24. The hazard ratio and the confidence intervals on the left and the right sides of the inflection point were 13.05 (0.52 to 327.64) and 0.20 (0.07 to 0.57), respectively. It suggested that AGR was positively associated with OS when AGR was larger than 1.24, for every 1 unit increase in AGR, the risk of death lowered approximately by 80%. CONCLUSIONS: The relationship between AGR and the OS for advanced NSCLC patients with anlotinib is non-linear. AGR level is an independent protective factor for OS in advanced NSCLC patients who received anlotinib therapy.

Low complexity adaptive ultrasound image beamformer combined with improved multiphase apodization with cross-correlation.

In this paper, an ultrasound imaging method combined with low-complexity adaptive beamformer (LCA) and improved multiphase apodization with cross-correlation (IMPAX) is proposed to improve image resolution and contrast with low hardware cost. Firstly, the delayed echo signal is apodized by the LCA to obtain a narrow mainlobe width echo signal and LCA output. Then, multiple pairs of complementary square-wave phase apodizations are applied to the apodized echo signal to obtain corresponding signal pairs, which are used to calculate the normalized cross-correlation (NCC) matrix. Finally, the average value of the NCC matrices is filtered by 2-D means, and the filtered result is introduced as the weighting factor for the LCA output. The simulation and experimental results show that the proposed LCA-IMPAX can effectively reduce the mainlobe width, suppress clutter, and be robust to noise. Compared with DAS, LCA, and MPAX, for simulated point targets, the full-width at half-maximum (FWHM, -6dB) of LCA-IMPAX is reduced by 49.22%, 10.06%, and 48.67%, respectively. For simulated cyst, the CR is improved by 219.91%, 138.08%, and 103.44%, respectively. For experimental cysts, the CR is improved by an average of 145.00%, 136.14%, and 55.09%, respectively. The results of human heart data indicate that LCA-IMPAX has good imaging quality in vivo. Since the proposed method does not involve covariance matrix inversion, it can be applied in real-time imaging systems.

A green synthesized medicine residue carbon-based iron composite for the removal of chromium (VI) and cadmium (II): Performance, kinetics and mechanism.

Nowadays, clean-up of heavy metals from wastewaters using waste residue carbon-based material has received increasing attention. In this work, a novel Chinese medicine residue carbon-based nano zero-valent iron composite (CM-nZVI) had been successfully prepared using the combined Chinese medicine residue, FeCl3 and green tea extract. Cr(VI) and/ or Cd(II) removal in water by the CM-nZVI were systematacially investigated with a series of batch experiments. The most relevant findings indicated the adsorption efficiecy and capacity of Cr(VI) by CM-nZVI were respecitvely nearly 98% and 26 mg/g under optimized reaction conditions. The negative influences of the cations on the Cr(VI) removal followed the order of Al3+ > Ca2+ > Mg2+ Na+ > K+, but the anions followed the order of HCO3- > PO43- > NO3- > Cl- > SO42-. Humic acid (HA) and ionic strength with high concentrations severely inhibited Cr(VI) removal. The Cr(VI) adsorption on CM-nZVI fitted well by the pseudo-second-order kinetic and Langmuir models. A monolayer endothermic chemisorption occurred on Cr(VI) adsorption over CM-nZVI, and Cr(VI) removal by CM-nZVI primarily involved in the absorption, reduction, precipitation and complexation processes. Both Cr(VI) and Cd(II) removals had been achieved by CM-nZVI at their low concentrations. This CM-nZVI showed a better reusability proprity for Cr(VI) and Cd(II) removal with the regeneration of CM-nZVI through simple pickling. The outcomes of this work show that CM-nZVI could be used an effective material for heavy metals removal from water.

The deacetylation of Akt by SIRT1 inhibits inflammation in macrophages and protects against sepsis.

Sepsis is characterized by uncontrolled inflammatory response and altered polarization of macrophages at the early phase. Akt is known to drive macrophage inflammatory response. However, how macrophage inflammatory response is fine-tuned by Akt is poorly understood. Here, we found that Lys14 and Lys20 of Akt is deacetylated by the histone deacetylase SIRT1 during macrophage activation to suppress macrophages inflammatory response. Mechanistically, SIRT1 promotes Akt deacetylation to inhibit the activation of NF-κB and pro-inflammatory cytokines. Loss of SIRT1 facilitates Akt acetylation and thus promotes inflammatory cytokines in mouse macrophages, potentially worsen the progression of sepsis in mice. By contrast, the upregulation of SIRT1 in macrophages further contributes to the inhibition of pro-inflammatory cytokines via Akt activation in sepsis. Taken together, our findings establish Akt deacetylation as an essential negative regulatory mechanism that curtails M1 polarization.