Synthesis of phenol formaldehyde resin (PFR) based fluorescence resonance energy transfer (FRET) composites for double channel detection of latent fingerprints.

A reversible two-channel fluorescent nanocomposite with fluorescence resonance energy transfer (FRET) effect was designed for the development, analysis, and characterization of latent fingerprints (LFPs). For the construction of the FRET probe, a core of mesoporous silicas (MSNs) were used to encapsulate the organic dye rhodamine 6G (RhD-6) as an acceptor, while green-emitting monodisperse phenolic resin nanoparticles (PFR NPs) were selected as a donor. The up-conversion material (UC) of NaYF4:Yb,Er was synthesized using a simple hydrothermal method, and the MSNs-RhD-6/PFR (PRM) was electrostatically adsorbed onto the UC nanoparticles using a layer-by-layer method to obtain MSNs-RhD-6/PFR-UC (PMU). Compared to ordinary single-channel materials, PMU can be excited by different light sources (365 nm UV/980 nm laser) and its fluorescence can be reversibly switched between yellow and green, demonstrating excellent light reversibility. The PMU composites were successfully used to visualize and detect LFPs on various substrate surfaces using a simple powder coating method. Due to the existing FRET effect and dual-channel characteristics, this composite material displays excellent contrast, outperforming commercially available products for wider applicability. Even on complex backgrounds and after aging or washing treatments, it still clearly recognizes fingerprints in first-, second-, and third-level details, showing its great potential in latent fingerprint detection.

Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma.

Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored. Using a phylogeographic approach, we sequence genomes and transcriptomes from 235 spatially informed sectors across 13 hepatocellular carcinomas (HCC), generating one of the largest datasets for studying sITH. We find that tumor heterogeneity in HCC segregates into spatially variegated blocks with large genotypic and phenotypic differences. By dissecting the transcriptomic heterogeneity, we discover that 30% of patients had a "spatially competing distribution" (SCD), where different spatial blocks have distinct transcriptomic subtypes co-existing within a tumor, capturing the critical transition period in disease progression. Interestingly, the tumor regions with more advanced transcriptomic subtypes (e.g., higher cell cycle) often take clonal dominance with a wider geographic range, rejecting neutral evolution for SCD patients. Extending the statistical tests for detecting natural selection to many non-SCD patients reveal varying levels of selective signal across different tumors, implying that many evolutionary forces including natural selection and geographic isolation can influence the overall pattern of sITH. Taken together, tumor phylogeography unravels a dynamic landscape of sITH, pinpointing important evolutionary and clinical consequences of spatial heterogeneity in cancer.

Rectifying METTL4-Mediated N6-Methyladenine Excess in Mitochondrial DNA Alleviates Heart Failure.

BACKGROUND: Myocardial mitochondrial dysfunction underpins the pathogenesis of heart failure (HF), yet therapeutic options to restore myocardial mitochondrial function are scarce. Epigenetic modifications of mitochondrial DNA (mtDNA), such as methylation, play a pivotal role in modulating mitochondrial homeostasis. However, their involvement in HF remains unclear. METHODS: Experimental HF models were established through continuous angiotensin II and phenylephrine (AngII/PE) infusion or prolonged myocardial ischemia/reperfusion injury. The landscape of N6-methyladenine (6mA) methylation within failing cardiomyocyte mtDNA was characterized using high-resolution mass spectrometry and methylated DNA immunoprecipitation sequencing. A tamoxifen-inducible cardiomyocyte-specific Mettl4 knockout mouse model and adeno-associated virus vectors designed for cardiomyocyte-targeted manipulation of METTL4 (methyltransferase-like protein 4) expression were used to ascertain the role of mtDNA 6mA and its methyltransferase METTL4 in HF. RESULTS: METTL4 was predominantly localized within adult cardiomyocyte mitochondria. 6mA modifications were significantly more abundant in mtDNA than in nuclear DNA. Postnatal cardiomyocyte maturation presented with a reduction in 6mA levels within mtDNA, coinciding with a decrease in METTL4 expression. However, an increase in both mtDNA 6mA level and METTL4 expression was observed in failing adult cardiomyocytes, suggesting a shift toward a neonatal-like state. METTL4 preferentially targeted mtDNA promoter regions, which resulted in interference with transcription initiation complex assembly, mtDNA transcriptional stalling, and ultimately mitochondrial dysfunction. Amplifying cardiomyocyte mtDNA 6mA through METTL4 overexpression led to spontaneous mitochondrial dysfunction and HF phenotypes. The transcription factor p53 was identified as a direct regulator of METTL4 transcription in response to HF-provoking stress, thereby revealing a stress-responsive mechanism that controls METTL4 expression and mtDNA 6mA. Cardiomyocyte-specific deletion of the Mettl4 gene eliminated mtDNA 6mA excess, preserved mitochondrial function, and mitigated the development of HF upon continuous infusion of AngII/PE. In addition, specific silencing of METTL4 in cardiomyocytes restored mitochondrial function and offered therapeutic relief in mice with preexisting HF, irrespective of whether the condition was induced by AngII/PE infusion or myocardial ischemia/reperfusion injury. CONCLUSIONS: Our findings identify a pivotal role of cardiomyocyte mtDNA 6mA and the corresponding methyltransferase, METTL4, in the pathogenesis of mitochondrial dysfunction and HF. Targeted suppression of METTL4 to rectify mtDNA 6mA excess emerges as a promising strategy for developing mitochondria-focused HF interventions.

IL-13 alleviates acute kidney injury and promotes regeneration via activating the JAK-STAT signaling pathway in a rat kidney transplantation model.

AIMS: To identify whether and how a younger systemic internal milieu alleviates acute kidney injury (AKI) in grafts after kidney transplantation. MATERIALS AND METHODS: We conducted an allogenic heterotopic rat kidney transplantation model with young and adult recipients receiving similar donor kidneys. We evaluated the renal function, histological damage, apoptosis, dedifferentiation, proliferation, hub regulating cytokines, and signaling pathways involved in young and adult recipients based on transcriptomics, proteomics, and experimental validation. We also validated the protective effect and mechanism of interleukin-13 (IL-13) on tubular epithelial cell injury induced by transplantation in vivo and by cisplatin in vitro. KEY FINDINGS: Compared with adult recipients, the young recipients had lower levels of renal histological damage and apoptosis, while had higher levels of dedifferentiation and proliferation. Serum IL-13 levels were higher in young recipients both before and after surgery. Pretreating with IL-13 decreased apoptosis and promoted regeneration in injured rat tubular epithelial cells induced by cisplatin, while this effect can be counteracted by a JAK2 and STAT3 specific inhibitor, AG490. Recipients pretreated with IL-13 also had lower levels of histological damage and improved renal function. SIGNIFICANCE: Higher levels of IL-13 in young recipients ameliorates tubular epithelial cell apoptosis and promotes regeneration via activating the JAK-STAT signaling pathway both in vivo and in vitro. Our results suggest that IL-13 is a promising therapeutic strategy for alleviating AKI. The therapeutic potential of IL-13 in injury repair and immune regulation deserves further evaluation and clinical consideration.

[Preliminary application of foldable pedicled latissimus dorsi myocutaneous flap for repairing soft tissue defects in shoulder and back].

Objective: To explore the feasibility and effectiveness of a foldable pedicled latissimus dorsi myocutaneous flap to repair soft tissue defects in the shoulder and back. Methods: Between August 2018 and January 2023, the foldable pedicled latissimus dorsi myocutaneous flaps were used to repair soft tissue defects in the shoulder and back of 8 patients. There were 5 males and 3 females with the age ranged from 21 to 56 years (mean, 35.4 years). Wounds were located in the shoulder in 2 cases and in the shoulder and back in 6 cases. The causes of injury were chronic infection of skin and bone exposure in 2 cases, secondary wound after extensive resection of skin and soft tissue tumor in 4 cases, and wound formation caused by traffic accident in 2 cases. Skin defect areas ranged from 14 cm×13 cm to 20 cm×16 cm. The disease duration ranged from 12 days to 1 year (median, 6.6 months). A pedicled latissimus dorsi myocutaneous flap was designed and harvested. The flap was divided into A/B flap and then were folded to repair the wound, with the donor area of the flap being pulled and sutured in one stage. Results: All 7 flaps survived, with primary wound healing. One patient suffered from distal flap necrosis and delayed healing was achieved after dressing change. The incisions of all donor sites healed by first intention. All patients were followed up 6 months to 4 years (mean, 24.7 months). The skin flap has a good appearance with no swelling in the pedicle. At last follow-up, 6 patients had no significant difference in bilateral shoulder joint motion, and 2 patients had a slight decrease in abduction range of motion compared with the healthy side. The patients' daily life were not affected, and linear scar was left in the donor site. Conclusion: The foldable pedicled latissimus dorsi myocutaneous flap is an ideal method to repair the soft tissue defect of shoulder and back with simple operation, less damage to the donor site, and quick recovery after operation.

Genome-Wide Identification and Characterization of MYB Gene Family and Analysis of Its Sex-Biased Expression Pattern in Spinacia oleracea L.

The members of the myeloblastosis (MYB) family of transcription factors (TFs) participate in a variety of biological regulatory processes in plants, such as circadian rhythm, metabolism, and flower development. However, the characterization of MYB genes across the genomes of spinach Spinacia oleracea L. has not been reported. Here, we identified 140 MYB genes in spinach and described their characteristics using bioinformatics approaches. Among the MYB genes, 54 were 1R-MYB, 80 were 2R-MYB, 5 were 3R-MYB, and 1 was 4R-MYB. Almost all MYB genes were located in the 0-30 Mb region of autosomes; however, the 20 MYB genes were enriched at both ends of the sex chromosome (chromosome 4). Based on phylogeny, conserved motifs, and the structure of genes, 2R-MYB exhibited higher conservation relative to 1R-MYB genes. Tandem duplication and collinearity of spinach MYB genes drive their evolution, enabling the functional diversification of spinach genes. Subcellular localization prediction indicated that spinach MYB genes were mainly located in the nucleus. Cis-acting element analysis confirmed that MYB genes were involved in various processes of spinach growth and development, such as circadian rhythm, cell differentiation, and reproduction through hormone synthesis. Furthermore, through the transcriptome data analysis of male and female flower organs at five different periods, ten candidate genes showed biased expression in spinach males, suggesting that these genes might be related to the development of spinach anthers. Collectively, this study provides useful information for further investigating the function of MYB TFs and novel insights into the regulation of sex determination in spinach.

Surface-enhanced Raman spectroscopy analysis reveals biochemical difference in urine of patients with perianal fistula.

BACKGROUND & AIMS: Perianal fistulising Crohn's disease (PFCD) is different from the characteristics and outcomes of traditional non-inflammatory bowel disease (IBD) anal fistulas. The presence of perianal disease was a poor prognostic indicator for Crohn's disease (CD) patients and PFCD patients were more likely to bear an increased risk of recurrence. However, the effective and accurate diagnosis methods to early distinguish PFCD from simple perianal fistula were still scarce. The purpose of this study is to develop a non-invasive detecting approach to predict CD in patients with perianal fistulas. METHODS: Data on patients with anal fistulizing disease were collected from July 2020 to September 2020 in two IBD centers. Urine samples from PFCD and simple perianal fistula patients were investigated by surface-enhanced Raman spectroscopy (SERS). Principal component analysis (PCA)-support vector machine (SVM) was utilized to establish classification models to distinguish PFCD from simple perianal fistula. RESULTS: After a case-matched 1:1 selection by age and gender, 110 patients were included in the study. By analyzing the average SERS spectra of PFCD and simple perianal fistula patients, it revealed that there were significant differences in intensities at 11 Raman peaks. The established PCA-SVM model distinguished PFCD from simple perianal fistula with a sensitivity of 71.43%, specificity 80.00% and accuracy 75.71% in the leave-one-patient-out cross-validation. The accuracy of the model in validation cohort was 77.5%. CONCLUSIONS: Investigation of urine samples by SERS helps clinicians to predict Crohn's disease from perianal fistulas, which make patients achieve benefit from a more individualized treatment strategy.

Global analysis of iron metabolism-related genes identifies potential mechanisms of gliomagenesis and reveals novel targets.

AIMS: This study aimed to investigate key regulators of aberrant iron metabolism in gliomas, and evaluate their effect on biological functions and clinical translational relevance. METHODS: We used transcriptomic data from multiple cross-platform glioma cohorts to identify key iron metabolism-related genes (IMRGs) based on a series of bioinformatic and machine learning methods. The associations between IMRGs and prognosis, mesenchymal phenotype, and genomic alterations were analyzed in silico. The performance of the IMRGs-based signature in predicting temozolomide (TMZ) treatment sensitivity was evaluated. In vitro and in vivo experiments were used to explore the biological functions of these key IMRGs. RESULTS: HMOX1, LTF, and STEAP3 were identified as the most essential IMRGs in gliomas. The expression levels of these genes were strongly related to clinicopathological and molecular features. The robust IMRG-based gene signature could be used for prognosis prediction. These genes facilitate mesenchymal transformation, driver gene mutations, and oncogenic alterations in gliomas. The gene signature was also associated with TMZ resistance. HMOX1, LTF, and STEAP3 knockdown in glioma cells significantly reduced cell proliferation, colony formation, migration, and malignant invasion. CONCLUSION: The study presented a comprehensive view of key regulators underpinning iron metabolism in gliomas and provided new insights into novel therapeutic approaches.

Prior information-guided reconstruction network for positron emission tomography images.

Background: Deep learning has recently shown great potential in medical image reconstruction tasks. For positron emission tomography (PET) images, the direct reconstruction from raw data to radioactivity images using deep learning without any constraint may lead to the production of nonexistent structures. The aim of this study was to specifically develop and test a flexibly deep learning-based reconstruction network guided by any form of prior knowledge to achieve high quality and high reliability reconstruction. Methods: We developed a novel prior information-guided reconstruction network (PIGRN) with a dual-channel generator and a 2-scale discriminator based on a conditional generative adversarial network (cGAN). Besides the raw data channel, an additional channel is provided in the generator for prior information (PI) to guide the training phase. The PI can be reconstructed images obtained via conventional methods, nuclear medical images from other modalities, attenuation correction maps from time-of-flight-PET (TOF-PET) data, or any other physical parameters. For this study, the reconstructed images generated by filtered back projection (FBP) were chosen as the input of the additional channel. To improve the image quality, a 2-scale discriminator was adopted which can focus on both the coarse and fine field of the reconstruction images. Experiments were carried out on both a simulation dataset and a real Sprague Dawley (SD) rat dataset. Results: Two classic deep learning-based reconstruction networks, including U-Net and Deep-PET, were compared in our study. Compared with these two methods, our method could provide much higher quality PET image reconstruction in the study of the simulation dataset. The peak signal-to-noise ratio (PSNR) value reached 31.8498, and the structure similarity index measure (SSIM) value reached 0.9754. The real study on SD rats indicated that the proposed network also has strong generalization ability. Conclusions: The flexible PIGRN based on cGAN for PET images combines both raw data and PI. The results of comparison experiments and a generalization experiment based on simulation and SD rat datasets demonstrated that the proposed PIGRN has the ability to improve image quality and has strong generalization ability.

[Application of plantar medial thin skin flaps preserving plantar fascia with its superficial fascia tissue to repair skin defects in hands and feet].

Objective: To explore the feasibility and effectiveness of plantar medial thin skin flaps preserving plantar fascia with its superficial fascia tissue to repair skin defects in hands and feet. Methods: Between July 2017 and January 2023, 35 cases of hand and foot defects were repaired with plantar medial thin skin flaps preserving plantar fascia with its superficial fascia tissue (13 pedicled flaps and 22 free flaps). There were 18 males and 17 females, with an average age of 38.8 years (range, 8-56 years). Thirty cases of defects were caused by trauma, and the interval between injury and admission ranged from 2 to 6 hours (mean, 3.3 hours). Three cases were ulcer wounds with a course of 3.0, 3.8, and 7.0 months, respectively. Two cases were malignant melanoma. Eight cases of wounds located in the fingers, 13 cases in the palm, 12 cases in the heel, and 2 cases in the distal foot. The size of skin defects ranged from 4.0 cm×3.5 cm to 12.0 cm×10.0 cm, and the size of flap ranged from 5.0 cm×4.5 cm to 13.0 cm×11.0 cm. The donor sites were repaired with skin grafts. Results: All flaps were survived and the wounds healed by first intention after operation. The partial necrosis at the edge of the skin graft occurred in 1 case, which healed after dressing change; the other skin grafts survived successfully. All patients were followed up 6-24 months (mean, 18 months). The flaps exhibited similar color and thickness to the surrounding hand and foot skin. Two-point discrimination ranged from 7 to 10 mm in the flaps with an average of 8 mm. The donor sites had no painful scars or sensory abnormalities. Foot and ankle functions were good and gaits were normal. Conclusion: Application of plantar medial thin skin flaps preserving plantar fascia with its superficial fascia tissue to repair skin defects in hands and feet had good flap shape, high survival rate of skin graft at the donor site, and no obvious complications.

Nrf2 Mitigates RANKL and M-CSF Induced Osteoclast Differentiation via ROS-Dependent Mechanisms.

Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been shown to be a negative regulator of osteoclast differentiation, but the precise mechanisms have not yet been established. We examined the precise roles of Nrf2 in regulating antioxidants and reactive oxygen species (ROS) levels, especially the cytoplasmic and mitochondrial ROS during osteoclastogenesis in vitro. In the current study, we found that the absence of Nrf2 promotes osteoclast differentiation in bone-marrow-derived macrophages (BMMs) and RAW 264.7 cells. The receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) significantly lowered the levels of Nrf2 and its downstream antioxidant enzymes at mRNA and/or protein levels during osteoclast differentiation in the BMMs of mice and RAW 264.7 mouse leukemic monocytes. Compared to the wild-type cells, Nrf2-deficient cells exhibited heightened sensitivity to both transient RANKL-induced cytoplasmic ROS and prolonged RANKL and M-CSF-induced cytoplasmic and mitochondrial ROS accumulation. Furthermore, exogenous antioxidant agents, including N-acetyl-cysteine (NAC), diphenyleneiodonium chloride (DPI), and mitoquinone mesylate (MitoQ), exhibited substantial capability to suppress the elevation of ROS levels during osteoclast differentiation induced by Nrf2 deficiency, and they consequently inhibited osteoclast differentiation augmented by the lack of Nrf2. The activation of phosphorylated c-FOS resulting from elevated ROS promoted osteoclast differentiation. The inhibition of c-FOS blocked osteoclast differentiation, which was elevated by Nrf2-deficiency. Taken together, these data reveal that Nrf2 effectively decreased the accumulation of intracellular ROS and the phosphorylation of c-FOS during osteoclastic differentiation by regulating antioxidant enzymes and subsequently inhibited RANKL-induced osteoclast differentiation.

The promoting effect and mechanism of MAD2L2 on stemness maintenance and malignant progression in glioma.

BACKGROUND: Glioblastoma, the most common primary malignant tumor of the brain, is associated with poor prognosis. Glioblastoma cells exhibit high proliferative and invasive properties, and glioblastoma stem cells (GSCs) have been shown to play a crucial role in the malignant behavior of glioblastoma cells. This study aims to investigate the molecular mechanisms involved in GSCs maintenance and malignant progression. METHODS: Bioinformatics analysis was performed based on data from public databases to explore the expression profile of Mitotic arrest deficient 2 like 2 (MAD2L2) and its potential function in glioma. The impact of MAD2L2 on glioblastoma cell behaviors was assessed through cell viability assays (CCK8), colony formation assays, 5-Ethynyl-2'-deoxyuridine (EDU) incorporation assays, scratch assays, and transwell migration/invasion assays. The findings from in vitro experiments were further validated in vivo using xenograft tumor model. GSCs were isolated from the U87 and LN229 cell lines through flow cytometry and the stemness characteristics were verified by immunofluorescence staining. The sphere-forming ability of GSCs was examined using the stem cell sphere formation assay. Bioinformatics methods were conducted to identified the potential downstream target genes of MAD2L2, followed by in vitro experimental validation. Furthermore, potential upstream transcription factors that regulate MAD2L2 expression were confirmed through chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: The MAD2L2 exhibited high expression in glioblastoma samples and showed significant correlation with patient prognosis. In vitro and in vivo experiments confirmed that silencing of MAD2L2 led to decreased proliferation, invasion, and migration capabilities of glioblastoma cells, while decreasing stemness characteristics of glioblastoma stem cells. Conversely, overexpression of MAD2L2 enhanced these malignant behaviors. Further investigation revealed that MYC proto-oncogene (c-MYC) mediated the functional role of MAD2L2 in glioblastoma, which was further validated through a rescue experiment. Moreover, using dual-luciferase reporter gene assays and ChIP assays determined that the upstream transcription factor E2F-1 regulated the expression of MAD2L2. CONCLUSION: Our study elucidated the role of MAD2L2 in maintaining glioblastoma stemness and promoting malignant behaviors through the regulation of c-MYC, suggesting its potential as a therapeutic target.

Serum amyloid A as a biomarker for immunoglobulin resistance in Kawasaki disease.

BACKGROUND: Intravenous immunoglobulin (IVIG) resistance is of prime importance in Kawasaki disease (KD). In this study, we examined the value and mechanism of serum amyloid A (SAA) level in predicting IVIG resistance in patients with KD. METHODS: SAA levels were measured in 497 consecutive patients with KD before IVIG therapy in the training set. The patients were divided into two groups (IVIG-responsive and IVIG-resistant) according to the American Heart Association (AHA) definition of IVIG resistance. Demographic, echocardiographic, and laboratory data were also retrospectively analyzed and tabulated to predict IVIG resistance. The predictive value of SAA was validated on test sets of prospective data. Cytokine microarrays were analyzed from 4 patients with resistant to IVIG, 4 patients with responsive to IVIG and 4 healthy volunteers. RESULTS: During the training set, 409 patients with KD were enrolled, of whom 43 (10.5%) were resistant to initial IVIG treatment and 47 (11.49%) had coronary artery lesions (CALs). Serum levels of SAA were higher in the IVIG resistant group compared to the IVIG responsive group, (380.00 [204.40-547.25] vs 230.85 [105.40-490.00] mg/L; p = .008). The values of total bilirubin, C-reactive protein, neutrophils, alanine aminotransferase, aspartate aminotransferase, interleukin-6(IL-6), and procalcitonin were significantly higher in the IVIG-resistant group than in the IVIG-responsive group (p < .05); however, the lymphocytes, platelets, serum sodium levels, and duration of fever before IVIG therapy were significantly lower (p < .05). There was no significant difference in SAA levels between patients with KD with and without CALs. Binary logistic regression analysis showed that SAA (p = .008), neutrophils (p < .001), total bilirubin (p = .001), platelet count (p = .004), and serum sodium level (p = .019) were independent factors influencing IVIG resistance. The optimal cutoff value of SAA for IVIG resistance prediction was 252.45 mg/L, with a corresponding clinical sensitivity of 69.8% and specificity of 54.4%. Based on receiver operating characteristic (ROC) curve analyses, the area under the curve (AUC) of combined detection with these five indicators was 0.800, clinical sensitivity was 69.8%, and specificity was 76.2%. In the prospective data, the sensitivity, specificity, and accuracy of SAA for identifying IVIG resistance KD were 77.8%,69.0%, and 70.0%, respectively. Compared with IVIG- responsive group and healthy children, the levels of IL-6 was upregulated significantly in IVIG-resistant group through cytokine microarrays. CONCLUSIONS: SAA may be a potential biomarker for predicting IVIG responsiveness to KD, Combined detection of SAA levels, total bilirubin, neutrophil count, platelet count, and serum sodium levels is superior to that of any other single indicator for predicting IVIG resistance in KD. And elevated SAA may accompany with IL-6 in KD patients, its use in clinical practice may be helpful for treatment management.

SONAR enables cell type deconvolution with spatially weighted Poisson-Gamma model for spatial transcriptomics.

Recent advancements in spatial transcriptomic technologies have enabled the measurement of whole transcriptome profiles with preserved spatial context. However, limited by spatial resolution, the measured expressions at each spot are often from a mixture of multiple cells. Computational deconvolution methods designed for spatial transcriptomic data rarely make use of the valuable spatial information as well as the neighboring similarity information. Here, we propose SONAR, a Spatially weighted pOissoN-gAmma Regression model for cell-type deconvolution with spatial transcriptomic data. SONAR directly models the raw counts of spatial transcriptomic data and applies a geographically weighted regression framework that incorporates neighboring information to enhance local estimation of regional cell type composition. In addition, SONAR applies an additional elastic weighting step to adaptively filter dissimilar neighbors, which effectively prevents the introduction of local estimation bias in transition regions with sharp boundaries. We demonstrate the performance of SONAR over other state-of-the-art methods on synthetic data with various spatial patterns. We find that SONAR can accurately map region-specific cell types in real spatial transcriptomic data including mouse brain, human heart and human pancreatic ductal adenocarcinoma. We further show that SONAR can reveal the detailed distributions and fine-grained co-localization of immune cells within the microenvironment at the tumor-normal tissue margin in human liver cancer.

Predictors and dynamic online nomogram for postoperative delayed hyponatremia after endoscopic transsphenoidal surgery for pituitary adenomas: a single-center, retrospective, observational cohort study with external validation.

BACKGROUND: Postoperative delayed hyponatremia (PDH) is a major cause of readmission after endoscopic transsphenoidal surgery (eTSS) for pituitary adenomas (PAs). However, the risk factors associated with PDH have not been well established, and the development of a dynamic online nomogram for predicting PDH is yet to be realized. We aimed to investigate the predictive factors for PDH and construct a dynamic online nomogram to aid in its prediction. METHODS: We analyzed the data of 226 consecutive patients who underwent eTSS for PAs at the Department of Neurosurgery in Jinling Hospital between January 2018 and October 2020. An additional 97 external patients were included for external validation. PDH was defined as a serum sodium level below 137 mmol/L, occurring on the third postoperative day (POD) or later. RESULTS: Hyponatremia on POD 1-2 (OR = 2.64, P = 0.033), prothrombin time (PT) (OR = 1.78, P = 0.008), and percentage of monocytes (OR = 1.22, P = 0.047) were identified as predictive factors for PDH via multivariable logistic regression analysis. Based on these predictors, a nomogram was constructed with great discrimination in internal validation (adjusted AUC: 0.613-0.688) and external validation (AUC: 0.594-0.617). Furthermore, the nomogram demonstrated good performance in calibration plot, Brier Score, and decision curve analysis. Subgroup analysis revealed robust predictive performance in patients with various clinical subtypes and mild to moderate PDH. CONCLUSIONS: Preoperative PT and the percentage of monocytes were, for the first time, identified as predictive factors for PDH. The dynamic nomogram proved to be a valuable tool for predicting PDH after eTSS for PAs and demonstrated good generalizability. Patients could benefit from early identification of PDH and optimized treatment decisions.

The impact of surgery and age on mortality with primary trachea malignant tumors: a retrospective study based on propensity-score matching analysis.

PURPOSE: This study aimed to explore the survival significance of surgery and age on the prognosis of patients with primary trachea malignancies. METHODS: The entire cohort of 637 patients with primary malignant trachea tumors was used to perform the main analyses. The data of those patients were from a public database. Overall survival (OS) curves were drawn by the Kaplan-Meier method and compared by the Log-rank test. The univariable and multivariable Cox regression analyses calculated the hazard ratio (HR) and 95% confidence interval (CI) for overall mortality. The propensity-score matching analysis was used to reduce the selection bias. RESULTS: Age, surgery, histological type, N classification, M classification, marital status, and tumor grading were identified as independent prognostic factors after eliminating confounding factors. The results of the Kaplan-Meier method revealed that patients with age < 65 had a survival advantage over those with age ≥ 65 (HR = 1.908, 95% CI 1.549-2.348, P < 0.001). The 5-year OS rates were 28% and 8% in the group with age < 65 and age ≥ 65, respectively (P < 0.001). Cases with surgery had better survival over patients without surgery (HR = 0.372, 95% CI 0.265-0.522, P < 0.001). Compared with patients who did not undergo operations, patients with surgery had a higher median survival time (20 vs. 174 months). For patients with surgery, young age was considered a survival-promoting factor (HR 2.484; 95% CI 1.238-4.983, P = 0.010). CONCLUSION: We suggested that age and surgery were the independent prognostic factors in patients with primary malignant trachea tumors. Besides, age serves as an essential indicator for evaluating the prognosis of postoperative patients.

MRI radiomics for brain metastasis sub-pathology classification from non-small cell lung cancer: a machine learning, multicenter study.

The objective of this study is to develop a machine-learning model that can accurately distinguish between different histologic types of brain lesions in patients with non-small cell lung cancer (NSCLC) when it is not safe or feasible to perform a biopsy. To achieve this goal, the study utilized data from two patient cohorts: 116 patients from Xiangya Hospital and 35 patients from Yueyang Central Hospital. A total of eight machine learning algorithms, including Xgboost, were compared. Additionally, a 3-dimensional convolutional neural network was trained using transfer learning to further evaluate the performance of these models. The SHapley Additive exPlanations (SHAP) method was developed to determine the most important features in the best-performing model after hyperparameter optimization. The results showed that the area under the curve (AUC) for the classification of brain lesions as either lung adenocarcinoma or squamous carcinoma ranged from 0.60 to 0.87. The model based on single radiomics features extracted from contrast-enhanced T1 MRI and utilizing the Xgboost algorithm demonstrated the highest performance (AUC: 0.85) in the internal validation set and adequate performance (AUC: 0.80) in the independent external validation set. The SHAP values also revealed the impact of individual features on the classification results. In conclusion, the use of a radiomics model incorporating contrast-enhanced T1 MRI, Xgboost, and SHAP algorithms shows promise in accurately and interpretably identifying brain lesions in patients with NSCLC.

Effect of lard plus soybean oil on blood pressure and other cardiometabolic risk factors in healthy subjects: a randomized controlled-feeding trial.

Lard has been consumed by humans for thousands of years, but its consumption has declined substantially in the last few decades, because of negative publicity about the consumption of animal-derived saturated fats. Emerging evidence highlights that lard plus soybean oil (blend oil) could be more beneficial for body weight and liver function than the individual use of the two oils. This study aimed to evaluate the effects of blend oil on cardiometabolic risk factors in healthy subjects. This was a parallel, three-arm, randomized controlled-feeding trial. 334 healthy subjects (mean age: 33.1 years, 60% women) were randomized into three isoenergetic diet groups with three different edible oils (30 g day-1) (soybean oil, lard, and blend oil [50% lard and 50% soybean oil]) for 12 weeks. 245 (73.4%) participants completed the study. After the 12-week intervention, reductions in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were greater in the blend oil group than in the other two groups (P = 0.023 and 0.008 for the interaction between the diet group and time, respectively). Reductions of SBP and DBP in the blend oil group were more significant than those in the soybean oil group with P = 0.008 and P = 0.026 and the lard group with P < 0.001 and P < 0.001. Changes in SBP/DBP at 12 weeks were -6.0 (95% CI: -8.6 to -3.4)/0.8 (95% CI: -1.7 to 3.2) mmHg in the blend oil group, -3.3 (95% CI: -5.7 to -0.9)/1.5 (95% CI: -1.0 to 4.0) mmHg in the soybean oil group and -1.2 (95% CI: -3.7 to 1.4)/3.3 (95% CI: 0.9 to 5.8) mmHg in the lard group. Subgroup analyses showed that blend oil significantly decreased SBP and DBP compared with the other two groups in participants with BP ≥ 130/80 mmHg and body mass index ≥25. There were no significant differences in the changes in body weight, waist circumference, serum lipids, or glucose between groups. In conclusion, our findings suggest that blend oil (lard plus soybean oil) reduces BP compared with soybean oil and lard in healthy subjects.

AMG-510 and cisplatin combination increases antitumor effect in lung adenocarcinoma with mutation of KRAS G12C: a preclinical and translational research.

BACKGROUND: The efficacy of monotherapy of AMG-510 is limited. This study explored whether the AMG-510 and cisplatin combination increases the anti-tumor effect in lung adenocarcinoma with the mutation of Kirsten rat sarcoma viral oncogene (KRAS) G12C. METHODS: Patients' data were used to analyze the proportion of KRAS G12C mutation. Besides, the next-generation sequencing data was used to uncover information about co-mutations. The cell viability assay, the concentration inhibiting 50% of cell viability (IC50) determination, colony formation, and cell-derived xenografts were conducted to explore the anti-tumor effect of AMG-510, Cisplatin, and their combination in vivo. The bioinformatic analysis was conducted to reveal the potential mechanism of drug combination with improved anticancer effect. RESULTS: The proportion of KRAS mutation was 2.2% (11/495). In this cohort with KRAS mutation, the proportion of G12D was higher than others. Besides, KRAS G12A mutated tumors had the likelihood of concurrent serine/threonine kinase 11 (STK11) and kelch-like ECH-associated protein 1 (KEAP1) mutations. KRAS G12C and tumor protein p53 (TP53) mutations could appear at the same time. In addition, KRAS G12D mutations and C-Ros oncogene 1 (ROS1) rearrangement were likely to be present in one tumor simultaneously. When the two drugs were combined, the respective IC50 values were lower than when used alone. In addition, there was a minimum number of clones among all wells in the drug combination. In in vivo experiments, the tumor size reduction in the drug combination group was more than twice that of the single drug group (p < 0.05). The differential expression genes were enriched in the pathways of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt) signaling and extracellular matrix (ECM) proteoglycans compared the combination group to the control group. CONCLUSIONS: The anticancer effect of the drug combination was confirmed to be better than monotherapy in vitro and in vivo. The results of this study may provide some information for the plan of neoadjuvant therapy and the design of clinical trials for lung adenocarcinoma patients with KRAS G12C mutation.

Nrf2 protects against renal fibrosis induced by chronic cadmium exposure in mice.

Environmental cadmium (Cd) exposure is a serious public health concern, as the kidney is the primary target for Cd exposure. The present study aimed to investigate the role and underlying mechanisms of nuclear factor erythroid-derived 2-like 2 (Nrf2) in renal fibrosis induced by chronic Cd exposure. Nrf2 knockout (Nrf2-KO) mice and their wild-type littermates (Nrf2-WT) were exposed to 100 or 200 ppm Cd in drinking water for up to 16 or 24 weeks. Following the Cd exposures, Nrf2-KO mice showed elevated urinary neutrophil gelatinase-associated lipocalin (NGAL) and BUN levels compared to Nrf2-WT mice. Masson's trichrome staining and expression of fibrosis-associated proteins revealed that more severe renal fibrosis occurred in Nrf2-KO than that in Nrf2-WT mice. Renal Cd content in the Nrf2-KO mice exposed to 200 ppm Cd was lower than that in Nrf2-WT mice, which might be a consequence of the severe renal fibrosis in the Nrf2-KO mice. Mechanistic studies showed that Nrf2-KO mice exhibited higher levels of oxidative damage, lower antioxidant levels, and more regulated cell death, apoptosis in particular, than those in Nrf2-WT mice caused by Cd exposure. In conclusion, Nrf2-KO mice were more prone to develop renal fibrosis induced by chronic Cd exposure, partially due to a weakened antioxidant, detoxification capacity and increased oxidative damage.