Radiomics analysis of dual-layer spectral-detector CT-derived iodine maps for predicting tumor deposits in colorectal cancer.

OBJECTIVE: To investigate the value of radiomics analysis of dual-layer spectral-detector computed tomography (DLSCT)-derived iodine maps for predicting tumor deposits (TDs) preoperatively in patients with colorectal cancer (CRC). MATERIALS AND METHODS: A total of 264 pathologically confirmed CRC patients (TDs + (n = 80); TDs - (n = 184)) who underwent preoperative DLSCT from two hospitals were retrospectively enrolled, and divided into training (n = 124), testing (n = 54), and external validation cohort (n = 86). Conventional CT features and iodine concentration (IC) were analyzed and measured. Radiomics features were derived from venous phase iodine maps from DLSCT. The least absolute shrinkage and selection operator (LASSO) was performed for feature selection. Finally, a support vector machine (SVM) algorithm was employed to develop clinical, radiomics, and combined models based on the most valuable clinical parameters and radiomics features. Area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis were used to evaluate the model's efficacy. RESULTS: The combined model incorporating the valuable clinical parameters and radiomics features demonstrated excellent performance in predicting TDs in CRC (AUCs of 0.926, 0.881, and 0.887 in the training, testing, and external validation cohorts, respectively), which outperformed the clinical model in the training cohort and external validation cohorts (AUC: 0.839 and 0.695; p: 0.003 and 0.014) and the radiomics model in two cohorts (AUC: 0.922 and 0.792; p: 0.014 and 0.035). CONCLUSION: Radiomics analysis of DLSCT-derived iodine maps showed excellent predictive efficiency for preoperatively diagnosing TDs in CRC, and could guide clinicians in making individualized treatment strategies. CLINICAL RELEVANCE STATEMENT: The radiomics model based on DLSCT iodine maps has the potential to aid in the accurate preoperative prediction of TDs in CRC patients, offering valuable guidance for clinical decision-making. KEY POINTS: Accurately predicting TDs in CRC patients preoperatively based on conventional CT features poses a challenge. The Radiomics model based on DLSCT iodine maps outperformed conventional CT in predicting TDs. The model combing DLSCT iodine maps radiomics features and conventional CT features performed excellently in predicting TDs.

Plasma Ionomic Profile and Interaction Patterns in Coronary Artery Disease Patients.

Humans are exposed to various chemical elements that have been associated with the development and progression of diseases such as coronary artery disease (CAD). Unlike previous research, we employed a multi-element approach to investigate CAD patients and those with comorbid conditions such as diabetes (CAD-DM2), high blood pressure (CAD-HBP), or high blood lipids (CAD-HBL). Plasma concentrations of 21 elements, including lithium (Li), boron (B), aluminum (Al), calcium (Ca), titanium (Ti), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), strontium (Sr), cadmium (Cd), tin (Sn), stibium (Sb), barium (Ba), and lead (Pb), were measured in CAD patients (n = 201) and healthy subjects (n = 110) using inductively coupled plasma-mass spectrometry (ICP-MS). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were utilized to analyze the ionomic profiles. Spearman correlation analysis was employed to identify the interaction patterns among individual elements. We found that levels of Ba, Li, Ni, Zn and Pb were elevated in the CAD group compared to the healthy group, while Sb, Ca, Cu, Ti, Fe, and Se were lower. Furthermore, the CAD-DM2 group exhibited higher levels of Ni and Cd, while the CAD-HBP group showed lower levels of Co and Mn. In the CAD-HBL group, Ti was increased, whereas Ba, Cr, Cu, Co, Mn, and Ni were reduced. In conclusion, ionomic profiles can be utilized to differentiate CAD patients from healthy individuals, potentially providing insights for future treatment or dietary interventions.

Spatiotemporal release of non-nucleotide STING agonist and AKT inhibitor from implantable 3D-printed scaffold for amplified cancer immunotherapy.

Immunotherapy through the activation of the stimulator of interferon genes (STING) signaling pathway is increasingly recognized for its robust anti-tumor efficacy. However, the effectiveness of STING activation is often compromised by inadequate anti-tumor immunity and a scarcity of primed immune cells in the tumor microenvironment. Herein, we design and fabricate a co-axial 3D-printed scaffold integrating a non-nucleotide STING agonist, SR-717, and an AKT inhibitor, MK-2206, in its respective shell and core layers, to synergistically enhance STING activation, thereby suppressing tumor recurrence and growth. SR-717 initiates the STING activation to enhance the phosphorylation of the factors along the STING pathway, while MK-2206 concurrently inhibits the AKT phosphorylation to facilitate the TBK1 phosphorylation of the STING pathway. The sequential and sustained release of SR-717 and MK-2206 from the scaffold results in a synergistic STING activation, demonstrating substantial anti-tumor efficacy across multiple tumor models. Furthermore, the scaffold promotes the recruitment and enrichment of activated dendritic cells and M1 macrophages, subsequently stimulating anti-tumor T cell activity, thereby amplifying the immunotherapeutic effect. This precise and synergistic activation of STING by the scaffold offers promising potential in tumor immunotherapy.

The influence factors of tour guides' professional identity and professional decision before and after the COVID-19 pandemic.

The COVID-19 pandemic has significantly impacted the tourism sector, particularly tour guides (TGs), affecting their professional identity (TGPI) and intentions to return to work. As China strives to revive its tourism industry, it is crucial to understand the current state of TGPI, its evolution, influencing factors, and its impact on TGs' return intentions. This study employed a quantitative approach, using comparative analysis and binary logistic regression, to investigate these issues among frontline TGs in China, pre- and post-pandemic. Cross-sectional surveys were conducted with 422 participants in 2019 and 398 in 2022, yielding 370 and 342 valid responses, respectively. The questionnaire utilized a five-point Likert scale. Findings reveal that (1) The overall TGPI level in 2022 post-pandemic is medium (3.93), showing a significant decrease from the pre-pandemic level in 2019 (4.15). (2) Influencing factors of TGPI are predominantly material, reflected in social insurance and income changes pre- and post-pandemic. (3) This study presents a novel definition and scale of TGPI, encompassing tour guides' professional value identity (TGPVI), emotion identity (TGPEI), relationship identity (TGPRI), and behavior tendency (TGPBT). (4) The two dimensions of the TGPI, TGPVI and TGPRI, income and education level, significantly influence TGs' return intentions. The study provides valuable academic and practical insights into TGPI and offers significant implications for enhancing TGs' return intentions and policymaking for post-pandemic tourism industry development.

WRKY47 transcription factor modulates leaf senescence through regulating PCD-associated genes in Arabidopsis.

Transcription factors play crucial roles in almost all physiological processes including leaf senescence. Cell death is a typical symptom appearing in senescing leaves, which is also classified as developmental programmed cell death (PCD). However, the link between PCD and leaf senescence still remains unclear. Here, we found a WRKY transcription factor WRKY47 positively modulates age-dependent leaf senescence in Arabidopsis (Arabidopsis thaliana). WRKY47 was expressed preferentially in senescing leaves. A subcellular localization assay indicated that WRKY47 was exclusively localized in nuclei. Overexpression of WRKY47 showed precocious leaf senescence, with less chlorophyll content and higher electrolyte leakage, but loss-of-function mutants of WRKY47 delayed this biological process. Through qRT-PCR and dual luciferase reporter assays, we found that WRKY47 could activate the expression of senescence-associated genes (SAGs) and PCD-associated genes to regulate leaf senescence. Furthermore, through electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-qPCR, WRKY47 was found to bind to W-box fragments in promoter regions of BFN1 (Bifunctional Nuclease 1) and MC6 (Metacaspase 6) directly. In general, our research revealed that WRKY47 regulates age-dependent leaf senescence by activating the transcription of two PCD-associated genes.

A probe for NIR-II imaging and multimodal analysis of early Alzheimer's disease by targeting CTGF.

To date, earlier diagnosis of Alzheimer's disease (AD) is still challenging. Recent studies revealed the elevated expression of connective tissue growth factor (CTGF) in AD brain is an upstream regulator of amyloid-beta (Aß) plaque, thus CTGF could be an earlier diagnostic biomarker of AD than Aß plaque. Herein, we develop a peptide-coated gold nanocluster that specifically targets CTGF with high affinity (KD ~ 21.9 nM). The probe can well penetrate the blood-brain-barrier (BBB) of APP/PS1 transgenic mice at early-stage (earlier than 3-month-old) in vivo, allowing non-invasive NIR-II imaging of CTGF when there is no appearance of Aß plaque deposition. Notably, this probe can also be applied to measuring CTGF on postmortem brain sections by multimodal analysis, including fluorescence imaging, peroxidase-like chromogenic imaging, and ICP-MS quantitation, which enables distinguishment between the brains of AD patients and healthy people. This probe possesses great potential for precise diagnosis of earlier AD before Aß plaque formation.

Metabolomics reveals that ferroptosis participates in bisphenol A-induced testicular injury.

Objective: Bisphenol A (BPA) is a common environmental endocrine disruptor that negatively impairs male reproductive ability. This study aimed to explore the alterations in serum metabolomics that occur following BPA exposure and the mechanism via which BPA induces the death of testicular cells in a male mouse model. Methods: The mice were classified into two groups: BPA-exposed and control groups, and samples were collected for metabolomic determination, semen quality analysis, electron microscopy, enzyme-linked immunosorbent assay, quantitative real-time PCR, pathological staining, and Western blot analysis. Results: BPA exposure caused testicular damage and significantly decreased sperm quality in mice. Combined with non-target metabolomic analysis, this was closely related to ferroptosis induced by abnormal metabolites of arachidonic acid and phosphatidylcholine, and the expression of its related genes, acyl CoA synthetase 4, glutathione peroxidase 4, lysophosphatidylcholine acyltransferase 3, and phosphatidylethanolamine-binding protein 1 were altered. Conclusion: BPA induced ferroptosis, caused testicular damage, and reduced fertility by affecting lipid metabolism in male mice. Inhibiting ferroptosis may potentially function as a therapeutic strategy to mitigate the male reproductive toxicity induced by BPA.

Microvascular Decompression Using the Gelatin Sponge Insertion Technique for Trigeminal Neuralgia: A Retrospective Cohort Study.

BACKGROUND AND OBJECTIVES: Microvascular decompression (MVD) is the primary surgical intervention for trigeminal neuralgia (TN), with Teflon being the most conventional decompressing material. However, Teflon has been associated with adhesion and granulomas after MVD, which closely correlated with the recurrence of TN. Therefore, we developed a new technique to prevent direct contact between Teflon and nerve. The purpose of this study is to compare the efficacy of MVD using the gelatin sponge (GS) insertion technique with that of Teflon inserted alone in treating primary TN. METHODS: We retrospectively analyzed the medical records and the follow-up data of 734 patients with unilateral primary TN who underwent MVD at our center from January 2014 to December 2019. After exclusions, we identified 313 cases of GS-inserted MVD and 347 cases of traditional MVD. The follow-up exceeded 3 years. RESULTS: The operating time of the GS-inserted group was longer than that of the Teflon group (109.38 ± 14.77 vs 103.53 ± 16.02 minutes, P < .001). There was no difference between 2 groups in immediate surgical outcomes and postoperative complications. The yearly recurrence rate for GS-inserted MVD was lower at first (1.0%), second (1.2%), and third (1.2%) years after surgery, compared with its counterpart of Teflon group (3.7%, 2.9%, and 1.7% respectively). The first-year recurrence rate (P = .031) and total recurrence rate in 3 years (P = .013) was significantly lower in the GS-inserted group than Teflon group. Kaplan-Meier survival analysis demonstrated better outcomes in GS-inserted MVD groups (P = .020). CONCLUSION: The application of the GS insertion technique in MVD reduced first-year postoperative recurrence of TN, with similar complications rates compared with traditional MVD.

Surface nanocoating-based universal platform for programmed delivery of microorganisms in complicated digestive tract.

Microbial therapies have promising applications in the treatment of a broad range of diseases. However, effective colonization of the target region by therapeutic microorganisms remains a significant challenge owing to the complexity of the intestinal system. Here, we developed surface nanocoating-based universal platform (SNUP), which enabled the manipulation of controlled release and targeted colonization of therapeutic microbes in the digestive tract without the utilization of any targeting molecules. The system controlled the decomposition time of SNUP in the gut by regulating different modification layers and modification sequences on the microorganism's surface, so that the microorganism was released at a predetermined time and space. With the SNUP nanomodification technology, we could effectively deliver therapeutic microorganisms to specific complex intestinal regions such as the small intestine and colon, and protect the bioactivity of therapeutic microorganisms from destruction by both strong acids and digestive enzymes. In this study, we found that two layers SNUP-encapsulated Liiliilactobacillus salivarius (LS@CCMC) could efficiently colonize the small intestine and significantly improve the symptoms of a mouse model of Parkinson's disease through sustained secretion of γ-aminobutyric acid (GABA). This surface nanocoating-based universal platform system does not require the design of specific targeting molecules, providing a simple and universal method for colonized microbial therapy, target theranostics, precision medicine, and personalized medicine.

The transcription factor WRKY22 modulates ethylene biosynthesis and root development through transactivating the transcription of ACS5 and ACO5 in Arabidopsis.

The WRKY transcription factor (TF) genes form a large family in higher plants, with 72 members in Arabidopsis (Arabidopsis thaliana). The gaseous phytohormone ethylene (ET) regulates multiple physiological processes in plants. It is known that 1-aminocyclopropane-1-carboxylic acid (ACC) synthases (ACSs, EC 4.4.1.14) limit the enzymatic reaction rate of ethylene synthesis. However, whether WRKY TFs regulate the expression of ACSs and/or ACC oxidases (ACOs, EC 1.14.17.4) remains largely elusive. Here, we demonstrated that Arabidopsis WRKY22 positively regulated the expression of a few ACS and ACO genes, thus promoting ethylene production. Inducible overexpression of WRKY22 caused shorter hypocotyls without ACC treatment. A qRT-PCR screening demonstrated that overexpression of WRKY22 activates the expression of several ACS and ACO genes. The promoter regions of ACS5, ACS11, and ACO5 were also activated by WRKY22, which was revealed by a dual luciferase reporter assay. A follow-up chromatin immunoprecipitation coupled with quantitative PCR (ChIP-qPCR) and electrophoretic mobility shift assay (EMSA) showed that the promoter regions of ACS5 and ACO5 could be bound by WRKY22 directly. Moreover, wrky22 mutants had longer primary roots and more lateral roots than wild type, while WRKY22-overexpressing lines showed the opposite phenotype. In conclusion, this study revealed that WRKY22 acts as a novel TF activating, at least, the expression of ACS5 and ACO5 to increase ethylene synthesis and modulate root development.

Predictive model for assessing malnutrition in elderly hospitalized cancer patients: A machine learning approach.

BACKGROUND: Malnutrition is prevalent among elderly cancer patients. This study aims to develop a predictive model for malnutrition in hospitalized elderly cancer patients. METHODS: Data from January 2022 to January 2023 on cancer patients aged 60+ were collected, involving 22 variables. Key variables were identified using the LASSO (Least Absolute Shrinkage and Selection Operator) method, and nine machine learning models were tested. SHAP was used to interpret the XGBoost model. Malnutrition prevalence was assessed. RESULTS: Among 450 participants, 46.4 % were malnourished. Key predictors identified were ADL (Activities of Daily Living), ALB (Albumin), BMI (Body Mass Index) and age. XGBoost had the highest AUC of 0.945, accuracy of 0.872, and sensitivity of 0.968. Higher ADL and age increased malnutrition risk, while lower ALB and BMI reduced it. CONCLUSIONS: The XGBoost model is highly effective in detecting malnutrition in elderly cancer patients, enabling early and rapid nutritional assessments.

Targeted silencing of SOCS1 by DNMT1 promotes stemness of human liver cancer stem-like cells.

BACKGROUND: Human liver cancer stem-like cells (HLCSLCs) are widely acknowledged as significant factors in the recurrence and eradication of hepatocellular carcinoma (HCC). The sustenance of HLCSLCs' stemness is hypothesized to be intricately linked to the epigenetic process of DNA methylation modification of genes associated with anticancer properties. The present study aimed to elucidate the stemness-maintaining mechanism of HLCSLCs and provide a novel idea for the clearance of HLCSLCs. METHODS: The clinical relevance of DNMT1 and SOCS1 in hepatocellular carcinoma (HCC) patients was evaluated through the GEO and TCGA databases. Cellular immunofluorescence assay, methylation-specific PCR, chromatin immunoprecipitation were conducted to explore the expression of DNMT1 and SOCS1 and the regulatory relationship between them in HLCSLCs. Spheroid formation, soft agar colony formation, expression of stemness-associated molecules, and tumorigenicity of xenograft in nude mice were used to evaluate the stemness of HLCSLCs. RESULTS: The current analysis revealed a significant upregulation of DNMT1 and downregulation of SOCS1 in HCC tumor tissues compared to adjacent normal liver tissues. Furthermore, patients exhibiting an elevated DNMT1 expression or a reduced SOCS1 expression had low survival. This study illustrated the pronounced expression and activity of DNMT1 in HLCSLCs, which effectively targeted the promoter region of SOCS1 and induced hypermethylation, consequently suppressing the expression of SOCS1. Notably, the stemness of HLCSLCs was reduced upon treatment with DNMT1 inhibitors in a concentration-dependent manner. Additionally, the overexpression of SOCS1 in HLCSLCs significantly mitigated their stemness. The knockdown of SOCS1 expression reversed the effect of DNMT1 inhibitor on the stemness of HLCSLCs. DNMT1 directly binds to the SOCS1 promoter. In vivo, DNMT1 inhibitors suppressed SOCS1 expression and inhibited the growth of xenograft. CONCLUSION: DNMT1 targets the promoter region of SOCS1, induces hypermethylation of its CpG islands, and silences its expression, thereby promoting the stemness of HLCSLCs.

Comparative genomic sequencing to characterize Mycoplasma pneumoniae genome, typing, and drug resistance.

To analyze the characteristics of Mycoplasma pneumoniae as well as macrolide antibiotic resistance through whole-genome sequencing and comparative genomics. Thirteen clinical strains isolated from 2003 to 2019 were selected, 10 of which were resistant to erythromycin (MIC >64 µg/mL), including 8 P1-type I and 2 P1-type II. Three were sensitive (<1 µg/mL) and P1-type II. One resistant strain had an A→G point mutation at position 2064 in region V of the 23S rRNA, the others had it at position 2063, while the three sensitive strains had no mutation here. Genome assembly and comparative genome analysis revealed a high level of genome consistency within the P1 type, and the primary differences in genome sequences concentrated in the region encoding the P1 protein. In P1-type II strains, three specific gene mutations were identified: C162A and A430G in L4 gene and T1112G mutation in the CARDS gene. Clinical information showed seven cases were diagnosed with severe pneumonia, all of which were infected with drug-resistant strains. Notably, BS610A4 and CYM219A1 exhibited a gene multi-copy phenomenon and shared a conserved functional domain with the DUF31 protein family. Clinically, the patients had severe refractory pneumonia, with pleural effusion, necessitating treatment with glucocorticoids and bronchoalveolar lavage. The primary variations between strains occur among different P1-types, while there is a high level of genomic consistency within P1-types. Three mutation loci associated with specific types were identified, and no specific genetic alterations directly related to clinical presentation were observed.IMPORTANCEMycoplasma pneumoniae is an important pathogen of community-acquired pneumonia, and macrolide resistance brings difficulties to clinical treatment. We analyzed the characteristics of M. pneumoniae as well as macrolide antibiotic resistance through whole-genome sequencing and comparative genomics. The work addressed primary variations between strains that occur among different P1-types, while there is a high level of genomic consistency within P1-types. In P1-type II strains, three specific gene mutations were identified: C162A and A430G in L4 gene and T1112G mutation in the CARDS gene. All the strains isolated from severe pneumonia cases were drug-resistant, two of which exhibited a gene multi-copy phenomenon, sharing a conserved functional domain with the DUF31 protein family. Three mutation loci associated with specific types were identified, and no specific genetic alterations directly related to clinical presentation were observed.

Effect of compressive and tensile forces on glucose concentration and cell viability within the intervertebral disc: A finite element study.

Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.

FOXP4-mediated induction of PTK7 activates the Wnt/ß-catenin pathway and promotes ovarian cancer development.

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

Life disturbance and hospital visit experiences among Chinese patients with benign prostatic hyperplasia: a qualitative study.

BACKGROUND: The impact of lower urinary tract symptoms (LUTS) on the quality of life of patients with benign prostatic hyperplasia (BPH) has been rarely reported. Additionally, the challenges faced by these patients in seeking medical care have often been overlooked. In order to explore the personal struggles caused by LUTS and the difficulties or barriers experienced by Chinese patients with BPH when seeking help, we conducted a qualitative interview study. METHODS: Qualitative interviews were conducted among 46 patients with BPH who were hospitalized in three tertiary hospitals in China from July 2021 to November 2022. Grounded theory was adopted as the methodology for the qualitative study. After obtaining written informed consent from the study participants, semi-structured interviews were conducted according to the question guidelines. The interview process was audio-recorded; subsequently, the recordings were transcribed, coded, and thematically analyzed. RESULTS: The difficulties faced by Chinese patients with BPH were classified into seven main themes: (i) disturbed life, (ii) mental burden, (iii) disease cognition and communication, (iv) delayed treatment, (v) medication status, (vi) hospital visits barriers, and (vii) medical insurance issues. Further, each theme was subdivided into 2-5 sub-themes. CONCLUSIONS: LUTS have a certain effect on the life and spirit of patients with BPH. These patients face different degrees of difficulties in treatment and hospital visits. Therefore, better healthcare systems and additional social support are crucial for improving the current plight of these patients.

Rapeseed PP2C37 Interacts with PYR/PYL Abscisic Acid Receptors and Negatively Regulates Drought Tolerance.

Global water deficit is a severe abiotic stress threatening the yielding and quality of crops. Abscisic acid (ABA) is a phytohormone that mediates drought tolerance. Protein kinases and phosphatases function as molecular switches in eukaryotes. Protein phosphatases type 2C (PP2Cs) are a major family that play essential roles in ABA signaling and stress responses. However, the role and underlying mechanism of PP2C in rapeseed (Brassica napus L.) mediating drought response has not been reported yet. Here, we characterized a PP2C family member, BnaPP2C37, and its expression level was highly induced by ABA and dehydration treatments. It negatively regulates drought tolerance in rapeseed. We further identified that BnaPP2C37 interacted with multiple PYR/PYL receptors and a drought regulator BnaCPK5 (calcium-dependent protein kinase 5) through yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays. Specifically, BnaPYL1 and BnaPYL9 repress BnaPP2C37 phosphatase activity. Moreover, the pull-down assay and phosphatase assays show BnaPP2C37 interacts with BnaCPK5 to dephosphorylate BnaCPK5 and its downstream BnaABF3. Furthermore, a dual-luciferase assay revealed BnaPP2C37 transcript level was enhanced by BnaABF3 and BnaABF4, forming a negative feedback regulation to ABA response. In summary, we identified that BnaPP2C37 functions negatively in drought tolerance of rapeseed, and its phosphatase activity is repressed by BnaPYL1/9 whereas its transcriptional level is upregulated by BnaABF3/4.

HIF1A-dependent overexpression of MTFP1 promotes lung squamous cell carcinoma development by activating the glycolysis pathway.

Introduction: Mitochondrial fission process 1 (MTFP1) is an inner mitochondrial membrane (IMM) protein implicated in the development and progression of various tumors, particularly lung squamous cell carcinoma (LUSC). This study aims to provide a more theoretical basis for the treatment of LUSC. Methods: Through bioinformatics analysis, MTFP1 was identified as a novel target gene of HIF1A. MTFP1 expression in LUSC was examined using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Proteomics Data Commons (PDC) databases. The Kaplan-Meier plotter (KM plotter) database was utilized to evaluate its correlation with patient survival. Western blot and chromatin immunoprecipitation (ChIP) assays were employed to confirm the regulatory relationship between MTFP1 and HIF1A. Additionally, cell proliferation, colony formation, and migration assays were conducted to investigate the mechanism by which MTFP1 enhances LUSC cell proliferation and metastasis. Results: Our findings revealed that MTFP1 overexpression correlated with poor prognosis in LUSC patients(P < 0.05). Moreover, MTFP1 was closely associated with hypoxia and glycolysis in LUSC (R = 0.203; P < 0.001, R = 0.391; P < 0.001). HIF1A was identified as a positive regulator of MTFP1. Functional enrichment analysis demonstrated that MTFP1 played a role in controlling LUSC cell proliferation. Cell proliferation, colony formation, and migration assays indicated that MTFP1 promoted LUSC cell proliferation and metastasis by activating the glycolytic pathway (P < 0.05). Conclusions: This study establishes MTFP1 as a novel HIF1A target gene that promotes LUSC growth by activating the glycolytic pathway. Investigating MTFP1 may contribute to the development of effective therapies for LUSC patients, particularly those lacking targeted oncogene therapies.

Organ-Targeted Ionizable Lipid Nanoparticles Facilitate Sequence-Activated Fluorogenic Probe for Precise Imaging of Inflammatory Liver Disease.

Activatable near-infrared (NIR) fluorogenic probes offer a potent tool for real-time, in situ detection of hepatic biomarkers, significantly advancing the precision in diagnosing inflammatory liver disease (ILD). However, the limited distribution of small molecule fluorogenic probes in the liver and their rapid clearance impair the accuracy of fluorescence imaging and in ILD diagnosis. In this study, an effective utilization of ionizable lipid nanoparticles (iLNPs) is presented as liver-targeted carriers for efficient delivery of fluorogenic probes, aiming to overcome biodistribution barriers and achieve accurate detection of hepatic biomarkers. Based on this strategy, a liver-targeted NIR fluorogenic nanoprobe hCy-H2O2@iLNP is prepared using hCy-H2O2 as a small molecule reporter for visualizing the over-produced hydrogen peroxide (H2O2) in situ of liver. Notably, iLNPs not only significantly enhance probe accumulation in the liver, but also enable sequence activation of fluorescent nanoprobes. This response is achieved through primary liposome-dissociation release and secondary hCy-H2O2 response with pathological H2O2, enabling high-precision detection of oxidative stress in hepatocytes. These distinctive features facilitate accurate early diagnosis of acetaminophen (APAP)-induced inflammatory liver injury as well as lipopolysaccharide (LPS)-induced hepatitis. Therefore, the organ-targeted nanoprobe design strategy showcasts great potential for early and accurate diagnosis of lesions in situ in different organs.

Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo.

Nucleic acid therapeutics offer tremendous promise for addressing a wide range of common public health conditions. However, the in vivo nucleic acids delivery faces significant biological challenges. Lipid nanoparticles (LNPs) possess several advantages, such as simple preparation, high stability, efficient cellular uptake, endosome escape capabilities, etc., making them suitable for delivery vectors. However, the extensive hepatic accumulation of LNPs poses a challenge for successful development of LNPs-based nucleic acid therapeutics for extrahepatic diseases. To overcome this hurdle, researchers have been focusing on modifying the surface properties of LNPs to achieve precise delivery. The review aims to provide current insights into strategies for LNPs-based organ-selective nucleic acid delivery. In addition, it delves into the general design principles, targeting mechanisms, and clinical development of organ-selective LNPs. In conclusion, this review provides a comprehensive overview to provide guidance and valuable insights for further research and development of organ-selective nucleic acid delivery systems.