Characterization of GABAergic marker expression in prefrontal cortex in dexamethasone induced depression/anxiety model.

Background: The pivotal responsibility of GABAergic interneurons is inhibitory neurotransmission; in this way, their significance lies in regulating the maintenance of excitation/inhibition (E/I) balance in cortical circuits. An abundance of glucocorticoids (GCs) exposure results in a disorder of GABAergic interneurons in the prefrontal cortex (PFC); the relationship between this status and an enhanced vulnerability to neuropsychiatric ailments, like depression and anxiety, has been identified, but this connection is still poorly understood because systematic and comprehensive research is lacking. Here, we aim to investigate the impact of dexamethasone (DEX, a GC receptor agonist) on GABAergic interneurons in the PFC of eight-week-old adult male mice. Methods: A double-blind study was conducted where thirty-two mice were treated subcutaneously either saline or DEX (0.2 mg/10 ml per kg of body weight) dissolved in saline daily for 21 days. Weight measurements were taken at five-day intervals to assess the emotional changes in mice as well as the response to DEX treatment. Following the 21-day regimen of DEX injections, mice underwent examinations for depression/anxiety-like behaviours and GABAergic marker expression in PFC. Results: In a depression/anxiety model generated by chronic DEX treatment, we found that our DEX procedure did trigger depression/anxiety-like behaviors in mice. Furthermore, DEX treatment reduced the expression levels of a GABA-synthesizing enzyme (GAD67), Reelin, calcium-binding proteins (parvalbumin and calretinin) and neuropeptides co-expressed in GABAergic neurons (somatostatin, neuropeptide Y and vasoactive intestinal peptide) in the PFC were reduced after 21 days of DEX treatment; these reductions were accompanied by decreases in brain size and cerebral cortex thickness. Conclusion: Our results indicate that a reduction in the number of GABAergic interneurons may result in deficiencies in cortical inhibitory neurotransmission, potentially causing an E/I imbalance in the PFC; this insight suggests a potential breakthrough strategy for the treatment of depression and anxiety.

PD-1+CD8+ T Cell-Mediated Hepatocyte Pyroptosis Promotes Progression of Murine Autoimmune Liver Disease.

The specific mechanisms underlying effector pathways in autoimmune liver disease remain enigmatic and therefore constructing appropriate murine models to investigate disease pathogenesis becomes critical. A spontaneous severe murine model of autoimmune liver disease has been previously established in dnTGFßRII Aire-/- mice, exhibiting disease phenotypes that resemble both human primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH). The data suggests that auto-reactive liver-specific CD8+ T cells are the primary pathogenic cells in liver injury. In this study, these data are advanced through the use of both single-cell sequencing and extensive in vitro analysis. The results identify a specific expanded pathogenic subset of PD-1+CD8+ T cells in the liver, exhibiting strong functional activity and cytotoxicity against target cells. Depletion of PD-1+CD8+ T cells using CAR-T cells effectively alleviates the disease. GSDMD-mediated pyroptosis is found to be aberrantly activated in the livers of model mice, and treatment with a GSDMD-specific inhibitor significantly inhibits disease progression. In vitro experiments reveal that PD-1+CD8+ T cells can induce the pyroptosis of hepatocytes through elevated production of granzyme B and perforin-1. These results provide a novel explanation for the cytotoxic activity of pathogenic liver PD-1+CD8+ T cells in autoimmune liver diseases and offer potential therapeutic targets.

Long-Term Subjective Efficacy of Female Stress Urinary Incontinence with Tension-Free Vaginal Tape-Obturator Technique.

INTRODUCTION AND HYPOTHESIS: The objective was to evaluate the long-term subjective efficacy of the tension-free vaginal tape-obturator (TVT-O) technique in the treatment of female stress urinary incontinence (SUI). METHODS: A retrospective analysis was performed on 84 patients who underwent TVT-O surgery for SUI in a tertiary center between January 2007 and December 2013. All patients filled in the Urinary Incontinence Quality of Life Questionnaire (I-QOL), the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire short form (PISQ-12). Subjective efficacy, including surgical efficacy, clinical severity of SUI, improvement in quality of life (QoL), and sexual activity with regard to TVT-O were compared before and after surgery (≥ 10 years). RESULTS: The average postoperative follow-up time was 12.6 ± 1.9 years, range, 10-16 years. The overall subjective effectiveness of the surgery was 94.0% (79 out of 84). The subjective clinical severity significantly improved more than 10 years after surgery compared with the preoperative value (p = 0.000). The median I-QOL score was 88.1 (84.1-92.0) preoperatively and 98.3 (94.3-99.7) postoperatively, and the long-term QoL of postoperative patients was significantly improved (p < 0.05). The median ICIQ-SF score was 10.5 (8-15) preoperatively, and 3 (0-5) postoperatively, and the ICIQ-SF score before and after surgery showed significant improvement in urinary incontinence symptoms (p < 0.05). No difference was observed in the PISQ-12 scores before and after surgery in the sexually active population. CONCLUSIONS: The TVT-O technique still has good subjective efficacy in SUI more than 10 years after surgery and significantly improves the QoL of patients.

Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a retrospective study.

BACKGROUND: Dyslipidemia is prominently associated with adverse outcomes in patients with coronary artery disease (CAD). The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel comprehensive lipid index. However, limited evidence exists on the relationship of the NHHR with the risk of adverse outcomes in patients with CAD. This study aimed to explore the associations between the NHHR and adverse outcomes and identify the optimal NHHR ranges linked to the lowest adverse outcome risk in patients with CAD undergoing percutaneous coronary intervention (PCI). METHODS: Among 2253 patients with CAD undergoing PCI, 2251 with available total cholesterol and HDL-C levels were analyzed. Furthermore, all patients were classified into quintiles based on the NHHR. The primary outcome was the incidence of MACCEs, comprising cardiac mortality, acute myocardial infarction, stroke, and repeat revascularization. Multivariable logistic regression analysis was used to assess the relationship between the NHHR and MACCEs. Moreover, restricted cubic spline (RCS) analysis was performed to quantify nonlinearity. Lastly, the consistency between these associations was confirmed by conducting subgroup and interaction analyses. RESULTS: A total of 270 patients experienced MACCEs over a median follow-up of 29.8 months (interquartile range, 25.6-34 months). After adjustment for confounding variables, the adjusted ORs (95% CIs) of the patients in quintiles 2, 3, 4, and 5 were 0.79 (0.52-1.20), 0.64 (0.42-0.99), 1.00 (0.67-1.48), and 1.17 (0.74-1.64), respectively (reference group: quintile 1). Additionally, RCS analysis demonstrated a U-shaped relationship between the NHHR and MACCEs, with an inflection point at an NHHR of 3.119 using a two-piecewise regression model. This relationship was consistent across the various subgroups, while significant interactions were not observed in these associations.The ORs and 95% CIs to the left and right of the inflection point were 0.734 (0.551-0.978) and 1.231 (1.038-1.460), respectively. CONCLUSIONS: This study reveals a U-shaped association between baseline NHHR and MACCE incidence in patients with CAD undergoing PCI.

Photoredox/HAT-Catalyzed Intramolecular Hydrocyclization of Alkenes toward 2,3-Fused Quinazolinones and Dihydroquinazolinones.

New photochemical approaches to 2,3-fused quinazolinones and dihydroquinazolinones are disclosed. The intramolecular hydrocyclization proceeds in moderate to excellent yields across diverse alkenes with high regioselectivity and diastereocontrol. Mechanistic studies indicated that the radical cascade processes involve thiophenol acting as single-electron transfer and hydrogen atom transfer reagents. The success of the gram-scale synthesis proves the strategy can be used for practical applications.

Transcriptomic and Proteomic Analyses of the Immune Mechanism in Pathogenetic and Resistant Chinese Soft-Shelled Turtle (Pelodiscus sinensis) Infected with Aeromonas hydrophila.

BACKGROUND: As intensive aquaculture practices have progressed, the prevalence of bacterial diseases in the Chinese soft-shell turtle (Pelodiscus sinensis) has escalated, particularly infections caused by Aeromonas hydrophila, such as ulcerative dermatitis and abscess disease. Despite this, little is known about their immune defenses against this pathogen. METHODS: Our study pioneers an integrated analysis of transcriptomics and proteomics to investigate the immune responses of Chinese soft-shelled turtles to A. hydrophila infection. RESULTS: The investigation revealed significant differences in immune-related pathways between groups susceptible and resistant to A. hydrophila infection after 4 days. A total of 4667 and 3417 differentially expressed genes (DEGs), 763 and 568 differentially expressed proteins (DEPs), and 13 and 5 correlated differentially expressed genes and proteins (cor-DEGs-DEPs) were identified in susceptible and resistant Chinese soft-shelled turtles, respectively. In the resistant group, upregulation of immune-related genes, such as CD3ε and CD45, enhanced T-cell activation and the immune response. The proteomic analysis indicated that immune proteins, such as NF-κB1, were significantly upregulated in the resistant group. The correlation analysis between transcriptomics and proteomics demonstrated that the CD40 gene and protein, differentially expressed in the resistant group compared to the control group, were commonly upregulated within the Toll-like receptor signaling pathway. CONCLUSIONS: The transcriptomic and proteomic data obtained from this study provide a scientific foundation for understanding the immune mechanisms that enable the Chinese soft-shelled turtle to resist A. hydrophila infection.

The synergistic effects of anoikis-related genes and EMT-related genes in the prognostic prediction of Wilms tumor.

Wilms tumor (WT) is the most common type of malignant abdominal tumor in children; it exhibits a high degree of malignancy, grow rapidly, and is prone to metastasis. This study aimed to construct a prognosis model based on anoikis-related genes (ARGs) and epithelial-mesenchymal transition (EMT)-related genes (ERGs) for WT patients; we assessed the characteristics of the tumor microenvironment and treatment efficacy, as well as identifying potential therapeutic targets. To this end, we downloaded transcriptome sequencing data and clinical data for WT and normal renal cortices and used R to construct and validate the prognostic model based on ARGs and ERGs. Additionally, we performed clinical feature analysis, nomogram construction, mutation analysis, drug sensitivity analysis, Connectivity Map (cMAP) analysis, functional enrichment analysis, and immune infiltration analysis. Finally, we screened the hub gene using the STRING database and validated it via experiments. In this way, we constructed a model with good accuracy and robustness, which was composed of seven anoikis- and EMT-related genes. Paclitaxel and mesna were selected as potential chemotherapeutic drugs and adjuvant chemotherapeutic drugs for the WT high-risk group by using the Genomics of Drug Sensitivity in Cancer (GDSC) and cMAP compound libraries, respectively. We proved the existence of a strong correlation between invasive immune cells and prognostic genes and risk scores. Next, we selected NTRK2 as the hub gene, and in vitro experiments confirmed that its inhibition can significantly inhibit the proliferation and migration of tumor cells and promote late apoptosis. In summary, we screened out the potential biomarkers and chemotherapeutic drugs that can improve the prognosis of patients with WT.

Research Progress of Chinese Medicine Monomers in Treatment of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.

Transfer of pesticides and metabolites in corn: Production, processing, and livestock dietary burden.

Corn stover is widely used in livestock feed but has received limited attention regarding its potential risks. In this study, pesticide residues were monitored across 12 provinces in China, and terminal residues of four pesticides, chlorantraniliprole, thiamethoxam, epoxiconazole, and pyraclostrobin, were tested. In addition, the silage processing experiment was conducted. All processing factors (PF) were <1, indicating pesticide degradation. The physicochemical properties of pesticides, especially log P, were related to degradation efficiency. Pesticides with higher log P values showed higher PFs (0.43 to 0.85), indicating lower degradation efficiency. The dietary burden of livestock before and after silage processing was calculated using OECD livestock dietary burden calculator. Results showed that after silage fermentation, the dietary burden was reduced by 28.8 % to 79.2 %. Throughout the entire production and processing process, the fastest degradation of all pesticides in whole corn was primarily observed from the pesticide application time to the harvest time, with some pesticides also showing accelerated degradation during subsequent processing stages. Therefore, in actual production, especially for pesticides which are difficult to degrade, appropriate extension of the safety interval or selection of suitable processing methods can be taken to further reduce pesticide residues in agricultural products.

Enhanced Accumulation of Health-Promoting Cajaninstilbene Acid in Pigeon Pea Hairy Root Cultures Cocultured with an Endophytic Fungus during Early Stages of Colonization.

Endophytic fungi can effectively regulate the biosynthesis of health-beneficial metabolites in plants. However, few studies have revealed how the accumulation of host metabolites varies during interactions with endophytic fungi. Here, pigeon pea hairy root cultures (PPHRCs) were cocultured with an endophytic fungus Penicillium rubens to explore the impact on the biosynthesis and accumulation of cajaninstilbene acid (CSA). The results showed that CSA accumulation in PPHRCs increased significantly (15.29-fold) during the early stages of P. rubens colonization (fungal attachment and invasion phases). Once P. rubens successfully colonized the intercellular gap of hairy roots to form a symbiotic relationship, the CSA levels in PPHRCs decreased drastically. Moreover, P. rubens could be recognized by plant pattern recognition receptors that regulate immunity/symbiosis, triggering the expression of genes related to pathogenesis, CSA biosynthesis, and ABC transporter. Overall, P. rubens could enhance the accumulation of health-promoting CSA in PPHRCs during the early stages of colonization.

Maize DLR1/NHX7 Is Required for Root Development Under Potassium Deficiency.

Root System Architecture (RSA) is a crucial plant trait that governs a plant's ability to absorb water and nutrients. In this study, we describe a mutant with nutrient-dependent defects in root development, affecting both the primary root and lateral roots (LRs). This mutant, identified through a screen for defects in LR development, has been designated dlr1-1. The dlr1-1 mutant exhibits impaired LR emergence rather than defects in the LR primordium (LRP) formation, particularly under potassium (K+)-deprivation conditions. This impairment likely stems from inhibited cell proliferation caused by the dlr1-1 mutation. K+ deprivation specifically leads to the accumulation of salicylic acid (SA) in the dlr1-1 mutant, consistent with the upregulation of SA biosynthesis genes. Moreover, exogenous application of SA to wild-type plants (B73) mimics the dlr1-1 phenotype. Conversely, treatment of the dlr1-1 mutant with 2-aminoindane-2-phosphonic acid, an SA biosynthesis inhibitor, partially restores LR emergence, indicating that elevated SA levels may be responsible for the mutant's developmental defects. MutMap analysis and allelism tests confirmed that the phenotypes of the dlr1-1 mutant results from the loss of the Na+/H+ antiporter, ZmNHX7. Additionally, the application of NaCl exacerbates the dlr1-1 mutant phenotype, suggesting that the root defects in dlr1-1 mutant depend on ion homoeostasis. In conclusion, our findings demonstrate that maize DLR1/NHX7 is essential for root development under potassium deprivation.

Fine-Grain High-Performance Densified Oxide Fibers Produced by Open Ultrafast High-Temperature Sintering.

The considerable grain growth occurring during the long-term high-temperature sintering of polycrystalline oxide fibers negatively affects their mechanical properties, which highlights the need for alternative sintering methods. Herein, open ultrafast high-temperature sintering (OUHS) in air, characterized by rapid heating/cooling (>10000 K min-1) and a short high-temperature holding time (<10 s), is used to produce 3 mol% yttria-stabilized zirconia continuous fibers with coherent boundaries forming robust connections between fine grains. The tensile strength of these fibers (2.33 GPa on average, sintering temperature = 1673 K) notably exceeds that of their counterparts produced by traditional sintering (1.17 GPa). The effects of pores on fiber mechanical properties are analyzed using experimental and theoretical methods. For a versatility demonstration, OUHS is applied to several types of polycrystalline oxide fibers (HfO2, Al2O3, TiO2, Y2O3, and La2Zr2O7), considerably improving their mechanical properties and enabling crystalline phase control, which demonstrates the suitability of this procedure for the development of high-performance materials.

Hydrogel-based formulations for urothelial cancer therapy.

Drug infusion therapy after surgery for urothelial carcinoma is an effective measure to reduce cancer recurrence rate. Hydrogels are drug carriers with good biocompatibility and high drug loading capacity, which can optimize the pharmacokinetics of drugs in the urinary system to improve the therapeutic effect. Compared with the traditional free drug in situ perfusion, the hydrogel drug loading system can still maintain effective drug concentration in the face of continuous urinary flushing due to its good mucosal adhesion effect. The significantly prolonged drug retention time can not only improve the therapeutic effect of drugs, but also reduce the discomfort and risk of urinary tract infections caused by frequent drug infusion, and improve patient compliance. In addition, the combination of hydrogel with nanoparticles and magnetic materials can also improve the mucosal permeability and targeting effect of the hydrogel drug loading system, so as to overcome the mucus layer of urinary epithelium and the physiological barrier of tumor and minimize the impact on normal tissue and cell functions. At present, the research of hydrogels for urothelial cancer treatment involves chemotherapy, immunotherapy, gene therapy, inhibition of metabolism and multi strategy synergistic therapy. This review summarizes the research progress of hydrogels for the treatment of urothelial carcinoma, hoping to provide a reference for the future research of safe, reliable, effective, and advanced hydrogels with little side effects.

Biomarkers of lymph node metastasis in esophageal cancer.

Esophageal cancer (EC) is among the most aggressive malignancies, ranking as the seventh most prevalent malignant tumor worldwide. Lymph node metastasis (LNM) indicates localized spread of cancer and often correlates with a poorer prognosis, emphasizing the necessity for neoadjuvant systemic therapy before surgery. However, accurate identification of LNM in EC presents challenges due to the lack of satisfactory diagnostic techniques. Imaging techniques, including ultrasound and computerized tomography scans, have low sensitivity and accuracy in assessing LNM. Additionally, the existing serological detection lacks precise biomarkers. The intricate and not fully understood molecular processes involved in LNM of EC contribute to current detective limitations. Recent research has shown potential in using various molecules, circulating tumor cells (CTCs), and changes in the microbiota to identify LNM in individuals with EC. Through summarizing potential biomarkers associated with LNM in EC and organizing the underlying mechanisms involved, this review aims to provide insights that facilitate biomarker development, enhance our understanding of the underlying mechanisms, and ultimately address the diagnostic challenges of LNM in clinical practice.

Proteomic Analysis Provides a New Sight Into the CRABP1 Expression in the Pathogenesis of Hirschsprung Disease.

Hirschsprung's disease (HSCR) is the most common developmental disorder of the enteric nervous system and its etiology and pathogenesis remain largely unknown. This study aims to identify the differential proteomic patterns linked to the occurrence and development of Hirschsprung disease in colonic tissues. Biopsies were obtained from the aganglionic colon in human HSCR and the corresponding ganglionic colon segments for direct quantitative determination of the data-independent acquisition (DIA) followed by bioinformatics analysis. The differentially expressed main proteins were confirmed by Western blot and immunostaining. A total of 5832 proteins were identified in human colon tissues. Among them, 97 differentially expressed proteins (DEP) with fold change (FC) > 1.2 were screened, including 18 upregulated proteins and 79 downregulated proteins, and GO and KEGG enrichment analyses were performed on differential proteins. By comparing down-regulated proteins with highly connected protein nodes in the PPI network with those related to intracellular metabolic processes in the above analysis, we identified cellular retinoic acid binding protein 1(CRABP1). Its expression was verified in the aganglionic part of the colon by western blotting in an expanded sample set (P = 0.0031). The immunostaining results revealed that CRABP1 was highly expressed in the myenteric plexus ganglion in ganglionic colons compared to aganglionic segments (P = 0.0004). This study demonstrated the down-regulation of CRABP1 in the aganglionic hindgut of HSCR, which could provide potential markers or promising new candidate actors for the pathogenesis of HSCR.

Investigating the impact of long-term bristlegrass coverage on rhizosphere microbiota, soil metabolites, and carbon-nitrogen dynamics for pear agronomic traits in orchards.

Background: Grass coverage (GC) under no-tillage systems in orchards signifcantly infuences underground carbon (C) and nitrogen (N) sequestration, primarily through promoting mineral nutrient utilization by rhizospheric microorganisms. However, the comprehensive impact of GC on microbial communities and plant responses using soil metabolomics remains inadequately recognized. Methods: We investigated two rhizosphere types established since 2002: bristlegrass (Setaria viridis (L.) P. Beauv.) coverage (SC) and clean cultivation (CC) to assess their efects on soil parameters, enzyme activities, and key pear agronomic traits, including yield (single fruit weight (SFW)) and qualities (soluble solids content (SSC), and total soluble sugar (TSS)). We combined microbiological analysis (16S rRNA sequencing) and non-targeted metabolomics (UPLC-MS/MS and GC-MS) to explore how microbial communities infuence fruit agronomic traits and soil nutrient dynamics in pear orchards under SC conditions. Results: Our fndings indicate that SC signifcantly enhances soil organic carbon (SOC), soil organic nitrogen (SON), the C:N ratio, and available nitrogen (AN). Moreover, SC leads to pronounced increases in soil enzyme activities involved in the C cycle and storage, including soil sucrase, ß-glucosidase, polyphenol oxidase and cellulase. Microbiome analysis revealed substantial diferences in microbial community composition and diversity indices between SC and CC rhizosphere soils within the 0-40 cm depth. Metabolomic analysis demonstrated significant alterations in metabolite profiles across both the 0-20 cm and 20-40 cm layers under SC conditions. The identifed metabolites primarily involve sugar and amino acid-related metabolic pathways, refecting perturbations in C and N metabolism consistent with shifts in bacterial community structure. Several plant growth-promoting rhizobacteria (PGPRs) taxa (e.g., Haliangium, Bacteroides, mle1-7, Subgroup_22, Ellin6067, MND1, Flavobacterium, and Cellvibrio) were enriched under SC, associated with metabolites such as sucrose, N-acetyl-D-glucosamine, N-acetyl-L-glutamic acid, rhamnose, UDP-GlcNAc and D-maltose. These fndings suggest their roles in promoting C and N sequestration processes through sucrose synthesis and glycolytic pathways in the soil, which was signifcantly correlated with the formation of agronomic traits such as fruit yield, SFW SSC and TSS (p<0.05), and SC treatments signifcantly increased yields by 35.40-62.72% and sucrose content in TSS by 2.43-3.96 times than CC treatments. Conclusion: This study provides valuable insights into the efects of SC on soil microbial communities and plant physiology, enhancing our understanding of their implications for sustainable orchard management.

Arabidopsis pentatricopeptide repeat protein GEND2 participates in mitochondrial RNA editing.

In Arabidopsis, RNA editing alters more than 500 cytidines (C) to uridines (U) in mitochondrial transcripts, a process involving the family of pentatricopeptide repeat (PPR) proteins. Here, we report a previously uncharacterized mitochondrial PLS-type PPR protein, GEND2, which functions in the mitochondrial RNA editing. The T-DNA insertion in the 5'-untranslated region of GEND2, referred to as gend2-1, results in defective root development compared to wild-type (WT) plants. A comprehensive examination of mitochondrial RNA editing sites revealed a significant reduction in the gend2-1 mutant compared to WT plants, affecting six specific mitochondrial RNA editing sites, notably within the mitochondrial genes CcmFn-1, RPSL2 and ORFX. These genes encode critical components of cytochrome protein maturation pathway, mitochondrial ribosomal subunit, and twin arginine translocation subunits, respectively. Further analysis of the transcriptional profile of the gend2-1 mutant and wild type revealed a striking induction of expression in a cluster of genes associated with mitochondrial dysfunction and regulated by ANAC017, a key regulator coordinating organelle functions and stress responses. Intriguingly, the gend2-1 mutation activated an ANAC017-dependent signaling aimed at countering cell wall damage induced by cellulose synthase inhibitors, as well as an ANAC017-independent pathway that retarded root growth under normal condition. Collectively, our findings identify a novel mitochondrial PLS-type PPR protein GEND2, which participates in the editing of six specific mitochondrial RNA editing sites. Furthermore, the gend2-1 mutation triggers two distinct pathways in plants: an ANAC017-dependent pathway and ANAC017-independent pathway.

Clinical multi-dimensional prognostic nomogram for predicting the efficacy of immunotherapy in NSCLC.

The advent of immunotherapy has greatly improved the prognosis of non-small cell lung (NSCLC) patients. However, given its low response rate and high cost of treatment, the search for valuable predictive markers of treatment efficacy is necessary. Considering the complexity and heterogeneity of the tumour and tumour microenvironment, the construction of a multi-dimensional prediction model is necessary. Therefore, we aimed to integrate clinical parameters, radiomic features, and immune signature data from NSCLC patients receiving immunotherapy to construct a multi-dimensional prediction model to better predict the efficacy of immunotherapy. The current study enrolled 137 NSCLC patients who received immunotherapy. We collected baseline clinical information, CT images, and tumour tissue specimens. Using 3D-Slicer software, radiomic features were extracted from patient CT images, and tumor tissue samples obtained before immunotherapy were subjected to immunohistochemical staining. Then, the least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to downscale the data, and the radiomic features and immune signatures associated with the prognosis of immunotherapy patients were identified. The modified lung immune predictive index (mLIPI), radiomics score (Radioscore), immune score and multi-dimensional model nomogram were constructed. The C-index and area under the curve (AUC) were applied to evaluate the predictive efficacy of the models. Three radiomic features and three immune signatures that could predict the efficacy of immunotherapy were eventually screened. Multivariate analysis showed that the mLIPI, Radioscore, and immune score were independent predictive factors for PFS and OS (P < 0.05 for all models). The multi-dimensional model combining the three models showed better predictive efficacy than the mLIPI, Radioscore, and immune score (PFS: 0.721 vs. 0.662 vs. 0.610 vs. 0.610; OS: 0.727 vs. 0.661 vs. 0.601 vs. 0.602 respectively). The multi-dimensional model showed the best predictive efficacy, with C-index for PFS and OS higher than mLIPI, radioscore and immune score: 0.721 vs. 0.662 vs. 0.610 vs. 0.610 for PFS and 0.727 vs. 0.661 vs. 0.601 vs. 0.602 for OS, respectively. The AUC for the multi-dimensional model also performed better than those of the individual models: 0.771 vs. 0.684 vs. 0.715 vs. 0.711 for PFS and 0.768 vs. 0.662 vs. 0.661 vs. 0.658 for OS, respectively. The multi-dimensional model combining the three models had better predictive efficacy than any single model and was more likely to help provide patients personalized and precision medicine.

Multiple Primary Cavernous Hemangiomas of the Skull.

Multiple primary cavernous hemangiomas of the skull are exceedingly rare, with surgery often being the treatment of choice. The complexity of radiologic diagnosis means that the identification of these hemangiomas still largely depends on pathologic analysis. This article outlines the diagnostic and therapeutic journey of a 52-year-old female patient afflicted with multiple primary cavernous hemangiomas of the skull. Although the occurrence of multiple cavernous hemangiomas in this patient may seem fortuitous, the authors aim to contribute to understanding the pathogenesis of such conditions through this case report.