Clinicopathological factors correlated with lymph node metastasis in gastric cancer: A retrospective cohort study involving 5606 patients.

BACKGROUND: The identification of risk factors associated with lymph node metastasis (LNM) in gastric cancer will establish a crucial foundation for the implementation of endoscopic operation and multidisciplinary treatment program. METHODS: 5606 gastric cancer patients with comprehensive clinicopathological data were enrolled through systematic searching and rigorous screening. Of the 5606 patients, 1438 were diagnosed with early gastric cancer (EGC), which would be utilized for further analysis. Subsequently, univariate and multivariate logistic regression analyses were conducted to identified the risk factors. RESULTS: The rates of LNM in T1a, T1b, T2, T3, T4a, and T4b stage gastric cancer were 7.0%, 19.4%, 48.4%, 77.1%, 83.8%, and 89.6% respectively. Female [odds ratio (OR)=1.559, P=0.032], lower tumor location (OR=1.773, P=0.023), tumor size >2cm (OR=2.007, P<0.001), mixed (OR=2.371, P=0.001) and undifferentiated histological types (OR=2.952, P<0.001), T1b stage (OR=2.041, P<0.001), presence of ulceration (OR=1.758, P=0.027), and lymphovascular invasion (LVI) (OR=5.722, P<0.001) were identified as independent risk factors for LNM in EGC. A nomogram was constructed using appropriate predictors to preoperatively predict the risk of LNM in EGC cases. CONCLUSIONS: This study identified the clinicopathological factors associated with LNM in EGC and developed a prediction model, thereby facilitating the integration of diverse treatment modalities in managing EGC patients.

Nanomaterials in modulating tumor-associated macrophages and enhancing immunotherapy.

Tumor-associated macrophages (TAMs) are predominantly present in the tumor microenvironment (TME) and play a crucial role in shaping the efficacy of tumor immunotherapy. These TAMs primarily exhibit a tumor-promoting M2-like phenotype, which is associated with the suppression of immune responses and facilitation of tumor progression. Interestingly, recent research has highlighted the potential of repolarizing TAMs from an M2 to a pro-inflammatory M1 status-a shift that has shown promise in impeding tumor growth and enhancing immune responsiveness. This concept is particularly intriguing as it offers a new dimension to cancer therapy by targeting the tumor microenvironment, which is a significant departure from traditional approaches that focus solely on tumor cells. However, the clinical application of TAM-modulating agents is often challenged by issues such as insufficient tumor accumulation and off-target effects, limiting their effectiveness and safety. In this regard, nanomaterials have emerged as a novel solution. They serve a dual role: as delivery vehicles that can enhance the accumulation of therapeutic agents in the tumor site and as TAM-modulators. This dual functionality of nanomaterials is a significant advancement as it addresses the key limitations of current TAM-modulating strategies and opens up new avenues for more efficient and targeted therapies. This review provides a comprehensive overview of the latest mechanisms and strategies involving nanomaterials in modulating macrophage polarization within the TME. It delves into the intricate interactions between nanomaterials and macrophages, elucidating how these interactions can be exploited to drive macrophage polarization towards a phenotype that is more conducive to anti-tumor immunity. Additionally, the review explores the burgeoning field of TAM-associated nanomedicines in combination with tumor immunotherapy. This combination approach is particularly promising as it leverages the strengths of both nanomedicine and immunotherapy, potentially leading to synergistic effects in combating cancer.

Integration of single-nucleus and exosome RNA sequencing dissected inter-cellular communication and biomarkers in pancreatic ductal adenocarcinoma.

Background: Mounting evidence underscores the importance of cell communication within the tumor microenvironment, which is pivotal in tumor proliferation, invasion, and metastasis. Exosomes play a crucial role in cell-to-cell communication. Although single-cell RNA sequencing (scRNA-seq) provides insights into individual cell transcriptional characteristics, it falls short of comprehensively capturing exosome-mediated intercellular communication. Method: We analyzed Pancreatic Ductal Adenocarcinoma (PDAC) tissues, separating supernatant and precipitate for exosome purification and single-cell nucleus suspension. We then constructed Single-nucleus RNA sequencing (snRNA-seq) and small RNA-seq libraries from these components. Our bioinformatic analysis integrated these sequences with ligand-receptor analysis and public miRNA data to map the cell communication network. Results: We established intercellular communication networks using bioinformatic analysis to track exosome miRNA effects and ligand-receptor pairs. Significantly, hsa-miR-1293 emerged as a prognostic biomarker for pancreatic cancer, linked to immune evasion, increased myeloid-derived suppressor cells, and poorer prognosis. Targeting this miRNA may enhance anti-tumor immunity and improve outcomes. Conclusion: Our study offers a novel approach to constructing intercellular communication networks using snRNA-seq and exosome-small RNA sequencing. By integrating miRNA tracing with ligand-receptor analysis, we illuminate the complex interactions in the pancreatic cancer microenvironment, highlighting the pivotal role of miRNAs and identifying potential biomarkers and therapeutic targets.

Risk factors associated with lymph node metastasis in early-stage distal gastric cancer.

OBJECTS: This study was designed to explore the risk factors of lymph node metastasis (LNM) in distal gastric cancer with early stage, and to provide reference for the choice of treatment protocols. METHODS: In this retrospective observational study, 824 early distal gastric cancer (EDGC) cases who treated at our unit from 2010 to 2020 were selected as research objects. Subsequently, univariate and multivariate logistic regression analyses were conducted to investigate the associations between LNM and clinicopathological features. RESULTS: Of these 824 EDGC cases, 140 (17.0%) developed LNM, including 72 N1 stage and 68 N2-3 stage LNM. Multivariate logistic regression analysis identified the tumor diameter ≥1.75 cm (odds ratio (OR) = 2.361, p < 0.001), tumor location (OR = 1.552, p = 0.046), histological classification (p = 0.004), tumor infiltration depth (OR = 2.154, p = 0.001), and vascular infiltration (OR = 4.354, p < 0.001) as independent predictors for LNM. Logistic regression analyses based on 756 N0-1 LNM cases identified the smoking history (OR = 0.507, p = 0.043), tumor diameter ≥1.75 cm (OR = 2.265, p = 0.010), tumor location (OR = 1.834, p = 0.036), histological classification (p = 0.018), tumor infiltration depth (OR = 1.939, p = 0.034), and vascular infiltration (OR = 3.225, p < 0.001) as independent predictors for N1 LNM. Moreover, preoperative hypoalbuminemia (OR = 7.087, p = 0.015), significant preoperative weight loss (OR = 2.724, p = 0.023), tumor diameter ≥1.75 cm (OR = 5.484, p = 0.001), multiple tumors (OR = 9.986, p = 0.038), histological classification (p = 0.029), and vascular infiltration (OR = 33.704, p < 0.001) were proved to be associated with LNM for T1a tumors. CONCLUSIONS: The tumor diameter, location and infiltration depth, histological classification, and vascular infiltration were expected to be used as predictors of LNM in EDGC, and preoperative hypoalbuminemia, significant weight loss, tumor diameter and number, histological classification, and vascular infiltration were associated with LNM for T1a tumors.

Casein hydrolysate in naturally-fermented buckwheat sourdough: Effects on fermented and physicochemical characteristics, texture, and bacterial microbial composition.

The effect of a casein hydrolysate (CH) on the fermentation and quality of a naturally-fermented buckwheat sourdough (NFBS) were investigated, through assessing the fermentation characteristics, carbohydrate and protein degradation, texture, and bacterial composition of NFBS. According to the assaying data, CH might both increase the amount of lactic acid bacteria by 2.62 % and shorten the fermentation period by at least 3 h, subsequently leading to enhanced degradation of carbohydrate and protein, accompanied by a softer texture. More importantly, CH increased the relative abundance of lactobacillus in NFBS, making it the dominant bacterial genus and inhibited the growth of spoilage bacteria. In addition, Spearman correlation analysis indicated that the pH value, lactic and acetic acid contents, carbohydrates, protease activity, and these textural indices like hardness, elasticity, and adhesion had a positive/negative correlation with the bacterial composition of NFBS (Spearman correlation coefficient: -0.93-0.95). CH was thus regarded to be helpful to NFBS processing and production mainly by shortening its fermentation time, improving its fermentation performance, causing a finer texture and microstructure, and changing bacterial composition.

Unveiling the Dissolution Regularities of the Lignin-Carbohydrate Complex in Bamboo Cell Walls during Alkali Pretreatment.

Bamboo is a promising biomass resource. However, the complex multilayered structure and chemical composition of bamboo cell walls create a unique anti-depolymerization barrier, which increases the difficulty of separation and utilization of bamboo. In this study, the relationship between the connections of lignin-carbohydrate complexes (LCCs) within bamboo cell walls and their multilayered structural compositions was investigated. The chemical composition, structural properties, dissolution processes, and migration mechanisms of LCCs were analyzed. Alkali-stabilized LCC bonds were found to be predominantly characterized by phenyl glycoside (PhGlc) bonds along with numerous p-coumaric acid (PCA) linkage structures. As demonstrated by the NMR and CLSM results, the dissolution of the LCC during the alkaline pretreatment process was observed to migrate from the inner secondary wall (S-layer) of the bamboo fiber cell walls to the cell corner middle lamella (CCML) and compound middle lamella (CML), ultimately leading to its release from the bamboo. Furthermore, the presence of H-type lignin-FA-arabinoxylan linkage structures within the bamboo LCC was identified with their primary dissolution observed in the S-layer of the bamboo fiber cell walls. The study results provided a clear target for breaking down the anti-depolymerization barrier in bamboo, signifying a major advancement in achieving the comprehensive separation of bamboo components.

Intratumoral CD38+CD19+B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: The widespread involvement of tumor-infiltrating B cells highlights their potential role in tumor behavior. However, B cell heterogeneity in PDAC remains unexplored. Studying TIL-Bs in PDAC aims to identify new treatment strategies. METHODS: We performed single-cell RNA sequencing to study the heterogeneity of B cells in PDAC. The prognostic and immunologic value of the identified CD38+ B cells was explored in FUSCC (n = 147) and TCGA (n = 176) cohorts. Flow cytometry was conducted to characterize the relationship between CD38+ B cells and other immune cells, as well as their phenotypic features. In vitro and in vivo experiments were performed to assess the putative effect of CD38+ B cells on antitumor immunity. FINDINGS: The presence of CD38+ B cells in PDAC was associated with unfavorable clinicopathological features and poorer overall survival (p < 0.001). Increased infiltration of CD38+ B cells was accompanied by reduced natural killer (NK) cells (p = 0.021) and increased regulatory T cells (p = 0.016). Molecular profiling revealed high expression of IL-10, IL-35, TGF-ß, GZMB, TIM-1, CD5 and CD21, confirming their putative regulatory B cell-like features. Co-culture experiments demonstrated suppression of NK cell cytotoxicity by CD38+ B cell-derived IL-10 (p < 0.001). Finally, in vivo experiments suggested adoptive transfer of CD38+ B cells reduced antitumor immunity and administration of a CD38 inhibitor hampered tumor growth (p < 0.001). INTERPRETATION: We discovered regulatory B cell-like CD38+ B cell infiltration as an independent prognostic factor in PDAC. The use of CD38 inhibitor may provide new possibilities for PDAC immunotherapy. FUNDING: This study was supported by the National Natural Science Foundation of China (U21A20374), Shanghai Municipal Science and Technology Major Project (21JC1401500), Scientific Innovation Project of Shanghai Education Committee (2019-01-07-00-07-E00057), Special Project for Clinical Research in the Health Industry of the Shanghai Health Commission (No. 20204Y0265) and Natural Science Foundation of Shanghai (23ZR1479300).

Genetic evidence for splicing-dependent structural and functional plasticity in CASK protein.

BACKGROUND: Pontocerebellar hypoplasia (PCH) may present with supratentorial phenotypes and is often accompanied by microcephaly. Damaging mutations in the X-linked gene CASK produce self-limiting microcephaly with PCH in females but are often lethal in males. CASK deficiency leads to early degeneration of cerebellar granule cells but its role in other regions of the brain remains uncertain. METHOD: We generated a conditional Cask knockout mice and deleted Cask ubiquitously after birth at different times. We examined the clinical features in several subjects with damaging mutations clustered in the central part of the CASK protein. We have performed phylogenetic analysis and RT-PCR to assess the splicing pattern within the same protein region and performed in silico structural analysis to examine the effect of splicing on the CASK's structure. RESULT: We demonstrate that deletion of murine Cask after adulthood does not affect survival but leads to cerebellar degeneration and ataxia over time. Intriguingly, damaging hemizygous CASK mutations in boys who display microcephaly and cerebral dysfunction but without PCH are known. These mutations are present in two vertebrate-specific CASK exons. These exons are subject to alternative splicing both in forebrain and hindbrain. Inclusion of these exons differentially affects the molecular structure and hence possibly the function/s of the CASK C-terminus. CONCLUSION: Loss of CASK function disproportionately affects the cerebellum. Clinical data, however, suggest that CASK may have additional vertebrate-specific function/s that play a role in the mammalian forebrain. Thus, CASK has an ancient function shared between invertebrates and vertebrates as well as novel vertebrate-specific function/s.

Artesunate Alleviates Kidney Fibrosis in Type 1 Diabetes with Periodontitis Rats via Promoting Autophagy and Suppression of Inflammation.

To explore the effect of periodontal disease on the progression of diabetic kidney disease (DKD), to observe the effects of artesunate (ART) intervention on periodontal and kidney tissues in type 1 diabetic rats with periodontitis, and to explore the possibility of ART for the treatment of DKD. Rat models of diabetes mellitus, periodontitis, and diabetes mellitus with periodontitis were established through streptozotocin (STZ) intraperitoneal injection, maxillary first molar ligation, and P. gingivalis ligation applied sequentially. Ten weeks after modeling, ART gavage treatment was given for 4 weeks. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were used to investigate the inflammatory factors, fibrogenisis, autophagy-related factors, and proteins in periodontal and kidney tissues, and 16S rDNA sequencing was used to detect the changes in dental plaque fluid and kidney tissue flora. Compared to the control group, the protein expression levels of transforming growth factor ß1 (TGF-ß1) and COL-IV in the periodontal disease (PD) group were increased. The protein expression of TGF-ß1, Smad3, and COL-IV increased in the DM group and the DM + PD group, and the expression of TGF-ß1, Smad3, and COL-IV was upregulated in the DM + PD group. These results suggest that periodontal disease enhances renal fibrosis and that this process is related to the TGF-ß1/Smad/COL-IV signaling pathway. Among the top five dominant bacteria in the kidney of the DM + PD group, the abundance of Proteobacteria increased most significantly, followed by Actinobacteria and Firmicutes with mild increases. The relative abundance of Proteobacteria, Actinobacteria, and Firmicutes in the kidney tissues of DM and PD groups also showed an increasing trend compared with the CON group. Proteobacteria and Firmicutes in the kidney of the PD group and DM + PD group showed an increasing trend, which may mediate the increase of oxidative stress in the kidney and promote the occurrence and development of DN. Periodontal disease may lead to an imbalance of renal flora, aggravate renal damage in T1DM, cause glomerular inflammation and renal tubulointerstitial fibrosis, and reduce the level of autophagy. ART delays the process of renal fibrosis by inhibiting the TGF-ß-Smad signaling pathway.

Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Ontology-based modeling, integration, and analysis of heterogeneous clinical, pathological, and molecular kidney data for precision medicine.

Many data resources generate, process, store, or provide kidney related molecular, pathological, and clinical data. Reference ontologies offer an opportunity to support knowledge and data integration. The Kidney Precision Medicine Project (KPMP) team contributed to the representation and addition of 329 kidney phenotype terms to the Human Phenotype Ontology (HPO), and identified many subcategories of acute kidney injury (AKI) or chronic kidney disease (CKD). The Kidney Tissue Atlas Ontology (KTAO) imports and integrates kidney-related terms from existing ontologies (e.g., HPO, CL, and Uberon) and represents 259 kidney-related biomarkers. We also developed a precision medicine metadata ontology (PMMO) to integrate 50 variables from KPMP and CZ CellxGene data resources and applied PMMO for integrative kidney data analysis. The gene expression profiles of kidney gene biomarkers were specifically analyzed under healthy control or AKI/CKD disease statuses. This work demonstrates how ontology-based approaches support multi-domain data and knowledge integration in precision medicine.

Utilization of a novel patient-specific 3D-printing template for percutaneous endoscopic transforaminal discectomy: results from a randomized controlled trial.

Background: The learning curve for percutaneous endoscopic transforaminal discectomy (PETD) is steep, especially for the puncturing and localization procedures. The implementation of 3D printing technology may solve this problem. Methods: A novel individualized 3D-printing template (3D-PT) was designed and utilized in PETD. A prospective randomized controlled trial was performed. A total of 28 patients with lumbar disc herniation treated with PETD were analyzed. Of these, 14 patients were treated with the assistance of 3D printing technology (3D-PT group) in conjunction with fluoroscopy, while the remaining 14 patients were treated exclusively under the guidance of C-arm fluoroscopy (control group). Results: The number of puncture attempts in the 3D-PT group was significantly less than in the control group (1.36 ± 0.63 vs. 6.07 ± 3.08, p = 0.000). The 3D-PT group exhibited a significant reduction in both intraoperative puncture fluoroscopies (2.71 ± 1.27 vs. 12.14 ± 6.15, p = 0.000) and the overall number of fluoroscopies (2.71 ± 1.27 vs. 17.43 ± 6.27, p = 0.000). In the 3D-PT group, there was a significant reduction in both the puncture time (5.77 ± 1.82 vs. 13.99 ± 4.36, p = 0.000) and the total operation time (60.39 ± 9.78 vs. 76.25 ± 17.78, p = 0.007). Complications were not observed in either group. Conclusion: The application of the novel individualized 3D-PT for PETD is effective and safe. The technique has substantial potential and is worth widely promoting.

GPX4 degradation contributes to fluoride-induced neuronal ferroptosis and cognitive impairment via mtROS-chaperone-mediated autophagy.

Ferroptosis is a newly recognized type of programmed cell death that is implicated in the pathophysiological process of neurological disorders. Our previous studies have revealed that exposure to high concentrations of fluoride for long periods of time induces hippocampal neural injury and cognitive deficits. However, whether ferroptosis is involved in fluoride-induced neuronal death and the underlying mechanism remain unknown. In this study, the results indicated that exposure to high fluoride triggered ferroptosis in SH-SY5Y cells and in the hippocampus of mice. Fluoride exposure accelerated the lysosomal degradation of GPX4 and led to neuronal ferroptosis, while GPX4 overexpression protected SH-SY5Y cells against fluoride-induced neurotoxicity. Intriguingly, the enhanced chaperone-mediated autophagy (CMA) induced by fluoride stimulation was responsible for GPX4 degradation because the inhibition of CMA activity by LAMP2A knockdown effectively prevented fluoride-induced GPX4 loss. Furthermore, mitochondrial ROS (mtROS) accumulation caused by fluoride contributed to CMA activation-mediated GPX4 degradation and subsequent neuronal ferroptosis. Notably, the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) or the ROS scavenger N-acetyl-L-cysteine (NAC) alleviated fluoride-evoked hippocampal neuronal death and synaptic injury as well as cognitive deficits in mice. The present studies indicates that ferroptosis is a novel mechanism of fluoride-induced neurotoxicity and that chronic fluoride exposure facilitates GPX4 degradation via mtROS chaperone-mediated autophagy, leading to neuronal ferroptosis and cognitive impairment.

Bifidobacterium Relieved Fluoride-Induced Hepatic and Ileal Toxicity via Inflammatory Response and Bile Acid Transporters in Mice.

Fluoride is a pervasive environmental contaminant. Prolonged excessive fluoride intake can inflict severe damage on the liver and intestines. Previous 16S rDNA sequencing revealed a decrease in ileal Bifidobacterium abundance during fluoride-induced hepatointestinal injury. Hence, this work aimed to investigate the possible mitigating function of Bifidobacterium on hepatointestinal injury caused by fluoride. Thirty-six 6-week-old C57BL/6J mice (equally divided between males and females) were allotted randomly to three groups: Ctrl group (distilled water), NaF group, and NaF + Ba group (100 mg/L NaF distilled water). After 10 weeks, the mice were given 1 × 109 CFU/mL Bifidobacterium solution (0.2 mL/day) intragastrically in the NaF + Ba group for 8 weeks, and the mice in other groups were given the same amount of distilled water. Dental damage, bone fluoride content, blood routine, liver and intestinal microstructure and function, inflammatory factors, and regulatory cholic acid transporters were examined. Our results showed that fluoride increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) activities, and the levels of lipopolysaccharide (LPS), IL-1ß, IL-6, TNF-α, and IL-10 levels in serum, liver, and ileum. However, Bifidobacterium intervention alleviated fluoride-induced changes in the above indicators. In addition, Bifidobacterium reduced the mRNA expression levels of bile acid transporters ASBT, IBABP, OST-α, and OST-ß in the ileum. In summary, Bifidobacterium supplementation relieved fluoride-induced hepatic and ileal toxicity via an inflammatory response and bile acid transporters in the liver and ileum of mice.

Toughening Hydrogels with Fibrillar Connected Double Networks.

Biological tissues, such as tendons or cartilage, possess high strength and toughness with very low plastic deformations. In contrast, current strategies to prepare tough hydrogels commonly utilize energy dissipation mechanisms based on physical bonds that lead to irreversible large plastic deformations, thus limiting their load-bearing applications. This article reports a strategy to toughen hydrogels using fibrillar connected double networks (fc-DN), which consist of two distinct but chemically interconnected polymer networks, that is, a polyacrylamide network and an acrylated agarose fibril network. The fc-DN design allows efficient stress transfer between the two networks and high fibril alignment during deformation, both contributing to high strength and toughness, while the chemical crosslinking ensures low plastic deformations after undergoing high strains. The mechanical properties of the fc-DN network can be readily tuned to reach an ultimate tensile strength of 8 MPa and a toughness of above 55 MJ m-3, which is 3 and 3.5 times more than that of fibrillar double network hydrogels without chemical connections, respectively. The application potential of the fc-DN hydrogel is demonstrated as load-bearing damping material for a jointed robotic lander. The fc-DN design provides a new toughening mechanism for hydrogels that can be used for soft robotics or bioelectronic applications.

Safety factor diagnostic for tokamak core plasma from three-dimensional reconstruction of pellet ablation trail.

Using a stereo camera system, a new diagnostic for the safety factor of the core plasma based on the pellet ablation trail is applied on the Experimental Advanced Superconducting Tokamak (EAST). In EAST discharge No. 128 874, a shattered pellet injection system is applied to inject a shattered neon pellet into the EAST. Since the strong magnetic field in tokamaks binds the ablated pellet material, the orientation of the pellet ablation trail is the same as the local magnetic field direction. Thus, from the three-dimensional reconstruction result of the pellet ablation trail, the local safety factor q can be obtained. The motional Stark effect (MSE) diagnostic is applied to determine the safety factor q profile in this shot. The determined safety factor q results for this new diagnostic are in quantitative agreement with those from the MSE diagnostic with the mean relative difference of only 6.8%, confirming the effectiveness of this new diagnostic of the safety factor.

Projection Stereolithography 3D Printing High-Conductive Hydrogel for Flexible Passive Wireless Sensing.

Hydrogel-based electronics have inherent similarities to biological tissues and hold potential for wearable applications. However, low conductivity, poor stretchability, nonpersonalizability, and uncontrollable dehydration during use limit their further development. In this study, projection stereolithography 3D printing high-conductive hydrogel for flexible passive wireless sensing is reported. The prepared photocurable silver-based hydrogel is rapidly planarized into antenna shapes on substrates using surface projection stereolithography. After partial dehydration, silver flakes within the circuits form sufficient conductive pathways to achieve high conductivity (387 S cm-1). By sealing the circuits to prevent further dehydration, the resistance remains stable when tensile strain is less than 100% for at least 30 days. Besides, the sealing materials provide versatile functionalities, such as stretchability and shape memory property. Customized flexible radio frequency identification tags are fabricated by integrating with commercial chips to complete the accurate recognition of eye movement, realizing passive wireless sensing.

Unveiling unique alternative splicing responses to low temperature in Zoysia japonica through ZjRTD1.0, a high-quality reference transcript dataset.

Inadequate reference databases in RNA-seq analysis can hinder data utilization and interpretation. In this study, we have successfully constructed a high-quality reference transcript dataset, ZjRTD1.0, for Zoysia japonica, a widely-used turfgrass with exceptional tolerance to various abiotic stress, including low temperatures and salinity. This dataset comprises 113,089 transcripts from 57,143 genes. BUSCO analysis demonstrates exceptional completeness (92.4%) in ZjRTD1.0, with reduced proportions of fragmented (3.3%) and missing (4.3%) orthologs compared to prior datasets. ZjRTD1.0 enables more precise analyses, including transcript quantification and alternative splicing assessments using public datasets, which identified a substantial number of differentially expressed transcripts (DETs) and differential alternative splicing (DAS) events, leading to several novel findings on Z. japonica's responses to abiotic stresses. First, spliceosome gene expression influenced alternative splicing significantly under abiotic stress, with a greater impact observed during low-temperature stress. Then, a significant positive correlation was found between the number of differentially expressed genes (DEGs) encoding protein kinases and the frequency of DAS events, suggesting the role of protein phosphorylation in regulating alternative splicing. Additionally, our results suggest possible involvement of serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoproteins (hnRNPs) in generating inclusion/exclusion isoforms under low-temperature stress. Furthermore, our investigation revealed a significantly enhanced overlap between DEGs and differentially alternatively spliced genes (DASGs) in response to low-temperature stress, suggesting a unique co-regulatory mechanism governing transcription and splicing in the context of low-temperature response. In conclusion, we have proven that ZjRTD1.0 will serve as a reliable and useful resource for future transcriptomic analyses in Z. japonica.

I2 Catalyzed and TBHP/Ammonium-Promoted Conversion of Arylethanone to Nitriles via ß-Scission of Iminyl Radicals.

Herein, we report a general I2-catalyzed and TBHP/ammonium-promoted conversion of arylethanone to aromatic nitriles under air. This procedure proceeded with the ß-scission of iminyl radical, which was facilitated via quenching the released alkyl radical by tert-butyl peroxyl radical leading to peroxide followed with Kornblum-DeLaMare rearrangement. A series of aryl methyl ketone and alkyl aryl ketone worked well with good functional group tolerance in high yields. As such, this metal-free procedure represents a facile, safe, green, and practical procedure in conversion of arylethanone to aromatic nitriles.

Cadmium exposure induced neuronal ferroptosis and cognitive deficits via the mtROS-ferritinophagy pathway.

Exposure to environmental cadmium (Cd) is known to cause neuronal death and cognitive decline in humans. Ferroptosis, a novel iron-dependent type of regulated cell death, is involved in various neurological disorders. In the present study, Cd exposure triggered ferroptosis in the mouse hippocampus and in the HT22 murine hippocampal neuronal cell line, as indicated by significant increases in ferroptotic marker expression, intracellular iron levels, and lipid peroxidation. Interestingly, ferroptosis of hippocampal neurons in response to Cd exposure relied on the induction of autophagy since the suppression of autophagy by 3-methyladenine (3-MA) and chloroquine (CQ) substantially ameliorated Cd-induced ferroptosis. Furthermore, nuclear receptor coactivator 4 (NCOA4)-mediated degradation of ferritin was required for the Cd-induced ferroptosis of hippocampal neurons, demonstrating that NCOA4 knockdown decreased intracellular iron levels and lipid peroxidation and increased cell survival, following Cd exposure. Moreover, Cd-induced mitochondrial reactive oxygen species (mtROS) generation was essential for the ferritinophagy-mediated ferroptosis of hippocampal neurons. Importantly, pretreatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1) effectively attenuated Cd-induced hippocampal neuronal death and cognitive impairment in mice. Taken together, these findings indicate that ferroptosis is a novel mechanism underlying Cd-induced neurotoxicity and cognitive impairment and that the mtROS-ferritinophagy axis modulates Cd-induced neuronal ferroptosis.