Transcriptomic and metabolomic analysis of poplar response to feeding by Hyphantria cunea.

Populus cathayana × canadansis 'Xinlin 1' ('P.'xin lin 1') with the characteristics of rapid growth and high yield, is frequently attacked by herbivorous insects. However, little is known about how it defenses against Hyphantria cunea (H. cunea) at molecular and biochemical levels. Differences in the transcriptome and metabolome were analyzed after 'P. 'xin lin 1' leaves were fed to H. cunea for 0h, 2h, 4h, 8h, 16h and 24h. In the five comparison groups including 2h vs. CK, 4h vs. CK, 8h vs. CK, 16h vs. CK, and 24h vs. CK, a total of 8925 genes and 842 metabolites were differentially expressed. A total of 825 transcription factors (TFs) were identified, which encoded 56 TF families. The results showed that the top four families with the highest number of TFs were AP2/ERF, MYB, C2C2, bHLH. Analyses of leaves which were fed to H. cunea showed that the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were significantly enriched in plant hormone signal transduction pathway, MAPK signaling pathway, flavonoid, flavone and flavonol and anthocyanin biosynthesis pathway. Additionally, there were a number of genes significantly up-regulated in MAPK signaling pathway. Some compounds involved in plant hormone signal transduction and flavonoid/flavone and flavonol/ anthocyanin pathways such as jasmonic acid (JA), jasmonoyl-L-Isoleucine (JA-Ile), kaempferol and cyanidin-3-O-glucoside were induced in infested 'P.'xin lin 1'. This study provides a new understanding for exploring the dynamic response mechanism of poplar to the infestation of H. cunea.

AFSC: A self-supervised augmentation-free spatial clustering method based on contrastive learning for identifying spatial domains.

Recent research in spatial transcriptomics allows researchers to analyze gene expression without losing spatial information. Spatial information can assist in cell communication, identification of new cell subtypes, which provides important research methods for multiple fields such as microenvironment interactions and pathological processes of diseases. Identifying spatial domains is an important step in spatial transcriptomics analysis, and improving spatial clustering methods can benefit for identifying spatial domains. In addition to eliminating noise in original gene expression, how to use spatial information to assist clustering has also become a new problem. A variety of calculating methods have been applied to spatial clustering, including contrastive learning methods. However, existing spatial clustering methods based on contrastive learning use data augmentation to generate positive and negative pairs, which will inevitably destroy the biological meaning of the data. We propose a new self-supervised spatial clustering method based on contrastive learning, Augmentation-Free Spatial Clustering (AFSC), which integrates spatial information and gene expression to learn latent representations. We construct a contrastive learning module without negative pairs or data augmentation by designing Teacher and Student Encoder. We also design an unsupervised clustering module to make clustering and contrastive learning be trained together. Experiments on multiple spatial transcriptomics datasets at different resolutions demonstrate that our method performs well in self-supervised spatial clustering tasks. Furthermore, the learned representations can be used for various downstream tasks including visualization and trajectory inference.

Lactyllysine Esterification Enables Efficient Lactylprotein Expression via Genetic Code Expansion and Supports Functional Proteomics Studies.

Lysine lactylation has recently been discovered and demonstrated to be an essential player in immunity, cancer and neurodegenerative diseases. Genetic code expansion (GCE) technique is powerful in uncovering lactylation functions, since it allows site-specific incorporation of lactyllysine (Klac) into proteins of interest (POIs) in living cells. However, the inefficient uptake of Klac into cells, due to its high hydrophilicity, results in limited expression of lactylated POIs. To address this challenge, here we designed esterified Klac derivatives, exemplified by ethylated Klac (KlacOEt), to enhance Klac's lipophilicity and improve its cellular uptake. The expression level of site-specifically lactylated POIs was doubled using KlacOEt in both Escherichia coli and HEK293T cells. Immunoprecipitation mass spectrometry analysis verified the significantly increased yield of the precisely lactylated fructose-bisphosphate aldolase A using KlacOEt. Furthermore, in conjunction with the Target Responsive Accessibility Profiling approach, we found that lactylation at ALDOA-K147 altered the protein's conformation, which may explain the lactylation-induced reduction in enzyme activity. Together, we demonstrate that, through enhancing the yield of lactylated proteins with Klac esters via GCE, we are able to site-specifically reveal the effects of lactylation on POIs' interactions, conformations and activities using a suite of functional proteomics and biochemical tools.

Operational space robust impedance control of the redundant surgical robot for minimally invasive surgery.

The motion accuracy, compliance, and control smoothness for the surgical robot are of great importance to improve the safety of human-robot interaction. However, the end effector that interacts with soft tissue during surgery affects the dynamics of the robot. The control performance of the controller may be decreased if the changing dynamics are not identified and updated in time. This paper proposes a robust impedance controller for the redundant remote center of motion manipulator influenced by external disturbances, including external torque, uncertainties, and unmodeled terms in the dynamics. To achieve the desired impedance, a continuously switching sliding manifold is proposed. When the sliding manifold is driven to zero, the motion error will converge to a bounded region. This can overcome the adverse effects of external disturbances while guaranteeing motion accuracy and compliance. Chattering of the sliding mode control is alleviated through the formulated continuously switching sliding manifold and integrated nonlinear disturbance observer. Simulations and experiments demonstrate that the proposed controller has excellent motion accuracy, compliance, and control smoothness. This provides potential application prospects for the redundant surgical robot to guarantee safe human-robot interaction.

Platinum-Selenopeptide Interfaces in Support of High Fidelity Electrochemical Biomarker Quantification in Complex Biological Matrices.

The real world applications of conventional antifouling biosensors based on gold-thiol (Au-S) interfaces are hampered by the progressive competitive displacement of key functionality by ubiquitous biothiols. To overcome this limitation, we introduce here novel platinum-selenium (Pt-Se) interfaces. Thiol displacement tests, antifouling analyses, and density functional theory calculations confirm markedly improved interfacial stability. This was then leveraged through the application of a seleno-multifunctional peptide platform, tailored to the detection of murine double minute 2, in biological samples. A derived amperometric sensing platform exhibited a notably lower detection limit and more accurate target quantification than that supported by analogous Au-S and Pt-S interfaces. We believe that this work broadens the scope of electrochemical sensor construction and holds significant promise for the development of high-fidelity impactful bioassay platforms.

Mutual Influence Between Allergic Rhinitis and Sleep: Factors, Mechanisms, and interventions-A Narrative Review.

Patients with allergic rhinitis (AR) have a high incidence of sleep disorders, such as insomnia, which can easily exacerbate nasal symptoms. The aggravation of nasal symptoms further promotes the deterioration of sleep disorders, forming a vicious cycle. Severe cases may even trigger psychological and neurological issues, such as anxiety, depression, and cognitive impairment, causing significant distress to patients, making clinical diagnosis and treatment difficult, and increasing costs. Furthermore, satisfactory therapeutics remain lacking. As the pathogenesis of AR-associated sleep disorders is not clear and research is still insufficient, paying attention to and understanding AR-related sleep disorders is crucial in clinical practice. Multiple studies have shown that the most crucial issues in current research on AR and sleep are analyzing the relationship between AR and sleep disorders, searching for the influencing factors, and investigating potential targets for diagnosis and treatment. This review aimed to identify and summarize the results of relevant studies using "AR" and "sleep disorders" as search terms. In addition, we evaluated the correlation between AR and sleep disorders and examined their interaction and potential mechanisms, offering a foundation for additional screening of potential diagnostic biomarkers and therapeutic targets.

[Accurate repair of oral and maxillofacial soft tissue defects with ulnar artery flap].

Objective: To investigate the characteristics of the clinical application of ulnar artery flap in the repair of oral and maxillofacial soft tissue defects. Methods: The clinical data of 12 patients with oral and maxillofacial defects repaired with ulnar artery flap between June 2021 and July 2023 was retrospectively analyzed. Among them, 11 cases were male and 1 case was female; their ages ranged from 28 to 76 years, with a mean age of 54.8 years. The lesions were located in the lateral margin of the tongue in 3 cases, the root of the tongue in 2 cases, the base of the tongue in 4 cases, and the buccal region, upper gingiva, and lower lip in 1 case each. The pathological types were squamous cell carcinoma in 11 cases and adenoid cystic carcinoma in 1 case; according to the TNM staging of the International Union Against Cancer (UICC), there were 5 cases of T 3N 0M 0, 2 cases of T 3N 1M 0, 1 case of T 4aN 0M 0, 1 case of T 4aN 1M 0, 1 case of T 4aN 2bM 0, and 2 cases of T 4aN 2cM 0. After complete resection of the lesion, the defect ranged from 6 cm×3 cm to 8 cm×5 cm. Preoperatively, colour Doppler ultrasound was used to detect the non-dominant forearm, measure the thickness of the subcutaneous fat in the donor area, confirm and mark the ulnar artery and reflux vein, and measure the diameter of the vessels, flow velocity, and the perforator position; intraoperatively, the flap was designed, prepared, anastomosed, and positioned according to the corresponding data. The vessels were all anastommosed with one artery and two veins to form a super-reflux. After complete hemostasis, the defects were repaired with sliding flap (2 cases), direct suture (4 cases), biomembrane (2 cases), or razor thin skin graft (4 cases). Results: No vascular crisis occurred after operation, and all the flaps survived in 12 cases. Wounds in the donor site healed by first intention in 10 cases and by second intention in 2 cases. Wounds in the recipient site healed by first intention in all cases. All 12 patients were followed up 5-18 months, with an average of 11.4 months. The colour and texture of the flap were normal. The function of hand and upper limb was evaluated according to the trial standard of upper limb function assessment of the Chinese Society of Hand Surgery of the Chinese Medical Association, and the score was 65-81 (mean, 71.3), and achieved excellent in 1 case and good in 11 cases. The score of Oral Health Impact Scale (OHIP) was 9-18, with an average of 14.2, and the oral function was satisfactory. During the follow-up, 1 case had local recurrence and underwent extended resection again, while the other patients had no recurrence or metastasis. Conclusion: For moderate soft tissue defects with complex oral and maxillofacial function, ulnar artery flap repair is effective.

Calibration Methods for Large-Scale and High-Precision Globalization of Local Point Cloud Data Based on iGPS.

The point cloud is one of the measurement results of local measurement and is widely used because of its high measurement accuracy, high data density, and low environmental impact. However, since point cloud data from a single measurement are generally small in spatial extent, it is necessary to accurately globalize the local point cloud to measure large components. In this paper, the method of using an iGPS (indoor Global Positioning System) as an external measurement device to realize high-accuracy globalization of local point cloud data is proposed. Two calibration models are also discussed for different application scenarios. Verification experiments prove that the average calibration errors of these two calibration models are 0.12 mm and 0.17 mm, respectively. The proposed method can maintain calibration precision in a large spatial range (about 10 m × 10 m × 5 m), which is of high value for engineering applications.

Proteogenomic characterization of skull-base chordoma.

Skull-base chordoma is a rare, aggressive bone cancer with a high recurrence rate. Despite advances in genomic studies, its molecular characteristics and effective therapies remain unknown. Here, we conduct integrative genomics, transcriptomics, proteomics, and phosphoproteomics analyses of 187 skull-base chordoma tumors. In our study, chromosome instability is identified as a prognostic predictor and potential therapeutic target. Multi-omics data reveals downstream effects of chromosome instability, with RPRD1B as a putative target for radiotherapy-resistant patients. Chromosome 1q gain, associated with chromosome instability and upregulated mitochondrial functions, lead to poorer clinical outcomes. Immune subtyping identify an immune cold subtype linked to chromosome 9p/10q loss and immune evasion. Proteomics-based classification reveals subtypes (P-II and P-III) with high chromosome instability and immune cold features, with P-II tumors showing increased invasiveness. These findings, confirmed in 17 paired samples, provide insights into the biology and treatment of skull-base chordoma.

Evaluation of Cardiac Function Recovery in Patients with Paroxysmal Atrial Fibrillation after Catheter Radiofrequency Ablation Using Two-Dimensional Speckle Tracking Imaging and Real-Time Three-Dimensional Echocardiography.

INTRODUCTION: The aim of this study was to evaluate the utility of 2D-STI and real-time three-dimensional echocardiography (RT-3DE) in assessing changes in left atrial (LA) structure and function in patients with paroxysmal atrial fibrillation (PAF) post-radiofrequency catheter ablation (RFCA). METHODS: A retrospective analysis was conducted on 44 PAF patients who underwent RFCA at BA Hospital from March 2022 to March 2023. An age- and gender-matched control group of 32 healthy individuals was also included. Comprehensive echocardiographic parameters including LA dimensions (LAAPD, LALRD), volumes (LAVmin, LAVmax), ejection fraction (LAEF), and tissue velocities (a', Ar) were compared between groups. Post-RFCA changes in these parameters were also assessed at 1, 3, and 6 months. RESULTS: Pre-RFCA, PAF patients demonstrated larger LA dimensions and volumes with reduced LAEF and tissue velocities compared to controls. Post-RFCA, there was a significant improvement in LAEF and left ventricular ejection fraction at 1, 3, and 6 months, with the most pronounced changes observed at 6 months. LA dimensions increased initially but then decreased from 1 to 6 months post-RFCA. Notably, strain rate (SRS, SRE, SRA) measurements in various LA segments improved progressively, with the most significant enhancements at 6 months, suggesting improved atrial mechanics. CONCLUSION: The application of 2D-STI and RT-3DE provides a quantitative means to evaluate the structural and functional changes in the LA of PAF patients following RFCA. The progressive improvements in LA dimensions, volumes, and strain measurements up to 6-month post-RFCA indicate the potential of these techniques in monitoring treatment efficacy and patient recovery.

Iron Level in Pregnant Rats is Associated with Caries Susceptibility in Offsprings.

Iron deficiency anemia (IDA) is a prevalent issue in pregnant women and children. However, the causal relationship between IDA in pregnancy and caries susceptivity in offspring remains unclear. This study aimed to explore the role of iron level during pregnancy on caries susceptivity of offsprings. Here, low-iron (LI) and high-iron (HI) models were established in maternal rats, and iron-related characteristics were examined in maternal rats and their offsprings. After induction of caries in rat offsprings, the carious lesions were evaluated by the Keyes scores, and microstructural damages in molars were observed by scanning electron microscopy. The results showed that LI in maternal rats induced IDA in rat offsprings, and HI only increased serum ferritin in offsprings. LI and HI in maternal rats had no effect on the morphological structure of salivary glands in rat offsprings. After inducing caries, rat offsprings in the LI group exhibited significant increase in enamel lesions at the smooth surface, and on enamel, slight dentinal, and moderate dentinal lesions at the sulcal surface. Only enamel lesions at the sulcal surface were significantly weakened in the HI group. Additionally, visible enamel damages were observed in the LI group. To sum up, iron deficiency during pregnancy enhances caries susceptibility in rat offsprings.

Impact of ovalbumin allergy on oral and gut microbiome dynamics in 6-week-old BALB/c mice.

Background: The gut microbiota is known to have a significant impact on the development of food allergy, and several recent studies have suggested that both oral microbiota, which first come into contact with allergenic foods, may have a profound influence on the development of food allergy. Methods: In this study, we have established an ovalbumin-sensitive mice model by utilizing ovalbumin as a sensitizing agent. Subsequently, we performed a comprehensive analysis of the gut and oral microbiota in ovalbumin-sensitive mice and the control mice using full-length 16S rRNA sequencing analysis. Results: Interestingly, both the gut and oral microbiota of ovalbumin-sensitized mice exhibited significant dysbiosis. The relative abundance of s__Lactobacillus_intestinalis in the gut microbiota of ovalbumin-sensitive mice exhibited a significant decrease, whereas the abundance of s__Agrobacterium_radiobacter and s__Acinetobacter_sp__CIP_56_2 displayed a significant increase. Furthermore, the relative abundance of s__unclassified_g__Staphylococcus, s__Streptococcus_hyointestinalis, and s__unclassified_g__Dechloromonas in the oral microbiota of ovalbumin-sensitive mice revealed a significant decrease. In contrast, the abundance of 63 other species, including s__Proteiniclasticum_ruminis, s__Guggenheimella_bovis, and s__Romboutsia_timonensis, demonstrated a significant increase. The random forest classifier achieved the best accuracy in predicting the outcome of food allergy using three gut and three oral biomarkers, with accuracies of 94.12 and 100%, respectively. Based on the predictions of the PICRUSt2 analysis, the only consistent finding observed across multiple samples from both the groups of mice was a significant up-regulation of the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway in the ovalbumin-sensitized mice. Conclusion: Our study demonstrates that ovalbumin-sensitized mice experience substantial alterations in both gut and oral microbial composition and structure, and specific strains identified in this study may serve as potential biomarkers for food allergy screening. Moreover, our findings highlight that the oral environment, under the same experimental conditions, exhibited greater precision in detecting a larger number of species. Additionally, it is worth noting that the NOD-like receptor signaling pathway plays a vital role in the pathogenesis of OVA (ovalbumin)-induced allergy. These findings will generate novel concepts and strategies in the realm of food allergy prevention and treatment.

Fullerene on non-iron cluster-matrix co-catalysts promotes collaborative H2 and N2 activation for ammonia synthesis.

Developing highly effective catalysts for ammonia (NH3) synthesis is a challenging task. Even the current, prevalent iron-derived catalysts used for industrial NH3 synthesis require harsh reaction conditions and involve massive energy consumption. Here we show that anchoring buckminsterfullerene (C60) onto non-iron transition metals yields cluster-matrix co-catalysts that are highly efficient for NH3 synthesis. Such co-catalysts feature separate catalytic active sites for hydrogen and nitrogen. The 'electron buffer' behaviour of C60 balances the electron density at catalytic transition metal sites and enables the synergistic activation of nitrogen on transition metals in addition to the activation and migration of hydrogen on C60 sites. As demonstrated in long-term, continuous runs, the C60-promoting transition metal co-catalysts exhibit higher NH3 synthesis rates than catalysts without C60. With the involvement of C60, the rate-determining step in the cluster-matrix co-catalysis is found to be the hydrogenation of *NH2. C60 incorporation exemplifies a practical approach for solving hydrogen poisoning on a wide variety of oxide-supported Ru catalysts.

Efficacy and Safety of Low-Fluence 730-nm Picosecond Laser in the Treatment of Melasma in Chinese Patients.

BACKGROUND: The 730-nm picosecond laser has shown promise in treating various benign pigmentary conditions, and it is yet to be determined whether it is effective and safe for melasma. OBJECTIVE: The aim of this study was to investigate the potential benefits and risks of using the 730-nm picosecond laser to remove melasma. MATERIALS AND METHODS: This is a retrospective review of all patients who presented to the clinic between April 2021 and April 2022 for the treatment of melasma with 730-nm picosecond laser alone. The efficacy of the laser was assessed based on the Melasma Area and Severity Index (MASI) score using high-resolution photographs evaluated by blinded dermatologists. RESULTS: A total of 25 Chinese with Fitzpatrick skin Type II to IV were included. Patients were treated for an average of 3.56 ± 0.77 treatment sessions. The mean MASI scores decreased by 33.7% from 11.38 ± 6.60 to 7.55 ± 6.08 at an average of 8.48 ± 2.16 weeks of follow-up (p < .001). Among the patients, 1 experienced a 79% decrease, 6 had a decrease ranging from 51% to 75%, 10 had a decrease ranging from 26% to 50%, 5 had a decrease of less than 25%, and 3 experienced no changes in MASI scores. No hyper/hypopigmentation was observed. CONCLUSION: Low-fluence 730-nm picosecond laser is an effective and safe modality for the treatment of melasma in Chinese patients.

A Systematic Review and Developmental Perspective on Origin of CMS Genes in Crops.

Cytoplasmic male sterility (CMS) arises from the incompatibility between the nucleus and cytoplasm as typical representatives of the chimeric structures in the mitochondrial genome (mitogenome), which has been extensively applied for hybrid seed production in various crops. The frequent occurrence of chimeric mitochondrial genes leading to CMS is consistent with the mitochondrial DNA (mtDNA) evolution. The sequence conservation resulting from faithfully maternal inheritance and the chimeric structure caused by frequent sequence recombination have been defined as two major features of the mitogenome. However, when and how these chimeric mitochondrial genes appear in the context of the highly conserved reproduction of mitochondria is an enigma. This review, therefore, presents the critical view of the research on CMS in plants to elucidate the mechanisms of this phenomenon. Generally, distant hybridization is the main mechanism to generate an original CMS source in natural populations and in breeding. Mitochondria and mitogenomes show pleomorphic and dynamic changes at key stages of the life cycle. The promitochondria in dry seeds develop into fully functioning mitochondria during seed imbibition, followed by massive mitochondria or mitogenome fusion and fission in the germination stage along with changes in the mtDNA structure and quantity. The mitogenome stability is controlled by nuclear loci, such as the nuclear gene Msh1. Its suppression leads to the rearrangement of mtDNA and the production of heritable CMS genes. An abundant recombination of mtDNA is also often found in distant hybrids and somatic/cybrid hybrids. Since mtDNA recombination is ubiquitous in distant hybridization, we put forward a hypothesis that the original CMS genes originated from mtDNA recombination during the germination of the hybrid seeds produced from distant hybridizations to solve the nucleo-cytoplasmic incompatibility resulting from the allogenic nuclear genome during seed germination.

Understanding and manipulating the recognition of necrosis-inducing secreted protein 1 (NIS1) by BRI1-associated receptor kinase 1 (BAK1).

Necrosis-inducing secreted protein 1 (NIS1) is a core effector of Ascomycota and Basidiomycota fungi. They inhibit the immune responses of host plants mainly through interaction with the multi-functional coreceptor BRI1-associated receptor kinase 1 (BAK1). However, the structural mechanism of the NIS1 family and how they are recognized by BAK1 are unknown. Herein, we report the first crystal structure of the NIS1 family protein, the Magnaporthe oryzae NIS1 (MoNIS1), analyze the recognition mechanism of NIS1s by BAK1, and explore regulation of the NIS1-BAK1 interaction by a chemical compound. MoNIS1 exists as a ß barrel formed by eight ß strands, a folding mode that has not been reported. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) assay suggested that ß4-ß5 loop and ß5 strand of MoNIS1 participate in OsBAK1 interaction, which was supported by further single-point mutational assays. For OsBAK1, HDX-MS assay suggested four regions involved in MoNIS1 interaction. Additionally, we identified a compound that blocks MoNIS1-OsBAK1 interaction in vitro and inhibits the virulence of M. oryzae on rice. Collectively, we determined the first structure of NIS1 family effectors, presented the recognition mechanism of NIS1 by BAK1, and showed that blocking NIS1-BAK1 interaction could be a new target for fungicide development.

Machine learning developed a macrophage signature for predicting prognosis, immune infiltration and immunotherapy features in head and neck squamous cell carcinoma.

Macrophages played an important role in the progression and treatment of head and neck squamous cell carcinoma (HNSCC). We employed weighted gene co-expression network analysis (WGCNA) to identify macrophage-related genes (MRGs) and classify patients with HNSCC into two distinct subtypes. A macrophage-related risk signature (MRS) model, comprising nine genes: IGF2BP2, PPP1R14C, SLC7A5, KRT9, RAC2, NTN4, CTLA4, APOC1, and CYP27A1, was formulated by integrating 101 machine learning algorithm combinations. We observed lower overall survival (OS) in the high-risk group and the high-risk group showed elevated expression levels in most of the immune checkpoint and human leukocyte antigen (HLA) genes, suggesting a strong immune evasion capacity. Correspondingly, TIDE score positively correlated with risk score, implying that high-risk tumors may resist immunotherapy more effectively. At the single-cell level, we noted macrophages in the tumor microenvironment (TME) predominantly stalled in the G2/M phase, potentially hindering epithelial-mesenchymal transition and playing a crucial role in the inhibition of tumor progression. Finally, the proliferation and migration abilities of HNSCC cells significantly decreased after the expression of IGF2BP2 and SLC7A5 reduced. It also decreased migration ability of macrophages and facilitated their polarization towards the M1 direction. Our study constructed a novel MRS for HNSCC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy for HNSCC patients.

RELA-mediated upregulation of LINC03047 promotes ferroptosis in silica-induced pulmonary fibrosis via SLC39A14.

Long non-coding RNAs play a key role in silicosis, a fatal fibrotic lung disease, and there is an urgent need to develop new treatment targets. Long intergenic non-protein-coding RNA 3047 (LINC03047) is associated with cancer, but its role and mechanism in the progression of silicosis require further elucidation. This study investigated the function of LINC03047 in the epithelial-mesenchymal transition (EMT) during silicosis progression. LINC03047 expression was upregulated in SiO2-treated BEAS-2B and A549 cells, promoting SiO2-induced ferroptosis and subsequent EMT. Moreover, knockdown of LINC03047 significantly decreased the expression of solute carrier family 39 member 14 (SLC39A14), a ferrous iron transporter, and inhibition of SLC39A14 alleviated the ferroptosis and EMT caused by LINC03047 overexpression. We further investigated that NF-κB p65 (RELA) was critical for LINC03047 transcription in SiO2-treated BEAS-2B and A549 cells. In vivo experiments showed that SLC39A14 deficiency improved SiO2-induced lipid peroxidation and EMT. Collectively, our study reveals the function of the RELA/LINC03047/SLC39A14 axis in SiO2-induced ferroptosis and EMT, thereby contributing to the identification of novel drug targets for silicosis therapy.

Melatonin derivative 6a protects Caenorhabditis elegans from formaldehyde neurotoxicity via ADH5.

Formaldehyde (FA) is a carcinogen that is not only widespread in the environment, but is also produced endogenously by metabolic processes. In organisms, FA is converted to formic acid in a glutathione (GSH)-dependent manner by alcohol dehydrogenase 5 (ADH5). The abnormal accumulation of FA in the body can cause a variety of diseases, especially cognitive impairment leading to Alzheimer's disease (AD). In this study, melatonin derivative 6a (MD6a) markedly improved the survival and chemotactic performance of wild-type Caenorhabditis elegans exposed to high concentrations of FA. MD6a lowered FA levels in the nematodes by enhancing the release of covalently-bound GSH from S-hydroxymethyl-GSH in an adh-5-dependent manner. In addition, MD6a protected against mitochondrial dysfunction and cognitive impairment in beta-amyloid protein (Aß) transgenic nematodes by lowering endogenous FA levels and reducing Aß aggregation in an adh-5-dependent manner. Our findings suggest that MD6a detoxifies FA via ADH5 and protects against Aß toxicity by reducing endogenous FA levels in the C. elegans AD models. Thus, ADH5 might be a potential therapeutic target for FA toxicity and AD.

Molecular characteristics of patients with colorectal signet-ring cell carcinoma with different ABO blood groups.

Background: Colorectal signet-ring cell carcinoma (SRCC) is a rare subtype of malignant adenocarcinoma, accounting for approximately 1 % of colorectal cancer (CRC) cases. Its biomarkers and molecular characteristics remain controversial, and there are no specific therapeutic targets or strategies for its clinical treatment. Methods: A retrospective study was conducted between January 2010 and December 2021. 1058 colorectal cancer cases from the Sun Yat-sen University Cancer Center and 489 cases from the Tumor Genome Atlas Project were included in the analysis, of which 64 were SRCC. Data extraction included patient demographics, blood types and risk factors, including clinical variables and genomics (either a 19-gene panel NGS or 1021-gene panel NGS). Univariate analyses were performed to identify factors significantly associated with overall survival. Results: The blood groups of 27 (42.2 %), 18 (28.1 %), 12 (18.8 %), and seven (10.9 %) patients were classified as O, A, B, and AB, respectively. We found that O was a unique blood group characterized by a low frequency of KRAS mutations, a high frequency of heterozygosity at each HLA class I locus, and a high tumor mutational burden (TMB). Patients in blood group A with high-frequency KRAS mutations and those in blood group B with anemia and metabolic abnormalities required targeted treatment. Furthermore, genetic alterations in SRCC differed from those in adenocarcinoma and mucinous adenocarcinoma. Conclusions: Our study revealed genomic changes in SRCC patients across different blood groups, which could advance the understanding and precise treatment of colorectal SRCC.