Simultaneous stabilization of particulate and bioavailable arsenic in soils from the realgar mining area by polyacrylamide, nano-SiO2, and ferrihydrite composite materials.

Arsenic (As) contamination in realgar mining areas poses a severe environmental and health risk, highlighting the critical need for effective strategies to manage As migration, particularly in its particulate and bioavailable states. Soil erosion and water leaching serve as significant pathways for spreading As, emphasizing the imperative to curtail its mobility. In the present study, we proposed an effective strategy that combines the utilization of polyacrylamide (PAM), nano-SiO2 (NS), and ferrihydrite (Fh) to elevate the stability of As in soils from a realgar mining area. The results show that this composite material demonstrates the capability to concurrently regulate soil erosion and mitigate the leaching of bioavailable As. The combination of the three materials in the proportion of 0.5 % PAM +0.1 % NS + 1.0 % Fh can reduce the soil particulate and bioavailable As content by 99.11 % and 93.98 %, respectively. The unconfined compressive strength of the soil can be increased by about 30 % under this condition. The SEM analyses show that the addition of PAM and NS can significantly enhance the aggregation of soil particles and then reduce the soil erosion rate. These findings highlight the significant potential of the proposed approach in mitigating As contamination in soil within mining environments. The approach offers a sustainable and comprehensive solution to address the transport of heavy metal contaminants in both particulate and bioavailable states in mining areas.

A systematic analysis of ARM genes revealed that GhARM144 regulates the resistance against Verticillium dahliae via interaction with GhOSM34.

Proteins of the armadillo repeat gene family play important roles in plant pathogen response. Here, 169 armadillo (ARM) genes were identified in upland cotton (Gossypium hirsutum). Phylogenetic analysis grouped these into 11 subfamilies, with conserved protein structures within each subfamily. The results signify that the expansion of the gene family occurred via whole genome duplication and dispersed duplication. Expression profiling and network analysis suggest that GhARM144 may regulate cotton resistance to Verticillium dahliae. GhARM144 was upregulated in roots by V. dahliae infection or salicylic acid treatment. This upregulation indicates a negative regulatory role of GhARM144' in the cotton immune responses, potentially by manipulating salicylic acid biosynthesis. Protein interaction studies found that GhARM144 associates with an osmotin-like protein, GhOSM34, at the plasma membrane. Silencing GhOSM34 reduced the resistance to V. dahliae, suggesting it may play a positive regulatory role. The results demonstrate that GhARM144 modulates cotton immunity through interaction with GhOSM34 and salicylic acid signalling. Further study of these proteins may yield insights into disease resistance mechanisms in cotton and other plants.

Effects of Hydrogenation on the Corrosion Behavior of Zircaloy-4.

Hydrogen plays an important role in the corrosion of zirconium alloys, and the degree of influence highly depends on the alloy composition and conditions. In this work, the effects of hydrogenation on the corrosion behavior of Zircaloy-4 in water containing 3.5 ppm Li + 1000 ppm B at 360 °C/18.6 MPa were investigated. The results revealed that hydrogenation can shorten the corrosion transition time and increase the corrosion rates of Zircaloy-4. The higher corrosion rates can be ascribed to the larger stress in the oxide film of hydrogenated samples, which can accelerate the evolution of the microstructure of the oxide film. In addition, we also found that hydrogenation has little effect on the t-ZrO2 content in the oxide film and there is no direct correspondence between the t-ZrO2 content and the corrosion resistance of the Zircaloy-4.

Identification of necroptosis-associated miRNA signature for predicting prognosis and immune landscape in stomach adenocarcinoma.

PURPOSE: This study aims to identify the potential necroptosis related genes (NRGs)-associated miRNAs signature and explore the impact on the prognosis of stomach adenocarcinoma (STAD). METHODS: Employing rigorous methodologies, we utilized univariate Cox, Lasso and multivariate Cox regression analyses to develop a prognostic signature. Kaplan-Meier (K-M) and ROC curves were applied to assess the prognostic value of signature in a training group and an independent test group. Furthermore, we conducted Gene Set Enrichment Analysis (GSEA) for enrichment of tumor-related pathways. The risk score was calculated for each patient based on the expression of miRNAs which were enrolled in the signature. Patients were stratified into high- and low-risk groups. The immune cell infiltration and immunotherapy were compared between the two groups. Finally, the diagnostic potential of the miRNA was explored by RT-qPCR. RESULTS: We constructed a prognostic model based on 6 NRGs-associated miRNAs. K-M plots underscored superior survival outcomes in the low-risk group. GSEA results revealed the enrichment of several tumor-related pathways in the high-risk group. Notably, CD8+ T cells, Tregs and activated memory CD4+ T cells exhibited negative correlations with the risk score. Additionally, a few immune checkpoint genes, such as CTLA4, PD1 and PD-L1, were significantly upregulated in the low-risk group. Furthermore, the serum expression levels of all these 6 miRNAs were significantly elevated in STAD patients. CONCLUSIONS: Our study identified a robust risk score derived from a signature of 6 NRGs-associated miRNAs, demonstrating high efficacy for prognosis of STAD. These results not only contributed to our understanding of STAD pathogenesis, but also held promise for potential clinical applications, particularly in the realm of personalized immunotherapy for STAD patients.

Transcriptomic analysis of Vibrio alginolyticus challenged by Rhizoma coptidis reveals mechanisms of virulence genes.

Rhizoma coptidis, a Chinese herbal medicine widely used to treat various bacterial infections, has the potential to develop antibiotic substitutes to overcome the drug resistance of Vibrio alginolyticus. To study the inhibitory effect of R. coptidis on V. alginolyticus, we sequenced the transcriptomes of three groups of samples of wild-type V. alginolyticus (CK) and V. alginolyticus, which were stressed by 5 mg/mL R. coptidis for 2 h (RC_2 h) and 4 h (RC_4 h). CK was compared with RC_2 h and RC_4 h, respectively, and a total of 1565 differentially expressed genes (DEGs) (988 up-regulated and 577 down-regulated) and 1737 DEGs (1152 up-regulated and 585 down-regulated) were identified. Comparing RC_2 h with RC_4 h, 156 DEGs (114 up-regulated and 42 down-regulated) were identified. The ability of biofilm formation and motility of V. alginolyticus altered upon with different concentrations of R. coptidis. Interestingly, relative expression patterns of virulence genes appeared statistically significantly varied, upon different concentrations of R. coptidis extract. DEGs were annotated to the Gene Ontology (GO) database for function enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the results showed that the main enriched pathways, was those related to the virulence of V. alginolyticus. This study provides a new perspective for understanding the complex pathogenic mechanism of V. alginolyticus. R. coptidis could potnetially be used as alternative or complimnetary to antibiotics to treat infections after further research.

Quantitative anatomical analysis of lumbar interspaces based on 3D CT imaging: optimized segment selection for lumbar puncture in different age groups.

BACKGROUND: Optimal lumbar puncture segment selection remains controversial. This study aims to analyze anatomical differences among L3-4, L4-5, and L5-S1 segments across age groups and provide quantitative evidence for optimized selection. METHODS: 80 cases of CT images were collected with patients aged 10-80 years old. Threedimensional models containing L3-S1 vertebrae, dural sac, and nerve roots were reconstructed. Computer simulation determined the optimal puncture angles for the L3-4, L4-5, and L5-S1 segments. The effective dural sac area (ALDS), traversing nerve root area (ATNR), and area of the lumbar inter-laminar space (ALILS) were measured. Puncture efficacy ratio (ALDS/ALILS) and nerve injury risk ratio (ATNR/ALILS) were calculated. Cases were divided into four groups: A (10-20 years), B (21-40 years), C (41-60 years), and D (61-80 years). Statistical analysis was performed using SPSS. RESULTS: 1) ALDS was similar among segments; 2) ATNR was greatest at L5-S1; 3) ALILS was greatest at L5-S1; 4) Puncture efficacy ratio was highest at L3-4 and lowest at L5-S1; 5) Nerve injury risk was highest at L5-S1. In group D, L5-S1 ALDS was larger than L3-4 and L4-5. ALDS decreased after age 40. Age variations were minimal across parameters. CONCLUSION: The comprehensive analysis demonstrated L3-4 as the optimal first-choice segment for ages 10-60 years, conferring maximal efficacy and safety. L5-S1 can serve as an alternative option for ages 61-80 years when upper interspaces narrow. This study provides quantitative imaging evidence supporting age-specific, optimized lumbar puncture segment selection.

Interfacial Crack Growth-Based Fatigue Lifetime Prediction of Thermoelectric Modules under Thermal Cycling.

As a result of the complexity and difficulty of the lifetime assessment of the thermoelectric (TE) module, the related research is still immature. In this work, to predict the lifetime of the Bi2Te3-based TE module from the perspective of cyclic thermal stress leading to interface cracking, the viscoplastic behavior of the solder layer is first described by the Anand material ontology model, and then the sprouting and expansion of interface cracking of the module are simulated by combining the Darveaux model and the viscoplastic dissipation energy accumulated during the thermal stress cyclic loading. After that, the complete lifetime prediction model of the TE module is established on the basis of the thermal cycling experiments and the finite element simulation calculation data, which can simply and efficiently predict the cycle number of the module resistance rise and its rise rate. The prediction deviations are 6.1 and 6.7%, respectively, verifying the feasibility of the model. The work in this paper can provide a reference for the life evaluation of TE modules.

Fast Attack Detection for Cyber-Physical Systems Using Dynamic Data Encryption.

To defend the cyber-physical system (CPSs) from cyber-attacks, this work proposes an unified intrusion detection mechanism which is capable to fast hunt various types of attacks. Focusing on securing the data transmission, a novel dynamic data encryption scheme is developed and historical system data is used to dynamically update a secret key involved in the encryption. The core idea of the dynamic data encryption scheme is to establish a dynamic relationship between original data, secret key, ciphertext and its decrypted value, and in particular, this dynamic relationship will be destroyed once an attack occurs, which can be used to detect attacks. Then, based on dynamic data encryption, a unified fast attack detection method is proposed to detect different attacks, including replay, false data injection (FDI), zero-dynamics, and setpoint attacks. Extensive comparison studies are conducted by using the power system and flight control system. It is verified that the proposed method can immediately trigger the alarm as soon as attacks are launched while the conventional χ2 detection could only capture the attacks after the estimation residual goes over the predetermined threshold. Furthermore, the proposed method does not degrade the system performance. Last but not the least, the proposed dynamic encryption scheme turns to normal operation mode as the attacks stop.

Giant Solitary Fibrous Tumor of the Ascending Aortic Wall Causing Reversible Heart Failure: A Case Report and Review of the Literature.

A 56-year-old woman was admitted to our hospital with a 2-week history of chest tightness and fatigue, and an echocardiogram revealed a massive polyserous cavity effusion. A massive (13.5 cm maximum diameter) intrapericardial mass was discovered using computed tomography (CT) and cardiovascular magnetic resonance imaging (MRI) in the ascending aortic wall. A pericardial biopsy was performed and diagnosed as a solitary fibrous tumor (SFT). After successful mass resection, an immunohistochemical test was positive for CD34, STAT-6, CD34, and Bcl2, which indicates a giant benign solitary fibrous tumor of the ascending aortic wall. After three years of follow-up, the patient is symptom-free, and histological indications of malignancy were absent. A giant benign solitary fibrous tumor is extremely rare in the heart, especially from the ascending aorta wall, and experience with this tumor location is limited, so close follow-up at regular intervals is considered necessary. We present this case, followed by a literature review on SFTs involving the heart and management approaches.

HimGNN: a novel hierarchical molecular graph representation learning framework for property prediction.

Accurate prediction of molecular properties is an important topic in drug discovery. Recent works have developed various representation schemes for molecular structures to capture different chemical information in molecules. The atom and motif can be viewed as hierarchical molecular structures that are widely used for learning molecular representations to predict chemical properties. Previous works have attempted to exploit both atom and motif to address the problem of information loss in single representation learning for various tasks. To further fuse such hierarchical information, the correspondence between learned chemical features from different molecular structures should be considered. Herein, we propose a novel framework for molecular property prediction, called hierarchical molecular graph neural networks (HimGNN). HimGNN learns hierarchical topology representations by applying graph neural networks on atom- and motif-based graphs. In order to boost the representational power of the motif feature, we design a Transformer-based local augmentation module to enrich motif features by introducing heterogeneous atom information in motif representation learning. Besides, we focus on the molecular hierarchical relationship and propose a simple yet effective rescaling module, called contextual self-rescaling, that adaptively recalibrates molecular representations by explicitly modelling interdependencies between atom and motif features. Extensive computational experiments demonstrate that HimGNN can achieve promising performances over state-of-the-art baselines on both classification and regression tasks in molecular property prediction.

Comprehensive analysis of m6A regulators and relationship with tumor microenvironment, immunotherapy strategies in colorectal adenocarcinoma.

BACKGROUND: The N6-methyladenosine (m6A) RNA modification is the most prevalent and abundant type found in eukaryotic cells. It plays a crucial role in the initiation and progression of cancers. In this study, we aimed to comprehensively investigate the landscape of m6A regulators and their association with tumor microenvironment (TME), immunotherapeutic strategies in colon adenocarcinoma (COAD). RESULTS: The differential expression, mutation, CNV frequency and prognostic value of 27 m6A regulators were systematically analyzed in COAD. Patients were classified into two clusters based on m6A regulators through consistent clustering analysis, with cluster A showing significant survival benefits. Most of the m6A regulators were negatively correlated with immune cells, except for WTAP, IGF2BP3, FTO, ALKBH5, which showed a positive correlation. We developed an m6A scoring system to calculate the m6Ascore for each patient. Patients with a high-m6Ascore had a better outcome, with the AUC of 0.775. An independent cohort of 416 COAD patients acquired from GSE38832 database was used to validate the prognosis prediction ability of m6Ascore. Moreover, the m6Ascore was negatively correlated with infiltration of anti-tumor immune cells. Additionally, patients with a high-m6Ascore responded better to anti-PD1 and anti-CTLA4 therapies, and those with MSI-H had a higher m6Ascore. Finally, we investigated the value of m6Ascore in predicting the response of patients to 15 commonly used drugs. CONCLUSIONS: We comprehensively analyzed m6A regulators in COAD, including RNA expression, CNV changes, mutations and their correlation with TME. Our results showed that the m6A scoring system had significant predictive power for the prognosis of COAD patients, potentially leading to new personalized immunotherapy strategies.

The structure of the RBD-E77 Fab complex reveals neutralization and immune escape of SARS-CoV-2.

The spike protein (S) of SARS-CoV-2 is the major target of neutralizing antibodies and vaccines. Antibodies that target the receptor-binding domain (RBD) of S have high potency in preventing viral infection. The ongoing evolution of SARS-CoV-2, especially mutations occurring in the RBD of new variants, has severely challenged the development of neutralizing antibodies and vaccines. Here, a murine monoclonal antibody (mAb) designated E77 is reported which engages the prototype RBD with high affinity and potently neutralizes SARS-CoV-2 pseudoviruses. However, the capability of E77 to bind RBDs vanishes upon encountering variants of concern (VOCs) which carry the N501Y mutation, such as Alpha, Beta, Gamma and Omicron, in contrast to its performance with the Delta variant. To explain the discrepancy, cryo-electron microscopy was used to analyze the structure of an RBD-E77 Fab complex, which reveals that the binding site of E77 on RBD belongs to the RBD-1 epitope, which largely overlaps with the binding site of human angiotensin-converting enzyme 2 (hACE2). Both the heavy chain and the light chain of E77 interact extensively with RBD and contribute to the strong binding of RBD. E77 employs CDRL1 to engage Asn501 of RBD and the Asn-to-Tyr mutation could generate steric hindrance, abolishing the binding. In sum, the data provide the landscape for an in-depth understanding of immune escape of VOCs and rational antibody engineering against emerging variants of SARS-CoV-2.

The glycoside hydrolase 28 member VdEPG1 is a virulence factor of Verticillium dahliae and interacts with the jasmonic acid pathway-related gene GhOPR9.

Glycoside hydrolase (GH) family members act as virulence factors and regulate plant immune responses during pathogen infection. Here, we characterized the GH28 family member endopolygalacturonase VdEPG1 in Verticillium dahliae. VdEPG1 acts as a virulence factor during V. dahliae infection. The expression level of VdEPG1 was greatly increased in V. dahliae inoculated on cotton roots. VdEPG1 suppressed VdNLP1-mediated cell death by modulating pathogenesis-related genes in Nicotiana benthamiana. Knocking out VdEPG1 led to a significant decrease in the pathogenicity of V. dahliae in cotton. The deletion strains were more susceptible to osmotic stress and the ability of V. dahliae to utilize carbon sources was deficient. In addition, the deletion strains lost the ability to penetrate cellophane membrane, with mycelia showing a disordered arrangement on the membrane, and spore development was affected. A jasmonic acid (JA) pathway-related gene, GhOPR9, was identified as interacting with VdEPG1 in the yeast two-hybrid system. The interaction was further confirmed by bimolecular fluorescence complementation and luciferase complementation imaging assays in N. benthamiana leaves. GhOPR9 plays a positive role in the resistance of cotton to V. dahliae by regulating JA biosynthesis. These results indicate that VdEPG1 may be able to regulate host immune responses as a virulence factor through modulating the GhOPR9-mediated JA biosynthesis.

Identification and screening of fungicides against Piper nigrum basal Fusarium wilt disease in Hainan, China.

Fusarium wilt has occurred in the main Piper nigrum cultivation regions, which seriously affects the yield and quality of P. nigrum. To identify the pathogen of this disease, the diseased roots were collected from a demonstration base in Hainan Province. The pathogen was obtained by tissue isolation method and confirmed by pathogenicity test. Based on the morphological observation, sequence analyses of TEF1-α nuclear gene, Fusarium solani was identified as the pathogen causing P. nigrum Fusarium wilt and induced symptoms on inoculated plants, including chlorosis, necrotic spots, wilt, drying, and root rot. The experiments for the antifungal activity showed that all the 11 fungicides selected in this study showed certain inhibitory effects on the colony growth of F. solani, where 2% kasugamycin AS, 45% prochloraz EW, 25 g·L-1 fludioxonil SC and 430 g·L-1 tebuconazole SC exhibited relative higher inhibitory effects with EC50 as 0.065, 0.205, 0.395, and 0.483 mg·L-1 , respectively, and were selected to perform SEM analysis and test in seeds in vitro. The SEM analysis showed that kasugamycin, prochloraz, fludioxonil, and tebuconazole might have exerted their antifungal effect by damaging F. solani mycelia or microconidia. These preparations were applied as a seed coating of P. nigrum Reyin-1. The kasugamycin treatment was most effective in reducing the harmful impact of F. solani on the seed germination. These results presented herein provide useful guidance for the effective control of P. nigrum Fusarium wilt.

First Report of Pestalotiopsis clavispora causing Leaf Spot on Pandanus amaryllifolius in China.

Pandanus amaryllifolius, also known as pandan, is a perennial herb, growing in Indonesia, China and the Maluku Islands (Wakte et al. 2009). It is the only plant with aromatic leaves in the Pandanaceae. It is widely used in food, medicine, cosmetics and other industries, and is also known as "Oriental Vanilla." Pandan is planted in Hainan province over 1,300 ha and is the main plant intercropped among the forest trees. From 2020, the leaf spot was surveyed for three years. Diseased leaves occurred on 30 to 80% of the surveyed plants, with an incidence of 70% and yield losses of 40%. The disease occured from mid-November to April and was most severe at low temperatures and humidity. Initial symptoms were pale green spots, that formed dark brown, nearly circular lesions. As the lesions expanded, their centers became greyish white, with yellow halos at the junction of the diseased and healthy tissue. When the humidity was high, there were small black spots scattered in the center of the lesion. Symptomatic leaf samples were collected from four different sites. The leaf surface was disinfested with 75% ethyl alcohol for 30 s and washed with sterile distilled water three times. Samples from the junction of diseased and healthy tissue (0.5 × 0.5 cm) were removed and placed on potato dextrose agar (PDA) medium containing 100 µg/mL of cefotaxime sodium and cultivated in a dark incubator at 28°C. After two days, hyphal tips from the edges of growing colonies were transferred to fresh PDA plates for further purification. Following Koch's postulates, colonies from strains were used as inoculum in pathogenicity tests. Colonies with 5 mm diameter were inoculated upside onto fresh and healthy pandan leaves via wounding method (pinpricked by sterilized needles) and non-wounding method. Sterilized PDA was used as control. All plants were setted three replicates and were incubated at 28℃ for 3 to 5 days. When symptoms on leaves similar to those in the field appeared, the fungus were reisolated The colonies formed on PDA were also consistent with the original isolate (Scandiani et al, 2003). After seven days, the colony covered the whole petri dish with white, petal-shaped growth with a slight concentric, annular bulge in the center, irregular edges, with black acervuli emerging at a later stage of colony growth. Conidia were fusiform, 18.1±1.6 × 6.4±0.3 µm, showing four septations and five cells, the middle three cells were brownish black to olivaceous, and the apical cell colorless with two to three filaments, 21.8±3.5 µm long. The caudate cell was colorless with one stalk 5.9±1.8 µm long (Zhang et al. 2021; Shu et al. 2020). According to the colony and conidia characteristics, the pathogen was initially identified as Pestalotiopsis spp. (Benjamin et al. 1961). To confirm the pathogen identity, we used the universal primers ITS1/ITS4, targeting primers EF1-728F/EF1-986R and Bt2a/Bt2b sequences (Tian et al. 2018). The sequences of the PCR products were deposited in NCBI GenBank with accession numbers OQ165166 (ITS), OQ352149 (TEF1-α) and OQ352150 (TUB2). BLAST results showed that the sequences of the ITS, TEF1-α and TUB2 genes shared 100% homology with the sequences of Pestalotiopsis clavispora. The maximum likelihood method was used in the phylogenetic analysis. The result showed that LSS112 was clustered with Pestalotiopsis clavispora with a support rate of 99%. Based on morphological and molecular characteristics, the pathogen was confirmed as Pestalotiopsis clavispora. To our knowledge, this is the first report of leaf spot of pandan caused by Pestalotiopsis clavispora in China. This research will be immediately helpful for the diagnosis and control the disease on pandan.

The mechanism of STING autoinhibition and activation.

2',3'-cGAMP, produced by the DNA sensor cGAS, activates stimulator of interferon genes (STING) and triggers immune response during infection. Tremendous effort has been placed on unraveling the mechanism of STING activation. However, little is known about STING inhibition. Here, we found that apo-STING exhibits a bilayer with head-to-head as well as side-by-side packing, mediated by its ligand-binding domain (LBD). This type of assembly holds two endoplasmic reticulum (ER) membranes together not only to prevent STING ER exit but also to eliminate the recruitment of TBK1, representing the autoinhibited state of STING. Additionally, we obtained the filament structure of the STING/2',3'-cGAMP complex, which adopts a bent monolayer assembly mediated by LBD and transmembrane domain (TMD). The active, curved STING polymer could deform ER membrane to support its ER exit and anterograde transportation. Our data together provide a panoramic vision regarding STING autoinhibition and activation, which adds substantially to current understanding of the cGAS-STING pathway.

Prediction of no reflow phenomenon in percutaneous coronary intervention with optical coherence tomography and analysis of risk factors.

Objective :To investigate the predictive value of no reflow phenomenon in interventional therapy by measuring plaque quantitatively with optical coherence tomography (OCT).  Methods:196 patients with acute ST segment elevation myocardial infarction who visited the Department of Cardiology of the Second Affiliated Hospital of Zhengzhou University from January 2020 to January 2022 were selected as the study objects. According to whether there was no reflow during the operation, they were divided into no reflow group (46 cases) and normal flow group (150 cases). Systematically collect general clinical data and coronary angiography related data of patients through inpatient cases, measure fiber cap thickness and lipid core angle of diseased vascular plaque through optical coherence tomography, and analyze the relationship between fiber cap thickness and no reflow phenomenon   Results:BMI, LDL, phospholipase A, the proportion of family history of coronary heart disease, and the thrombus load in the no reflow group were higher than those in the normal flow group (P<0.05), while the thickness of the fibrous cap was lower than that in the normal flow group (P<0.05); Further multivariate logistic regression analysis showed that fiber cap thickness, phospholipase A and severe thrombosis load were independent risk factors for non reflow phenomenon (P<0.05); Further ROC curve analysis found that the thickness of fiber cap had a high predictive value for no reflow phenomenon, and the best cutoff value for no reflow was 95, AUC: 0.926 (95% CI: 0.891-0.961, P<0.001). Conclusions: Optical coherence tomography can predict the occurrence of no reflow phenomenon by measuring the fiber cap thickness quantitatively. The prediction effect is the best when the fiber cap thickness is 95.

Comprehensive analysis of cuproptosis-related long noncoding RNA for predicting prognostic and diagnostic value and immune landscape in colorectal adenocarcinoma.

BACKGROUND: Cuproptosis, as a copper-induced mitochondrial cell death, has attracted extensive attention recently, especially in cancer. Although some key regulatory genes have been identified in cuproptosis, the related lncRNAs have not been further studied. Exploring the prognostic and diagnostic value of cuproptosis-related lncRNAs (CRLs) in colon adenocarcinoma and providing guidance for individualized immunotherapy for patients are of great significance. RESULTS: A total of 2003 lncRNAs were correlated with cuproptosis genes and considered as CRLs. We screened 33 survival-associated CRLs and established a prognostic signature base on 7 CRLs in the training group. The patients in the low-risk group had better outcomes in both training group (P < 0.001) and test group (P = 0.016). More exciting, our model showed good prognosis prediction in both stage I-II (P = 0.020) and stage III-IV (P = 0.001). The nomogram model could further improve the accuracy of prognosis prediction. Interestingly, glucose-related metabolic pathways, which were closely related to cuproptosis, were enriched in the low-risk group. Meanwhile, the immune infiltration scores were lower in the high-risk group. The high-risk group was more sensitive to OSI.906 and ABT.888, while low-risk group was more sensitive to Sorafenib. Three lncRNAs, FALEC, AC083967.1 and AC010997.4, were highly expressed in serum of COAD patients, and the AUC was 0.772, 0.726 and 0.714, respectively, indicating their valuable diagnostic value. CONCLUSIONS: Our research constructed a prognostic signature based on 7 CRLs and found three promising diagnostic markers for COAD patients. Our results provided a reference to the personalized immunotherapy strategies.

Establishment of a PPP2CA homozygous knockout human embryonic stem cell line via CRISPR/Cas9 system.

Protein phosphatase 2A (PPP2CA) is one of the four main Ser/Thr phosphatase enzymes, which involved in the negative control of cell growth and division. PPP2CA is the main protein phosphatase in the heart, which regulates Ca (2+) through a series of ion channels and transporters. In this study, we generated a PPP2CA homozygous knockout human embryonic stem cell line WAe009-A-25 based on the transient expression CRISPR/Cas9 system to investigate functional effect of PP1 deficiency. This cell line has multidirectional differentiation potential, normal karyotypic and trilineage differentiation potential in vivo.

Prognosis and Personalized Treatment Prediction in Different Mutation-Signature Hepatocellular Carcinoma.

Introduction: Mutation patterns have been extensively explored to decipher the etiologies of hepatocellular carcinoma (HCC). However, the study and potential clinical role of mutation patterns to stratify high-risk patients and optimize precision therapeutic strategies remain elusive in HCC. Methods: Using exon-sequencing data in public (n=362) and in-house (n=30) cohorts, mutation signatures were extracted to decipher relationships with the etiology and prognosis in HCC. The proteomics (n=159) and cell-line transcriptome data (n=1019) were collected to screen the implication of sensitive drugs. A novel multi-step machine-learning framework was then performed to construct a classification predictor, including recognizing stable reversed gene pairs, establishing a robust prediction model, and validating the robustness of the predictor in five independent cohorts (n=900). Results: Two heterogeneous mutation signature clusters were identified, and a high-risk prognosis cluster was recognized for further analysis. Notably, mutation signature cluster 1 (MSC1) was featured by activated anti-tumor immune and metabolism dysfunctional states, higher genomic instability (high TMB, SNV neoantigen, indel neoantigens, and total neoantigens), and a dismal prognosis. Notably, MSC performed as an independent risk factor than clinical traits (eg, stage, vascular invasion). Additionally, afatinib and canertinib were recognized which might have potential therapeutic implications in MSC1, and the targets of these drugs presented a higher expression in both gene and protein levels in HCC. Discussion: Our studies may provide a promising platform for improving prognosis and tailoring therapy in HCC.