Brain Stimulation of Dorsolateral Prefrontal Cortices Influences Impulsivity in Delay Discounting Choices.

Intertemporal decision-making is pivotal for human interests and health. Recently, studies instructed participants to make intertemporal choices for both themselves and others, but the specific mechanisms are still debated. To address the issue, in the current study, the cost-unneeded conditions (i.e., "Self Immediately - Self Delay" and "Other Immediately - Other Delay" conditions) and the cost-needed conditions (i.e., "Self Immediately - Other Delay" and "Self delay - Other immediately" conditions) were set with the identity of OTHER being a stranger. We manipulated the magnitude of reward (Experiment 1) and disrupted the activation of the dorsolateral prefrontal cortex with repetitive transcranial magnetic stimulation (rTMS; Experiment 2). We found that both the behavioral and rTMS manipulations increased smaller but sooner choice probability via reducing self-control function. The reduced self-control function elicited by rTMS affected both self- and other-related intertemporal choices via increasing the choice preference for SS options, which may help people deeply understand the relationship between self- and other-related intertemporal choices in processing mechanism, especially when the "OTHER" condition is set as a stranger.

A fluorescent aptasensor for enzyme-free and sensitive detection of kanamycin based on entropy-driven strand displacement reaction.

BACKGROUND: Kanamycin is an antibiotic that can easily cause adverse side effects if used improperly. Due to the extremely low concentrations of kanamycin in food, quantitative detection of kanamycin becomes a challenge. As one of the DNA self-assembly strategies, entropy-driven strand displacement reaction (EDSDR) does not require enzymes or hairpins to participate in the reaction, which greatly reduces the instability of detection results. Therefore, it is a very beneficial attempt to construct a highly sensitive and specific fluorescence detection method based on EDSDR that can detect kanamycin easily and quickly while ensuring that the results are effective and stable. RESULTS: We created an enzyme-free fluorescent aptamer sensor with high specificity and sensitivity for detecting kanamycin in milk by taking advantage of EDSDR and the high specific binding between the target and its aptamer. The specific binding can result in the release of the promoter chain, which then sets off the pre-planned EDSDR cycle. Fluorescent label modification on DNA combined with the fluorescence quenching-recovery mechanism gives the sensor impressive fluorescence response capabilities. The research results showed that within the concentration range of 0.1 nM-50 nM, there was a good relationship between the fluorescence intensity of the solution and the concentration of kanamycin. Specificity experiments and actual sample detection experiments confirmed that the biosensor could achieve highly sensitive and specific detection of trace amounts of kanamycin in food, with a detection limit of 0.053 nM (S/N = 3). SIGNIFICANCE: To our knowledge, this is the first strategy to combine EDSDR with fluorescence to detect kanamycin in food. Accurate results can be obtained in as little as 90 min with no enzymes or hairpins involved in the reaction. Furthermore, our enzyme-free biosensing method is straightforward, highly sensitive, and extremely specific. It has many possible applications, including monitoring antibiotic residues and food safety.

Proposer's moral identity modulates fairness processing in the ultimatum game: Evidence from behavior and brain potentials.

Economic decision-making is pivotal to both human private interests and the national economy. People pursue fairness in economic decision-making, but a proposer's moral identity can influence fairness processing. Previous ERP studies have revealed that moral identity has an effect on fairness considerations in the Ultimatum Game (UG), but the findings are inconsistent. To address the issue, we revised the moral-related sentences and used the ERP technique to measure the corresponding neural mechanism. We have observed that the fairness effect in UG can be mirrored in both MFN and P300 changes, whereas the moral identity effect on fairness in UG can be reflected by MFN but not P300 changes. These findings indicate that the moral identity of the proposer can modulate fairness processing in UG. The current study opens new avenues for clarifying the temporal course of the relationship between the proposer's moral identity and fairness in economic decision-making, which is beneficial for understanding the influencing mechanism of fairness processing and fair allocations in complex social contexts.

XBP1s activates METTL3/METTL14 for ER-phagy and paclitaxel sensitivity regulation in breast cancer.

Cancer cells employ the unfolded protein response (UPR) or induce autophagy, especially selective removal of certain ER domains via reticulophagy (termed ER-phagy), to mitigate endoplasmic reticulum (ER) stress for ER homeostasis when encountering microenvironmental stress. N6-methyladenosine (m6A) is one of the most abundant epitranscriptional modifications and plays important roles in various biological processes. However, the molecular mechanism of m6A modification in the ER stress response is poorly understood. In this study, we first found that ER stress could dramatically elevate m6A methylation levels through XBP1s-dependent transcriptional upregulation of METTL3/METTL14 in breast cancer (BC) cells. Further MeRIP sequencing and relevant validation results confirmed that ER stress caused m6A methylation enrichment on target genes for ER-phagy. Mechanistically, METTL3/METTL14 increased ER-phagy machinery formation by promoting m6A modification of the ER-phagy regulators CALCOCO1 and p62, thus enhancing their mRNA stability. Of note, we further confirmed that the chemotherapeutic drug paclitaxel (PTX) could induce ER stress and increase m6A methylation for ER-phagy. Furthermore, the combination of METTL3/METTL14 inhibitors with PTX demonstrated a significant synergistic therapeutic effect in both BC cells and xenograft mice. Thus, our data built a novel bridge on the crosstalk between ER stress, m6A methylation and ER-phagy. Most importantly, our work provides novel evidence of METTL3 and METTL14 as potential therapeutic targets for PTX sensitization in breast cancer.

Transcriptome exploration of ferroptosis-related genes in TGFß- induced lens epithelial to mesenchymal transition during posterior capsular opacification development.

BACKGROUND: Posterior capsular opacification (PCO) is the main reason affecting the long-term postoperative result of cataract patient, and it is well accepted that fibrotic PCO is driven by transforming growth factor beta (TGFß) signaling. Ferroptosis, closely related to various ocular diseases, but has not been explored in PCO. METHODS: RNA sequencing (RNA-seq) was performed on both TGF-ß2 treated and untreated primary lens epithelial cells (pLECs). Differentially expressed genes (DEGs) associated with ferroptosis were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to investigate their biological function. Additionally, protein-to-protein interactions among selected ferroptosis-related genes by PPI network and the top 10 genes with the highest score (MCC algorithm) were selected as the hub genes. The top 20 genes with significant fold change values were validated using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our analysis revealed 1253 DEGs between TGF-ß2 treated and untreated pLECs, uncovering 38 ferroptosis-related genes between two groups. Among these 38 ferroptosis-related genes,the most prominent GO enrichment analysis process involved in the response to oxidative stress (BPs), apical part of cell (CCs),antioxidant activity (MFs). KEGG were mainly concentrated in fluid shear stress and atherosclerosis, IL-17 and TNF signaling pathways, and validation of top 20 genes with significant fold change value were consistent with RNA-seq. CONCLUSIONS: Our RNA-Seq data identified 38 ferroptosis-related genes in TGF-ß2 treated and untreated pLECs, which is the first observation of ferroptosis related genes in primary human lens epithelial cells under TGF-ß2 stimulation.

Copper-Induced In Vivo Gene Amplification in Budding Yeast.

In the biotechnological industry, multicopy gene integration represents an effective strategy to maintain a high-level production of recombinant proteins and to assemble multigene biochemical pathways. In this study, we developed copper-induced in vivo gene amplification in budding yeast for multicopy gene expressions. To make copper as an effective selection pressure, we first constructed a copper-sensitive yeast strain by deleting the CUP1 gene encoding a small metallothionein-like protein for copper resistance. Subsequently, the reporter gene fused with a proline-glutamate-serine-threonine-destabilized CUP1 was integrated at the δ sites of retrotransposon (Ty) elements to counter the copper toxicity at 100 µM Cu2+. We further demonstrated the feasibility of modulating chromosomal rearrangements for increased protein expression under higher copper concentrations. In addition, we also demonstrated a simplified design of integrating the expression cassette at the CUP1 locus to achieve tandem duplication under high concentrations of copper. Taken together, we envision that this method of copper-induced in vivo gene amplification would serve as a robust and useful method for protein overproduction and metabolic engineering applications in budding yeast.

Novel fluorescence nano-orbital biosensor for highly sensitive microRNA detection.

BACKGROUND: MicroRNAs play an important role in regulating cell function and gene expression. Early prevention and clinical diagnosis of diseases have high requirements for high-sensitivity detection of microRNAs. Due to the limitations of tedious operation and large sample size, miRNA with small molecular weight and low expression abundance cannot be accurately detected in traditional miRNA detection. To improve the sensitivity and accuracy of detection, we established a novel biosensor based on nucleic acid circuit of signal amplification, which converted miRNA recognition into a fluorescence signal for amplification. RESULTS: We designed a biosensor based on an exponential amplification reaction with cascaded HCR and DNAzyme nucleic acid circuit (named E-NOF biosensor) by amplicon sub-fragments to trigger the construction of fluorescence nano-orbitals (NOF), which could be used to detect miRNA ultrasensitively. By modifying two fluorophores (Cy3 and Cy5) on the chain of constructing nano-orbitals, when the amplicon triggered the construction of nano-orbitals, fluorescence resonance energy transfer (FRET) occurred between Cy3 and Cy5, and then two fluorescence signals with different trends could be observed. Therefore, through the ratio of the two signals, we could quantitatively and quickly detect the miRNA from 1 fM to 100 nM, and the E-NOF biosensor detection limit was as low as 0.129 fM. Furthermore, the HCR nucleic acid circuit cascaded with DNAzyme could enrich the fluorophores on the nano-orbitals and significantly enhance the fluorescence signal by accelerating the reaction rate. SIGNIFICANCE: According to our understanding, the E-NOF biosensor is the first strategy to cascade EXPAR with HCR and DNAzyme nucleic acid circuit for miRNA-1246 detection. Accurate results can be obtained in only 120 min. Compared with the traditional HCR system, the sensitivity of the new E-NOF biosensor is increased by 1 × 109 times. Furthermore, the biosensor can also detect biomarkers in human serum samples. It has great potential in miRNA detection and identification.

Synthesis and Optoelectronic Properties of a Novel Pt(IV)(C∧N∧C)(Cl)2(DMSO) Complex Cyclometalated by Tridentate Diphenylpyridine.

A novel tridentate-cyclometalating Pt(IV) complex, namely, Pt(IV)(C∧N∧C)(Cl)2(DMSO), is initially synthesized through a series of reactions using Pt(II) complexes. The optoelectronic properties of Pt(IV)(C∧N∧C)(Cl)2(DMSO) are fully studied by adequate characterizations.

Cascaded amplifying circuit enables sensitive detection of fungal pathogens.

The rapid and accurate detection of fungal pathogens is of utmost importance in the fields of healthcare, food safety, and environmental monitoring. In this study, we implemented a cascaded amplifying circuit in Saccharomyces cerevisiae to improve the G protein-coupled receptor (GPCR) mediated fungal detection. The GPCR signaling pathway was coupled with the galactose-regulated (GAL) system and a positive feedback loop was implemented to enhance the performance of yeast biosensor. We systematically compared four generations of biosensors for detecting the mating pheromone of Candida albicans, and the best biosensor exhibited the limit of detection (LOD) as low as 0.25 pM and the limit of quantification (LOQ) of 1 pM after 2 h incubation. Subsequently, we developed a betaxanthin-based colorimetric module for the easy visualization of signal outputs, and the resulting biosensors can give reliable naked-eye readouts. In summary, we demonstrated that cascaded amplifying circuits could substantially improve the engineered yeast biosensors with a better sensitivity and signal output magnitude, which will pave the way for their real-world applications in public health.

[Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia].

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION: VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Chidamide, Decitabine, Cytarabine, Aclarubicin, and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Retrospective Study from a Single-Center.

OBJECTIVE: Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia. However, their efficacy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains unclear. METHODS: Clinical data of R/R AML patients who received a CDCAG regimen (chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor) from July 1, 2018 to October 31, 2021 at our center were retrospectively assessed, and the safety and efficacy of the CDCAG regimen were evaluated. Patients were followed up until November 30, 2021, with a median follow-up of 21.6 months (95% CI: 10.0-33.2 months). RESULTS: A total of 67 patients were enrolled. Two patients died within 3 weeks after the initiation, and therefore only 65 patients underwent the assement for clinical response and survival. It was found that 56.9% patients achieved complete remission with a median overall survival (OS) of 9.6 months. The median OS of responders was 25.9 months, while that of non-responders was 5.0 months (P<0.0001). Patients with gene mutations had a superior overall response rate (ORR) (80.4% vs. 45.5%, P=0.043) compared to those without gene mutations. The presence of DNA methyltransferase 3 A (DNMT3A), ten-eleven translocation-2 (TET2), and isocitrate dehydrogenase 1/2 (IDH1/2) mutations did not affect the response rate (88.2% vs. 68.9%, P=0.220) and reflected a better OS (not attained vs. 9.0 months, P=0.05). The most common non-hematologic adverse events were pulmonary infection (73.1%), followed by febrile neutropenia (23.9%) and sepsis (19.4%). CONCLUSIONS: The CDCAG regimen was effective and well-tolerated in R/R AML patients, increasing the potential for allogeneic hematopoietic stem cell transplantation. Moreover, patients with DNMT3A, TET2, and IDH1/2 mutations might benefit from this regimen.

[Correlation between rhizosphere environment and content of medicinal components of Arnebia euchroma].

This study aimed to explore the correlation between rhizosphere soil microorganisms of wild Arnebia euchroma and the content of medicinal components to provide guidance for the selection of the ecological planting base. The total DNA of rhizosphere soil microorganisms of wild A. euchroma was extracted, and the microbial community structure of rhizosphere soil microorganisms was analyzed by IlluminaMiseq high-throughput sequencing technology. The content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin in medicinal materials was determined by high-performance liquid chromatography(HPLC). The physicochemical pro-perties of rhizosphere soil of wild A. euchroma in main producing areas were determined, and the correlation of soil microbial abundance with index component content and soil physicochemical properties was analyzed by SPSS software. The results showed that the species composition of rhizosphere fungi and bacteria in A. euchroma from different habitats was similar at the phylum and genus levels, but their relative abundance, richness index(Chao1), and community diversity(Simpson) index were different. Correlation analysis showed that the content of available phosphorus in soil was positively correlated with the content of total hydroxynaphthoquinone pigment and ß,ß'-dimethylacrylalkannin, and the abundance of five fungal genera such as Solicoccozyma and six bacterial genera such as Pseudo-nocardia and Bradyrhizobium was positively correlated with the content of medicinal components in medicinal materials. The abundance of Bradyrhizobium was significantly positively correlated with the content of ß,ß'-dimethylacrylalkanin. The abundance of fungi such as Archaeorhizomyces was significantly positively correlated with the content of available phosphorus in rhizosphere soil, and Bradyrhizobium was significantly negatively correlated with soil pH. Therefore, the abundance of fungi and bacteria in the rhizosphere of A. euchroma has a certain correlation with the medicinal components and the physicochemical properties of the rhizosphere soil, which can provide a scientific basis for the selection of ecological planting bases in the later stage.

Reshaping the yeast galactose regulon via GPCR signaling cascade.

Dynamically regulated systems are preferable to control metabolic pathways for an improved strain performance with better productivity. Here, we harnessed to the G protein-coupled receptor (GPCR) signaling pathway to reshape the yeast galactose regulon. The galactose-regulated (GAL) system was coupled with the GPCR signaling pathway for mating pheromone via a synthetic transcription factor. In this study, we refabricated the dynamic range, sensitivity, and response time of the GAL system to α factor by modulating the key components of the GPCR signaling cascade. A series of engineered yeasts with self-secretion of α factor were constructed to achieve quorum-sensing behaviors. In addition, we also repurposed the GAL system to make it responsive to heat shock. Taken together, our work showcases the great potential of synthetic biology in creating user-defined metabolic controls. We envision that the plasticity of our genetic design would be of significant interest for the future fabrication of novel gene expression systems.

Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss.

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

A Layered Genetic Design Enables the Yeast Galactose Regulon to Respond to Cyanamide.

The commonly used expression systems in Saccharomyces cerevisiae typically rely on either constitutive or galactose-regulated promoters. The lack of inducible systems in S. cerevisiae limits the precise temporal regulation of protein function and yeast metabolism. We herein repurposed the galactose-regulated system to make it respond to cyanamide. By using a cyanamide-inducible DDI2 promoter to control Gal4 expression in CEN.PK2-1C with Δgal80, a tight and graded cyanamide-inducible GAL system with an enhanced signal output was constructed. Subsequently, we demonstrated that the cyanamide-inducible GAL system was capable of tightly regulating the pentafunctional Aro1 protein to achieve conditional shikimate pathway activity. Taken together, the cyanamide-inducible GAL system could be implemented for both fundamental research and applied biotechnology.

Characterizing RNA-binding ligands on structures, chemical information, binding affinity and drug-likeness.

Recent studies suggest RNAs act as promising drug targets. However, limited development has been achieved in detecting RNA-ligand interactions. To guide the discovery of RNA-binding ligands, it is necessary to characterize them comprehensively, especially in the binding specificity, binding affinity and drug-like properties. We established a database, RNALID (http://biomed.nscc-gz.cn/RNALID/html/index.html#/database), which collects RNA-ligand interactions validated by low-throughput experiment. RNALID contains 358 RNA-ligand interactions. Comparing to the fellow database, 94.5% of ligands in RNALID are completely or partially novel collections, and 51.78% have novel two-dimensional (2D) structures. Through the analysis of ligand structure, binding affinity and cheminformatic parameters we found that multivalent (MV) ligands mainly binding to RNA repeats are more structurally conserved in both 2D and 3D structures than other ligand types, exhibit higher binding specificity and binding affinity than ligands binding to non-repeat RNAs, but deviate far from the Lipinski's rule of five. In contrary, small molecule (SM) ligands binding to virus RNA exhibit higher affinity and more resemble protein-ligands, but potentially possess low binding specificity. Further analysis on 28 detailed drug-likeness properties indicated that RNA-ligands' development need to balance between the binding affinity and the drug-likeness because of the significant linear co-relationship between the two. Comparing RNALID ligands to FDA-approved drugs and ligands without bioactivity indicated that RNA-binding ligands are different from them in chemical properties, structural properties and drug-likeness. Thus, characterizing the RNA-ligand interactions in RNALID in multiple respects provides new insights into discovering and designing druggable ligands binding with RNA.

[Establishment and Clinical Significance of Prognostic Nomogram Model for Diffuse Large B-Cell Lymphoma Based on Immunohistochemistry Markers and International Prognostic Index Scores].

OBJECTIVE: To retrospectively analyze clinical characteristics and survival time of patients with diffuse large B-cell lymphoma (DLBCL), detect prognosis-related markers, and establish a nomogram prognostic model of clinical factors combined with biomarkers. METHODS: One hundred and thirty-seven patients with DLBCL were included in this study from January 2014 to March 2019 in the First Affiliated Hospital of Nanchang University. The expression of GCET1, LMO2, BCL-6, BCL-2 and MYC protein were detected by immunohistochemistry (IHC), then the influences of these proteins on the survival and prognosis of the patients were analyzed. Univariate and multivariate Cox regression analysis were used to gradually screen the prognostic factors in nomogram model. Finally, nomogram model was established according to the result of multivariate analysis. RESULTS: The positive expression of GCET1 protein was more common in patients with Ann Arbor staging I/II (P =0.011). Compared with negative patients, patients with positive expression of LMO2 protein did not often show B symptoms (P =0.042), and could achieve better short-term curative effect (P =0.005). The overall survival (OS) time of patients with positive expression of LMO2 protein was significantly longer than those with negative expression of LMO2 protein (P =0.018), though the expression of LMO2 protein did not correlate with progression-free survival (PFS) (P >0.05). However, the expression of GCET1 protein had no significant correlation with OS and PFS. Multivariate Cox regression analysis showed that nomogram model consisted of 5 prognostic factors, including international prognostic index (IPI), LMO2 protein, BCL-2 protein, MYC protein and rituximab. The C-index applied to the nomogram model for predicting 4-year OS rate was 0.847. Moreover, the calibrated curve of 4-year OS showed that nomogram prediction had good agreement with actual prognosis. CONCLUSION: The nomogram model incorporating clinical characteristics and IHC biomarkers has good discrimination and calibration, which provides a useful tool for the risk stratification of DLBCL.

A Pseudomonas Lysogenic Bacteriophage Crossing the Antarctic and Arctic, Representing a New Genus of Autographiviridae.

Polar regions tend to support simple food webs, which are vulnerable to phage-induced gene transfer or microbial death. To further investigate phage-host interactions in polar regions and the potential linkage of phage communities between the two poles, we induced the release of a lysogenic phage, vB_PaeM-G11, from Pseudomonas sp. D3 isolated from the Antarctic, which formed clear phage plaques on the lawn of Pseudomonas sp. G11 isolated from the Arctic. From permafrost metagenomic data of the Arctic tundra, we found the genome with high-similarity to that of vB_PaeM-G11, demonstrating that vB_PaeM-G11 may have a distribution in both the Antarctic and Arctic. Phylogenetic analysis indicated that vB_PaeM-G11 is homologous to five uncultured viruses, and that they may represent a new genus in the Autographiviridae family, named Fildesvirus here. vB_PaeM-G11 was stable in a temperature range (4-40 °C) and pH (4-11), with latent and rise periods of about 40 and 10 min, respectively. This study is the first isolation and characterization study of a Pseudomonas phage distributed in both the Antarctic and Arctic, identifying its lysogenic host and lysis host, and thus provides essential information for further understanding the interaction between polar phages and their hosts and the ecological functions of phages in polar regions.

Small-Molecule Organic Cathodes with Carbon Coating for Highly Efficient Potassium-ion Batteries.

Small-molecule organic cathodes face dissolution in potassium-ion batteries (PIBs). For the first time, an interesting and effective strategy is unveiled to resolve this issue by designing a new soluble small-molecule organic compound namely [N,N'-bis(2-anthraquinone)]-1,4,5,8-naphthalenetetracarboxdiimide (NTCDI-DAQ, 237 mAh g-1 ): Through the precise manipulation of carbonization temperature and time, the molecules on the surface of NTCDI-DAQ particles can be transformed into amorphous carbon with controllable thickness. This strategy called surface self-carbonization can form a carbon protective layer on organic cathodes and significantly increase their insolubility against liquid electrolytes without affecting the electrochemical behavior of bulk particles. As a result, the as-obtained NTCDI-DAQ@C sample displays significantly improved cathode performance in PIBs. In half cells, NTCDI-DAQ@C shows superior capacity stability of 84 % compared to 35 % of NTCDI-DAQ during 30 cycles under the same conditions. In full cells with a KC8 anode, NTCDI-DAQ@C delivers a peak discharge capacity of 236 mAh g-1 cathode and a high energy density of 255 Wh kg-1 cathode in 0.1-2.8 V, with 40 % capacity retention during 3000 cycles at 1 A g-1 . To the best of our knowledge, the integrated performance of NTCDI-DAQ@C is among the best of soluble organic cathodes reported in PIBs.

Translocator protein 18 kDa regulates retinal neuron apoptosis and pyroptosis in glaucoma.

Glaucoma is the leading cause of blindness worldwide. However, our insufficient understanding of the pathogenesis of glaucoma has limited the development of effective treatments. Because recent research has highlighted the importance of non-coding RNAs (ncRNAs) in various diseases, we investigated their roles in glaucoma. Specifically, we detected expression changes of ncRNAs in cell and animal models of acute glaucoma. Further analysis revealed that the Ier2/miR-1839/TSPO axis was critical to cell loss and retinal damage. The knockdown of Ier2, the overexpression of miR-1839, and the silencing of TSPO effectively prevented retinal damage and cell loss. Furthermore, we found that the Ier2/miR-1839/TSPO axis regulated the pyroptosis and apoptosis of retinal neurons through the NLRP3/caspase1/GSDMD, cleaved-caspase3 pathways. In addition to high expression in the retina, TSPO expression was found to be significantly higher in the dorsal lateral geniculate nucleus (DLG) of the brain in the pathologically high intraocular pressure (ph-IOP) rat model, as well as in the peripheral blood mononuclear cells (PBMCs) of glaucoma patients with high IOP. These results indicate that TSPO, which is regulated by Ier2/miR-1839, plays an important role in the pathogenesis of glaucoma, and this study provides a theoretical basis and a new target for the diagnosis and treatment of glaucoma.