A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma.

BACKGROUND: Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL). METHODS: We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay. RESULTS: The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL. CONCLUSION: The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.

Converting inorganic sulfur into degradable thermoplastics and adhesives by copolymerization with cyclic disulfides.

Converting elementary sulfur into sulfur-rich polymers provides a sustainable strategy to replace fossil-fuel-based plastics. However, the low ring strain of eight-membered rings, i.e., S8 monomers, compromises their ring-opening polymerization (ROP) due to lack of an enthalpic driving force and as a consequence, poly(sulfur) is inherently unstable. Here we report that copolymerization with cyclic disulfides, e.g., 1,2-dithiolanes, can enable a simple and energy-saving way to convert elementary sulfur into sulfur-rich thermoplastics. The key strategy is to combine two types of ROP-both mediated by disulfide bond exchange-to tackle the thermodynamic instability of poly(sulfur). Meanwhile, the readily modifiable sidechain of the cyclic disulfides provides chemical space to engineer the mechanical properties and dynamic functions over a large range, e.g., self-repairing ability and degradability. Thus, this simple and robust system is expected to be a starting point for the organic transformation of inorganic sulfur toward sulfur-rich functional and green plastics.

Exploring the Mechanisms of Yishen Tongluo Decoction on Repairing DNA Damage in Mouse Spermatogonia Cells Based on Whole Transcriptome Sequencing.

The aim of this study was to investigate the potential mechanism through which Yishen Tongluo decoction (YSTL) repairs DNA damage caused by benzo(a)pyrene diol epoxide (BPDE) in mouse spermatocytes (GC-2). The GC-2 cells were divided randomly into the control group, BPDE group, and low-, medium-, and high-dose YSTL groups of YSTL decoction. A comet assay was used to detect the DNA fragment index (DFI) of cells in each group. Based on the DFI results, whole transcriptome sequencing was conducted, followed by trend analysis, gene ontology (GO) enrichment analysis, kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and ceRNA network analysis. Compared with the control group, the BPDE group reported a significant increase in the DNA fragmentation index (DFI) (p < .05). Compared with the BPDE group, the low-, high- and medium-dose YSTL groups had a significantly reduced DFI (p < .05). Whole-transcriptome sequencing revealed seven differentially expressed circRNAs, 203 differentially expressed miRNAs, and 3,662 differentially expressed mRNAs between the control group and the BPDE group. There was a total of 12 differentially expressed circRNAs, 204 miRNAs, and 2150 mRNAs between the BPDE group and the traditional Chinese medicine group. The pathways involved include DNA repair pathway, nucleotide excision repair pathway, base excision repair pathway, etc. The ceRNA network reported that Hmga2 was the core protein involved, novel_cir_000117 and mmu-miR-466c-3p were located upstream of Hmga2, and they were regulatory factors associated with Hmga2. Finally, we conclude that YSTL decoction may repair sperm DNA damage caused by BPDE through the novel_cir_000117-mmu-miR-466c-3p-Hmga2 pathway.

Surface Reconstruction for Selective Oxidation of Tetrahydroisoquinoline.

Integration of hydrogen evolution with the oxidation of organic substances in one electrochemical system is highly desirable. However, achieving selective oxidation of organic substances in the integrated system is still highly challenging. In this study, a phosphorylated NiMoO4 nanoneedle-like array was designed as the catalytic active electrode for the integration of highly selective electrochemical dehydrogenation of tetrahydroisoquinolines (THIQs) with hydrogen production. The leaching of anions, including MoO42- and PO43-, facilitates the reconstruction of the catalyst. As a result, nickel oxyhydroxides with the doping of PO43- and richness of defects are in situ formed. In situ Raman and density functional theory calculations have shown that the high catalytic activity is attributed to the in situ formed PO43- involved NiOOH substance. In the dehydrogenation process, the involved C-H bond but not the N-H bond is first destroyed. A two-electrode system was then fabricated with the optimized electrode that shows a benchmark current density of 10 mA cm-2 at 1.783 V, providing a yield of 70% for dihydroisoquinolines. A robust stability was also shown for this integrated electrochemical system. The understanding of the reconstruction behavior and the achievement of selective dehydrogenation will provide some hints for electrochemical synthesis.

TFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia.

Bleeding and thrombosis are known as common complications of polycythemia for a long time. However, the role of coagulation system in erythropoiesis is unclear. Here, we discover that an anticoagulant protein tissue factor pathway inhibitor (TFPI) plays an essential role in erythropoiesis via the control of heme biosynthesis in central macrophages. TFPI levels are elevated in erythroblasts of human erythroblastic islands with JAK2V617F mutation and hypoxia condition. Erythroid lineage-specific knockout TFPI results in impaired erythropoiesis through decreasing ferrochelatase expression and heme biosynthesis in central macrophages. Mechanistically, the TFPI interacts with thrombomodulin to promote the downstream ERK1/2-GATA1 signaling pathway to induce heme biosynthesis in central macrophages. Furthermore, TFPI blockade impairs human erythropoiesis in vitro, and normalizes the erythroid compartment in mice with polycythemia. These results show that erythroblast-derived TFPI plays an important role in the regulation of erythropoiesis and reveal an interplay between erythroblasts and central macrophages.

METAVISION: a novel system for quantifying metamorphopsia in patients with myopic traction maculopathy.

PURPOSE: To develop a novel system for quantifying metamorphopsia in patients with myopic traction maculopathy (MTM) and to explore the metamorphopsia pattern of MTM. DESIGN: Observational, cross-sectional study. METHODS: We designed a new system. RESULTS: Of the 445 eyes tested, 188 (42.25%) were deemed by patients to have metamorphopsia impacting their daily lives while 257 (57.75%) were considered to have no metamorphopsia symptoms. The Amsler grid, M-CHARTS and METAVISION tests displayed sensitivities for metamorphopsia of 95.74%, 89.89% and 100%, respectively. The specificities of the Amsler grid, M-CHARTS and METAVISION tests are 100%. The metamorphopsia questionnaire and METAVISION scores were highly consistent (average intraclass correlation coefficient=0.951, p<0.001) and strongly correlated (R=0.879, p<0.001). The METAVISION score was highly correlated with the stages of MTM (R=0.837, p<0.001), whereas there was a moderate correlation between the M-CHARTS M-score and the stages of MTM (R=0.679, p<0.001). CONCLUSIONS: Quantification of metamorphopsia is important and useful for MTM management. The METAVISION is a clinically applicable and comprehensive approach for quantifying metamorphopsia, which can be used in clinical settings.

Hydroxygenkwanin suppresses peritoneal metastasis in colorectal cancer by modulating tumor-associated macrophages polarization.

Peritoneal metastasis is an important cause of high mortality and poor prognosis in colorectal cancer (CRC) patients. Therefore, the development of compounds with unique anti-CRC Peritoneal metastasis activities is urgently needed to improve the survival of CRC patients. Hydroxygenkwanin (HGK),a natural flavonoid compound, have been shown to display anti-inflammatory, antioxidant, antitumor, and immunoregulatory effects. Here, we employed CRC peritoneal metastasis mouse model with MC38 cells to examine the antitumor activity of HGK. The result showed that HGK not only inhibited peritoneal metastasis, but also significantly increased the proportion of M1-like macrophages while decreasing the proportion of M2-like macrophages within the tumor microenvironment (TME). Furthermore, we demonstrated that the inhibitory effect of HGK on peritoneal metastasis of CRC depended on macrophages in vitro and in vivo. Moreover, we revealed that HGK promoted the polarization of TAMs into M1-like macrophages and inhibited their polarization into M2-like macrophages in a LPS- or IL-4-induced bone marrow-derived macrophages (BMDMs) model and co-culture system. Finally, we also investigated the regulatory mechanism of HGK on TAMs polarization that HGK may active p-STAT5, p-NF-κB signaling in M1-like macrophages and inhibit p-STAT6, JMJD3, PPARγ expression in M2-like macrophages. Taken together, our findings suggest that HGK is a natural candidate for effective prevention of peritoneal metastasis in colorectal cancer, which provides a potential strategy for clinical treatment of colorectal cancer.

Effects of different assembly strategies on gene annotation in activated sludge.

Activated sludge comprises diverse bacteria, fungi, and other microorganisms, featuring a rich repertoire of genes involved in antibiotic resistance, pollutant degradation, and elemental cycling. In this regard, hybrid assembly technology can revolutionize metagenomics by detecting greater gene diversity in environmental samples. Nonetheless, the optimal utilization and comparability of genomic information between hybrid assembly and short- or long-read technology remain unclear. To address this gap, we compared the performance of the hybrid assembly, short- and long-read technologies, abundance and diversity of annotated genes, and taxonomic diversity by analysing 46, 161, and 45 activated sludge metagenomic datasets, respectively. The results revealed that hybrid assembly technology exhibited the best performance, generating the most contiguous and longest contigs but with a lower proportion of high-quality metagenome-assembled genomes than short-read technology. Compared with short- or long-read technologies, hybrid assembly technology can detect a greater diversity of microbiota and antibiotic resistance genes, as well as a wider range of potential hosts. However, this approach may yield lower gene abundance and pathogen detection. Our study revealed the specific advantages and disadvantages of hybrid assembly and short- and long-read applications in wastewater treatment plants, and our approach could serve as a blueprint to be extended to terrestrial environments.

Methods for assessing spillover effects between concurrent green initiatives.

This research presents the methods that are used to examine the dynamics and potential spillover effects of various global environmental conservation programs. We specifically show the data and models that we use to analyze the interactions and mutual influences between the U.S.'s Conservation Reserve Program (CRP) and Environmental Quality Incentives Program (EQIP), as well as those between China's Grain-to-Green Program (GTGP) and Forest Ecological Benefit Compensation (FEBC). Additionally, this study illustrates information about global initiatives, their interconnected impacts, and the associated policy strategies for environmental conservation. By utilizing multivariate regression, logistic regression, eigenvector spatial filtering, and scenario modeling, the research aims to understand the collective influence of these initiatives on broader environmental objectives. The findings of this study provide valuable insights for improving conservation policy designs and effectiveness.•Multivariate and logistic regression analyses to dissect global environmental conservation program interactions and mutual influences.•Eigenvector spatial filtering to address spatial autocorrelation and enhance the accuracy of the model results and our interpretations.•Scenario modeling to project potential future outcomes and impacts.

20(S)-ginsenoside Rh2 ameliorates ATRA resistance in APL by modulating lactylation-driven METTL3.

Background: 20(S)-ginsenoside Rh2(GRh2), an effective natural histone deacetylase inhibitor, can inhibit acute myeloid leukemia (AML) cell proliferation. Lactate regulated histone lactylation, which has different temporal dynamics from acetylation. However, whether the high level of lactylation modification that we first detected in acute promyelocytic leukemia (APL) is associated with all-trans retinoic acid (ATRA) resistance has not been reported. Furthermore, Whether GRh2 can regulate lactylation modification in ATRA-resistant APL remains unknown. Methods: Lactylation and METTL3 expression levels in ATRA-sensitive and ATRA-resistant APL cells were detected by Western blot analysis, qRT-PCR and CO-IP. Flow cytometry (FCM) and APL xenograft mouse models were used to determine the effect of METTL3 and GRh2 on ATRA-resistance. Results: Histone lactylation and METTL3 expression levels were considerably upregulated in ATRA-resistant APL cells. METTL3 was regulated by histone lactylation and direct lactylation modification. Overexpression of METTL3 promoted ATRA-resistance. GRh2 ameliorated ATRA-resistance by downregulated lactylation level and directly inhibiting METTL3. Conclusions: This study suggests that lactylation-modified METTL3 could provide a promising strategy for ameliorating ATRA-resistance in APL, and GRh2 could act as a potential lactylation-modified METTL3 inhibitor to ameliorate ATRA-resistance in APL.

Dual N-linked glycosylation at residues 133 and 158 in the hemagglutinin are essential for the efficacy of H7N9 avian influenza virus like particle vaccine in chickens and mice.

H7N9 subtype avian influenza virus (AIV) poses a great challenge to poultry industry. Virus-like particle (VLP) is a prospective alternative for the traditional egg-based influenza vaccines. N-linked glycosylation (NLG) regulates the efficacy of influenza vaccines, whereas the impact of NLG modifications on the efficacy of influenza VLP vaccines remains unclear. Here, H7N9 VLPs were assembled in insect cells through co-infection with the baculoviruses expressing the NLG-modified hemagglutinin (HA), neuraminidase and matrix proteins, and the VLP vaccines were assessed in chickens and mice. NLG modifications significantly enhanced hemagglutination-inhibition and virus neutralization antibody responses in mice, rather than in chickens, because different immunization strategies were used in these animal models. The presence of dual NLG at residues 133 and 158 significantly elevated HA-binding IgG titers in chickens and mice. The VLP vaccines conferred complete protection and significantly suppressed virus replication and lung pathology post challenge with H7N9 viruses in chickens and mice. VLP immunization activated T cell immunity-related cytokine response and inhibited inflammatory cytokine response in mouse lung. Of note, the presence of dual NLG at residues 133 and 158 optimized the capacity of the VLP vaccine to stimulate interleukin-4 expression, inhibit virus shedding or alleviate lung pathology in chickens or mice. Intriguingly, the VLP vaccine with NLG addition at residue 133 provided partial cross-protection against the H5Nx subtype AIVs in chickens and mice. In conclusion, dual NLG at residues 133 and 158 in HA can be potentially used to enhance the efficacy of H7N9 VLP vaccines in chickens and mammals.

Inseparable RNA binding and chromatin modification activities of a nucleosome-interacting surface in EZH2.

Polycomb repressive complex 2 (PRC2) interacts with RNA in cells, but there is no consensus on how RNA regulates PRC2 canonical functions, including chromatin modification and the maintenance of transcription programs in lineage-committed cells. We assayed two separation-of-function mutants of the PRC2 catalytic subunit EZH2, defective in RNA binding but functional in methyltransferase activity. We find that part of the RNA-binding surface of EZH2 is required for chromatin modification, yet this activity is independent of RNA. Mechanistically, the RNA-binding surface within EZH2 is required for chromatin modification in vitro and in cells, through interactions with nucleosomal DNA. Contrarily, an RNA-binding-defective mutant exhibited normal chromatin modification activity in vitro and in lineage-committed cells, accompanied by normal gene repression activity. Collectively, we show that part of the RNA-binding surface of EZH2, rather than the RNA-binding activity per se, is required for the histone methylation in vitro and in cells, through interactions with the substrate nucleosome.

Global One Health index for zoonoses: A performance assessment in 160 countries and territories.

The One Health (OH) approach is used to control/prevent zoonotic events. However, there is a lack of tools for systematically assessing OH practices. Here, we applied the Global OH Index (GOHI) to evaluate the global OH performance for zoonoses (GOHI-Zoonoses). The fuzzy analytic hierarchy process algorithm and fuzzy comparison matrix were used to calculate the weights and scores of five key indicators, 16 subindicators, and 31 datasets for 160 countries and territories worldwide. The distribution of GOHI-Zoonoses scores varies significantly across countries and regions, reflecting the strengths and weaknesses in controlling or responding to zoonotic threats. Correlation analyses revealed that the GOHI-Zoonoses score was associated with economic, sociodemographic, environmental, climatic, and zoological factors. Additionally, the Human Development Index had a positive effect on the score. This study provides an evidence-based reference and guidance for global, regional, and country-level efforts to optimize the health of people, animals, and the environment.

Exceeding Three-Electron Reactions in Polyanionic Cathode To Achieve High-Energy Density for Sodium-Ion Batteries.

Activating multielectron reactions of sodium superionic conductor (NASICON)-type cathodes toward higher energy density remains imperative to boost their application feasibility. However, multisodium storage with high stability is difficult to achieve due to the sluggish reaction kinetics, irreversible phase transitions, and negative structural degradation. Herein, a kind of NASICON-type Na2.5V1.5Ti0.5(PO4)3/C (NVTP-0.5) hierarchical microsphere consisting of abundant primary nanoparticles is designed, realizing a reversible 3.2-electron reaction with high stability. The optimized NVTP-0.5 cathode demonstrates an ultrahigh discharge capacity of 192.42 mAh g-1, energy density of up to 497.3 Wh kg-1 at 20 mA g-1, and capacity retention ratio of 94.1% after 1000 cycles at 1 A g-1. Additionally, the NVTP-0.5 cathode delivers excellent tolerance to extreme temperatures while also achieving a high-energy density of 400 Wh kg-1 (based on the cathode mass) in a full-cell configuration. Systematic in situ/ex situ analysis results confirm the multisodium storage processes of NVTP-0.5 involving successive redox reactions (V2+/V3+, Ti3+/Ti4+, and V3+/V4+ redox couples) and reversible structure evolution (solid-solution and biphasic mechanisms), which contribute to the high capacity and excellent cycling stability. This work indicates that the rational regulation of components with different functions can unlock more possibilities for the development of NASICON-type cathodes.

Development and validation of a novel colonoscopy withdrawal time indicator based on YOLOv5.

BACKGROUND AND AIM: The study aims to introduce a novel indicator, effective withdrawal time (WTS), which measures the time spent actively searching for suspicious lesions during colonoscopy and to compare WTS and the conventional withdrawal time (WT). METHODS: Colonoscopy video data from 472 patients across two hospitals were retrospectively analyzed. WTS was computed through a combination of artificial intelligence (AI) and manual verification. The results obtained through WTS were compared with those generated by the AI system. Patients were categorized into four groups based on the presence of polyps and whether resections or biopsies were performed. Bland Altman plots were utilized to compare AI-computed WTS with manually verified WTS. Scatterplots were used to illustrate WTS within the four groups, among different hospitals, and across various physicians. A parallel box plot was employed to depict the proportions of WTS relative to WT within each of the four groups. RESULTS: The study included 472 patients, with a median age of 55 years, and 57.8% were male. A significant correlation with manually verified WTS (r = 0.918) was observed in AI-computed WTS. Significant differences in WTS/WT among the four groups were revealed by the parallel box plot (P < 0.001). The group with no detected polyps had the highest WTS/WT, with a median of 0.69 (interquartile range: 0.40, 0.97). WTS patterns were found to be varied between the two hospitals and among senior and junior physicians. CONCLUSIONS: A promising alternative to traditional WT for quality control and training assessment in colonoscopy is offered by AI-assisted computation of WTS.

Balanced Mass Transfer and Active Sites Density in Hierarchical Porous Catalytic Metal-Organic Framework for Enhancing Redox Reaction in Lithium-Sulfur Batteries.

Developing highly efficient catalysts, characterized by controllable pore architecture and effective utilization of active sites, is paramount in addressing the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs) in lithium-sulfur batteries (LSBs), which, however, remains a formidable challenge. In this study, a hierarchical porous catalytic metal-organic framework (HPC-MOF) with both appropriate porosity and abundant exposed catalytic sites is achieved through time-controlled precise pore engineering. It is revealed that the evolution of the porous structure and catalytic site density is time-dependent during the etching processes. The moderately etched HPC-MOF-M attains heterogeneous pores at various scales, where large apertures ensure fast mass transfer and micropores inherit high-density catalytic sites, enhancing utilization and catalytic kinetics at internal catalytic sites. Capitalizing on these advantages, LSB incorporating the HPC-MOF-M interlayer demonstrates a 164.6% improvement in discharge capability and an 83.3% lower decay rate over long-term cycling at 1.0C. Even under high sulfur loading of 7.1 mg cm-2 and lean electrolyte conditions, the LSB exhibits stable cycling for over 100 cycles. This work highlights the significance of balancing the relationship between mass transfer and catalytic sites through precise chemical regulation of the porous structure in catalytic MOFs, which are anticipated to inspire the development of advanced catalysts for LSBs.

Influence factors of metagenomic next-generation sequencing negative results in diagnosed patients with spinal infection.

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.

Postassembly Modification of Peptides by Histidine-Directed ß-C(sp3)-H Arylation of Alanine at the Internal Positions: Overcoming the Inhibitory Effect of Peptide Bonds.

Peptide modification by C(sp3)-H functionalization of residues at the internal positions remains underdeveloped due to the inhibitory effect of backbone amides. In this study, using histidine (His) as an endogenous directing group, we developed a novel method for the ß-C(sp3)-H functionalization of alanine (Ala) at diverse positions of peptides. Through this approach, a wide range of linear peptides were modified on the side-chain of Ala adjacent to His to afford the functionalized peptides in moderate to good yield and excellent position selectivity. Furthermore, conjugation of peptides with functional molecules such as glucuronide, oleanolic acid, dipeptide, and fluorophore derivatives was achieved.

A prediction method of interaction based on Bilinear Attention Networks for designing polyphenol-protein complexes delivery systems.

Polyphenol-protein complexes delivery systems are gaining attention for their potential health benefits and food industry development. However, creating an ideal delivery system requires extensive wet-lab experimentation. To address this, we collected 525 ligand-protein interaction data pairs and established an interaction prediction model using Bilinear Attention Networks. We utilized 10-fold cross validation to address potential overfitting issues in the model, resulting in showed higher average AUROC (0.8443), AUPRC (0.7872), and F1 (0.8164). The optimal threshold (0.3739) was selected for the model to be used for subsequent analysis. Based on the model prediction results and optimal threshold, by verifying experimental analysis, the interaction of paeonol with the following proteins was obtained, including bovine serum albumin (lgKa = 6.2759), bovine ß-lactoglobulin (lgKa = 6.7479), egg ovalbumin (lgKa = 5.1806), zein (lgKa = 6.0122), bovine α-lactalbumin (lgKa = 3.9170), bovine lactoferrin (lgKa = 4.5380), the first four proteins are consistent with the predicted results of the model, with lgKa >5. The established model can accurately and rapidly predict the interaction of polyphenol-protein complexes. This study is the first to combine open ligand-protein interaction experiments with Deep Learning algorithms in the food industry, greatly improving research efficiency and providing a novel perspective for future complex delivery system construction.