Two-Dimensional Silver-Isocyanide Frameworks.

Metal-organic frameworks (MOFs) have been widely studied due to their versatile applications and easily tunable structures. However, heteroatom-metal coordination dominates the MOFs community, and the rational synthesis of carbon-metal coordination-based MOFs remains a significant challenge. Herein, two-dimensional (2D) MOFs based on silver-carbon linkages are synthesized through the coordination between silver(I) salt and isocyanide-based monomers at ambient condition. The as-synthesized 2D MOFs possess well-defined crystalline structures and a staggered AB stacking mode. Most interestingly, these 2D MOFs, without π-π stacking between layers, exhibit narrow bandgaps down to 1.42 eV. As electrochemical catalysts for converting CO2 to CO, such 2D MOFs demonstrate Faradaic efficiency over 92%. Surprisingly, the CO2 reduction catalyzed by these MOFs indicates favorable adsorption of CO2 and *COOH on the active carbon sites of the isocyanide groups rather than on silver sites. This is attributed to the critical σ donor role of isocyanides and the corresponding ligand-to-metal charge-transfer effect. This work not only paves the way toward a new family of MOFs based on metal-isocyanide coordination but also offers a rare platform for understanding the electrocatalysis processes on strongly polarized carbon species.

Generation of canine neutralizing antibodies against canine parvovirus by single B cell antibody technology.

Canine parvovirus (CPV) is a significant threat to canines and is widely distributed worldwide. While vaccination is currently the most effective preventive measure, existing vaccines are not able to offer comprehensive and dependable protection against CPV infection. Hence, there is a need to explore alternative or complementary strategies to tackle this problem. In this study, we present an approach for the efficient screening of canine antibodies targeting CPV using a single B cell antibody technique. We sorted single IgM- IgG+ CPV+ B cells from canine peripheral blood mononuclear cells using fluorescence-activated cell sorting (FACS) and obtained the variable region genes of heavy and light chains (VH and VL) by nested PCR amplification. Canine monoclonal antibodies were expressed in HEK293 cells, and a total of 60 antibodies were obtained, five of which demonstrated neutralizing activity against CPV. Those findings demonstrate the effectiveness of the method for obtaining canine monoclonal antibodies, which in turn aids in the identification and screening of neutralizing antibodies against various canine pathogens.

Copper ions coordination-promoted self-assembly of DNA nanoflowers as cascade catalytic nanoreactor for colorimetric biosensor.

The controllable geometry and multifunctionality of DNA nano-bioreactors hold immense promise for disease diagnosis. Herein, a facile rolling circle amplification (RCA)-based crystallization method has been developed for highly efficient self-assembly of three-dimensional (3D) DNA nano-bioreactors, which show excellent cascade catalytic performance by confining bio-enzyme (glucose oxidase (GOx) used in this case) and copper ions (Cu2+) in DNA nanoflowers (DNFs) structure. The participation of Cu2+ during the self-assembly process not only endows the nano-bioreactors (designated as GOx/Cu@DNFs) with inspiring peroxidase-like activity but also greatly improves the assembly efficiency and yield via the effective coordination between Cu2+ and RCA-generated long concatemeric DNAs. The integration of GOx and Cu2+ in the constrained flower-like DNA nanomatrices makes for the efficient inter-catalyst communication, resulting in the striking enhancement of biocatalytic cascade activity. Based on the prepared nano-bioreactors, a colorimetric biosensor has been constructed for glucose detection, achieving a wide linear range (2-400 µM) and a low detection limit (0.45 µM). Furthermore, the proposed sensing strategy enables the accurate determination and discrimination of glucose levels in healthy and diabetic sera, delivering gratifying outcomes. Overall, the meticulously crafted cascade nano-bioreactors not only illuminate the design of multifunctional nanomaterials based on RCA, but also expand the conceptual framework of the universal analytical method for determining small molecules with catalytic reactions to generate H2O2.

A DNA nanowire based-DNAzyme walker for amplified imaging of microRNA in tumor cells.

Sensitive imaging of microRNAs (miRNAs) in tumor cells holds great significance in the domains of pathology, drug development, and personalized diagnosis and treatment. DNA nanostructures possess excellent biostability and programmability and are suitable as carriers for intracellular imaging probes. With its highly controllable motion mechanism and remarkable target recognition specificity, the DNA walker is an ideal tool for living cell imaging. Here, we report a DNA nanowire based-DNAzyme Walker (D-Walker), which loads the DNAzyme based-molecular beacon (D-MB) onto DNA nanowires (NWs) functionalized with aptamers. The experimental results demonstrated that the intracellular target miRNA can specifically activate the pre-locked DNAzyme through a strand displacement reaction, thereby triggering the cleavage of its substrate molecular beacon (MB) and subsequent fluorescence emission. NWs decorated with aptamers can effectively prevent the degradation of the D-Walker by nuclease, and can enter target cells without any transfection reagents, which enhances the stability and reliability of cell imaging. Furthermore, the D-Walker exhibited a remarkable sensitivity with a limit of detection (LOD) of 61 pM and was capable of distinguishing miRNA-21 from other closely related family members. This study provides a novel strategy for intracellular miRNA imaging, offering a promising tool for cancer diagnosis and treatment.

A lysosome-targeting rhodamine fluorescent probe for Cu2+ detection and its applications in test kits and zebrafish imaging.

Tracing copper ions levels in the environment and subcellular microenvironment is crucial due to the key role copper ions play in physiological and pathological processes. Herein, a novel naphthalimide-fused rhodamine probe Rh-Naph-Cu was prepared through modification with phenylhydrazine to produce a closed and non-fluorescent spirolactam. Based on the copper-induced spirolactam ring-opening and hydrolysis process, Rh-Naph-Cu can be employed as a fluorescence off-on probe for copper ions with high selectivity, high sensitivity (limit of detection: 33.0 nM), broad pH-response range (pH: 5.0-10.0), and color change visible with the naked eye. Rh-Nap-Cu could be made into test strips for the in-situ chromogenic detection of Cu2+. Significantly, Rh-Naph-Cu can be utilized for the detection of copper ions in living HeLa cells and zebrafish, and exhibits excellent lysosomal-targeting ability with high Pearson's correlation coefficient (PCC) of 0.96.

Four cyclometalated Ir(iii) complexes and insights into their luminescence, cytotoxicity and DNA/BSA binding performance.

Four cyclometalated Ir(iii) complexes based on 4'-p-N,N-bis(2-hydroxyethyl)benzyl-2,2':6',2''-terpyridine (TPYOH) and 4'-p-N,N-bis(2-hydroxyethyl)benzyl-6'-benzyl-2,2'-bipyridine (PhbpyOH) were synthesized and characterized. All the Ir(iii) complexes exhibited strong MLCT absorption peaks at about 450 nm, broad emission bands in the range of 500-700 nm. Z-scan results revealed that only complex Ir1A could exhibit certain two-photon absorption with maximal cross section values of 215 GM at 890 nm. When excited by 700-850 nm femtosecond laser, complex Ir1A gave a TPEF peak around 567 nm. All four complexes exhibited enhanced cell growth inhibitory activity against MCF-7 tumour cells under light irradiation comparing to their dark toxicity, with Ir1B showing the highest PI value (>50). The pathways and efficiencies of ROS generation by Ir(iii) complexes varied, with Ir2A being more effective in producing 1O2 while Ir1A mainly generating O2˙-. The Ir(iii) complexes undergo hydrogen bonding with DNA bases/phosphodiester through two O-H bonds on the bis(hydroxyethyl)amino group. The free pyridine-N atom in Ir1A forms additional hydrogen bond with DNA base, while the ligand TPYOH in Ir2A has better molecular planarity due to adopting {N, N, N} coordination mode, thus these two complexes show better DNA affinity. The complexes demonstrated weak interactions with BSA, through hydrogen bonding with amino acid residues at different regions of BSA molecule.

Microbiome-host interactions in the pathogenesis of acute exacerbation of chronic obstructive pulmonary disease.

Objective: To explore the underlying mechanisms the airway microbiome contributes to Acute Exacerbation of Chronic Obstructive Pulmonary Disease(AECOPD). Methods: We enrolled 31 AECOPD patients and 26 stable COPD patients, their sputum samples were collected for metagenomic and RNA sequencing, and then subjected to bioinformatic analyses. The expression of host genes was validated by Quantitative Real-time PCR(qPCR) using the same batch of specimens. Results: Our results indicated a higher expression of Rothia mucilaginosa(p=0.015) in the AECOPD group and Haemophilus influenzae(p=0.005) in the COPD group. The Different expressed genes(DEGs) detected were significantly enriched in "type I interferon signaling pathway"(p<0.001, q=0.001) in gene function annotation, and "Cytosolic DNA-sensing pathway"(p=0.002, q=0.024), "Toll-like receptor signaling pathway"(p=0.006, q=0.045), and "TNF signaling pathway"(p=0.006, q=0.045) in KEGG enrichment analysis. qPCR amplification experiment verified that the expression of OASL and IL6 increased significantly in the AECOPD group. Conclusion: Pulmonary bacteria dysbiosis may regulate the pathogenesis of AECOPD through innate immune system pathways like type I interferon signaling pathway and Toll-like receptor signaling pathway.

A comprehensive prognostic and immune infiltration analysis of UBA1 in pan-cancer: A computational analysis and in vitro experiments.

Ubiquitin like modifier activating enzyme 1 (UBA1) plays an important role in immune regulation and cellular function. However, the functional mechanism and role of UBA1 in pan-cancer have not been fully elucidated and its value in haematological tumours (diffuse large B cell lymphoma (DLBC/DLBCL) and acute myeloid leukaemia (AML/LAML)) has not been explored. We conducted a comprehensive analysis of the functional mechanism and role of UBA1 in pan-cancer using multiple databases, including differential expression analysis, clinical pathological staging analysis, prognosis analysis and immune analysis. Then, we confirmed the function of UBA1 in haematological tumours through cell experiments. The results showed that the expression of UBA1 was significantly increased in most cancers and the differential expression of UBA1 was mainly concentrated in digestive tumours, haematological tumours and brain tumours. Moreover, the high expression of UBA1 had poor prognosis in most tumours, which may be related to its involvement in various cancer-related pathways such as cell cycle, as well as its methylation level, protein phosphorylation level, immune cell infiltration and immune therapy response. Cell experiments have confirmed that UBA1 can significantly regulate the cycle progression and apoptosis of DLBCL cells and AML cells. Therefore, UBA1 may be a potential therapeutic target for haematological tumours. In summary, our study not only comprehensively analysed the functional mechanisms and clinical value of UBA1 in pan-cancer, but also validated for the first time the regulatory role of UBA1 in haematological tumours.

Prior disulfide bond-mediated Ser/Thr ligation.

In this work, we developed a novel strategy, prior disulfide bond-mediated Ser/Thr ligation (PD-STL), for the chemical synthesis of peptides and proteins. This approach combines disulfide bond-forming chemistry with Ser/Thr ligation (STL), converting intermolecular STL into intramolecular STL to effectively proceed regardless of concentrations. We demonstrated the effectiveness of PD-STL under high dilution conditions, even for the relatively inert C-terminal proline at the ligation site. Additionally, we applied this method to synthesize the N-terminal cytoplasmic domain (2-104) of caveolin-1 and its Tyr14 phosphorylated form.

Developing an institutional control framework for contaminated sites in China: An analytical case study.

Institutional controls, as an important measure for risk management of contaminated sites, is widely used in site management by the United States, Canada and European countries. At present, some regions in China have also begun to explore the implementation of institutional controls, but its path, safeguard mechanism, and tracking evaluation are still unclear. Based on China's unique contaminated site remediation control system and land management system, this paper proposes a framework for the whole life cycle institutional controls of China's contaminated sites: (1) evaluate the need for institutional controls; (2) establish the objectives of institutional controls; (3) identify the restrictive requirements of institutional controls; (4) establish the implementation form of institutional controls; and (5) regularly review the effectiveness of institutional controls. To demonstrate the applicability of the institutional control framework, a case demonstration study was conducted at a petrochemical contaminated site in China. By analyzing the information on residual pollutants after the implementation of risk management measures at the site, the exposure pathways and hazards in case of re-release, and the engineering facilities, we proposed eight restrictive requirements, including the prohibition of disturbing and damaging the clean and planted soil layers of the site and the protection of long-term monitoring wells. At the same time, we constructed a multi-departmental pathway to implement institutional controls in conjunction with ecological environment, natural resources and housing departments to ensure effective implementation of institutional controls. Eventually, we summarized a set of replicable and generalizable institutional controls application models, which provide valuable theoretical and practical support for China and other local governments in the implementation of institutional controls at contaminated sites.

The novel HLA-A*02:1146 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*02:1146 differs from HLA-A*02:01:01:01 by one nucleotide in exon 1.

SNCA is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients.

Cuprotosis related genes (CRGs) have been proved to be potential therapeutic targets for coronavirus disease 2019 (COVID-19) and cancer, but their immune and molecular mechanisms in COVID-19 infection in Diffuse Large B-cell Lymphoma (DLBC/DLBCL) patients are rarely reported. Our research goal is first to screen the key CRGs in COVID-19 through univariate analysis, machine learning and clinical samples. Secondly, we determined the expression and prognostic role of key CRGs in DLBCL through pan-cancer analysis. We validated the expression levels and prognosis using multiple datasets and independent clinical samples and validated the functional role of key CRGs in DLBCL through cell experiments. Finally, we validated the expression levels of CRGs in COVID-19 infected DLBCL patients samples and analyzed their common pathways in COVID-19 and DLBCL. The results show that synuclein-alpha (SNCA) is the common key differential gene of COVID-19 and DLBCL. DLBCL cells confirm that high expression of SNCA can significantly promote cell apoptosis and significantly inhibit the cycle progression of DLBCL. High expression of SNCA can regulate the binding of major histocompatibility complexes (MHCs) and T cell receptor (TCR) by regulating immune infiltration of Dendritic cells, effectively enhancing T cell-mediated anti-tumor immunity and clearing cancer cells. In conclusion, SNCA may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our study provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL patients.

Clickable tryptophan modification for late-stage diversification of native peptides.

As the least abundant residue in proteins, tryptophan widely exists in peptide drugs and bioactive natural products and contributes to drug-target interactions in multiple ways. We report here a clickable tryptophan modification for late-stage diversification of native peptides, via catalyst-free C2-sulfenylation with 8-quinoline thiosulfonate reagents in trifluoroacetic acid (TFA). A wide range of groups including trifluoromethylthio (SCF3), difluoromethylthio (SCF2H), (ethoxycarbonyl)difluoromethylthio (SCF2CO2Et), alkylthio, and arylthio were readily incorporated. The rapid reaction kinetics of Trp modification and full tolerance with other 19 proteinogenic amino acids, as well as the super dissolving capability of TFA, render this method suitable for all kinds of Trp-containing peptides without limitations from sequences, hydrophobicity, and aggregation propensity. The late-stage modification of 15 therapeutic peptides (1.0 to 7.6 kilodaltons) and the improved bioactivity and serum stability of SCF3- and SCF2H-modified melittin analogs illustrated the effectiveness of this method and its potential in pharmacokinetic property improvement.

Fifteen acute retrobulbar optic neuritis associated with COVID-19: A case report and review of literature.

BACKGROUND: A subtype of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is suggested to be responsible for the outbreak in Northern China since the quarantine was lifted in December 2022. The coronavirus disease 2019 virus is primarily responsible for the development of respiratory illnesses, however, it can present a plethora of symptoms affecting a myriad of body organs. This virus has been theorized to be linked to demyelinating lesions of the peripheral and central nervous system including transverse myelitis and acute retrobulbar optic neuritis (ARON). For example, magnetic resonance imaging (MRI) of the orbit and brain showed enlargement of the retrobulbar intraorbital segments of the optic nerve with high T2 signal, and no abnormalities were seen in the brain tissue. In this case series, we analyzed the connection between SARS-CoV-2 infection and the onset of ARON. CASE SUMMARY: Fifteen patients, and a teenage boy who did not have any pre-existing ocular or demyelinating diseases suddenly experienced a loss of vision after SARS-CoV-2 infection. The patients expressed a central scotoma and a fever as the primary concern. The results of the fundus photography were found to be normal. However, the automated perimetry and MRI scans showed evidence of some typical signs. Out of the 15 patients diagnosed with ARON after SARS-CoV-2 infection, only one individual tested positive for the aquaporin-4 antibody. CONCLUSION: Direct viral invasion of the central nervous system and an immune-related process are the two primary causes of SARS-CoV-2-related ARON.

Depth-Guided Bilateral Grid Feature Fusion Network for Dehazing.

In adverse foggy weather conditions, images captured are adversely affected by natural environmental factors, resulting in reduced image contrast and diminished visibility. Traditional image dehazing methods typically rely on prior knowledge, but their efficacy diminishes in practical, complex environments. Deep learning methods have shown promise in single-image dehazing tasks, but often struggle to fully leverage depth and edge information, leading to blurred edges and incomplete dehazing effects. To address these challenges, this paper proposes a deep-guided bilateral grid feature fusion dehazing network. This network extracts depth information through a dedicated module, derives bilateral grid features via Unet, employs depth information to guide the sampling of bilateral grid features, reconstructs features using a dedicated module, and finally estimates dehazed images through two layers of convolutional layers and residual connections with the original images. The experimental results demonstrate the effectiveness of the proposed method on public datasets, successfully removing fog while preserving image details.

Recurrent Multiscale Feature Modulation for Geometry Consistent Depth Learning.

The U-Net-like coarse-to-fine network design is currently the dominant choice for dense prediction tasks. Although this design can often achieve competitive performance, it suffers from some inherent limitations, such as training error propagation from low to high resolution and the dependency on the deeper and heavier backbones. To design an effective network that performs better, we instead propose Recurrent Multiscale Feature Modulation (R-MSFM), a new lightweight network design for self-supervised monocular depth estimation. R-MSFM extracts per-pixel features, builds a multiscale feature modulation module, and performs recurrent depth refinement through a parameter-shared decoder at a fixed resolution. This network design enables our R-MSFM to maintain a more lightweight architecture and fundamentally avoid error propagation caused by the coarse-to-fine design. Furthermore, we introduce the mask geometry consistency loss to facilitate our R-MSFM for geometry consistent depth learning. This loss penalizes the inconsistency of the estimated depths between adjacent views within the nonoccluded and nonstationary regions. Experimental results demonstrate the superiority of our proposed R-MSFM both at model size and inference speed, and show state-of-the-art results on two datasets: KITTI and Make3D. The code is available at https://github.com/jsczzzk/R-MSFM.

Neratinib stimulates senescence of mammary cancer cells by reducing the levels of SIRT1.

Neratinib, a typical small-molecule, pan-human tyrosine kinase inhibitor (TKI), has been licensed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the underlying pharmacological mechanism is still unknown. In the current study, we report a novel function of Neratinib by showing that its treatment stimulates senescence of the mammary cancer AU565 cells. Our results demonstrate that Neratinib induces mitochondrial injury by increasing mitochondrial reactive oxygen species (ROS) and reducing intracellular adenosine triphosphate (ATP). Also, we found that Neratinib induced DNA damage by increasing the levels of 8-Hydroxy-desoxyguanosine (8-OHdG) and γH2AX in AU565 cells. Additionally, Neratinib reduced the levels of telomerase activity after 7 and 14 days incubation. Importantly, the senescence-associated-ß-galactosidase (SA-ß-Gal) assay revealed that Neratinib stimulated senescence of AU565 cells. Neratinib decreased the gene levels of human telomerase reverse transcriptase (hTERT) but increased those of telomeric repeat-binding factor 2 (TERF2) in AU565 cells. Further study displayed that Neratinib upregulated the expression of K382 acetylation of p53 (ac-K382) and p21 but reduced the levels of sirtuin-1 (SIRT1). However, overexpression of SIRT1 abolished the effects of Neratinib in cellular senescence. These findings provide strong preclinical evidence of Neratinib's treatment of breast cancer.

Transition-metal-based nanozymes for biosensing and catalytic tumor therapy.

Nanozymes, as an emerging class of enzyme mimics, have attracted much attention due to their adjustable catalytic activity, low cost, easy modification, and good stability. Researchers have made great efforts in developing and applying high-performance nanozymes. Recently, transition-metal-based nanozymes have been designed and widely developed because they possess unique photoelectric properties and high enzyme-like catalytic activities. To highlight these achievements and help researchers to understand the research status of transition-metal-based nanozymes, the development of transition-metal-based nanozymes from material characteristics to biological applications is summarized. Herein, we focus on introducing six categories of transition-metal-based nanozymes and highlight their progress in biomarker sensing and catalytic therapy for tumors. We hope that this review can guide the further development of transition-metal-based nanozymes and promote their practical applications in cancer diagnosis and treatment.

DLD is a potential therapeutic target for COVID-19 infection in diffuse large B-cell lymphoma patients.

Since the discovery of copper induces cell death(cuprotosis) in 2022, it has been one of the biggest research hotspots. cuprotosis related genes (CRGs) has been demonstrated to be a potential therapeutic target for cancer, however, the molecular mechanism of CRGs in coronavirus disease 2019 (COVID-19) infected in DLBCL patients has not been reported yet. Therefore, our research objective is first to elucidate the mechanism and role of CRGs in COVID-19. Secondly, we conducted univariate and multivariate analysis and machine learning to screen for CRGs with common expression differences in COVID-19 and DLBCL. Finally, the functional role and immune mechanism of genes in DLBCL were confirmed through cell experiments and immune analysis. The research results show that CRGs play an important role in the occurrence and development of COVID-19. Univariate analysis and machine learning confirm that dihydrolipoamide dehydrogenase (DLD) is the common key gene of COVID-19 and DLBCL. Inhibiting the expression of DLD can significantly inhibit the cycle progression and promote cell apoptosis of DLBCL cells and can target positive regulation of Lysine-specific demethylase 1 (LSD1, also known as KDM1A) to inhibit the proliferation of DLBCL cells and promote cell apoptosis. The immune analysis results show that high-expression of DLD may reduce T cell-mediated anti-tumor immunity by regulating immune infiltration of CD8 + T cells and positively regulating immune checkpoints LAG3 and CD276. Reducing the expression of DLD can effectively enhance T cell-mediated anti-tumor immunity, thereby clearing cancer cells and preventing cancer growth. In conclusion, DLD may be a potential therapeutic target for COVID-19 infection in DLBCL patients. Our research provides a theoretical basis for improving the clinical treatment of COVID-19 infection in DLBCL.

Metal-Organic Framework PCN-224 Combined Cobalt Oxide Nanoparticles for Hypoxia Relief and Synergistic Photodynamic/Chemodynamic Therapy.

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are promising tumor treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive. However, the hypoxia of tumor microenvironment and poor target ability often reduce the therapeutic effect. Here we propose a tumor targeted nanoplatform PCN-224@Co3O4-HA for enhanced PDT and synergistic CDT, constructed by hyaluronate-modified Co3O4 nanoparticles decorated metal-organic framework PCN-224. Co3O4 can catalyze the decomposition of highly expressed H2O2 in tumor cells to produce oxygen and alleviate the problem of hypoxia. It can also produce hydroxyl radicals according to the Fenton-like reaction for chemical dynamic therapy, significantly improving the therapeutic effect. The cell survival experiment showed that after in vitro treatment, 4T1 and MCF-7 cancer cells died in a large area under the anaerobic state, while the survival ability of normal cell L02 was nearly unchanged. This result effectively indicated that PCN-224@Co3O4-HA could effectively relieve tumor hypoxia and improve the effect of PDT and synergistic CDT. Cell uptake experiments showed that PCN-224@Co3O4-HA had good targeting properties and could effectively aggregate in tumor cells. In vivo experiments on mice, PCN-224@Co3O4-HA presented reliable biosafety performance, and can cooperate with PDT and CDT therapy to prevent the growth of tumor.