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.

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.

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.

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.

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.

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.

Major influencing factors identification and probabilistic health risk assessment of soil potentially toxic elements pollution in coal and metal mines across China: A systematic review.

Deposition of potentially toxic elements (PTEs) in soils due to different types of mining activities has been an increasingly important concern worldwide. Quantitative differences of soil PTEs contamination and related health risk among typical mines remain unclear. Herein, data from 110 coal mines and 168 metal mines across China were analyzed based on 265 published literatures to evaluate pollution characteristics, spatial distribution, and probabilistic health risks of soil PTEs. The results showed that PTE levels in soil from both mine types significantly exceeded background values. The geoaccumulation index (Igeo) revealed metal-mine soil pollution levels exceeded those of coal mines, with average Igeo values for Cd, Hg, As, Pb, Cu, and Zn being 3.02-15.60 times higher. Spearman correlation and redundancy analysis identified natural and anthropogenic factors affecting soil PTE contamination in both mine types. Mining activities posed a significant carcinogenic risk, with metal-mine soils showing a total carcinogenic risk an order of magnitude higher than in coal-mine soils. This study provides policymakers a quantitative foundation for developing differentiated strategies for sustainable remediation and risk-based management of PTEs in typical mining soils.

Ultrabright Xanthene Fluorescence Probe for Mitochondrial Super-Resolution Imaging.

Mitochondria are important organelles that provide energy for cellular physiological activities. Changes in their structures may indicate the occurrence of diseases, and the super-resolution imaging of mitochondria is of great significance. However, developing fluorescent probes for mitochondrial super-resolution visualization still remains challenging due to insufficient fluorescence brightness and poor stability. Herein, we rationally synthesized an ultrabright xanthene fluorescence probe Me-hNR for mitochondria-specific super-resolution imaging using structured illumination microscopy (SIM). The rigid structure of Me-hNR provided its ultrahigh fluorescence quantum yield of up to 0.92 and ultrahigh brightness of up to 16,000. Occupying the para-position of the O atom in the xanthene skeleton by utilizing the smallest methyl group ensured its excellent stability. The study of the photophysical process indicated that Me-hNR mainly emitted fluorescence via radiative decay, and nonradiative decay and inter-system crossing were rare due to the slow nonradiative decay rate and large energy gap (ΔEst = 0.55 eV). Owing to these excellent merits, Me-hNR can specifically light up mitochondria at ultralow concentrations down to 5 nM. The unprecedented spatial resolution for mitochondria with an fwhm of 174 nm was also achieved. Therefore, this ultrabright xanthene fluorescence probe has great potential in visualizing the structural changes of mitochondria and revealing the pathogenesis of related diseases using SIM.

CRISPR/Cas systems combined with DNA nanostructures for biomedical applications.

DNA nanostructures are easy to design and construct, have good biocompatibility, and show great potential in biosensing and drug delivery. Numerous distinctive and versatile DNA nanostructures have been developed and explored for biomedical applications. In addition to DNA nanostructures that are completely assembled from DNA, composite DNA nanostructures obtained by combining DNA with other organic or inorganic materials are also widely used in related research. The CRISPR/Cas system has attracted great attention as a powerful gene editing technology and is also widely used in biomedical diagnosis. Many researchers are committed to exploring new possibilities by combining DNA nanostructures with CRISPR/Cas systems. These explorations provide support for the development of new detection methods and cargo delivery pathways, provide inspiration for improving relevant gene editing platforms, and further expand the application scope of DNA nanostructures and CRISPR/Cas systems. This paper mainly reviews the design principles and biomedical applications of CRISPR/Cas combined with DNA nanostructures based on the types of DNA nanostructures. Finally, the application status, challenges and development prospects of CRISPR/Cas combined with DNA nanostructures in detection and delivery are summarized. It is expected that this review will enable researchers to better understand the current state of the field and provide insights into the application of CRISPR/Cas systems and the development of DNA nanostructures.

A novel dual-mode aptasensor based on a multiple amplification system for ultrasensitive detection of lead ions using fluorescence and surface-enhanced Raman spectroscopy.

In this work, we develop a dual recycling amplification aptasensor for sensitive and rapid detection of lead ions (Pb2+) using fluorescence and surface-enhanced Raman scattering (FL-SERS). The aptasensor allows targeted cleavage of substrates through specifically binding with the Pb2+-dependent aptamer (M-PS2.M). Ultrasensitive detection of trace Pb2+ has been achieved using an enzyme-free nonlinear hybridization chain reaction (HCR) and the FL-SERS technique. The lower limit of detection (LOD = 3σ/k) is 0.115 pM in FL mode and 1.261 fM in SERS mode. The aptasensor is characterized by high reliability and specificity, among other things, to distinguish Pb2+ from other metal ions. In addition, the aptasensor can detect Pb2+ in actual water with good recovery. Compared with the single-mode aptasensor, the dual-mode aptasensor is characterized by high reliability, an extensive detection range, and high specificity.

GPX4 is a potential diagnostic and therapeutic biomarker associated with diffuse large B lymphoma cell proliferation and B cell immune infiltration.

At present, GPX4's role in the occurrence and development of diffuse large B lymphoma (DLBCL) is rarely reported. This study's purpose is to explore GPX4's significance in the diagnosis, treatment, and pathological mechanisms of DLBCL. The TIMER 2.0, GEPIA, and GEO databases were used to analyze GPX4's expression levels in DLBCL tissue, peripheral blood, and single cells, and evaluate its potential performance as a therapeutic and diagnostic marker. Cell experiments validate GPX4's role in DLBCL cells. And revealed the potential mechanism of GPX4's action from three aspects: immunity, pathogenic gene expression, and protein interaction. The results indicate that GPX4 can be used as a biomarker for treatment and diagnosis (FC > 1.5, P < 0.05, AUC>0.8, KM-P value < 0.05). In single cell data, GPX4 also showed high expression in immune cells. Besides, cell experiments have confirmed that GPX4's high expression can inhibit DLBCL cells' proliferation. Meanwhile, we found a negative correlation between GPX4 and the 16 core DLBCL's pathogenic genes, and a significant negative correlation with immune B cell infiltration. In summary, GPX4 can serve as a potential therapeutic and diagnostic marker for DLBCL. GPX4's high expression can lead to a good prognosis in DLBCL patients, which may be related to its inhibition of cancer cell proliferation, high expression of key pathogenic genes, and infiltration of immune B cells.

Allo-HSCT with TBI-based preconditioning for hepatosplenic T-cell lymphoma: two case reports and systematic review of literature.

Hepatosplenic T cell lymphoma (HSTCL) is a particularly difficult-to-treat form of lymphoma, with many patients exhibiting primary resistance to chemotherapy. At present, no effective strategy for treating relapsed and refractory HSTCL has been established, with treatment being hampered by questions of how best to overcome chemoresistance to allow patients to attain more durable therapeutic benefits. While there have been marked advances in immunotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains one of the primary approaches to curing HSTCL. Of patients who undergo immunochemotherapeutic treatment, many are resistant to conventional chemotherapeutic drugs yet remain sensitive to radiotherapy. We selected to employ a transplant pretreatment regimen consisting of total -body irradiation (TBI) and administered this regimen to two patients with HSTCL. Both patients achieved complete remission (CR) after transplantation, demonstrating extended periods without disease recurrence. We systematic reviewed previously published instances involving allo-HSCT in patients with HSTCL. We have found a total of 67 patients who have received allo-HSCT. In general, age<45 and the status of CR at HSCT may have a more favorable prognosis. Although the impact of TBI on prognosis was not found to be substantial, patients in the TBI group had higher 3-year overall survival (66.7% vs. 71.1%) and 5-year overall survival (58.4% vs. 71.1%) compared to patients in the non-TBI group. In addition, the relapse rate of the TBI group is approximately half that of the non-TBI group. This regimen is well tolerated and associated with low recurrence rates or complications, suggesting that it represents a viable pretreatment regimen for young HSTCL patients undergoing allogeneic HSCT.

ST11 KPC-2-Producing Klebsiella pneumoniae Isolated from Patient with Acute Myelocytic Leukemia.

Background: The emergence of the ST11-CRKP (ST11-CRKP) strain is expected to become a serious public health problem in China. As one of the most serious complications in patients with acute myeloid lymphoma, infections can cause systemic infection and life-threatening sepsis, seriously affecting the morbidity, mortality, and quality of life of patients. Thus, ST11-CRKP infections in patients with acute myeloid lymphoma are worthy of our attention. Aim: To investigate the occurrence and genetic characteristics of the ST11-CRKP from a patient with acute myeloid lymphoma. Methods: Species identification was determined by MALDI-TOF MS. Antimicrobial susceptibility testing (AST) was conducted by VITEK 2 system with AST-N335 panel. Whole-genome sequencing was performed on the Illumina NovaSeq 6000 platform. Phylogenetic analyses were performed using Snippy based on the core-genome SNPs. Findings: S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and Whole-genome analysis indicated blaKPC-2 genes were located on plasmids with a conserved genetic environment. Moreover, the eight ST11-CRKP strains carry a variety of antimicrobial resistance genes (ARGs) and virulence factors. The ability of biofilm formation of eight strains was verified by a crystal violet assay. Core genome single-nucleotide polymorphism (cgSNP) analysis suggesting a possible bacterial translocation event. Conclusion: We performed a comprehensive analysis of ST11-CRKP strains from a patient with acute myelocytic leukemia. Our study emphasized the need for continuous surveillance of ST11-CRKP in the clinic especially in the immunocompromised population.

Simulation-Assisted DNA Nanodevice Serve as a General Optical Platform for Multiplexed Analysis of Micrornas.

Small frame nucleic acids (FNAs) serve as excellent carrier materials for various functional nucleic acid molecules, showcasing extensive potential applications in biomedicine development. The carrier module and function module combination is crucial for probe design, where an improper combination can significantly impede the functionality of sensing platforms. This study explores the effect of various combinations on the sensing performance of nanodevices through simulations and experimental approaches. Variances in response velocities, sensitivities, and cell uptake efficiencies across different structures are observed. Factors such as the number of functional molecules loaded, loading positions, and intermodular distances affect the rigidity and stability of the nanostructure. The findings reveal that the structures with full loads and moderate distances between modules have the lowest potential energy. Based on these insights, a multisignal detection platform that offers optimal sensitivity and response speed is developed. This research offers valuable insights for designing FNAs-based probes and presents a streamlined method for the conceptualization and optimization of DNA nanodevices.

The novel HLA-DRB1*09:01:14 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DRB1*09:01:14 differs from HLA-DRB1*09:01:02:01 by one nucleotide in exon 2.

NIR-driven photoelectrochemical-fluorescent dual-mode biosensor based on bipedal DNA walker for ultrasensitive detection of microRNA.

Optical biosensors have become powerful tools for bioanalysis, but most of them are limited by optic damage, autofluorescence, as well as poor penetration ability of ultraviolet (UV) and visible (Vis) light. Herein, a near-infrared light (NIR)-driven photoelectrochemical (PEC)-fluorescence (FL) dual-mode biosensor has been proposed for ultrasensitive detection of microRNA (miRNA) based on bipedal DNA walker with cascade amplification. Fueled by toehold-mediated strand displacement (TMSD), the bipedal DNA walker triggered by target miRNA-21 is formed through catalytic hairpin assembly (CHA), which can efficiently move along DNA tracks on CdS nanoparticles (CdS NPs)-modified fluorine doped tin oxide (FTO) electrode, resulting in the introduction of upconversion nanoparticles (UCNPs) on electrode surface. Under 980 nm laser irradiation, the UCNPs serve as the energy donor to emit UV/Vis light and excite CdS NPs to generate photocurrent for PEC detection, while the upconversion luminescence (UCL) at 803 nm is monitored for FL detection. This PEC-FL dual-mode biosensor has achieved the ultrasensitive and accurate analysis of miRNA-21 in human serum and different gynecological cancer cells. Overall, the proposed dual-mode biosensor can not only couple the inherent features of each single-mode biosensor but also provide mutual authentication of testing results, which opens up a new avenue for early diagnosis of miRNA-related diseases in clinic.

A pulmonary abscess caused by Porphyromonas endodontalis infection:A case report and literature review.

Porphyromonas endodontalis is an oral anaerobic bacterium associated with periodontitis but seldomly been detected in other diseases. Only one case of respiratory disease caused by Porphyromonas endodontalis, pyopneumothorax, has been reported so far. A 53-year-old man with refractory periodontitis was admitted due to an indeterminate lung space-occupying lesion. Following mNGS analysis of the liquefaction necrotic area and solid component of the lesion through biopsy, Porphyromonas endodontalis and Parvimonas micra were detected. Therefore, the patient was diagnosed with an aspiration lung abscess and discharged after receiving effective antibacterial treatment. The Chest computed tomography (CT) scan revealed a remarkable improvement during outpatient follow-up. In this study, we applied mNGS to diagnose a case of lung abscess attributed to an uncommon bacterium successfully, suggesting that when patients complicated with periodontal diseases and clinical respiratory symptoms, the possibility of inhalation disease caused by oral pathogens should be considered.

Immobilization of horseradish peroxidase on metal-organic framework to imporve enzyme activity for enhanced chemodynamic therapy.

Bio-enzymes have the advantages of strong substrate specificity, high catalytic efficiency, and minimal toxic side effects, making them promising drugs in cancer therapy. However, the poor stability and cellular penetrability of uncoated protein in the physiological environment severely restricts the direct application of Bio-enzyme. To address it, we report a metal-organic framework (MOF), Hf-DBA (H2DBA, biphenyl carboxylic acid ligands). The morphology of the Hf-DBA was revealed by TEM and the diameter was in the range of 200 to 350 nm. Hf-DBA acted a carrier for intracellular delivery and protection of horseradish peroxidase (HRP). The prepared HRP@Hf-DBA can catalyze the excess H2O2 in the tumor cells to generation of •OH for chemodynamic therapy (CDT). Compared with free HRP, the catalytic activity of HRP@Hf-DBA is significantly improved, and the optimal catalytic conditions are explored. The catalytic stability of HRP@Hf-DBA remained above 70% after 12 cycles of catalysis. After treatment with HRP@Hf-DBA, the apoptosis rates of A549 and Hela cells was 71.64%, and 76.86%. The results in vitro show that HRP@Hf-DBA can effectively inhibit the growth of tumor cells through enhanced CDT.