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.

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.

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.

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.

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.

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.

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.

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.

Analysis of sputum microbial flora in chronic obstructive pulmonary disease patients with different phenotypes during acute exacerbations.

BACKGROUND: Increasing studies have shown that the imbalance of the respiratory microbial flora is related to the occurrence of COPD, the severity and frequency of exacerbations and mortality.However, it remains unclear how the sputum microbial flora differs during exacerbations in COPD patients manifesting emphysema phenotype, chronic bronchitis with emphysema phenotype and asthma-COPD overlap phenotype. METHODS: Sputum samples were obtained from 29 COPD patients experiencing acute exacerbations who had not received antibiotics or systemic corticosteroids within the past four weeks.Patients were divided into three groups;emphysema phenotype(E);chronic bronchitis with emphysema phenotype(B+E) and asthma-COPD overlap phenotype(ACO).We utilized metagenomic Next Generation Sequencing (mNGS) technology to analyze the sputum microbial flora in COPD patients with different phenotypes during exacerbations. RESULTS: There was no significant difference in alpha diversity and beta diversity among three groups.The microbial flora composition was similar in all three groups during exacerbations except for a significant increase in Streptococcus mitis in ACO.Through network analysis,we found Candidatus Saccharibacteria oral taxon TM7x and Fusobacterium necrophorum were the core nodes of the co-occurrence network in ACO and E respectively.They were positively correlated with some species and play a synergistic role.In B+E,Haemophilus pittmaniae and Klebsiella pneumoniae had a synergistic effect.Besides,some species among the three groups play a synergistic or antagonistic role.Through Spearman analysis,we found the relative abundance of Streptococcus mitis was negatively correlated with the number of hospitalizations in the past year(r = -0.410,P = 0.027).We also observed that the relative abundance of Prevotella and Prevotella melaninogenica was negatively correlated with age(r = -0.534,P = 0.003;r = -0.567,P = 0.001),while the relative abundance of Streptococcus oralis and Actinomyces odontolyticus was positively correlated with age(r = 0.570,P = 0.001;r = 0.480,P = 0.008).In addition,the relative abundance of Prevotella melaninogenica was negatively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio(r = -0.479,P = 0.009;r = -0.555,P = 0.002),while the relative abundance of Streptococcus sanguinis was positively correlated with peripheral blood neutrophil ratio and neutrophil to lymphocyte ratio (r = 0.450,P = 0.014;r = 0.501,P = 0.006).There was also a significant positive correlation between Oribacterium and blood eosinophil counts(r = 0.491,P = 0.007). CONCLUSION: Overall,we analyzed the sputum microbiota of COPD patients with different phenotypes and its relationship with clinical indicators, and explored the relationships between microbiota and inflammation in COPD.We hope to alter the prognosis of patients by inhibiting specific bacterial taxa related to inflammation and using guide individualized treatment in the future research.

Ratiometric fluorescent aptasensor for convenient detection of ochratoxin A in beer and orange juice.

Based on the principle of fluorescence resonance energy transfer (FRET), a simple ratiometric fluorescent aptasensor for convenient detection of ochratoxin A (OTA), a Group IIB carcinogen secreted by some fungi, was established. Initially, the anti-OTA aptamer with a quadruplex structure was flanked with FAM and BHQ1, and its partially complementary DNA (cDNA) was tagged with Cy3. In the absence of OTA, this aptamer hybridized with the cDNA strand forming a DNA duplex structure, in which BHQ1 was adjacent to Cy3 and distant from FAM. Due to the FRET principle, the fluorescence intensity emitted by Cy3 (FCy3) was quenched by BHQ1, and the fluorescence intensity emitted by FAM (FFAM) recovered. In the presence of OTA, the prepared aptamer preferred to bind with OTA instead of cDNA, forming an aptamer-OTA complex structure in which BHQ1 was adjacent to FAM and distant from Cy3. As a result, FFAM was quenched and FCy3 was restored. OTA can be accurately detected via the determination of the FCy3/FFAM ratio value. Under optimal conditions, this ratiometric fluorescent aptasensor offers excellent OTA detection in the range of 0.6 nmol L-1-5 µmol L-1, with a limit of detection (LOD) of 0.3 nmol L-1. This ratiometric aptasensor showed the advantages of easy operation, accuracy and sensitive analysis. Good specificity of this aptasensor was demonstrated. This ratiometric aptasensor could be used for the detection of OTA in real samples, e.g. beer and orange juice, showing its promising application potential.

The Recent Research Progress of NF-κB Signaling on the Proliferation, Migration, Invasion, Immune Escape and Drug Resistance of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common and invasive primary central nervous system tumor in humans, accounting for approximately 45-50% of all primary brain tumors. How to conduct early diagnosis, targeted intervention, and prognostic evaluation of GBM, in order to improve the survival rate of glioblastoma patients, has always been an urgent clinical problem to be solved. Therefore, a deeper understanding of the molecular mechanisms underlying the occurrence and development of GBM is also needed. Like many other cancers, NF-κB signaling plays a crucial role in tumor growth and therapeutic resistance in GBM. However, the molecular mechanism underlying the high activity of NF-κB in GBM remains to be elucidated. This review aims to identify and summarize the NF-κB signaling involved in the recent pathogenesis of GBM, as well as basic therapy for GBM via NF-κB signaling.

Electrochemical sensor propelled by exonuclease III for highly efficient microRNA-155 detection.

MicroRNA-155 is highly expressed in tumor cells such as lung cancer, liver cancer and lymphoma. As such, it is increasingly used for the early diagnosis and monitoring of cancer diseases. Herein, we designed an electrochemical sensor propelled by exonuclease III, which is coupled with multiple signal amplification strategies for highly efficient microRNA-155 detection. In the presence of miRNA-155, a DNA hairpin probe with exposed bases at both ends was found to form a flat end, which can be hydrolyzed by exonuclease III. The produced single-stranded DNA enters the next cycle for further cleavage to produce another single-stranded DNA. The end product can trigger a hybridization chain reaction on the electrode surface, which is used for electrochemical detection with methylene blue as an electrochemical signaling indicator. Under optimal reaction conditions, there is good linear correlation between the logarithm of the target concentration and the current signal, with the concentration ranging from 0.1 fM to 0.1 nM. The detection limit is as low as 0.035 fM. Overall, the strategy for miRNA detection offers good prospects for early cancer screening.

CeO2-Decorated Metal-Organic Framework for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) is quickly developing as a hopeful cancer treatment. However, hypoxic tumors, poor targeting, and photosensitizers (PS) aggregation limited the efficiency of PDT. Here, we report a hyaluronic acid (HA)-modified CeO2-nanoparticle-decorated metal-organic framework (PCN-224@CeO2-HA) to enhance PDT and achieve targeted treatment. CeO2 catalyzes H2O2 to produce O2 to solve hypoxia problems. HA could target the CD44 receptor, which is highly expressed on the tumor cell membranes. The growth of tumor cells 4T1 and MCF-7 was controlled distinctly after being incubated with PCN-224@CeO2-HA under laser irradiation, while the survival ability of normal cell LO2 was nearly unchanged. Importantly, PCN-224@CeO2-HA could be effectively aggregated within the tumor area after 12 h of injection, and the tumor growth was remarkably inhibited under laser irradiation. PCN-224@CeO2-HA presented good biocompatibility and an excellent antitumor effect, providing a new strategy to produce O2 in situ for enhanced PDT.

The Crucial Roles of Bmi-1 in Cancer: Implications in Pathogenesis, Metastasis, Drug Resistance, and Targeted Therapies.

B-cell-specific Moloney murine leukemia virus integration region 1 (Bmi-1, also known as RNF51 or PCGF4) is one of the important members of the PcG gene family, and is involved in regulating cell proliferation, differentiation and senescence, and maintaining the self-renewal of stem cells. Many studies in recent years have emphasized the role of Bmi-1 in the occurrence and development of tumors. In fact, Bmi-1 has multiple functions in cancer biology and is closely related to many classical molecules, including Akt, c-MYC, Pten, etc. This review summarizes the regulatory mechanisms of Bmi-1 in multiple pathways, and the interaction of Bmi-1 with noncoding RNAs. In particular, we focus on the pathological processes of Bmi-1 in cancer, and explore the clinical relevance of Bmi-1 in cancer biomarkers and prognosis, as well as its implications for chemoresistance and radioresistance. In conclusion, we summarize the role of Bmi-1 in tumor progression, reveal the pathophysiological process and molecular mechanism of Bmi-1 in tumors, and provide useful information for tumor diagnosis, treatment, and prognosis.

RAI14 Promotes Melanoma Progression by Regulating the FBXO32/c-MYC Pathway.

Melanoma originates from the malignant transformation of melanocytes. Compared with other skin cancers, melanoma has a higher fatality rate. The 5-year survival rate of patients with early-stage primary melanoma through surgical resection can reach more than 90%. However, the 5-year survival rate of patients with metastatic melanoma is only 25%. Therefore, accurate assessment of melanoma progression is critical. Previous studies have found that Retinoic Acid Induced 14(RAI14) is critical in tumorigenesis. However, the biological function of RAI14 for the development of melanoma is unclear. In this study, RAI14 is highly expressed in melanoma and correlated with prognosis. The expression of RAI14 can affect the proliferation, migration and invasion of melanoma cells. F-Box Protein 32(FBXO32) is an E3 ubiquitin ligase of c-MYC. We found that RAI14 affects the transcriptional expression of FBXO32 and regulates the stability of c-MYC. These results suggest that RAI14 play an important role in the growth of melanoma and is expected to be a therapeutic target for melanoma.

Porphyrin-Based Metal-Organic Framework Probe: Highly Selective and Sensitive Fluorescent Turn-On Sensor for M3+ (Al3+, Cr3+, and Fe3+) Ions.

The development of porphyrin-based metal-organic frameworks (MOFs) has attracted significant interest in the scientific community in recent years because of their versatile applications particularly in optical and electronic fields. In this study, a highly selective and sensitive fluorescent turn-on sensor using a porphyrinic MOF, Tb-TCPP, is presented, which displays a 10-fold fluorescence enhancement in the presence of Al3+, Cr3+, and Fe3+ ions. The detection limit is in the nM region. For the Al3+ ion, it could be visually detected at concentrations as low as 5 mM within 15 min. Tb-TCPP could also be used as an indicator for acidic or alkaline solutions at pH values of >9 and <3. The studies on the detection mechanism illustrate that cation exchange proceed between Tb-TCPP and these M3+ ions, and consequently, energy transfer from TCPP to Tb3+ is suppressed and π*-π energy transfer of the porphyrin ligand is significantly enhanced.

Cell synchronization by Rapamycin improves the developmental competence of buffalos (Bubalus bubalis) somatic cell nuclear transfer embryos.

This study mainly explored the effects of Rapamycin on the growth of the Buffalo ear fibroblast (BEF) and embryonic developmental competence of somatic cell nuclear transfer (SCNT). The results show that the appropriate concentration (1 µM) of Rapamycin could significantly improve the proportion of the G0/G1 phase in BEF cells treated at a certain time (72 hr). Simultaneously, the percentage of the G0/G1 phase also was significantly higher than the serum starvation and control group. This may be related to Rapamycin inhibiting the phosphorylation of mTOR and affecting the expression of cell cycle-related genes (CDK2, CDK4, P27, CycleD1, and CycleD3). Besides, compared with the control group and serum-starved group, Rapamycin significantly decreased BEF cell apoptosis by reducing ROS generation. Moreover, these results also indicated that the proportion of BEF cells with normal chromosome multiples treated by Rapamycin is significantly higher than that of the serum-starved group (p < .05). Finally, this study explored the effects of Rapamycin and serum starvation on the embryonic developmental competence of SCNT. The results show that Rapamycin significantly increased the rate of 8-cell and blastocyst, compared with the control group and serum starvation group (p < .05). To summarize, these results indicate that Rapamycin improved the embryonic development competence of SCNT, which may be related to Rapamycin increasing the percentage of G0/G1 phase and maintaining BEF cell quality.

Enhanced transmission through sub-wavelength aperture in specific frequency band by using topology optimized metamaterials.

Aiming at achieving metamaterials (MTM)-based enhanced transmission through the sub-wavelength aperture on a metallic isolating plate in specific frequency band, the topology optimization method for MTM microstructure design was proposed. The MTM was inserted in the sub-wavelength aperture and perpendicular to the isolating plate. A piecewise preset function was employed to describe the expected enhanced and non-enhanced transmission frequency band. The transmission coefficient of the waveguide system with the designed MTM was mapped to a step mapping function. In the topology optimization of the MTM configuration, matching the mapping function to the preset function was chosen as the design objective. Three designs aiming at different specific enhanced transmission frequency band were carried out. The design satisfied the demand for the specific enhanced transmission frequency band, which was also validated by experiment.

Temperature-Dependent Mechanochemical Wear of Silicon in Water: The Role of Si-OH Surfacial Groups.

Mechanochemical wear has attracted much attention due to its critical role in micro/nanodevice applications, reliable microscopy, and ultraprecision manufacturing. As a process of stress-associated chemical reactions, mechanochemical wear strongly depends on temperature; however, the impact mechanism is not fully understood at any length scale. Here, we reported different water-temperature dependence of mechanochemical wear on two typical single crystal silicon (Si) surfaces, involving oxide-covered Si partially terminated with Si-OH groups and oxide-free Si fully terminated with Si-H groups. As the water temperature increased from 10 to 80 °C, the mechanochemical wear of the oxide-covered Si underwent a process from no obvious surface damage to significant material removal but that occurring at all temperatures decreased gradually on the oxide-free Si surface. The opposite temperature-dependence was found to have a strong relation to the growth or degeneration of the Si-OH surfacial groups. The mechanochemical wear on the both Si surfaces decreased with the Si-OH coverage rising, which facilitated the growth of strongly hydrogen-bonded ordered water and then suppressed the chemical reaction between the sliding interfaces. These results can provide new insight into the mechanism of the surrounding temperature affecting the reliable micro/nanodevices, manufacturing, and microscopy.

DNA-Functionalized Metal-Organic Framework: Cell Imaging, Targeting Drug Delivery and Photodynamic Therapy.

Here, DNA-functionalized nanoscale PCN-224 is established with the aptamer of A549 lung cancer cells. The aptamer was modified with carboxyl and fluorescein at the two terminals. When touching the A549 cells, DOX@PCN-224-DNA can trace tumor cells and present good targeting therapy by the combination of chemotherapy and photodynamic therapy. This facile aptamer functionalization of PCN-224 offers an opportunity to develop metal-organic framework-based target-directed therapy and biosensors.