Inhibitory effects of Belamcanda extract on inflammatory response and antiviral mechanism in H9N2 Avian influenza virus: insights from in vitro and in vivo studies.

Avian influenza, particularly the H9N2 subtype, presents significant challenges to poultry health, underscoring the need for effective antiviral interventions. This study explores the antiviral capabilities of Belamcanda extract, a traditional Chinese medicinal herb, against H9N2 Avian influenza virus (AIV) in specific pathogen-free (SPF) chicks. Through a comprehensive approach, we evaluated the impact of the extract on cytokine modulation and crucial immunological signaling pathways, essential for understanding the host-virus interaction. Our findings demonstrate that Belamcanda extract significantly modulates the expression of key inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6), which are pivotal to the host's response to H9N2 AIV infection. Western blot analysis further revealed that the extract markedly reduces the expression of critical immune signaling molecules such as toll-like receptor 3 (TLR3), TIR-domain-containing adapter-inducing interferon-ß (TRIF), and nuclear factor kappa B (NF-κB). These insights into the mechanisms by which Belamcanda extract influences host immune responses and hinders viral replication highlight its potential as an innovative antiviral agent for poultry health management. The study advances our comprehension of natural compounds' antiviral mechanisms and lays the groundwork for developing strategies to manage viral infections in poultry. The demonstrated ability of Belamcanda extract to modulate immune responses and inhibit viral replication establishes it as a promising candidate for future antiviral therapy development, especially in light of the need for effective treatments against evolving influenza virus strains and the critical demand for enhanced poultry health management strategies.

Effects of Hydrogen Blending Ratio and Equivalence Ratio on the Dynamic Characteristics of Deflagration Shock Waves of CH4/H2 Mixtures.

To evaluate the explosion hazard of CH4/H2 mixtures, experiments were conducted in a long and closed pipeline with a length-to-diameter ratio of 51 and built-in obstacles, and the characteristic parameters of deflagration shock waves were analyzed under different hydrogen blending ratios (0 ≤ λ ≤ 100%) and equivalence ratios (0.5 ≤ Φ ≤ 3). The results indicate that within the range of Φ = 0.8-1.2, the explosion overpressure (P P) exhibits a "two-zone" structure distribution. When 0 ≤ λ ≤ 80%, P P shows an initial increase and then a decrease in both regions, while deflagration to detonation transition (DDT) occurs in the second evolution region when λ = 100%, which is caused by the different strengths of the positive feedback mechanism coupled with flames and shock waves. The P max, (dP/dt)max, and V a show a trend of first increasing and then decreasing and monotonically increasing with the increase of the equivalence ratio and hydrogen blending ratio, respectively, and reach their maximum values at Φ = 1.0 and λ = 100%. For CH4/H2 mixtures with low hydrogen blending ratios (λ = 0 and 20%), the P max and (dP/dt)max in the fuel-lean conditions (Φ = 0.9 and 0.8) are higher than those in the fuel-rich conditions (Φ = 1.1 and 1.2), while the CH4/H2 mixtures under high hydrogen blending ratios (λ = 80 and 100%) are the opposite. Overall, the increase in H2 at a high hydrogen blending ratio and the increase in the equivalence ratio at a fuel-lean condition significantly enhance the average V a. In addition, chemical kinetics analysis found that R38 and R52 elementary reactions are the dominant elementary reactions that promote and inhibit temperature increase, respectively. Their temperature sensitivity coefficients are negatively correlated with the hydrogen blending ratio and positively correlated with the equivalence ratio. The research results provide vital information for evaluating the explosion hazards of CH4/H2 mixtures and developing safety protection measures.

Comprehensive analyses of the ARF gene family in cannabis reveals their potential roles in regulating cannabidiol biosynthesis and male flower development.

Background: Cannabidiol (CBD), as an important therapeutic property of the cannabis plants, is mainly produced in the flower organs. Auxin response factors (ARFs) are play a crucial role in flower development and secondary metabolite production. However, the specific roles of ARF gene family in cannabis remain unknown. Methods: In this study, various bioinformatics analysis of CsARF genes were conducted using online website and bioinformatics, quantitative real time PCR technology was used to investigate the expression patterns of the CsARF gene family in different tissues of different cannabis varieties, and subcellular localization analysis was performed in tobacco leaf. Results: In this study, 22 CsARF genes were identified and found to be unevenly distributed across 9 chromosomes of the cannabis genome. Phylogenetic analysis revealed that the ARF proteins were divided into 4 subgroups. Duplication analysis identified one pair of segmental/whole-genome duplicated CsARF, and three pairs of tandemly duplicated CsARF. Collinearity analysis revealed that two CsARF genes, CsARF4 and CsARF19, were orthologous in both rice and soybean. Furthermore, subcellular localization analysis showed that CsARF2 was localized in the nucleus. Tissue-specific expression analysis revealed that six genes were highly expressed in cannabis male flowers, and among these genes, 3 genes were further found to be highly expressed at different developmental stages of male flowers. Meanwhile, correlation analysis between the expression level of CsARF genes and CBD content in two cultivars 'H8' and 'Y7' showed that the expression level of CsARF13 was negatively correlated with CBD content, while the expression levels of six genes were positively correlated with CBD content. In addition, most of CsARF genes were responsive to IAA treatment. Conclusion: Our study laid a foundation for the further studies of CsARFs function in cannabis, and provides candidate genes for breeding varieties with high CBD yield in cannabis production.

Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation.

In our research, we explored a natural substance called Oxymatrine, found in a traditional Chinese medicinal plant, to fight against a common bird flu virus known as H9N2. This virus not only affects birds but can also pose a threat to human health. We focused on how this natural compound can help in stopping the virus from spreading in cells that line the lungs of birds and potentially humans. Our findings show that Oxymatrine can both directly block the virus and boost the body's immune response against it. This dual-action mechanism is particularly interesting because it indicates that Oxymatrine might be a useful tool in developing new ways to prevent and treat this type of bird flu. Understanding how Oxymatrine works against the H9N2 virus could lead to safer and more natural ways to combat viral infections in animals and humans, contributing to the health and well-being of society. The H9N2 Avian Influenza Virus (AIV) is a persistent health threat because of its rapid mutation rate and the limited efficacy of vaccines, underscoring the urgent need for innovative therapies. This study investigated the H9N2 AIV antiviral properties of Oxymatrine (OMT), a compound derived from traditional Chinese medicine, particularly focusing on its interaction with pulmonary microvascular endothelial cells (PMVECs). Employing an array of in vitro assays, including 50% tissue culture infectious dose, Cell Counting Kit-8, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blot, we systematically elucidated the multifaceted effects of OMT. OMT dose-dependently inhibited critical antiviral proteins (PKR and Mx1) and modulated the expression of type I interferons and key cytokines (IFN-α, IFN-ß, IL-6, and TNF-α), thereby affecting TLR3 signaling and its downstream elements (NF-κB and IRF-3). OMT's antiviral efficacy extended beyond TLR3-mediated responses, suggesting its potential as a versatile antiviral agent. This study not only contributes to the growing body of research on the use of natural compounds as antiviral agents but also underscores the importance of further investigating the broader application of OMT for combating viral infections.

Efficacy and safety of flumatinib in the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase: A real-world single-center retrospective study, with a focus on premature drug discontinuation.

PURPOSE: To assess the real-world efficacy and safety of flumatinib as first-line and post-line treatments for chronic myeloid leukemia in the chronic phase (CML-CP). RESULTS: Among 141 patients receiving flumatinib as first-line and post-line treatment, the 12-month major molecular response (MMR) rates were 69.4% and 67.6%, respectively. The median time to response was 6 and 10.5 months, respectively. In post-line treatment, the early molecular response (EMR) of flumatinib as second-line is significantly superior to that of third-line treatment (3-month EMR rate: 79.2% vs. 39.3%, P<0.001; 3-month MMR rate: 45.8% vs. 21.4%, P=0.033). Contrastively, patients who switched to flumatinib due to intolerance had significantly higher MMR rates at 3, 6, and 12 months compared to patients who switched due to inadequate response (60.6% vs. 24.2%, P=0.003; 66.7% vs. 36.0%, P=0.027; 84.2% vs. 50.0%, P=0.038). Premature drug discontinuation was observed in 28.4% of the patients. Grades 3-4 hematologic adverse events (AEs) were identified as independent risk factors for premature drug discontinuation. Patients who discontinued treatment and those who previously received only imatinib therapy had a poorer molecular response and failure-free survival. CONCLUSIONS: Flumatinib demonstrates favorable efficacy and safety. Treatment discontinuation can result in a poorer molecular response and long-term prognosis.

Design of Machine Learning Algorithms and Internal Validation of a Kidney Risk Prediction Model for Type 2 Diabetes Mellitus.

Objective: This study aimed to explore specific biochemical indicators and construct a risk prediction model for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Methods: This study included 234 T2D patients, of whom 166 had DKD, at the First Hospital of Jilin University from January 2021 to July 2022. Clinical characteristics, such as age, gender, and typical hematological parameters, were collected and used for modeling. Five machine learning algorithms [Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF)] were used to identify critical clinical and pathological features and to build a risk prediction model for DKD. Additionally, clinical data from 70 patients (nT2D = 20, nDKD = 50) were collected for external validation from the Third Hospital of Jilin University. Results: The RF algorithm demonstrated the best performance in predicting progression to DKD, identifying five major indicators: estimated glomerular filtration rate (eGFR), glycated albumin (GA), Uric acid, HbA1c, and Zinc (Zn). The prediction model showed sufficient predictive accuracy with area under the curve (AUC) values of 0.960 (95% CI: 0.936-0.984) and 0.9326 (95% CI: 0.8747-0.9885) in the internal validation set and external validation set, respectively. The diagnostic efficacy of the RF model (AUC = 0.960) was significantly higher than each of the five features screened with the highest feature importance in the RF model. Conclusion: The online DKD risk prediction model constructed using the RF algorithm was selected based on its strong performance in the internal validation.

Cecropin AD reduces viral load and inflammatory response against H9N2 avian influenza virus in chickens.

Introduction: This study focuses on evaluating the therapeutic efficacy of cecropin AD, an antimicrobial peptide, against H9N2 avian influenza virus (AIV) in chickens. Given the global impact of H9N2 AIV on poultry health, identifying effective treatments is crucial. Methods: To assess the impact of cecropin AD, we conducted in vivo experiments involving 108 5-week-old chickens divided into control, infected, and various treatment groups based on cecropin AD dosage levels (high, medium, and low). The methodologies included hemagglutination (HA) tests for viral titers, histopathological examination and toluidine blue (TB) staining for lung pathology, real-time PCR for viral detection, and enzyme-linked immunosorbent assays for measuring serum levels of inflammatory markers. Results: The findings revealed that cecropin AD substantially reduced lung pathology and viral load, especially at higher dosages, comparing favorably with the effects seen from conventional treatments. Moreover, cecropin AD effectively modulated mast cell activity and the levels of inflammatory markers such as IL-6, TNF-α, IFN-γ, and 5-HT, indicating its potential to diminish inflammation and viral spread. Discussion: Cecropin AD presents a significant potential as an alternative treatment for H9N2 AIV in chickens, as evidenced by its ability to lessen lung damage, decrease viral presence, and adjust immune responses. This positions cecropin AD as a promising candidate for further exploration in the management of H9N2 AIV infections in poultry.

Isorhamnetin Regulates Programmed Death Ligand-1 Expression by Suppressing the EGFR-STAT3 Signaling Pathway in Canine Mammary Tumors.

Programmed death ligand-1 (PD-L1) is highly expressed in a variety of cancer cells and suggests a poorer prognosis for patients. The natural compound isorhamnetin (ISO) shows promise in treating cancers and causing damage to canine mammary tumor (CMT) cells. We investigated the mechanism of ISO in reducing PD-L1 expression in CMT cells. Clustered, regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9) was used to mediate CD274 knockout in U27 cells. Then, monoclonal cells were screened and cultured. Nucleotide sequencing and expression of PD-L1 were detected. Additionally, we examined cell migration, invasion, and damage. Immunofluorescent staining of PD-L1 was examined in U27 cells. The signaling pathways were measured by Western blotting. Murine xenotransplantation models and murine immunocompetent allograft mammary tumor models were established to evaluate the effect of ISO therapy. Expression of Ki-67, caspase3, and PD-L1 were analyzed by immunohistochemistry. A pull-down assay was used to explore which proteins could bind to ISO. Canine EGFR protein was purified and used to detect whether it directly binds to ISO using a surface plasmon resonance assay. ISO inhibited the EGFR-STAT3-PD-L1 signaling pathway and blocked cancer growth, significantly increasing the survival rate of healthy cells. The cell membrane receptor EGFR was identified as a direct target of ISO. ISO could be exploited as an antineoplastic treatment of CMT by targeting EGFR to suppress PD-L1 expression.

Development of Low-Pressure He-MC-MIP-MS and Its Application for Oxygen Isotopic Analysis.

In Ar-based inductively coupled plasma mass spectrometry (MS), Ar-related interference and the low ionization capacity of the Ar-ion source prevent facile and precise determination of certain elements. To address this problem, we investigated the application of microwave-induced plasma (MIP), and we improved its ionization capacity using He as the working gas. The MIP ion source was connected to a multicollector mass spectrometry (MC-MS) apparatus to improve the accuracy and precision of the isotopic analysis. A vacuum pump was used to achieve a low pressure (200-300 Pa) at the interface. The analytical figures of merit were discussed and evaluated by measuring the oxygen isotopes in oxygen. With the application of low-pressure He-MC-MIP-MS, the degree of ionization of oxygen could be significantly improved with He plasma. The interference of oxygen from the atmosphere could also be eliminated with low-pressure plasma, and the determination precision of oxygen isotopes could be improved with the application of MC-MS. Subsequently, using this method, 16O18O/16O16O was applied as the analytical ratio to investigate the interference, sensitivity, and precision. With this constructed method, the obtained long-term producibility of δ18O was 0.16‰ (2 SD), and the measured result for oxygen was consistent with that obtained by MAT 253 within the uncertainty limit. The development of low-pressure He-MC-MIP-MS can pave the way for the accurate measurement of nonmetal isotopes and easily interfered isotopes in Ar plasma.

1,8-Cineole Alleviates OGD/R-Induced Oxidative Damage and Restores Mitochondrial Function by Promoting the Nrf2 Pathway.

This study examined the effects of 1,8-cineole on reducing oxidative stress injury and restoring mitochondrial function in oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 cells via the nuclear factor erythrocyte 2 related factor 2 (Nrf2) pathway. The optimal concentration of 1,8-cineole to reduce OGD/R injury was screened via cell morphology, cell survival rate, and lactate dehydrogenase (LDH) leakage rate. Oxidative damage was observed by measuring superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) activities, and reactive oxygen species (ROS), glutathione (GSH), protein carbonyl, malondialdehyde (MDA), lipid peroxidation (LPO) content, and 8-hydroxy-2 deoxyguanosine (8-OHDG) expression. Mitochondrial function was observed by mitochondrial membrane potential (MMP) and ATPase activity. Nrf2 pathways were observed by the expression levels of total Nrf2, nucleus Nrf2, reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H): quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), the mRNA levels of HO-1 and NQO1. Among different concentrations of 1,8-cineole for promoting HT22 cell proliferation and attenuated OGD/R injury, 10 µmol/L 1,8-cineole was the best. After 1,8-cineole treatment, SOD, GSH-PX, and CAT activities and GSH content increased, while ROS, MDA, LPO, protein carbonyl, and 8-OHDG levels decreased. 1,8-Cineole could restore MMP and increase mitochondrial enzyme activity. It could also increase the total Nrf2, nucleus Nrf2, NQO1, and HO-1, and Nrf2 inhibitor brusatol reduced the effect of 1,8-cineole. Immunofluorescence assay showed that 1,8-cineole could facilitate the transfer of Nrf2 into the nucleus. 1,8-cineole increased the mRNA levels of NQO1 and HO-1. The above results showed that 1,8-cineole could alleviate OGD/R-induced oxidative damage and restores mitochondrial function by activating the Nrf2 signal pathway.

Experimental study on the leakage temperature field of buried CO2 pipelines.

The leakage of small holes in the buried CO2 pipeline is not easy to detect, which leads to the problem of the inability to accurately trace the source of the pipeline repair in the later stage. This paper designs and builds an experimental system to simulate the leakage of buried CO2 pipelines and conducts experiments on the leakage of small holes in buried CO2 pipelines to investigate the changes in the surrounding soil temperature when they leak. The results showed that the type of movement of CO2 in porous media after it is released from the leak is "funneling." At a distance of about 50 mm from the horizontal, the temperature difference in the horizontal surface is smallest at the 50 cm closest to the vertical distance of the leak, while at a distance of 225 mm from the horizontal, the temperature difference in the horizontal surface is largest at the 70 cm farthest from the vertical distance of the leak. The research results can provide a theoretical basis for the later development of technologies that can quickly locate the leakage points of buried CO2 pipelines and accurately determine their leakage status.

The Damage to Thick Steel Plates by Local Contact Explosions.

The paper presents the damage results of thick steel plates subjected to local blast loading using experimental and numerical approaches. Three steel plates with a thickness of 17 mm under the local contact explosion of trinitrotoluene (TNT) explosives were tested, and the damaged parts of the steel plates were scanned using a scanning electron microscope (SEM). ANSYS LS-DYNA software was used to simulate the damage results of the steel plate. By analyzing and comparing the experimental results with the numerical simulation results, the influence law of the TNT acting on the steel plate, the damage mode of the steel plate, the reliability verification of the numerical simulation, and the criterion for judging the damage mode of the steel plate were obtained. Results show that the damage mode of the steel plate changes with the changes in the explosive charge. The diameter of the crater on the surface of the steel plate is mainly related to the diameter of the contact surface between the explosive and the steel plate. The fracture mode of the steel plate in the process of generating cracks is a quasi-cleavage fracture, and the process of generating craters and perforations in the steel plate is a ductile fracture. The damage mode of the steel plates can be divided into three types. The numerical simulation results have minor errors and high reliability, and numerical simulation can be used as an auxiliary tool for experiments. A new criterion is proposed to predict the damage mode of the steel plates under contact explosion.

Effects of Pipeline Pressure on Diffusion Characteristics of Leaked Natural Gas in Tunnel Space.

Pipeline transportation has become the main mode of natural gas transportation. Due to inevitable aging, corrosion, and third-party damage, natural gas pipeline leakage accidents occur frequently. Leakage in the tunnel will lead to the leakage and accumulation of natural gas, and the potential explosion risk will threaten the tunnel's safety. It is significant to elaborate on the diffusion behavior of leaked natural gas in tunnel space for the traceability of leakage points and the formulation of safety technical measures. In this paper, a scale-down experimental platform for natural gas pipeline leakage in the tunnel is built, and the influence of pipeline pressure on natural gas diffusion characteristics is described. The results show that the diffusion process of leaked natural gas in the tunnel space shows obvious segmentation characteristics, and the concentration of natural gas reaches the maximum at the end of the continuous leakage stage. The increased pipeline pressure promotes natural gas diffusion, and the concentration of natural gas under 1.0 and 1.2 MPa rises sharply. First dangerous time (FDT) and maximum accumulated concentration (MAC) have a negative correlation with the leakage distance, while FDT and MAC have a good exponential and linear relationship with the pipeline pressure (0.2-1.2 MPa), respectively.

Buyang Huanwu decoction alleviates oxidative injury of cerebral ischemia-reperfusion through PKCε/Nrf2 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke is a significant risk factor for human health, and Buyang Huanwu Decoction is a classical and famous Chinese formula for treating it, but without clear pharmacological mechanism. AIM OF THE STUDY: The aim of this study was to investigate that the molecular mechanism of BYHWD activation of the PKCε/Nrf2 signaling pathway to attenuate cerebral ischemia-reperfusion (I/R) oxidative damage. MATERIALS AND METHODS: The MCAO method was used to establish a brain I/R injury model in SD rats, and neurological deficits were evaluated by neurological function score. Neuronal damage was observed by Nissl staining and immunofluorescence detection of MAP2 expression. Oxidative damage was observed by ROS, SOD, GSH-PX, MDA, and 8-OHdG. Changes in mitochondrial membrane potential were detected by using the fluorescent probe JC-1. The Western blot analysis detected protein expression of PKCε, P-PKCε, total Nrf2, nuclear Nrf2, HO-1, and NQO1. RESULTS: BYHWD significantly enhanced neural function, reduced neuronal damage, inhibited the production of ROS, decreased MDA and 8-OHdG levels, increased SOD and GSH-PX activity to reduce oxidative damage, and restored mitochondrial membrane potential. BYHWD and Nrf2 activator TBHQ increased total Nrf2, nucleus Nrf2 protein expression, and its downstream HO-1 and NQO1 proteins, and the administration of the Nrf2 inhibitor brusatol reduced the enhancing effect of BYHWD. Meanwhile, BYHWD increased the expression of PKCε and P-PKCε and the administration of the PKCε inhibitor εV1-2 reduced the effect of BYHWD in increasing the expression of PKCε, P-PKCε, nuclear Nrf2, and HO-1, as well as promoting the effect of Nrf2 translocation to the nucleus. CONCLUSION: This study marks the first to demonstrate that BYHWD ameliorates oxidative damage and attenuates brain I/R injury by activating the PKCε/Nrf2/HO-1 pathway.

Experimental and Numerical Study of Natural Gas Leakage and Explosion Characteristics.

Frequent occurrence of indoor natural gas explosion accidents seriously threatens the safety of people and property. To determine the law of indoor natural gas leakage and explosion hazards, based on experiment and simulation, the nature of natural gas explosion, the distribution law of natural gas volume fraction, flame propagation, temperature, and shock wave overpressure were studied. The results show that the flame structure can be divided into three zones, i.e., preheat zone, reaction zone, and product zone. OH + CO ⇔ H + CO2 is the main exothermic reaction in the combustion process. The overall distribution law of natural gas volume fraction shows that the higher the position, the greater the volume fraction, and the closer the distance to the leak source at the same height, the greater the volume fraction, and the natural gas volume fraction of the hose falling off is the largest under different leakage conditions. The difference in the wrapping structure of the kitchen package has a significant impact on the diffusion distribution of natural gas. The flame development goes through five stages of ignition, slow burning, detonation, slow burning, and extinguishing. The indoor temperature reaches about 1400 °C. Although the simulated value of shock wave overpressure is larger than the experimental value, the relationship between overpressure and distance is expressed by Y = A + B * ln(X + C). This study can provide certain technical support for natural gas accident rescue. The research can provide certain technical support for natural gas accident rescue and can also be used for accident investigation to form the determination procedure and method of leakage location and leakage amount.

Preparation of an Intelligent Oleophobic Hydrogel and Its Application in the Replacement of Locally Damaged Oil Pipelines.

In the pipeline transportation process for crude oil, the most important and popular maintenance method for perforated and ruptured oil pipelines is the replacement of the damaged pipeline segment. However, this method has several disadvantages, including a complex process, large time consumption, and excessively high costs. The present study reported the preparation of a strong cross-linking hydrogel that served as a temporary blocking material during the long-distance oil pipeline partial replacement process. The prepared product was characterized by infrared spectroscopy, X-ray diffraction analysis, and scanning electron microscopy to analyze the microscopic reactions and structures. Orthogonal experiments for shear stress were performed to determine the optimal synthesis condition. The relevant experiments indicated that the proposed product can effectively isolate oil and oil gas, and a 4.5 m long hydrogel can resist the force of a 0.57 MPa overpressure. The blocked pipeline turned to a dredged state on changing the pipeline pressure. The flame resistance experiment showed that the hydrogel exhibited excellent flame resistance and could therefore ensure the safety of the hot work. On the basis of this hydrogel material, a new method for replacing the partially damaged oil pipeline was proposed.

Synthesis and performance characterization of an efficient coal dust suppressant for synergistic combustion with coal dust.

Coal dust diffusion during coal transportation and storage causes serious environmental pollution. The existing dust suppressant in previous studies was unable to achieve the expected effects owing to severe wind damage and rain erosion. Therefore, the current study synthesized and prepared an efficient and applicable dust suppressant for coal transportation and storage. Infrared spectroscopy and scanning electron microscope experiments were conducted during the synthesis to analyze the microstructure changes in the synthetic products. Moreover, viscosity was used as the evaluation index in the single-factor experiments to obtain the optimal synthesis conditions. Performance measurement results showed that the prepared dust suppressant had a strong protective effect on coal powder and could effectively resist the impact of wind damage and rain erosion. Compared with other dust suppressants, the proposed dust suppressant prepared showed more evident positive effects and longer lasting action time in the quantitative test. Moreover, the dried product could synergistically combust with coal powder, thereby possibly mitigating the tedious post-treatment process and increasing the utilization rate of resources.

ErCas12a CRISPR-MAD7 for Model Generation in Human Cells, Mice, and Rats.

MAD7 is an engineered class 2 type V-A CRISPR-Cas (Cas12a/Cpf1) system isolated from Eubacterium rectale. Analogous to Cas9, it is an RNA-guided nuclease with demonstrated gene editing activity in Escherichia coli and yeast cells. Here, we report that MAD7 is capable of generating indels and fluorescent gene tagging of endogenous genes in human HCT116 and U2OS cancer cell lines, respectively. In addition, MAD7 is highly proficient in generating indels, small DNA insertions (23 bases), and larger integrations ranging from 1 to 14 kb in size in mouse and rat embryos, resulting in live-born transgenic animals. Due to the different protospacer adjacent motif requirement, small-guide RNA, and highly efficient targeted gene disruption and insertions, MAD7 can expand the CRISPR toolbox for genome enginnering across different systems and model organisms.

A Novel BCL-2 Inhibitor APG-2575 Exerts Synthetic Lethality With BTK or MDM2-p53 Inhibitor in Diffuse Large B-Cell Lymphoma.

Despite therapeutic advances, the effective treatment for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) remains a major clinical challenge. Evasion of apoptosis through upregulating antiapoptotic B-cell lymphoma-2 (BCL-2) family members and p53 inactivation, and abnormal activation of B-cell receptor signaling pathway are two important pathogenic factors for DLBCL. In this study, our aim is to explore a rational combination of BCL-2 inhibitor plus Brutons tyrosine kinase (BTK) blockade or p53 activation for treating DLBCL with the above characteristics. We demonstrated that a novel BCL-2 selective inhibitor APG-2575 effectively suppressed DLBCL with BCL-2 high expression via activating the mitochondrial apoptosis pathway. BTK inhibitor ibrutinib combined with BCL-2 inhibitors showed synergistic antitumor effect in DLBCL with mean expression of BCL-2 and myeloid cell leukemia-1 (MCL-1) through upregulating the expression level of BIM and modulating MCL-1 and p-Akt expression. For p53 wild-type DLBCL with high expression of BCL-2, APG-2575 showed strong synergic effect with mouse double minute 2 (MDM2)p53 inhibitor APG-115 that can achieve potent antitumor effect and markedly prolong survival in animal models. Collectively, our data provide an effective and precise therapeutic strategy through rational combination of BCL-2 and BTK or MDM2p53 inhibitors for DLBCL, which deserves further clinical investigation.

Serum Apolipoprotein A-I Combined With C-Reactive Protein Serves As A Novel Prognostic Stratification System For Colorectal Cancer.

BACKGROUND AND OBJECTIVE: Noninvasive prognostic tools for colorectal cancer (CRC) are urgently needed. This study was designed to investigate the prognostic value of preoperative serum lipid and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) and CRP levels retrospectively in CRC patients. METHODS: Preoperative serum lipid and lipoprotein concentrations (including ApoA-I, Apo-B, HDL-C, LDL-C, TC and TG) and CRP levels were analyzed retrospectively in 250 patients with CRC. The prognostic significance of these indexes was determined by univariate and multivariate Cox hazard models. RESULTS: CRC patients with higher levels of ApoA-I and HDL-C and lower levels of CRP had significantly longer overall survival (OS, log rank test, p<0.05). Based on univariate analysis, ApoA-I levels (p=0.002), CRP levels (p=0.007), HDL-C levels (p=0.005), pT classification (p=0.005), pN classification (p<0.001), pM classification (p<0.001) and pTNM stage (p<0.001) were significantly associated with OS. Multivariate Cox proportional hazards regression analysis indicated that ApoA-I levels (HR: 1.52, p=0.023), CRP levels (HR: 1.85, p=0.035) and pTNM stage (HR: 2.53, p< 0.001) were independent predictors of CRC survival. The included patients were then stratified into three tiers based on the ApoA-I and CRP levels. In the whole cohort, the OS and disease-free survival differed significantly between the low-risk (ApoA-I≥1.08 mg/dL and CRP<3.04 mg/dL), medium-risk (ApoA-I≥1.08 mg/dL or CRP<3.04 mg/dL), and high-risk (ApoA-I<1.08 mg/dL and CRP ≥3.04 mg/dL) groups (p=0.001 and p=0.004). CONCLUSION: Decreased levels of ApoA-I and HDL-C and increased levels of CRP were predictive of poor prognosis among patients with CRC. In addition, the combination of ApoA-I and CRP can serve as a novel prognostic stratification system for more accurate clinical staging of CRC.