Macrophage Membrane Spontaneously Encapsulated Cyclodextrin-Based Nanomedicines for Improving Lipid Metabolism and Inflammation in Atherosclerosis.

Atherosclerosis is a persistent inflammatory condition of the blood vessels associated with abnormalities in lipid metabolism. Development of biomimetic nanoplatforms provides an effective strategy. Herein, inspired by the peptide CLIKKPF spontaneously coupling to phosphatidylserine (PS) on the inner leaflet of cell membranes specifically, MM@NPs were constructed by macrophage membrane spontaneous encapsulation of cyclodextrin-based nanoparticles modified with the peptide CLIKKPF and loaded with the hydrophobic compound resveratrol. MM@NPs could be specifically phagocytized by the activated endothelium with the overexpressed VCAM-1 for enhancing target delivery into the pathological lesion. Additionally, for the ApoE-/- mice, MM@NPs provide comprehensive treatment efficiency in reducing oxidant stress, alleviating the inherent inflammation, and decreasing cholesterol deposition, subsequently resulting in the atherosclerotic plaque regression. Therefore, MM@NPs could be one possible candidate for improving lipid metabolism and inflammation in atherosclerosis.

Metformin combined with cisplatin reduces anticancer activity via ATM/CHK2-dependent upregulation of Rad51 pathway in ovarian cancer.

Ovarian cancer (OC) is the deadliest malignancy of the female reproductive system. The standard first-line therapy for OC involves cytoreductive surgical debulking followed by chemotherapy based on platinum and paclitaxel. Despite these treatments, there remains a high rate of tumor recurrence and resistance to platinum. Recent studies have highlighted the potential anti-tumor properties of metformin (met), a traditional diabetes drug. In our study, we investigated the impact of met on the anticancer activities of cisplatin (cDDP) both in vitro and in vivo. Our findings revealed that combining met with cisplatin significantly reduced apoptosis in OC cells, decreased DNA damage, and induced resistance to cDDP. Furthermore, our mechanistic study indicated that the resistance induced by met is primarily driven by the inhibition of the ATM/CHK2 pathway and the upregulation of the Rad51 protein. Using an ATM inhibitor, KU55933, effectively reversed the cisplatin resistance phenotype. In conclusion, our results suggest that met can antagonize the effects of cDDP in specific types of OC cells, leading to a reduction in the chemotherapeutic efficacy of cDDP.

Identification of PANoptosis-relevant subgroups and predicting signature to evaluate the prognosis and immune landscape of patients with biliary tract cancer.

BACKGROUND: This study conducted molecular subtyping of biliary tract cancer patients based on 19 PANoptosis-related gene signatures. METHODS: Through consensus clustering, patients were categorized into two subtypes, A and B. By integrating multi-omics data and clinical information from different cohorts, we elucidated the association between different subtypes of biliary tract cancer and patient prognosis, which correlated with the immune infiltration characteristics of patients. RESULTS: LASSO regression analysis was performed on the 19 gene signatures, and we constructed and validated a 9-gene risk score prognostic model that accurately predicts the overall survival rate of different biliary tract cancer patients. Additionally, we developed a predictive nomogram demonstrating the clinical utility and robustness of our model. Further analysis of the risk score-based immune landscape highlighted potential associations with immune cell infiltration, chemotherapy, and immune therapy response. CONCLUSION: Our study provides valuable insights into personalized treatment strategies for biliary tract cancer, which are crucial for improving patient prognosis and guiding treatment decisions in clinical practice.

Glutathione hybrid poly (beta-amino ester)-plasmid nanoparticles for enhancing gene delivery and biosafety.

INTRODUCTION: CRISPR/Cas9 gene editing technology has significantly advanced gene therapy, with gene vectors being one of the key factors for its success. Poly (beta-amino ester) (PBAE), a distinguished non-viral cationic gene vector, is known to elevate intracellular reactive oxygen species (ROS) levels, which may cause cytotoxicity and, consequently, impact gene transfection efficacy (T.E.). OBJECTIVES: To develop a simple but efficient strategy to improve the gene delivery ability and biosafety of PBAE both in vivo and in vitro. METHODS: We used glutathione (GSH), a clinically utilized drug with capability to modulating intracellular ROS level, to prepare a hybrid system with PBAE-plasmid nanoparticles (NPs). This system was characterized by flow cytometry, RNA-seq, Polymerase Chain Reaction (PCR) and Sanger sequencing in vitro, and its safety and efficacy in vivo was evaluated by imaging, PCR, Sanger sequencing and histology analysis. RESULTS: The particle size of GSH-PBAE-plasmid NPs were 168.31 nm with a ζ-potential of 15.21 mV. An enhancement in T.E. and gene editing efficiency, ranging from 10 % to 100 %, was observed compared to GSH-free PBAE-plasmid NPs in various cell lines. In vitro results proved that GSH-PBAE-plasmid NPs reduced intracellular ROS levels by 25 %-40 %, decreased the total number of upregulated/downregulated genes from 4,952 to 789, and significantly avoided the disturbance in gene expression related to cellular oxidative stress-response and cell growth regulation signaling pathway compared to PBAE-plasmid NPs. They also demonstrated lower impact on the cell cycle, slighter hemolysis, and higher cell viability after gene transfection. Furthermore, GSH hybrid PBAE-plasmid NPs exhibited superior safety and improved tumor suppression ability in an Epstein-Barr virus (EBV)-infected murine tumor model, via targeting cleavage the EBV related oncogene by delivering CRISPR/Cas9 gene editing system and down-regulating the expression levels. This simple but effective strategy is expected to promote clinical applications of non-viral vector gene delivery.

Red Blood Cell Membrane Spontaneously Coated Nanoprodrug Based on Phosphatidylserine for Antiatherosclerosis Applications.

Atherosclerosis (AS) is characterized by the accumulation of lipids within the walls of coronary arteries, leading to arterial narrowing and hardening. It serves as the primary etiology and pathological basis for cardiovascular diseases affecting the heart and brain. However, conventional pharmacotherapy is constrained by inadequate drug delivery and pronounced toxic side effects. Moreover, the inefficacy of nanomedicine delivery systems in controlling disease progression may be attributed to nonspecific clearance by the mononuclear phagocyte system. Thus, a biomimetic platform spontaneously enveloped by red blood cell membrane is exploited for anti-atherosclerosis applications, offering favorable biocompatibility. The CLIKKPF polypeptide is introduced to develop red blood cell membrane spontaneously encapsulated nanotherapeutics only through simple coincubation. Given the functional modifications, RBC@P-LVTNPs is beneficial to facilitate the target drug delivery to the atherosclerotic lesion, responding precisely to the pathological ROS accumulation, thereby accelerating the on-demand drug release. Both in vivo and in vitro results also confirm the significant therapeutic efficacy and favorable biocompatibility of the biomimetic nanomedicine delivery system, thus providing a promising candidate for nanotherapeutics against AS.

Elimination of GGTA1, CMAH, ß4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions.

BACKGROUND: Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic, while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs. Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure, in which process the MHC II molecule plays critical roles. METHODS: Thus, we generate a 4-gene (GGTA1, CMAH, ß4GalNT2, and CIITA) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously. RESULTS: We successfully obtained 4KO piglets with deficiency in all alleles of genes, and at cellular and tissue levels. Additionally, the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping. Piglets have survived for more than one year in the barrier, and also survived for more than 3 months in the conventional environment, suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional environment. CONCLUSIONS: 4KO piglets have lower immunogenicity, are safe in genomic level, and are easier to breed than the model with both MHC I and II deletion.

Comparative Genome-Wide Identification of the Fatty Acid Desaturase Gene Family in Tea and Oil Tea.

Camellia oil is valuable as an edible oil and serves as a base material for a range of high-value products. Camellia plants of significant economic importance, such as Camellia sinensis and Camellia oleifera, have been classified into sect. Thea and sect. Oleifera, respectively. Fatty acid desaturases play a crucial role in catalyzing the formation of double bonds at specific positions of fatty acid chains, leading to the production of unsaturated fatty acids and contributing to lipid synthesis. Comparative genomics results have revealed that expanded gene families in oil tea are enriched in functions related to lipid, fatty acid, and seed processes. To explore the function of the FAD gene family, a total of 82 FAD genes were identified in tea and oil tea. Transcriptome data showed the differential expression of the FAD gene family in mature seeds of tea tree and oil tea tree. Furthermore, the structural analysis and clustering of FAD proteins provided insights for the further exploration of the function of the FAD gene family and its role in lipid synthesis. Overall, these findings shed light on the role of the FAD gene family in Camellia plants and their involvement in lipid metabolism, as well as provide a reference for understanding their function in oil synthesis.

Integrated sequence-based genomic, transcriptomic, and methylation characterization of the susceptibility to tuberculosis in monozygous twins.

Background: Tuberculosis (TB) is a complex disease with a spectrum of outcomes for more than six decades; however, the genomic and epigenetic mechanisms underlying the highly heritable susceptibility to TB remain unclear. Methods: Integrated sequence-based genomic, transcriptomic, and methylation analyses were conducted to identity the genetic factors associated with susceptibility to TB in two pairs of Mongolian monozygous twins. In this study, whole-genome sequencing was employed to analyze single nucleotide polymorphisms (SNPs), insertions and deletions (InDels), and copy number variations (CNVs). Gene expression was assessed through RNA sequencing, and methylation patterns were examined using the Illumina Infinium Methylation EPIC BeadChip. The gene-gene interaction network was analyzed using differentially expressed genes. Results: Our study revealed no significant difference in SNP and InDel profiles between participants with and without TB. Genes with CNVs were involved in human immunity (human leukocyte antigen [HLA] family and interferon [IFN] pathway) and the inflammatory response. Different DNA methylation patterns and mRNA expression profiles were observed in genes participating in immunity (HLA family) and inflammatory responses (IFNA, interleukin 10 receptor [IL-10R], IL-12B, Toll-like receptor, and IL-1B). Conclusions: The results of this study suggested that susceptibility to TB is associated with transcriptional and epigenetic alternations of genes involved in immune and inflammatory responses. The genes in the HLA family (HLA-A, HLA-B, and HLA-DRB1) and IFN pathway (IFN-α and IFN-γ) may play major roles in susceptibility to TB.

Optimization of mid-infrared noninvasive blood-glucose prediction model by support vector regression coupled with different spectral features.

Mid-infrared spectral analysis of glucose in subcutaneous interstitial fluid has been widely employed as a noninvasive alternative to the standard blood-glucose detection requiring blood-sampling via skin-puncturing, but improving the confidence level of such a replacement remains highly desirable. Here, we show that with an innovative metric of attributes in measurements and data-management, a high accuracy in correlating the test results of our improved spectral analysis to those of the standard detection is accomplished. First, our comparative laser speckle contrast imaging of subcutaneous interstitial fluid in fingertips, thenar and hypothenar reveal that spectral measurements from hypothenar, with an attenuated total reflection Fourier transform infrared spectrometer, give much stronger signals than the stereotype measurements from fingertips. Second, we demonstrate that discriminative selection of the spectral locations and ranges, to minimize spectral interference and maximize signal-to-noise, are critically important. The optimal band is pinned at that between 1000 ± 3 cm-1 and1040 ± 3 cm-1. Third, we propose an individual exclusive prediction model by adopting the support vector regression analysis of the spectral data from four subjects. The average predicted coefficient of determination, root mean square error and mean absolute error of four subjects are 0.97, 0.21 mmol/L, 0.17 mmol/L, respectively, and the average probability of being in Zone A of the Clark error grid is 100.00 %. Additionally, we demonstrate with the Bland and Altman plot that our proposed model has the highest consistency with portable blood glucose meter detection method.

The mechanism of Traditional Mongolian medicine Daruqi particles on inflammation.

Daruqi is a Traditional Mongolian medicine with anti-inflammatory, anti-bacterial, and immune-regulatory effects. However, the mechanisms of its activity were unclear. In the present study, we confirmed the anti-inflammation effect of Daruqi on inflammation induced by LPS using animal models. Then, THP-1 cells treated with LPS was used as a positive control to explore the effective component of Daruqi on inflammation. We identified that Oxymatrine was the essential effector of Daruqi. Furthermore, the mechanism of Oxymatrine on inflammation was verified through proteomics analyses and validation assays. Our results demonstrated that Oxymatrine significantly reduced the levels of inflammatory cytokine, including IL-8, IL-1α, and IL-1ß, in LPS induced THP-1 cells. Based on tandem mass tag -labeled quantitative proteomics, 428 differentially expressed proteins were screened, involved in TNF signaling pathway, Ferroptosis, IL-17 signaling pathway, etc. Among these differential expressed proteins (DEPs), 23 proteins were verified with parallel reaction monitoring analysis. The results showed that LPS treatment potentiated the protein level of PLEK, ACSL5 and CYBB, which could be reversed by Oxymatrine. By contrast, the protein expression of SPRYD4 and EMR2 was suppressed after LPS treatment, which could be rescued by Oxymatrine. In summary, Oxymatrine has excellent protective effects in LPS induced THP-1 cells. The five proteins, including PLEK, ACSL5, CYBB, SPRYD4 and EMR2, might serve as the targets of Oxymatrine, and as candidates regulating inflammation in future therapies.

Reactive oxygen species-responsive nano-platform with dual-targeting and fluorescent lipid-specific imaging capabilities for the management of atherosclerotic plaques.

Atherosclerosis (AS), a pathological cause of cardiovascular disease, results from endothelial injury, local progressive inflammation, and excessive lipid accumulation. AS plaques rich in foam cells are prone to rupture and form thrombus, which can cause life-threatening complications. Therefore, the assessment of atherosclerotic plaque vulnerability and early intervention are crucial in reducing the mortality rates associated with cardiovascular disease. In this work, A fluorescent probe FC-TPA was synthesized, which switches the fluorescence state between protonated and non-protonated, reducing background fluorescence and enhancing imaging signal-to-noise ratio. On this basis, FC-TPA is loaded into cyclodextrin (CD) modified with phosphatidylserine targeting peptide (PTP) and coated with hyaluronic acid (HA) to construct the intelligent responsive diagnostic nanoplatform (HA@PCFT). HA@PCFT effectively targets atherosclerotic plaques, utilizing dual targeting mechanisms. HA binds strongly to CD44, while PTP binds to phosphatidylserine, enabling nanoparticle aggregation at the lesion site. ROS acts as a smart release switch for probes. Both in vitro and in vivo evaluations confirm impressive lipid-specific fluorescence imaging capabilities of HA@PCFT nanoparticles (NPs). The detection of lipid load in atherosclerotic plaque by fluorescence imaging will aid in assessing the vulnerability of atherosclerotic plaque. STATEMENT OF SIGNIFICANCE: Currently, numerous fluorescent probes have been developed for lipid imaging. However, some challenges including inadequate water solubility, nonspecific distribution patterns, and fluorescence background interference, have greatly limited their further applications in vivo. To overcome these limitations, a fluorescent molecule has been designed and synthesized, thoroughly investigating its photophysical properties through both theoretical and experimental approaches. Interestingly, this fluorescent molecule exhibits the reversible fluorescence switching capabilities, mediated by hydrogen bonds, which effectively mitigate background fluorescence interference. Additionally, the fluorescent molecules has been successfully loaded into nanocarriers functionalized with the active targeting abilities, which has significantly improved the solubility of the fluorescent molecules and reduced their nonspecific distribution in vivo for an efficient target imaging in atherosclerosis. This study provides a valuable reference for evaluating the performance of such fluorescent dyes, and offers a promising perspective on the design of the target delivery systems for atherosclerosis.

Luteolin attenuates CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11.

BACKGROUND: Luteolin (3,4,5,7-tetrahydroxy flavone) is reported to strongly protect from acute carbon tetrachloride (CCl4) -induced liver injury or fibrosis. Ferroptosis can be induced by hepatic injury, and contributes to liver fibrosis development. The exact functional mechanism underlying luteolin inhibition of hepatic injury and whether ferroptosis is involved are unclear. METHODS: Mice model and cell model of liver injury were constructed or induced to explore the effect and molecular mechanisms of Luteolin in the treatment of hepatic injury using CCl4. Cell Counting Kit-8 (CCK-8) and flow cytometry were used to evaluate HepG2 cell viability and apoptosis. The differential expressed genes involved in liver injury were scanned using RNA-seq and confirmed using functional study. Western blot was used to detect the indicators related to ferroptosis. RESULTS: Luteolin attenuated hepatic injury by alleviating cell morphology and decreasing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels in vivo mice models, and increasing cell viability, downregulating arachidonate 12-lipoxygenase (ALOX12), cyclooxygenase-2 (COX-2) and P21 protein expression, suppressing apoptosis in vitro cell models. Luteolin also inhibited ferroptosis by stimulating glutathione peroxidase 4 (GPX4) and mitochondrial ferritin (FTMT) protein expression, increasing glutathione (GSH) content, and minimizing Fe2+ and malondialdehyde (MDA) levels. Solute carrier family 7a member 11 (SLC7A11) was identified to be a key regulatory gene that participated in luteolin attenuation of CCl4-induced hepatic injuries in HepG2 cells using Microarray assay. Functional study showed that SLC7A11 can alleviate hepatic injury and ferroptosis. CONCLUSION: Luteolin attenuated CCl4-induced hepatic injury by inhibiting ferroptosis via SLC7A11. SLC7A11 may serve as a novel alternative therapeutic target for hepatic injury.

Frontline combination of dasatinib and low-intensity chemotherapy in adults with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia.

BACKGROUND: Studies on dasatinib-based low-intensity induction regimens and post-remission strategies are limited in China. Therefore, we conducted a single-center phase 2 trial in newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) to establish the efficacy and safety of this treatment approach. RESEARCH DESIGN AND METHODS: Patients received one month of dasatinib plus low-intensity chemotherapy and two months of dasatinib monotherapy for induction, followed by a single course of high-dose methotrexate for consolidation. Subsequently, they underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) or tyrosine kinase inhibitor (TKI)-based treatment for maintenance therapy between October 2015 and August 2022. RESULTS: Twenty-two patients were enrolled. Median age was 45 years (range, 20-71). The rates of major and complete molecular responses in the third month were 18.2% and 40.9% respectively. With a median follow-up of 15 months (range, 5-89), the estimated 3-year disease-free survival (DFS) and overall survival (OS) were 52.4% and 73.2%, respectively. The TKI-based cohort had a significantly poorer DFS (p = 0.014) and OS (p = 0.008) than the allo-HSCT cohort. CONCLUSIONS: Our results suggest that dasatinib-based low-intensity chemotherapy is safe and effective as an induction strategy in the Chinese population. Allo-HSCT plays a crucial role in the long-term outcomes of patients with Ph+ ALL. CLINICAL TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as NCT02690922.

A Multiplex Recombinase-Aided qPCR Assay for Highly Sensitive and Rapid Detection of khe, blaKPC -2, and blaNDM -1 Genes in Klebsiella pneumoniae.

OBJECTIVE: This study aimed to establish a highly sensitive and rapid single-tube, two-stage, multiplex recombinase-aided qPCR (mRAP) assay to specifically detect the khe, blaKPC-2, and blaNDM-1 genes in Klebsiella pneumoniae. METHODS: mRAP was carried out in a qPCR instrument within 1 h. The analytical sensitivities of mRAP for khe, blaKPC-2, and blaNDM-1 genes were tested using recombinant plasmids and dilutions of reference strains. A total of 137 clinical isolates and 86 sputum samples were used to validate the clinical performance of mRAP. RESULTS: mRAP achieved the sensitivities of 10, 8, and 14 copies/reaction for khe, blaKPC-2, and blaNDM-1 genes, respectively, superior to qPCR. The Kappa value of qPCR and mRAP for detecting khe, blaKPC-2, and blaNDM-1 genes was 1, 0.855, and 1, respectively (p < 0.05). CONCLUSION: mRAP is a rapid and highly sensitive assay for potential clinical identification of khe, blaKPC-2, and blaNDM-1 genes in K. pneumoniae.

Combination of chidamide and PD-1 blockade in Refractory/Relapsed aggressive large B-cell lymphomas with high risk of failing CAR-T therapy.

BACKGROUND: Refractoriness and relapse after chimeric antigen receptor T-cell therapy have emerged as major challenges for immunotherapy of aggressive large B-cell lymphoma. Thus far, there is no consensus on how to address treatment failure and whether to administer maintenance therapy following CAR-T cell therapy. METHODS: From August 2017 through November 2022, 52 patients with refractory/relapsed aggressive LBCL who had a high risk of resistance to CAR-T cell therapy were given chidamide in combination with a PD-1 inhibitor as maintenance therapy following either CAR19/22 T-cell cocktail therapy or CAR19/22 T-cell cocktail therapy plus autologous stem cell transplantation (ASCT). Another 52 aggressive LBCL patients who had comparable baseline characteristics and received similar therapeutic regimens but did not receive any interventions following CAR-T cell therapy or CAR-T cell therapy plus ASCT were regarded as the control group to evaluate the efficacy and safety of the combination of chidamide and a PD-1 inhibitor. RESULTS: Among the 52 patients who received chidamide and a PD-1 inhibitor as maintenance therapy, with a median follow-up of 26.5 months (range: 1.1-53.8), neither the median progression-free survival (PFS) nor overall survival (OS) was reached, and the expected 2-year OS and PFS rates were 89 % and 77 %, respectively, which were superior to those of the control group (p < 0.001). Long-term chidamide administration and a specific genetic subtype of EZB were strongly associated with a better response after chidamide plus PD-1 blockade therapy. Additionally, long-term chidamide administration was significantly associated with prolonged persistence and reactivation of CD19-directed CAR-T cells in the peripheral blood. Adverse effects (AEs) were moderate and reversible, and no treatment-related deaths occurred. CONCLUSION: Our results indicate that the combination of chidamide and PD-1 blockade as maintenance therapy could improve the outcomes of aggressive LBCL patients at high risk of failing CAR-T cell therapy.

Clinical performance of metagenomic next-generation sequencing for diagnosis of pulmonary Aspergillus infection and colonization.

Background: Investigations assessing the value of metagenomic next-generation sequencing (mNGS) for distinguish Aspergillus infection from colonization are currently insufficient. Methods: The performance of mNGS in distinguishing Aspergillus infection from colonization, along with the differences in patients' characteristics, antibiotic adjustment, and lung microbiota, were analyzed. Results: The abundance of Aspergillus significantly differed between patients with Aspergillus infection (n=36) and colonization (n=32) (P < 0.0001). Receiver operating characteristic (ROC) curve result for bronchoalveolar lavage fluid (BALF) mNGS indicated an area under the curve of 0.894 (95%CI: 0.811-0.976), with an optimal threshold value of 23 for discriminating between Aspergillus infection and colonization. The infection group exhibited a higher proportion of antibiotic adjustments in comparison to the colonization group (50% vs. 12.5%, P = 0.001), with antibiotic escalation being more dominant. Age, length of hospital stay, hemoglobin, cough and chest distress were significantly positively correlated with Aspergillus infection. The abundance of A. fumigatus and Epstein-Barr virus (EBV) significantly increased in the infection group, whereas the colonization group exhibited higher abundance of A. niger. Conclusion: BALF mNGS is a valuable tool for differentiating between colonization and infection of Aspergillus. Variations in patients' age, length of hospital stay, hemoglobin, cough and chest distress are observable between patients with Aspergillus infection and colonization.

TNF-α is a predictive marker in distinguishing myeloproliferative neoplasm and idiopathic erythrocytosis/thrombocytosis: development and validation of a non-invasive diagnostic model.

Purpose: Philadelphia-chromosome negative myeloproliferative neoplasms (MPN) exhibit phenotypic similarities with JAK/STAT-unmutated idiopathic erythrocytosis and thrombocytosis (IE/IT). We aimed to develop a clinical diagnostic model to discern MPN and IE/IT. Methods: A retrospective study was performed on 77 MPN patients and 32 IE/IT patients in our center from January 2018 to December 2023. We investigated the role of hemogram, cytokine and spleen size in differentiating MPN and IE/IT among newly onset erythrocytosis and thrombocytosis patients. Independent influencing factors were integrated into a nomogram for individualized risk prediction. The calibration and discrimination ability of the model were evaluated by concordance index (C-index), calibration curve. Results: MPN had significantly higher TNF-α level than IE/IT, and the TNF-α level is correlated with MF-grade. Multivariable analyses revealed that TNF-α, PLT count, age, size of spleen were independent diagnostic factors in differentiating MPN and IE/IT. Nomograms integrated the above 4 factors for differentiating MPN and IE/IT was internally validated and had good performance, the C-index of the model is 0.979. Conclusion: The elevation of serum TNF-α in MPN patients is of diagnostic significance and is correlated with the severity of myelofibrosis. The nomogram incorporating TNF-α with age, PLT count and spleen size presents a noteworthy tool in the preliminary discrimination of MPN patients and those with idiopathic erythrocytosis or thrombocytosis. This highlights the potential of cytokines as biomarkers in hematologic disorders.

Calculation method of spherically expanding flame propagation radius to consider ignition electrode effects.

Ignition electrodes have an immense impact on the accurate measurement of the flame propagation spherical radius. In this study, a flame-radius calculation method is designed. The method is able to eliminate effects due to the ignition electrodes. The adaptability and optimization effects of the proposed method are analyzed. The results show that the ratio of the angle is affected by the ignition electrodes under the Han II method. There are three obvious divisions include a high-value area, a sharp-variation area, and a mild-variation area. The ratio of the angle affected by the ignition electrodes is only applicable to the mild-variation region when the flame presents respective convex and concave distributions. For these distributions, the increment rate of the mean radius is 0.4-0.85% and 0.42-3.19%. The reduced rate of the standard deviation of the radius extraction value is 11.91-22.1% and 5.13-17.99%, and the reduced rate of the radius extraction value range is 20.32-39.51% and 0.32-8.09%.

Genome-Wide Identification and Transcriptome Analysis of the Hsp70 Gene Family in Monodonta labio Reveals Its Role in Response to Nanoplastics Stress.

For marine invertebrates, the disruption of organismal physiology and behavior by nanoplastics (NPs) has been extensively reported. Heat shock proteins (Hsps) are important for redundant protein breakdown, environmental changes, and intracellular protein transport. An exhaustive identification of Hsp70 genes and an experiment where different concentrations of NPs were stressed were performed to study how Hsp70 genes respond to NPs stress in Monodonta labio. Our results identified 15 members of Hsp70 within the genome of M. labio and provided insights into their responses to different concentrations of acute NP stress. Phylogenetic analyses revealed extensive amplification of the Hsp70 genes from the Hsc70 subfamily, with gene duplication events. As a result of NP stress, five of fifteen genes showed significant upregulation or downregulation. Three Hsp70 genes were highly expressed at an NP concentration of 0.1 mg/L, and no genes were downregulated. At 10 mg/L, they showed significant upregulation of two genes and significant downregulation of two genes. At 1 mg/L treatment, three genes were significantly downregulated, and no genes were significantly upregulated. Moreover, a purifying selection was revealed using a selection test conducted on duplicate gene pairs, indicating functional redundancy. This work is the first thorough examination of the Hsp70s in Archaeogastropoda. The findings improve knowledge of Hsp70s in molluscan adaptation to NP stress and intertidal living and offer essential data for the biological study of M. labio.