Associations Between ABO Blood Groups and Diseases in the Digestive System and Vein.

Purpose: The ABO blood type system is crucial for human blood transfusions. However, the relationships between ABO blood groups and diseases in the digestive system and vein have not been elucidated. We investigated the relationships between ABO blood groups and diseases in the digestive system and vein in this study. Patients and Methods: A retrospective study on a Chinese population, including 1432 Crohn's disease (CD), 416 ulcerative colitis (UC), 1140 stomach cancer (SC), 841 colorectal cancer (CRC), 384 pancreatic cancer (PC), 520 liver cancer (LC), and 563 venous thrombosis (VT) patients, was performed. Furthermore, 896 healthy subjects were enrolled as normal controls (NC) in this study. The demographic characteristics of patients and NC were compared using the unpaired t-test and χ2 test. Multivariate logistic regression model was used to evaluate the association between ABO blood groups and CD and VT. Results: ABO blood groups distributions in UC, SC, CRC, PC, and LC patients did not differ from that of NC, but CD and VT patients had significant difference of ABO blood group distribution from that of NC (p = 0.015 and p = 0.002, respectively). Patients with CD and VT had considerably lower rates of type O blood (p = 0.011 and p = 0.001, respectively) and significantly higher rates of type AB blood (p = 0.013 and p = 0.022, respectively) than those with NC. Multivariate logistic regression analysis showed the association of CD and VT with non-O blood types was still significant with a higher risk than with blood group O after adjusting for age and gender (OR = 1.355, 95% CI = 1.100-1.670, p = 0.004 and OR = 1.465, 95% CI = 1.131-1.903, p = 0.004, respectively). Conclusion: ABO blood groups distributions in CD and VT patients significantly differed from that of NC. Non-O blood group could be a new predictor for CD and VT.

Abnormal biochemical indicators of neonatal inherited metabolic disease in carriers.

BACKGROUND: Traditional biochemical screening for neonatal inherited metabolic diseases has high false-positive rates and low positive predictive values, which are not conducive to early diagnosis and increase parents' anxiety. This study analysed the relationship between gene variant carriers and their biochemical indicators in traditional biochemical screening, aiming to find explanations for false positives in newborns. RESULTS: This retrospective study included 962 newborns. Newborns underwent traditional biochemical screening at birth using blood staining and genomic sequencing of their stored blood staining using the NeoSeq Pro panel, which was able to detect 154 pathogenic genes and 86 diseases. A total of 632 newborns were carriers of gene variants. 56% of congenital hypothyroidism carriers had higher thyroid-stimulating hormone levels than normal newborns. Abnormal biochemical indices were detected in 71% of carriers of organic acid metabolic diseases, 69% of carriers of amino acid metabolic diseases, and 85% of carriers of fatty acid ß oxidation disorders. In carriers associated with organic acid metabolic diseases, the propionylcarnitine (C3), C3/acetylcarnitine (C2), and methylmalonylcarnitine (C4DC) + 3-hydroxyisovalerylcarnitine (C5OH) levels were higher than those in non-carriers (C3: 4.12 vs. 1.66 µmol/L; C3/C2: 0.15 vs. 0.09; C4DC + C5OH: 0.22 vs. 0.19 µmol/L). In carriers associated with amino acid metabolic diseases, phenylalanine levels were higher than those in non-carriers (68.00 vs. 52.05 µmol/L). For carriers of fatty acid ß oxidation disorders, butyrylcarnitine levels were higher than those in non-carriers (0.31 vs. 0.21 µmol/L), while the free carnitine levels were lower than those in non-carriers (14.65 vs. 21.87 µmol/L). There was a higher occurrence of carriers among newborns who received false-positive results for amino acid metabolic diseases compared to those who received negative results (15.52% vs. 6.71%). Similarly, there was a higher occurrence of carriers among newborns who received false-positive results for fatty acid ß oxidation disorders compared to those who received negative results (28.30% vs. 7.29%). CONCLUSIONS: This study showed that the carriers comprised a large number of newborns. Carriers had abnormal biochemical indicators compared with non-carriers, which could explain the false-positive rate for newborns using traditional newborn biochemical screening, especially in amino acid metabolic and fatty acid ß oxidation disorders.

Monitoring hepatocellular carcinoma using tumor content in circulating cell-free DNA.

PURPOSE: To evaluate the utility of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. METHODS: We included 67 hepatitis B virus (HBV)-related HCC patients, of whom 17 had paired pre- and post-treatment samples, and 90 controls. Additionally, in a prospective cohort with HBV surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA. RESULTS: High tumor content was associated with advanced tumor stage (P < 0.001) and a poor survival after HCC diagnosis (HR=12.35; 95% confidence interval [CI]=1.413-107.9; P = 0.023). Tumor content turned negative after surgery (P = 0.027), while remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95%CI=92.2%-99.7%). In pre-HCC samples, tumor content increased from 0.014 in 4 years before diagnosis to 0.026 in 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95%CI=11.5%-37.8%) within one year before diagnosis to 30.4% (95%CI=13.2%-52.9%) at BCLC stage 0/A, 81.8% (95%CI=59.7%-94.8%) at stage B, and 95.5% (95%CI=77.2%-99.9%) at stage C. CONCLUSIONS: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC one year earlier than clinical diagnosis and in predicting patient prognosis.

Heat-Localized and Salt-Resistant 3D Hierarchical Porous Ceramic Platform for Efficient Solar-Driven Interfacial Evaporation.

Solar-driven interfacial evaporation (SDIE) is a highly promising approach to achieve sustainable desalination and tackle the global freshwater crisis. Despite advancements in this field, achieving balanced thermal localization and salt resistance remains a challenge. Herein, the study presents a 3D hierarchical porous ceramic platform for SDIE applications. The utilized alumina foam ceramics (AFCs) exhibit remarkable corrosion resistance and chemical stability, ensuring a prolonged operational lifespan in seawater or brines. The millimeter-scale air-filled pores in AFCs prevent thermal losses through conduction with bulk water, resulting in heat-localized interfaces. The hydrophilic nature of macroporous AFC skeletons facilitates rapid water replenishment on the evaporating surface for effective salt-resistant desalination. Benefiting from its self-radiation adsorption and side-assisted evaporation capabilities, the AFC-based evaporators exhibit high indoor evaporation rates of 2.99 and 3.54 kg m-2 h-1 under one-sided and three-sided illumination under 1.0 sun, respectively. The AFC-based evaporator maintains a high evaporation rate of ≈2.77 kg m-2 h-1 throughout the 21-day long-term test. Furthermore, it achieves a daily water productivity of ≈10.44 kg m-2 in outdoor operations. This work demonstrates the potential of 3D hierarchical porous ceramics in addressing the trade-off between heat localization and salt resistance, and contributes to the development of durable solar steam generators.

Preventing thermal aggregation of ovalbumin through dielectric-barrier discharge plasma treatment and enhancing its emulsification properties.

The impact of Dielectric-Barrier Discharge (DBD) plasma treatment on the prevention of heat-induced aggregation of Ovalbumin (OVA) and improvement in emulsification properties was investigated. Results highlighted the effective inhibition of thermal aggregation of OVA following exposure to plasma. Structural analysis revealed that the plasma-induced oxidation of sulfhydryl and intermolecular disulfide bonds played a pivotal role in inhibiting the thermal aggregation, considered by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE), multiplies spectroscopy, and analysis of dynamic exchange of sulfhydryl-disulfide bonds. Meanwhile, the oxidation of exposed hydrophobic sites due to plasma treatment resulted in the transformation of the OVA molecule's surface from hydrophobic to hydrophilic, contributing significantly to the aggregation inhibition. Additionally, compared to an untreated sample of OVA, almost one-fold increase in emulsifying ability (EAI) and 1.5-fold in emulsifying stability (ESI) was observed after 4 min of plasma treatment. These findings demonstrated that plasma treatment not only enhanced the thermal stability of OVA, but also improved its emulsification properties.

Electrospinning Silk-Fibroin-Based Fibrous Membranes with AgNPs for Antimicrobial Application.

Silk fibroin (SF) has excellent biocompatibility and is one of the most commonly used polymer materials. However, SF fibers have serious drawbacks as antibacterial materials due to their lack of stability and bacterial resistance. Therefore, it is of paramount significance to enhance the stability and bolster the bacterial resistance of SF fibers. In this study, SF fibers were fabricated and loaded with Ag nanoparticles (AgNPs) to improve the antimicrobial properties of the fibers. The impact of reduction conditions on the size of AgNPs was also investigated. In an antibacterial test, the fibers that were prepared exhibited over 98% bacterial resistance against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). Therefore, as an efficient antibacterial material, these fibers are expected to become a candidate material in medical and textile fields. This study offers a novel approach for the utilization of SF fibers in the realm of antibacterial applications.

Substrate types and applications of MXene for surface-enhanced Raman spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) has been widely used in the analysis of analytes because of its unique fingerprint characteristics, high sensitivity, and fast detection response. MXene is widely used in SERS studies among the various substrates due to its ultra-high chemical stability, excellent conductivity, hydrophilicity, and low fabrication cost. This mini-review summarizes MXene's research in the SERS field from two aspects. We reviewed MXene materials used as SERS substrates alone and combined with noble metal particles primarily. Subsequently, we outlined representative applications of MXene-based SERS in biomedicine, food safety, and environmental monitoring. Moreover, we discussed the technical bottleneck and the prospect of future development in this field.

Visual authenticating hazardous adulterant phenolphthalein in slimming foods: Target-mimicking hapten epitope improved immunoassay.

Screening for the hazardous adulterant phenolphthalein (PTH) in slimming foods is necessary. Herein, the linkage of the PTH target epitope with various spacer arms was proposed for hapten design, aiming to produce highly sensitive and specific antibodies targeting PTH. To understand the influence of spacer arms on epitope, comprehensive evaluations were conducted using computer-aided chemistry and animal immunization. The resulting antibody exhibited maximal half-inhibitory concentration (IC50) of 0.25 ng/mL. Then, a lateral flow immunoassay (LFIA) was established with detection capability for screening (CCß) of less than 140, 240, and 25 ng/g for PTH in tea, instant coffee, and oral liquid, respectively. Furthermore, blind sample results agreed well with LFIA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Therefore, this work not only provides a robust tool for detecting PTH adulteration but also suggests that the careful pairing of spacer arms with hapten epitope is a key factor in advancing rational hapten design.

Restoring T and B cell generation in X-linked severe combined immunodeficiency mice through hematopoietic stem cells adenine base editing.

Base editing of hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematologic diseases. However, the feasibility of using adenine-base-edited HSPCs for treating X-linked severe combined immunodeficiency (SCID-X1), the influence of dose-response relationships on immune cell generation, and the potential risks have not been demonstrated in vivo. Here, a humanized SCID-X1 mouse model was established, and 86.67% ± 2.52% (n = 3) of mouse hematopoietic stem cell (HSC) pathogenic mutations were corrected, with no single-guide-RNA (sgRNA)-dependent off-target effects detected. Analysis of peripheral blood over 16 weeks post-transplantation in mice with different immunodeficiency backgrounds revealed efficient immune cell generation following transplantation of different amounts of modified HSCs. Therefore, a large-scale infusion of gene-corrected HSCs within a safe range can achieve rapid, stable, and durable immune cell regeneration. Tissue-section staining further demonstrated the restoration of immune organ tissue structures, with no tumor formation in multiple organs. Collectively, these data suggest that base-edited HSCs are a potential therapeutic approach for SCID-X1 and that a threshold infusion dose of gene-corrected cells is required for immune cell regeneration. This study lays a theoretical foundation for the clinical application of base-edited HSCs in treating SCID-X1.

Role of iron oxide in retarding the graphitization of de-oiled asphaltenes for amorphous carbon.

The solvent deasphalting (SDA) process is widely recognized as a significant technology in processing inferior oil. However, de-oiled asphaltene (DOA), which accounts for about 30% of feedstocks, is not well utilized in conventional processing methods to date. Considering its complicated structure and high heteroatom and metal contents, DOA is suitable for preparing amorphous carbon. Herein, we obtained amorphous carbon from inferior de-oiled asphaltene through direct carbonization of a mixture of DOA and Fe2O3 and revealed the mechanism of iron oxide in retarding graphitization to increase the disordered structure content. After the addition of Fe2O3, XRD results showed that the content of amorphous carbon increased from 25.57% to 59.48%, and a higher defect degree could also be observed in Raman spectra, thus resulting in better electrochemical performance in Na-ion half-cells. As a coke core, Fe2O3 could accelerate the polycondensation of asphaltene molecules; meanwhile, oxygen species derived from Fe2O3 could capture excess H free radicals in the initial pyrolysis stage, which inhibited the formation of planar polycyclic aromatic molecules and weakened π-π interactions. Moreover, O atoms could embed into the carbon skeleton by reacting with DOA at higher temperatures, which could further twist and break the intact carbon layer. Both of the factors enhanced the proportion of amorphous carbon. This work not only provides a new understanding of controlling the carbonization process, but it also promotes the development of the SDA process.

CDKL1 potentiates the antitumor efficacy of radioimmunotherapy by binding to transcription factor YBX1 and blocking PD-L1 expression in lung cancer.

BACKGROUND: The evasion of the immune response by tumor cells through programmed death-ligand 1 (PD-L1) has been identified as a factor contributing to resistance to radioimmunotherapy in lung cancer patients. However, the precise molecular mechanisms underlying the regulation of PD-L1 remain incompletely understood. This study aimed to investigate the role of cyclin-dependent kinase-like 1 (CDKL1) in the modulation of PD-L1 expression and the response to radioimmunotherapy in lung cancer. METHODS: The tumorigenic roles of CDKL1 were assessed via cell growth, colony formation, and EdU assays and an in vivo nude mouse xenograft model. The in vitro radiosensitization effect of CDKL1 was evaluated using a neutral comet assay, γH2AX foci formation analysis, and a clonogenic cell survival assay. The protein‒protein interactions were confirmed via coimmunoprecipitation and GST pulldown assays. The regulation of PD-L1 by CDKL1 was evaluated via chromatin immunoprecipitation (ChIP), real-time quantitative PCR, and flow cytometry analysis. An in vitro conditioned culture model and an in vivo C57BL/6J mouse xenograft model were developed to detect the activation markers of CD8+ T cells and evaluate the efficacy of CDKL1 overexpression combined with radiotherapy (RT) and an anti-PD-L1 antibody in treating lung cancer. RESULTS: CDKL1 was downregulated and suppressed the growth and proliferation of lung cancer cells and increased radiosensitivity in vitro and in vivo. Mechanistically, CDKL1 interacted with the transcription factor YBX1 and decreased the binding affinity of YBX1 for the PD-L1 gene promoter, which consequently inhibits the expression of PD-L1, ultimately leading to the activation of CD8+ T cells and the inhibition of immune evasion in lung cancer. Moreover, the combination of CDKL1 overexpression, RT, and anti-PD-L1 antibody therapy exhibited the most potent antitumor efficacy against lung cancer. CONCLUSIONS: Our findings demonstrate that CDKL1 plays a crucial role in regulating PD-L1 expression, thereby enhancing the antitumor effects of radioimmunotherapy. These results suggest that CDKL1 may be a promising therapeutic target for the treatment of lung cancer.

Construction of test strips for lung cancer detection based on aptamers.

Lung cancer is the most common malignancy worldwide. Early diagnosis helps to reduce mortality and improve survival. Aptamers are widely used in cancer screening because of their high specificity, good stability and low cost. In this study, using the specific aptamer of lung cancer serum, the sandwich method colloidal gold test strip was prepared by isothermal amplification technique and the principle of nucleic acid hybridisation for the early diagnosis of lung cancer. The results showed that the test strip was positive in 8 patients with lung cancer, which was consistent with the actual cases. The test strip can accurately identify lung cancer patients. The concentration range of nucleic acid detection is 1 × 10-4 - 7 × 10-4 mol/L, and the detection limit is 0.67 mM. The test strip detection method has low cost and simple operation, and provides a reference for the development of home portable tumor early detection.

A proteomic landscape of pharmacologic perturbations for functional relevance.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Ononin promotes radiosensitivity in lung cancer by inhibiting HIF-1α/VEGF pathway.

BACKGROUND: In our previous study, we provided evidence that Astragalus mongholicus Bunge(AM) and its extracts possess a protective capability against radiation-induced damage, potentially mediated through the reduction of reactive oxygen species (ROS) and nitric oxide (NO). However, we were pleasantly surprised to discover during our experimentation that AM not only offers protection against radiation damage but also exhibits a radiation sensitization effect. This effect may be attributed to a specific small molecule present in AM known as ononin. Currently, radiation sensitizers are predominantly found in nitrazole drugs and nanomaterials, with no existing reports on the radiation sensitization properties of ononin, nor its underlying mechanism. PURPOSE: This study aims to investigate the sensitization effect of the small molecule ononin derived from AM on lung cancer radiotherapy, elucidating its specific molecular mechanism of action. Additionally, the safety profile of combining astragalus small molecule ononin with radiation therapy will be evaluated. METHODS: The effective concentration of ononin was determined through cell survival experiments, and the impact of ononin combined with varying doses of radiation on lung cancer cells was observed using CCK-8 and cell cloning experiments. The apoptotic effect of ononin combined with radiation on lung cancer cells was assessed using Hochester staining, flow cytometry, and WB assay. Additionally, WB and immunofluorescence analysis were conducted to investigate the influence of ononin on HIF-1α/VEGF pathway. Furthermore, Molecular Dynamics Simulation was employed to validate the targeted binding ability of ononin and HIF-1α. A lung cancer cell line was established to investigate the effects of knockdown and overexpression of HIF-1α. Subsequently, the experiment was repeated using tumor bearing nude mice and C57BL/6 mouse models in an in vivo study. Tumor volume was measured using a vernier caliper, while HE, immunohistochemistry, and immunofluorescence techniques were employed to observe the effects of ononin combined with radiation on tumor morphology, proliferation, and apoptosis. Additionally, Immunofluorescence was employed to examine the impact of ononin on HIF-1α/VEGF pathway in vivo, and its effect on liver function in mice was assessed through biochemistry analysis. RESULTS: At a concentration of 25 µM, ononin did not affect the proliferation of lung epithelial cells but inhibited the survival of lung cancer cells. In vitro experiments demonstrated that the combination of ononin and radiation could effectively inhibit the growth of lung cancer cells, induce apoptosis, and suppress the excessive activation of the Hypoxia inducible factor 1 alpha/Vascular endothelial growth factor pathway. In vivo experiments showed that the combination of ononin and radiation reduced the size and proliferation of lung cancer tumors, promoted cancer cell apoptosis, mitigated abnormal activation of the Hypoxia inducible factor 1 alpha pathway, and protected against liver function damage. CONCLUSION: This study provides evidence that the combination of AM and its small molecule ononin can enhance the sensitivity of lung cancer to radiation. Additionally, it has been observed that this combination can specifically target HIF-1α and exert its effects. Notably, ononin exhibits the unique ability to protect liver function from damage while simultaneously enhancing the tumor-killing effects of radiation, thereby demonstrating a synergistic and detoxifying role in tumor radiotherapy. These findings contribute to the establishment of a solid basis for the development of novel radiation sensitizers derived from traditional Chinese medicine.

Drought responses and population differentiation of Calohypnum plumiforme inferred from comparative transcriptome analysis.

Bryophytes, known as poikilohydric plants, possess vegetative desiccation-tolerant (DT) ability to withstand water deficit stress. Consequently, they offer valuable genetic resources for enhancing resistance to water scarcity stress. In this research, we examined the physiological, phytohormonal, and transcriptomic changes in DT mosses Calohypnum plumiforme from two populations, with and without desiccation treatment. Comparative analysis revealed population differentiation at physiological, gene sequence, and expression levels. Under desiccation stress, the activities of superoxide dismutase (SOD) and peroxidase (POD) showed significant increases, along with elevation of soluble sugars and proteins, consistent with the transcriptome changes. Notable activation of the bypass pathway of JA biosynthesis suggested their roles in compensating for JA accumulation. Furthermore, our analysis revealed significant correlations among phytohormones and DEGs in their respective signaling pathway, indicating potential complex interplays of hormones in C plumiforme. Protein phosphatase 2C (PP2C) in the abscisic acid signaling pathway emerged as the pivotal hub in the phytohormone crosstalk regulation network. Overall, this study was one of the first comprehensive transcriptome analyses of moss C. plumiforme under slow desiccation rates, expanding our knowledge of bryophyte transcriptomes and shedding light on the gene regulatory network involved in response to desiccation, as well as the evolutionary processes of local adaptation across moss populations.

Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation.

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.

Fraxini cortex: Progresses in phytochemistry, pharmacology and ethnomedicinal uses.

ETHNOPHARMACOLOGICAL RELEVANCE: Fraxini cortex, which has been widely used as a traditional Chinese medicine for 2000 years, is made from the dried bark of four plant species: Fraxinus chinensis subsp. rhynchophylla (Hance) A.E.Murray, Fraxinus chinensis Roxb., Fraxinus chinensis subsp. chinensis and Fraxinus stylosa Lingelsh.. In Chinese traditional medicine, it possesses the properties of heat-clearing and dampness-drying, asthma relief and cough suppression, as well as vision improvement. It is utilized for treating bacterial disorders, enteritis, leukorrhea, chronic bronitis, painful red eyes with swelling, lacrimation due to windward exposure, psoriasis, and other diseases or related symptoms. AIM OF THE STUDY: Fraxini cortex is abundant in chemical constituents and has garnered significant attention from plant chemists, particularly regarding coumarins, as evidenced by the recently identified three coumarin compounds. Considering the current dearth of systematic reporting on studies pertaining to Fraxini cortex, herein we provide a comprehensive summary of the advancements in phytochemistry, pharmacology, detection methods, and ethnomedicinal applications of Fraxini cortex. MATERIALS AND METHODS: We conducted a comprehensive search across online data sources (Web of Science, Public Medicine (PubMed), China National Knowledge Infrastructure (CNKI), as well as Chinese dissertations) and traditional Chinese medicine classics to gather the necessary literature resources for this review. RESULTS: Briefly, The Fraxini cortex yielded a total of 132 phytochemicals, including coumarins, lignans, secoiridoids, phenylethanol glycosides, flavonoids, triterpenoids, and other compounds. Among them, the main active ingredients are coumarins which possess a diverse range of pharmacological activities such as anti-inflammatory effects, anti-tumor properties, prevention of tissue fibrosis and oxidation damage as well as cardioprotective effects. CONCLUSIONS: All types of research conducted on Fraxini cortex, particularly in the field of ethnopharmacology, phytochemistry, and pharmacology, have been thoroughly reviewed. However, certain traditional applications and pharmacological activities of Fraxini cortex lack scientific evaluation or convincing evidence due to incomplete methodologies and ambiguous results, as well as a lack of clinical data. To validate its pharmacological activity, clinical efficacy, and safety profile, a systematic and comprehensive research evaluation is imperative. As an important traditional Chinese medicine, Fraxini cortex should be further explored to facilitate the development of novel drugs and therapeutics for various diseases. Greater attention should be given to how it can be better utilized.

Bmpali, Bmb1 and Bmcap are necessary for uric acid granule formation in Bombyx mori.

Uric acid is the end-product of nitrogen metabolism of the silkworm and other lepidopterans. The accumulation of uric acid particles in the epidermis causes the larval silkworm to appear white and opaque. However, the mechanism of uric acid granule formation is still unclear. Silkworm epidermis color is linked to the genes responsible for uric acid particle formation. We first identified two genes in the Bombyx mori genome that encode subunits of the Bloc-1 (Biogenesis of Lysosome-related Organelles Complex-1) by homology to these genes in other eukaryotes, Bmpali and Bmb1. Mutation in these genes caused a transparent phenotype in the silkworm larvae, and the loss of BmBloc-1 subunit gene Bmcap resulted in the same phenotype. These three genes are highly conserved between human and silkworm. We discovered that Bmpali, Bmcap, and Bmb1 localize in the cytoplasm of BmN cells. Yeast two-hybrid assays demonstrated that the Bmpali physically interacts with both Bmcap and Bmb1. Investigating the roles of Bmpali, Bmb1, and Bmcap is essential for uric acid granule formation understanding in Bombyx mori. These mutants present a valuable silkworm model for studying the biogenesis of lysosome-related organelles (LROs).

Nanoparticles loaded withß-Lapachone and Fe3+exhibit enhanced chemodynamic therapy by producing H2O2through cascaded amplification.

The rapid, irreversible change of active Fe2+to inactive Fe3+after the Fenton reaction occurring reduces the chemodynamic therapeutic (CDT) effect. Therefore, manipulation of the tumor microenvironment to provide sufficient hydrogen peroxide (H2O2) while maintaining metal ion catalyst activity is critical for effective CDT. Here,ß-Lapachone (LPC) was loaded by mesoporous silica nanoparticles (MSNs) and coated with polydopamine (PDA) to further chelate Fe3+and link aptamer AS1411, and a pH-controlled released, chemotherapy-photothermal therapy (PTT)-enhanced CDT-small molecule therapy combination drug delivery system with passive and active tumor targeting was engineered (designated asß-LPC@MSN@PDA/Fe3+-AS1411, LMPFA). The results showed that LFMPA nanoparticles massively accumulated in tumor tissues to achieve tumor targeting through AS1411 mediating and enhanced permeability and retention (EPR) effect. Subsequently, PDA released Fe3+and LPC through acid response to exhibited CDT and chemotherapeutic therapy. Meanwhile, the photothermal effect of PDA promoted the release of LPC from the pores of MSN. LPC exerted chemotherapy effect and cyclically producing of H2O2by the catalysis of NQO1, which enhanced the CDT activated by Fe3+. In addition, while serving as a targeted ligand, AS1411 could also exhibit a small molecule therapeutic effect by binding to nucleoli of tumor cells. This unique nano delivery system achieved the combination of chemotherapy, PTT, enhanced CDT and small molecule therapy, and fought against malignant tumors synergistically through multi-target and multi-dimension.