Cu,Ce-containing phosphotungstates as laccase-like nanozyme for colorimetric detection of Cr(VI) and Fe(â ¢).

Herein, a nanocomposite of Cu,Ce-containing phosphotungstates (Cu,Ce-PTs) with outstanding laccase-like activity was fabricated via a one-pot microwave-assisted hydrothermal method. Notably, it was discovered that both Fe3+ and Cr6+ could significantly enhance the electron transfer rates of Ce3+ and Ce4+, along with generous Cu2+ with high catalytic activity, thereby promoting the laccase-like activity of Cu,Ce-PTs. The proposed system can be used for the detection of Fe3+ and Cr6+ in a range of 0.667-333.33 µg/mL and 0.033-33.33 µg/mL with a low detection limit of 0.135 µg/mL and 0.0288 µg/mL, respectively. The proposed assay exhibits excellent reusability and selectivity and can be used in traditional Chinese medicine samples analysis.

A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer.

Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (•OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.

Trimetallic Ni-CuCoN0.6 Ohmic junction for the enhanced oxidation of methanol and urea.

Methanol oxidation reaction (MOR) and urea oxidation reaction (UOR) can be utilized as effective alternatives to the anodic oxygen evolution reaction (OER) in overall water-splitting. Nevertheless, the development of cost-effective, highly efficient and durable electrocatalysts for MOR and UOR remains a significant challenge. Herein, the Ohmic junction (Ni-CuCoN0.6@CC) comprising CuCoN0.6 nanosheets and Ni nanoparticles anchored on carbon cloth (CC) was successfully synthesized via a two-step hydrothermal process followed by pyrolysis. The Ni-CuCoN0.6@CC demonstrates exceptional performance in both MOR (1.334 V@10 mA cm-2) and UOR (1.335 V@10 mA cm-2), coupled with outstanding durability, maintaining 88.70 % current density for MOR and 88.92 % for UOR after a rigorous 50-h stability test. Furthermore, the Ni-CuCoN0.6@CC demonstrates a high selectivity for oxidizing methanol to formic acid, achieving Faraday efficiencies exceeding 90 % at various current densities in the context of MOR. The outstanding performance of Ni-CuCoN0.6@CC in terms of MOR and UOR either surpasses or closely approaches the levels reported in previous literature, primarily due to the synergistic effect resulting from the Ohmic junction: in this system, Ni serves as the principal active component, Co augments catalytic activity and diminishes onset potential, while Cu enhances long-term durability. Moreover, CuCoN0.6 nanosheets effectively modulate electronic structure and optimize the morphology of Ni, leading to the exposure of numerous defects that provide a wealth of active sites for the reaction. Additionally, the exceptional hydrophilic and aerophobic surface promotes enhanced mass transfer. Density functional theory (DFT) calculations show that Ni-CuCoN0.6@CC enhances reactant adsorption and product desorption, reducing energy barriers and expediting MOR and UOR kinetics.

Construction of 2D/2D S-scheme Bi2MoO6/Zn-TCPP heterojunction via in-situ self-assembly growth strategy to enhance interface effect for efficient photocatalytic hydrogen production.

Two-dimensional/two-dimensional (2D/2D) heterojunctions are considered to be an effective strategy for forming strong interface effects and facilitating photogenerated carrier separation. However, it is usually limited by the size mismatch of the materials, even at the expense of its redox capability. Herein, 2D/2D S-scheme heterojunction photocatalyst Bi2MoO6/Zn-TCPP (BMO/ZTP) composed of 2D Bi2MoO6 and 2D Zn-TCPP (TCPP: tetrakis (4-carboxyphenyl) porphyrin) (MOFs) was constructed by in-situ self-assembly growth strategy. The size-compatible 2D/2D composites had abundant surface active sites and strong interactions. In addition, band bending and interfacial electric field (IEF) effect based on S-scheme heterojunction could accelerate the separation and migration of photogenerated carriers in BMO/ZTP. The best hydrogen precipitation rate of the BMO/ZTP was 10900.94 umol·g-1·h-1, which was 38.90 and 3.24 times higher than that of Bi2MoO6 (280.26 umol·g-1·h-1) and Zn-TCPP (3360.34 umol·g-1·h-1), respectively. The results indicated that 2D/2D BMO/ZTP S-scheme heterojunction could enhance the interface effect and retain strong reducing electrons to achieve efficient photocatalytic hydrogen production, which was confirmed by ultraviolet photoelectron spectroscopy (UPS), Tafel curve, electron spin resonance (ESR) and time-resolved photoluminescence (TRPL) characterization and density functional theory (DFT) calculations. This work provided a general strategy for constructing 2D Bi2MoO6 and 2D MOFs S-scheme heterojunctions to enhance interface effects for achieving efficient photocatalytic hydrogen production.

Up-conversion luminescence and temperature sensing properties of Ho3+-, Tm3+-, and Yb3+-codoped Bi2WO6 materials in a water environment.

A series of x%Ho3+, 5 %Tm3+, y%Yb3+:Bi2WO6 (x = 0, 0.5, 1, 3, 5; y = 0.5, 1, 3) luminescent materials was prepared using a high-temperature solid-phase method. The microstructure, up-conversion luminescence, and temperature sensing properties of the synthesized powders were analyzed. X-ray diffraction patterns revealed that doping with Ho3+, Tm3+, and Yb3+ ions at certain concentrations did not affect the orthorhombic crystal structure of the Bi2WO6 host. Scanning electron microscopy revealed that the morphology of the sample consisted of lumpy particles with a particle size range of 1-5 µm and agglomeration. SEM mapping and energy-dispersive X-ray spectroscopy analyses revealed that each element was relatively uniformly distributed on the particle surface. Under 980 nm excitation (380 mW), the strongest luminescence of the sample was obtained when both Ho3+ and Yb3+ doping concentrations were 1 %. Compared with the luminescence of the 5 %Tm3+ and 1 %Yb3+:Bi2WO6 sample, with increasing Ho3+ concentrations, the luminescence intensity of Tm3+ was first enhanced and subsequently weakened, whereas the luminescence of Ho3+ was significantly weakened, which indicates the positive energy transfer from Ho3+ â†’ Tm3+. At 980 nm (80-380 mW), for the 1 %Ho3+, 5 %Tm3+, and 1 %Yb3+:Bi2WO6 sample, the 538 nm, 545 nm, 660 nm, and 804 nm emission peaks originated from the two-photon absorption. FIR660 nm/804 nm, FIR545 nm/804 nm, and FIR538 nm/804 nm were used to characterize the temperature and corresponded to temperature sensitivities Sr of 0.0046 K-1, 0.022 K-1 and 0.024 K-1 at 573 K, respectively. At 498 K, the minimum temperature resolution δT values were 0.03384 K, 0.03203 K and 0.04373 K. When the temperature increased from 298 K to 573 K, the powder sample luminescence gradually shifted from the yellow-green region to the red region. The results of environmental discoloration and thermochromic performance tests indicate that this sample has potential application in optical anti-counterfeiting. FIR804 nm /660 nm and FIR804 nm /538 nm were obtained for the 40 NTU turbidity suspension under identical excitation conditions. At 298 K, for the 40 NTU turbidity sample, the maximum Sr values were 0.0197 K-1 and 0.0405 K-1; at 340 K, the minimum temperature resolutions δT values were 0.54037 K and 0.66237 K. When the temperature decreased from 340 K to 298 K, the luminescence of the 40 NTU suspension samples gradually shifted from the yellow region to the green region.

Structural Maintenance of Chromosomes Complexes.

The Structural Maintenance of Chromosomes (SMC) protein complexes are DNA-binding molecular machines required to shape chromosomes into functional units and to safeguard the genome through cell division. These ring-shaped multi-subunit protein complexes, which are present in all kingdoms of life, achieve this by organizing chromosomes in three-dimensional space. Mechanistically, the SMC complexes hydrolyze ATP to either stably entrap DNA molecules within their lumen, or rapidly reel DNA into large loops, which allow them to link two stretches of DNA in cis or trans. In this chapter, the canonical structure of the SMC complexes is first introduced, followed by a description of the composition and general functions of the main types of eukaryotic and prokaryotic SMC complexes. Thereafter, the current model for how SMC complexes perform in vitro DNA loop extrusion is presented. Lastly, chromosome loop formation by SMC complexes is introduced, and how the DNA loop extrusion mechanism contributes to chromosome looping by SMC complexes in cells is discussed.

Hydrogen production from dry reforming of methane, using CO2 previously chemisorbed in the Li6Zn1-xNixO4 solid solution.

Li6ZnO4 was chemically modified by nickel addition, in order to develop different compositions of the solid solution Li6Zn1-xNixO4. These materials were evaluated bifunctionally; analyzing their CO2 capture performances, as well as on their catalytic properties for H2 production via dry reforming of methane (DRM). The crystal structures of Li6Zn1-xNixO4 solid solution samples were determined through X-ray diffraction, which confirmed the integration of nickel ions up to a concentration around 20 mol%, meanwhile beyond this value, a secondary phase was detected. These results were supported by XPS and TEM analyses. Then, dynamic and isothermal thermogravimetric analyses of CO2 capture revealed that Li6Zn1-xNixO4 solid solution samples exhibited good CO2 chemisorption efficiencies, similarly to the pristine Li6ZnO4 chemisorption trends observed. Moreover, a kinetic analysis of CO2 isothermal chemisorptions, using the Avrami-Erofeev model, evidenced an increment of the constant rates as a function of the Ni content. Since Ni2+ ions incorporation did not reduce the CO2 capture efficiency and kinetics, the catalytic properties of these materials were evaluated in the DRM process. Results demonstrated that nickel ions favored hydrogen (H2) production over the pristine Li6ZnO4 phase, despite a second H2 production reaction was determined, methane decomposition. Thereby, Li6Zn1-xNixO4 ceramics can be employed as bifunctional materials.

Perylene Bisimide-Functionalized Triphenylmethyl Radicals Showing High Stability and Reversible Electrochemical Redox Properties.

This study presents a series of triphenylmethyl monoradicals incorporating varying numbers of peripheral perylene bisimide (PBI) substituents (1PBI-TTM·, 2PBI-TTM· and 3PBI-TTM·). The incorporation of electron-withdrawing PBI substituents significantly enhances the stability of these carbon radicals, enabling them to display exceptional electrochemical redox reversibility. Notably, the electronic interplay between the PBI substituents and the central triphenylmethyl core facilitates unique and reversible multi-step redox reactions. Among the reported redicals, the tris-PBI functionalized radical (3PBI-TTM·) demonstrates the remarkable ability to accommodate up to seven electrons under negative potentials, forming high valence anions. This research pioneers the development of highly stable carbon radicals with superior electrochemical oxidation-reduction processes, presenting promising avenues for the advancement of electric energy storage technologies.

The impact of Trifolium pratense extract on apoptosis and autophagy in NALM-6 cells: implications for B-ALL intervention.

B-cell acute lymphoblastic leukemia (B-ALL), a prevalent malignancy predominantly affecting children, poses challenges such as drug resistance and cytotoxicity despite available treatment methods. The persistence of these challenges underscores the necessity for innovative therapeutic approaches to enhance efficacy. Natural compounds derived from plants, recognized for their potential to inhibit cancer cell growth, have drawn attention. Trifolium pratense extract, known for its significant anticancer properties in previous studies, was the focus of this investigation. This experimental study aimed to explore the impact of T. pratense extract on apoptosis and autophagy in NALM-6 cells. The cells were exposed to varying concentrations of the extract at specific time intervals, with viability and metabolic activity assessed using Trypan blue exclusion and MTT assays. Flow cytometry was employed to evaluate apoptosis using Annexin V/PI staining and ROS production using DCFH-DA staining. Real-time PCR was used to quantify gene expression related to apoptosis, autophagy, and oxidative stress, with data analysis performed using GraphPad PRISM software. Trifolium pratense extract demonstrated the capacity to induce apoptosis, autophagy, and significantly increase ROS production in NALM-6 cells. These effects were facilitated by the upregulation of corresponding genes. The MTT assay revealed an IC50 of 231 µg/mL at 48 h, and Flow cytometry analysis showed a 51.8% increase in apoptosis in this cell line. Overall, this study emphasizes the effectiveness of T. pratense extract in inducing autophagy and apoptosis pathways in NALM-6 cells derived from B-cell acute lymphoblastic leukemia, suggesting its potential as a candidate for further investigation as a supplement in ALL treatment.

A genome-wide CRISPR/Cas9 knockout screen identifies SEMA3F gene for resistance to cyclin-dependent kinase 4 and 6 inhibitors in breast cancer.

BACKGROUND: Palbociclib is a cell-cycle targeted small molecule agent used as one of the standards of care in combination with endocrine therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Although several gene alterations such as loss of Rb gene and amplification of p16 gene are known to be conventional resistance mechanisms to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, the comprehensive landscape of resistance is not yet fully elucidated. The purpose of this study is to identify the novel resistant genes to the CDK4/6 inhibitors in HR-positive HER2-negative breast cancer. METHODS: The whole genome knockout screen using CRISPR/Cas9 genome editing was conducted in MCF7 to identify resistant genes to palbociclib. The candidate genes for resistance were selected by NGS analysis and GSEA analysis and validated by cell viability assay and mouse xenograft models. RESULTS: We identified eight genes including RET, TIRAP, GNRH1, SEMA3F, SEMA5A, GATA4, NOD1, SSTR1 as candidate genes from the whole genome knockout screen. Among those, knockdown of SEMA3F by siRNA significantly and consistently increased the cell viability in the presence of CDK4/6 inhibitors in vitro and in vivo. Furthermore, the level of p-Rb was maintained in the palbociclib treated SEMA3F-downregulated cells, indicating that the resistance is driven by increased activity of cyclin kinases. CONCLUSION: Our observation provided the first evidence of SEMA3F as a regulator of sensitivity to CDK4/6 inhibitors in breast cancer. The detailed mechanisms of resistance deserve further functional studies to develop the better strategy to overcome resistance in CDK4/6 inhibitors.

Study on the expression and prognostic relationship of MYL6B in liver cancer based on bioinformatics.

BACKGROUND: Primary liver cancer is a prevalent and deadly cancer type. Despite treatment advances, prognosis remains poor, with high recurrence rates. Early detection is crucial but challenging due to the disease's insidious nature. Myosin proteins play significant roles in cancer development, influencing cell migration, invasion, and tumor suppression. MYL6B, a myosin light chain, is involved in various cellular processes and has been associated with poor prognosis in colorectal adenocarcinoma and potential as a biomarker in breast cancer. AIM: To investigate the expression of MYL6B in liver hepatocellular carcinoma (LIHC) and its impact on prognosis and potential mechanisms of action using bioinformatics methods. METHODS: The expression of MYL6B in pan-cancer and normal tissues was analyzed using the gene expression profiling interactive analysis 2 and tumor immune estimation resource databases. The expression level of MYL6B in LIHC tissues and its relationship with prognosis were analyzed, immunohistochemical analysis of MYL6B and its effect on immune cell infiltration, and the protein network were further studied. RESULTS: MYL6B was highly expressed in diffuse large b-cell lymphoma, LIHC, pancreatic adenocarcinoma, skin cutaneous melanoma, thymoma, uterine corpus endometrial carcinoma, uterine carcinosarcoma, and lowly expressed in kidney chromophobe, acute myeloid leukemia, testicular germ cell tumors. The expression level of MYL6B was significantly different between cancer and normal tissues. It had a significant impact on both overall survival and disease-free survival. MYL6B is highly expressed in hepatocellular carcinoma and its expression level increases with cancer progression. High MYL6B expression is associated with poor prognosis in terms of overall survival and recurrence-free survival. The immunohistochemical level of MYL6B is high in hepatocellular carcinoma tissues, and MYL6B has a high level of immune infiltration inflammation. In protein network analysis, MYL6B is correlated with MYL2, MYL6, MYL9, MYLK4, MYLK2, MYL12A, MYL12B, MYH11, MYH9 and MYH10. CONCLUSION: The expression level of MYL6B in LIHC was significantly higher than in normal liver tissues, and it was correlated with the degree of differentiation survival rate, and immune infiltration. MYL6B is a potential target for LIHC treatment.

Reductive Dissolution of NCM Cathode through Anaerobic Respiration by Shewanella putrefaciens.

The consumption of lithium-ion batteries (LIBs) has considerably increased over the past decade, leading to a rapid increase in the number of spent LIBs. Exposing spent LIBs to the environment can cause serious environmental harm; however, there is a lack of experimentally obtained information regarding the environmental impacts of abandoned cathode materials. Here, we report the interactions between Shewanella putrefaciens, a microorganism commonly found in diverse low-oxygen natural settings, and LiNi0.6Co0.2Mn0.2O2 (NCM622) under anaerobic conditions. We present compelling evidence that the anaerobic respiration of Shewanella putrefaciens triggers ∼59 and ∼78% dissolution of 0.2 g/L pristine and spent NCM622, respectively. We observed that Shewanella putrefaciens interacted with the pristine and the spent NCM622 under anaerobic conditions at a neutral pH and room temperature and induced the reduction of Ni, Co, and Mn, resulting in the subsequent dissolution of Li, Ni, Co, and Mn. Moreover, we found that secondary mineralization occurred on the surface of reacted NCM622. These findings not only shed light on the substantial impact of microbial respiration on the fate of discarded cathode materials in anaerobic environments but also reveal the potential for sustainable bioleaching of cathodes in spent LIBs.

Where You Protonate Matters: Deciphering the Unimolecular Chemistry of Protonated Myrcene and Linalool.

The unimolecular reactions of protonated myrcene and linalool were investigated by collision-induced dissociation and density functional theory calculations. Experiments on a triple quadrupole mass spectrometer showed that protonated myrcene undergoes two major unimolecular reactions losing propene and isobutene, and two minor reactions of ethene and propane loss. In each case, the product ion consists of a substituted five-member ring. Protonation of myrcene was found to form four distinct protomers, three of which can be significantly populated in the ion source. The observed fragmentation reactions were calculated and found to depend on the starting protomer. Each pathway consisted of several hydrogen-migration and ring-forming/opening steps on the way to the observed products. Likewise, protonation of linalool also produces three distinct protomers, with the global minimum being formed by protonation of a central double bond. The major reaction is water loss to form protonated myrcene, but two minor channels were also observed resulting in loss of acetone and isobutene. The calculated minimum energy reaction pathways were found to be consistent with the relative abundances of the ions in the experimental breakdown diagrams.

Influence of Th1 versus Th2 immune bias on viral, pathological, and immunological dynamics in SARS-CoV-2 variant-infected human ACE2 knock-in mice.

BACKGROUND: Mouse models that recapitulate key features of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are important tools for understanding complex interactions between host genetics, immune responses, and SARS-CoV-2 pathogenesis. Little is known about how predominantly cellular (Th1 type) versus humoral (Th2 type) immune responses influence SARS-CoV-2 dynamics, including infectivity and disease course. METHODS: We generated knock-in (KI) mice expressing human ACE2 (hACE2) and/or human TMPRSS2 (hTMPRSS2) on Th1-biased (C57BL/6; B6) and Th2-biased (BALB/c) genetic backgrounds. Mice were infected intranasally with SARS-CoV-2 Delta (B.1.617.2) or Omicron BA.1 (B.1.1.529) variants, followed by assessment of disease course, respiratory tract infection, lung histopathology, and humoral and cellular immune responses. FINDINGS: In both B6 and BALB/c mice, hACE2 expression was required for infection of the lungs with Delta, but not Omicron BA.1. Disease severity was greater in Omicron BA.1-infected hTMPRSS2-KI and double-KI BALB/c mice compared with B6 mice, and in Delta-infected double-KI B6 and BALB/c mice compared with hACE2-KI mice. hACE2-KI B6 mice developed more severe lung pathology and more robust SARS-CoV-2-specific splenic CD8 T cell responses compared with hACE2-KI BALB/c mice. There were no notable differences between the two genetic backgrounds in plasma cell, germinal center B cell, or antibody responses to SARS-CoV-2. INTERPRETATION: SARS-CoV-2 Delta and Omicron BA.1 infection, disease course, and CD8 T cell response are influenced by the host genetic background. These humanized mice hold promise as important tools for investigating the mechanisms underlying the heterogeneity of SARS-CoV-2-induced pathogenesis and immune response. FUNDING: This work was funded by NIH U19 AI142790-02S1, the GHR Foundation, the Arvin Gottleib Foundation, and the Overton family (to SS and EOS); Prebys Foundation (to SS); NIH R44 AI157900 (to KJ); and by an American Association of Immunologists Career Reentry Fellowship (FASB).

Bio-Mechanical Analysis of Porous Ti-6Al-4V scaffold: A comprehensive review on unit cell structures in Orthopaedic application.

A scaffold is a three-dimensional porous structure that is used as a template to provide structural support for cell adhesion and the formation of new cells. Metallic cellular scaffolds are a good choice as a replacement for human bones in orthopaedic implants, which enhances the quality and longevity of human life. In contrast to conventional methods that produce irregular pore distributions, 3D printing, or additive manufacturing, is characterized by high precision and controlled manufacturing processes. AM processes can precisely control the scaffold's porosity, which makes it possible to produce patient specific implants and achieve regular pore distribution. This review paper explores the potential of Ti-6Al-4V scaffolds produced via the SLM method as a bone substitute. A state-of-the-art review on the effect of design parameters, material, and surface modification on biological and mechanical properties is presented. The desired features of the human tibia and femur bones are compared to bulk and porous Ti6Al4V scaffold. Furthermore, the properties of various porous scaffolds with varying unit cell structures and design parameters are compared to find out the designs that can mimic human bone properties. Porosity up to 65% and pore size of 600 µm was found to give optimum trade-off between mechanical and biological properties. Current manufacturing constraints, biocompatibility of Ti-6Al-4V material, influence of various factors on bio-mechanical properties, and complex interrelation between design parameters are discussed herein. Finally, the most appropriate combination of design parameters that offers a good trade-off between mechanical strength and cell ingrowth are summarized. .

Endometrial regeneration cell-derived exosomes loaded with siSLAMF6 inhibit cardiac allograft rejection through the suppression of desialylation modification.

BACKGROUNDS: Acute transplant rejection is a major component of poor prognoses for organ transplantation. Owing to the multiple complex mechanisms involved, new treatments are still under exploration. Endometrial regenerative cells (ERCs) have been widely used in various refractory immune-related diseases, but the role of ERC-derived exosomes (ERC-Exos) in alleviating transplant rejection has not been extensively studied. Signaling lymphocyte activation molecule family 6 (SLAMF6) plays an important role in regulating immune responses. In this study, we explored the main mechanism by which ERC-Exos loaded with siSLAMF6 can alleviate allogeneic transplant rejection. METHODS: C57BL/6 mouse recipients of BALB/c mouse kidney transplants were randomly divided into four groups and treated with exosomes. The graft pathology was evaluated by H&E staining. Splenic and transplanted heart immune cell populations were analyzed by flow cytometry. Recipient serum cytokine profiles were determined by enzyme-linked immunosorbent assay (ELISA). The proliferation and differentiation capacity of CD4+ T cell populations were evaluated in vitro. The α-2,6-sialylation levels in the CD4+ T cells were determined by SNA blotting. RESULTS: In vivo, mice treated with ERC-siSLAMF6 Exo achieved significantly prolonged allograft survival. The serum cytokine profiles of the recipients were significantly altered in the ERC-siSLAMF6 Exo-treated recipients. In vitro, we found that ERC-siSLAMF6-Exo considerably downregulated α-2,6-sialyltransferase (ST6GAL1) expression in CD4+ T cells, and significantly reduced α-2,6-sialylation levels. Through desialylation, ERC-siSLAMF6 Exo therapy significantly decreased CD4+ T cell proliferation and inhibited CD4+ T cell differentiation into Th1 and Th17 cells while promoting regulatory T cell (Treg) differentiation. CONCLUSIONS: Our study indicated that ERC-Exos loaded with siSLAMF6 reduce the amount of sialic acid connected to α-2,6 at the end of the N-glycan chain on the CD4+ T cell surface, increase the number of therapeutic exosomes endocytosed into CD4+ T cells, and inhibit the activation of T cell receptor signaling pathways, which prolongs allograft survival. This study confirms the feasibility of using ERC-Exos as natural carriers combined with gene therapy, which could be used as a potential therapeutic strategy to alleviate allograft rejection.

High-yield production of completely linear dextrans and isomalto-oligosaccharides by a truncated dextransucrase from Ligilactobacillus animalis TMW 1.971.

Several lactic acid bacteria are capable of producing water-soluble exopolysaccharides such as dextran from sucrose by using glucansucrases. Several recombinant glucansucrases were described, however, yields were often limited and most dextrans were branched at position O3. In this study, the dextransucrase from Ligilactobacillus animalis TMW 1.971 was recombinantly produced without its N-terminal variable region and used for dextran synthesis. The enzyme expressed well and showed very high total as well as transferase activities compared to other glucansucrases. It was able to transfer nearly all glucose from sucrose to oligo- and polymeric products under certain conditions (about 95 % of glucose transferred). The high efficiency of the enzyme made it possible to obtain absolute dextran yields of up to 214.9 g/L from a 1.5 M sucrose solution. Structural characterization of the products showed that the dextrans produced have a rather low molecular weight, a narrow size distribution, and are completely linear. Furthermore, we showed that various low molecular weight dextrans or 1,6-linked isomalto-oligosaccharides can be efficiently produced by acid hydrolysis. Overall, we demonstrated that Ligilactobacillus animalis TMW 1.971 dextransucrase can be used to efficiently synthesize dextrans with a quite unique structural composition. The dextrans produced have a high potential for further applications such as synthesis of copolymers or size standards with a very defined molecular structure.

Comparative accuracy of CA-153 and KL-6 as diagnostic and prognostic biomarkers for interstitial lung disease.

BACKGROUNDS: To discern the potential of KL-6 and CA-153 as diagnostic tools for interstitial lung disease (ILD), understand their relationship with GAP (Gender, Age, and Physiology) stage, and analyze their predictive capacities alongside CT features. This research aims to enhance ILD detection and management in autoimmune patients, emphasizing the diagnostic utility of these biomarkers. METHODS: From Mar 2017 to Mar 2023, 398 patients from Taichung Veterans General Hospital's Division of Allergy, Immunology, and Rheumatology with autoimmune diseases were prospectively enrolled. ILD diagnoses were confirmed using High-Resolution Computed Tomography (HRCT) or lung biopsy and characterized by radiologists. GAP scores were calculated for IPF prognosis. 583 serum samples were collected and tested for KL-6, CA-153, CA-199, and CA-125 using specific assays. Statistical analyses compared patients, assessed variables, determined missingness, and predicted ILD, with tools like ROC analysis and logistic regressions. Analyses were performed with IBM SPSS and MedCalc. RESULTS: ILD patients were older, predominantly male, and had more smokers compared to non-ILD. Both KL-6 and CA-153 were higher in ILD and showed a significant, but non-interchangeable correlation. Age, BMI, smoking, and biomarker levels influenced ILD odds, with KL-6 and CA-153 being the strongest predictors. HRCT imaging highlighted these markers' roles, especially in detecting specific features. Both markers also strongly associated with GAP stages. Stratified analyses emphasized KL-6's significance in predicting ILD across both AD and non-AD groups. Complete data sensitivity analysis reinforced KL-6 and CA-153 as key ILD predictors. CONCLUSIONS: This research emphasizes CA-153 as a feasible, cost-effective alternative to KL-6 in diagnosing and monitoring ILD. Both CA-153 and KL-6 levels were notably elevated in ILD patients, displaying a strong correlation, especially at CA-153 levels of ≤100 U/ml. They both also have significant associations with CT characteristics and GAP stages. The study reinforces the potential of CA-153, particularly in settings where KL-6 testing might be inaccessible or expensive.

Phytol exerts sedative-like effects and modulates the diazepam and flumazenil's action, possibly through the GABAA receptor interaction pathway.

This study aimed at the evaluation of the sedative effect of phytol (PHY) with possible molecular mechanisms through in vivo and in silico studies. For this, adult male mice were randomly divided into six individual groups, namely control (vehicle), two standards (DZP: diazepam at 2 m/kg, FLU: flumazenil at 0.1 mg/kg), three test groups (PHY at 25, 50, and 75 mg/kg), and three combined groups with the DZP-2 and/or FLU-0.1 with PHY-75 mg/kg. After thirty minutes, each animal was treated with thiopental sodium (TS) at 40 mg/kg to produce sedation and observed for latency and duration of sleep up to 4 h. In silico studies were performed with the 6X3X protein of the GABAA receptor α1 and ß2 subunits. The results demonstrate that PHY dose-dependently enhanced sleep duration in animals. However, it produced an insignificant sleep duration compared to the control and standard groups. It also significantly (p < 0.05) decreased the latency and increased the duration of sleep with DZP-2, while reducing these parameters with FLU-0.1. In in silico studies, DZP and FLU exhibited binding affinities with 6X3X by -6.8 and -6.9 kcal/mol, respectively, while PHY exhibited -6.9 kcal/mol. Taken together, PHY may exert a sedative-like effect in TS-induced sleeping mice and modulate the effects of DZP and FLU, possibly through interacting with the 6X3X protein of the GABAA receptor. PHY may be one of the good candidates for the management of sleep disturbances, such as insomnia.

Epigenomic and transcriptomic profiling of solitary fibrous tumors identifies site-specific patterns and candidate genes regulated by DNA methylation.

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm which can arise at any anatomic site and is characterized by recurrent NAB2::STAT6 fusions and metastatic progression in 10-30%. The cell of origin has not been identified. Despite some progress in understanding the contribution of heterogeneous fusion types and secondary mutations to SFT biology, epigenetic alterations in extrameningeal SFT remain largely unexplored, and most sarcoma research to date has focused on the use of methylation profiling for tumor classification. We interrogated genome-wide DNA methylation in 79 SFTs to identify informative epigenetic changes. RNA-seq data from targeted panels and data from the Cancer Genome Atlas (TCGA) were used for orthogonal validation of selected findings. In unsupervised clustering analysis, the top 500 most variable CpGs segregated SFTs by primary anatomic site. Differentially methylated genes (DMGs) associated with primary SFT site included EGFR, TBX15, multiple HOX genes and their cofactors EBF1, EBF3, and PBX1, as well as RUNX1 and MEIS1. Of the 20 DMGs that were interrogated on the RNA-seq panel, twelve were significantly differentially expressed according to site. However, with the exception of TBX15, most of these also showed differential expression according to NAB2::STAT6 fusion type, suggesting that the fusion oncogene contributes to transcriptional regulation of these genes. Transcriptomic data confirmed an inverse correlation between gene methylation and the expression of TBX15 in both SFT and TCGA sarcomas. TBX15 also showed differential mRNA expression and 5' UTR methylation between tumors located in different anatomic sites in TCGA data. In all analyses, TBX15 methylation and mRNA expression retained the strongest association with tissue of origin in SFT and other sarcomas, suggesting a possible marker to distinguish metastatic tumors from new primaries without genomic profiling. Epigenetic signatures may further help to identify SFT progenitor cells at different anatomic sites.