Dipolar Chemical Bridge Induced CsPbI3 Perovskite Solar Cells with 21.86 % Efficiency.

CsPbI3 perovskite receives tremendous attention for photovoltaic applications due to its ideal band gap and good thermal stability. However, CsPbI3 perovskite solar cells (PSCs) significantly suffer from photovoltage deficits because of serious interfacial energy losses within the PSCs, which to a large extent affects the photovoltaic performance of PSCs. Herein, a dipolar chemical bridge (DCB) is constructed between the perovskite and TiO2 layers to lower interfacial energy losses and thus improve the charge extraction of PSCs. The results reveal that the DCB could form a beneficial interfacial dipole between the perovskite and TiO2 layers, which could optimize the interfacial energetics of perovskite/TiO2 layers and thus improve the energy level alignment within the PSCs. Meanwhile, the constructed DCB could also simultaneously passivate the surface defects of perovskite and TiO2 layers, greatly lowering interfacial recombination. Consequently, the photovoltage deficit of CsPbI3 PSCs is largely reduced, leading to a record efficiency of 21.86 % being realized. Meanwhile, the operation stability of PSCs is also largely improved due to the high-quality perovskite films with released interfacial tensile strain being obtained after forming the DCB within the PSCs.

Effect of Preoperative Lifestyle Management and Prehabilitation on Postoperative Capability of Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The surgical intervention serves as the paramount and prevalent remedy for individuals afflicted with colorectal malignancies, with the significance of perioperative stewardship and convalescence being indisputable. Prehabilitation coupled with preoperative lifestyle modulation has demonstrated efficacy in patients subjected to certain classifications of abdominal procedures. However, the evidence pertaining to its impact on those battling colorectal cancer remains equivocal. METHODS: A meta-analysis, grounded in pairwise contrast, of randomized controlled trials (RCTs) was orchestrated, coupled with a systematic review, to probe the efficacy of preoperative lifestyle modulation and prehabilitation on patients' postoperative functionality and recuperation. An exhaustive exploration of 8 electronic databases and trial registries was undertaken to encompass all pertinent RCTs disseminated in English or Chinese from January 2012 through December 2022. Employing a random-effects model, we evaluated parameters such as the 6-minute walk test (6 MWT), complications, quality of life (QoL), aggregate and postoperative duration of hospitalization (tLHS and postLHS), and healthcare expenditure (HExp) for postoperative patients. RESULTS: A total of 28 RCTs were incorporated into the systematic review and meta-analysis. Relative to conventional preoperative care, rehabilitation or preoperative lifestyle management was found to enhance postoperative 6MWT (SMD 1.30, 95% CI 0.30 to 2.29) and diminish the complication rate (OR 0.53, 95% CI 0.40 to 0.69). Nonetheless, no significant discrepancies were observed in QoL (SMD 1.81, 95% CI -0.26 to 3.87), tLHS (SMD -0.26, 95% CI -0.68 to 0.15), and postLHS (SMD -1.46, 95% CI -3.12 to 0.20) between the groups. HExp could not be evaluated due to a lack of sufficient data for synthesis. Most pooled outcomes exhibited significant heterogeneity, urging a cautious interpretation. Subgroup analysis revealed that nutritional interventions could mitigate the incidence of complications, and preoperative exercise could improve tLHS and postLHS. A combined approach of physical, nutritional, and psychological intervention or prehabilitation proved superior to any single intervention in enhancing postoperative capabilities. CONCLUSION: This meta-analysis delineated the efficacy of preoperative interventions on postoperative capabilities in patients with colorectal cancer, thereby offering evidence for clinical practice. It was concluded that preoperative interventions are unequivocally beneficial for postoperative functional recovery and the reduction of complication rates in patients with colorectal cancer. Nonetheless, the acquisition of more high-level evidence is still necessitated to further ascertain the effectiveness of this strategy for other patient groups and to establish its best practices. The heterogeneity in the pooled outcomes underlines the need for future studies to be more uniform in their design and reporting, which would facilitate more robust and reliable meta-analyses.

Single-Atom Ni Supported on TiO2 for Catalyzing Hydrogen Storage in MgH2.

As an efficient and clean energy carrier, hydrogen is expected to play a key role in future energy systems. However, hydrogen-storage technology must be safe with a high hydrogen-storage density, which is difficult to achieve. MgH2 is a promising solid-state hydrogen-storage material owing to its large hydrogen-storage capacity (7.6 wt %) and excellent reversibility, but its large-scale utilization is restricted by slow hydrogen-desorption kinetics. Although catalysts can improve the hydrogen-storage kinetics of MgH2, they reduce the hydrogen-storage capacity. Single-atom catalysts maximize the atom utilization ratio and the number of interfacial sites to boost the catalytic activity, while easy aggregation at high temperatures limits further application. Herein, we designed a single-atom Ni-loaded TiO2 catalyst with superior thermal stability and catalytic activity. The optimized 15wt%-Ni0.034@TiO2 catalyst reduced the onset dehydrogenation temperature of MgH2 to 200 °C. At 300 °C, the H2 released and absorbed 4.6 wt % within 5 min and 6.53 wt % within 10 s, respectively. The apparent activation energies of MgH2 dehydrogenation and hydrogenation were reduced to 64.35 and 35.17 kJ/mol of H2, respectively. Even after 100 cycles of hydrogenation and dehydrogenation, there was still a capacity retention rate of 97.26%. The superior catalytic effect is attributed to the highly synergistic catalytic activity of single-atom Ni, numerous oxygen vacancies, and multivalent Tix+ in the TiO2 support, in which the single-atom Ni plays the dominant role, accelerating electron transfer between Mg2+ and H- and weakening the Mg-H bonds. This work paves the way for superior hydrogen-storage materials for practical unitization and also extends the application of single-atom catalysis in high-temperature solid-state reactions.

Identification and characterization of the receptors of a microneme adhesive repeat domain of Eimeria maxima microneme protein 3 in chicken intestine epithelial cells.

Eimeria maxima microneme protein 3 (EmMIC3) is pivotal in the initial recognition and attachment of E. maxima sporozoites to host cells. EmMIC3 comprises 5 tandem Type I microneme adhesive repeat (MAR) domains, among which MAR2 of EmMIC3 (EmMAR2) has been identified as the primary determinant of EmMIC3-mediated tissue tropism. Nonetheless, the mechanisms through which EmMAR2 guides the parasite to its invasion site through interactions with host receptors remained largely uncharted. In this study, we employed yeast two-hybrid (YTH) screening assays and shotgun LC-MS/MS analysis to identify EmMAR2 receptors in chicken intestine epithelial cells. ATPase H+ transporting V1 subunit G1 (ATP6V1G1), receptor accessory protein 5 (REEP5), transmembrane p24 trafficking protein (TMED2), and delta 4-desaturase sphingolipid 1 (DEGS1) were characterized as the 4 receptors of EmMAR2 by both assays. By blocking the interaction of EmMAR2 with each receptor using specific antibodies, we observed varying levels of inhibition on the invasion of E. maxima sporozoites, and the combined usage of all 4 antibodies resulted in the most pronounced inhibitory effect. Additionally, the spatio-temporal expression profiles of ATP6V1G1, REEP5, TMED2, and DEGS1 were assessed. The tissue-specific expression patterns of EmMAR2 receptors throughout E. maxima infection suggested that ATP6V1G1 and DEGS1 might play a role in early-stage invasion, whereas TMED2 could be involved in middle and late-stage invasion and REEP5 and DEGS1 may participate primarily in late-stage invasion. Consequently, E. maxima may employ a multitude of ligand-receptor interactions to drive invasion during different stages of infection. This study marks the first report of EmMAR2 receptors at the interface between E. maxima and the host, providing insights into the invasion mechanisms of E. maxima and the pathogenesis of coccidiosis.

A Millimeter-Scale Multilocomotion Microrobot Capable of Controlled Crawling and Jumping.

Insects and animals in nature generally have powerful muscles to guarantee their complex motion, such as crawling, running, and jumping. It is challenging for insect-sized robots to achieve controlled crawling and jumping within the scale of millimeters and milligrams. This article proposes a novelty bionic muscle actuator, where an electrical pulse is applied to generate joule heat to expand the actuator's chamber. Under the restoring force of the spring element, the chamber contracts back to the initial state to finish a complete cycle. The actuator can obtain high-frequency vibration under the high-frequency electrical signal. We propose a microrobot based on the novelty actuator to achieve controlled crawling and jumping over the obstacle of the millimeter-sized robot. The robot is fabricated with two actuators as a crawling module and one actuator as a jumping module, with a mass of 52 mg, length of 9.3 mm, width of 9.1 mm, and height of 4 mm. The microrobot has a maximum crawling turning velocity of 0.73 rad/s, a maximum jump height of 42 mm (10.5 times body height), and a maximum jump velocity of 0.91 m/s. This study extends the potential for applying the novelty bionic-muscle actuator to the microrobot.

Elucidating the pharmacodynamic mechanisms of Yuquan pill in T2DM rats through comprehensive multi-omics analyses.

Background: Yuquan Pill (YQW) is a modern concentrated pill preparation of six herbs, namely, Ge Gen (Pueraria lobata Ohwi), Di huang (Rehmannia glutinosa Libosch.), Tian Huafen (Trichosanthes kirilowii Maxim.), Mai Dong (Ophiopogon japonicus (L. f.) Ker Gawl.), Wu Weizi (Schisandra chinensis (Turcz.) Baill.) and Gan Cao (Glycyrrhiza uralensis Fisch.). It is extensively used to treat type 2 diabetes-related glucose and lipid metabolism disorders. But what's the pharmacodynamic substance and how it works in the treatment of Type 2 diabetes mellitus (T2DM) are still unclear. Purpose: The purpose of this study is to determine the likely pharmacological components and molecular mechanism of YQW's intervention on T2DM by combining serum pharmacochemistry, network analysis and transcriptomics. Methods: The efficacy and prototypical components of blood entry were determined after oral administration of YQW aqueous solution to T2DM rats induced by high-fat feed and low-dose streptozotocin (STZ), and the key targets and pathways for these compounds to intervene in T2DM rats were predicted and integrated using network analysis and transcriptomics techniques. Results: In diabetic rats, YQW can lower TG, CHO, NO, and MDA levels (p < 0.05) while increasing HDL-C levels (p < 0.01), and protecting the liver and kidney. 22 prototype components (including puerarin, daidzein, 3'-methoxypuerarin, and liquiritigenin, among others) were found in the serum of rats after oral administration of YQW for 90 min, which might be used as a possible important ingredient for YQW to intervene in T2DM rats. 538 YQW pharmacodynamic components-related targets and 1,667 disease-related targets were projected through the PharmMapper database, with 217 common targets between the two, all of which were engaged in regulating PI3K-Akt, MAPK, Ras and FoxO signal pathway. Finally, the mRNA expression profiles of liver tissues from rats in the control, model, and YQW groups were investigated using high-throughput mRNA sequencing technology. YQW can regulate the abnormal expression of 89 differential genes in a disease state, including 28 genes with abnormally high expression and 61 genes with abnormally low expression. Five common genes (Kit, Ppard, Ppara, Fabp4, and Tymp) and two extensively used regulatory pathways (PI3K-Akt and MAPK signaling pathways) were revealed by the integrated transcriptomics and network analysis study. Conclusion: The mechanism of YQW's intervention in T2DM rats could be linked to 22 important components like puerarin, daidzein, and glycyrrhetinic acid further activating PI3K-Akt and MAPK signaling pathways by regulating key targets Kit, Ppard, Ppara, Fabp4, and Tymp, and thus improving lipid metabolism disorder, oxidative stress, and inflammation levels in T2DM rats. On the topic, more research into the pharmacological ingredient foundation and mechanism of YQW intervention in T2DM rats can be done.

The microneme adhesive repeat domain of MIC3 protein determined the site specificity of Eimeria acervulina, Eimeria maxima, and Eimeria mitis.

Understanding the determinants of host and tissue tropisms among parasites of veterinary and medical importance has long posed a substantial challenge. Among the seven species of Eimeria known to parasitize the chicken intestine, a wide variation in tissue tropisms has been observed. Prior research suggested that microneme protein (MIC) composed of microneme adhesive repeat (MAR) domain responsible for initial host cell recognition and attachment likely dictated the tissue tropism of Eimeria parasites. This study aimed to explore the roles of MICs and their associated MARs in conferring site-specific development of E. acervuline, E. maxima, and E. mitis within the host. Immunofluorescence assays revealed that MIC3 of E. acervuline (EaMIC3), MIC3 of E. maxima (EmMIC3), MIC3 of E. mitis (EmiMIC3), MAR3 of EaMIC3 (EaMIC3-MAR3), MAR2 of EmMIC3 (EmMIC3-MAR2), and MAR4 of EmiMIC3 (EmiMIC3-MAR4), exhibited binding capabilities to the specific intestinal tract where these parasites infect. In contrast, the invasion of sporozoites into host intestinal cells could be significantly inhibited by antibodies targeting EaMIC3, EmMIC3, EmiMIC3, EaMIC3-MAR3, EmMIC3-MAR2, and EmiMIC3-MAR4. Substitution experiments involving MAR domains highlighted the crucial roles of EaMIC3-MAR3, EmMIC3-MAR2, and EmiMIC3-MAR4 in governing interactions with host ligands. Furthermore, animal experiments substantiated the significant contribution of EmiMIC3, EmiMIC3-MAR4, and their polyclonal antibodies in conferring protective immunity to Eimeria-affiliated birds. In summary, EaMIC3, EmMIC3, and EmiMIC3 are the underlying factors behind the diverse tissue tropisms exhibited by E. acervuline, E. maxima, and E. mitis, and EaMIC3-MAR3, EmMIC3-MAR2, and EmiMIC3-MAR4 are the major determinants of MIC-mediated tissue tropism of each parasite. The results illuminated the molecular basis of the modes of action of Eimeria MICs, thereby facilitating an understanding and rationalization of the marked differences in tissue tropisms among E. acervuline, E. maxima, and E. mitis.

Integration of systematic review, lipidomics with experiment verification reveals abnormal sphingolipids facilitate diabetic retinopathy by inducing oxidative stress on RMECs.

OBJECTIVE: This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR). METHODS: Systematic review of diabetic metabolomics was used to screen the differential metabolites and related pathways during the development of DM. Non-targeted lipidomics of rat plasma was performed to explore the differential metabolites in the development of DM into DR in vivo. To verify the effects of differential metabolites in inducing retinal microvascular endothelial cells (RMECs) injury by increasing oxidative stress, high glucose medium containing differential metabolites was used to induce rat RMECs injury and cell viability, malondialdehyde (MDA) contents, superoxide dismutase (SOD) activities, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in vitro. Network pharmacology was performed to explore the potential mechanism of differential metabolites in inducing DR. RESULTS: Through the systematic review, 148 differential metabolites were obtained and the sphingolipid metabolic pathway attracted our attention. Plasma non-targeted lipidomics found that sphingolipids were accompanied by the development of DM into DR. In vitro experiments showed sphinganine and sphingosine-1-phosphate aggravated rat RMECs injury induced by high glucose, further increased MDA and ROS levels, and further decreased SOD activities and MMP. Network pharmacology revealed sphinganine and sphingosine-1-phosphate may induce DR by regulating the AGE-RAGE and HIF-1 signaling pathways. CONCLUSIONS: Integrated systematic review, lipidomics and experiment verification reveal that abnormal sphingolipid metabolism facilitates DR by inducing oxidative stress on RMECs. Our study could provide the experimental basis for finding potential biomarkers for the diagnosis and treatment of DR.

A retrospective analysis for investigating the relationship between FIGO stage IVA/IVB and cytoreductive surgery with prognosis in epithelial ovarian cancer.

Objective: To investigate the effect of primary debulking surgery (PDS), NACT followed by interval debulking surgery (NACT-IDS), and chemotherapy alone on the prognosis of FIGO stage IV epithelial ovarian cancer (EOC) with different metastatic patterns. Methods: We retrospectively analyzed 133 cases of FIGO stage IV EOC with pleural effusion (stage IVA), parenchymal metastases (stage IVB), or extra-abdominal lymph node metastases (stage IVB) at our Hospital between January 2014 and July 2021. Results: Among 133 cases with stage IV disease, 16.5% (n=22) presented with pleural effusion, 46.6% (n=62) with parenchymal metastases, and 36.9% (n=49) with extra-abdominal lymph node metastases. Regardless of the metastatic patterns, the 90.2% (n=120) of cases who underwent PDS/NACT-IDS exhibited a significantly superior overall survival (OS) compared to the 9.8% cases (n=13) who received chemotherapy alone (32 vs 17 months, p=0.000). The cohort was further stratified into 58 cases (48.3%) with R0, 41 cases (34.2%) with R1, and 21 cases (17.5%) with R2. The median OS of cases with R0 was significantly better than that of cases with R1/R2 (74 vs 27 months, p=0.000). There was no significant difference in median OS between PDS and NACT-IDS (43 vs 31 months, p=0.676), as well as between FIGO IVA and IVB (35 vs 31 months, p=0.582). Additionally, the metastatic patterns and the number of neoadjuvant chemotherapy cycles (≤4 or >4) did not demonstrate any prognostic significance for median OS (p=0.820 and 33 vs 26 months, p=0.280, respectively). Conclusion: Regardless of FIGO IVA and IVB stages or metastatic patterns, patients diagnosed with stage IV EOC may benefit from cytoreductive surgery with abdominal R0, compared with chemotherapy alone.

Quality evaluation of Sojae Semen Praeparatum by HPLC combined with HS-GC-MS.

Sojae Semen Praeparatum is a popular fermented legume product in China, with a delicious flavour and health benefits. However, the quality control methods for Sojae Semen Praeparatum are now incomplete, and there are no standards for defining its degree of fermentation. In this study, we introduced colour, acid value, ethanol-soluble extractives and six flavonoid components' content to evaluate the quality of Sojae Semen Praeparatum comprehensively. Multiple linear regression was used to streamline the 11 evaluation indicators to 4 and confirm the evaluating feasibility of the four indicators. The degree of fermentation and odour of Sojae Semen Praeparatum were analyzed on headspace-gas chromatography-mass, and two types of odours, 'pungent' and 'unpleasant', could distinguish over-fermented Sojae Semen Praeparatum. Our research developed fermentation specifications and quality standards for Sojae Semen Praeparatum.

Jiawei Xiaoyao San in treatment of anxiety disorder and anxiety: A review.

Jiawei Xiaoyao San (JWXYS) has shown excellent clinical efficacy in anxiety disorder, but has not yet attracted widespread attention. The animal experiments, clinical trials and mechanism studies of JWXYS were reviewed in this article, which may provide a reference for developing new anxiolytic drugs based on this prescription. The literature was searched in PubMed and CNKI and the documents written in English or with English abstracts were selected. JWXYS could reduce the anxiety symptoms of patients alone and reduce the adverse reactions when it is used in combination with other drugs in the clinic. In preclinical studies, JWXYS also showed therapeutic effects in reducing anxiety-like behavior. The mechanisms may include improving the hypothalamic-pituitaryadrenal (HPA) axis and hormone disorders, increasing neurotransmitter content, neurogenesis, and regulating the synthesis of related enzymes. This article shows that JWXYS could effectively treat anxiety disorders by regulating the central nervous system. In the future, with the participation of more researchers, it is expected to develop innovative drugs for the treatment of anxiety disorders based on JWXYS.

Integration of non-targeted metabolomics with network pharmacology deciphers the anxiolytic mechanisms of Platycladi Semen extracts in CUMS mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycladi Semen was recorded in Shen Nong's Herbal Classic and was considered a herbal medicine with low toxicity after long-term medication. Multiple traditional Chinese medicine prescriptions containing Platycladi Semen have been used to treat insomnia. Modern clinical practitioners commonly use Platycladi Semen to treat anxiety disorders, but there are few studies on its composition and anxiolytic mechanisms. AIM OF THE STUDY: To describe the main components of Platycladi Semen and investigate its anxiolytic effects and mechanisms. MATERIALS AND METHODS: The main components of Platycladi Semen were characterized by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). The anxiolytic effects of oral Platycladi Semen were evaluated in chronic unpredictable mild stress (CUMS) induced mice. To explore the anxiolytic mechanisms of Platycladi Semen, serum non-targeted metabolomics combined with network pharmacology and molecular docking was performed. RESULTS: Fourteen compounds were identified in the 50% methanol extract and 11 fatty acid derivatives were identified in the methyl-esterified fatty oil of Platycladi Semen. In CUMS mice, both the aqueous extract and fatty oil of Platycladi Semen had anxiolytic effects, which were shown by the increase in the time and frequency of mice entering the open arm in the elevated plus maze (EPM) experiment. Through serum non-targeted metabolomics, 34 differential metabolites were identified, and lipid metabolic pathways such as sphingolipid metabolism, steroidogenesis, alpha-linoleic acid, and linoleic acid metabolism were enriched. Through network pharmacology, 109 targets of the main components in Platycladi Semen were identified, and the 'neuroactive ligand-receptor interaction' and 'lipid metabolism' were enriched. The molecular docking results showed that the main components in Platycladi Semen could bind to the key targets such as peroxisome proliferator-activated receptor delta (PPARD), peroxisome proliferator-activated receptor alpha (PPARA), fatty acid binding protein 5 (FABP5), fatty acid binding protein 3 (FABP3), peroxisome proliferator-activated receptor gamma (PPARG), arachidonate 5-lipoxygenase (ALOX5) and fatty acid amide hydrolase (FAAH). CONCLUSION: This study indicated that Platycladi Semen has anxiolytic effects, and the anxiolytic mechanisms may be the regulation of lipid metabolism and the neuroactive ligand-receptor interaction.

Asymmetric Low-Frequency Pulsed Strategy Enables Ultralong CO2 Reduction Stability and Controllable Product Selectivity.

Copper-based catalysts are widely explored in electrochemical CO2 reduction (CO2RR) because of their ability to convert CO2 into high-value-added multicarbon products. However, the poor stability and low selectivity limit the practical applications of these catalysts. Here, we proposed a simple and efficient asymmetric low-frequency pulsed strategy (ALPS) to significantly enhance the stability and the selectivity of the Cu-dimethylpyrazole complex Cu3(DMPz)3 catalyst in CO2RR. Under traditional potentiostatic conditions, Cu3(DMPz)3 exhibited poor CO2RR performance with the Faradaic efficiency (FE) of 34.5% for C2H4 and FE of 5.9% for CH4 as well as the low stability for less than 1 h. We optimized two distinguished ALPS methods toward CH4 and C2H4, correspondingly. The high selectivities of catalytic product CH4 (FECH4 = 80.3% and above 76.6% within 24 h) and C2H4 (FEC2H4 = 70.7% and above 66.8% within 24 h) can be obtained, respectively. The ultralong stability for 300 h (FECH4 > 60%) and 145 h (FEC2H4 > 50%) was also recorded with the ALPS method. Microscopy (HRTEM, SAED, and HAADF) measurements revealed that the ALPS method in situ generated and stabilized extremely dispersive and active Cu-based clusters (∼2.7 nm) from Cu3(DMPz)3. Meanwhile, ex situ spectroscopies (XPS, AES, and XANES) and in situ XANES indicated that this ALPS method modulated the Cu oxidation states, such as Cu(0 and I) with C2H4 selectivity and Cu(I and II) with CH4 selectivity. The mechanism under the ALPS methods was explored by in situ ATR-FTIR, in situ Raman, and DFT computation. The ALPS methods provide a new opportunity to boost the selectivity and stability of CO2RR.

Integrated metabolomics and molecular docking reveal berberrubine inhibits thrombosis by regulating the vitamin K catalytic cycle in mice.

OBJECTIVE: Natural product berberine was reported to inhibit platelet activation and thrombosis by suppressing the class Ⅰ PI3Kß/Rasa3/Rap1 pathway. This study aims to investigate the effects and mechanisms of berberrubine, a main metabolite of berberine, to inhibit thrombus formation. METHODS: Carrageenan-induced mouse tail thrombosis model was used to evaluate the effects of berberrubine hydrochloride (BBB) on thrombus formation in vivo. Non-targeted metabolomics was performed with UPLC-Q-TOF/MS to explore the potential mechanisms of BBB in inhibiting thrombosis. The effects of BBB on bleeding risk and prothrombin time were determined. And molecular docking was used to identify the possible target of BBB. RESULTS: After oral administration, BBB significantly inhibited carrageenan-induced thrombosis in mice without prolonging bleeding time. The results of non-targeted metabolomics showed that oral BBB could regulate 'Phenylalanine, tyrosine and tryptophan biosynthesis' and 'Ubiquinone and other terpenoid-quinone biosynthesis', which is closely related to the vitamin K catalytic cycle. Molecular docking revealed BBB could combine and interact with vitamin K epoxide reductase (VKOR) and γ-Glutamyl carboxylase (GGCX), which was mutually confirmed with the experimental results that oral BBB could significantly prolong prothrombin time. CONCLUSIONS: Integrated metabolomics and molecular docking reveal BBB inhibited thrombosis by regulating the vitamin K catalytic cycle. Our research is helpful in deeply understanding the antithrombotic material basis of oral berberine, and also could provide scientific evidence for developing new antithrombotic drugs based on BBB in the future.

Insights into the Role of Sialylation in Cancer Metastasis, Immunity, and Therapeutic Opportunity.

Sialylation is an enzymatic process that covalently attaches sialic acids to glycoproteins and glycolipids and terminates them by creating sialic acid-containing glycans (sialoglycans). Sialoglycans, usually located in the outmost layers of cells, play crucial biological roles, notably in tumor transformation, growth, metastasis, and immune evasion. Thus, a deeper comprehension of sialylation in cancer will help to facilitate the development of innovative cancer therapies. Cancer sialylation-related articles have consistently increased over the last four years. The primary subjects of these studies are sialylation, cancer, immunotherapy, and metastasis. Tumor cells activate endothelial cells and metastasize to distant organs in part by the interactions of abnormally sialylated integrins with selectins. Furthermore, cancer sialylation masks tumor antigenic epitopes and induces an immunosuppressive environment, allowing cancer cells to escape immune monitoring. Cytotoxic T lymphocytes develop different recognition epitopes for glycosylated and nonglycosylated peptides. Therefore, targeting tumor-derived sialoglycans is a promising approach to cancer treatments for limiting the dissemination of tumor cells, revealing immunogenic tumor antigens, and boosting anti-cancer immunity. Exploring the exact tumor sialoglycans may facilitate the identification of new glycan targets, paving the way for the development of customized cancer treatments.

Whole-cell tumor vaccines desialylated to uncover tumor antigenic Gal/GalNAc epitopes elicit anti-tumor immunity.

BACKGROUND: Aberrant sialoglycans on the surface of tumor cells shield potential tumor antigen epitopes, escape recognition, and suppress activation of immunocytes. α2,3/α2,6Gal- and α2,6GalNAc (Gal/GalNAc)-linked sialic acid residues of sialoglycans could affect macrophage galactose-type lectins (MGL) mediated-antigen uptake and presentation and promote sialic acid-binding immunoglobulin-like lectins (Siglecs) mediated-immunosuppression. Desialylating sialoglycans on tumor cells could present tumor antigens with Gal/GalNAc residues and overcome glyco-immune checkpoints. Thus, we explored whether vaccination with desialylated whole-cell tumor vaccines (DWCTVs) triggers anti-tumor immunity in ovarian cancer (OC). METHODS: Sialic acid (Sia) and Gal/GalNAc residues on OC A2780, OVCAR3, and ID8 cells treated with α2-3 neuraminidase (α2-3NA) and α2-6NA, and Sigec-9 or Siglec-E and MGL on DCs pulsed with desialylated OC cells were identified using flow cytometry (FCM); RT-qPCR determined IFNG expression of T cells, TRBV was sequenced using Sanger sequencing and cytotoxicity of αß T cells was measured with LDH assay; Anti-tumor immunity in vivo was validated via vaccination with desialylated whole-cell ID8 vaccine (ID8 DWCTVs). RESULTS: Gal/GalNAc but not Sia residues were significantly increased in the desialylated OC cells. α2-3NA-modified DWCTV increased MGL but decreased Siglec-9 or Siglec E expression on DCs. MGLbright/Siglec-9dim DCs significantly up-regulated IFNG expression and CD4/CD8 ratio of T cells and diversified the TCR repertoire of αß T-cells that showed enhanced cytotoxic activity. Vaccination with α2-3NA-modified ID8 DWCTVs increased MGLbright/Siglec-Edim DCs in draining lymph nodes, limited tumor growth, and extended survival in tumor-challenged mice. CONCLUSION: Desialylated tumor cell vaccine could promote anti-tumor immunity and provide a strategy for OC immunotherapy in a clinical setting.

Effects of sphingolipid metabolism disorders on endothelial cells.

Many cardiovascular disorders, including atherosclerosis, hypertension, coronary heart disease, diabetes, etc., are characterized by endothelial cell dysfunction. Endothelial cell function is closely related to sphingolipid metabolism, and normal sphingolipid metabolism is critical for maintaining endothelial cell homeostasis. Sphingolipid metabolites or key enzymes in abnormal situation, including sphingosine, ceramide (Cer), sphingosine-1-phosphate (S1P), serine, sphingosine kinase (SPHK), ceramide kinase (Cerk), sphingosine-1-phosphate lyase (S1PL) etc., may have a protective or damaging effect on the function of endothelial cells. This review summarizes the effects of sphingolipid metabolites and key enzymes disordering in sphingolipid metabolism on endothelial cells, offering some insights into further research on the pathogenesis of cardiovascular diseases and corresponding therapeutic targets.

Eimeria tenella 14-kDa phosphohistidine phosphatase stimulates maturation of chicken dendritic cells and mediates DC-induced T cell priming in a Th1 cytokine interface.

Given the central role of dendritic cells (DCs) in directing cell-mediated immunity, this study investigated the capability of Eimeria tenella 14-kDa phosphohistidine phosphatase (EtPHP14) to mature chicken DCs and initiate DC-induced T cell immunity. With the aim of identifying novel protective Eimeria antigen, EtPHP14 gene was successfully cloned and EtPHP14 recombinant protein (rEtPHP14) was expressed in Escherichia coli expression system. rEtPHP14 binding was identified on the surface of chicken DCs by Immunofluorescence assay. DC phenotypes were evaluated by flow cytometry and results indicated that MHCII, CD80, CD86, CD1.1 and CD11c were up-modulated in DCs following rEtPHP14 treatment. RT-qPCR showed increased transcript levels of DC maturation markers CCL5, CCR7 and CD83 in rEtPHP14-treated DCs. Moreover, transcript profile of genes associated with intracellular signaling pathways that characterize the immunogenic (TLR signaling) or tolerogenic (Wnt signaling) state of DCs revealed that TLR signaling was stimulated and Wnt signaling was inhibited in rEtPHP14-treated DCs. Furthermore, proliferation of T cells and differentiation of CD4+ cells were promoted when rEtPHP14-treated DCs were co-cultured with autologous T cells. DCs incubated with rEtPHP14 alone expressed increased IL-12 and IFN-γ levels while IL-10 and TGF-ß levels remained unaffected. Likewise, similar trend of IFN-γ expression was noted in rEtPHP14 treated DC-T cell coculture, whereas IL-4 expression remained unchanged. These findings indicate that EtPHP14 is an important molecule that can upregulate host immune response, particularly Th1, during host-parasite interaction, suggesting its importance as a novel candidate for coccidiosis vaccine.

Serum metabolomics study of anxiety disorder patients based on LC-MS.

BACKGROUND: In the current environment of increasing social pressure, anxiety disorder has become a kind of health problem that needs to be solved urgently. However, the pathological mechanism of anxiety is still unclear, the classification of clinical diagnosis and symptoms is complex, and there is still a lack of biomarkers that can be identified and judged. METHODS: This study used LC-MS and non-targeted metabolomics to analyze the clinically collected plasma of 18 samples from anxiety disorder patients and 31 samples from healthy people to screen differential metabolites and perform subsequent metabolic pathway analysis. Binary Logistic regression was used to construct the anxiety disorder diagnosis prediction model and evaluate the prediction efficacy. RESULTS: The results showed that 22 metabolites were disturbed in the plasma of anxiety patients compared with healthy people. These metabolites mainly participate in 6 metabolic pathways. The combined diagnostic factors 4-Acetamidobutanoate, 3-Hydroxysebacic acid, and Cytosine were used to construct the diagnosis prediction model. The prediction probability of the model is 91.8%, the Youden index is 0.889, the sensitivity is 0.889, and the specificity is 1.000, so the prediction effect is good. CONCLUSIONS: This study preliminarily analyzed and explored the differences between plasma samples from patients with anxiety disorder and healthy individuals, increased the types of potential biomarkers for anxiety disorder, and provided a valuable reference for subsequent research related to anxiety disorder.

Anti-L1 antibody-bound HPV16 pseudovirus is degraded intracellularly via TRIM21/proteasomal pathway.

BACKGROUND: Persistent HPV16 infection is the leading risk factor for developing cervical cancer. Anti-L1 antibodies against HPV16 produced in HPV16 infections play diverse roles in the clearance of virus infection and prevention of persistence. It has been implicated that the cervicovaginal squamous epithelial cells actually express TRIM21 and that some HPV16 particles could escape leaky endosomal compartment into the cytosol and that Fc receptor TRIM21 directly neutralize infection by targeting antibody-opsonized viruses for proteasomal degradation. We explored whether anti-L1 antibody opsonized HPV16 pseudovirus (PsV) entered into the cytosol could be neutralized by TRIM21-mediated activation of a proteasomal pathway to reduce the chance of persistent HPV16 infection. METHODS: HPV16 PsV were generated and extracted in HEK 293FT cells co-transfected with pcDNA3.1-eGFP and p16sheLL plasmids according to the standard protocol. The HPV16 PsV with capsid protein L1 was characterized by fluorescence microscopy and western blot, and the HPV16 PsV titer and anti-L1-bound PsV entry efficiency were detected by flow cytometry. The expressions of transcription factors (TF) and cytokines elicited by the TRIM21-activated proteasomal pathway were confirmed by dual-luciferase reporter assay and RT-qPCR. The changes in HPV16 PsV load with or without inhibitors in the infected HEK 293FT cells were determinated by qPCR. RESULTS: Simultaneous transfection with pcDNA3.1-eGFP and p16sheLL plasmids into the HEK 293FT cells resulted in the self-assembly of HPV16 PsV with capsid protein L1. Both HPV16 PsV and anti-L1-bound HPV16 PsV could infect HEK 293FT cells. Anti-L1-bound PsV up-regulated TRIM21 mediated-activation of proteasome and increased expressions of TF and cytokines in the infected cells where HPV16 PsV load reduced by ~ 1000-fold in the presence of anti-L1 antibody, but inhibition of proteasomal activity increased HPV16 PsV load. CONCLUSION: Our preliminary results indicate that anti-L1 antibody entered with HPV16 PsV into the cells could mediate degradation of HPV16 PsV by TRIM21-activated proteasomal pathway intracellularly, giving anti-capsid protein L1 antibody a role in host defense of persistent HPV16 infection.