Achieving High-Temperature Phosphorescence by Organic Cocrystal Engineering.

Organic phosphors offer a promising alternative in optoelectronics, but their temperature-sensitive feature has restricted their applications in high-temperature scenarios, and the attainment of high-temperature phosphorescence (HTP) is still challenging. Herein, a series of organic cocrystal phosphors are constructed by supramolecular assembly with an ultralong emission lifetime of up to 2.16 s. Intriguingly, remarkable stabilization of triplet excitons can also be realized at elevated temperature, and green phosphorescence is still exhibited in solid state even up to 150 °C. From special molecular packing within the crystal lattice, it has been observed that the orientation of isolated water cluster and well-controlled molecular organization via multiple interactions can favor the structural rigidity of cocrystals more effectively to suppress the nonradiative transition, thus resulting in efficient room-temperature phosphorescence and unprecedented survival of HTP.

Isoflavones isolated from chickpea sprouts alleviate ovariectomy-induced osteoporosis in rats by dual regulation of bone remodeling.

Osteoporosis is a common systemic skeletal disease and a predominant underlying factor in the increased occurrence of fractures. The structure of isoflavones resembles that of estrogen and can confer similar but weaker effects. This study investigated the potential inhibitory effects of isoflavones from chickpea sprouts (ICS) on ovariectomy (OVX)-induced osteoporosis in vitro and in vivo. Notably, we found that ICS treatment could attenuate bone loss and improve trabecular microarchitecture and biomechanical properties of the fourth lumbar vertebra in OVX-induced osteoporotic rats and could also inhibit the development of a hyperosteometabolic state in this model. The osteogenic differentiation of bone marrow stem cells (BMSCs) was significantly enhanced by ICS intervention in vitro, and we confirmed that estrogen receptor α signaling was required for this increased osteogenic differentiation. Additionally, ICS has been shown to inhibit bone resorption via ERa modulation of the OPG/RANKL pathway. RANKL-induced osteoclastogenesis was reduced under ICS treatment, supporting that NF-κB signaling was inhibited by ICS. Thus, ICS attenuates osteoporosis progression by promoting osteogenic differentiation and inhibiting osteoclastic resorption. These results support the further exploration and development of ICS as a pharmacological agent for the treatment and prevention of osteoporosis.

Oncolytic Therapy of Solid Tumors by Modified Vesicular Stomatitis Virus.

Vesicular stomatitis virus (VSV) is a promising oncolytic virus for treating solid tumors. We recently engineered a replicating VSV that specifically targets and destroys Her2/neu-expressing cancer cells. This virus was created by eliminating its natural binding site and adding a coding sequence for a single chain antibody to the Her2/neu receptor into its genome. Such an approach can be tailored to target various cellular surface molecules. This mini review will discuss genomic modifications of VSVs and their role in oncolytic therapy and discuss some challenges for moving VSVs to clinical applications.

Enhanced Photocatalytic Activity of π-Conjugated Pyridine Rings-Modified C3N4/Bi@BiOCl Z-Scheme Heterogeneous Material.

The enhanced photocatalytic properties of Z-Scheme Bi@BiOCl/C3N4-DPY heterojunction materials were successfully prepared by the ultrasonic-assisted coprecipitation method. The Bi@BiOCl/C3N4-DPY heterojunction exhibited remarkable photocatalytic activity under visible light irradiation, and the degradation rate of methyl orange (MO) was about 90.6% in 180 min. This impressive efficiency is mainly due to the Z-Scheme charge transfer mechanism in Bi@BiOCl/C3N4-DPY, resulting in the efficient separation of charge carriers and an increase in the REDOX potential of photogenerated electrons and holes. C3N4 was modified with a π-deficient conjugated pyridine ring, which caused the light absorption redshift, promoted the formation of oxidizing •O2-, and improved the photocatalytic activity. At the same time, a well-aligned heterojunction is formed at the interface between C3N4-DPY and BiOCl, facilitating the seamless transfer of light-induced electrons from the LUMO of C3N4-DPY to the CB of BiOCl. In addition, the addition of Bi introduces a unique band gap reduction effect, resulting in a change in the density of the band states, which further promotes charge transfer and separation. It is worth noting that the introduction of metallic bismuth (Bi) brings about a unique band gap reduction effect, resulting in a change in the density of states within the band, which ultimately promotes charge transfer and separation. The Z-scheme charge migration inside Bi@BiOCl/C3N4-DPY further promotes the efficient separation of photogenerated electron-hole pairs, greatly improving the overall efficiency of the material. The Z-structured photocatalyst developed in this study has great application potential in various fields of photocatalysis.

Regulating Isolated-Molecular and Aggregated-State Phosphorescence for Multicolor Afterglow by Photoactivation.

Ultralong organic phosphorescence (UOP) materials have attracted considerable attention in recent years. Herein, a new type of flexible films is fabricated by doping amphipathic pyrene tetrasulfonic acid sodium salts into amorphous poly(vinyl alcohol) matrix, which enables the realization of color-tunable UOP spanning from orange-red to green after excitation light is switched off. Interestingly, precise control of the proportion of isolated-molecular and aggregated-state phosphorescence is demonstrated for colorful afterglow using photo-activation. An increase in the dynamic phosphorescence lifetime of isolated molecules is observed from 894.75 to 1735.71 ms following an 8 min irradiation under ambient conditions. The photo-activation, however, showed little influence on aggreated-state phosphorescence. This flexible and processable film exhibits versatile applications in multicolor afterglow displays, ultraviolet detection, multilevel information encryption, etc. This study not only provides a strategy for the rational regulation of UOP colors but also expands the application potential of color-tunable UOP materials.

Preparing Data for Artificial Intelligence in Pathology with Clinical-Grade Performance.

The pathology is decisive for disease diagnosis but relies heavily on experienced pathologists. In recent years, there has been growing interest in the use of artificial intelligence in pathology (AIP) to enhance diagnostic accuracy and efficiency. However, the impressive performance of deep learning-based AIP in laboratory settings often proves challenging to replicate in clinical practice. As the data preparation is important for AIP, the paper has reviewed AIP-related studies in the PubMed database published from January 2017 to February 2022, and 118 studies were included. An in-depth analysis of data preparation methods is conducted, encompassing the acquisition of pathological tissue slides, data cleaning, screening, and subsequent digitization. Expert review, image annotation, dataset division for model training and validation are also discussed. Furthermore, we delve into the reasons behind the challenges in reproducing the high performance of AIP in clinical settings and present effective strategies to enhance AIP's clinical performance. The robustness of AIP depends on a randomized collection of representative disease slides, incorporating rigorous quality control and screening, correction of digital discrepancies, reasonable annotation, and sufficient data volume. Digital pathology is fundamental in clinical-grade AIP, and the techniques of data standardization and weakly supervised learning methods based on whole slide image (WSI) are effective ways to overcome obstacles of performance reproduction. The key to performance reproducibility lies in having representative data, an adequate amount of labeling, and ensuring consistency across multiple centers. Digital pathology for clinical diagnosis, data standardization and the technique of WSI-based weakly supervised learning will hopefully build clinical-grade AIP.

Isoacids supplementation improves growth performance and feed fiber digestibility associated with ruminal bacterial community in yaks.

Introduction: This study was conducted to assess the effect of mixed isoacid (MI) supplementation on fermentation characteristics, nutrient apparent digestibility, growth performance, and rumen bacterial community in yaks. Methods: A 72-h in vitro fermentation experiment was performed on an ANKOM RF gas production system. MI was added to five treatments at doses of 0, 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% on the dry matter (DM) basis of substrates using a total of 26 bottles (4 bottles per treatment and 2 bottles as the blank). Cumulative gas production was measured at 4, 8, 16, 24, 36, 48, and 72 h. Fermentation characteristics including pH, the concentration of volatile fatty acids (VFAs), ammonia nitrogen (NH3-N), microbial proteins (MCP), and the disappearance rate of dry matter (DMD), neutral detergent fiber (NDFD), and acid detergent fiber (ADFD) were measured after a 72-h in vitro fermentation to determine an optimal MI dose. Fourteen Maiwa male yaks (180-220 kg, 3-4 years old of age) were randomly assigned to the control group (without MI, n = 7) and the supplemented MI group (n = 7, supplemented with 0.3% MI on DM basis) for the 85-d animal experiment. Growth performance, nutrient apparent digestibility, rumen fermentation parameters, and rumen bacterial diversity were measured. Results: Supplementation with 0.3% MI achieved the greatest propionate and butyrate content, NDFD and ADFD compared with other groups (P < 0.05). Therefore, 0.3% was used for the animal experiment. Supplementation with 0.3% MI significantly increased the apparent digestibility of NDF and ADF (P < 0.05), and the average daily weight gain of yaks (P < 0.05) without affecting the ruminal concentration of NH3-N, MCP, and VFAs. 0.3% MI induced rumen bacteria to form significantly different communities when compared to the control group (P < 0.05). g__norank_f__Bacteroidales_BS11_gut_group, g__norank_f__Muribaculaceae, g__Veillonellaceae_UCG-001, g__Ruminococcus_gauvreauii_group, g__norank_f__norank_o__RF39 and g__Flexilinea were identified as the biomarker taxa in responding to supplementation with 0.3% MI. Meanwhile, the abundance of g__Flexilinea and g__norank_f__norank_o__RF39 were significantly positively correlated with the NDF digestibility (P < 0.05). Conclusion: In conclusion, supplementation with 0.3% MI improved the in vitro rumen fermentation characteristics, feed fiber digestibility, and growth performance in yaks, which was associated with changes of the abundance of g__Flexilinea and g__norank_f__norank_o__RF39.

Screening of Potential Circulating Diagnostic Biomarkers and Molecular Mechanisms of Systemic Lupus Erythematosus-Related Myocardial Infarction by Integrative Analysis.

Background: The risk of acute myocardial infarction (AMI) is elevated in patients with systemic lupus erythematosus (SLE), and it is of great clinical value to identify potential molecular mechanisms and diagnostic markers of AMI associated with SLE by analyzing public database data and transcriptome sequencing data. Methods: AMI and SLE-related sequencing datasets GSE62646, GSE60993, GSE50772 and GSE81622 were downloaded from the Gene Expression Omnibus (GEO) database and divided into prediction and validation cohorts. To identify the key genes associated with AMI related to SLE, WGCNA and DEGs analysis were performed for the prediction and validation cohorts, respectively. The related signaling pathways were identified by GO/KEGG enrichment analysis. Peripheral blood mononuclear cells (PBMCs) from patients with AMI were collected for transcriptome sequencing to validate the expression of key genes in patients with AMI. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to screen diagnostic biomarkers. The diagnostic efficacy of biomarkers was validated by ROC analysis, and the CIBERSORTx platform was used to analyze the composition of immune cells in AMI and SLE. Results: A total of 108 genes closely related to AMI and SLE were identified in the prediction cohort, and GO/KEGG analysis showed significantly enriched signaling pathways. The results of differential analysis in validation cohort were consistent with them. By transcriptional sequencing of PBMCs from peripheral blood of AMI patients, combined with the results of prediction and validation cohort analysis, seven genes were finally screened out. LASSO analysis finally identifies DYSF, LRG1 and CSF3R as diagnostic biomarkers of SLE-related-AMI. CIBERSORTx analysis revealed that the biomarkers were highly correlated with neutrophils. Conclusion: Neutrophil degranulation and NETs formation play important roles in SLE-related AMI, and DYSF, LRG1 and CSF3R were identified as important diagnostic markers for the development and progression of SLE-related AMI.

Dietary supplementation with xylooligosaccharides and exogenous enzyme improves milk production, energy utilization efficiency and reduces enteric methane emissions of Jersey cows.

BACKGROUND: Sustainable strategies for enteric methane (CH4) mitigation of dairy cows have been extensively explored to improve production performance and alleviate environmental pressure. The present study aimed to investigate the effects of dietary xylooligosaccharides (XOS) and exogenous enzyme (EXE) supplementation on milk production, nutrient digestibility, enteric CH4 emissions, energy utilization efficiency of lactating Jersey dairy cows. Forty-eight lactating cows were randomly assigned to one of 4 treatments: (1) control diet (CON), (2) CON with 25 g/d XOS (XOS), (3) CON with 15 g/d EXE (EXE), and (4) CON with 25 g/d XOS and 15 g/d EXE (XOS + EXE). The 60-d experimental period consisted of a 14-d adaptation period and a 46-d sampling period. The enteric CO2 and CH4 emissions and O2 consumption were measured using two GreenFeed units, which were further used to determine the energy utilization efficiency of cows. RESULTS: Compared with CON, cows fed XOS, EXE or XOS + EXE significantly (P < 0.05) increased milk yield, true protein and fat concentration, and energy-corrected milk yield (ECM)/DM intake, which could be reflected by the significant improvement (P < 0.05) of dietary NDF and ADF digestibility. The results showed that dietary supplementation of XOS, EXE or XOS + EXE significantly (P < 0.05) reduced CH4 emission, CH4/milk yield, and CH4/ECM. Furthermore, cows fed XOS demonstrated highest (P < 0.05) metabolizable energy intake, milk energy output but lowest (P < 0.05) of CH4 energy output and CH4 energy output as a proportion of gross energy intake compared with the remaining treatments. CONCLUSIONS: Dietary supplementary of XOS, EXE or combination of XOS and EXE contributed to the improvement of lactation performance, nutrient digestibility, and energy utilization efficiency, as well as reduction of enteric CH4 emissions of lactating Jersey cows. This promising mitigation method may need further research to validate its long-term effect and mode of action for dairy cows.

Vesicular Stomatitis Virus (VSV) G Glycoprotein Can Be Modified to Create a Her2/Neu-Targeted VSV That Eliminates Large Implanted Mammary Tumors.

Viral oncolytic immunotherapy is a nascent field that is developing tools to direct the immune system to find and eliminate cancer cells. Safety is improved by using cancer-targeted viruses that infect or grow poorly on normal cells. The recent discovery of the low-density lipoprotein (LDL) receptor as the major vesicular stomatitis virus (VSV) binding site allowed for the creation of a Her2/neu-targeted replicating recombinant VSV (rrVSV-G) by eliminating the LDL receptor binding site in the VSV-G glycoprotein (gp) and adding a sequence coding for a single chain antibody (SCA) to the Her2/neu receptor. The virus was adapted by serial passage on Her2/neu-expressing cancer cells resulting in a virus that yielded a 15- to 25-fold higher titer following in vitro infection of Her2/neu+-expressing cell lines than that of Her2/neu-negative cells (~1 × 108/mL versus 4 × 106 to 8 × 106/mL). An essential mutation resulting in a higher titer virus was a threonine-to-arginine change that produced an N-glycosylation site in the SCA. Infection of Her2/neu+ subcutaneous tumors yielded >10-fold more virus on days 1 and 2 than Her2/neu- tumors, and virus production continued for 5 days in Her2/neu+ tumors compared with 3 days that of 3 days in Her2/neu- tumors. rrVSV-G cured 70% of large 5-day peritoneal tumors compared with a 10% cure by a previously targeted rrVSV with a modified Sindbis gp. rrVSV-G also cured 33% of very large 7-day tumors. rrVSV-G is a new targeted oncolytic virus that has potent antitumor capabilities and allows for heterologous combination with other targeted oncolytic viruses. IMPORTANCE A new form of vesicular stomatitis virus (VSV) was created that specifically targets and destroys cancer cells that express the Her2/neu receptor. This receptor is commonly found in human breast cancer and is associated with a poor prognosis. In laboratory tests using mouse models, the virus was highly effective at eliminating implanted tumors and creating a strong immune response against cancer. VSV has many advantages as a cancer treatment, including high levels of safety and efficacy and the ability to be combined with other oncolytic viruses to enhance treatment results or to create an effective cancer vaccine. This new virus can also be easily modified to target other cancer cell surface molecules and to add immune-modifying genes. Overall, this new VSV is a promising candidate for further development as an immune-based cancer therapy.

Supercooled Liquids with Dynamic Room Temperature Phosphorescence Using Terminal Hydroxyl Engineering.

Dynamic room temperature phosphorescence (RTP) materials have potential applications in optoelectronics, which inevitably suffer from poor processability, flexibility or stretchability. Herein, we report a concise strategy to develop supercooled liquids (SCLs) with dynamic RTP behavior using terminal hydroxyl engineering. The terminal hydroxyls effectively hinder the nucleation process of molecules for the formation of stable SCLs after thermal annealing. Impressively, the SCLs show reversible RTP emission via alternant stimulation by UV light and heat. Photoactivated SCLs have phosphorescent efficiency of 8.50 % and a lifetime of 31.54 ms under ambient conditions. Regarding the dynamic RTP behavior and stretchability of SCLs, we demonstrate the applications in erasable data encryption and patterns on flexible substrates. This finding provides a design principle for obtaining SCLs with RTP and expands the potential applications of RTP materials in flexible optoelectronics.

Automatic Classification of Histopathology Images across Multiple Cancers Based on Heterogeneous Transfer Learning.

BACKGROUND: Current artificial intelligence (AI) in histopathology typically specializes on a single task, resulting in a heavy workload of collecting and labeling a sufficient number of images for each type of cancer. Heterogeneous transfer learning (HTL) is expected to alleviate the data bottlenecks and establish models with performance comparable to supervised learning (SL). METHODS: An accurate source domain model was trained using 28,634 colorectal patches. Additionally, 1000 sentinel lymph node patches and 1008 breast patches were used to train two target domain models. The feature distribution difference between sentinel lymph node metastasis or breast cancer and CRC was reduced by heterogeneous domain adaptation, and the maximum mean difference between subdomains was used for knowledge transfer to achieve accurate classification across multiple cancers. RESULT: HTL on 1000 sentinel lymph node patches (L-HTL-1000) outperforms SL on 1000 sentinel lymph node patches (L-SL-1-1000) (average area under the curve (AUC) and standard deviation of L-HTL-1000 vs. L-SL-1-1000: 0.949 ± 0.004 vs. 0.931 ± 0.008, p value = 0.008). There is no significant difference between L-HTL-1000 and SL on 7104 patches (L-SL-2-7104) (0.949 ± 0.004 vs. 0.948 ± 0.008, p value = 0.742). Similar results are observed for breast cancer. B-HTL-1008 vs. B-SL-1-1008: 0.962 ± 0.017 vs. 0.943 ± 0.018, p value = 0.008; B-HTL-1008 vs. B-SL-2-5232: 0.962 ± 0.017 vs. 0.951 ± 0.023, p value = 0.148. CONCLUSIONS: HTL is capable of building accurate AI models for similar cancers using a small amount of data based on a large dataset for a certain type of cancer. HTL holds great promise for accelerating the development of AI in histopathology.

Anti-tumor memory CD4 and CD8 T-cells quantified by bulk T-cell receptor (TCR) clonal analysis.

Simple, reliable methods to detect anti-tumor memory T-cells are necessary to develop a clinical tumor vaccination program. A mouse model of curative viral onco-immunotherapy found that peritoneal tumor challenge following cure identified an oligoclonal anti-tumor memory CD4 and CD8 T-cell response. Clonotypes differed among the challenged animals but were congruent in blood, spleen and peritoneal cells (PC) of the same animal. Adoptive transfer demonstrated that the high-frequency responding T-cells were tumor specific. Tetramer analysis confirmed that clonotype frequency determined by T-cell receptor (TCR)- chain (TRB) analysis closely approximated cell clone frequency. The mean frequency of resting anti-tumor memory CD4 T-cells in unchallenged spleen was 0.028% and of memory CD8 T-cells was 0.11% which was not high enough to distinguish them from background. Stimulation produced a mean ~10-fold increase in splenic and 100-fold increase in peritoneal anti-tumor memory T-cell clonotypes. This methodology can be developed to use blood and tissue sampling to rapidly quantify the effectiveness of a tumor vaccine or any vaccine generating therapeutic T-cells.

Comprehensive analysis of atherosclerotic plaques reveals crucial genes and molecular mechanisms associated with plaque progression and rupture.

Background: Plaque rupture and acute atherothrombosis, resulting from continued progression of atherosclerotic plaques (APs), are major contributors to acute clinical events such as stroke or myocardial infarction. This article aimed to explore the gene signatures and potential molecular mechanisms in the progression and instability of APs and to identify novel biomarkers and interventional targets for AP rupture. Methods: The microarray data were downloaded from the Gene Expression Omnibus (GEO) database and grouped into discovery and validation cohorts. In the discovery cohort, Weighted Gene Co-Expression Network Analysis was performed for finding co-expression modules, and the Metascape database was used to perform functional enrichment analysis. Differential Expression Genes analysis subsequently was performed in the validation cohort for verification of the obtained results. Common genes were introduced into Metascape database for protein-protein interaction and functional enrichment analysis. We constructed the miRNAs-mRNAs network with the hub genes. Moreover, gene expression profiles of peripheral blood mononuclear cells (PBMCs) from peripheral blood of patients with plaque rupture were analyzed by high-throughput sequencing, and the diagnostic power of hub genes was verified by receiver operating characteristic (ROC) analysis. Results: In the discovery cohort, the brown module in GSE28829 and the turquoise module in GSE163154 were the most significant co-expression modules. Functional enrichment analysis of shared genes suggested that "Neutrophil degranulation" was the most significantly enriched pathway. These conclusions were also demonstrated by the validation cohort. A total of 16 hub genes were identified. The miRNA-mRNA network revealed that hsa-miR-665 and hsa-miR-512-3p might regulate the "Neutrophil degranulation" pathway through PLAU and SIRPA, which might play a significant role in AP progression and instability. Five hub genes, including PLAUR, FCER1G, PLAU, ITGB2, and SLC2A5, showed significantly increased expression in PBMCs from patients with plaque rupture compared with controls. ROC analysis finally identified three hub genes PLAUR, FCER1G, and PLAU that could effectively distinguish patients with APs rupture from controls. Conclusions: The present study demonstrated that the "neutrophil degranulation" signaling pathways and identified novel mRNA and miRNA candidates are closely associated with plaque progression and instability. The hub genes FCER1G, PLAUR, and PLAU may serve as biomarkers for the prospective prediction of AP rupture.

Toxic effects of Tripterygium glycoside tablets on the reproductive system of male rats by metabolomics, cytotoxicity, and molecular docking.

BACKGROUND: Tripterygium glycoside tablets (TGT) is the most common preparation from Tripterygium wilfordii Hook F, which is widely used in clinical for treating rheumatoid arthritis (RA) and other autoimmune diseases. However, its serious reproductive toxicity limits its application. PURPOSE: This study aimed to elucidate the toxic effects of TGT on the reproductive system of male RA rats and its potential toxic components and mechanism. METHODS: Collagen-induced arthritis (CIA) rat model was established, and TGT suspension was given at low, medium, and high doses. Gonadal index, pathological changes, and the number of spermatogenic cells were used to evaluate the toxic effects of TGT on the reproductive system. Non-targeted metabolomics of testicular tissue was conducted by UHPLC-QTOF/MS. Combined with network toxicology, the key targets of TGT-induced reproductive toxicity were screened and RT-qPCR was used to validation. In vitro toxicity of 19 components of TGT was evaluated using TM3 and TM4 cell lines. Molecular docking was used to predict the interaction between toxic components and key targets. RESULTS: TGT reduced testicular and epididymis weight. Pathology analysis showed a lot of deformed and atrophic spermatogenic tubules. The number of spermatogenic cells decreased significantly (P<0.0001). A total of 58 different metabolites including platelet-activating factor (PAF), lysophosphatidylcholine (Lyso PC), phosphatidylinositol (PI), glutathione (GSH), and adenosine monophosphate (AMP) were identified by testicular metabolomics. Glycerophospholipid metabolism, ether lipid metabolism, and glutathione metabolism were key pathways responsible for the reproductive toxicity of TGT. Ten key reproductive toxicity targets were screened by network toxicology. The cytotoxicity test showed that triptolide, triptonide, celastrol, and demethylzeylasteral could significantly reduce the viability of TM3 and TM4 cells. Alkaloids had no apparent toxic effects. Molecular docking showed that the four toxic components had a good affinity with 10 key targets. All binding energies were less than -7 kcal/mol. The RT-qPCR results showed the Cyp19a1 level was significantly up-regulated. Pik3ca and Pik3cg levels were significantly down-regulated. CONCLUSION: Through testicular metabolomics, we found that TGT may cause reproductive toxicity through CYP19A1, PIK3CA, and PIK3CG three target, which was preliminarily revealed. This study laid the foundation for elucidating the toxicity mechanism of TGT and evaluating its safety and quality.

Integrated metabolomics and network analysis reveal changes in lipid metabolisms of tripterygium glycosides tablets in rats with collagen-induced arthritis.

Tripterygium glycosides tablets (TGT) are the commonly used preparation for rheumatoid arthritis (RA). However, the changes in TGT on RA are still unclear at the metabolic level. This study aimed to reveal the biological processes of TGT in collagen-induced arthritis (CIA) rats through integrated metabolomics and network analysis. First, the CIA model in rats was established, and the CIA rats were given three doses of TGT. Then, the endogenous metabolites in the serum from normal rats, CIA rats, and CIA rats treated with varying doses of TGT were detected by UHPLC-QTOF-MS/MS. Next, univariate and multivariate statistical analyses were performed to find the differential metabolites. Finally, differential metabolites, metabolic pathways, and hub genes were analyzed integrally to reveal the biological processes of TGT in CIA rats. The paw diameter, arthritis score, immunoglobulin G (IgG) concentration, CT image, and histological assay showed that TGT had evident therapeutic effects on CIA rats. Untargeted metabolomics revealed that TGT could ameliorate the down-regulation of lipid levels in CIA rats. Four key differential metabolites were found including LysoP(18:0), LysoPA(20:4), LysoPA(18:2), and PS(O-20:0/17:1). The glycerophospholipid metabolic pathway was perturbed in treating CIA with TGT. A total of 24 genes, including PLD1, LPCAT4, AGPAT1, and PLA2G4A, were found to be the hub genes of TGT in CIA rats. In conclusion, the integrated analysis provided a novel and holistic perspective on the biological processes of TGT in CIA rats, which could give helpful guidance for further TGT on RA. Future studies based on human samples are necessary.

Biochemical characterization, and anti-inflammatory and antitumor activities of glycoprotein from lamb abomasum.

ETHNOPHARMACOLOGICAL RELEVANCE: Lamb abomasum is used as an edible medicinal source in traditional Chinese medicine for the treatment of gastrointestinal disorders. Lamb abomasum sourced biochemical drug Lamb's trip extract and Vitamin B12 capsule used for the clinical treatment of chronic gastritis, gastric ulcer, and reversal of intestinal metaplasia. Therefore, claimed to have prevention of gastric cancer activity. AIM OF THE STUDY: In this study, we aim to assess whether the glycoprotein has biological activity in the cure of gastric disorder and conduct a structure-activity relationship. MATERIALS AND METHODS: Glycoproteins' extraction conditions were optimized by the response surface method and purified with DEAE-cellulose and Sephadex G-50 chromatography. Two homogenous glycoproteins' physiochemical structures were studied with electrophoresis, HPLC analysis, peroxide oxidation, and ß-elimination, FT-IR, CD, LC-MS/MS, and EDS analysis. The antiinflammation activity of the glycoprotein was determined against COX-2 and LOX-15 enzyme inhibitory ability in vitro, and antitumor activity against HT-29 and HGC-25, and cytotoxicity on L-02 cells was determined in vivo with the MTT method. RESULTS: The abomasum was abundant in glycoprotein and the extraction yield of glycoprotein was up to 24.6 ± 2.1% under optimized conditions. Two homogeneous glycoproteins SAGP-I and SAGP-II determined to be ribose-conjugated and sulfated glycoproteins with a molecular weight of 15.6 kDa and 6.4 kDa. And according to the structural analysis, SAGP-I was a mucin-type ribose-conjugated glycoprotein with 14 O-glycosylation and one N- glycosylation site. SAGP-I and SAGP-II have remarkable anti-inflammatory activity against COX-2 enzyme with the IC50 of 17.64 ± 1.25 µg/mL and 16.14 ± 1.11 µg/mL, respectively. Meanwhile, the two glycoproteins showed strong antitumor activity against HT-29 with the EC50 of 19.19 ± 1.46 µg/mL and 184.9 ± 5.6 µg/mL, respectively. CONCLUSION: The Highly purified glycoprotein SAGP-1 and SAGP-II showed anti-inflammatory activity against the COX-2 enzyme, and antitumor activity against HT-29 human colon cancer cells and noun-inhibitory activity against LOX-15 enzyme and HGC-25. Both glycoproteins are ribose conjugated and sulfated whose characters are related to their anti-inflammatory and anti-tumor activity. Such results suggest the possibility of anti-inflammatory and pre-cancer activity. And in some degree explains the pharmacy of abomasum's traditional use in gastric disorder and clinical use of lamb abomasum APIs drugs' in gastric disorders and gastric cancer development. This study provides a preliminary basis for the further study of the per-cancer mechanism of lamb abomasum glycoprotein. And, would be the material basis of the clinical use of Lamb's trip extract and Vitamin B12 capsule.

Revealment study on the regulation of lipid metabolism by Lingguizhugan Decoction in heart failure treatment based on integrated lipidomics and proteomics.

Lingguizhugan Decoction (LGZGD) is a classical traditional Chinese medicine prescription. Our previous studies found that disorders of lipid metabolism were reversed by LGZGD in heart failure (HF) mice. This study aimed to reveal the regulation of lipid metabolism of LGZGD. A mice model of HF was established by intraperitoneal injection of doxorubicin. The components of LGZGD were identified with the UHPLC-QTOF-MS method. The regulation of lipid metabolism by LGZGD was detected by serum lipidomics and heart tissue proteomics. Molecular docking was further performed to screen active components. A total of 78 compounds in LGZGD were identified. Results of lipidomics showed that 37 lipids illustrated a significant recovery trend to normal after the treatment of LGZGD. Results of proteomics demonstrated that 55 proteins were altered by the administration of LGZGD in HF mice. After enrichment analysis, the Prakg2/Ucp2/Plin1 axis on the Apelin pathway plays a vital role in HF treatment by LGZGD. Nine active components exhibited the outstanding ability of binding to the apelin receptor with MM-GBSA value lower than -60 Kcal/mol. In conclusion, all results combined together revealed that multi-component in the LGZGD had beneficial effects on the HF through ameliorating lipid disorders, which provides a novel insight into the cardioprotective effects of LGZGD and its clinical application.

Consumer satisfaction-oriented emotional marketing in foreign trade.

This research uses an experimental approach to investigate the relationship between market orientation of a company and its level of success in international business. The aim of the study was to develop and use a market orientation scale that is appropriate to the sector. It was discovered that there are four hidden traits that drive market orientation. These include customers, rivals, departmental response, and overall customer satisfaction. According to the results, orientation toward one's customers is more essential than any of the other traits, while orientation toward one's competitors has an inverted U-shaped connection with performance. The performance of the firm was not found to correlate in any way with the responsiveness of its departments. With the help of the comprehensive conceptualization, managers are able to develop specific kinds of orientations that are essential for higher levels of performance.

Single-Cell RNA Sequencing of Peripheral Blood Mononuclear Cells From Acute Myocardial Infarction.

Background: Acute myocardial infarction (AMI) can occur in patients with atherosclerotic disease, with or without plaque rupture. Previous studies have indicated a set of immune responses to plaque rupture. However, the specific circulating immune cell subsets that mediate inflammatory plaque rupture remain elusive. Methods: Ten AMI patients were enrolled in our study (five with and five without plaque rupture; plaque characteristics were identified by optical coherence tomography). By single-cell RNA sequencing, we analyzed the transcriptomic profile of peripheral blood mononuclear cells. Results: We identified 27 cell clusters among 82,550 cells, including monocytes, T cells, NK cells, B cells, megakaryocytes, and CD34+ cells. Classical and non-classical monocytes constitute the major inflammatory cell types, and pro-inflammatory genes such as CCL5, TLR7, and CX3CR1 were significantly upregulated in patients with plaque rupture, while the neutrophil activation and degranulation genes FPR2, MMP9, and CLEC4D were significantly expressed in the intermediate monocytes derived from patients without plaque rupture. We also found that CD4+ effector T cells may contribute to plaque rupture by producing a range of cytokines and inflammatory-related chemokines, while CD8+ effector T cells express more effector molecules in patients without plaque rupture, such as GZMB, GNLY, and PRF1, which may contribute to the progress of plaque erosion. Additionally, NK and B cells played a significant role in activating inflammatory cells and promoting chemokine production in the plaque rupture. Cell-cell communication elaborated characteristics in signaling pathways dominated by inflammatory activation of classical monocytes in patients with plaque rupture. Conclusions: Our studies demonstrate that the circulating immune cells of patients with plaque rupture exhibit highly pro-inflammatory characteristics, while plaque erosion is mainly associated with intermediate monocyte amplification, neutrophil activation, and degranulation. These findings may provide novel targets for the precise treatment of patients with AMI.