Polymeric monolithic columns based on natural wood for rapid purification of targeted protein.

With multiscale hierarchical structure, wood is suitable for a range of high-value applications, especially as a chromatographic matrix. Here, we have aimed to provide a weak anion-exchange polymeric monolithic column based on natural wood with high permeability and stability for effectively separating the targeted protein. The wood-polymeric monolithic column was synthesized by in situ polymerization of glycidyl methacrylate and ethylene glycol dimethacrylate in wood, and coupled with diethylaminoethyl hydrochloride. The wood-polymeric monolithic column can be integrated with fast-protein liquid chromatography for large-scale protein purification. According to the results, the wood-polymeric monolithic column showed high hydrophilicity, permeability and stability. Separation experiments verified that the wood-polymeric monolithic column could purify the targeted protein (spike protein of SARS-COV-2 and ovalbumin) from the mixed proteins by ion exchange, and the static adsorption capacity was 33.04 mg mL-1 and the dynamic adsorption capacity was 24.51 mg mL-1. In addition, the wood-polymerized monolithic column had good stability, and a negligible decrease in the dynamic adsorption capacity after 20 cycles. This wood-polymerized monolithic column can provide a novel, efficient, and green matrix for monolithic chromatographic columns.

Comparison of total percutaneous in situ microneedle puncture and chimney technique for left subclavian artery fenestration in thoracic endovascular aortic repair for type B aortic dissection.

OBJECTIVE: To compare the outcomes of totally percutaneous in situ microneedle puncture for left subclavian artery (LSA) fenestration (ISMF) and chimney technique in type B aortic dissection (TBAD) during thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Data on patients who underwent either chimney-TEVAR (n = 89) or ISMF-TEVAR (n = 113) from October 2018 to April 2022 were analyzed retrospectively. The primary outcomes were mortality and major complications at 30 days and during follow-up. RESULTS: The technical success rate was 84.3% in the chimney group and 93.8% in the ISMF group (p = 0.027). The incidence of immediate endoleakage was significantly higher in the chimney than ISMF group (15.7% vs 6.2%, respectively; p = 0.027). The 1- and 3-year survival rates in the chimney and ISMF groups were 98.9% ± 1.1% vs 98.1% ± 0.9% and 86.5% ± 6.3% vs 92.6% ± 4.1%, respectively (log-rank p = 0.715). The 3-year rate of cumulative freedom from branch occlusion in the chimney and ISMF group was 95.4% ± 2.3% vs 100%, respectively (log-rank p = 0.023). CONCLUSION: Both ISMF-TEVAR and chimney-TEVAR achieved satisfactory short- and mid-term outcomes for the preservation of the LSA in patients with TBAD. ISMF-TEVAR appears to offer better clinical outcomes with higher patency and lower reintervention rates. However, ISMF-TEVAR had longer operation times with higher procedure expenses. CLINICAL RELEVANCE STATEMENT: When LSA revascularization is required during TEVAR, in situ, fenestration, and chimney techniques are all safe and effective methods; in situ, fenestration-TEVAR appears to offer better clinical outcomes, but takes longer and is more complicated. KEY POINTS: LSA revascularization during TEVAR reduces post-operative complication rates. Both in situ ISMF-TEVAR and chimney-TEVAR are safe and effective techniques for the preservation of the LSA during TEVAR. The chimney technique is associated with a higher incidence of endoleakage and branch occlusion, but ISMF-TEVAR is a more complicated and expensive technique.

Typhoon disaster state information extraction for Chinese texts.

Typhoon disasters undergo a complex evolutionary process influenced by temporal changes, and investigating this process constitutes the central focus of geographical research. As a key node within the typhoon disaster process, the state serves as the foundation for gauging the dynamics of the disaster. The majority of current approaches to disaster information extraction rely on event extraction methods to acquire fundamental elements, including disaster-causing factors, disaster-bearing bodies, disaster-pregnant environment and the extent of damage. Due to the dispersion of various disaster information and the diversity of time and space, it is a challenge for supporting the analysis of the typhoon disaster process. In this paper, a typhoon disaster state information extraction (TDSIE) method for Chinese texts is proposed, which aims to facilitate the systematic integration of fragmented typhoon disaster information. First, the integration of part-of-speech tagging with spatio-temporal information extraction is employed to achieve the tagging of typhoon disaster texts. Second, within the framework of spatio-temporal semantic units, the typhoon disaster semantic vector is constructed to facilitate the identification of information elements of typhoon disaster states. Third, co-referential state information fusion is performed based on spatio-temporal cues. Experimental analysis, conducted using online news as the data source, reveals that the TDSIE achieves precision and recall rates consistently surpassing 85%. The typhoon disaster state information derived from the TDSIE allows for the analysis of spatio-temporal patterns, evolutionary characteristics, and activity modes of typhoon disasters across various scales. Therefore, TDSIE serves as valuable support for investigating the inherent process properties of typhoon disasters.

White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy-based therapy.

BACKGROUND AND PURPOSE: White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. EXPERIMENTAL APPROACH: WAT status of healthy and adjuvant-induced arthritis (AIA) rats were compared. The contribution of WAT to RA pathology was evaluated by pre-adipocyte transplant experiments and by dissecting perirenal fat pads of AIA rats. The impact of RA on WAT was investigated by culturing pre-adipocytes. Proteins differentially expressed in WAT of healthy and AIA rats were identified by the UPLC/MS2 method. These together with PPARγ siRNA and agonist were used to treat pre-adipocytes in vitro. The medium was used for THP-1 monocyte culture. KEY RESULTS: Compared with healthy controls, AIA WAT was smaller but secreted more leptin, eNAMPT, MCP-1, TNF-α, and IL-6. AIA rat pre-adipocytes increased the levels of these adipokines in healthy recipients. RA patients' serum induced a similar secretion change and impaired differentiation of pre-adipocytes. Adipectomy eased AIA-related immune abnormalities and arthritic manifestations. Hepatokines PON1, IGFBP4, and GPIHBP1 were among the differential proteins in high levels in RA blood, and induced inflammatory secretions by pre-adipocytes. GPIHBP1 inhibited PPARγ expression and caused differentiation impairment and inflammatory secretion by pre-adipocytes, a similar outcome to PPARγ-silencing. This endowed the cells with an ability to activate monocytes, which can be abrogated by rosiglitazone. CONCLUSION AND IMPLICATIONS: Certain hepatokines potentiate inflammatory secretions by pre-adipocytes and expedite RA progression by inhibiting PPARγ. Targeting this signalling or abnormal WAT secretion by various approaches may reduce RA severity.

Identification of a cinnamoyl-CoA reductase from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis.

MAIN CONCLUSION: The identification of a functional cinnamoyl-CoA reductase enzyme from Cinnamomum cassia involved in trans-cinnamaldehyde biosynthesis offers the potential for enhancing trans-cinnamaldehyde production through genetic engineering. A significant accumulation of trans-cinnamaldehyde has been found in the bark tissues of C. cassia, used in traditional Chinese medicine. trans-Cinnamaldehyde exhibits various pharmacological properties such as anti-inflammatory, analgesic, and protection of the stomach and the digestive tract. However, further elucidation and characterization of the biosynthetic pathway for trans-cinnamaldehyde is required. In this study, we conducted an integrated analysis of trans-cinnamaldehyde accumulation profiles and transcriptomic data from five different C. cassia tissues to identify the genes involved in its biosynthesis. The transcriptome data we obtained included nearly all genes associated with the trans-cinnamaldehyde pathway, with the majority demonstrating high abundance in branch barks and trunk barks. We successfully cloned four C. cassia cinnamoyl-CoA reductases (CcCCRs), a key gene in trans-cinnamaldehyde biosynthesis. We found that the recombinant CcCCR1 protein was the only one that more efficiently converted cinnamoyl-CoA into trans-cinnamaldehyde. CcCCR1 exhibited approximately 14.7-fold higher catalytic efficiency (kcat/Km) compared to the Arabidopsis thaliana cinnamoyl-CoA reductase 1 (AtCCR1); therefore, it can be utilized for engineering higher trans-cinnamaldehyde production as previously reported. Molecular docking studies and mutagenesis experiments also validated the superior catalytic activity of CcCCR1 compared to AtCCR1. These findings provide valuable insights for the functional characterization of enzyme-coding genes and hold potential for future engineering of trans-cinnamaldehyde biosynthetic pathways.

Angiotensin II type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway.

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

[IL-1ß inhibits macrophage M2 polarization by down-regulating CD200 expression in human umbilical cord mesenchymal stem cells].

Objective To investigate the regulation of IL-1ß on the expression of CD200 in human umbilical cord mesenchymal stem cells (hUC-MSCs), its role in macrophage polarization and the underlying mechanism. Methods hUC-MSCs were isolated and cultured in serum-free medium. Morphological observation and the expressions of CD73, CD90, CD105, CD14, CD34, CD45 and HLA-DR were detected by flow cytometry to confirm the properties of mesenchymal stem cells. hUC-MSCs were treated with IL-1ß at the final concentration of 20 ng/mL for 24 hours. The proportion of CD200 positive cells was measured by flow cytometry. Real-time quantitative PCR and Western blot analysis were used to detect CD200 mRNA and protein expression levels. hUC-MSCs infected with CD200 overexpression (OE-CD200) and its negative control (OE-NC) lectin virus were treated with IL-1ß and co-cultured with PMA-activated THP-1 macrophages. The proportion of CD11c and CD206 positive cells was measured by flow cytometry. hUC-MSCs were treated with IL-1ß in combination with PD98059, and the expression of MAPK signaling pathway-related proteins and its effect on CD200 expression were detected by Western blot analysis. Results IL-1ß significantly down-regulated the expression of CD200 protein and the proportion of CD200 positive cells. Overexpression of CD200 significantly up-regulated the expression of CD200 in hUC-MSCs, and increased the proportion of CD206-positive macrophages. IL-1ß activated the ERK1/2 signaling pathway in hUC-MSCs, and PD98059 up-regulated the expression of CD200 protein in hUC-MSCs treated with IL-1ß. Conclusion IL-1ß inhibits the expression of CD200 by activating ERK1/2 signaling pathway, and reduces the immunosuppressive effect of hUC-MSCs on regulating the M2-type polarization of macrophages.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Bioinspired and biomimetic strategies for inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory bowel disease with high morbidity and an increased risk of cancer or death, resulting in a heavy societal medical burden. While current treatment modalities have been successful in achieving long-term remission and reducing the risk of complications, IBD remains incurable. Nanomedicine has the potential to address the high toxic side effects and low efficacy in IBD treatment. However, synthesized nanomedicines typically exhibit some degree of immune rejection, off-target effects, and a poor ability to cross biological barriers, limiting the development of clinical applications. The emergence of bionic materials and bionic technologies has reshaped the landscape in novel pharmaceutical fields. Biomimetic drug-delivery systems can effectively improve biocompatibility and reduce immunogenicity. Some bioinspired strategies can mimic specific components, targets or immune mechanisms in pathological processes to produce targeting effects for precise disease control. This article highlights recent research on bioinspired and biomimetic strategies for the treatment of IBD and discusses the challenges and future directions in the field to advance the treatment of IBD.

Oyster (Ostrea Plicatula Gmelin) Peptides Improve Exercise Endurance Capacity via Activating AMPK and HO-1.

Objective: Previous studies have shown that oyster peptides (OPs) have antioxidant and anti-fatigue activities. This study aimed to investigate the effects of OPs on swimming endurance in mice and the underlying mechanisms.Methods: The mice were subjected to gavage with OPs and subjected to exercise training. After 14 days, various biochemical indicators in the blood and gastrocnemius muscle of mice were assessed, and real-time PCR was utilized to detect the level of signal pathway regulation by OPs in the gastrocnemius muscle. Molecular docking technology was employed to observe the potential active components in OPs that regulate signal pathways.Results: In this study, OPs supplementation combined with and without exercise significantly extended swimming time compared to the sedentary group. OPs supplementation with exercise also increased glycogen levels and decreased blood urea nitrogen, lactate dehydrogenase, and lactic acid levels. Additionally, mice in the exercise with OPs group exhibited higher activities of antioxidant enzymes. OPs can upregulate metabolic regulatory factors such as AMP-activated protein kinase, peroxisome proliferator-activated receptor gamma coactivator-1 alpha, peroxisome proliferator-activated receptor delta, and glucose transporter 4, thereby increasing energy supply during exercise. Additionally, OPs enhances the expression of heme oxygenase 1 and superoxide dismutase 2, thereby reducing oxidative stress during physical activity. Molecular docking analyses revealed that peptides found in OPs formed hydrogen bonds with AMPK and HO-1, indicating that they can exert bioactivity by activating target proteins such as AMPK and HO-1.Conclusions: OPs supplementation improved energy reserves, modulated energy metabolism pathways, and coordinated antioxidative stress responses, ultimately enhancing swimming endurance. These findings suggest that OPs have the potential to improve exercise levels by promoting metabolism and improving energy utilization efficiency.

Pan-cancer and single-cell analysis reveal THRAP3 as a prognostic and immunological biomarker for multiple cancer types.

Background: Thyroid hormone receptor-associated protein 3 (THRAP3) is of great significance in DNA damage response, pre-mRNA processing, and nuclear export. However, the biological activities of THRAP3 in pan-cancer remain unexplored. We aimed to conduct a comprehensive analysis of THRAP3 and validate its expression levels in lung cancer. Methods: A pan-cancer analysis was conducted to study the correlation of THRAP3 expression with clinical outcome and the tumor microenvironment based on the available bioinformatics databases. The protein levels of THRAP3 were explored in lung cancer by immunohistochemistry (IHC) analysis. Single-cell sequencing (ScRNA-seq) analysis was employed to investigate the proportions of each cell type in lung adenocarcinoma (LUAD) and adjacent normal tissues, along with the expression levels of THRAP3 within each cell type. Results: THRAP3 is upregulated in multiple cancer types but exhibits low expression in lung squamous cell carcinoma (LUSC). immunohistochemistry results showed that THRAP3 is a lowly expression in LUAD and LUSC. THRAP3 elevation had a poor prognosis in kidney renal clear cell carcinoma and a prolonged survival time in kidney chromophobe, brain lower-grade glioma and skin cutaneous melanoma, as indicated by the KM curve. Single-cell analysis confirmed that the proportions of T/B cells, macrophages, and fibroblasts were significantly elevated in LUAD tissues, and THRAP3 is specifically overexpressed in mast cells. Conclusion: Our findings uncover that THRAP3 is a promising prognostic biomarker and immunotherapeutic target in multiple cancers, but in LUAD and LUSC, it may be a protective gene.

Measuring entanglement entropy and its topological signature for phononic systems.

Entanglement entropy is a fundamental concept with rising importance in various fields ranging from quantum information science, black holes to materials science. In complex materials and systems, entanglement entropy provides insight into the collective degrees of freedom that underlie the systems' complex behaviours. As well-known predictions, the entanglement entropy exhibits area laws for systems with gapped excitations, whereas it follows the Gioev-Klich-Widom scaling law in gapless fermion systems. However, many of these fundamental predictions have not yet been confirmed in experiments due to the difficulties in measuring entanglement entropy in physical systems. Here, we report the experimental verification of the above predictions by probing the nonlocal correlations in phononic systems. We obtain the entanglement entropy and entanglement spectrum for phononic systems with the fermion filling analog. With these measurements, we verify the Gioev-Klich-Widom scaling law. We further observe the salient signatures of topological phases in entanglement entropy and entanglement spectrum.

Photocatalytic Synthesis of Indanone, Pyrone, and Pyridinone Derivatives with Diazo Compounds as Radical Precursors.

We disclose herein a photocatalytic radical cascade cyclization of diazoalkanes for the divergent synthesis of important carbocycles and heterocycles. Under the optimal reaction conditions, various indanone, pyrone, and pyridinone derivatives can be obtained in moderate to good yields. Mechanistic experiments support the formation of carbon-centered radicals from diazoalkanes through the proton-coupled electron transfer process. Scale-up reaction using continuous flow technology and useful downstream application of the formed heterocycles further render the strategy attractive and valuable.

Prognostic implication of UBE2C + CD8 + T cell in neoadjuvant immune checkpoint blockade plus chemotherapy for locally advanced esophageal cancer.

BACKGROUND: Immune checkpoint blockers (ICBs) plus chemotherapy as neoadjuvant therapy for patients with esophageal cancer (EC) has gained substantial attention. This study aimed to investigate the early and mid-term outcome of neoadjuvant ICBs plus chemotherapy and discover immune-associated predictors of major pathological response (MPR) for locally advanced EC. METHOD: Patients with locally advanced EC who received neoadjuvant ICBs plus chemotherapy were retrospectively included between June 2019 to December 2021. Conjoint analysis of Bulk-RNA seq (GSE165252) and scRNA seq (GSE188900) were used to investigate potential prognostic factors and immunological mechanisms, then multiplexed immunofluorescence was applied to validate. RESULTS: 76 patients were included. A total of 21 (27.6 %) patients achieved MPR, with 13 (17.1 %) attaining a pathological complete response. Over a median follow-up of 1.8 years, 6 (7.9 %) patients died and 21 (27.6 %) experienced disease recurrence within 0.6 to 2.1 years after surgery. The overall survival rate and recurrence-free survival rate were 93.3 + 2.9 % and 84.8 + 4.2 % at 12 months, 90.8 + 3.7 % and 67.1 + 6.4 % at 24 months, and 90.8 + 3.7 % and 62.9 + 7.2 % at 36 months, respectively. Patients achieving MPR had a significantly lower risk of recurrence compared to non-responders (9.5 % vs 34.5 %, P = 0.017). Analysis of bulk-RNA seq and scRNA-seq revealed that UBE2C and UBE2C + CD8 + T cells were adverse prognostic factors. Immunohistochemistry demonstrated that the non-MPR group had a higher infiltration of UBE2C + immune cells than MPR group after neoadjuvant treatment. Multiplexed immunofluorescence confirmed that infiltrating UBE2C + CD8 + T cells in MPR group were significantly fewer than non-MPR group after neoadjuvant treatment, indicating their poor prognostic role for EC. CONCLUSIONS: Neoadjuvant ICBs plus chemotherapy shows promising efficacy in locally advanced EC, with MPR being a significant predictor of lower recurrence risk. Immunological analyses identified UBE2C + CD8 + T cells as adverse prognostic factors, suggesting their potential as biomarkers for patient stratification and treatment response.

A novel IQ mismatch compensation method in wideband direct-conversion receivers.

Direct-conversion receivers (DCRs) have been widely used in recent years due to their small size and low power consumption. However, the mismatch between the in-phase (I) and the quadrature (Q) branches will seriously affect the performance of the DCRs. This paper proposes a novel blind compensation method to suppress the interference introduced by IQ mismatch. Based on the Hilbert transform, our proposed method can obtain the orthogonal signal of the I-channel signal by utilizing the Weaver architecture. Compared with traditional compensation methods, the main difference of the proposed method is that it ignores prior information, training sequences, and additional hardware circuits. Furthermore, the complexity of the proposed blind compensation method is low because no iterative operations are involved in the compensation process. The simulation results show that the proposed method has an excellent compensation performance, especially in wideband applications.

GRK2-YAP signaling is implicated in pulmonary arterial hypertension development.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown. METHODS: GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2 -knockout mice ( Grk2ΔSM22 ), and littermate controls ( Grk2flox/flox ) were grouped into control and hypoxia mice ( n  = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP ) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2'-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. RESULTS: The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2ΔSM22 mice compared with littermate controls. The amelioration of PH in Grk2ΔSM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2 . We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. CONCLUSION: Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Characterization of dicaffeoylspermidine derivatives related glucosyltransferases during fruit development of goji berry.

The fruit of Lycium barbarum (Lb), known as red goji berry, is a "superfruit" due to its abundance of bioactive compounds. Among these compounds, dicaffeoylspermidine derivatives (DCSPDs) have anti-oxidant and anti-Alzheimer's Disease activity. This study employed ultra-high-performance liquid chromatography with tandem mass spectrometry to investigate metabolic changes during the development and ripening stages of red goji berries. Totally 97 compounds, including 51 DCSPDs, were tentatively identified. Correlation analysis of these DCSPDs revealed that glycosyltransferases (GTs) play an important role in the formation of glycosylated DCSPDs. In vitro experiments characterized 3 novel GTs could add a glucosyl moiety to N1-caffeoyl-N10-dihydrocaffeoyl spermidine. Homologous GTs from L. ruthenicum (Lr) exhibited similar activity, despite the absence of abundant glycosylated DCSPDs in Lr. These findings provide insights into the metabolic changes and interconnections among active compounds in red goji berries. The identified GTs hold potential for metabolic engineering of DCSPDs and functional food development.

Neutral polysaccharide from Gastrodia elata alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis-mediated neuroinflammation via the NRF2/HO-1 signaling pathway.

AIMS: The crosstalk between ferroptosis and neuroinflammation considerably impacts the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Neutral polysaccharide from Gastrodia elata (NPGE) has shown significant effects against oxidative stress and inflammation. This study investigated the potential effects of NPGE on CIRI neuropathology. METHODS: The effects of NPGE were studied in a mouse model of ischemic stroke (IS) and in oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cells. RESULTS: NPGE treatment decreased neurological deficits, reduced infarct volume, and alleviated cerebral edema in IS mice, and promoted the survival of OGD/R-induced HT22 cells. Mechanistically, NPGE treatment alleviated neuronal ferroptosis by upregulating GPX4 levels, lowering reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+ excessive hoarding, and meliorating GSH levels and SOD activity. Additionally, it inhibited neuroinflammation by down-regulating the level of IL-1ß, IL-6, TNF-α, NLRP3, and HMGB1. Meanwhile, NPGE treatment alleviated ferroptosis and inflammation in erastin-stimulated HT22 cells. Furthermore, NPGE up-regulated the expression of NRF2 and HO-1 and promoted the translocation of NRF2 into the nucleus. Using the NRF2 inhibitor brusatol, we verified that NRF2/HO-1 signaling mediated the anti-ferroptotic and anti-inflammatory properties of NPGE. CONCLUSION: Collectively, our results demonstrate the protective effects of NPGE and highlight its therapeutic potential as a drug component for CIRI treatment.