ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Organoid technology has become a highly promising in vitro model in biomedical research, but its traditional culture relies on animal-derived basement membrane matrices, which suffer from batch-to-batch variability, undefined biochemical composition, and poorly controllable mechanical properties. Recent studies have confirmed that matrix stiffness, viscoelasticity, topography, and temporal mechanical dynamics play regulatory roles equally as critical as biochemical signals in stem cell self-organization, lineage specification, and functional maturation of organoids. This review systematically summarizes the progress in understanding how extracellular matrix (ECM) mechanical properties regulate organoid formation. Focusing on the YAP/TAZ factors and the integrin receptors, which engage in crosstalk with biochemical signals to synergistically determine cell fate. We then elaborate how specific mechanical parameters, such as stiffness, viscoelasticity, and topography, influence each distinct stage of organoid development, from initial aggregation and compaction, through proliferative expansion, to lineage-committed differentiation and terminal functional maturation. Appropriate stiffness facilitates efficient aggregation and symmetry breaking, while excessive rigidity impairs proliferation and accelerates cellular senescence. In hepatic organoid expansion where only stiffness matching liver tissue(~6.2 kPa) supported robust growth. Viscoelastic stress relaxation promotes integrin clustering, enhances focal adhesion maturation, and stimulates endogenous ECM deposition, thereby supporting self-organized crypt-villus architecture and basement membrane assembly. Notably, dynamic softening of hydrogels enables optimal crypt budding, whereas rapid stress relaxation permits nephron segment coiling and drives vascular organoid maturation toward arteriole differentiation, highlighting stress relaxation as a key temporal parameter. Topographical cues provide contact guidance that directs polarized outgrowth, lumen formation, and neuronal orientation, all of which are essential for achieving organotypic architecture. The embedded 3D printing of complex neural networks enables precise control over branching geometries, facilitating studies of morphogenesis under spatial constraints. The engineered mechanical microenvironments have been successfully applied to recapitulate disease phenotypes: stiff matrices induce fibrosis and epithelial-mesenchymal transition in liver organoids, promote chemoresistance in cholangiocarcinoma. Furthermore, we summarize engineering strategies for both natural and synthetic hydrogels aimed at creating mechanically defined culture platforms. Natural biomaterial modifications achieve spatial separation of mechanical constraints from biochemical support, enabling self-limited compressive stimulation within a defined time window. Synthetic polymers allow independent tuning of stiffness, ligand density, and viscoelasticity through adjustable crosslinking and dynamic non-covalent interactions, thus providing orthogonal control over multiple mechanical parameters. Dynamic microenvironments that mimic progressive stiffening as observed in development, tumor evolution, or fibrosis can be constructed using composites that undergo spontaneous structural transitions. In the future, critical challenges include deciphering the synergistic rules governing mechanical-biochemical interplay, developing spatiotemporally programmable hydrogels that enable on-demand modulation of local mechanics, establishing comprehensive databases of tissue-specific mechanical parameter windows, and advancing standardized high-throughput screening platforms to accelerate preclinical validation and clinical translation. Moreover, integrating real-time mechanical sensors and non-invasive imaging techniques would allow dynamic monitoring of intracellular forces and tissue-level stress during culture. Ultimately, this review aims to provide a theoretical foundation for deepening our understanding of mechano-biological coupling mechanisms and for rationally designing high-fidelity, physiologically relevant organoid culture platforms that fully harness the regulatory power of mechanical cues.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

AIM To compare the effects of Shaoling Formula emulsion versus its decoction on epidermal barrier function in a psoriasis mouse model.METHODS The Shaoling Formula emulsion was prepared by emulsification,whereas the decoction was produced by aqueous extraction.A psoriasis-like mouse model was established by topical application of 5％imiquimod cream(50 mg).The mice were randomly assigned to normal control,model control,Shaoling Formula emulsion group(13.26 g/kg),Shaoling Formula decoction group(13.26 g/kg),blank emulsion group,and positive control group(calcipotriol betamethasone ointment group,2.5 g/kg).After treatment for six consecutive days,the mice had their severity of skin lesions assessed with psoriasis area and severity index(PASI)scoring.Upon the completion of the treatment,the mice had transepidermal water loss(TEWL)and stratum corneum hydration(SCH)determined by the GPSkin Barrier;their histopathological changes in skin lesions observed using HE staining;their levels of TNF-α,IL-6,IL-17A,IL-22,and IL-23 in lesions detected by ELISA;and their Aquaporin 3(AQP3)expression analyzed by Western blot.RESULTS Compared to the model group,both the Shaoling Formula emulsion and positive control group demonstrated significant reductions in PASI scores(P＜0.01)and increased SCH(P＜0.01);decreased serum levels of TNF-α,IL-6,IL-17A,IL-22 and IL-23(P＜0.05,P＜0.01);histopathological improvements including attenuated parakeratosis/hyperkeratosis,reduced acanthosis,diminished dermal inflammatory cell infiltration,and normalized vasodilation;and upregulated AQP3 expression(P＜0.05).The Shaoling Formula decoction group exhibited reduced PASI scores(P＜0.01);and increased SCH(P＜0.05);decreased levels of IL-6,IL-17A,IL-22 and IL-23 in skin lesions(P＜0.05,P＜0.01).Notably,the emulsion group exhibited higher AQP3 protein expression than the decoction group(P＜0.05).CONCLUSION Shaoling Formula emulsion outperforms its decoction in restoring epidermal barrier function in psoriatic mice.This superiority is mechanistically linked to enhanced AQP3 protein expression and improved SCH.

Food,drug and environment related cases are becoming more and more frequent,and the demand for on-site rapid detection is also increasing.Nanozymes are nanomaterials with enzyme-like catalytic activity,which have the advantages of high catalytic efficiency,good stability,economy,adjustability,multifunctionality and large-scale preparation.The colorimetric sensing technology based on nanozymes combined with smart phones has wide range of applications in the field of food,drugs and environment detection,and is expected to become an important means for relevant departments to combat crime.This paper summarized the progresses of nanozymes in the field of environmental,food and drug crime(EFDC)detection,focusing on the detection mechanism of different types of nanozymes and the current status of research on the detection of EFDC,and prospected the future development of nanozymes.The possible future prospects of machine learning(ML)in the field of nanozymes colorimetric sensing technology and the challenges in detection of EFDC were also discussed.

Cyclic GMP-AMP synthase(cGAS)is a congenital immune sensor that can recognize cytoplasm abnormal dsDNA.By catalyzing the second messenger cyclic GMP-AMP(cGAMP)formation,it activates stimulator of interferon genes(STING),releases type Ⅰ interferon and inflammatory cytokines,activates the host immune response,and participates in cerebral ischemia reperfusion injury(CIRI)cascade reaction.This article reviews the research progress of the mechanism of cGAS-STING signaling pathway participation in CIRI,hoping to provide ideas for its treatment.

Objective:To investigate the impact of fibroblast growth factor(FGF)on recurrence following segmen-tal mastectomy in patients with plasma cell mastitis.Methods:A total of 162 female patients diagnosed with plasma cell mastitis(PCM)were selected from our hospital from October 2021 to May 2023.All patients underwent segmental mastectomy.They were divided into recurrence group(n=28)and non-recurrence group(n=134)according to the follow-up survey on recurrence.Conduct a univariate analysis on the factors influencing recurrence in patients with PCM who undergo segmental mastectomy.After correcting for confounding factors,conduct a multiple linear regression analysis.Using a multivariate logistic regression model to explore the independent risk factors for recurrence in patients undergo-ing segmental mastectomy for PCM.Utilizing logistic regression analysis to explore the independent,multiplicative,or additive interaction between FGF and angiogenic factor in the management of recurrence in PCM patients undergoing segmental mastectomy.The Local Weighted Regression Scatter Method(LOWESS)is used to analyze the two-dimensional curve relationship of continuous variables.Evaluate the predictive efficacy of FGF for PCM recurrence fol-lowing segmental mastectomy using Receiver Operating Characteristic(ROC)curves.Results:The results of univariate analysis showed that the body mass index(BMI),estradiol,prolactin levels,nipple depression,and sinus phase propor-tion of patients in the recurrent group were significantly higher than those in the non recurrent group,and the differ-ences were statistically significant(P＜0.05).Before surgery and 1 and 3 months after surgery,the levels of FGF,vascu-lar endothelial growth factor(VEGF),endostatin(ES),and VEGF/ES in the recurrent group were higher than those in the non recurrent group,with statistically significant differences between the groups(P＜0.05).The intra group comparison results showed that compared with before surgery,all indicators in both groups of patients were significantly reduced at 1 month after surgery(P＜0.05),while in the recurrent group,all indicators were significantly increased at 3 months after surgery(P＜0.001).Logistic regression analysis showed that patients with elevated FGF had a higher risk of recurrence in PCM(P＜0.05).LOWESS analysis found that there is a certain non-linear relationship between PCM recurrence rate and FGF.FGF has good predictive performance for PCM recurrence.After further adjusting for various confounding fac-tors such as BMI,it was found that the angiogenic factor is related to FGF.The interaction results show that there is an additive or multiplicative interaction between FGF and VEGF/ES.Conclusion:FGF elevation increases the risk of re-currence after segmental mastectomy for PCM.FGF and VEGF/ES exhibit additive or multiplicative interactions.FGF has good predictive performance for PCM recurrence.

Aim To investigate the effect of N6-methy-ladenosine(m6A)demethylase ALKBH5 on the prolif-eration and migration of cardiac fibroblasts(CFs)in-duced by high glucose.Methods Primary CFs were isolated from neonatal mouse hearts and identified u-sing optical and confocal microscopy.Cell activation was induced using a high-glucose medium(33 mmol·L-1 glucose).An ALKBH5 overexpression model was established by transfecting CFs with an ALKBH5 ex-pression vector in a high-glucose medium.The expres-sion of ALKBH5 in CFs was assessed through immuno-fluorescence staining,Western blot and RT-qPCR.Changes in m6A levels were evaluated using Dot blot a-nalysis.Additionally,Alterations in the expression of proliferating cell nuclear antigen(PCNA)and collagenⅠ,a pivotal fibrosis indicator,were measured using Western blot.The proliferation and migration ability of CFs were assessed through EdU staining and Transwell migration assay,respectively.Results Following treatment with high glucose,the expression of ALKBH5 in CFs notably decreased,while m6A level increased.This was accompanied by a significant increase in the expression of the proliferation marker PCNA and the fi-brosis marker collagen Ⅰ.Additionally,there was a sig-nificant improvement in the ability of proliferation and migration.Overexpression of ALKBH5 resulted in a significant decrease in the expressions of PCNA and collagen Ⅰ,leading to the inhibition of both proliferation and migration in CFs.Conclusion Overexpression of ALKBH5 suppresses the expression of PCNA and colla-gen Ⅰ,consequently reducing the proliferation and mi-gration of CFs,potentially through m6A methylation modification.

Since 1973,the World Symposium on Pulmonary Hypertension(WSPH)has served as a pivotal platform for the advancing research in pulmonary hypertension(PH).At the 6th WSPH in 2018,the WSPH expert group refined the definitions related to cardiopulmonary physiology and right ventricular(RV)failure,thereby underscoring the critical role of RV dysfunction in the progression of PH.With ongoing advances in the field,RV failure associated with PH has received increasing attention and is now recognized as an important determinant of the prognosis of PH.The 7th WSPH,held in Barcelona,Spain,in 2024,presented the latest perspectives on the RV pathophysiology and its interaction with the pulmonary vasculature.The symposium emphasized new insights into the pathology of RV failure,RV phenotypes across different PH subgroups,and progress in therapeutic approaches targeting RV dysfunction.Additionally,the WSPH expert group delineated prospective research directions and identified unresolved issues.This article will review the RV function-related updates from the 7th WSPH and summarize recent findings,providing a systematic review of the evolution and breakthroughs in RV function research within the context of PH.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.