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.

Objective: To evaluate the comprehensive intervention effect of lunch for primary and secondary school students in Minhang District, so as to provide a theoretical and practical basis for lunch intervention in school. Methods: From October to December 2023, a convenience sampling method was used to select 1 937 students from one primary and secondary school in Minhang District.A comprehensive intervention measure focusing on "reducing oil and salt" for lunch recipe optimization and nutrition education was carried out, and a questionnaire survey was conducted to evaluate the intervention effect three months later. Chi square test and Wilcoxon rank test were used to compare the data before and after the intervention. Results: After intervention, the use of cooking oil and salt, the supply of protein and fat in primary and secondary school lunches were reduced, and had no obvious impact on energy and other major nutrients. After intervention, compared to before intervention, the proportion of primary school students who felt that lunch was greasy decreased (8.9%, 6.2%, χ 2=4.35), and the proportion of primary and secondary school students who felt that lunch were delicious decreased significantly (33.2%, 23.2%; 63.9%, 53.5%, χ 2=26.39, 17.52) ( P < 0.05 ). Secondary school students also felt reduced variety of food ingredients (46.9%, 38.3%, χ 2=16.05, P <0.05). In addition, after intervention, the total surplus rate of primary school students meals decreased (7.4%, 4.4%, χ 2=5.73), mainly reflected in the decrease of the surplus rate of staple foods (7.1%, 2.4%, χ 2=17.39), while the surplus rate of vegetable dishes increased ( 16.0 %, 21.2%, χ 2=6.01) ( P <0.05). Although there was no significant change in the total surplus rate of meals for secondary school students, the surplus rate of staple foods decreased (12.9%, 5.4%, χ 2=33.52), while the surplus rates of meat and vegetable dishes increased (11.2%, 26.9%; 17.5%, 33.2%, χ 2=74.26, 61.88) ( P <0.05). After intervention, there was no statistically significant difference in the overweight and obesity rates of primary school students ( χ 2=0.11,0.43) and secondary school students ( χ 2=0.01,0.00) compared to before intervention( P >0.05). After intervention, the lung capacity of primary school students [1 564 (1 269,1 890) mL] and sitting forward flexion [11.3 (7.6, 15.2) cm] increased compared to before intervention [1 522 (1 259, 1 819 ) mL, 10.5 (6.3, 13.5) cm] ( Z =2.20, 4.68, P <0.01), but there was no statistically significant difference in lung capacity and sitting forward flexion of secondary school students before and after intervention ( Z =-0.46, -0.08, P >0.05). Conclusion The comprehensive intervention of school lunch has promoted a significant decrease in the use of oil and salt in lunch and improved the quality of recipes, and has a positive impact on the situation of leftover lunch and the health of students to a certain extent.

To study the differences in transcript levels among different organs of Spatholobus suberectus and to explore the genes encoding enzymes related to the catechin biosynthesis pathway, this study utilized the genome and full-length transcriptome data of S. suberectus as references. Transcriptome sequencing and bioinformatics analysis were performed on five different organs of S. suberectus-roots, stems, leaves, flowers, and fruits-using the Illumina NovaSeq 6000 platform. A total of 115.28 Gb of clean data were obtained, with GC content values ranging from 45.19% to 47.54%, Q20 bases at 94.17% and above, and an overall comparison rate with the reference genome around 90%. In comparisons between the stem and root, stem and leaf, stem and flower, and stem and fruit, 10 666, 9 674, 9 320, and 5 896 differentially expressed genes(DEGs) were identified, respectively. The lowest number of DEGs was found in the stem and root comparison group. KEGG enrichment analysis revealed that the DEGs were mainly concentrated in the pathways of phytohormone signaling, phenylalanine biosynthesis, etc. A total of 39 genes were annotated in the catechin biosynthesis pathway, with at least one highly expressed gene found in all organs. Among these, PAL1, PAL2, C4H1, C4H3, 4CL1, 4CL2, and DFR2 showed high expression in the stems, suggesting that they may play important roles in the biosynthesis of flavonoids in S. suberectus. This study aims to provide important information for the in-depth exploration of the regulation of catechin biosynthesis in S. suberectus through transcriptome analysis of its different organs and to provide a reference for the further realization of S. suberectus varietal improvement and molecular breeding.
Catechin/biosynthesis* ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Fabaceae/metabolism* ; Transcriptome ; Flowers/metabolism* ; Plant Stems/metabolism* ; Plant Leaves/metabolism* ; Plant Roots/metabolism* ; Fruit/metabolism*

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

Objective:To investigate the correlation between the hemodynamic pattern of non-culprit vessel stenosis and long-term vessel-oriented composite outcome(VOCO) in patients with acute ST-segment elevation myocardial infarction (STEMI).Methods:From January 2019 to December 2021, 233 consecutive patients with STEMI and non-culprit vessel stenosis were prospectively enrolled at Shanghai East Hospital. The median follow-up duration was 3.9 years. The 367 non-culprit vessels of the 233 patients were divided into the VOCO group (33 vessels, 9.0%) and the non-VOCO group (334 vessels, 91.0%). Parameters pertaining to the hemodynamic pattern of non-culprit vessel stenosis between the two groups were compared. Receiver operating characteristic (ROC) curves were used to assess the correlation between hemodynamic pattern and VOCO, and Cox multivariate regression and logistic multivariate regression analyses were applied to identify independent predictors of VOCO.Results:The 233 enrolled patients were aged (62.5±12.9) years, with 193 males (82.8%). In the VOCO group, the maximum quantitative flow ratio (QFR) decreased within 20 mm of the QFR-assessed segment, the difference in QFR across the entire vessel, the length of functionally significant vessel, and the maximum gradient of QFR decrease (dQFR/dsmax) were significantly greater than those in the non-VOCO group. ROC curve analysis showed that the optimal threshold for predicting VOCO using dQFR/dsmax was 0.009 6 (area under the curve: 0.691, 95% CI: 0.606-0.775, P<0.001). Multivariable Cox regression analysis revealed that dQFR/dsmax was an independent predictor of VOCO ( HR=1.199, 95% CI: 1.070-1.343, P=0.002). When anatomical and functional stenosis severities were included in the model, a high pullback pressure gradient (PPG) index ( HR=1.572, 95% CI: 1.052-2.351, P=0.027) emerged as an independent predictor of VOCO. Multivariable logistic regression analysis revealed that a low PPG index( OR=2.851, 95% CI: 1.945-4.178, P<0.001) was an independent predictor of QFR≤0.80 without long-term VOCO. Conclusion:In patients with STEMI, localized hemodynamic patterns of coronary artery stenosis, characterized by high dQFR/dsmax and high PPG index, are associated with long-term VOCO.

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

AIM To evaluate the chemical constituent consistency in formula granules and traditional decoctions of Gouteng Jiangya Formula.METHODS HPLC characteristic chromatograms were established,the analysis was performed on a 30 ℃ thermostatic YMC-Triart C18 column(4.6 mm× 250 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.Puerarin was used as an internal standard to calculate the relative correction factors of 3'-methoxy puerarin,puerarin apioside,magnolflorine,paeoniflora,daidzin,baicalin,palmatine,berberine,wogonoside and benzoylpaeoniflorin,after which the content detemination was made by quantitative analysis of multi-components by single-marker(QAMS).RESULTS The characteristic chromatograms of 9 batches of formula granules and 15 bacthes of traditional decoctions demonstrated the similarities of more than 0.90 at the detection wavelengths of 192,210,240,260,280,300,320,360 nm,along with similar total peak areas.Eleven constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 97.27％-101.64％with the RSDs of 0.36％-1.11％,the result obtained by QAMS and external standard method demonstrated no significant differences(P＞0.05).The contents of various constituents in the formula granules approximated those in the traditional decoctions.CONCLUSION The consistent kinds and contents of various constituents are obversable in formula granules and traditional decoctions of Gouteng Jiangya Formula,which can provide a reference for the reasonable clinical application of this formula.

Objective To develop a deep learning method for small sample multi-omics data using attention mechanism and Meta-learning for the establishment of autism diagnosis model.Methods MLAN(Meta-learning based attentive network)consisting of the omics feature pre-reduction module,the multi-omics data fusion and feature learning module,and the parameter optimization module was designed.Firstly,differential expression analysis was performed on high-dimensional multi-omics data to preliminarily screen out unimportant features.Secondly,a multi-channel attention mechanism was used to learn the importances of every set of omics data and to realize data fusion,and a two-layer fully connected network was constructed to further extract latent features and realize the diagnosis task.Finally,the Meta-learning algorithm Reptile was used to optimize the initial parameters of the above model to obtain the optimal parameters.A total of 58 children's saliva samples were collected,including 21 children diagnosed with autism,12 children with social disorders,and 25 healthy controls,and the protein and metabolomics data were detected by mass spectrometry.All data were randomly divided into training set and test set by 4∶1,and the training set was divided into training data and validation data in the same way for model training and validation.The test set was used for the final evaluation of the model effect.Five baseline models and three ablated models were constructed and evaluated along with MLAN based on metrics including multi-classification accuracy,F1-macro and F1-weighted scores.Results The constructed multi-classification autism diagnosis model MLAN achieved multi-classification accuracy,F1-macro and F1-weighted scores of 0.850±0.066,0.817±0.103 and 0.834±0.087.The values of all three indicators were better than those of baseline models and the ablated models.Conclusion The proposed MLAN can effectively deal with heterogeneous multi-omics data with small samples and achieve good results,which is expected to provide assistance for the clinical diagnosis of autism.

AIM To compare total sugar,total protein,total phenol,total flavonoid,calycosin-7-O-β-D-glucoside,liquiritin,lobetyolin,quercetin,isoferulic acid,hesperidin,glycyrrhizic acid contents and their antioxidant activities,hypoglycemic activities of big honey pill,small honey pill,water pill,concentrated pill,granule,mixture and decoction of Buzhong Yiqi Recipe.METHODS Anthraquinone-sulfuric acid method,Coomassie brilliant blue method,Folin-phenol colorimetry method,sodium nitrite-aluminum nitrate method and HPLC were adopted in the content determination of total sugar,total protein,total phenol,total flavonoid and seven constituents,respectively,after which the scavenging capacities,reducing powers on DPPH·free radical,ABTS+free radical,hydroxyl free radical,and inhibition capacity on α-glucosidase activity were detected.Subsequently,correlation analysis was performed.RESULTS Total sugar,total protein,total phenol and total flavonoid contents demonstrated significant differences among different dosage forms(P＜0.05,P＜0.01).Calycosin-7-O-β-D-glucoside,glycyrrhizin,codonoside and quercetin displayed the highest contents in the decoction,while those of isoferulic acid,hesperidin and glycyrrhizin were observable in the mixture.The water pill exhibited the strongest antioxidant activity,while those of the concentrated pill and mixture were weak;the big honey pill exhibited the strongest hypoglycemic activity,while that of the decoction was the weakest.Total protein,total phenol,total flavonoid and liquiritin contents displayed significant positive correlations between antioxidant activity(P＜0.05,P＜0.01),while hesperidin content displayed significant negative correlation between the latter(P＜0.05);total protein,calycosin-7-O-β-D-glucoside,codonoside and quercetin contents displayed significant negative correlations between hypoglycemic activity(P＜0.05,P＜0.01).CONCLUSION Active constituent contents and their biological activities of Buzhong Yiqi Recipe with different dosage forms exist differences,total sugar,total protein,total flavonoids,calycosin-7-O-β-D-glucoside,licorice glycoside,hesperidin,codonoside and quercetin can be taken as quality control indices for this prescription.

AIM To study the chemical constituents from the water fraction of rhizoma of Smilax trinervula Miq.and their biological activities.METHODS Polyamide,silica gel,Sephadex LH-20,ODS and semi-preparative HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT mothod,and the inhibitory activities on α-glucosidase were determined by PNPG method.RESULTS Eleven compounds were isolated and identified as tyrosine(1),uridine(2),2-(2',3',4'-trihydroxybutyl)-6-(2",3",4"-trihydroxybutyl)-pyrazine(3),2-(1',2',3',4'-tetrahydroxybutyl)-6-(2",3",4"-trihydroxybutyl)-pyrazine(4),2-(1',2',3',4'-tetrahydroxybutyl)-5-(2",3",4"-trihydroxybutyl)-pyrazine(5),uracil(6),2-(1',2',3',4'-tetrahydroxybutyl)-5-(1",2",3",4"-tetrahydroxybutyl)-pyrazine(7),dioscin(8),shikimic acid(9),pyrazine(10),3,4-dihydroxyphenyethyl alcohol 8-O-β-D-glycopyranoside(11).The IC50 values of compounds 8 to human breast cancer cell MCF-7 was(2.36±0.26)μg/mL,and the IC50 values of compounds 3-5 and 7 to α-glucosidase were(1.54±0.15)-(10.53±0.38)μg/mL.CONCLUSION Compounds 1-7,10 are isolated from Smilax genus for the first time,and compound 9,11 are first isolated from this plant.Compound 8 has anti-tumor activity,and compounds 3-5,7 have α-glucosidase inhibitory activities.