Investigating the therapeutic mechanism of Jiedu-Quyu-Ziyin Fang on systemic lupus erythematosus through the ERα-miRNA-TLR7 immune axis.

Jiedu-Quyu-Ziyin Fang (JQZF) is a formula that has been empirically used for the treatment of SLE in clinical practice. JQZF has become an approved hospital prescription in China. Fifteen MRL/lpr mice were randomly divided into three groups: Model, JQZF, and JQZF + GC, with five mice in each group. Five MRL/MPJ mice were used as the Blank group. After 8 weeks of administration, peripheral blood serum was collected to detect anti-dsDNA antibodies and complement C3 levels. Spleen B cells were collected to detect the expression of TLR7 and NF-κBp65 mRNA, and correlation analysis was performed. Transcriptome sequencing analysis was also performed on spleen B cells. Further, key miRNA and key gene mRNA expression were detected by RT-qPCR, and key protein expression levels were detected by Western blot method. Bioinformatics methods predicted that ESR1 is a key target of JQZF action on SLE, hsa-miR-146a-5p is one of the key miRNAs, and KEGG pathway analysis showed that NF-κB signaling pathway is its key signaling pathway. Transcriptome sequencing of MRL/lpr mouse spleen B cells revealed that the differential genes between the JQZF and Model groups were enriched in Toll-like receptor signaling pathway, NF-κB signaling pathway, Estrogen signaling pathway, etc. Animal studies show that JQZF treatment significantly boosts serum C3 and lowers anti-dsDNA antibodies (P < 0.01). On the molecular level, JQZF suppresses TLR7 and NF-κBp65 mRNA in spleen B cells, with TLR7 mRNA positively linked to anti-dsDNA titers and negatively to serum C3. Further cellular work demonstrates that JQZF reverses the increased IRAK1 and TRAF6 expression seen after miR146a inhibition. Additionally, post-ERα inhibition, JQZF continues to upregulate miR146a and more significantly reduces TLR7 mRNA expression (P < 0.01), pointing to ERα's pivotal role in the miR146a-TLR7 axis. These results indicate JQZF alleviates SLE by adjusting the ERα-miR146a-TLR7 loop, showcasing its mechanism and therapeutic potential for SLE.

Dietary pectin and inulin: a promising adjuvant supplement for collagen-induced arthritis through gut microbiome restoration and CD4+ T cell reconstitution.

Dietary strategies rich in fiber have been demonstrated to offer benefits to individuals afflicted with rheumatoid arthritis (RA). However, the specific mechanisms through which a high-fiber diet (HFD) mitigates RA's autoimmunity remain elusive. Herein, we investigate the influence of pectin- and inulin-rich HFD on collagen-induced arthritis (CIA). We establish that HFD significantly alleviates arthritis in CIA mice by regulating the Th17/Treg balance. The rectification of aberrant T cell differentiation by the HFD is linked to the modulation of gut microbiota, augmenting the abundance of butyrate in feces. Concurrently, adding butyrate to the drinking water mirrors the HFD's impact on ameliorating CIA, encompassing arthritis mitigation, regulating intestinal barrier integrity, and restoring the Th17/Treg equilibrium. Butyrate reshapes the metabolic profile of CD4+ T cells in an AMPK-dependent manner. Our research underscores the importance of dietary interventions in rectifying gut microbiota for RA management and offers an explanation of how diet-derived microbial metabolites influence RA's immune-inflammatory-reaction.

A genomic instability-associated lncRNA signature for predicting prognosis and biomarkers in lung adenocarcinoma.

Genomic instability (GI) was associated with tumorigenesis. However, GI-related lncRNA signature (GILncSig) in lung adenocarcinoma (LUAD) is still unknown. In this study, the lncRNA expression data, somatic mutation information and clinical survival information of LUAD were downloaded from The Cancer Genome Atlas (TCGA) and performed differential analysis. Functional and prognosis analysis revealed that multiple GI-related pathways were enriched. By using univariate and multivariate Cox regression analysis, 5 GI-associated lncRNAs (AC012085.2, FAM83A-AS1, MIR223HG, MIR193BHG, LINC01116) were identified and used to construct a GILncSig model. Mutation burden analysis indicated that the high-risk GI group had much higher somatic mutation count and the risk score constructed by the 5 GI-associated lncRNAs was an independent predictor for overall survival (OS) (P < 0.05). Overall, our study provides valuable insights into the involvement of GI-associated lncRNAs in LUAD and highlights their potential as therapeutic targets.

Antiphospholipid antibodies and the risk of adverse pregnancy outcomes in patients with systemic lupus erythematosus: a systematic review and meta-analysis.

OBJECTIVE: This article aims to evaluate the magnitude of adverse pregnancy outcomes (APOs) risks associated with different antiphospholipid antibody (aPL) profiles in women with systemic lupus erythematosus (SLE). METHODS: Multiple databases were investigated to identify articles that explored the relationship between aPLs and APOs in SLE patients. A random effects model was used for calculating pooled odds ratios (OR). Stata version 15.0 was utilized to conduct the meta-analysis. RESULTS: There were 5234 patients involved in 30 studies. Overall aPL was linked to an increased incidence of any kind of APOs, fetal loss, and preterm birth. Any kind of APOs and preterm delivery were more common in patients with lupus anticoagulant (LA) positive. Anticardiolipin antibody (aCL) was associated with an increased risk of any kind of APOs and fetal loss. The association between aCL-IgM and fetal loss was also significant. Patients with anti-beta2-glycoprotein1 antibody (antiß2GP1) positivity had an increased risk of fetal loss. CONCLUSIONS: Both LA and aCL were risk factors of APOs in patients with SLE. Not only ACL, particularly aCL-IgM, but antiß2GP1 were associated with an increased risk of fetal loss, while LA appeared to indicate the risk of preterm birth.PROSPERO (CRD42023388122).

The mechanism of Langchuangding in treatment of systemic lupus erythematosus via modulating TLR7-IRF7-IFNα pathway.

Object: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by aberrant activity of the immune system. Plasmacytoid dendritic cells (pDCs) which the main producer of activated type I interferon, are related to SLE disease activity. To investigate the mechanism of Langchuangding (LCD) improving SLE based on TLR7-IRF7-IFNα pathway. Methods: SLE patients were randomly divided into Chinese medicine combined with western medicine (CWM) group and western medicine (WM) group, to observe the effect of LCD. The percent of pDCs in peripheral blood of SLE patients were detected by flow cytometry, and the influence of LCD on gene expression in SLE patients were detected by gene microarray. Mouse bone marrow cells were differentiated into dendritic like cells (DLC), then divided into Blank, immune complex (IC), LCD and dexamethasone (DXM) group. Employed RT-qPCR to detect MyD88, and IRF7 mRNA, and western blotting to determinate TLR7, MyD88, and p-IRF7 proteins. The IFNα in SLE patients were detected by enzyme-linked immunosorbent assay (ELISA). Employ dual luciferase to observe the interferon stimulated response element (ISRE) gene. Results: pDCs in WM group was higher than that of CWM group. The plasma IFNα in CWM group was significantly lower than that in WM group. The gene microarray showed that the gene expression of IFNα related signaling pathway in peripheral blood mononuclear cell (PBMC) and genes related to activation and proliferation of immune cells were down-regulated after LCD treatment. The DLCs MyD88, and IRF7 mRNA were down-regulated, TLR7, MyD88, and p-IRF7 proteins were significantly reduced, and the supernatant IFNα was significantly decreased in LCD group. LCD were mildly inhibited activation of ISRE in 293T cells. Conclusions: In certain degree, LCD is beneficial to SLE patients. LCD therapy SLE may be through TLR7 signaling pathway, and IRF7 may be a promising therapeutic target for the treatment of SLE.

Vaccination and the risk of systemic lupus erythematosus: a meta-analysis of observational studies.

OBJECTIVE: This meta-analysis aims to explore the potential link between vaccines and systemic lupus erythematosus (SLE). METHODS: We systematically searched PubMed, Cochrane Library, and Embase for observational studies from inception to September 3, 2023, using medical subject headings (MeSH) and keywords. Study quality was assessed using the NOS scale. Statistical analyses were conducted using STATA software (version 14.0). Publication bias was evaluated using funnel plots and Egger's regression. RESULTS: The meta-analysis incorporated 17 studies, encompassing 45,067,349 individuals with follow-up periods ranging from 0.5 to 2 years. The pooled analysis revealed no significant association between vaccinations and an increased risk of SLE [OR = 1.14, 95% CI (0.86-1.52), I2 = 78.1%, P = 0.348]. Subgroup analyses indicated that HBV vaccination was significantly associated with an elevated risk of SLE [OR =2.11, 95% CI (1.11-4.00), I2 = 63.3%, P = 0.02], HPV vaccination was slightly associated with an increased risk of SLE [OR = 1.43, 95% CI (0.88-2.31), I2 = 72.4%, P = 0.148], influenza vaccination showed no association with an increased risk of SLE [OR = 0.96, 95% CI (0.82-1.12), I2 = 0.0%, P = 0.559], and COVID-19 vaccine was marginally associated with a decreased risk of SLE [OR = 0.44, 95% CI (0.18-1.21), I2 = 91.3%, P = 0.118]. CONCLUSIONS: This study suggests that vaccinations are not linked to an increased risk of SLE. Our meta-analysis results provide valuable insights, alleviating concerns about SLE risk post-vaccination and supporting further vaccine development efforts.

Assessing the causal relationships of gut microbial genera with hyperuricemia and gout using two-sample Mendelian randomization.

BACKGROUND AND AIMS: The causal relationship between gut microbiota and gout and hyperuricemia (HUA) has not been clarified. The objective of this research was to evaluate the potential causal effects of gut microbiota on HUA and gout using a two-sample Mendelian randomization (MR) approach. METHODS AND RESULTS: Genetic instruments were selected using summary statistics from genome-wide association studies (GWASs) comprising a substantial number of individuals, including 18,473 participants for gut microbiome, 288,649 for serum urate (SU), and 763,813 for gout. Two-sample MR analyses were performed to determine the possible causal associations of gut microbial genera with the risk of HUA and gout using the inverse-variance weighted (IVW) method, and robustness of the results was confirmed by several sensitivity analyses. A reverse MR analysis was conducted on the bacterial taxa that were identified in forward MR analysis. Based on the results of MR analyses, Escherichia-Shigella (OR = 1.05; 95% CI, 1.01-1.08; P = 0.009) exhibited a positive association with SU levels, while Lachnospiraceae NC2004 group (OR = 0.95; 95% CI, 0.92-0.98; P = 0.001) and Family XIII AD3011 group (OR = 0.94; 95% CI, 0.90-0.99; P = 0.015) were associated with a reduced HUA risk. Moreover, Coprococcus 3 (OR = 1.17, 95% CI: 1.01-1.34, P = 0.031) was causally associated with a higher gout risk. In reverse MR analysis, no causal relationships were identified between these bacterial genera and HUA or gout. CONCLUSION: This study provides evidence for a causal association between gut microbial genera and HUA or gout, and further investigations of the underlying mechanism are warranted.

Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis.

Systemic lupus erythematosus (SLE), a severe autoimmune disorder, is characterized by systemic inflammatory response, autoantibody accumulation and damage to organs. The dysregulation of double-negative (DN) T cells is considered as a crucial commander during SLE. Neddylation, a significant type of protein post-translational modification (PTM), has been well-proved to regulate T cell-mediated immune response. However, the function of neddylation in SLE is still unknown. Here, we reported that neddylation inactivation with MLN4924, a specific inhibitor of NEDD8-activating enzyme E1 (NAE1), or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus development. Further investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells, contributing to the apoptosis of the accumulated DN T cells in lupus mice. Then double knockout (KO) lupus-prone mice (Ube2m-/-Bim-/-lpr) were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus progression. Our findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus progression. Clinically, we also found that in SLE patients, the proportion of DN T cells was raised and their apoptosis was reduced. Moreover, compared to healthy groups, SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation levels. Meantime, the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE patients. Altogether, our findings provide the direct evidence about the function of neddylation during lupus, suggesting a promising therapeutic approach for this disease.

The reporting checklist for Chinese patent medicine guidelines: RIGHT for CPM.

Existing reporting checklists lack the necessary level of detail and comprehensiveness to be used in guidelines on Chinese patent medicines (CPM). This study aims to develop a reporting guidance for CPM guidelines based on the Reporting Items of Practice Guidelines in Healthcare (RIGHT) statement. We extracted information from CPM guidelines, existing reporting standards for traditional Chinese medicine (TCM), and the RIGHT statement and its extensions to form the initial pool of reporting items for CPM guidelines. Seventeen experts from diverse disciplines participated in two rounds of Delphi process to refine and clarify the items. Finally, 18 authoritative consultants in the field of TCM and reporting guidelines reviewed and approved the RIGHT for CPM checklist. We added 16 new items and modified two items of the original RIGHT statement to form the RIGHT for CPM checklist, which contains 51 items grouped into seven sections and 23 topics. The new and revised items are distributed across four sections (Basic information, Background, Evidence, and Recommendations) and seven topics: title/subtitle (one new and one revised item), Registration information (one new item), Brief description of the health problem (four new items), Guideline development groups (one revised item), Health care questions (two new items), Recommendations (two new items), and Rationale/explanation for recommendations (six new items). The RIGHT for CPM checklist is committed to providing users with guidance for detailed, comprehensive and transparent reporting, and help practitioners better understand and implement CPM guidelines.

Mutational landscape of head and neck cancer and cervical cancer in Chinese and Western population.

BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.

Efficacy and safety of acupuncture therapy combined with conventional pharmacotherapy in the treatment of systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Currently, the mainstream treatments for systemic lupus erythematosus (SLE) are based on glucocorticoids and immunosuppressants, which are known to have considerable adverse effects. This meta-analysis is aimed at confirming the efficacy and safety of acupuncture therapy in combination with traditional medications in the treatment of SLE. METHODS: Multiple databases were searched for randomized controlled trials using acupuncture therapy in combination with conventional pharmacotherapy for the treatment of SLE, from the establishment of the database to March 2023. Study selection, data collection, as well as quality assessment were conducted by 2 reviewers independently. RevMan 5.4 and Stata 17 software were used for Meta-analysis. RESULTS: Seven eligible studies involving 514 patients with SLE were included. Meta-analysis demonstrated that in SLE patients, extra treatment with acupuncture was superior to drug therapy alone in improving the overall response rate (RR = 1.20, 95% confidence intervals [1.11, 1.29], P < .00001, heterogeneity P = .69, I2 = 0%) and regulating immunological indicators (C3, C4, IgG, T lymphocyte subpopulation, IL-6, ds-DNA, ESR) while reducing TCM symptom scores, the SLE Disease Activity Index (SLEDAI) and the incidence of adverse events on treatment (P ≤ 0.05). Additionally, it was able to reduce BUN, Scr and 24 hours urine protein, suggesting that acupuncture treatment had a protective effect on the kidneys. CONCLUSIONS: Acupuncture therapy combined with conventional pharmacotherapy is an efficient and safe way in the treatment of SLE. However, the conclusions drawn from this meta-analysis have some limitations due to the small number and uneven quality of the included studies, leading to heterogeneity and bias. Thus more relevant high-quality randomized controlled trials are needed for further evaluation in the future.

Risk factors and prognosis of interstitial lung disease for primary Sjögren syndrome patients: A retrospective case‒control study.

OBJECTIVE: To determine the prevalence, clinical features, risk factors, and prognosis of interstitial lung disease (ILD) in patients with primary Sjogren's syndrome (pSS). METHODS: Data from 274 pSS patients from August 2013 to August 2022 were reviewed. The clinical features of pSS with ILD were revealed. Logistic regression was used to determine risk factors for ILD in pSS patients. Survival analysis and Cox regression were used to analyse the prognosis and prognostic factors of pSS patients. RESULTS: In pSS patients, the prevalence of ILD was 22.3% (61/274). The pSS patients with ILD were characterized by a late onset and long disease course, with a nonspecific interstitial pneumonia (NSIP) pattern as the predominant high-resolution computed tomography (HRCT) finding. Logistic regression results indicated that an age over 50 years old (OR 4.786, 95% CI 1.602-14.299; P = 0.005), purpuric rash (OR 4.695, 95% CI 1.537-14.339; P = 0.007), AMA-M2 antibody positivity (OR 2.582, 95% CI 1.166-5.722; P = 0.019), and diabetes (OR 2.514, 95% CI 1.025-6.167; P = 0.044) were risk factors for ILD in pSS patients. Cox regression results showed that advanced age (HR 1.240, 95% CI 1.088-1.413; P = 0.001) and cancer history (HR 8.411, 95% CI 1.771-39.934; P = 0.007) were risk factors for pSS patient survival. CONCLUSION: This study showed that pSS patients with ILD tended to have a late onset and long course of pSS. An age over 50 years, purpuric rash, AMA-M2 antibody positivity, and diabetes were risk factors for ILD in pSS patients. Advanced age and cancer history were prognostic factors in pSS patients. Key Points • This study showed that pSS patients with ILD tended to have a late-onset and lengthy course of pSS, with the NSIP pattern as the predominant lung image. • The risk factors for ILD in pSS patients determined in this study were an age over 50 years, purpuric rash, AMA-M2 antibody positivity, and diabetes. • The prognostic risk factors for pSS patients were advanced age and cancer history.

Jiedu-Quyu-Ziyin Fang (JQZF) inhibits the proliferation and activation of B cells in MRL/lpr mice via modulating the AKT/mTOR/c-Myc signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiedu-Quyu-Ziyin Fang (JQZF) is a new herbal formula improved based on "Sheng Ma Bie Jia Tang" in the Golden Chamber, has been proved to be effective in the treatment of SLE. The ability of JQZF to prevent lymphocyte growth and survival has been demonstrated in earlier investigations. However, the specific mechanism of JQZF on SLE has not been fully investigated. AIM OF THE STUDY: To reveal the potential mechanisms of JQZF inhibiting B cell proliferation and activation in MRL/lpr mice. MATERIALS AND METHODS: MRL/lpr mice were treated with low-dose, high-dose JQZF and normal saline for 6 weeks. The effect of JQZF on disease improvement in MRL/lpr mice was studied using enzyme-linked immunosorbent assay (ELISA), histopathological staining, serum biochemical parameters and urinary protein levels. The changes of B lymphocyte subsets in the spleen were analyzed by flow cytometry. The contents of ATP and PA in B lymphocytes from the spleens of mice were determined by ATP content assay kit and PA assay kit. Raji cells (a B lymphocyte line) were selected as the cell model in vitro. The effects of JQZF on the proliferation and apoptosis of B cells were detected by flow cytometry and CCK8. The effect of JQZF on the AKT/mTOR/c-Myc signaling pathway in B cells were detected via western blot. RESULTS: JQZF, especially at high dose, significantly improved the disease development of MRL/lpr mice. Flow cytometry results showed that JQZF affected the proliferation and activation of B cells. In addition, JQZF inhibited the production of ATP and PA in B lymphocytes. In vitro cell experiments further confirmed that JQZF can inhibit Raji proliferation and promote cell apoptosis through AKT/mTOR/c-Myc signaling pathway. CONCLUSION: JQZF may affect the proliferation and activation of B cells by inhibiting the AKT/mTOR/c-Myc signaling pathway.

Efficacy and safety of tofacitinib combined with methotrexate in the treatment of rheumatoid arthritis: A systematic review and meta-analysis.

Objective: To evaluate the efficacy and safety of tofacitinib in combination with methotrexate (MTX) versus MTX monotherapy in patients with active rheumatoid arthritis (RA). Methods: Trials were identified from four electronic databases: PubMed, Web of science, Cochrane Library and EMBASE from inception to April 2022. Two independent reviewers evaluated each database to scan the title, abstract and keywords of each record retrieved. Full articles were further assessed when the information suggested that the study was a randomized clinical trial (RCT) comparing tofacitinib combined with MTX vs. MTX monotherapy in patients with active RA. Data were extracted from the literature, and the methodological quality of the included literature were evaluated and screened by two reviewers independently. The results were analyzed using RevMan5.3 software. The full text of the studies and extracted data were reviewed independently according to PRISMA guidelines. The outcome indicators were ACR 20, ACR 50, ACR 70, Disease activity score 28 (DAS28), erythrocyte sedimentation Rate (ESR) and adverse events (AEs). Results: Of 1152 studies yielded by the search, 4 were retained, totaling 1782 patients (1345 treated with tofacitinib combined with MTX vs 437 received MTX. In the trial of insufficient response to MTX treatment, tofacitinib combined with MTX had significant advantages compared with MTX monotherapy. Numerically higher ACR20, ACR50 and ACR70 response rates were observed in the tofacitinib combined with MTX groups versus MTX monotherapy. ACR20 (odds ratio (OR), 3.62; 95% CI, 2.84-4.61; P < 0.001), ACR50 (OR, 5.17; 95% CI, 3.62-7.38; P < 0.001), and ACR70 (OR, 8.44; 95% CI, 4.34-16.41; P < 0.001), DAS28 (ESR) < 2.6 (OR, 4.71, 95% CI, 2.06-10.77; P < 0.001). The probability of adverse events of tofacitinib combined with MTX was lower than that of MTX monotherapy (OR, 1.42; 95% CI, 1.08-1.88; P = 0.01). The number of cases discontinued due to lack of efficacy or adverse events was similar in both groups (OR, 0.93; 95% CI, 0.52-1.68). The probability of abnormal liver enzymes in the treatment of tofacitinib combined with MTX was significantly lower than that of MTX monotherapy (OR, 1.86; 95% CI, 1.35-2.56). However, there was no significant difference between the two groups in severe adverse reactions, neutropenia, anemia and cardiovascular disease. Conclusions: In terms of ACR20/50/70 and DAS28 (ESR), tofacitinib combined with MTX demonstrated superiority to MTX monotherapy in the treatment of patients with refractory RA. Considering the hepatoprotective and observably therapeutic efficacy, tofacitinib combined with MTX could be effective in treating refractory RA. However, in terms of hepatoprotective, it requires further large-scale and high-quality clinical trials to confirm.

Dietary Dried Jujube Fruit Powder (DJFP) Supplementation Improves Growth Performance, Antioxidant Stability, and Meat Composition in Broilers.

Nowadays, broiler production is faced with great challenges due to intensive culture modes, and chickens are more susceptible to oxidative stress. Consequently, synthetic antioxidants have been used to reduce this process, but their use has shown potential health risks. Thus, the use of natural ingredients has been suggested as a strategy to prevent oxidative stress. This study investigated how dietary dried jujube fruit powder (DJFP) supplementation influences the growth performance, antioxidant stability, meat composition, and nutritional quality of Cobb broilers. A total of 360 unsexed broilers (1-day-old) were randomly assigned to treatments that varied in DJFP levels: a basal diet without DJFP (control) and diets supplemented with 50 g/kg DJFP (P1), 100 g/kg DJFP (P2), and 150 g/kg DJFP (P3), with 9 replicates per treatment (90 broilers/treatment or 10 broilers/replicate). The results demonstrated improvement in the growth performance of broilers in terms of body weight (BW), body weight gain (WG), average daily body weight gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) following dietary DJFP supplementation. In addition, the antioxidant stabilities in the DJFP-treated broilers were improved and inhibited the production of lipid oxidation products compared with the control, with those in the P2 group showing the most marked effect. Moreover, dietary DJFP supplementation significantly increased (p < 0.05) the activity of antioxidant enzymes in broilers. Furthermore, the breast meat of the broilers displayed an increased protein content with a simultaneous reduction in the fat content after DJFP treatment (p < 0.05). Essential amino acid levels were higher in the DJFP-supplemented groups (p < 0.05). The sum of saturated fatty acids was lower, and that of monounsaturated fatty acids (MUFAs) and the polyunsaturated fatty acid/saturated fatty acid ratio (PUFA/SFA) were higher in the DJFP-supplemented groups (p < 0.05). Together, these results indicate that up to 100 g/kg of dietary DJFP supplementation can enhance the growth performance and antioxidant capacity, meat composition, and amino acid and fatty acid composition in broiler breast meat. In conclusion, dietary DJFP supplementation is a healthy alternative to the use of synthetic antioxidants in broiler production, especially in regions rich in jujube resources.

Ribosome footprint profiling enables elucidating the systemic regulation of fatty acid accumulation in Acer truncatum.

BACKGROUND: The accumulation of fatty acids in plants covers a wide range of functions in plant physiology and thereby affects adaptations and characteristics of species. As the famous woody oilseed crop, Acer truncatum accumulates unsaturated fatty acids and could serve as the model to understand the regulation and trait formation in oil-accumulation crops. Here, we performed Ribosome footprint profiling combing with a multi-omics strategy towards vital time points during seed development, and finally constructed systematic profiling from transcription to proteomes. Additionally, we characterized the small open reading frames (ORFs) and revealed that the translational efficiencies of focused genes were highly influenced by their sequence features. RESULTS: The comprehensive multi-omics analysis of lipid metabolism was conducted in A. truncatum. We applied the Ribo-seq and RNA-seq techniques, and the analyses of transcriptional and translational profiles of seeds collected at 85 and 115 DAF were compared. Key members of biosynthesis-related structural genes (LACS, FAD2, FAD3, and KCS) were characterized fully. More meaningfully, the regulators (MYB, ABI, bZIP, and Dof) were identified and revealed to affect lipid biosynthesis via post-translational regulations. The translational features results showed that translation efficiency tended to be lower for the genes with a translated uORF than for the genes with a non-translated uORF. They provide new insights into the global mechanisms underlying the developmental regulation of lipid metabolism. CONCLUSIONS: We performed Ribosome footprint profiling combing with a multi-omics strategy in A. truncatum seed development, which provides an example of the use of Ribosome footprint profiling in deciphering the complex regulation network and will be useful for elucidating the metabolism of A. truncatum seed oil and the regulatory mechanisms.

Methotrexate and Triptolide regulate Notch signaling pathway by targeting the Nedd4-Numb axis.

Methotrexate (MTX) is used to treat rheumatoid arthritis, acute leukemia, and psoriasis. MTX can cause certain side effects, such as myelosuppression, while the exact mechanism of myelosuppression caused by MTX is unknown. Notch signaling pathway has been considered to be essential to regulate hematopoietic stem cell (HSC) regeneration and homeostasis, thus contributing to bone marrow hematopoiesis. However, whether MTX affects Notch signaling remains unexplored. Here, our study provides evidence that MTX strongly suppresses the Notch signaling pathway. We found that MTX inhibited the interaction between Nedd4 with Numb, thus restricting K48-linked polyubiquitination of Numb and stabilizing Numb proteins. This in turn inhibited the Notch signaling pathway by reducing Notch1 protein levels. Interestingly, we found that a monomeric drug, Triptolide, is capable of alleviating the inhibitory effect of MTX on Notch signaling pathway. This study promotes our understanding of MTX-mediated regulation of Notch signaling and could provide ideas to alleviate MTX-induced myelosuppression.

Data-mining-based of ancient traditional Chinese medicine records from 475 BC to 1949 to potentially treat COVID-19.

Traditional Chinese Medicine (TCM) plays a role in preventing and treating COVID-19 in China. Based on the manifestations and symptoms of COVID-19, our study used the data mining method to summarize related therapeutic experience left by predecessors who used TCM to treat epidemics in their eras. Initially, we collected abundant medical records with similar manifestations of COVID-19 in Chinese ancient times. The key words including wen (), yi (), li (), and zhang () were searched in ZhongyiZhiku (https://www.zk120.com/) from Warring States Period (475 BC-221 BC) to the Republic of China era (1912-1949) to locate ancient medical records according to inclusion criteria and exclusion criteria. Moreover, COVID-19-related manifestations and corresponding medications in those records were categorized. Eventually, Traditional Chinese Medicine Inheritance Support System version 2.5 was used to build a medical record database of TCM treating COVID-19. Our study collected 263 epidemic medical records comprising COVID-19 related manifestations and found that Chinese Materia Medica (CMM) combinations excavated from ancient medical records included Ren Shen Bai Du San, Wu Ling San, Xiao Chai Hu Tang, Da Cheng Qi Tang, Da Chai Hu Tang, Ling Gui Zhu Gan Tang, and Qing Wen Bai Du Yin. The recurrent CMMs with a high frequency for treating COVID-19 manifestations were Scutellariae Radix (Huang Qin), Paeoniae Alba Radix (Bai Shao), Poria (Fu Ling), and Bupleuri Radix (Chai Hu). Our study suggests that TCM might offer new therapeutic strategies for COVID-19.

Deconvolution of overlapping peaks in ion mobility spectrometry based on a multiobjective dynamic teaching-learning-based optimization.

RATIONALE: Because of its powerful analytical ability, ion mobility spectrometry (IMS) plays an important role in the field of mass spectrometry. However, one of the main defects of IMS is its low structural resolution, which leads to the phenomenon of peak overlap in the analysis of compounds with similar mass charge ratio. METHODS: A multiobjective dynamic teaching-learning-based optimization (MDTLBO) method was proposed to separate IMS overlapping peaks. This method prevents local optimization and identifies peak model coefficients efficiently. In addition, the position information of particles largely reflects the half-peak width of IMS, which makes single peaks difficult to appear and coefficient identification easier. RESULTS: The performance comparison of MDTLBO with other deconvolution methods (genetic algorithm, improved particle swarm optimization algorithm, and dynamic inertia weight particle swarm optimization algorithm) shows that the maximum deconvolution error of MDTLBO is only 0.7%, which is much lower than that for the other three methods. In addition, robustness is a performance index that reflects the advantages and disadvantages of the algorithm. CONCLUSION: MBTLBO is more robust than other algorithms for separating overlapping peaks. The algorithm can separate the heavily overlapped mobility peaks, produce better analysis results, and improve the resolution of IMS.

A Promising Target of Langchuangding Prescription Treating Systemic Lupus Erythaematosus Integrated Network Pharmacology with HPLC-MS and Molecular Docking.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder affecting almost any organ system without effective treatment. Based on accumulating evidence, activated T cells are key cause promoting the pathogenesis of SLE. A traditional clinic Langchuangding formula (LCD) is an effective clinical traditional Chinese medicine prescription for SLE with few side effects and good patient compliance. However, the mechanism of how LCD affects SLE remains unclear. METHODS: Targets related to LCD and SLE were predicted and overlapped to construct protein-protein interaction (PPI) for screening core target. Subsequently, flow cytometry analysis and Western-blot method were used to verify the expression levels of target gene in LCD serum treated-Jurkat T cells. The main compounds of LCD were identified by HPLC-MS and further docked with the core targe. RESULTS: 283 protein targets in LCD, 1498 SLE targets and 150 common targets were obtained to construct protein-protein interaction (PPI). Network pharmacology results suggested that LCD was closely related to CASP3 target. To verify the prediction of pharmacological mechanism of LCD treatment for SLE, we investigated the anti-proliferative effects of LCD-treated rat serum on ß-oestradiol (300 pg/mL)-activated Jurkat T cells in vitro using a CCK-8 kit and flow cytometry analysis and then analyzed the CASP3 expression levels. Vitro experiments confirmed that LCD serum could suppress the proliferation (p < 0.05) and induce apoptosis of the activated T cells through up-regulating CASP3 expression levels. Interactions between CASP3 target and LCD were further validated integrating HPLC-MS analysis and molecular docking. CONCLUSIONS: The results showed that LCD could relieve SLE, which might be attributed to inducing the activated T cells apoptosis by up-regulating CASP3 expression levels. The network pharmacology and molecular docking approach provide a new insight for deepening understanding about TCM. LCD potentially represents a promising therapeutic prescription for SLE supplement treatment with no adverse effects.