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Abstract Limited research has explored the connection between consuming dietary probiotics in the diet and cancer-related deaths. This study aimed to examine how the intake levels of three different groups of dietary probiotics are associated with the risk of dying from cancer in a representative sample of adults in the United States. Using data from the USDA Food Survey Nutrient Database, researchers categorized foods based on their microbial levels as low (104 CFU/g), medium (104–107 CFU/g), or high (> 107 CFU/g). They then used Cox proportional risk regression models to assess the risk of cancer-specific death, with follow-up periods until December 31, 2019. The study included 36,894 participants aged 20 and older, representing 148,639,331 U.S. citizens. After adjusting for various factors, the results showed that low and moderate intake of probiotics significantly reduced the risk of cancer mortality, with no significant association found for high probiotic intake. The findings suggest a notable link between dietary probiotics and cancer-specific mortality, highlighting the potential impact of dietary choices on cancer survival and indicating areas for healthcare interventions.

Abstract Objective To evaluate the prognostic importance of sex in lupus nephritis (LN). Methods A retrospective cohort of 1048 biopsy-confirmed LN patients, diagnosed between January 1, 1996, and December 31, 2018, was analyzed. Demographics, clinical characteristics, laboratory findings, and renal pathology were assessed. The primary outcome was mortality, and the secondary outcomes included doubling of serum creatinine and end-stage renal disease (ESRD). Sex-associated risks were evaluated using Cox regression models. Results Among the1048 patients, 178 (17%) were male and 870 (83%) were female. Male patients exhibited more aggressive features: higher blood pressure, earlier disease onset, and elevated levels of serum creatinine (Scr), uric acid, blood urea nitrogen. Intriguingly, male patients also displayed more severe histopathological alterations, such as more total crescents, cellular crescents formations, higher level of glomerular leukocyte infiltration and Activity Index (AI), even when overall renal pathology was comparable between sexes. During a median follow-up of 112 months, mortality was registered in 141 patients (15.3%). Mortality rates were conspicuously higher in males (24.2% males vs. 13.4% females, p = 0.0029). Secondary outcomes did not show significant sex differences. Cox regression analysis highlighted male, age of renal biopsy, eGFR, and Chronicity Index (CI) as independent risk factors for survival in LN patients. Notably, infections emerged as the leading cause of mortality among LN patients, with a significant higher rate in male patients. Conclusion In our cohort with LN, there was a higher rate of all-cause mortality and proportion of infection-related death in male. Recognizing and further exploring these sex disparities is crucial for optimized LN patients care. Graphical Abstract

Abstract Background The objectives of this study were twofold: (1) to compare gait characteristics between cerebral small vessel disease (CSVD) patients with low-risk oral frailty (OF) and high-risk OF, particularly during dual-task walking (DTW); (2) to investigate the association of OF, the gait characteristics of DTW, and falls among older adults patients with CSVD. Methods A total of 126 hospitalized patients diagnosed with CSVD were recruited and classified into a low-risk group (n = 90) and a high-risk group (n = 36) based on OF status in our study. Comprehensive data pertaining to basic parameters (cadence, as well as stride time, velocity and length), variability, asymmetry, and coordination were gathered during both single-task walking (STW) and DTW. Additionally, the number of falls was calculated. Subsequently, t-test or chi-squared test was used for comparison between the two groups. Furthermore, linear regression analysis was employed to elucidate the association of the OF index-8 score and gait parameters during cognitive DTW. Also, logistic regression models were utilized to assess the independent association of OF risk and falls. Results During cognitive DTW, the high-risk group demonstrated inferior performance in terms of basic parameters (p

Abstract Magnaporthe oryzae is a devastating fungal pathogen that causes the rice blast disease worldwide. The post-translational modification of ADP-ribosylation holds significant importance in various fundamental biological processes. However, the specific function of this modification in M. oryzae remains unknown. This study revealed that Poly(ADP-ribosyl)ation (PARylation) executes a critical function in M. oryzae. M. oryzae Poly(ADP-ribose) polymerase 1 (PARP1) exhibits robust PARylation activity. Disruption of PARylation by PARP1 knock-out or chemical inhibition reveals its involvement in M. oryzae virulence, particularly in appressorium formation. Furthermore, we identified two M. oryzae 14-3-3 proteins, GRF1 and GRF2, as substrates of PARP1. Deletion of GRF1 or GRF2 results in delayed and dysfunctional appressorium, diminished plant penetration, and reduced virulence of the fungus. Biochemical and genetic evidence suggest that PARylation of 14-3-3s is essential for its function in M. oryzae virulence. Moreover, PARylation regulates 14-3-3 dimerization and is required for the activation of the mitogen-activated protein kinases (MAPKs), Pmk1 and Mps1. GRF1 interacts with both Mst7 and Pmk1, and bridges their interaction in a PARylation-dependent manner. This study unveils a distinctive mechanism that PARylation of 14-3-3 proteins controls appressorium formation through MAPK activation, and could facilitate the development of new strategies of rice blast disease control.

The breeding of flax and industrial hemp in China began in the 1950s. After the end of the 20th century, the development of related breeding technologies has been accelerating. The current main breeding techniques include cross breeding, mutagenesis, distant hybridization, utilization of male sterile flax, haploid breeding, hybrid breeding, tissue culture, transgene, gene editing, molecular marker assisted selection, and other technologies. Despite many new breeding techniques, cross breeding still are the main breeding method for flax and industrial hemp now. This paper introduced the production status, breeding history, germplasm collection, standard formulation, breeding methods, and new varieties of flax and industrial hemp. Analyzed some problems in flax and industrial hemp breeding, and put forward some suggestions.

Abstract Background The 2016 Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria redefined the poor responders as low prognosis patients. The embryo transfer strategy for POSEIDON patients remained to be addressed. This study aimed to investigate the optimized number of embryos to transfer for unexpected low-prognosis patients (POSEIDON Group 1 and Group 2) with blastocyst transfer in their first frozen cycle. Methods A retrospective cohort study of 2970 patients who underwent frozen-thawed embryo transfer (FET) between January 2018 and December 2021. Patients from POSEIDON Group 1 (N = 219) and Group 2 (N = 135) who underwent blastocyst transfer in their first FET cycles were included and divided into the elective single embryo transfer (eSET) group and the double embryo transfer (DET) group. Results For POSEIDON Group 1, the live birth rate per embryo transfer of the DET group was slightly higher than the eSET group (52.17% vs 46.15%, OR 0.786, 95% CI 0.462–1.337, P = 0.374; adjusted OR (aOR) 0.622, 95% CI 0.340–1.140, P = 0.124), while a significant increase of 20.00% in the multiple birth rate was shown. For Group 2, higher live birth rates were observed in the DET group compared to the eSET group (38.46% vs 20.48%, OR 0.412, 95% CI 0.190–0.892, P = 0.024; aOR 0.358, 95% CI 0.155–0.828, P = 0.016). The difference in the multiple birth rate was 20.00% without statistical significance. Univariate and multivariate analyses revealed that age (OR 0.759, 95% CI .624–0.922, P = 0.006 and OR 0.751, 95% CI 0.605–0.932, P = 0.009) and the number of transferred embryos (OR 0.412, 95% CI 0.190–0.892, P = 0.024 and OR 0.367, 95% CI 0.161–0.840, P = 0.018) were significant variables for the live birth rate in POSEIDON Group 2. Conclusions The findings in the present study showed that eSET was preferred in the first frozen cycle for POSEIDON Group 1 to avoid unnecessary risks. Double embryo transfer strategy could be considered to improve the success rate for POSEIDON Group 2 with caution. Further stratification by age is needed for a more scientific discussion about the embryo transfer strategy for POSEIDON patients.

Non-optimal temperature is a leading risk factor for global disease burden. Most epidemiological studies assessed only outdoor temperature, with important uncertainties on personal exposure misclassification. The CKB-Air study measured personal, household (kitchen and living room), and outdoor temperatures in the summer (MAY-SEP 2017) and winter (NOV 2017-JAN 2018) in 477 participants in China. After data cleaning, ∼88,000 person-hours of data were recorded across each microenvironment. Using multivariable linear regression (MLR) and random forest (RF) models, we identified key predictors and constructed personal temperature exposure prediction models. We used generalised additive mixed effect models to examine the relationships of personal and outdoor temperatures with heart rate. The 24-hour mean (SD) personal and outdoor temperatures were 29.2 (3.8) °C and 27.6 (6.4) °C in summer, and 12.0 (4.0) °C and 7.5 (4.2) °C in winter, respectively. The temperatures across microenvironments were strongly correlated (Spearman’s ρ: 0.86–0.92) in summer. In winter, personal temperature was strongly related to household temperatures (ρ: 0.74–0.79) but poorly related to outdoor temperature (ρ: 0.30). RF algorithm identified household and outdoor temperatures and study date as top predictors of personal temperature exposure for both seasons, and heating-related factors were important in winter. The final MLR and RF models incorporating questionnaire and device data performed satisfactorily in predicting personal exposure in both seasons (R2summer: 0.92; R2winter: 0.68–0.70). We found consistent U-shaped associations between measured and predicted personal temperature exposures and heart rate (lowest at ∼ 14.5 °C), but a weak positive linear association with outdoor temperature. Personal and outdoor temperatures differ substantially winter, but prediction models incorporating household and outdoor temperatures and questionnaire data performed satisfactorily. Exposure misclassification from using outdoor temperature may produce inappropriate epidemiological findings.

Abstract The emergence of drug-resistant Enterobacteriaceae carrying plasmid-mediated β-lactamase genes has become a significant threat to public health. Organisms in the Enterobacteriaceae family containing New Delhi metallo-β-lactamase‑1 (NDM-1) and its variants, which are capable of hydrolyzing nearly all β-lactam antibacterial agents, including carbapenems, are referred to as superbugs and distributed worldwide. Despite efforts over the past decade, the discovery of an NDM-1 inhibitor that can reach the clinic remains a challenge. Here, we identified oxidized glutathione (GSSG) as a metabolic biomarker for bla NDM-1 using a non-targeted metabolomics approach and demonstrated that GSSG supplementation could restore carbapenem susceptibility in Escherichia coli carrying bla NDM-1 in vitro and in vivo. We showed that exogenous GSSG promotes the bactericidal effects of carbapenems by interfering with intracellular redox homeostasis and inhibiting the expression of NDM-1 in drug-resistant E. coli. This study establishes a metabolomics-based strategy to potentiate metabolism-dependent antibiotic efficacy for the treatment of antibiotic-resistant bacteria.

BackgroundCardiac open-heart surgery, which usually involves thoracotomy and cardiopulmonary bypass, is associated with a high incidence of postoperative mortality and adverse events. In recent years, sarcopenia, as a common condition in older patients, has been associated with an increased incidence of adverse prognosis.MethodsWe conducted a search of databases including PubMed, Embase, and Cochrane, with the search date up to January 1, 2024, to identify all studies related to elective cardiac open-heart surgery in older patients. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence.ResultsA total of 12 cohort studies were included in this meta-analysis for analysis. This meta-analysis revealed that patients with sarcopenia had a higher risk of postoperative mortality. Furthermore, the total length of hospital stay and ICU stay were longer after surgery. Moreover, there was a higher number of patients requiring further healthcare after discharge. Regarding postoperative complications, sarcopenia patients had an increased risk of developing renal failure and stroke.ConclusionSarcopenia served as a tool to identify high-risk older patients undergoing elective cardiac open-heart surgery. By identifying this risk factor early on, healthcare professionals took targeted steps to improve perioperative function and made informed clinical decisions.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023426026.

This work investigates the nonlinear response of a conical premixed flame to dual-frequency excitation through experiments and G-equation analysis. In addition to the responses at excitation frequencies, f1 and f2, a notable flame response can also be identified at the difference frequency, fd. The fd response is particularly significant in the high-frequency regime, characterized by multiple wavelengths of both f1 and f2 on the flame front. This distinct behavior of difference-frequency response can be attributed to the spatial superposition of the intensified flame fluctuation waves at the two forcing frequencies. As the excitation enhances at either f1 or f2, the nonlinear effect suppresses the responses of the upper-part flame at both f1 and f2 while promoting the bulk flame response at fd. Based on a third-order expansion of the G-equation, it is shown that the nonlinear flame dynamics necessarily generate the observed interaction component when the flame is perturbed by dual-frequency excitations. The present results emphasize the importance of nonlinear flame dynamics in inducing flame responses at interaction frequencies, offering insights into thermoacoustic oscillations of multiple frequencies.

Abstract To investigate the hydraulic fracture extension pattern of single-hole shale during hydraulic fracturing under fluid–solid coupling, this paper utilizes seepage–stress–damage coupling software to establish a mechanical model of hydraulic fracture initiation in single-hole shale under different pore pressure increments in seven groups. The results reveal that under the action of a single-hole pressure gradient, shale is destabilized and destroyed by shale instability after two damage degradations under the coupled action of hydraulic and peripheral pressures, the fracture network is fully developed, and the stress decreases sharply. The final damage pattern of the hydraulic fracture distribution is categorized into two types: “X” and “Y”. The hydraulic gradient under hydraulic fracturing is distributed as a closed-loop strip, the hydraulic gradient decreases layer by layer from the inside to the outside, the seepage field and stress field interact with each other, and the pore water pressure and stress are coupled with each other, resulting in increasingly complete fracture development.

Abstract Objective To analyze the motion characteristics of lumbar facet joints and to observe the effect of weight-bearing on lumbar facet joints in the sitting position. Methods Ten normal subjects (5 males and 5 females) were recruited and scanned by CT, and their lumbar 3D models were reconstructed by software. The images of flexion and extension of lumbar facet joints in the sitting position were collected without weight-bearing and weight-bearing 10 kg, and the 2D model was constructed by software. The 2D-3D model was matched to restore the flexion and extension motion changes of the subjects’ lumbar spine in the sitting position. Coordinates were established in the middle of the vertebral body and copied to the facet joints. Measure and record the lumbar facet joint movement distance through coordinate system. The relevant data of facet joints were collected. Results In the L3/4 segment, after weight loading, the displacement of the left facet joint in the X axis became larger, while that in the Y axis and Z axis decreased. The displacement of the right facet joint in the X axis and Y axis increased, and the Z axis displacement decreased. The rotation angle of the bilateral facet joints also decreased. In the L4/5 segment, after loading, the displacements of the X, Y, and Z axis displacements of both sides increase, while the rotation angles of α and β increase, while the rotation angle of γ decreases. In the L5/S1 segment, the displacements of the X, Y, and Z axes on the left side decrease. The displacement of the X and Y axes on the right side decreases, while the displacement on the Z axis increases. The rotation angles of α and γ increase, and the rotation angle of the β axis decreases. Conclusion When sitting, the flexion and extension distance and rotational displacement of lumbar facet joints are not affected by weight-bearing. In addition, there is asymmetry in the movement of the left and right facet joints, and weight bearing has no effect on the asymmetry of the motion.

Background and Objectives: This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Materials and Methods: Baseline characteristics and clinical outcomes of 387 patients with LN were retrospectively collected from 2007 to 2017. PH was defined as pulmonary artery systolic pressure ≥40 mmHg assessed by resting transthoracic echocardiography. The primary endpoint was all-cause mortality. The secondary endpoint was renal events, defined as the doubling of baseline serum creatinine or end-stage renal disease. Associations between PH and outcomes were analyzed by Cox regression models. Results: A total of 15.3% (59/387) of patients with LN were diagnosed with PH, and the prevalence of PH was higher for patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 compared to those with an eGFR ≥ 30 mL/min/1.73 m2 (31.5% vs. 12.6%). Higher mean arterial pressure, lower hemoglobin, and lower triglyceride levels were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with a higher risk for death (HR: 2.01; 95% CI: 1.01–4.00; p = 0.047) and renal events (HR: 2.07; 95% CI: 1.04–4.12; p = 0.039). Conclusions: PH is an independent risk factor for all-cause mortality and adverse renal outcomes in patients with LN.

Abstract Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum‐induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta‐like1 (DLL1)/Notch‐dependent manner. Blocking DLL1 attenuates ILC3s’ effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.

Objective This study retrospectively compared the safety and efficacy of oral corticosteroid therapy (OCT) and corticosteroid pulse therapy (CPT) in the treatment of IgA nephropathy.Methods One ninety-two patients were diagnosed with IgA nephropathy and had an estimated glomerular filtration rate > 15mL/min/1.73m2 and 24-h urine protein level of 0.75-3.5g. Patients were divided into CPT and OCT groups according to the treatment protocol. The differences in the efficacy and safety between the two groups were assessed by logistic regression analysis and propensity score matching.Results Significant differences at baseline, including 24-h urine protein level and eGFR, were observed between the two groups. Logistic regression analysis indicated that the remission rate increased significantly, while the incidences of total adverse events and infections decreased in CPT group compared with the OCT group after adjusting the potential confounding factors. Forty-seven pairs of subjects are matched by using propensity score matching with similar baseline data. The results indicate that the total remission rate and complete remission rate were significantly higher, while the incidences of total adverse events were lower (p = 0.008) in the CPT group than in the OCT group. The subgroup analysis showed that CPT group was more likely to achieve remission in patients with initial 24-h urine protein levels falling into the range of 2–3.5 g and Oxford Classification of S1 or C1/2 (p

1-naphthol (1-NAP) is the main metabolite of pesticide carbaryl and naphthalene, and is also a genotoxic and carcinogenic intermediate in the synthesis of organic compound, dyes, pigment and pharmaceutical industry. In this work, two novel haptens were designed and synthesized for developing a competitive indirect enzyme-linked immunosorbent assay (ciELISA) method for 1-NAP in urine samples. The assay showed a limit of detection of 2.21 ng/mL and working range from 4.02 ng/mL to 31.25 ng/mL for 1-NAP in optimized working buffer. The matrix effect of samples was eliminated via 15-fold dilution of optimized working buffer. Good average recoveries (102.4%-123.4%) with a coefficient of variation from 11.7% to 14.7% was obtained for spiked urine samples. Subsequent instrument verification test showed good correlation between the results of ciELISA and high-performance liquid chromatography. The developed ciELISA is a high-throughput tool to monitor 1-NAP in urine, which can provide technical support for the establishment of biological exposure level for the exposure to carbaryl, naphthalene and other related pollutants.

Abstract Background This study aims to investigate the value of myocardial work (MW) parameters during the isovolumic relaxation (IVR) period in patients with left ventricular diastolic dysfunction (LVDD). Methods This study prospectively recruited 448 patients with risks for LVDD and 95 healthy subjects. An additional 42 patients with invasive measurements of left ventricular (LV) diastolic function were prospectively included. The MW parameters during IVR were noninvasively measured using EchoPAC. Results The total myocardial work during IVR (MWIVR), myocardial constructive work during IVR (MCWIVR), myocardial wasted work during IVR (MWWIVR), and myocardial work efficiency during IVR (MWEIVR) of these patients were 122.5 ± 60.1 mmHg%, 85.7 ± 47.8 mmHg%, 36.7 ± 30.6 mmHg%, and 69.4 ± 17.8%, respectively. The MW during IVR was significantly different between patients and healthy subjects. For patients, MWEIVR and MCWIVR were significantly correlated with the LV E/e’ ratio and left atrial volume index, MWEIVR exhibited a significant correlation with the maximal rate of decrease in LV pressure (dp/dt per min) and tau, and the MWEIVR corrected by IVRT also exhibited a significant correlation with tau. Conclusions MW during IVR significantly changes in patients with risks for LVDD, and is correlated to LV conventional diastolic indices, including dp/dt min and tau. Noninvasive MW during IVR may be a promising tool to evaluate the LV diastolic function.

Objective End-stage kidney disease (ESKD) patients have a higher risk of antibiotic-associated encephalopathy (AAE) than other patients. We aimed to evaluate the prevalence, risk factors and outcomes of AAE in ESKD patients.Method A retrospective study of ESKD patients treated with intravenous antibiotics in our hospital from Jan. 1, 2006, to Dec. 31, 2015 was performed. AAE was diagnosed by the modified Delphi method. Control individuals were randomly selected from the remaining patients who did not exhibit neurologic symptoms. Logistic regression analysis was used to identify risk factors for AAE as well as the association between AAE and outcome.Result A total of 2104 patients were included in the study. The prevalence of AAE in our study was 4.4% (92/2104). The multivariate logistic regression analysis revealed that anuria (OR = 8.04, 95% CI: 4.13–15.65, p

Abstract Background Color is the major ornamental feature of the Rhododendron genus, and it is related to the contents of flavonoid in petals. However, the regulatory mechanism of flavonoid biosynthesis in Rhododendron pulchrum remains unknown. The transcriptome and metabolome analysis of Rhododendron pulchrum with white, pink and purple color in this study aimed to reveal the mechanism of flavonoid biosynthesis and to provide insight for improving the petal color. Results Flavonoids and flavonols are the major components of flavonoid metabolites in R.pulchrum, such as laricitrin, apigenin, tricin, luteolin, isoorientin, isoscutellarein, diosmetin and their glycosides derivatives. With transcriptome and metabolome analysis, we found CHS, FLS, F3’H, F3′5’H, DFR, ANS, GT, FNS, IFR and FAOMT genes showed significantly differential expression in cultivar ‘Zihe'. FNS and IFR were discovered to be associated with coloration in R.pulchrum for the first time. The FNS gene existed in the form of FNSI. The IFR gene and its related metabolites of medicarpin derivatives were highly expressed in purple petal. In cultivar ‘Fenhe', up-regulation of F3’H and F3′5’H and down-regulation of 4CL, DFR, ANS, and GT were associated with pink coloration. With the transcription factor analysis, a subfamily of DREBs was found to be specifically enriched in pink petals. This suggested that the DREB family play an important role in pink coloration. In cultivars ‘Baihe', flavonoid biosynthesis was inhibited by low expression of CHS, while pigment accumulation was inhibited by low expression of F3′5'H, DFR, and GT, which led to a white coloration. Conclusions By analyzing the transcriptome and metabolome of R.pulchrum, principal differential expression genes and metabolites of flavonoid biosynthesis pathway were identified. Many novel metabolites, genes, and transcription factors associated with coloration have been discovered. To reveal the mechanism of the coloration of different petals, a model of the flavonoid biosynthesis pathway of R.pulchrum was constructed. These results provide in depth information regarding the coloration of the petals and the flavonoid metabolism of R.pulcherum. The study of transcriptome and metabolome profiling gains insight for further genetic improvement in Rhododendron.

Abstract Extracellular matrix (ECM) is characterized as widespread, abundant, and pluripotent. Among ECM members, collagen is widely accepted as one of the most prominent components for its essential structural property that can provide a scaffold for other components of ECM and the rich biological functions, which has been extensively used in tissue engineering. Emerging evidence has shown that the balance of ECM degradation and remodeling is vital to regulations of maternal–fetal interface including menstrual cycling, decidualization, embryo implantation and pregnancy maintenance. Moreover, disorders in these events may eventually lead to failure of pregnancy. Although the improvement of assisted conception and embryo culture technologies bring hope to many infertile couples, some unfavorable outcomes, such as recurrent implantation failure (RIF), recurrent pregnancy loss (RPL) or recurrent miscarriage (RM), keep troubling the clinicians and patients. Recently, in vitro three-dimensional (3D) model mimicking the microenvironment of the maternal–fetal interface is developed to investigate the physiological and pathological conditions of conception and pregnancy. The progress of this technology is based on clarifying the role of ECM in the endometrium and the interaction between endometrium and conceptus. Focusing on collagen, the present review summarized the degradation and regulation of ECM and its role in normal menstruation, endometrium receptivity and unsatisfying events occurring in infertility treatments, as well as the application in therapeutic approaches to improve pregnancy outcomes. More investigations about ECM focusing on the maternal–fetal interface interaction with mesenchymal stem cells or local immunoregulation may inspire new thoughts and advancements in the clinical application of infertility treatments. Graphical abstract

Aim: The aim of this study was to investigate the role and mechanism of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3)-205 in renal inflammation and fibrosis in diabetic nephropathy (DN). Materials and Methods: lncRNA microarray profiling was used to examine differentially expressed lncRNAs of kidney tissues in db/db mice compared to db/m mice. Mouse mesangial cells (mMCs) were cultured in vitro with advanced glycation end products (AGEs) via transfection with lncRNA MEG3-205 siRNAs or plasmids. The role of lncRNA MEG3-205 in vivo was examined in db/db mice treated with long-acting lncRNA MEG3-205 siRNA. The interaction between lncRNA MEG3-205 and let-7a was investigated using luciferase assay and RNA immunoprecipitation assay. Results: lncRNA MEG3-205 was markedly upregulated in renal tissues of db/db mice, DN patients, and AGEs-treated mesangial cells. Overexpression of lncRNA MEG3-205 promoted the secretion of pro-inflammatory cytokines and synthesis of extracellular matrix proteins in mesangial cells. Both lncRNA MEG3-205 and myeloid differentiation primary-response protein 88 (MyD88) could bind to let-7a, and lncRNA MEG3-205 overexpression can significantly rescue the silencing effect of let-7a on MyD88 protein expression in mMCs. Mechanistically, we identified that lncRNA MEG3-205 could act as a competing endogenous RNA by binding with let-7a and thus regulate MyD88. Knockdown of lncRNA MEG3-205 alleviated albuminuria and attenuated renal inflammation and fibrosis in db/db mice. Conclusion: These findings indicated an important role of the lncRNA MEG3-205/let-7a/MyD88 axis in regulating renal inflammation and fibrosis in DN. Targeting lncRNA MEG3-205 might present a promising therapeutic strategy for DN.

Abstract Background As a class of the opioid receptors, the kappa opioid receptor (KOR) has been verified to be a potential biomarker and therapeutic target for human malignant tumors. However, a thorough understanding of whether KOR affects progression of esophageal squamous cell carcinoma (ESCC) is still lacking. This study focused on exploring the effect of knocking down KOR in ESCC and its underlying mechanism. Methods Bioinformatics analysis was used to compare the different expression level of OPRK1 (KOR gene) in tumor and adjacent normal tissues, and predict the relationship between KOR expression and overall survival. RNA-sequence analysis was performed to detect the altered functions and mechanisms after down regulating KOR. The in vitro and in vivo assays were used to detect the effects of down-regulated KOR on cell proliferation, migration and invasion. Substrate gel zymography and 3D cell culture assays were used to find the effect of KOR knockdown on the degradation of extracellular matrix (ECM), and immunefluorescence was performed to detect the altered cytoskeleton. Western blotting and immunohistochemistry were used to explore the underlying mechanism pathway. Results Bioinformatics analysis revealed that the expression of OPRK1 was lower in tumor tissue than that in adjacent normal tissues, and lowered expression of KOR was associated with poorer overall survival. The in vitro assays demonstrated that down-regulation of KOR enhanced ESCC proliferation, metastasis and invasion. Western blotting revealed that down-regulation of KOR could activate PDK1-AKT signaling pathway, which actively regulated the cancer progression. Down-regulation of KOR enhanced the formation of invadopodia, secretion of matrix metalloproteinase-2 (MMP2) and rearrangement of cytoskeleton, which were positively related with the invasion of ESCC. KOR knockdown enhanced the tumor invasion and elevated the AKT phosphorylation in nude mice. The AKT kinase inhibition could reverse the effect of down-regulation of KOR. Conclusion KOR might act as a tumor suppressor in ESCC and down-regulation of KOR could enhance the ESCC tumor phenotype. Graphical abstract Video Abstract

The evidence for chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence is well established. The hepatocyte epithelium carcinogenesis caused by HBV has been investigated and reviewed in depth. Nevertheless, recent findings from preclinical and observational studies suggested that chronic HBV infection is equally important in extrahepatic cancer occurrence and survival, specifically gastrointestinal system-derived cancers. Immune microenvironment changes (immune-suppressive cytokine infiltration), epigenetic modification (N6-methyladenosine), molecular signaling pathways (PI3K–Akt and Wnt), and serum biomarkers such as hepatitis B virus X (HBx) protein are potential underlying mechanisms in chronic HBV infection-induced extrahepatic cancers. This narrative review aimed to comprehensively summarize the most recent advances in evaluating the association between chronic HBV infection and extrahepatic cancer risk and explore the potential underlying molecular mechanisms in the carcinogenesis induction of extrahepatic cancers in chronic HBV conditions.

Abstract Background This study aimed to investigate fetal and maternal outcomes in women with active lupus nephritis (LN). Specifically, we compared women who had new-onset LN and those with pre-existing LN during pregnancy. Methods Patients with active LN during pregnancy were divided into the new-onset group (LN first occurred during pregnancy) and the pre-existing group (a history of LN) on the basis of the onset time of LN. Data on clinical features, laboratory findings, and pregnancy outcome were collected and analyzed between the two groups. Multivariate logistic regression analysis was used to compare the effects of active LN on adverse pregnancy outcomes. Results We studied 73 pregnancies in 69 women between 2010 and 2019. Of these, 38 pregnancies were in the pre-existing LN group and 35 were in the new-onset group. Patients with pre-existing LN had a higher risk of composite adverse fetal outcomes than those with new-onset LN [adjusted odds ratio (ORs), 44.59; 95% confidence interval (CI), 1.21–1664.82; P = 0.039]. However, the two groups had similar adverse maternal outcomes (ORs, 1.24; 95% CI, 0.36–4.29). Serum albumin and proteinuria significantly improved after pregnancy (P < 0.001). Kaplan–Meier analysis showed that the long-term renal outcome was similar between the two groups. Conclusions Pregnant patients with pre-existing LN were associated with a higher risk of composite adverse fetal outcomes than those with new-onset LN. However, these two groups of patients had similar adverse maternal outcomes. The long-term renal outcomes were not different after pregnancy between these two groups.

Docynia delavayi (Franch.) Schneid is an evergreen tree with multiple benefits and high development and utilization value. The fruit is consumed as fresh and dry fruit, juices, and other products. However, it is unknown the chemical changes that occur upon fruit maturation. The metabolite content of unripe and ripe fruit was examined using UPLC-MS/MS technology based on a broadly targeted metabolome. We identified 477 metabolites, of which 130 differed between ripe and unripe fruit. These compounds are primarily involved in the biosynthesis of secondary metabolites, such as pantothenic acid, flavonoids, and amino acids. Moreover, in ripe fruit, there are 94 metabolites that are upregulated, particularly flavonoids and terpenoids. In comparison, compounds associated with sour flavors (amino acids, phenolic acids, organic acids) are down-regulated. Remarkably, these metabolites have a strong relationship with the medicinal properties of D. delavayi. This study provides a global perspective of the D. delavayi fruit metabolome and a comprehensive analysis of metabolomic variations during fruit development, thereby increasing the knowledge of the metabolic basis of important fruit quality traits in D. delavayi fruit.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12964-022-00833-3.

This study was aimed to investigate the effect of vitamin E (Vit E) supplementation on endometrial thickness and pregnancy outcomes in infertile women. The literature was screened by two researchers and the data was extracted by searching published literature from 1999 to 2020 in the Cochrane library, PubMed, and Embase database. Seven clinical trials were included, with a total of 652 subjects. Here we found the mean endometrium was thicker in Vit E treatment group than that in the control group [SMD = 0.57, 95% CI (0.26, 0.87), P = 0.0002]. Subgroup analysis showed that no significant effect between administration of 400 IU (267 mg) or 100 mg Vit E per day. There was no significant difference between with or without Vit E on ongoing pregnancy rate [OR = 1.08, 95% CI (0.72, 1.62), P = 0.70]. The current evidence demonstrates that Vit E supplementation may increase endometrial thickness in women of reproductive age.

In this paper, the history of flax breeding, the types, research methods, occurrence, and genetic mechanism of apomixis were reviewed. The development and genetic mechanism of apomixis in polyembryonic flax, the progress in inducing methods and other aspects was discussed by cytology, embryology, genetics, and molecular biology, etc., methods in this paper. The purpose of this study was to reveal the rules of apomixis and to improve the utilization efficiency of apomixis in breeding. The problems existing in apomixis breeding of polyembryonic flax and the research direction of apomixis of flax were put forward.

Abstract Background The 5-hydroxytryptamine 1B receptor (5-HT1B) plays an essential role in the serotonin (5-HT) system and is widely involved in a variety of brain activities. HTR1B is the gene encoding 5-HT1B. Genome-wide association studies have shown that HTR1B polymorphisms are closely related to multiple mental and behavioral disorders; however, the functional mechanisms underlying these associations are unknown. This study investigated the effect of several HTR1B haplotypes on regulation of gene expression in vitro and the functional sequences in the 5′ regulatory region of HTR1B to determine their potential association with mental and behavioral disorders. Methods Six haplotypes consisting of rs4140535, rs1778258, rs17273700, rs1228814, rs11568817, and rs130058 and several truncated fragments of the 5′ regulatory region of HTR1B were transfected into SK-N-SH and HEK-293 cells. The relative fluorescence intensities of the different haplotypes and truncated fragments were detected using a dual-luciferase reporter assay system. Results Compared to the major haplotype T-G-T-C-T-A, the relative fluorescence intensities of haplotypes C-A-T-C-T-A, C-G-T-C-T-A, C-G-C-A-G-T, and C-G-T-A-T-A were significantly lower, and that of haplotype C-G-C-A-G-A was significantly higher. Furthermore, the effects of the rs4140535T allele, the rs17273700C-rs11568817G linkage combination, and the rs1228814A allele made their relative fluorescence intensities significantly higher than their counterparts at each locus. Conversely, the rs1778258A and rs130058T alleles decreased the relative fluorescence intensities. In addition, we found that regions from − 1587 to − 1371 bp (TSS, + 1), − 1149 to − 894 bp, − 39 to + 130 bp, + 130 to + 341 bp, and + 341 to + 505 bp upregulated gene expression. In contrast, regions − 603 to − 316 bp and + 130 to + 341 bp downregulated gene expression. Region + 341 to + 505 bp played a decisive role in gene transcription. Conclusions HTR1B 5′ regulatory region polymorphisms have regulatory effects on gene expression and potential correlate with several pathology and physiology conditions. This study suggests that a crucial sequence for transcription is located in region + 341 ~ + 505 bp. Regions − 1587 to − 1371 bp, − 1149 to − 894 bp, − 603 to − 316 bp, − 39 to + 130 bp, and + 130 to + 341 bp contain functional sequences that can promote or suppress the HTR1B gene expression.

Abstract Tumor metastasis accounts for the majority of cancer-related deaths; it is therefore important to develop preclinical models that faithfully recapitulate disease progression. Here, we generated paired organoids derived from primary tumors and matched liver metastases in the same colorectal cancer (CRC) patients. Despite the fact that paired organoids exhibit comparable gene expression and cell morphology, organoids from metastatic lesions demonstrate more aggressive phenotypes, tumorigenesis, and metastatic capacity than those from primary lesions. Transcriptional analyses of the paired organoids reveal signature genes and pathways altered during the progression of CRC, including SOX2. Further study shows that inducible knockdown of SOX2 attenuated invasion, proliferation, and liver metastasis outgrowth. Taken together, we use patient-derived paired primary and metastatic cancer organoids to model CRC metastasis and illustrate that SOX2 is associated with CRC progression and may serve as a potential prognostic biomarker and therapeutic target of CRC.

Abstract Background Significant progress has been made in cell replacement therapy for neural retinal diseases using retinal cells differentiated from human pluripotent stem cells. Low tumorigenicity and the ability to mature to form synaptic junctions make precursor cells a promising donor source. Here, we attempted to improve the yield of photoreceptor precursor cells in three-dimensional retinal organoids from human embryonic stem cells (hESCs). Methods A CRX-tdTomato-tagged hESC line was generated to track retinal precursors in 3D retinal organoids. COCO, a multifunctional antagonist of the Wnt, TGF-β, and BMP pathways, was employed to 3D organoid differentiation schemes for enhanced photoreceptor precursor cells. Organoid fluorescence intensity measurement was used to monitor retinalization tendency with the number of precursors further checked by flow cytometry. Signature gene expression during organoid differentiation were assessed by qPCR and immunocytochemistry after COCO supplementation. Results CRX-positive cells can be spatiotemporally tracked by tdTomato without affecting retinalization during retinal organoid differentiation. Fluorescence intensity of organoids, which turned out highly consistent with flow cytometry measurement, allowed us to determine the differentiation efficiency of precursors during organoid culturing directly. Using COCO as an auxiliary supplement, rather than alone, can yield an increased number of photoreceptor precursors in the early stage of organoid differentiation. Over a longer time-frame, photoreceptor precursors enhanced their fate of cones and decreased fate of rods after treatment with COCO. Conclusions Tracing with the CRX-reporter system showed that in retinal organoids derived from human pluripotent stem cells, COCO increased the differentiation efficiency of photoreceptor precursors and cones.

Abstract Background The CACNA1C gene was defined as a risk gene for schizophrenia in a large genome-wide association study of European ancestry performed by the Psychiatric Genomics Consortium. Previous meta-analyses focused on the association between the CACNA1C gene rs1006737 and schizophrenia. The present study focused on whether there was an ancestral difference in the effect of the CACNA1C gene rs1006737 on schizophrenia. rs2007044 and rs4765905 were analyzed for their effect on the risk of schizophrenia. Methods Pooled, subgroup, sensitivity, and publication bias analysis were conducted. Results A total of 18 studies met the inclusion criteria, including fourteen rs1006737 studies (15,213 cases, 19,412 controls), three rs2007044 studies (6007 cases, 6518 controls), and two rs4765905 studies (2435 cases, 2639 controls). An allele model study also related rs2007044 and rs4765905 to schizophrenia. The overall meta-analysis for rs1006737, which included the allele contrast, dominant, recessive, codominance, and complete overdominance models, showed significant differences between rs1006737 and schizophrenia. However, the ancestral-based subgroup analysis for rs1006737 found that the genotypes GG and GG + GA were only protective factors for schizophrenia in Europeans. In contrast, the rs1006737 GA genotype only reduced the risk of schizophrenia in Asians. Conclusions Rs1006737, rs2007044, and rs4765905 of the CACNA1C gene were associated with susceptibility to schizophrenia. However, the influence model for rs1006737 on schizophrenia in Asians and Europeans demonstrated both similarities and differences between the two ancestors.

Abstract Background Plasma fibrinogen is significantly associated with cardiovascular (CV) events and mortality in the general population. However, the association between plasma fibrinogen and mortality in patients undergoing peritoneal dialysis (PD) is unclear. Methods This was a prospective cohort study. A total of 1603 incident PD patients from a single center in South China were followed for a median of 46.7 months. A Cox regression analysis was used to evaluate the independent association of plasma fibrinogen with CV and all-cause mortality. Models were adjusted for age, sex, smoking, a history of CV events, diabetes, body mass index, systolic blood pressure, hemoglobin, blood platelet count, serum potassium, serum albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, hypersensitive C-reactive protein, estimated glomerular filtration rate, antiplatelet agents and lipid-lowering drugs. Results The mean age was 47.4 ± 15.3 years, 955 (59.6%) patients were male, 319 (19.9%) had a history of CV events, and 410 (25.6%) had diabetes. The average plasma fibrinogen level was 4.12 ± 1.38 g/L. Of the 474 (29.6%) patients who died during follow-up, 235 (49.6%) died due to CV events. In multivariable models, the adjusted hazard ratios (HRs) for quartile 1, quartile 3, and quartile 4 versus quartile 2 were 1.18 (95% confidence interval [CI], 0.72–1.95, P = 0.51), 1.47 (95% CI, 0.93–2.33, P = 0.10), and 1.78 (95% CI, 1.15–2.77, P = 0.01) for CV mortality and 1.20 (95% CI, 0.86–1.68, P = 0.28), 1.29 (95% CI, 0.93–1.78, P = 0.13), and 1.53 (95% CI, 1.12–2.09, P = 0.007) for all-cause mortality, respectively. A nonlinear relationship between plasma fibrinogen and CV and all-cause mortality was observed. Conclusions An elevated plasma fibrinogen level was significantly associated with an increased risk of CV and all-cause mortality in patients undergoing PD.

Abstract Background The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3′ regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3′ region of HTR1B. Results We found that the haplotype, A-G-Del-C-T-Ins-A, enhanced the expression level compared to the main haplotype; A-G-Del-C-G-Ins-A; G-G-Del-C-G-Ins-G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that + 2440 ~ + 2769 bp and + 1953 ~ + 2311 bp regions both had negative effects on gene expression. Conclusions The 3′ region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B-related disorders. In addition, the HTR1B 3′ region includes several effector binding sites that induce an inhibitory effect on gene expression.

Abstract Context The H19 long noncoding RNA (lncRNA) belongs to a highly conserved, imprinted gene cluster involved in embryonic development and growth control. We previously described a novel mechanism whereby the Anti-mullerian hormone (Amh) appears to be regulated by H19. However, the relationship between circulating H19 and markers of ovarian reserve including AMH not been investigated. Objective To determine whether H19 expression is altered in women with decreased ovarian reserve. Design Experimental study. Setting Yale School of Medicine (New Haven, USA) and Gazi University School of Medicine (Ankara, Turkey). Patients or other participants A total of 141 women undergoing infertility evaluation and treatment. Intervention Collection of discarded blood samples and cumulus cells at the time of baseline infertility evaluation and transvaginal oocyte retrieval, respectively. Main outcome measure Serum and cumulus cell H19 expression. Results Women with diminished ovarian reserve (as determined by AMH) had significantly lower serum H19 expression levels as compared to controls (p

Abstract Background The low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio constitutes a strong risk predictor of cardiovascular events. However, the association between this ratio and cardiovascular death in peritoneal dialysis (PD) patients is uncertain. The study aimed to investigate whether a high LDL-C/HDL-C ratio could predict both cardiovascular and all-cause mortalities in patients on PD. Methods A total of 1616 incident patients on PD included from January 1, 2006 to December 31, 2013 were followed up with until 31 December 2018 in this single-center prospective cohort study. Participants were divided into three categories according to LDL-C/HDL-C ratio tertile. The primary endpoint was cardiovascular mortality; the secondary endpoint was all-cause mortality. Results The mean age of the study cohort was 47.5 years and the mean body mass index (BMI) was 21.6 kg/m2. During a median follow-up period of 47.6 months, 492 patients died, including 246 (50.0%) due to cardiovascular disease (CVD). A multivariate analysis revealed that the highest LDL-C/HDL-C ratio tertile was significantly associated with increased CVD mortality [hazard ratio (HR): 1.69, 95% CI: 1.24–2.29; P = 0.001] and all-cause mortality (HR: 1.46, 95% CI: 1.18–1.81; P = 0.001) relative to the lowest tertile. After adjusting for covariates, the HRs of cardiovascular and all-cause mortalities were 1.84 (95% CI: 1.25–2.71; P = 0.002) and 1.35 (95% CI: 1.03–1.77; P = 0.032). Subgroup analysis showed that the risk of CVD death rose with a higher LDL-C/HDL-C ratio among PD patients who were female, younger than 65 years old, without being malnourished (BMI ≥ 18.5 kg/m2 or albumin ≥35 g/L), and with a history of diabetes or CVD, respectively. Conclusions A high LDL-C/HDL-C ratio is an independent risk factor for both cardiovascular and all-cause mortalities among PD patients.

Peanut shell is an agricultural waste having an urgent need to be utilized. The ethanolic extract of peanut shell extract, named as PSE, having enrichment of flavonoids with neurotrophic function, can develop as dietary supplements. In cultured PC12 cells, SH-SY5Y cells and rat primary neurons, the application of PSE increased the proportion of differentiated cells. In parallel, the neuronal differentiation markers, i.e. neurofilaments, were increased at both mRNA and protein levels under PSE treatment. In revealing the signaling cascade, extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B (Akt) were activated by PSE. The PSE-induced cell differentiation was blocked by the kinase inhibitors, U0126 and LY294002. The phytochemicals within PSE, e.g. luteolin, eriodictyol and 5,7-dihydroxychromone, induced transcription of neurofilaments in cultures, which in combination could partially account for the neurotrophic functions of PSE. This result supports the waste product from peanut production could be recycled in developing high value nutraceutical products.

BackgroundAlthough the ratio of apolipoprotein B (apo B) to apolipoprotein A1 (apo A1) (apo B/apo A1) seems to be associated with mortality in hemodialysis (HD) patients, the association of apo B/apo A1 ratio with death remains not clear in peritoneal dialysis (PD) patients.AimsThe study targets to examine the relationship of apo B/apo A1 ratio with survival in patients receiving PD treatment.MethodsIn this single-center prospective observational cohort study, we enrolled 1,616 patients receiving PD treatment with a median follow-up time of 47.6 months. We used a multivariable Cox proportional hazards model to examine the relationship between apo B/apo A1 ratio and cardiovascular (CV) and all-cause mortality. The association of apo B/apo A1 ratio with atherosclerotic and non-atherosclerotic CV mortality was further evaluated by competing risk regression models.ResultsDuring the follow-up, 508 (31.4%) patients died, 249 (49.0%) died from CV events, of which 149 (59.8%) were atherosclerotic CV mortality. In multivariable models, for 1-SD increase in apo B/apo A1 ratio level, the adjusted hazard ratios for CV and all-cause mortality were 1.26 [95% confidence interval (CI), 1.07–1.47; P = 0.005] and 1.20 (95% CI, 1.07–1.35; P = 0.003), respectively. The adjusted subdistribution hazard ratios for atherosclerotic and non-atherosclerotic CV mortality were 1.43 (95% CI, 1.19–1.73; P < 0.001) and 0.85 (95% CI, 0.64–1.13; P = 0.256), respectively. For quartile analysis, patients in quartile 4 had higher CV, all-cause, and atherosclerotic CV mortality compared with those in quartile 1. Moreover, apo B/apo A1 ratio had a diabetes-related difference in CV, all-cause, and atherosclerotic CV mortality.ConclusionElevated apo B/apo A1 ratio level was significantly associated with CV, all-cause, and atherosclerotic CV mortality in patients undergoing PD. Moreover, the association was especially statistically significant in patients with diabetes.

Docynia delavayi (Franch.) Schneid is a plant used both as food and traditional folk medicine. The leaves of D. delavayi are rich in polyphenols, plants with phenolic content are known to be extremely beneficial in terms of human nutrition. In the present study, we used metabolome technology (UPLC-ESI-MS/MS) to examine the young and mature D. delavayi leaves on metabolites changes, which were then analyzed and compared. As a result, 477 metabolites (including 111 flavonoids, 47 others (consisted of nine vitamin, 18 saccharides and alcohols, and 20 unassigned metabolites), 71 phenolic acids, 52 amino acids and derivatives, 18 alkaloids, 61 lipids, 24 terpenoids, 33 nucleotides and derivatives, 18 lignans and coumarins, 12 tannins, 30 organic acids) were identified, of which 281 differentially accumulated metabolites, including 146 up-regulated metabolites and 135 down-regulated metabolites. The result of clustering and PCA analyses showed that young and mature leaves were separated, which indicated that there was a great difference in metabolites between young and mature leaves. Meanwhile, we also found that both young and mature leaves displayed unique metabolites with important biological functions. KEGG enrichment analysis showed that 90 of the differential metabolites were mainly concentrated in 68 KEGG pathways. The result will greatly complement the existing knowledge on the D. delavayi leaves for lays a foundation for subsequent development and utilization.