Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis.

BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.

Does working memory training improve emotion regulation and reduce internalizing symptoms? A pair of three-level meta-analyses.

BACKGROUND: Emotional dysfunction is a core feature of many mental disorders. Working memory training (WM-T) is promising to improve emotion regulation and reduce internalizing symptoms (anxiety and depressive symptoms), but the results are mixed. Therefore, we conducted meta-analyses to clarify these mixed results. METHODS: We searched Web of Science, PubMed, ScienceDirect, and EBSCO to identify relevant studies and screened the references. The effect size was calculated using Hedges' g. Three-level, random-effects models were run using metafor in R. RESULTS: The current study included 44 articles, of which 29 were involved with emotion regulation, and 30 were involved with internalizing symptoms. The results showed that WM-T could yield emotional benefits, but the benefits were confined to enhancing explicit emotional regulation capacity and reducing anxiety symptoms. For the meta-analysis regarding the effect of WM-T on emotion regulation, there was no significant moderator. For the meta-analysis regarding the effect of WM-T on internalizing symptoms, the emotional valence of the material and control group were statistically significant moderators. CONCLUSION: WM-T could yield certain emotional effects, but only to improve explicit emotion regulation capacity and reduce anxiety symptoms. In addition, some measures could enhance the effect, such as targeting specific populations, increasing the number of training sessions (≥15) or duration (>450 minutes), using negative material, and using n-back training tasks.

Fabrication of polymeric microspheres for biomedical applications.

Polymeric microspheres (PMs) have attracted great attention in the field of biomedicine in the last several decades due to their small particle size, special functionalities shown on the surface and high surface-to-volume ratio. However, how to fabricate PMs which can meet the clinical needs and transform laboratory achievements to industrial scale-up still remains a challenge. Therefore, advanced fabrication technologies are pursued. In this review, we summarize the technologies used to fabricate PMs, including emulsion-based methods, microfluidics, spray drying, coacervation, supercritical fluid and superhydrophobic surface-mediated method and their advantages and disadvantages. We also review the different structures, properties and functions of the PMs and their applications in the fields of drug delivery, cell encapsulation and expansion, scaffolds in tissue engineering, transcatheter arterial embolization and artificial cells. Moreover, we discuss existing challenges and future perspectives for advancing fabrication technologies and biomedical applications of PMs.

Conflict Dynamics of Post-Retrieval Extinction: A Comparative Analysis of Unconditional and Conditional Reminders Using Skin Conductance Responses and EEG.

The post-retrieval extinction paradigm, rooted in reconsolidation theory, holds promise for enhancing extinction learning and addressing anxiety and trauma-related disorders. This study investigates the impact of two reminder types, mild US-reminder (US-R) and CS-reminder (CS-R), along with a no-reminder extinction, on fear recovery prevention in a categorical fear conditioning paradigm. Scalp EEG recordings during reminder and extinction processes were conducted in a three-day design. Results show that the US-R group exhibits a distinctive extinction learning pattern, characterized by a slowed-down yet successful process and pronounced theta-alpha desynchronization (source-located in the prefrontal cortex) during CS processing, followed by enhanced synchronization (source-located in the anterior cingulate) after shock cancellation in extinction trials. These neural dynamics correlate with the subtle advantage of US-R in the Day 3 recovery test, presenting faster spontaneous recovery fading and generally lower fear reinstatement responses. Conversely, the CS reminder elicits CS-specific effects in later episodic tests. The unique neural features of the US-R group suggest a larger prediction error and subsequent effortful conflict learning processes, warranting further exploration.

[Prenatal diagnosis of a case with Congenital myasthenic syndrome due to compound heterozygous variants of SCN4A gene].

OBJECTIVE: To explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16). METHODS: A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus. RESULTS: The couple's first pregnancy had resulted in a miscarriage at 27+5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30+5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c.3172C>T (p.R1058W) and paternal c.1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+PM2_supporting+PP3+PP4), whilst the c.1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+PM2_supporting+PP4). CONCLUSION: The c.3172C>T (p.R1058W) and c.1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.

In the anticipation of threat: Neural regulatory activity indicated by delta-beta correlation and its relation to anxiety.

The anticipation of oncoming threats is emotionally challenging and related to anxiety. The current study aimed to investigate the neural regulatory processes during the anticipatory preparations in stressful situations in relation to trait anxiety, especially in an uncertainty-related stressful situation. To this end, we measured within-subjects delta-beta amplitude-amplitude correlation (AAC) and phase-amplitude coupling (PAC) with electroencephalography using a well-defined stress-inducing paradigm in 28 high-trait-anxiety (HTA) and 29 low-trait-anxiety (LTA) college students. Specifically, a threat probability task was conducted, where participants anticipated the future stimuli under the uncertain (i.e., an average of 50% electric shocks), certain (i.e., 100% electric shocks) and no threat conditions, as well as a resting state task. Results showed a generally larger delta-beta AAC in the LTA group relative to the HTA group across conditions, supporting the hypothesis that delta-beta AAC reflects the efficiency of stress regulation and trait anxiety could compromise this adaptive regulatory activity. Furthermore, a larger delta-beta PAC was found under the uncertain threat condition relative to the no threat condition, indicating the sensitivity of delta-beta PAC in reflecting state anxiety. These findings indicate that while delta-beta AAC is more related to trait anxiety and could distinguish between high and low trait anxiety irrespective of conditions, delta-beta PAC is more related to state anxiety and is sensitive enough to detect the uncertainty-related anxious state.

Improving Anti-HIV activity and pharmacokinetics of enfuvirtide (T20) by modification with oligomannose.

Dendritic cells (DCs) play a pivotal role in controlling HIV-1 infections of CD4+ T cells. DC-SIGN, which is expressed on the surface of DCs, efficiently captures HIV-1 virions by binding to the highly mannosylated membrane protein, gp120, and then the DCs transport the virus to target T cells in lymphoid organs. This study explored the modification of T20, a peptide inhibitor of HIV-1 fusion, by conjugation of the N-terminus with varying sizes of oligomannose, which are DC-SIGN-specific carbohydrates, aiming to create dual-targeting HIV inhibitors. Mechanistic studies indicated the dual-target binding of the conjugates. Antiviral assays demonstrated that N-terminal mannosylation of T20 resulted in increased inhibition of the viral infection of TZM-b1 cells (EC50 = 0.3-0.8 vs. 1.4 nM). Pentamannosylated T20 (M5-T20) exhibited a stronger inhibitory effect on virus entry into DC-SIGN+ 293T cells compared with T20 (67% vs. 50% inhibition at 500 µM). M5-T20 displayed an extended half-life in rats relative to T20 (T1/2: 8.56 vs. 1.64 h, respectively). These conjugates represent a potential new treatment for HIV infections with improved antiviral activity and pharmacokinetics, and this strategy may prove useful in developing dual-target inhibitors for other pathogens that require DC-SIGN involvement for infection.

Nonspecific phospholipases C3 and C4 interact with PIN-FORMED2 to regulate growth and tropic responses in Arabidopsis.

The dynamic changes in membrane phospholipids affect membrane biophysical properties and cell signaling, thereby influencing numerous biological processes. Nonspecific phospholipase C (NPC) enzymes hydrolyze common phospholipids to release diacylglycerol (DAG), which is converted to phosphatidic acid (PA) and other lipids. In this study, two Arabidopsis (Arabidopsis thaliana) tandemly arrayed genes, NPC3 and NPC4, were identified as critical factors modulating auxin-controlled plant growth and tropic responses. Moreover, NPC3 and NPC4 were shown to interact with the auxin efflux transporter PIN-FORMED2 (PIN2). The loss of NPC3 and NPC4 enhanced the endocytosis and vacuolar degradation of PIN2, which disrupted auxin gradients and slowed gravitropic and halotropic responses. Furthermore, auxin-triggered activation of NPC3 and NPC4 is required for the asymmetric PA distribution that controls PIN2 trafficking dynamics and auxin-dependent tropic responses. Collectively, our study reveals an NPC-derived PA signaling pathway in Arabidopsis auxin fluxes that is essential for fine-tuning the balance between root growth and environmental responses.

Glycan-Modified Peptides for Dual Inhibition of Human Immunodeficiency Virus Entry into Dendritic Cells and T Cells.

Dendritic cells (DCs) play a crucial role in HIV-1 infection of CD4+ T cells. DC-SIGN, a lectin expressed on the surface of DCs, binds to the highly mannosylated viral membrane protein gp120 to capture HIV-1 virions and then transport them to target T cells. In this study, we modified peptide C34, an HIV-1 fusion inhibitor, at different sites using different sizes of the DC-SIGN-specific carbohydrates to provide dual-targeted HIV inhibition. The dual-target binding was confirmed by mechanistic studies. Pentamannose-modified C34 inhibited virus entry into both DC-SIGN+ 293T cells (52%-71% inhibition at 500 µM) and CD4+ TZM-b1 cells (EC50 = 0.7-1.7 nM). One conjugate, NC-M5, showed an extended half-life relative to C34 in rats (T1/2: 7.8 vs 1.02 h). These improvements in antiviral activity and pharmacokinetics have potential for HIV treatment and the development of dual-target inhibitors for pathogens that require the involvement of DC-SIGN for infection.

Transcriptomics combined with physiological analysis provided new insights into the Zn enrichment capacity and tolerance mechanism of Dendrobium denneanum Kerr.

In this study, we investigated the tolerance and accumulation capacity of Dendrobium denneanum Kerr (D.denneanum) by analyzing the growth and physiological changes of D.denneanum under different levels of Zn treatments, and further transcriptome sequencing of D.denneanum leaves to screen and analyze the differentially expressed genes. The results showed that Zn400 treatment (400 mg·kg-1) promoted the growth of D.denneanum while both Zn800 (800 mg·kg-1) and Zn1600 treatment (1600 mg·kg-1) caused stress to D.denneanum. Under Zn800 treatment (800 mg·kg-1), the resistance contribution of physiological indexes was the most obvious: antioxidant system, photosynthetic pigment, osmoregulation, phytochelatins, and ASA-GSH cycle (Ascorbic acid-Glutathione cycle). D.denneanum leaves stored the most Zn, followed by stems and roots. The BCF(Bioconcentration Factor) of the D.denneanum for Zn were all more than 1.0 under different Zn treatments, with the largest BCF (1.73) for Zn400. The transcriptome revealed that there were 1500 differentially expressed genes between Zn800 treatment and group CK, of which 842 genes were up-regulated and 658 genes were down-regulated. The genes such as C4H, PAL, JAZ, MYC2, PP2A, GS, and GST were significantly induced under the Zn treatments. The differentially expressed genes were associated with phenylpropane biosynthesis, phytohormone signaling, and glutathione metabolism. There were three main pathways of response to Zn stress in Dendrobium: antioxidant action, compartmentalization, and cellular chelation. This study provides new insights into the response mechanisms of D.denneanum to Zn stress and helps to evaluate the phytoremediation potential of D.denneanum in Zn-contaminated soils.

Prediction of survival of persons with advanced dementia using the advanced dementia prognostic tool: A 2-year prospective study.

BACKGROUND: In this prospective study, we evaluated the usefulness of the advanced dementia prognostic tool (ADEPT) for estimating the 2-year survival of persons with advanced dementia (AD) in China. METHODS: The study predicted the 2-year mortality of 115 persons with AD using the ADEPT score. RESULTS: In total, 115 persons with AD were included in the study. Of these persons, 48 died. The mean ADEPT score was 13.0. The AUROC for the prediction of the 2-year mortality rate using the ADEPT score was 0.62. The optimal threshold of the ADEPT score was 11.2, which had an AUROC of 0.63, specificity of 41.8, and sensitivity of 83.3. CONCLUSIONS: The ADEPT score based on a threshold of 11.2 may serve as a prognostic tool to determine the 2-year survival rate of persons with AD in Chongqing, China. However, further studies are needed to explore the nature of this relationship.

Brain network integration underpins differential susceptibility of adolescent anxiety.

BACKGROUND: Parenting is a common and potent environmental factor influencing adolescent anxiety. Yet, the underlying neurobiological susceptibility signatures remain elusive. Here, we used a longitudinal twin neuroimaging study to investigate the brain network integration and its heritable relation to underpin the neural differential susceptibility of adolescent anxiety to parenting environments. METHODS: 216 twins from the Beijing Twin Study completed the parenting and anxiety assessments and fMRI scanning. We first identified the brain network integration involved in the influences of parenting at age 12 on anxiety symptoms at age 15. We then estimated to what extent heritable sensitive factors are responsible for the susceptibility of brain network integration. RESULTS: Consistent with the differential susceptibility theory, the results showed that hypo-connectivity within the central executive network amplified the impact of maternal hostility on anxiety symptoms. A high anti-correlation between the anterior salience and default mode networks played a similar modulatory role in the susceptibility of adolescent anxiety to paternal hostility. Genetic influences (21.18%) were observed for the connectivity pattern in the central executive network. CONCLUSIONS: Brain network integration served as a promising neurobiological signature of the differential susceptibility to adolescent anxiety. Our findings deepen the understanding of the neural sensitivity in the developing brain and can inform early identification and personalized interventions for adolescents at risk of anxiety disorders.

Identification of SRSF10 as a promising prognostic biomarker with functional significance among SRSFs for glioma.

AIMS: The serine/arginine-rich splicing factor (SRSF) protein family members are essential mediators of the alternative splicing (AS) regulatory network, which is tightly implicated in cancer progression. However, the expression, clinical correlation, immune infiltration, and prognostic value of SRSFs in gliomas remain unclear. MATERIALS AND METHODS: Glioma samples were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets. Several databases, such as HPA, DAVID, UALCAN were used to comprehensively explore the roles of SRSFs. In addition, experimental validation of SRSF10 was also conducted. KEY FINDINGS: Here, we found the expression alterations of the SRSF family in glioma samples using data from the TCGA and CGGA_325 datasets. Among the 12 genes, most were found to be closely associated with glioma clinical features, which linked to poor prognosis in glioma patients. Interestingly, survival analysis identified only SRSF10 as a potential independent risk prognostic biomarker for glioma patients. Immune analysis indicated that glioma patients with high SRSF10 expression may respond well to immunotherapies targeting immune checkpoint (ICP) genes. Finally, knocking down SRSF10 reduced glioma cell viability, induced G1 cell cycle arrest, and induced the exclusion of bcl-2-associated transcription factor 1 (BCLAF1) exon 5a. SIGNIFICANCE: Overall, this study uncovers the oncogenic roles of most SRSF family members in glioma, with the exception of SRSF5, while highlighting SRSF10 as a potential novel independent prognostic biomarker for glioma.

Heat Stress Alleviation by Exogenous Calcium in the Orchid Dendrobium nobile Lindl: A Biochemical and Transcriptomic Analysis.

The growth of Dendrobium nobile is sensitive to heat stress. To find an effective method for enhancing heat tolerance, this study investigated the relieving effect of exogenous calcium at different concentrations (0 mmol/L, 5 mmol/L, 10 mmol/L, 15 mmol/L, 20 mmol/L CaCl2) on heat stress in D. nobile. Principal component analysis was used to screen the optimal exogenous calcium concentration, and transcriptome analysis was used to reveal its possible heat tolerance mechanism. The results showed that compared with the T0, a 10 mmol/L calcium treatment: increased the average leaf length, leaf width, plant height, and fresh matter accumulation of D. nobile by 76%, 103.39%, 12.97%, and 12.24%, respectively (p < 0.05); significantly increased chlorophyll a (Chla), chlorophyll b (Chlb), carotenoids(Car), ascorbic acid (ASA), glutathione (GSH), and flavonoids by 15.72%, 8.54%, 11.88%, 52.17%, 31.54%, and 36.12%, respectively; and effectively enhanced the enzyme activity of the antioxidant system, increasing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) by 1.38, 1.61, and 2.16 times, respectively (p < 0.05); At the same time, the treatment can effectively reduce the yellow leaf rate and defoliation rate of D. nobile under heat stress. The principal component analysis method and membership function were used to calculate the D value to rank the relief effects of each calcium treatment group, and the results also showed that 10 mmol/L CaCl2 had the best relief effect. Transcriptomics testing identified 7013 differentially expressed genes, of which 2719 were upregulated, and 294 were downregulated. Among them, genes such as HSPA1s, HSP90A, HSPBP1, ATG8, COMT, REF1, E1.11.1.7, along with transcription factors such as MYB, bHLH, WRKY, and NAC, formed the network of tolerance to heat stress in D. nobile. This study provides new insights for improving the cultivation techniques of D. nobile.

Alteration of Metabolic Profiles during the Progression of Alzheimer's Disease.

(1) Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that threatens the population health of older adults. However, the mechanisms of the altered metabolism involved in AD pathology are poorly understood. The aim of the study was to identify the potential biomarkers of AD and discover the metabolomic changes produced during the progression of the disease. (2) Methods: Gas chromatography-mass spectrometry (GC-MS) was used to measure the concentrations of the serum metabolites in a cohort of subjects with AD (n = 88) and a cognitively normal control (CN) group (n = 85). The patients were classified as very mild (n = 25), mild (n = 27), moderate (n = 25), and severe (n = 11). The serum metabolic profiles were analyzed using multivariate and univariate approaches. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to identify the potential biomarkers of AD. Biofunctional enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. (3) Results: Our results revealed considerable separation between the AD and CN groups. Six metabolites were identified as potential biomarkers of AD (AUC > 0.85), and the diagnostic model of three metabolites could predict the risk of AD with high accuracy (AUC = 0.984). The metabolic enrichment analysis revealed that carbohydrate metabolism deficiency and the disturbance of amino acid, fatty acid, and lipid metabolism were involved in AD progression. Especially, the pathway analysis highlighted that l-glutamate participated in four crucial nervous system pathways (including the GABAergic synapse, the glutamatergic synapse, retrograde endocannabinoid signaling, and the synaptic vesicle cycle). (4) Conclusions: Carbohydrate metabolism deficiency and amino acid dysregulation, fatty acid, and lipid metabolism disorders were pivotal events in AD progression. Our study may provide novel insights into the role of metabolic disorders in AD pathogenesis and identify new markers for AD diagnosis.

Characteristics of solid waste from common generation source in nonferrous smelting industry reveal a new classification method.

Solid waste produced by the nonferrous smelting industry has a significant number of notable differences. The lack of recognition of solid waste characteristics is the main factor restricting its disposal and utilization. In this study, we analyzed the main production processes of the nonferrous smelting industry; identified the key production nodes of solid waste; and clarified the characteristics, including the physical, chemical, and pollution characteristics of solid wastes, through a large sample statistical analysis. We found similarities among solid wastes from a common generation source as well as notable differences among the different generation sources: slags and sludges from waste acid treatment and wastewater treatment units had a water content of 27.43-52.71% and 51.14-68.27%, respectively, which were significantly higher than those of other metallurgy and dust collection units; the pH of slags from an electrorefining unit was strongly alkaline; the mineral phase of sludges from wastewater treatment was only calcite; slags from a waste acid treatment unit were mainly in phase of gypsum, claudetite, and anglesite; the chemical composition of slags from pyrometallurgy and hydrometallurgy units was mainly SiO2 and Fe2O3. In this paper, we discuss a new classification method based on a common generation source for the first time. These results are beneficial to guide the disposal, utilization, and management of solid waste.

Wilms' tumour gene 1 (WT1) enhances non-small cell lung cancer malignancy and is inhibited by microRNA-498-5p.

BACKGROUND: Wilms' tumour gene 1 (WT1) is clearly recognized as a tumour promoter in diversiform of human malignancies. Nevertheless, knowledge of its expression, functions and potential molecular mechanisms in non-small cell lung cancer (NSCLC) remains elusive. METHODS: Differential expression of WT1 mRNA and protein between NSCLC and normal tissues were assessed by analyzing RNA-seq data from Oncomine and protein data from Human Protein Atlas, respectively. Subsequently, prognosis significance and immune cell infiltration were analyzed by Kaplan-Meier plotter and CIBERSORT. 60 pairs of local NSCLC tissues were involved to validate WT1 expression by quantitative PCR (qPCR) and Western blot. Moreover, Cell Counting Kit-8 (CCK-8), colony formation, transwell, dual luciferase reporter assays and in vivo xenograft tumour growth experiments were conducted to explore the function and mechanism of WT1 in NSCLC. RESULTS: Our solid data indicated that WT1 was increased in NSCLC tissues and cell lines in comparison with their matched controls. In particular, its upregulation correlated with worse prognosis and immune infiltration of the patients. Functional assays demonstrated that knockdown of WT1 inhibited NSCLC malignancy, including inhibiting cell proliferation, survival and invasion. Further exploration discovered that microRNA-498-5p (miR-498-5p) was the upstream suppressor of WT1 by directly targeting the 3' untranslated region (UTR) of WT1 mRNA. Moreover, expression of miR-498-5p was notably decreased and inversely correlated with WT1 in NSCLC tissues. Finally, we proved that miR-498-5p was a potent tumour suppressor in NSCLC by suppressing cell proliferation, survival and invasion, while WT1 restoration could in turn disrupt this suppression both in vitro and in vivo. CONCLUSION: The abnormal increase in WT1 contributes to the malignant properties of NSCLC cells, and miR-498-5p is a natural inhibitor of WT1. Our findings might facilitate the development of novel therapeutic strategies against NSCLC in the future.

Transcriptome analysis reveals the role of polysaccharide biosynthesis in the detoxification of Dendrobium nobile under zinc stress.

Plants can bind excessive heavy metals by synthesizing compounds to alleviate the harm caused by heavy metals. To reveal the mechanism by which Dendrobium nobile alleviates zinc stress, metabolome combined transcriptome analysis was used in this research. The results showed that zinc was mainly enriched in the roots and leaves and the biomass of the roots and leaves of D. nobile decreased significantly by 18.21 % and 49.22 % (P < 0.05) compared to the control (CK), respectively. Meanwhile, the contents of nonprotein thiol(NPT), glutathione(GSH), and phytochelatins (PCs) in the roots were significantly increased by 48.8 %, 78.3 %, and 45.4 % compared to CK, respectively. Through TEM testing, it was found that D. nobile exhibited toxic symptoms. Metabolome analysis showed that the metabolites of D. nobile under zinc stress were mainly enriched in biosynthesis of other secondary metabolites and carbohydrate metabolism. Nova-seq results identified 1202 differentially expressed genes(DEGs), of which 603 were upregulated and 599 were downregulated. Through GO and KEGG annotation analysis of these DEGs, it was found that PMR6 and PECS-2.1, SS1 and GLU3 genes were significantly upregulated, leading to an increase in the biosynthesis of xylan, pectin, starch and other polysaccharides in D. nobile. These polysaccharides can form a "Polysaccharide-Zn" with excess zinc. Meanwhile, the GSTs in glutathione metabolism were significantly upregulated, leading to a significant increase in the content of NPT, GSH, and PCs. These zinc complexes were transported to vacuoles through ABC transporters for compartmentalization, effectively alleviating the damage of zinc. The results can provide new insights for phytoremediation and quality assurance of medicinal D. nobile.