[Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Complete androgen insensitivity syndrome due to a novel variant of AR gene].

OBJETIVE: To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS). METHODS: A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome (SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). RESULTS: The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46,XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c.1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister's first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PM4+PP3_Moderate+PP4). CONCLUSION: The c.1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians' thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction.

New molecular mechanisms of quercetin in improving recurrent spontaneous abortion based on in-depth network pharmacology and molecular docking.

Introduction: The increasing prevalence of recurrent spontaneous abortion (RSA) poses significant physical and psychological challenges for affected individuals. Quercetin, a natural plant flavonoid, shows promise in reducing miscarriage rates, yet its precise mechanism remains elusive. This study uses network pharmacology, molecular docking, and experimental validation to explore the molecular pathways through which quercetin mitigates RSA. Methods: Quercetin-related target genes were sourced from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and RSA target genes were retrieved from the Comparative Toxicogenomics Database (CTD), with overlapping targets identified using Venn diagrams. All genes were visualized using the STRING database, and core targets were selected with Cytoscape 3.7.3. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the DAVID and Reactome online resources. Subsequently, HTR-8/SVneo cells were stimulated with lipopolysaccharide (LPS) and treated with varying concentrations of quercetin (1, 5, and 10 µM), then subjected to CCK-8, wound healing, transwell, and annexin V-FITC/PI apoptosis assays. Reverse-transcription quantitative PCR was used to determine the mRNA expression levels of IL-1ß, TNF-α, and IL-6 in LPS-induced cells post-quercetin intervention, and western blotting was used to measure AKT1, MMP9, and caspase-3 protein levels. Results: A total of 139 quercetin-associated target genes were identified from the TCMSP database, and 98 disease-associated target genes were obtained from the CTD, resulting in 25 shared target genes. Gene ontology enrichment highlighted the involvement of these targets in positive regulation of apoptosis, response to hypoxia, and intrinsic apoptotic signaling pathway in response to DNA damage. KEGG pathway analysis indicated enrichment in pathways related to interleukin-4 and interleukin-13 signaling, cytokine signaling in the immune system, and apoptosis. Molecular docking studies revealed robust binding of quercetin with MMP9, AKT1, IL-1ß, TNF, and caspase-3. In vitro experiments demonstrated that quercetin enhanced LPS-induced cell activity, fostering proliferation, migration, and invasion, and reducing apoptosis. Moreover, quercetin reduced IL-1ß, TNF-α, and IL-6 mRNA expression, increased AKT1 and MMP9 protein levels, and reduced caspase-3 expression. Conclusion: Quercetin could mitigate the incidence of RSA by modulating inflammatory responses and apoptotic processes, through upregulation of AKT1 and MMP9, and downregulation of caspase-3, IL-1ß, TNF-α, and IL-6. Quercetin opens up a new way of thinking about treating RSA.

The deficit in cognitive reappraisal capacity in individuals with anxiety or depressive disorders: meta-analyses of behavioral and neuroimaging studies.

BACKGROUND: The deficit in cognitive reappraisal capacity is a key factor in developing and maintaining emotional disorders such as anxiety disorders and depressive disorders. However, the results from both neuroimaging and behavioral studies are mixed. Therefore, we systematically conducted a series of meta-analyses based on behavioral and neuroimaging studies to clarify this issue. METHODS: In behavioral meta-analyses, we used three-level random-effects models to summarize the overall effect sizes based on Hedges' g. In neuroimaging meta-analyses, we used SDM-PSI to summarize the brain activation patterns. RESULTS: Behavioral meta-analyses found that individuals with anxiety disorders or depressive disorders could reduce negative reactivity through reappraisal; the reduction of negative emotions through reappraisal by individuals with anxiety disorders was similar to that by healthy individuals; the reduction by depressive disorders was lower than that of healthy individuals. Neuroimaging meta-analyses showed that individuals with anxiety disorders or depressive disorders activated regions of cognitive control during cognitive reappraisal; the activation in individuals with anxiety disorders was lower than in healthy individuals; while the activation in individuals with depressive disorders was similar to that in healthy individuals. CONCLUSION: Individuals with anxiety and depressive disorders showed dissociation in behaviour and neuroimaging patterns of cognitive reappraisal capacity deficit.

Efficient ofloxacin degradation via peroxymonosulfate activation using an S-scheme MoS2/Co3O4 heterojunction composite under visible light: Performance and mechanistic insights.

Sulfate-radical-mediated photocatalysis technology peroxymonosulfate (PMS) activation via visible light irradiation shows great promise for water treatment applications. However, its effectiveness largely depends on the bifunctional performance of photocatalysis and PMS activation provided by the catalysts. In this study, we successfully synthesized a novel S-scheme MoS2/Co3O4 (MC) heterojunction composite by a hydrothermal method and employed it for the first time to activate PMS for ofloxacin (OFX) degradation under visible light irradiation. The MC-5/PMS/Vis system achieved an impressive 85.11% OFX degradation efficiency within 1 min and complete OFX removal within 15 min under optimal conditions, with an apparent first-order kinetics rate constant of 0.429 min-1. Reactive species trapping experiments and electron spin resonance analysis identified 1O2, h+, and •O2- as the primary active species responsible for OFX degradation. Photoelectrochemical analyses and density functional theory calculations indicated the formation of a built-in electric field between MoS2 and Co3O4, which enhanced the separation and migration of photoinduced carriers. Additionally, the Co-Mo interaction further increased the yield of dominant reactive species, thereby boosting photocatalytic activity. This work underscores the potential of visible-light-assisted PMS-mediated photocatalysis using Co3O4-based catalysts for effective pollutant control.

Quercetin promotes the proliferation, migration, and invasion of trophoblast cells by regulating the miR-149-3p/AKT1 axis.

Recurrent spontaneous abortion (RSA) has a complex pathogenesis with an increasing prevalence and is one of the most intractable clinical challenges in the field of reproductive medicine. Quercetin (QCT) is an effective active ingredient extracted from Semen Cuscutae and Herba Taxilli used in traditional Chinese medicine for tonifyng the kidneys and promoting fetal restoration. Although QCT helps improve adverse pregnancy outcomes, the specific mechanism remains unclear. The trophoblast cell line HTR-8/SVneo cultured in vitro was treated with different concentrations of QCT, and the cell counting kit-8 assay, wound healing assay, transwell assay, and western blotting were used to evaluate the effects and mechanisms of QCT on the proliferation, migration, and invasion of HTR-8/SVneo cells, respectively. To assess the expression levels of miR-149-3p and AKT serine/threonine kinase 1 (AKT1), quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were performed. A dual-luciferase reporter assay was used to investigate the potential regulatory relationship between miR-149-3p and AKT1. Our results showed that QCT promoted the proliferation, migration, and invasion of trophoblast cells, promoted the expression of MMP2, MMP9, and vimentin, and downregulated the expression of E-cadherin. Mechanistically, QCT downregulated the expression of miR-149-3p and upregulated the expression of AKT1, and miR-149-3p directly targets AKT1, negatively regulating its expression. Overexpression of miR-149-3p and silencing of AKT1 counteracted the promotional effects of QCT on trophoblast proliferation, migration, and invasion. Taken together, QCT regulates the migration and invasion abilities of HTR-8/SVneo cells through the miR-149-3p/AKT1 axis, which may provide a promising therapeutic approach for RSA.

The Influence of Maternal and Paternal Parenting on Adolescent Brain Structure.

BACKGROUND: Adolescents raised in families with different maternal and paternal parenting combinations exhibit variations in neurocognition and psychopathology; however, whether neural differences exist remains unexplored. This study used a longitudinal twin sample to delineate how different parenting combinations influence adolescent brain structure and to elucidate the genetic contribution. METHODS: A cohort of 216 twins participated in parenting assessments during early adolescence and underwent magnetic resonance imaging scanning during middle adolescence. We utilized latent profile analysis to distinguish between various maternal and paternal parenting profiles and subsequently investigated their influences on brain anatomy. Biometric analysis was applied to assess genetic influences on brain structure, and associations with internalizing symptoms were explored. RESULTS: In early adolescence, 4 parenting profiles emerged, which were characterized by levels of harshness and hostility in one or both parents. Compared with adolescents in "catparent" families (low harshness/hostility in both parents), those raised in "tigermom" families (harsh/hostile mother only) exhibited a smaller nucleus accumbens volume and larger temporal cortex surface area; those in "tigerdad" families demonstrated larger thalamus volumes; and those in "tigerparent" families displayed smaller volumes in the midanterior corpus callosum. Genetic risk factors contributed significantly to the observed brain structural heterogeneity and internalizing symptoms. However, the influences of parenting profiles and brain structure on internalizing symptoms were not significant. CONCLUSIONS: The findings underscore distinct brain structural features linked to maternal and paternal parenting combinations, particularly in terms of subcortical volume and cortical surface area. This study suggests an interdependent role of maternal and paternal parenting in shaping adolescent neurodevelopment.

Development of novel antivrial agents that induce the degradation of the main protease of human-infecting coronaviruses.

The family of human-infecting coronaviruses (HCoVs) poses a serious threat to global health and includes several highly pathogenic strains that cause severe respiratory illnesses. It is essential that we develop effective broad-spectrum anti-HCoV agents to prepare for future outbreaks. In this study, we used PROteolysis TArgeting Chimera (PROTAC) technology focused on degradation of the HCoV main protease (Mpro), a conserved enzyme essential for viral replication and pathogenicity. By adapting the Mpro inhibitor GC376, we produced two novel PROTACs, P2 and P3, which showed relatively broad-spectrum activity against the human-infecting CoVs HCoV-229E, HCoV-OC43, and SARS-CoV-2. The concentrations of these PROTACs that reduced virus replication by 50 % ranged from 0.71 to 4.6 µM, and neither showed cytotoxicity at 100 µM. Furthermore, mechanistic binding studies demonstrated that P2 and P3 effectively targeted HCoV-229E, HCoV-OC43, and SARS-CoV-2 by degrading Mpro within cells in vitro. This study highlights the potential of PROTAC technology in the development of broad-spectrum anti-HCoVs agents, presenting a novel approach for dealing with future viral outbreaks, particularly those stemming from CoVs.

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.

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.

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.

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.

[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, 2 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.