Ion adsorption-enrichment effect and its driving mechanism for nano-dots lithography with SPM probe on water-soluble crystal surfaces.

HYPOTHESIS: Water-soluble KDP (KH2PO4) crystals possess excellent optical properties and are employed as frequency converters in clean fusion energy. To improve their performances, there is an immediate necessity to lithograph surface nano-patterns on them. Although the Scanning Probe Microscope (SPM) provides a promising way to achieve this purpose through the water menisci, the driving mechanisms of the lithographic behaviors have not yet been revealed. SIMULATIONS AND EXPERIMENTS: Multi-scale investigations are constructed to explore the underlying driving mechanisms. The SPM probe-induced ion diffusion-transport behaviors are investigated by molecular dynamics. The ion adsorption-enrichment mechanisms are revealed by 18 adsorption models via the ab initio. The SPM probe-induced self-assembly experiments are performed to prove the local heavy concentration. A comprehensive model is developed to describe the lithography mechanisms of the probe-induced self-assembly nano-dots on water-soluble substrates. FINDINGS: It is interestingly found that the KDP growth units (H2PO4-) exhibit obvious adsorption-enrichment effect at 3.16 Å from the probe surface, causing local heavy concentration. The H2PO4- would spontaneously adsorb onto the probe surface, which is dominated by the Si-O bonding reactions. The nano-dots with the height of 27 âˆ¼ 48 nm and diameter of 2.0 âˆ¼ 2.7 µm are lithographed on the KDP substrate. The proposed model further confirms that the lithography processes are driven by the solution supersaturation, solute diffusion, and surface free energy.

Transcriptome analysis reveals methanol metabolism variations for the growth damage caused by overexpression of chimeric transactivators in Pichia pastoris.

Methanol is a promising substrate for sustainable biomanufacturing, and Pichia pastoris has become a commonly used yeast for methanol utilization due to its powerful methanol metabolic pathways and methanol inducible promoter. Previous reconstruction of gene circuits highly improved transcriptional activity, but excessive expression of chimeric transactivator damaged cell growth on methanol. Here we employed transcriptome analysis to investigate the effects of chimeric transactivator overexpression on cellular metabolism and regulatory networks. The results showed that strong expression of chimeric transactivator unexpectedly downregulated methanol metabolism, especially the alcohol oxidase 1 (AOX1), but without remarkable changes in expression of transcriptional factors. Meanwhile, the synthesis of peroxisomes also varied with chimeric transactivator expression. In addition, the enrichment analysis of differentially expressed genes revealed their impact on cellular metabolism. The gene expression patterns caused by different expression levels of chimeric transactivators have also been clarified. This work provides useful information to understand the transcriptional regulation of the AOX1 promoter and methanol signaling. It revealed the importance of balancing transcription factor expression for the host improvement.

A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury.

JOURNAL/nrgr/04.03/01300535-202502000-00028/figure1/v/2024-05-28T214302Z/r/image-tiff Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI (QK) are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases. However, conventional topical drug delivery often results in a burst release of the drug, leading to transient retention (inefficacy) and undesirable diffusion (toxicity) in vivo. Therefore, a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke. Matrix metalloproteinase-2 (MMP-2) is gradually upregulated after cerebral ischemia. Herein, vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG (TIMP) and customizable peptide amphiphilic (PA) molecules to construct nanofiber hydrogel PA-TIMP-QK. PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro. The results indicated that PA-TIMP-QK promoted neuronal survival, restored local blood circulation, reduced blood-brain barrier permeability, and restored motor function. These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

A comprehensive review of deactivation and modification of selective catalytic reaction catalysts installed in cement kilns.

After the ultralow emission transformation of coal-fired power plants, cement production became China's leading industrial emission source of nitrogen oxides. Flue gas dust contents at the outlet of cement kiln preheaters were as high as 80-100 g/m3, and the calcium oxide content in the dust exceeded 60%. Commercial V2O5(-WO3)/TiO2 catalysts suitable for coal-fired flue gas suffer from alkaline earth metal Ca poisoning of cement kiln flue gas. Recent studies have also identified the poisoning of cement kiln selective catalytic reaction (SCR) catalysts by the heavy metals lead and thallium. Investigation of the poisoning process is the primary basis for analyzing the catalytic lifetime. This review summarizes and analyzes the SCR catalytic mechanism and chronicles the research progress concerning this poisoning mechanism. Based on the catalytic and toxification mechanisms, it can be inferred that improving the anti-poisoning performance of a catalyst enhances its acidity, surface redox performance-active catalytic sites, and shell layer protection. The data provide support in guiding engineering practice and reducing operating costs of SCR plants. Finally, future research directions for SCR denitrification catalysts in the cement industry are discussed. This study provides critical support for the development and optimization of poisoning-resistant SCR denitrification catalysts.

Nicotine promotes M2 macrophage polarization through α5-nAChR/SOX2/CSF-1 axis in lung adenocarcinoma.

α5-nicotinic acetylcholine receptor (α5-nAChR) plays a vital part in lung adenocarcinoma (LUAD). However, it is not comprehensively understood that how the α5-nAChR affects LUAD. Through diverse bioinformatics analyses and immunohistochemistry, the expressions of α5-nAChR and SOX2 as well as their relations were dissected. α5-nAChR regulated the differentiation of monocytes into M2 macrophages by targeting the STAT3/SOX2/CSF-1 signaling in the coculture system by western blotting and ChIP. α5-nAChR-mediated macrophage-mediated LUAD cell migration via SOX2/CSF-1 signaling in the cocultured medium. Correlations of α5-nAChR, SOX2 and M2 phenotype tumor-associated macrophages (TAMs) were validated in mouse LUAD models and clinical samples. α5-nAChR expression was connected to SOX2 expression, smoking and bad prognosis of LUAD among clinical samples. Nicotine-induced SOX2 expression was mediated by α5-nAChR via STAT3. Additionally, SOX2-mediated macrophage colony-stimulating factor (CSF-1) expression contributed to LUAD progression in vitro. Furthermore, α5-nAChR expression was strongly linked to pSTAT3, SOX2 and M2 macrophage marker CD206 expression and negatively correlated with M1 macrophage marker CD86 expression in vivo. It is indicated that M2 macrophages are mediated by the new α5-nAChR /SOX2/CSF-1 axis in nicotine-related LUAD, which is a potential therapeutic strategy for cancer.

HIV persists in late coronary atheroma and is associated with increased local inflammation and disease progression.

Chronic inflammation contributes to the prevalence of cardiovascular disease in people living with HIV (PLWH). The immune mechanisms driving atherosclerosis progression in PLWH remain unclear. This study conducted comprehensive assessments of medium-sized coronary arteries and aorta from deceased PLWH and controls without HIV using DNA/RNA assays, spatial transcriptomics, and high-resolution mass spectrometry. Findings revealed more significant inflammation correlated with higher HIV copy numbers in late atheroma of PLWH. Enhanced CXCL12 and decreased ABCA1/ABCG1 expression in CD163+ macrophages were co-localized in coronaries of PLWH, suggesting a reduction in plasma lipoprotein clearance compared to controls. Spatial analyses identified potential therapeutic targets by revealing inflammatory changes in medium-sized arteries and the aorta. We examined the relationship between atherosclerotic phenotypes and inflammatory gene expression in Vanderbilts Biobank to study these findings in a larger clinical cohort. This established a significant association between ABCA1 and CXCL12 gene expressions with atherosclerosis, partly influenced by HIV.

Effects of phosphorylation on CsTT12 transport function: A comparative phosphoproteomic analysis of flavonoid biosynthesis in tea plants (Camellia sinensis).

Monomeric flavan-3-ols and their oligomeric forms, proanthocyanidins (PAs), are closely related to the bitterness of tea beverages. Monomeric flavan-3-ols are characteristic flavor compounds in tea. Increasing the content of PAs and anthocyanins enhances the resistance of tea plants to pathogen invasion but decreases the quality of tea beverages. MATE family transporters play a critical role in transferring monomeric flavan-3-ols and anthocyanins into vacuoles for storage or subsequent condensation into PAs. Their activities modulate the ratio of monomeric flavan-3-ols to PAs and increase anthocyanin content in tea plants. In this study, it was observed that the gene expression and protein phosphorylation level of the MATE transporter CsTT12, a vacuole-localized flavonoid transporter, were notably upregulated following exogenous sucrose treatment, promoting PA synthesis in tea plants. Further analysis revealed that overexpression of CsTT12 and CsTT12S17D significantly increased the content of anthocyanins and PAs in plants, whereas CsTT12S17A did not. In CsTT12 knockdown plants, PA's accumulation decreased significantly, while monomeric catechin content increased. Moreover, phosphorylation modification enhanced the vacuolar membrane localization of CsTT12, whereas dephosphorylation weakened its vacuolar membrane localization. This study uncovers the crucial role of phosphorylation in flavonoid biosynthesis and provides insights into balancing quality improvements and resistance enhancement.

Epigenetic Activation of the CMTM6-IGF2BP1-EP300 Positive Feedback Loop Drives Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with a dismal prognosis. Gemcitabine-based chemotherapy has emerged as a first-line treatment for PDAC. However, the development of gemcitabine resistance often results in therapeutic failure. In order to uncover the underlying mechanisms of gemcitabine resistance, gemcitabine-resistant PDAC cell lines and patient-derived xenograft (PDX) models are established and subjected to RNA sequencing. It is found that CMTM6 is closely related to gemcitabine resistance in PDAC. Multi-omics analysis revealed that EP300-mediated H3K27ac modification is involved in the transcriptional activation of CMTM6, which maintains IGF2BP1 expression by preventing its ubiquitination. The m6A reader IGF2BP1 stabilizes the EP300 and MYC mRNAs by recognizing m6A modifications, forming a positive feedback loop that enhances tumor stemness and ultimately contributes to PDAC resistance. The combined application of the EP300 inhibitor inobrodib and gemcitabine exerts a synergistic effect on PDAC. Overall, these findings reveal that the EP300-CMTM6-IGF2BP1 positive feedback loop facilitates gemcitabine resistance via epigenetic reprogramming and the combined use of inobrodib and gemcitabine represents a promising strategy for overcoming chemoresistance in PDAC, warranting further investigation in clinical trials.

The impact of cathepsins on liver hepatocellular carcinoma: Insights from genetic and functional analyses.

Liver Hepatocellular Carcinoma (LIHC), ranked as the second deadliest cancer globally, poses a major health challenge because of its widespread occurrence and poor prognosis. The mechanisms underlying LIHC development and progression remain unclear. Cathepsins are linked to tumorigenesis in other cancers, but their role in LIHC is underexplored. This study employed integrative analyses, including Mendelian Randomization (MR), bulk RNA-sequencing (bulk-seq), single-cell RNA sequencing (scRNA-seq), immunohistochemical (IHC) analysis, and cellular experiments with siRNA technology, to investigate the role of cathepsin E (CTSE) in LIHC. MR analysis identified CTSE as a factor associated with increased LIHC risk. Prognostic analysis using TCGA data showed that higher CTSE levels are linked to poorer survival, establishing CTSE as an independent prognostic risk factor. Integrative transcriptome analysis revealed close relation of CTSE to the extracellular matrix. scRNA-seq from TISCH2 demonstrated that CTSE is predominantly expressed in malignant LIHC cells. IHC confirmed higher CTSE expression in LIHC tissues compared to peritumoral tissues. Functional assays, such as qRT-PCR, Western blot, cell proliferation, and colony formation experiments, demonstrated that siRNA-mediated CTSE knockdown in HepG2 and Huh7 cell lines notably suppressed cell proliferation and altered the FAK/Paxillin/Akt signaling cascade. This research enhances our comprehension of LIHC development, emphasizing CTSE as a promising prognostic marker and potential therapeutic target. Inhibiting CTSE could slow the progression of LIHC, presenting novel opportunities for therapeutic approaches.

Integrated Health Education Programmes With Physical Activity Among Community-Dwelling Older Adults at Risk of Atherosclerotic Cardiovascular Disease: An Integrative Review of Experimental Studies.

AIMS: To examine the effects of integrated health education programmes with physical activity among community-dwelling older adults at risk of atherosclerotic cardiovascular disease (ASCVD). DESIGN: Integrative review. DATA SOURCES: A systematic search of experimental studies was conducted in six electronic databases and one registry from inception to December 2022. METHODS: Two researchers independently conducted the eligibility screening, quality appraisal and data extraction. A total of 11 studies, which were published between 1996 and 2021, were included in the review and were analysed by narrative synthesis. RESULTS: The 11 included studies involved 1973 participants. The findings indicate that integrated health education programmes with physical activity have potential benefit in short-term weight management among community-dwelling older adults at risk of ASCVD. Nevertheless, the programmes appear ineffective on body mass index, short-term lipid profiles, diastolic blood pressure (BP) and blood glucose. Further investigation is recommended to confirm the programme effects on physical activity level, exercise self-efficacy, systolic BP, waist circumference, long-term lipid profiles, long-term weight management and cardiac endurance. The findings suggest that body mass index may not be a sensitive indicator of obesity in the elderly population and should be measured along with waist circumference to better predict the risk of ASCVD. The available evidence is restricted in its robustness and generalisability. As most included studies were conducted in the United States, more studies should be implemented in other countries to enhance study generalisability. CONCLUSIONS: The effects of integrated health education programmes with physical activity among community-dwelling older adults at risk of ASCVD remain inconclusive. Further research with adequate statistical power and good methodology is warranted. IMPACT: The findings provide insights into whether health education programmes with physical activity effectively improve various outcomes, and suggest that researchers should include exercise self-efficacy and cardiac endurance in future studies. REPORTING METHOD: Adhered to PRISMA reporting guidelines. NO PATIENT OR PUBLIC CONTRIBUTION: This review was conducted without patient or public participation.

Optimization of the preparation process of Spirulina blended liquor and Spirulina fermented wine, analysis of volatile components and in vitro antioxidant study.

The optimal conditions were explored for the preparation of Spirulina blended liquor (SBL) and Spirulina fermented wine (SFW), respectively. The parameters obtaining highest alga polysaccharide were calculated by response surface methodology. The optimal conditions for SBL preparation were base liquor of 42% vol, ultrasonication time of 37-min and ultrasonic power of 80 W with polysaccharide content (PC) and alcohol content (AC) of 0.2181 g/L and 39.7% vol, respectively. In the case of SFW, optimum fermentation occurred at 22°C, with a 4% inoculum and 6-day period with PC and AC of 8.533 g/L and 11.2% vol, respectively. Headspace solid-phase microextraction-gas chromatography-mass spectrometry was used to quantitatively analyze the volatile components of SBL and SFW. There were 32 and 40 main aroma compounds in SBL and SFW, respectively. Volatile organic compounds, including α-ionone and ß-ionone, produced by Spirulina were detected in both SBL and SFW. Comparative evaluation of scavenging activity and total reducing power revealed the antioxidant capacity of SFW significantly outperformed that of SBL.

Characterization and Expression of the Cytochrome P450 Genes in Daphnia magna Exposed to Cerium Oxide Nanoparticles.

As cerium oxide nanoparticles (nCeO2) continue to infiltrate aquatic environments, the resulting health risks to exposed aquatic organisms are becoming evident. Cytochrome P450 (CYP) enzymes are integral to the detoxification processes in these species. Herein, we conducted a genomic analysis of CYPs in Daphnia magna, encompassing phylogenetic relationships, gene structure, and chromosomal localization. We identified twenty-six CYPs in D. magna, categorizing them into four clans and seven families, distributed across six chromosomes and one unanchored scaffold. The encoded CYP proteins varied in length from 99 to 585 amino acids, with molecular weights ranging from 11.6 kDa to 66.4 kDa. A quantitative real-time PCR analysis demonstrated a significant upregulation of CYP4C1.4, CYP4C1.5, CYP4C1.6, CYP4c3.3, and CYP4c3.6 in D. magna exposed to 150 mg/L nCeO2 for 24 h. The transcript levels of CYP4C1.3, CYP18a1, CYP4C1.1, and CYP4c3.9 were notably downregulated in D. magna exposed to 10 mg/L nCeO2 for 48 h. A further transcriptomic analysis identified differential expression patterns of eight CYP genes, including CYP4C1.3, in response to nCeO2 exposure. The differential regulation observed across most of the 26 CYPs highlights their potential role in xenobiotic detoxification in D. magna, thereby enhancing our understanding of CYP-mediated toxicological responses to metal nanoparticles in aquatic invertebrates.

The relationship between nutritional status and prognosis in advanced gastrointestinal cancer patients in palliative care: a prospective cohort study.

OBJECTIVE: The study aimed to determine the nutritional status and its prognostic effect on the survival of patients with advanced gastrointestinal cancer. METHODS: A prospective cohort study design was conducted in a tertiary hospital in Shanghai, China. The study consisted of 202 advanced gastrointestinal (GI) cancer patients from a palliative care unit. The following data were collected from the patients: biochemical indicators, i.e., anemia (hemoglobin levels), albumin, pre-albumin, C-reactive protein (CRP), and anthropometric parameters, i.e., body mass index (BMI), nutritional status by Patient-Generated Subjective Global Assessment (PG-SGA), and performance status by Karnofsky Performance Status (KPS). Severe malnutrition was confirmed with the PG-SGA score of ≥ 9. Kaplan-Meier survival analysis and the log-rank test were used to calculate overall survival (OS). The effect of nutritional status on survival was performed by Cox regression analysis. RESULTS: Severe malnutrition was found in 71.3% of patients according to the cutoff of the PG-SGA. PG-SGA score ≥ 9, albumin level < 35 g/L, and CRP level ≥ 10 mg/L predicted shortened life expectancy. Multivariate Cox regression analysis results showed that the PG-SGA score ≥ 9 and the albumin level < 35 g/L were predictive of OS. CONCLUSION: Our data support that severe malnutrition is a predictor for OS in patients with advanced GI cancer. Information on nutritional status should be considered to individualize palliative care plan for these patients, and hence improve their quality of life.

Early detection of anthracycline-induced cardiotoxicity.

Although anthracyclines are important anticancer agents, their use is limited due to various adverse effects, particularly cardiac toxicity. Mechanisms underlying anthracycline-induced cardiotoxicity (AIC) are complex. Given the irreplaceable role of anthracyclines in treatment of malignancies and other serious diseases, early monitoring of AIC is paramount. In recent years, multiple studies have investigated various biomarkers for early detection of AIC. Currently, the two most common are cardiac troponin and B-type natriuretic peptide. In addition, a range of other molecules, including RNAs, myeloperoxidase (MPO), C-reactive protein (CRP), various genes, and others, also play roles in AIC prediction. Unfortunately, current research indicates a need to validate their sensitivity and specificity of these biomarkers especially in large study populations. In this review, we summarize the mechanisms and potential biomarkers of AIC, although some remain preliminary.

Taurine Protects against Silica Nanoparticle-Induced Apoptosis and Inflammatory Response via Inhibition of Oxidative Stress in Porcine Ovarian Granulosa Cells.

Silica nanoparticles (SNPs) induce reproductive toxicity through ROS production, which significantly limits their application. The protective effects of taurine (Tau) against SNP-induced reproductive toxicity remain unexplored. So this study aims to investigate the impact of Tau on SNP-induced porcine ovarian granulosa cell toxicity. In vitro, granulosa cells were exposed to SNPs combined with Tau. The localization of SNPs was determined by TEM. Cell viability was examined by CCK-8 assay. ROS levels were measured by CLSM and FCM. SOD and CAT levels were evaluated using ELISA and qPCR. Cell apoptosis was detected by FCM, and pro-inflammatory cytokine transcription levels were measured by qPCR. The results showed that SNPs significantly decreased cell viability, while increased cell apoptosis and ROS levels. Moreover, SOD and CAT were decreased, while IFN-α, IFN-ß, IL-1ß, and IL-6 were increased after SNP exposures. Tau significantly decreased intracellular ROS, while it increased SOD and CAT compared to SNPs alone. Additionally, Tau exhibited anti-inflammatory effects and inhibited cell apoptosis. On the whole, these findings suggest that Tau mitigates SNP-induced cytotoxicity by reducing oxidative stress, inflammatory response, and cell apoptosis. Tau may be an effective strategy to alleviate SNP-induced toxicity and holds promising application prospects in the animal husbandry and veterinary industry.

The contributory role of GSK3ß in hypertension exacerbating atherosclerosis by regulating the OMA1/PGC1α pathway.

Atherosclerosis is closely related to endothelial dysfunction and hypertension. GSK3ß is a critical regulator in atherosclerosis. This study was carried out to investigate the effects of GSK3ß on hypertension exacerbating atherosclerosis in vitro and in vivo. L-NAME + HFD-ApoE-/- mice were used for this study for 12 weeks, and their endothelial dysfunction and inflammation were analyzed. Oil red O and H&E staining revealed that treatment with LiCl, an inhibitor of GSK3ß, reduced atherosclerotic lesions and lipid accumulation. The levels of lipid homeostasis and oxidation stress were attenuated following LiCl administration. LiCl-treated ApoE-/- mice showed lowered blood pressure. LiCl also suppressed the expressions of Drp1, Bax, ICAM1, VCAM1 and TNF-α compared to HFD + L-NAME induced mice and oxLDL + L-NAME-treated Human aorta endothelial cell line(HAECs). LiCl treatment increased the expressions of MFN2 and Bcl2. Mitotracker-red, MitoSOX and JC-1 staining indicated that LiCl treatment reduced mitochondrial division and ROS production, increased mitochondrial ΔΨm compared to oxLDL + L-NAME-treated HAECs. The expression of OMA1 was decreased by LiCl treatment, while PGC1α expression was increased. In HAECs, we found that OMA1 knockdown increased mitochondrial function and the expression of PGC1α. We also demonstrated LiCl increased OMA1 ubiquitination compared with the Control group, thus decreased OMA1 expression. Furthermore, siOMA1 antagonized the increased protein expressions of ICAM1, VCAM1, TNF-α, Bax and Drp1, decreased the protein expressions of Bcl2 and MFN2 by siPGC1α. Taken together, we demonstrated that GSK3ß could play a contributory role in hypertension exacerbating atherosclerosis by regulating the OMA1/PGC1α pathway and inhibiting mitochondrial function.

Inter3D: Capture of TAD Reorganization Endows Variant Patterns of Gene Transcription.

Topologically associating domain (TAD) reorganization commonly occurs in the cell nucleus and contributes to gene activation and inhibition through the separation or fusion of adjacent TADs. However, functional genes impacted by TAD alteration and the underlying mechanism of TAD reorganization regulating gene transcription remain to be fully elucidated. Here, we first developed a novel approach termed Inter3D to specifically identify genes regulated by TAD reorganization. Our study revealed that the segregation of TADs led to the disruption of intrachromosomal looping at the myosin light chain 12B (MYL12B) locus, via the meticulous reorganization of TADs mediating epigenomic landscapes within tumor cells, thereby exhibiting a significant correlation with the down-regulation of its transcriptional activity. Conversely, the fusion of TADs facilitated intrachromosomal interactions, suggesting a potential association with the activation of cytochrome P450 family 27 subfamily B member 1 (CYP27B1). Our study provides comprehensive insight into the capture of TAD rearrangement-mediated gene loci and moves toward understanding the functional role of TAD reorganization in gene transcription. The Inter3D pipeline developed in this study is freely available at https://github.com/bm2-lab/inter3D and https://ngdc.cncb.ac.cn/biocode/tool/BT7399.

A single dominant GLOBOSA allele accounts for repeated origins of hose-in-hose flowers in Sinningia (Gesneriaceae).

Plants bearing double flowers have long been cultivated as ornamental plants. Hose-in-hose flowers, bearing 2-whorled corolla tubes in whorls 1 and 2, are uncommon but recur in Sinningia (Gesnerioideae, Gesneriaceae). In this study, we selected 15 hose-in-hose cultivars as materials to explore the underlying molecular and genetic mechanisms of this floral architecture. We found that they originated from different hybridization events within the Dircaea clade. Three B-class MADS-box genes were globally expressed in all floral whorls, but only GLOBOSA1 (GLO1) has accumulated a dominant mutation, i.e., the insertion of a hAT-like miniature inverted-repeat transposable element (MITE) into its promoter, that co-segregated with the hose-in-hose phenotype. In addition, all 15 hose-in-hose cultivars contained the same dominant GLO1 allele. Transient gene expression assays confirmed the role of this MITE insertion in up-regulating the promoter activity of GLO1 by providing several cis-regulatory elements. Genetic transformation in heterologous Chirita pumila (Didymocarpoideae, Gesneriaceae) verified that this dominant GLO1 allele is sufficient to confer the hose-in-hose phenotype. We further demonstrated that both the GLO1 allele and the hAT-like MITE descended from wild S. cardinalis with single flowers. This study highlights the significance of wide hybridization in frequent gains of the dominant GLO1 allele and thereafter repeated occurrence of hose-in-hose flowers in Sinningia.

Effect of childhood trauma on cognitive function in individuals with major depressive disorder and healthy controls.

BACKGROUND: Individuals with major depressive disorder (MDD) exhibit cognitive impairment, while childhood trauma (CT) is associated with an elevated risk of both MDD and cognitive dysfunction. The effect of CT on cognitive function in MDD patients and healthy controls (HCs) is unclear. METHODS: MDD patients and HCs were enrolled between December 2013 and December 2016. The Childhood Trauma Questionnaire (CTQ) was used to assess CT. Depressive symptoms and cognitive function were assessed at baseline and after 8-week acute-phase treatment with selective serotonin reuptake inhibitors (SSRIs) in MDD patients. RESULTS: A total of 909 people were included in the analysis. The interaction between MDD and CT had a main effect on Digit Symbol-Coding Test (DSCT), Stroop Color Test (SCT), and Stroop Color-Word Test (SCWT) scores. The effect of CT on cognitive function disappeared after adjusting for MDD diagnosis and years of education. Neglect could predict poor performance on SCT and SCWT in the HC group. After acute-phase treatment with SSRIs, CT did not significantly predict changes in cognitive function or depressive symptoms. LIMITATIONS: The CTQ assessment might cause recall bias, and the cross-sectional design could not establish the causal link between CT and cognitive function. CONCLUSION: The effect of CT on cognitive function was modulated by MDD diagnosis and years of education. CT did not predict changes in depressive symptoms or cognitive function after acute-phase treatment with SSRIs. The direct influence of CT on cognitive function in MDD patients may be over-estimated. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02023567; registration date: December 2013.

Baiting bacteria with amino acidic and peptidic corona coated defect-engineered antimicrobial nanoclusters for optimized wound healing.

Keeping steps ahead of the bacteria in the race for more efficacious antibacterial strategies is increasingly difficult with the advent of bacterial resistance genes. Herein, we engineered copper sulfide nanoclusters (CuSx NCs) with variable sulfur defects for enhanced dual-treatment of bacterial infections by manipulating photothermal effects and Fenton-like activity. Next, by encasing CuSx NCs with a complex mixture of amino acids and short peptides derived from Luria-Bertani bacterial culture media as a protein corona, we managed to coax E. Coli to take up these CuSx NCs. As a whole, Amino-Pep-CuSx NCs was perceived as a food source and actively consumed by bacteria, enhancing their effective uptake by at least 1.5-fold greater than full length BSA protein BSA-corona CuSx NCs. Through strategically using defect-engineering, we successfully fine-tune photothermal effect and Fenton-like capacity of CuSx NCs. Increased sulfur defects lead to reduced but sufficient heat generation under solar-light irradiation and increased production of toxic hydroxyl radicals. By fine-tuning sulfur defects during synthesis, we achieve CuSx NCs with an optimal synergistic effect, significantly enhancing their bactericidal properties. These ultra-small and biodegradable CuSx NCs can rapidly break down after treatment for clearance. Thus, Amino-Pep-CuSx NCs demonstrate effective eradication of bacteria both in vitro and in vivo because of their relatively high uptake, optimal balanced photothermal and chemodynamic outcomes. Our study offers a straightforward and efficient method to enhance bacterial uptake of next generation of antibacterial agents.