Characterization and genetic differences analysis in adventitious roots development of 38 Populus germplasm resources.

To select poplar clones with excellent adventitious roots development (ARD) and deepen the understanding of its molecular mechanism, a comprehensive evaluation was conducted on 38 Populus germplasm resources with cuttings cultured in the greenhouse. Genetic differences between poplar clones with good ARD and with poor ARD were explored from the perspectives of genomics and transcriptomics. By cluster analysis of the seven adventitious roots (AR) traits, the materials were classified into three clusters, of which cluster I indicated excellent AR developmental capability and promising breeding potential, especially P.×canadensis 'Guariento', P. 'jingtong1', P. deltoides 'Zhongcheng5', P. deltoides 'Zhongcheng2'. At the genomic level, the cross-population composite likelihood ratio (XP-CLR) analysis identified 1944 positive selection regions related to ARD, and variation detection analysis identified 3426 specific SNPs and 687 specific Indels in the clones with good ARD, 3212 specific SNPs and 583 specific Indels in the clones with poor ARD, respectively. Through XP-CLR, variation detection, and weighted gene co-expression network analysis based on transcriptome data, eight major putative genes associated with poplar ARD were primary identified, and a co-expression network of eight genes was constructed, it was discovered that CSD1 and WRKY6 may be important in the ARD. Subsequently, we confirmed that SWEET17 had a non-synonymous mutation at the site of 928,404 in the clones with poor ARD, resulting in an alteration of the amino acid. After exploring phenotypic differences and the genetic variation of adventitious roots development in different poplar clones, this study provides valuable reference information for future poplar breeding and genetic improvement.

Combining GS-assisted GWAS and transcriptome analysis to mine candidate genes for nitrogen utilization efficiency in Populus cathayana.

BACKGROUND: Forest trees such as poplar, shrub willow, et al. are essential natural resources for sustainable and renewable energy production, and their wood can reduce dependence on fossil fuels and reduce environmental pollution. However, the productivity of forest trees is often limited by the availability of nitrogen (N), improving nitrogen use efficiency (NUE) is an important way to address it. Currently, NUE genetic resources are scarce in forest tree research, and more genetic resources are urgently needed. RESULTS: Here, we performed genome-wide association studies (GWAS) using the mixed linear model (MLM) to identify genetic loci regulating growth traits in Populus cathayana at two N levels, and attempted to enhance the signal strength of single nucleotide polymorphism (SNP) detection by performing genome selection (GS) assistance GWAS. The results of the two GWAS analyses identified 55 and 40 SNPs that were respectively associated with plant height (PH) and ground diameter (GD), and 92 and 69 candidate genes, including 30 overlapping genes. The prediction accuracy of the GS model (rrBLUP) for phenotype exceeds 0.9. Transcriptome analysis of 13 genotypes under two N levels showed that genes related to carbon and N metabolism, amino acid metabolism, energy metabolism, and signal transduction were differentially expressed in the xylem of P. cathayana under N treatment. Furthermore, we observed strong regional patterns in gene expression levels of P. cathayana, with significant differences between different regions. Among them, P. cathayana in Longquan region exhibited the highest response to N. Finally, through weighted gene co-expression network analysis (WGCNA), we identified a module closely related to the N metabolic process and eight hub genes. CONCLUSIONS: Integrating the GWAS, RNA-seq and WGCNA data, we ultimately identified four key regulatory genes (PtrNAC123, PtrNAC025, Potri.002G233100, and Potri.006G236200) involved in the wood formation process, and they may affect P. cathayana growth and wood formation by regulating nitrogen metabolism. This study will provide strong evidence for N regulation mechanisms, and reliable genetic resources for growth and NUE genetic improvement in poplar.

Inhibition of TRIM32 by ibr-7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway.

Pancreatic cancer is one of the most notorious diseases for being asymptomatic at early stage and high mortality rate thereafter. However, either chemotherapy or targeted therapy has rarely achieved success in recent clinical trials for pancreatic cancer. Novel therapeutic regimens or agents are urgently in need. Ibr-7 is a novel derivative of ibrutinib, displaying superior antitumour activity in pancreatic cancer cells than ibrutinib. In vitro studies showed that ibr-7 greatly inhibited the proliferation of BxPC-3, SW1990, CFPAC-1 and AsPC-1 cells via the induction of mitochondrial-mediated apoptosis and substantial suppression of mTOR/p70S6K pathway. Moreover, ibr-7 was able to sensitize pancreatic cancer cells to gemcitabine through the efficient repression of TRIM32, which was positively correlated with the proliferation and invasiveness of pancreatic cancer cells. Additionally, knockdown of TRIM32 diminished mTOR/p70S6K activity in pancreatic cancer cells, indicating a positive feedback loop between TRIM32 and mTOR/p70S6K pathway. To conclude, this work preliminarily explored the role of TRIM32 in the malignant properties of pancreatic cancer cells and evaluated the possibility of targeting TRIM32 to enhance effectiveness of gemcitabine, thereby providing a novel therapeutic target for pancreatic cancer.

Genome-Wide Analysis of the AAAP Gene Family in Populus and Functional Analysis of PsAAAP21 in Root Growth and Amino Acid Transport.

The adventitious root (AR) is the basis for successful propagation by plant cuttings and tissue culture and is essential for maintaining the positive traits of a variety. Members of the amino acid/auxin permease (AAAP) gene family play indispensable roles in various plant metabolisms and have few studies on root growth and amino acid transport. In this study, with a systematic bioinformatics analysis of the Populus AAAP family, 83 PtrAAAPs were identified from Populus trichocarpa and grouped into 8 subfamilies. Subsequently, chromosomal distribution, genetic structure, cis-elements analysis, and expression pattern analysis of the AAAP family were performed and the potential gene AAAP21 regulating root development was screened by combining the results of RNA-Seq and QTL mapping. PsAAAP21 was proven as promoting root development by enhancing AR formation. Differentially expressed genes (DEGs) from RNA-seq results of overexpressing lines were enriched to multiple amino acid-related pathways, and the amino acid treatment to transgenic lines indicated that PsAAAP21 regulated amino acid transport, including tyrosine, methionine, and arginine. Analysis of the AAAP gene family provided a theoretical basis for uncovering the functions of AAAP genes. The identification of PsAAAP21 on root promotion and amino acid transport in Populus will help with breeding new woody plant species with strong rooting ability.

Metal Nanoparticles for Photodynamic Therapy: A Potential Treatment for Breast Cancer.

Breast cancer (BC) is the most common malignant tumor in women worldwide, which seriously threatens women's physical and mental health. In recent years, photodynamic therapy (PDT) has shown significant advantages in cancer treatment. PDT involves activating photosensitizers with appropriate wavelengths of light, producing transient levels of reactive oxygen species (ROS). Compared with free photosensitizers, the use of nanoparticles in PDT shows great advantages in terms of solubility, early degradation, and biodistribution, as well as more effective intercellular penetration and targeted cancer cell uptake. Under the current circumstances, researchers have made promising efforts to develop nanocarrier photosensitizers. Reasonably designed photosensitizer (PS) nanoparticles can be achieved through non-covalent (self-aggregation, interfacial deposition, interfacial polymerization or core-shell embedding and physical adsorption) or covalent (chemical immobilization or coupling) processes and accumulate in certain tumors through passive and/or active targeting. These PS loading methods provide chemical and physical stability to the PS payload. Among nanoparticles, metal nanoparticles have the advantages of high stability, adjustable size, optical properties, and easy surface functionalization, making them more biocompatible in biological applications. In this review, we summarize the current development and application status of photodynamic therapy for breast cancer, especially the latest developments in the application of metal nanocarriers in breast cancer PDT, and highlight some of the recent synergistic therapies, hopefully providing an accessible overview of the current knowledge that may act as a basis for new ideas or systematic evaluations of already promising results.

Lactate-fueled oxidative metabolism drives DNA methyltransferase 1-mediated transcriptional co-activator with PDZ binding domain protein activation.

Activity of transcriptional co-activator with PDZ binding domain (TAZ) protein is strongly implicated in the pathogenesis of human cancer and is influenced by tumor metabolism. High levels of lactate concentration in the tumor microenvironment as a result of metabolic reprogramming are inversely correlated with patient overall survival. Herein, we investigated the role of lactate in the regulation of the activity of TAZ and showed that glycolysis-derived lactate efficiently increased TAZ expression and activity in lung cancer cells. We showed that the reactive oxygen species (ROS) generated by lactate-fueled oxidative phosphorylation (OXPHOS) in mitochondria activated AKT and thereby inhibited glycogen synthase kinase 3 beta/beta-transducin repeat-containing proteins (GSK-3ß/ß-TrCP)-mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1). Upregulation of DNMT1 by lactate caused hypermethylation of TAZ negative regulator of the LATS2 gene promoter, leading to TAZ activation. Moreover, TAZ binds to the promoter of DNMT1 and is necessary for DNMT1 transcription. Our study showed a molecular mechanism of DNMT1 in linking tumor metabolic reprogramming to the Hippo-TAZ pathway and functional significance of the DNMT1-TAZ feedback loop in the migratory and invasive potential of lung cancer cells.

Fecal lactoferrin in discriminating inflammatory bowel disease from irritable bowel syndrome: a diagnostic meta-analysis.

BACKGROUND: To perform a meta-analysis evaluating the diagnostic ability of fecal lactoferrin (FL) to distinguish inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). METHODS: The Medline, EMBASE, Web of Science, Cochrane library and CNKI databases were systematically searched for studies that used FL concentrations to distinguish between IBD and IBS. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. RESULTS: Seven studies, involving 1012 patients, were eligible for inclusion. In distinguishing IBD from IBS, FL had a pooled sensitivity of 0.78 (95% confidence interval [CI]: 0.75, 0.82), a specificity of 0.94 (95% CI: 0.91, 0.96), a positive likelihood ratio of 12.31 (95% CI: 5.93, 29.15), and a negative likelihood ratio of 0.23 (95% CI: 0.18, 0.29). The area under the summary receiver-operating characteristic curve was 0.94 (95% CI: 0.90, 0.98) and the diagnostic odds ratio was 52.65 (95% CI: 25.69, 107.91). CONCLUSIONS: FL, as a noninvasive and simple marker, is useful in differentiating between IBD and IBS.

Populus cathayana genome and population resequencing provide insights into its evolution and adaptation.

Populus cathayana Rehder, an indigenous poplar species of ecological and economic importance, is widely distributed in a high-elevation range from southwest to northeast China. Further development of this species as a sustainable poplar resource has been hindered by a lack of genome information the at the population level. Here, we produced a chromosome-level genome assembly of P. cathayana, covering 406.55 Mb (scaffold N50 = 20.86 Mb) and consisting of 19 chromosomes, with 35 977 protein-coding genes. Subsequently, we made a genomic variation atlas of 438 wild individuals covering 36 representative geographic areas of P. cathayana, which were divided into four geographic groups. It was inferred that the Northwest China regions served as the genetic diversity centers and a population bottleneck happened during the history of P. cathayana. By genotype-environment association analysis, 947 environment-association loci were significantly associated with temperature, solar radiation, precipitation, and altitude variables. We identified local adaptation genes involved in DNA repair and UV radiation response, among which UVR8, HY5, and CUL4 had key roles in high-altitude adaptation of P. cathayana. Predictions of adaptive potential under future climate conditions showed that P. cathayana populations in areas with drastic climate change were anticipated to have greater maladaptation risk. These results provide comprehensive insights for understanding wild poplar evolution and optimizing adaptive potential in molecular breeding.

Involvement of mitogen-activated protein kinase in signal transducer and activator of transcription-1 mediated differentiation induced by bortezomib in acute myeloid leukemia cells.

In this paper we report a new myeloid differentiation effect of bortezomib (BTZ) in acute myeloid leukemia (AML) cell lines and primary patient-derived AML cells; this effect was assayed by investigating growth-inhibition, cell morphology, differentiation markers, and nitro-blue tetrazolium reduction. We show that BTZ induces the phosphorylation of several mitogen-activated protein (MAP) kinases, including MEK/ERK, c-Jun N-terminal kinase (JNK), and p38 MAPK. BTZ-induced cell differentiation is almost completely reversed by PD98059, an inhibitor of MEK, which also attenuates the increase in phospho-JNK p46. However, p38 activation does not appear to be required for the differentiation induced by BTZ. Furthermore, the differentiation effect of BTZ is associated with increased protein level of signal transducer and activator of transcription-1 (STAT1), a molecular determinant of myeloid differentiation, due to effects on both its synthesis and degradation. In short, this study reveals that BTZ activates the MEK/ERK cascade, which further up-regulates the expression and activity of the key myeloid transcription factor STAT1, thus promoting myeloid differentiation. These findings contribute to an unexpected potential mechanism for the antitumor activity of BTZ in AML.

Combining radiomics and deep learning features of intra-tumoral and peri-tumoral regions for the classification of breast cancer lung metastasis and primary lung cancer with low-dose CT.

PURPOSE: To investigate the performance of deep learning and radiomics features of intra-tumoral region (ITR) and peri-tumoral region (PTR) in the diagnosing of breast cancer lung metastasis (BCLM) and primary lung cancer (PLC) with low-dose CT (LDCT). METHODS: We retrospectively collected the LDCT images of 100 breast cancer patients with lung lesions, comprising 60 cases of BCLM and 40 cases of PLC. We proposed a fusion model that combined deep learning features extracted from ResNet18-based multi-input residual convolution network with traditional radiomics features. Specifically, the fusion model adopted a multi-region strategy, incorporating the aforementioned features from both the ITR and PTR. Then, we randomly divided the dataset into training and validation sets using fivefold cross-validation approach. Comprehensive comparative experiments were performed between the proposed fusion model and other eight models, including the intra-tumoral deep learning model, the intra-tumoral radiomics model, the intra-tumoral deep-learning radiomics model, the peri-tumoral deep learning model, the peri-tumoral radiomics model, the peri-tumoral deep-learning radiomics model, the multi-region radiomics model, and the multi-region deep-learning model. RESULTS: The fusion model developed using deep-learning radiomics feature sets extracted from the ITR and PTR had the best classification performance, with the area under the curve of 0.913 (95% CI 0.840-0.960). This was significantly higher than that of the single region's radiomics model or deep learning model. CONCLUSIONS: The combination of radiomics and deep learning features was effective in discriminating BCLM and PLC. Additionally, the analysis of the PTR can mine more comprehensive tumor information.

Imaging application of an MMP2-sensitive tumor-targeted prussian blue fluorescent nanoprobe.

In recent years, the application of nanoimaging technology on standardize tumor diagnosis has become a new research hotspot, especially nanoprobes. Our research group has synthesized a kind of nanocarrier, mPEG2000-GPLGIAGQ-DSPE, which has the characteristic of matrix metalloproteinase-2 (MMP2) sensitive ability in tumor microenvironment. Meanwhile, the encapsulation method is adopted to prepare MMP2-sensitive tumor-targeted prussian blue fluorescent nanoprobe with mPEG2000-GPLGIAGQ-DSPE as the carrier. On the one hand, this novel nanoprobe not only can effectively improve the solubility of prussian blue, but is non-toxic and safe for cells. On the other hand, octapeptide (GPLGIAGQ) in mPEG2000-GPLGIAGQ-DSPE nanocarrier can specifically respond to MMP2 in tumor cells to release prussian blue, and achieve targeted intelligent imaging of tumor cells.

Current advances and development strategies of orally bioavailable PROTACs.

Proteolysis-targeting chimeras (PROTACs) have been an area of intensive research with the potential to extend drug space not target to traditional molecules. In the last half decade, we have witnessed several PROTACs initiated phase I/II/III clinical trials, which inspired us a lot. However, the structure of PROTACs beyond "rule of 5" resulted in developing PROTACs with acceptable oral pharmacokinetic (PK) properties remain one of the biggest bottleneck tasks. Many reports have demonstrated that it is possible to access orally bioavailable PROTACs through rational ligand and linker modifications. In this review, we systematically reviewed and highlighted the most recent advances in orally bioavailable PROTACs development, especially focused on the medicinal chemistry campaign of discovery process and in vivo oral PK properties. Moreover, the constructive strategies for developing oral PROTACs were proposed comprehensively. Collectively, we believe that the strategies summarized here may provide references for further development of oral PROTACs.

HZ-A-018, a novel inhibitor of Bruton tyrosine kinase, exerts anti-cancer activity and sensitizes 5-FU in gastric cancer cells.

Gastric cancer is the third leading cause of cancer related death worldwide. Due to the complexity and heterogeneity of gastric cancer, the development of targeted drugs is somehow limited, but is urgently needed. Since the expression of Bruton tyrosine kinase (BTK) was significantly associated with the prognosis of gastric cancer patients, we aimed to determine the anti-cancer activity of HZ-A-018, which was a novel derivative of ACP-196, in gastric cancer cells. As a result, HZ-A-018 presented a stronger anti-proliferation activity than ACP-196 via the substantial suppression of AKT/S6 pathway. In addition, HZ-A-018, but not ACP-196, exerted the synergistic effects in combined treatment with 5-FU both in vitro and in vivo, without exacerbating the adverse effects of 5-FU. Mechanismly, the combination of HZ-A-018 and 5-FU remarkably reduced the expression of RRM2, which played an essential role in proliferation and drug sensitivity in gastric cancer cells. In summary, our work demonstrated the stronger anti-cancer activity of HZ-A-018 than ACP-196 in gastric cancer cells, and revealed synergistic effects of HZ-A-018 and 5-FU combination probably through the inhibition of RRM2 via AKT/S6 pathway, thereby providing a promising therapeutic strategy in gastric cancer.

Potential of ATP5MG to Treat Metabolic Syndrome-Associated Cardiovascular Diseases.

Introduction: Metabolic syndrome-associated cardiovascular disease (MetS-CVD) is a cluster of metabolism-immunity highly integrated diseases. Emerging evidence hints that mitochondrial energy metabolism may be involved in MetS-CVD development. The physiopathological role of ATP5MG, a subunit of the F0 ATPase complex, has not been fully elucidated. Methods: In this study, we selected ATP5MG to identify the immunity-mediated pathway and mine drugs targeting this pathway for treating MetS-CVD. Using big data from public databases, we dissected co-expressed RNA (coRNA), competing endogenous RNA (ceRNA), and interacting RNA (interRNA) genes for ATP5MG. Results: It was identified that ATP5MG may form ceRNA with COX5A through hsa-miR-142-5p and interplay with NDUFB8, SOD1, and MDH2 through RNA-RNA interaction under the immune pathway. We dug out 251 chemicals that may target this network and identified some of them as clinical drugs. We proposed five medicines for treating MetS-CVD. Interestingly, six drugs are being tested to treat COVID-19, which unexpectedly offers a new potential host-targeting antiviral strategy. Conclusion: Collectively, we revealed the potential significance of the ATP5MG-centered network for developing drugs to treat MetS-CVD, which offers insights into the epigenetic regulation for metabolism-immunity highly integrated diseases.

Expression and Prognostic Value of Glucose Transporter 3 in Diffuse Large B Cell Lymphoma.

BACKGROUND: Several reports have suggested that glucose transporter 3 (GLUT-3) promotes tumor metastasis. The aim of this study was to examine the relationship between the expression level of GLUT-3 and the prognosis of patients with diffuse large B cell lymphoma (DLBCL). METHODS: The GLUT-3 expression levels in 91 DLBCL patients were evaluated by immunohistochemistry. The relationships between GLUT-3 expression level and clinicopathological characteristics and progression-free survival (PFS) of DLBCL patients were analyzed. The use of validation cohorts confirmed the predictive value of GLUT-3 expression. The correlation between GLUT-3 and immune cell infiltration was investigated using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts system and the analysis of the infiltrating score was obtained by single sample Gene Set Enrichment Analysis. RESULTS: Expression of GLUT-3, which is highly expressed in DLBCL patients, was significantly associated with elevated serum LDH level, recurrence and Ki-67 status. Kaplan-Meier analysis showed that high GLUT-3 expression levels in DLBCL were related to poor PFS. Univariate and multivariate analyses results showed that low GLUT-3 expression level was significantly but independently associated with favorable PFS in DLBCL patients. GLUT-3 expression was also correlated with immune cell infiltration and the analysis of the infiltrating score. CONCLUSION: Our results indicate that GLUT-3 may act as a potential independent prognostic factor in DLBCL patients. The difference of the immune microenvironment in DLBCL patients may be predicted by the expression level of GLUT-3.

A Potential Prognostic Marker for Recognizing VEGF-Positive Hepatocellular Carcinoma Based on Magnetic Resonance Radiomics Signature.

Objectives: The objective of our project is to explore a noninvasive radiomics model based on magnetic resonance imaging (MRI) that could recognize the expression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma before operation. Methods: 202 patients with proven single HCC were enlisted and stochastically distributed into a training set (n = 142) and a test set (n = 60). Arterial phase, portal venous phase, balanced phase, delayed phase, and hepatobiliary phase images were used to radiomics features extraction. We retrieved 1906 radiomic features from each phase of every participant's MRI images. The F-test was applied to choose the crucial features. A logistic regression model was adopted to generate a radiomics signature. By combining independent risk indicators from the fusion radiomics signature and clinico-radiological features, we developed a multivariable logistic regression model that could predict the VEGF status preoperatively through calculating the area under the curve (AUC). Results: The entire group comprised 108 VEGF-positive individuals and 94 VEGF-negative patients. AUCs of 0.892 (95% confidence interval [CI]: 0.839 - 0.945) in the training dataset and 0.800 (95% CI: 0.682 - 0.918) in the test dataset were achieved by utilizing radiomics features from two phase images (8 features from the portal venous phase and 5 features from the hepatobiliary phase). Furthermore, the nomogram relying on a combined model that included the clinical factors α-fetoprotein (AFP), irregular tumor margin, and the fusion radiomics signature performed well in both the training (AUC = 0.936, 95% CI: 0.898-0.974) and test (AUC = 0.836, 95% CI: 0.728-0.944) datasets. Conclusions: The combined model acquired from two phase (portal venous and hepatobiliary phase) pictures of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI could be considered as a credible prognostic marker for the level of VEGF in HCC.

Polygonum cuspidatum inhibits the growth of osteosarcoma cells via impeding Akt/ERK/EGFR signaling pathways.

ABBREVIATIONS: CC: Closeness centrality; OS: Osteosarcoma; TCM: Traditional Chinese medicine; NSCLC: Non-small cell lung cancer; DC: Degree centrality; CHM: Chinese herb medicine; BC: Betweenness centrality.

Inhibition of all-trans-retinoic acid-induced proteasome activation potentiates the differentiating effect of retinoid in acute myeloid leukemia cells.

All-trans retinoic acid (ATRA) is nowadays considered to be the sole efficient agent for differentiation-based therapy in leukemia; however, the mechanisms of ATRA's biological effects remain largely unknown. Here we first reported that ATRA-induced myeloid leukemia differentiation was accompanied with the increased level of ubiquitin-protein conjugates and the upregulation of proteasome activity. To explore the functional role of the activated proteasome in retinoic acid (RA) signaling, the effects of proteasome inhibitors on RA-induced cell differentiation were determined. Our results demonstrated that inhibition of ATRA-elevated proteasome activity obviously promoted the myeloid maturation program triggered by ATRA, suggesting that the overactivated proteasome is not beneficial for ATRA's effects. Further studies demonstrated that the synergistic differentiating effects of ATRA and proteasome inhibitors might be associated with the protection of retinoic acid receptor alpha (RARα) from degradation by the ubiquitin-proteasome pathway (UPP). Moreover, the accumulated RARα was able to enhance the transcription of its target gene, which might also contribute to the enhanced differentiation of leukemia cells. Together, by linking the UPP to ATRA-dependent signaling, our data provide a novel insight into studying the mechanisms of ATRA-elicited cellular effects and imply the possibility of combination of ATRA and proteasome inhibitors in leukemia therapy.

Association of Serum Melatonin Level with Mild Cognitive Impairment in Type 2 Diabetic Patients: A Cross-Sectional Study.

OBJECTIVES: Melatonin is an essential neuroendocrine hormone that participates in the regulation of sleep rhythm and cognitive function. This study aimed to determine serum melatonin levels with mild cognitive impairment (MCI) in patients with type 2 diabetes (T2DM). METHODS: A total of 247 T2DM patients were recruited in this retrospective study and divided into 75 subjects with MCI and 172 with normal cognition. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Their blood sample was examined for the level of melatonin and other biochemical parameters. RESULTS: Melatonin concentration was decreased in MCI patients to non-MCI patients (P < 0.001). Melatonin level was negatively correlated with age (r = -0.202; P = 0.001), diabetes duration (r = -0.282; P < 0.001), serum HbA1c (r = -0.195; P = 0.002), hs-CRP (r = -0.324; P < 0.001), and TSH (r = -0.184; P = 0.004) levels and positively correlated with MoCA score, serum HDL-C (r = 0.145; P < 0.001), FT3 (r = 0.241; P < 0.001), and FT4 (r = 0.169; P = 0.008) levels. The multivariable analysis indicated that fewer years of formal education, longer diabetes duration, higher serum HbA1c, higher serum hs-CRP, and lower serum melatonin are the predisposing factors for MCI. CONCLUSION: Lower melatonin level was associated with cognitive impairment in patients with T2DM. Melatonin might serve as a potential protective molecule against cognitive dysfunction in T2DM.

Corrigendum: Expression of Multiple Exogenous Insect Resistance and Salt Tolerance Genes in Populus nigra L.

[This corrects the article DOI: 10.3389/fpls.2020.01123.].