Whole-genome resequencing revealed the population structure and selection signal of 4 indigenous Chinese laying ducks.

The assessment of animal genetic structure had significant importance for the preservation and breeding of animal germplasm resources. Selection signals are genotype markers generated during the process of biological evolution, and the detection of selection signals could reveal the direction of species evolution. The aim of this study was to generate a whole-genome resequencing data from Jinding duck, Shanma duck, Youxian Partridge duck, and Taiwan Brown tsaiya duck to reveal their population structure and selection signals. The population structure analysis revealed significant genetic differences among the 4 indigenous laying ducks, indicating their independent lineage. Specifically, Shanma duck and Youxian partridge duck were closely and likely originated from a common ancestor. In addition, selection sweep analysis was performed using the population genetic differentiation coefficient (Fst) and nucleotide diversity ratio (π ratio). The top 5% was used as the threshold for the Fst and π ratio, and the 2 thresholds were combined to identify selected genomic regions. In the selected regions of the 3 comparison groups, 136, 143, and 268 candidate genes were detected. Further screening of all candidate genes revealed that 35 candidate genes appeared simultaneously in 3 comparative groups, with 16 genes annotated. The 16 genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The results revealed 5 functional genes (AQP3, PIK3C3, NOL6, RPP25, and DCTN3) that may be related to important economic traits in laying ducks and involved mainly invasopressin-regulated water reabsorption, ribosome biogenesis, and the PI3K signaling pathway. The results provide insights into the protection and exploitation of genetic resources of Chinese indigenous laying ducks.

Status and Influencing Factors of Foot Care Behavior for Patients with Diabetic Foot Amputation: Across-Sectional Study.

This study aimed to investigate the contemporary status and influencing factors of foot self-care behavior in diabetic foot amputation patients. A total of 250 patients with diabetic foot amputation were included. The general information questionnaire, Chinese Version of the Nottingham Assessment of Function Footcare (CNAFF), Knowledge of Diabetic Foot Questionnaire, and The Third Version of the Diabetes Attitude Scale were used to investigate the status and influencing factors of foot self-care behavior in patients with diabetic foot amputation. From our sample, the Chinese version of Nottingham foot care behavior score was 68.32 ± 10.35 points, which showed that the foot self-care behavior of patients with diabetic foot amputation is at a medium level. Multiple linear regression analysis showed that education level, the knowledge of how to choose shoes and socks, the knowledge of self-care for feet, the need for special training in education, and the patient's autonomy in diabetes care were the main factors influencing foot self-care behavior of patients with diabetic foot amputation (P < 0.05). The total variation of CNAFF score was 49%. The results of this study show that the level of foot care of diabetic amputees must be improved, and medical staffs need to take targeted intervention measures to help patients improve their self-care behavior after amputation, thereby reducing the recurrence rate of diabetic feet and improving their quality of life.

The Interplay Between Epilepsy and Parkinson's Disease: Gene Expression Profiling and Functional Analysis.

The results of many epidemiological studies suggest a bidirectional causality may exist between epilepsy and Parkinson's disease (PD). However, the underlying molecular landscape linking these two diseases remains largely unknown. This study aimed to explore this possible bidirectional causality by identifying differentially expressed genes (DEGs) in each disease as well as their intersection based on two respective disease-related datasets. We performed enrichment analyses and explored immune cell infiltration based on an intersection of the DEGs. Identifying a protein-protein interaction (PPI) network between epilepsy and PD, and this network was visualised using Cytoscape software to screen key modules and hub genes. Finally, exploring the diagnostic values of the identified hub genes. NetworkAnalyst 3.0 and Cytoscape software were also used to construct and visualise the transcription factor-micro-RNA regulatory and co-regulatory networks, the gene-microRNA interaction network, as well as gene-disease association. Based on the enrichment results, the intersection of the DEGs mainly revealed enrichment in immunity-, phosphorylation-, metabolism-, and inflammation-related pathways. The boxplots revealed similar trends in infiltration of many immune cells in epilepsy and Parkinson's disease, with greater infiltration in patients than in controls. A complex PPI network comprising 186 nodes and 512 edges were constructed. According to node connection degree, top 15 hub genes were considered the kernel targets of epilepsy and PD. The area under curve values of hub gene expression profiles confirmed their excellent diagnostic values. This study is the first to analyse the molecular landscape underlying the epidemiological link between epilepsy and Parkinson's disease. The two diseases are closely linked through immunity-, inflammation-, and metabolism-related pathways. This information was of great help in understanding the pathogenesis, diagnosis, and treatment of the diseases. The present results may provide guidance for further in-depth analysis about molecular mechanisms of epilepsy and PD and novel potential targets.

Polyethylenimine Triggers Dll4 Degradation to Regulate Angiogenesis In Vitro.

The Dll4-Notch signaling pathway plays a crucial role in the regulation of angiogenesis and is a promising therapeutic target for diseases associated with abnormal angiogenesis, such as cancer and ophthalmic diseases. Here, we find that polyethylenimine (PEI), a cationic polymer widely used as nucleic acid transfection reagents, can target the Notch ligand Dll4. By immunostaining and immunoblotting, we demonstrate that PEI significantly induces the clearance of cell-surface Dll4 and facilitates its degradation through the lysosomal pathway. As a result, the activation of Notch signaling in endothelial cells is effectively inhibited by PEI, as evidenced by the observed decrease in the generation of the activated form of Notch and expression of Notch target genes Hes1 and Hey1. Furthermore, through blocking Dll4-mediated Notch signaling, PEI treatment enhances angiogenesis in vitro. Together, our study reveals a novel biological effect of PEI and establishes a foundation for the development of a Dll4-targeted biomaterial for the treatment of angiogenesis-related disease.

The network regulation mechanism of the effects of heat stress on the production performance and egg quality of Jinding duck was analyzed by miRNA‒mRNA.

To explore the differential regulation mechanism of heat stress on the egg production performance and egg quality of Jinding ducks, 200 Jinding ducks (360-day-old) in good health and with similar body weights and a normal appetite were selected and randomly divided into a control (normal temperature [NT]) group (20°C-25°C) and a heat stress (HS) group (32°C-36°C), with 4 replicates in each group and 25 ducks in each replicate. The pretrial period was 1 wk, and the formal trial period was 4 wk. At the end of the 4th wk, 12 duck eggs were collected from each replicate to determine egg quality. Pituitary and ovarian tissues of Jinding ducks were collected, transcriptome sequencing was performed to screen differentially expressed miRNAs and mRNAs related to high temperature and heat stress, and a competitive endogenous RNA regulatory network was constructed. The sequencing data were verified by qRT‒PCR method. The following results were obtained: (1) Compared with the NT group, the HS group had a significantly lower laying rate, total egg weight, average egg weight, total feed intake, and feed intake per duck (P < 0.01), an extremely significantly higher feed-to-egg ratio (P < 0.01), and a higher mortality rate. (2) Compared with the NT group, the HS group had an extremely significantly lower egg weight, egg yolk weight, eggshell weight, and eggshell strength (P < 0.01) and an extremely significantly lower yolk ratio and eggshell thickness (P < 0.01, P < 0.05); however, there was no significant difference in the egg shape index, Haugh unit or protein height (P > 0.05). (3) A total of 1,974 and 1,202 genes were identified in the pituitary and ovary, respectively, and there were 5 significantly differentially expressed miRNAs. The differentially expressed genes were involved in the arginine and proline metabolism pathways, ether lipid metabolism pathway, and drug metabolism-cytochrome P450 pathway, which are speculated to be related to the egg production performance of Jingding ducks under high-temperature heat stress. (4) Novel_221 may target the PRPS1 gene to participate in egg production performance; novel_168 and novel_289 may target PIGW; novel_289 may target Q3MUY2; and novel_289 and novel_208 may target PIGN or genes that may be related to high-temperature heat stress. (5) In pituitary tissue, upregulated novel_141 (center of the network) formed a regulatory network with HSPB1 and HSP30A, and downregulated novel_366 (center of the network) formed a regulatory network with the JIP1 gene. In ovarian tissue, downregulated novel_289 (center of the network) formed a regulatory network with the ZSWM7, ABI3, and K1C23 genes, novel_221 formed a regulatory network with the IGF1, BCL7B, SMC6, APOA4, and FARP2 genes, and upregulated novel_40 formed a regulatory network with the HA1FF10 gene. In summary, heat stress affects the production performance and egg quality of Jinding ducks by regulating the secretion of endocrine-related hormones and the release of neurotransmitters as well as the expression of miRNAs and mRNAs in pituitary and ovarian tissues. The miRNA‒mRNA regulatory network provides a theoretical basis for the molecular mechanism that regulates the stress response in pituitary and ovarian tissues, egg quality, and production performance under heat stress.

In Situ Growth of Sub-50-nm Zirconium Aminobenzenedicarboxylate Metal-Organic Framework Nanocrystals for Carbon Dioxide Capture.

Controlled synthesis of sub-50-nm metal-organic frameworks (MOFs), which are usually called porous coordination polymers, exhibits huge potential applications in gas storage and separation. Herein, surface-confined growth of zirconium aminobenzenedicarboxylate MOF (UIO-66-NH2) nanocrystals on polypyrrole hollow spheres (PPyHSs) is achieved through covalently grafted benzene dicarboxylic acid ligands using bridged molecules. PPyHSs modified with ligand molecules prohibit excessive growth of UIO-66-NH2 nanocrystals on their confined surface, resulting in smaller-sized nanocrystals (<50 nm) and a monolayer UIO-66-NH2 coating. Benefiting from the homogeneous dispersion of UIO-66-NH2 nanocrystals with a smaller size (40 ± 10 nm), the as-prepared PPyHSs@UIO-66-NH2 hybrids with high specific surface area and pore volume exhibit remarkable CO2 capture performance. Moreover, the time required to reach the maximum CO2 adsorption capacity shortens with decreasing UIO-66-NH2 crystals size. As a proof of concept, the proposed covalent grafting strategy can be used for synthesizing sub-50-nm UIO-66-NH2 nanocrystals for CO2 capture.

Antimicrobial resistance and virulence profiles of staphylococci isolated from clinical bovine mastitis.

Staphylococci, mainly including Staphylococcus aureus and coagulase-negative staphylococci (CNS), are one of the most common pathogens causing bovine mastitis worldwide. In this study, we investigated the antimicrobial resistance and virulence profiles of staphylococci from clinical bovine mastitis in Ningxia Hui Autonomous Region of China. Antimicrobial resistance was determined by disc diffusion combined with E-test method. Genes of antimicrobial resistance and virulence factors were determined by PCR. A total of 332 staphylococcal isolates were confirmed from 1,519 mastitic milk samples, including 172 S. aureus and 160 CNS isolates. Fifteen CNS species were identified, with S. chromogenes being the most frequent found (49.4%), followed by S. equorum (13.8%). Noticeably, 2 S. agnetis isolates were found among the CNS isolates. To our knowledge, this is the first report documenting the presence of S. agnetis from bovine mastitis in China. The S. aureus and CNS isolates showed high resistance against penicillin, followed by erythromycin and tetracycline. Multidrug resistance was found in 11.6 and 16.3% of the S. aureus and CNS isolates, respectively. Resistance to penicillin was attributed to the presence of blaZ, erythromycin resistance to ermC (alone or combined with ermB) and tetracycline resistance to tetK (alone or combined with tetM). Notably, one S. equorum isolate and one S. saprophyticus isolate were both methicillin-resistant and mecA positive. Additionally, all S. aureus isolates carried the adhesin genes fnbpA, clfA, clfB, and sdrC, and most of them contained cna and sdrE. Conversely, only a few of the CNS isolates carried clfA, cna, and fnbA. Regarding toxin genes, all S. aureus isolates harbored hlb, and most of them were hlg positive. The lukE-lukD, lukM, sec, sed, sei, sen, seo, tst, seg, seh, and sej were also detected with low frequencies. However, no toxin genes were observed in CNS isolates. This study reveals high species diversity of staphylococci from clinical bovine mastitis in Ningxia Hui Autonomous Region of China. The findings for the genetic determinants of antimicrobial resistance and virulence factor provide valuable information for control and prevention of staphylococcal bovine mastitis.

Clinical Study on the Emotional Intervention of Patients with Asymptomatic and Mild Novel Coronavirus (COVID-19).

Background and Objectives: The aim was to explore the interventional effect of the traditional Chinese medicine (TCM) exercise of Tian Dan Shugan Tiaoxi on the emotions of patients with mild novel coronavirus (COVID-19). Materials and Methods: A total of 110 asymptomatic and mildly symptomatic COVID-19 patients from Hongkou Memorial Road Temporary Cabin Hospital and South Renji Hospital were selected between April 2022 and June 2022, and randomly divided into two groups: a control group and an intervention group. There were 55 participants in each group. The control group was treated with Lianhua Qingwen granules, and members of the intervention group were made to practice Tian Dan Shugan Tiaoxi (an exercise that soothes the liver and regulates emotions) every day for 5 days. The Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder questionnaire (GAD-7), and the Symptom Checklist 90 (SCL-90) were used to evaluate the data collected before and after the trial. Results: The incidence of anxiety and depression was high in the patients included in this study, at 73.64% and 69.09%, respectively. After intervention, the scores of the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder questionnaire (GAD-7) in the two groups had decreased in comparison with those recorded before intervention (p < 0.05). The PHQ-9 and GAD-7 scores in the intervention group were significantly better than those of the control group (p < 0.05). The factors of somatization, depression, anxiety, hostility, and fear in the SCL-90 in the intervention group were significantly improved after intervention, and generally, better than those in the control group (p < 0.05). Conclusions: Patients infected with novel coronavirus in shelter hospitals have different degrees of emotional abnormalities. Tian Dan Shugan Tiaoxi can reduce the anxiety and depression of people with mild novel coronavirus, and it can be practiced clinically to improve the recovery rate among infected people.

A cross-sectional observational study on the level of diabetes knowledge and related influencing factors among orthopaedic nurses.

AIM: To evaluate the level of diabetes knowledge and related influencing factors among Chinese orthopaedic nurses. DESIGN: A cross-sectional observational study. The STROBE checklist was followed. METHODS: A convenience sampling method was adopted by using the Questionnaire Star application to publish online questionnaire. The nurses' diabetes knowledge levels were assessed, including a total of 34 items from the "Orthopaedic Nurses Diabetes Knowledge Mastery Questionnaire" and the "Orthopaedic Nurses General Information Questionnaire" between July 2020 and September 2020. RESULTS: Altogether, 363 nurses participated in the survey. Their levels of diabetes-related knowledge were moderate or lower (16.51 ± 2.96 out of 25 points). The knowledge level was closely related to five factors: professional title, education level, whether the hospital employed diabetes specialist nurses or treated outpatients, type of diabetes-related training received and whether the individual was familiar with and adhered to current treatment guidelines. The knowledge level can be improved by providing additional training that accounts for these factors.

Effect of short-term acute moderate-intensity resistance exercise on blood glucose in older patients with type 2 diabetes mellitus and sarcopenia.

AIM: To investigate the effects of short-term acute moderate-intensity resistance exercise on blood glucose in older patients with type 2 diabetes mellitus and sarcopenia using ambulatory glucose monitoring technology. METHODS: This is a prospective intervention of an own-controlled before-and-after cohort study. A total of 24 older type 2 diabetes mellitus patients who met the enrollment criteria were selected, including 12 cases in the sarcopenia and 12 in the non-sarcopenia groups. First, they wore ambulatory glucose monitoring devices (Medtronic, Ipro2) and retained baseline data. Then they wore Ipro2 again and carried out two sessions of resistance exercise on alternate days. Blood glucose level, blood glucose fluctuation, and time in target range on the contrast and exercise days were compared and analyzed in both groups. RESULTS: The area under the curve of glucose level across 24 h and the mean blood glucose post exercise decreased (P < 0.05) in the sarcopenia group. On the exercise day, the coefficient of variation of glucose, the largest amplitude of glycemic excursions, amplitude of postprandial glucose excursions and low blood glucose index decreased, whereas the time in target range increased (P < 0.05). CONCLUSIONS: Short-term acute moderate-intensity resistance exercise is an effective and safe exercise modality, which can reduce blood glucose levels, blood glucose fluctuations and the risk of hypoglycemia, as well as improve the time in target range for older patients with type 2 diabetes mellitus and sarcopenia. Geriatr Gerontol Int 2022; 22: 653-659.

Rapid and sustained restoration of astrocytic functions by ketamine in depression model mice.

Molecules with fast-acting antidepressant effects have potentials to become new antidepressants. Here we report the fast-acting (1hr) antidepressant effects of ketamine (10 mg/kg, i.p.) in chronic adreno-cortico-tropic-hormone (ACTH)-induced and chronic unpredictable mild stress (CUMS)-induced depression mouse models. These behavioral anti-depressant effects are associated with normalized expression of glutamate transporter-1(GLT-1), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and eukaryotic elongation factor 2 phosphorylation (p-eEF2) in the prelimbic prefrontal cortex (PrL-PFC). Excitatory neurons in PrL also showed reduced ambient glutamate responses to synaptic stimulation, and reduced ambient NMDA receptor responses after ketamine injection. Interestingly, ketamine induced biochemical and electrophysiological changes still occurred with GLT-1 knockdown in PrL, suggesting that elevated GLT-1 level is not required for ketamine to exert its antidepressant effect. At the same time, ketamine did not elevate GLT-1 level in the isolated astrocytes, suggesting distinct contributions from neurons and astrocytes to ketamine-induced changes.

Phenotypic Spectrum and Prognosis of Epilepsy Patients With GABRG2 Variants.

Objective: This study aimed to obtain a comprehensive understanding of the genetic and phenotypic aspects of GABRG2-related epilepsy and its prognosis and to explore the potential prospects for personalized medicine. Methods: Through a multicenter collaboration in China, we analyzed the genotype-phenotype correlation and antiseizure medication (ASM) of patients with GABRG2-related epilepsy. The three-dimensional protein structure of the GABRG2 variant was modeled to predict the effect of GABRG2 missense variants using PyMOL 2.3 software. Results: In 35 patients with GABRG2 variants, 22 variants were de novo, and 18 variants were novel. The seizure onset age was ranged from 2 days after birth to 34 months (median age: 9 months). The seizure onset age was less than 1 year old in 22 patients (22/35, 62.9%). Seizure types included focal seizures (68.6%), generalized tonic-clonic seizures (60%), myoclonic seizures (14.3%), and absence seizures (11.4%). Other clinical features included fever-sensitive seizures (91.4%), cluster seizures (57.1%), and developmental delay (45.7%). Neuroimaging was abnormal in 2 patients, including dysplasia of the frontotemporal cortex and delayed myelination of white matter. Twelve patients were diagnosed with febrile seizures plus, eleven with epilepsy and developmental delay, two with Dravet syndrome, two with developmental and epileptic encephalopathy, two with focal epilepsy, two with febrile seizures, and four with unclassified epilepsy. The proportions of patients with missense variants in the extracellular region and the transmembrane region exhibiting developmental delay were 40% and 63.2%, respectively. The last follow-up age ranged from 11 months to 17 years. Seizures were controlled in 71.4% of patients, and 92% of their seizures were controlled by valproate and/or levetiracetam. Conclusion: The clinical features of GABRG2-related epilepsy included seizure onset, usually in infancy, and seizures were fever-sensitive. More than half of the patients had cluster seizures. Phenotypes of GABRG2-related epilepsy were ranged from mild febrile seizures to severe epileptic encephalopathies. Most patients with GABRG2 variants who experienced seizures had a good prognosis. Valproate and levetiracetam were effective treatments for most patients.

Hyaluronan-mediated motility receptor antisense RNA 1 promotes hepatitis B virus-related hepatocellular carcinoma progression by regulating miR-627-3p/High Mobility Group AT-hook 2 axis.

Hepatocellular carcinoma (HCC) is a common malignancy in the world, with high mortality and poor prognosis. Hepatitis B virus (HBV) is one of the key factors implicated in the occurrence of HCC. Increasing evidence suggests that miRNAs play important roles in the development and metastasis of HBV-associated HCC (HBV-HCC). Here, we performed CCK8 (Cell count kit-8), EdU (5-ethynyl-2'-deoxyuridine) incorporation assay, wound-healing assay, transwell assay to study the changes in the cellular phenotype. Luciferase reporter assay, RNA pull-down experiment, RT-qPCR and western blotting were employed to study molecular mechanism. In addition, we also constructed a mouse HCC xenograft model to verify the functional role of HMMR-AS1/miR-627-3p/HMGA2 signal axis in vivo. Our study demonstrated that HMMR-AS1 was highly expressed in HCC tissues and cell lines, suggesting its implication in the progression of HCC. In addition, in vitro experiments showed that high HMMR-AS1 expression facilitated the migration, invasion, and proliferation of HCC cells. We further revealed that HMMR-AS1 promoted the malignant phenotype of HCC cells by regulating miR-627-3p/HMGA2 axis. Together, our data suggest that HMMR-AS1 regulates HBV-HCC progression via miR-627-3p/HMGA2 axis.

Electrochromism of Viologen/Polymer Composite: From Gel to Insulating Bulk for High-Voltage Applications.

Power equipment operates under high voltages, inducing space charge accumulation on the surface of key insulating structures, which increases the risk of discharge/breakdown and the possibility of maintenance workers experiencing electric shock accidents. Hence, a visualized non-equipment space charge detection method is of great demand in the power industry. Typical electrochromic phenomenon is based on redox of the material, triggered by a voltage smaller than 5 V with a continuous current in µA~mA level, which is not applicable to high electric fields above 106 V/m with pA~nA operation current in power equipment. Until now, no naked-eye observation technique has been realized for space charge detection to ensure the operation of power systems as well as the safety of maintenance workers. In this work, a viologen/poly(vinylidene fluoride-co-hexafluoropropylene)(P(VDF-HFP)) composite is investigated from gel to insulating bulk configurations to achieve high-voltage electrical-insulating electrochromism. The results show that viologen/P(VDF-HFP) composite bulk can withstand high electric fields at the 107 V/m level, and its electrochromism is triggered by space charges. This electrochromism phenomenon can be visually extended by increasing viologen content towards 5 wt.% and shows a positive response to voltage amplitude and application duration. As viologen/P(VDF-HFP) composite bulk exhibits a typical electrical insulating performance, it could be attached to the surface of insulating structures or clamped between metal and insulating materials as a space charge accumulation indicator in high-voltage power equipment.

WNT3 hypomethylation counteracts low activity of the Wnt signaling pathway in the placenta of preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy. Many studies have shown that epigenetic mechanisms may play a role in preeclampsia. Moreover, our previous study indicated that the differentially methylated genes in preeclampsia were enriched in the Wnt/ß-catenin signaling pathway. This study aimed to identify differentially methylated Wnt/ß-catenin signaling pathway genes in the preeclamptic placenta and to study the roles of these genes in trophoblast cells in vitro. Using an Illumina Infinium HumanMethylation 850 K BeadChip, we found that the Wnt signaling pathway was globally hypermethylated in the preeclamptic group compared with the term birth group, but hypomethylated in the preeclamptic group compared with the preterm birth group. Among all Wnt/ß-catenin signaling pathway factors, WNT3 was the most significantly differentially expressed gene and was hypomethylated in the preeclamptic group compared to the nonhypertensive groups, namely, the preterm birth group and term birth group. This result was confirmed by pyrosequencing. Through quantitative real-time PCR and western blot analysis, the WNT3 gene was found to be highly expressed in preeclamptic placental tissues, in contrast to other WNT factors, which were previously reported to be expressed at low levels in placental tissues. Additionally, in the HTR8/SVneo cell line, knockdown of WNT3 suppressed the Wnt/ß-catenin signaling pathway, consistent with the findings for other WNT factors. These results prompted us to speculate that the WNT3 gene counteracts the low activation state of the Wnt signaling pathway in the preeclamptic placenta through methylation modification.

Intrinsic bioactivity of black phosphorus nanomaterials on mitotic centrosome destabilization through suppression of PLK1 kinase.

Although nanomaterials have shown promising biomedical application potential, incomplete understanding of their molecular interactions with biological systems prevents their inclusion into mainstream clinical applications. Here we show that black phosphorus (BP) nanomaterials directly affect the cell cycle's centrosome machinery. BP destabilizes mitotic centrosomes by attenuating the cohesion of pericentriolar material and consequently leads to centrosome fragmentation within mitosis. As a result, BP-treated cells exhibit multipolar spindles and mitotic delay, and ultimately undergo apoptosis. Mechanistically, BP compromises centrosome integrity by deactivating the centrosome kinase polo-like kinase 1 (PLK1). BP directly binds to PLK1, inducing its aggregation, decreasing its cytosolic mobility and eventually restricting its recruitment to centrosomes for activation. With this mechanism, BP nanomaterials show great anticancer potential in tumour xenografted mice. Together, our study reveals a molecular mechanism for the tumoricidal properties of BP and proposes a direction for biomedical application of nanomaterials by exploring their intrinsic bioactivities.

A novel pyrrole-imidazole polyamide targets Aurora kinase A and suppresses tumor growth in vivo.

Aurora kinase A (Aurora A) plays a critical role in regulating cell mitotic progression and has been considered as a promising drug target for cancer therapy. To develop a novel molecule targeting Aurora A with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide (PIP) Hoechst conjugate, PIP-Ht, targeting to a cell-cycle regulated DNA sequence locating at the promoter of human Aurora A gene (AURKA). PIP-Ht potently suppressed AURKA promoter activities, mRNA expression and protein level, induced tumor cell cycle delay and inhibited tumor cell proliferation in vitro. Furthermore, subcutaneous injection of PIP-Ht into mice bearing human cancer xenografts induced significant tumor growth suppression and cell apoptosis. Collectively, PIP-Ht exhibits the potential as an effective therapeutic candidate for the tumor treatment.

Coibamide A kills cancer cells through inhibiting autophagy.

Natural products are useful tools for biological mechanism research and drug discovery. Due to the excellent tumor cell growth inhibitory profile and sub-nanomolar potency, Coibamide A (CA), an N-methyl-stabilized depsipeptide isolated from marine cyanobacterium, has been considered as a promising lead compound for cancer treatment. However, the molecular anti-cancer mechanism of the action of CA remains unclear. Here, we showed that CA treatment induced caspase-independent cell death in breast cancer cells. CA treatment also led to severe lysosome defects, which was ascribed to the impaired glycosylation of lysosome membrane protein LAMP1 and LAMP2. As a consequence, the autophagosome-lysosome fusion was blocked upon CA treatment. In addition, we presented evidence that this autophagy defect partially contributed to the CA treatment-induced tumor cell death. Together, our work uncovers a novel mechanism underlying the anti-cancer action of CA, which will promote its further application for cancer therapy.

miR­18a­5p promotes melanoma cell proliferation and inhibits apoptosis and autophagy by targeting EPHA7 signaling.

Micro (mi)RNAs serve crucial roles in cancer development although little is known about their cellular mechanisms in the pathogenesis of melanoma. The present study explored the regulatory roles of miR­18a­5p in melanoma cell proliferation, apoptosis and autophagy, in addition to its target gene in melanoma cells. miRNA and ephrin receptor A7 (EPHA7) mRNA were analyzed by reverse transcription­quantitative PCR. Cell Counting Kit­8 and colony formation assays were performed to examine the cell proliferation rate. Hoechst staining and flow cytometry were performed to investigate cell apoptosis. Western blotting was used to estimate the abundance of proteins. Dual-luciferase reporter assay verified the binding of miRNA with target gene sequences. Melanoma tissues and cell lines exhibited markedly elevated miR­18a­5p expression. miR­18a­5p inhibitor inhibited proliferation rates, and triggered apoptosis and autophagy marker protein expression in WM266­4 and A375 cells. It also negatively regulated EPHA7 expression in WM266­4 and A375 cells by directly binding at the 3'­untranslated region of EPHA7. miR­18a­5p mimics reversed the EPHA7 overexpression­induced suppression of proliferation, and the EPHA7 overexpression­induced promotion of apoptosis and autophagy. miR­18a­5p triggered proliferation of melanoma cells and inhibited apoptosis and autophagy by directly targeting and inhibiting EPHA7 expression. Thus, the present study aided our understanding of miRNA­mediated melanoma pathogenesis.