Annotation of nuclear lncRNAs based on chromatin interactions.

The human genome is pervasively transcribed and produces a wide variety of long non-coding RNAs (lncRNAs), constituting the majority of transcripts across human cell types. Some specific nuclear lncRNAs have been shown to be important regulatory components acting locally. As RNA-chromatin interaction and Hi-C chromatin conformation data showed that chromatin interactions of nuclear lncRNAs are determined by the local chromatin 3D conformation, we used Hi-C data to identify potential target genes of lncRNAs. RNA-protein interaction data suggested that nuclear lncRNAs act as scaffolds to recruit regulatory proteins to target promoters and enhancers. Nuclear lncRNAs may therefore play a role in directing regulatory factors to locations spatially close to the lncRNA gene. We provide the analysis results through an interactive visualization web portal at https://fantom.gsc.riken.jp/zenbu/reports/#F6_3D_lncRNA.

Network analysis of suicide ideation and depression-anxiety symptoms among Chinese adolescents.

Background: The co-occurrence of depression and anxiety among adolescents is typically associated with suicide ideation. Aims: The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and anxiety. Methods: 1501 adolescents aged 12-19 years were assessed using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale, and 716 adolescents who scored ≥5 on both scales were selected as participants. Network analysis was used to identify the network structure of depressive symptoms and anxiety symptoms. Participants were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9. A comparison was made between the depression-anxiety symptom networks of the two groups. Results: 'Restlessness', 'sad mood' and 'trouble relaxing' were the most prominent central symptoms in the depression-anxiety symptom network, and 'restlessness', 'nervousness' and 'reduced movement' were the bridge symptoms in this network. 'Sad mood' was found to be directly related to 'suicide ideation' with the highest variance. The network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group, with 'restlessness' and 'sad mood' exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation group. Conclusion: Restlessness and sad mood could be targeted for the intervention of depression-anxiety symptoms among adolescents with suicide ideation.

The Development of a Series of Genomic DNA Reference Materials with Specific Copy Number Ratios for The Detection of Genetically Modified Maize DBN9936.

The genetically modified (GM) maize DBN9936 with a biosafety certificate will soon undergo commercial application. To monitor the safety of DBN9936 maize, three genomic DNA (gDNA) reference materials (RMs) (DBN9936a, DBN9936b, and DBN9936c) were prepared with nominal copy number ratios of 100%, 3%, and 1% for the DBN9936 event, respectively. DBN9936a was prepared from the leaf tissue gDNA of DBN9936 homozygotes, while DBN9936b and DBN9936c were prepared by the quantitative mixing of gDNA from the leaf tissues of DBN9936 homozygotes and non-GM counterparts. Validated DBN9936/zSSIIb duplex droplet digital PCR was demonstrated to be an accurate reference method for conducting homogeneity study, stability study, and collaborative characterization. The minimum intake for one measurement was determined to be 2 µL, and the gDNA RMs were stable during transport at 37 °C for 14 days and storage at -20 °C for 18 months. Each gDNA RM was certified for three property values: DBN9936 event copy number concentration, zSSIIb reference gene copy number concentration, and DBN9936/zSSIIb copy number ratio. The measurement uncertainty of the certified values took the uncertainty components related to possible inhomogeneity, instability, and characterization into account. This batch of gDNA RMs can be used for calibration and quality control when quantifying DBN9936 events.

Oxidative stress-activated Nrf2 remitted polystyrene nanoplastic-induced mitochondrial damage and inflammatory response in HepG2 cells.

Generated from plastics, microplastics (MPs) and nanoplastics (NPs) are difficult to completely degrade in the natural environment, which can accumulate in almost all lives. Liver is one of the main target organs. In this study, HepG2 and L02 cells were exposed to 0-50 µg/mL polystyrene (PS)-NPs to investigate the mechanism of mitochondrial damage and inflammation. The results showed mitochondria damage and inflammatory caused by NPs, and it can be inhibited by N-acetyl-L-cysteine (NAC). In addition, reactive oxygen species (ROS) activated nuclear factor erythroid-derived factor 2-related factor (Nrf2) pathway. Nrf2 siRNA exacerbated the injury, suggesting Nrf2 plays a protective role. Moreover, p62 siRNA increased ROS and mitochondrial damage by inhibiting Nrf2, but didn't affect the inflammation. In conclusion, Nrf2 was activated by ROS and played a protective role in PS-NPs-mediated hepatotoxicity. This study supplemented the data of liver injury caused by PS-NPs, providing a basis for the safe disposal of plastics.

Bridge symptoms between parenting styles and proximal psychological risk factors associated with adolescent suicidal thoughts: a network analysis.

BACKGROUND: Parenting styles and the associated proximal psychological factors are suggested to increase suicidal risks in adolescents. However, how the two factors interact and confer risks on the emergence of adolescent suicidal thoughts remains unclear. Herein, we used a network approach to investigate their interrelationship and explore whether the network properties predict adolescent suicidal thoughts. METHODS: Self-report questionnaires were completed by 1171 students aged 12-16. Network analyses were performed by Gaussian graphical models estimating the adolescent psychosocial network structure of parenting styles and psychological variables including depression, anxiety, affective lability, rumination, and resilience. Furthermore, we re-examined the network by adding a variable measuring active suicidal thoughts. Moreover, we conducted linear regressions to examine the predictive utility of bridge symptoms for adolescent suicidal thoughts. RESULTS: Resilience, Afraid, Rumination, Concentration, and affective lability (Anger) had the highest bridge strengths in the adolescent psychosocial network. Among the identified bridge symptoms, Resilience was negatively correlated with active suicidal thoughts (regularized edge weights = -0.181, bootstrapped 95% CIs: [-0.043, -0.155]), whereas affective lability (from Anxiety to Depression, Anger), Rumination, and Afraid were positively correlated with active suicidal thoughts, with edge weights (bootstrapped 95% CIs) ranging from 0.057 (0.001, 0.112) to 0.081(0.026, 0.136). Regression analysis showed that bridge strength was significantly correlated with active suicidal thoughts (R2 = 0.432, P = 0.001). CONCLUSION: Negative parenting styles may drive and maintain suicidal thoughts by modifying the key proximal psychological variables. Our findings highlight the important role of bridge symptoms, which may serve as vital targets for triggering adolescent suicide.

Comparative oxidative damages induced by silver nanoparticles with different sizes and coatings in Caenorhabditis elegans.

Silver nanoparticles (AgNPs) are widely used in many commercial and medical products. Serious concerns are paid on their adverse potentials to the environment and human health. In this study, toxic effects and oxidative stress induced by AgNPs with different sizes and coatings (20 nm AgNPs, 20 nm polyvinylpyrrolidone (PVP) -AgNPs and 50 nm AgNPs) in Caenorhabditis elegans (C. elegans) were investigated. The toxic effects including the shortened lifespan and decreased frequency of head thrashes and body bends of C. elegans were induced in a dose-dependent manner by AgNPs. The reactive oxygen species (ROS) production and the oxidative stress-related indicators including malondialdehyde (MDA) and glutathione (GSH) in nematodes were changed after exposure to three kinds of AgNPs. These effects were the most obvious in a 20 nm PVP-AgNPs exposure group. AgNPs could also induce the expression of genes related to oxidative stress in nematodes. In addition, the up-regulation of mtl-1 and mtl-2 in nematodes might reduce the oxidative damage caused by AgNPs, by using transgenic strains CF2222 and CL2120 nematodes. Metallothionein (MT), an antioxidant, could relieve the oxidative damage caused by AgNPs. These results suggested that 20 nm PVP-AgNPs with a smaller particle size and better dispersion have stronger toxic effects and the oxidative damage to nematodes. Mtl-1 and mtl-2 might be involved in alleviating the oxidative damage caused by AgNPs. Our findings provide clues for the safety evaluation and mechanism information of metal nanoparticles.

Posttraumatic stress symptoms in healthcare workers during the COVID-19 pandemic: A four-wave longitudinal study.

BACKGROUND: Posttraumatic stress symptoms of healthcare workers have become a significant public concern in the healthcare system that have long COVID-19. It is less known how the pandemic impacts the HCWs' PTSS longitudinally and long-term risk factors for it. METHODS: Four consecutive surveys were conducted among healthcare workers in China from 2019 to 2023 COVID-19 outbreaks. Multilevel mixed-effect models were used to examine longitudinal changes and risk factors. Network analysis was utilized to explore network centrality changes in PTSS symptoms. RESULTS: HCWs' PTSS symptoms were increased over time during the COVID-19 pandemic. Being female, being nurse, working in the emergency department, working longer hours, less frequently going back home and having COVID-19 infection are risk factors of PTSS for HCWs; unmarried is the protective factor. Significant interaction between symptom changes and profession exists. PTSS networks showed that Avoidance of thoughts, Emotional-cue activity, Exaggerated startle response and Hypervigilance were the central symptoms during four waves. The global strength of the PTSS network grows over time, and nodal strength of Avoidance of thoughts, Loss of interest and Negative beliefs increased by COVID-19. CONCLUSION: The pandemic's impacts on healthcare workers vary by professions. PTSS symptoms exacerbate, reinforce each other, and persists with recurring waves.

ROS-Drp1-mediated mitochondria fission contributes to hippocampal HT22 cell apoptosis induced by silver nanoparticles.

Silver nanoparticles (AgNPs) have widely used in industrial and medical applications for their excellent antibacterial activities. AgNPs can penetrate into the brain and cause neuronal death, but limited evidence focused on toxic effects and mechanic study in hippocampal neuron. This study aimed to investigate the molecular mechanisms of mitochondrial damage and apoptosis in mouse hippocampal HT22 cells and further to explore role of reactive oxygen species (ROS) and GTPase dynamin-related protein 1 (Drp1) in AgNPs-induced neurotoxicity. Our results showed that acute exposure to AgNPs at low doses (2-8 µg/mL) increased ROS generation, decreased mitochondrial membrane potential (MMP) and ATP synthesis in HT22 cells. In addition, AgNPs promoted mitochondrial fragmentation and mitochondria-dependent apoptosis via excessive mitochondrial fission/fusion by 8 µg/mL AgNPs treatment for 24 h. The mechanism was involved in increased protein expression of Drp1, mitochondrial fission protein 1 (Fis1), mitofusin 1/2 (Mfn1/2) and inhibited optic atrophy 1 (OPA1), and mainly mediated by phosphorylation of Drp1 Ser616. The AgNPs-induced mitochondrial impairment and apoptosis was mainly due to their particle-specific effect rather than silver ions release. Furthermore Drp1-mediated mitochondrial fission contributed to mitochondria-dependent apoptosis induced by AgNPs, all aforementioned changes were significantly rescued by N-acetyl-l-cysteine (NAC) and Mdivi-1 except for OPA1 protein expression. Hence, our results provide a novel neurotoxic mechanism to AgNPs-induced neurotoxicity and revealed that the mechanism of mitochondria-dependent apoptosis in HT22 cells was mediated by excessive activation of ROS-Drp1-mitochondrial fission axis. These findings can deepen current evidences on neurotoxicological evaluation of AgNPs and aid in guiding their proper applications in different areas, especially in biomedical use.

ROS and DRP1 interactions accelerate the mitochondrial injury induced by polystyrene nanoplastics in human liver HepG2 cells.

Microplastics have become a serious environmental pollutant and subsequently have harmful effects on human health. Thus, the impacts of microplastics on human cells need to be explored. In the present study, the cytotoxic effects at the subcellular-organelle levels to polystyrene nanoplastics (PS-NPs, diameter 21.5 ± 2.7 nm) were investigated in the human hepatocellular carcinoma (HepG2) cell line. The cell viability exposed to PS-NPs at the concentrations of 6.25, 12.5, 25 and 50 µg/mL for 24 h diminished in a concentration-dependent manner. The PS-NPs treatment induced mitochondrial injuries, including morphological changes, decreased adenosine triphosphate (ATP) production and the loss of mitochondrial membrane potentials (MMP). The PS-NPs treatment could further spark cell apoptosis by upregulating caspase 3, caspase 9, cytochrome c, and Bcl-2 associated X protein (Bax)/B-cell lymphoma-2 (Bcl-2) in HepG2 cells, which is related to the mitochondrial dysfunction. PS-NPs exposure stimulated the excessive cellular reactive oxygen species (ROS) production and also induced mitochondrial fission by upregulating dynamin-related protein 1 (DRP1) and P-DRP1, but downregulating optic atrophy protein 1 (OPA1) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α) expression levels. The above effects on mitochondria damage induced by PS-NPs were reversed by the pretreatment of N-acetylcysteine (NAC), mitochondrial division inhibitor 1 (Mdivi-1) and DRP1 siRNA. The results suggested that the interaction between ROS and DRP1-dependent mitochondrial division could promote mitochondrial lesions and mitochondria-related apoptosis caused by PS-NPs. These findings on molecular mechanisms provide a theoretical basis for preventing the hazards caused by microplastics to human health.

Using machine learning algorithm to predict the risk of post-traumatic stress disorder among firefighters in Changsha. / ç”¨æœºå™¨å­¦ä¹ ç®—æ³•é¢„æµ‹é•¿æ²™æ¶ˆé˜²å‘˜æ‚£åˆ›ä¼¤åŽåº”æ¿€éšœç¢çš„é£Žé™©.

OBJECTIVES: Firefighters are prone to suffer from psychological trauma and post-traumatic stress disorder (PTSD) in the workplace, and have a poor prognosis after PTSD. Reliable models for predicting PTSD allow for effective identification and intervention for patients with early PTSD. By collecting the psychological traits, psychological states and work situations of firefighters, this study aims to develop a machine learning algorithm with the aim of effectively and accurately identifying the onset of PTSD in firefighters, as well as detecting some important predictors of PTSD onset. METHODS: This study conducted a cross-sectional survey through convenient sampling of firefighters from 20 fire brigades in Changsha, which were evenly distributed across 6 districts and Changsha County, with a total of 628 firefighters. We used the synthetic minority oversampling technique (SMOTE) to process data sets and used grid search to finish the parameter tuning. The predictive capability of several commonly used machine learning models was compared by 5-fold cross-validation and using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, precision, recall, and F1 score. RESULTS: The random forest model achieved good performance in predicting PTSD with an average AUC score at 0.790. The mean accuracy of the model was 90.1%, with an F1 score of 0.945. The three most important predictors were perseverance, forced thinking, and reflective deep thinking, with weights of 0.165, 0.158, and 0.152, respectively. The next most important predictors were employment time, psychological power, and optimism. CONCLUSIONS: PTSD onset prediction model for Changsha firefighters constructed by random forest has strong predictive ability, and both psychological characteristics and work situation can be used as predictors of PTSD onset risk for firefighters. In the next step of the study, validation using other large datasets is needed to ensure that the predictive models can be used in clinical setting.

Recombinant human metallothionein-III alleviates oxidative damage induced by copper and cadmium in Caenorhabditis elegans.

Recombinant human metallothionein III (rh-MT-III) is a genetically engineered product produced by Escherichia coli fermentation technology. Its molecules contain abundant reducing sulfhydryl groups, which possess the ability to bind heavy metal ions. The present study was to evaluate the binding effects of rh-MT-III against copper and cadmium in vitro and to investigate the antioxidant activity of rh-MT-III using Caenorhabditis elegans in vivo. For in vitro experiments, the binding rates of copper and cadmium were 91.4% and 97.3% for rh-MT-III at a dosage of 200 µg/mL at 10 h, respectively. For in vivo assays, the oxidative stress induced by copper (CuSO4 , 10 µg/mL) and cadmium (CdCl2 , 10 µg/mL) was significantly reduced after 72 h of exposure to different doses of rh-MT-III (5-500 µg/mL), indicated by restoring locomotion behavior and growth, and reducing malondialdehyde and reactive oxygen species levels in C. elegans. Moreover, rh-MT-III decreased the deposition of lipofuscin and fat content, which could delay the progression of aging. In addition, rh-MT-III (500 µg/mL) promoted the up-regulation of Mtl-1 and Mtl-2 gene expression in C. elegans, which could enhance the resistance to oxidative stress by increasing the enzymatic activity of antioxidant defense system and scavenging free radicals. The results indicated that supplemental rh-MT-III could effectively protect C. elegans from heavy metal stress, providing an experimental basis for the future application and development of rh-MT-III.

A visual CRISPR/dCas9-mediated enzyme-linked immunosorbent assay for nucleic acid detection with single-base specificity.

Specific and economical nucleic acid detection is crucial for molecular diagnoses in resource-limited settings. Various facile readout approaches have been developed for nucleic acid detection, but they have limited specificity. Herein, nuclease-dead Cas9 (dCas9)/sgRNA was used as an excellent DNA recognition probe system to develop a visual clustered regularly interspaced short palindromic repeats (CRISPR)/dCas9-mediated enzyme-linked immunosorbent assay (ELISA) for specific and sensitive detection of cauliflwer mosaic virus 35s (CaMV35S) promoter in genetically modified (GM) crops. In this work, the CaMV35S promoter was amplified with biotinylated primers, and then precisely bound with dCas9 in the presence of sgRNA. The formed complex was captured by antibody-coated microplate and bound to a streptavidin-labeled horseradish peroxidase probe for the visual detection. Under the optimal conditions, dCas9-ELISA could detect CaMV35s promoter as low as 12.5 copies µL-1. Moreover, the proposed method was capable to distinguish the target sequence with single-base specificity. Coupled with one-step extraction and recombinase polymerase amplification, dCas9-ELISA can identify actual GM rice seeds within 1.5 h from sampling to results without expensive equipment and technical expertise. Therefore, the proposed method offers a specific, sensitive, rapid and cost-effective detection platform for molecular diagnoses.

Relationships between attitudes toward mental problems, doctor-patient relationships, and depression/anxiety levels in medical workers: A network analysis. / åŒ»åŠ¡äººå‘˜çœ‹å¾ ç²¾ç¥žç–¾ç— æ€åº¦ä¸ŽåŒ»æ‚£å ³ç³»å’ŒæŠ‘éƒç„¦è™‘æ°´å¹³å ³ç³»çš„ç½‘ç»œåˆ†æž.

OBJECTIVES: At present, the doctor-patient relationship is tense. The prevalence of negative emotions, such as depression and anxiety, among healthcare workers is increasing every year. Negative attitudes of medical workers toward mental problems may aggravate the doctor-patient conflict and psychological problems of medical workers. This study aims to explore the complex network relationships between outpatient medical workers' attitudes toward mental problems, doctor-patient relationships, and their depression/anxiety levels. METHODS: A total of 578 outpatient medical staff from the Second Xiangya Hospital of Central South University (167 males, 411 females) completed questionnaires on their attitudes toward mental problems, doctor-patient relationships, and depression/anxiety symptoms. Network analysis was conducted separately to construct the "attitude towards mental problems-doctor-patient relationship network" and "depression-anxiety related network". RESULTS: The edge between "M15 (insulting words)" and "D8 (waste time)" showed the strongest strength in the "attitude towards mental problems-doctor-patient relationship network", and "M15 (insulting words)" had the highest bridge strength in the network. For the analysis of emotional variables, "P1 (anhedonia)" showed the most obvious association with "D10 (communication difficulties)" in the doctor-patient relationship and "M2 (poor quality of life)" in the psychiatric attitudes, and "P1 (anhedonia)" was the key bridge symptom in the network. CONCLUSIONS: The "insulting words" may be an intervention target for medical workers' attitudes toward mental problems. The "anhedonia" in depression is the potential symptom that needs to be treated. Intervention targeting these variables may be beneficial to improve the mental health level of medical workers and the doctor-patient relationship.

Factor structure and psychometric properties of the affective lability scale-short form in Chinese adolescents.

Objective: Previous studies on the reliability and validity of the Affective Lability Scale short-form (ALS-SF) have only been evaluated in adults, which may not be able to generalize to the adolescent population. We aimed to examine the factor structure, the reliability and validity of ALS-SF among Chinese adolescents and construct an adolescent form of ALS (ALS-AF). Methods: A total of 1,439 middle school students were investigated with a broad survey including ALS-SF, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Connor-Davidson Resilience Scale 10-item (CD-RISC-10) and non-suicidal self-injury (NSSI) behavior self-report. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to investigate the structural validity of ALS-SF and construct ALS-AF. Cronbach's α was used to assess the internal consistency and reliability of the scale. Factor loading, Average Variance Extracted (AVE) and Composite Reliability (CR) were applied to measure the convergent validity and divergent validity. Besides, Correlation and regression analyses were used to explore the relationship between affective lability and depression, anxiety, NSSI and resilience. Results: Factor analysis failed to support the original three-factor model of 18-item ALS-SF and confirmed the three-factor model of 15-item ALS-AF. The ALS-AF showed good internal consistency as well as strong convergent and discriminative validity. Besides, ALS-AF was positively correlated with PHQ-9, GAD-7 and self-harm, and was negatively associated with resilience. Conclusion: Our study shows that the ALS-AF has good reliability and validity for testing affective lability in Chinese adolescents.

Qualitative and Quantitative Real-Time PCR Methods for Assessing False-Positive Rates in Genetically Modified Organisms Based on the Microbial-Infection-Linked HPT Gene.

The hygromycin phosphotransferase (HPT) gene as a selective marker is normally used in screening tests as a first step in detecting and quantifying genetically modified organisms (GMOs) in seeds, food, and feed materials. Nevertheless, if researchers only focus on the HPT gene, it is difficult to distinguish genetically modified (GM) crops from microbial infection, leading to miscalculation of the rate of GM materials in a given sample set. Here, we cloned the 7259 bp sequence carrying the HPT gene from soybean sprouts using the genome walking strategy. BLAST analysis revealed that this sequence was derived from plasmids naturally occurring in microorganisms, such as Escherichia coli, Klebsiella pneumoniae or Salmonella sp. Using the reconstructed plasmid pFP-hpt, qualitative PCR and quantitative real-time PCR (qPCR) methods were established, and 261 bp and 156 bp products were produced. The specificity of these assays was assessed against related pFP-hpt plasmids, plant species with important agronomic traits, and GM crops containing the HPT gene. No unexpected results were observed between samples using these qualitative PCR and qPCR methods. The sensitivity of this qualitative PCR assay was determined at 20 copies, while the limit of detection (LOD) and limit of quantification (LOQ) of qPCR were both 5 copies per reaction. Our in-house validation indicated that the amplification efficiency, linearity, and repeatability of this qPCR assay were in line with performance requirements. Furthermore, a qualitative and quantitative duplex PCR showed high reliability for the simultaneous detection of the HPT gene in a plant sample and environmental micro-organisms harboring the HPT gene in one PCR reaction. These qualitative PCR and qPCR assays were able to differentiate between plants infected with E. coli harboring the HPT gene from GM plants, indicating that these two methods are broadly applicable for routine GMO testing.

Total Burden of Cerebral Small Vessel Disease on MRI May Predict Cognitive Impairment in Parkinson's Disease.

(1) Objective: to investigate the association between the total burden of cerebral small vessel disease (CSVD) and cognitive function in Parkinson's disease (PD). (2) Methods: this retrospective study compared clinical and neuroimaging characteristics of 122 PD patients to determine the association between cognitive decline and total burden of CSVD in PD. All patients underwent brain MRI examinations, and their total CSVD burden scores were evaluated by silent lacunar infarction (SLI), cerebral microbleeds (CMB), white matter hyperintensities (WMH), and enlarged perivascular spaces (EPVS). The cognitive function was assessed by administering Mini-Mental State Examination (MMSE). Receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were performed to quantify the accuracy of the total burden of CSVD and PVH in discriminating PD patients with or without cognitive impairment. (3) Results: the PD patients with cognitive impairment had a significantly higher SLI, CMB, periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), enlarged perivascular spaces of basal ganglia (BG-EPVS), and the total CSVD score compared with no cognitive impairment. Total CSVD score and MMSE had a significant negative correlation (r = -0. 483). Furthermore, total burden of CSVD and PVH were the independent risk factors of cognitive impairment in PD, and their good accuracy in discriminating PD patients with cognitive impairment from those with no cognitive impairment was confirmed by the results of ROC curves. (4) Conclusions: total burden of CSVD tightly linked to cognitive impairment in PD patients. The total burden of CSVD or PVH may predict the cognitive impairment in PD.

The Application of the GP Model to Manage Controllable Risk Factors in Stroke Patients with Diabetes Can Effectively Improve the Prognosis and Reduce the Recurrence Rate.

Objective: The aim of this study is to examine the impacts of general practice model (GP) on prognosis and recurrence of stroke patients with diabetes. Methods: Ninety patients with stroke combined with diabetes mellitus admitted to our hospital from June 2019 to June 2020 were selected for the study and were randomly and equally divided into 45 cases each in the control and experimental groups for the prospective trial. The patients in the control group received routine treatment while those in the experimental group were treated with GP model. Comparison in treatment effects, patients satisfaction, psychological status, quality of life, glycosylated hemoglobin level, and stroke recurrence was carried out between the two groups. Results: The experimental group showed markedly better treatment effects (P < 0.05), higher satisfaction degree (P < 0.05), higher HAD (P < 0.05), GQOLI-74 score (P < 0.05), and BI index (P < 0.05), lower level of glycosylated hemoglobin (P < 0.05), and much lower recurrence rate (P < 0.05), as compared to the control group. Conclusion: The application of the GP model to manage controllable risk factors in stroke patients with diabetes can effectively improve the prognosis and reduce the recurrence rate, which is worthy of clinical application and promotion.

Silver nanoparticles induced hippocampal neuronal damage involved in mitophagy, mitochondrial biogenesis and synaptic degeneration.

Silver nanoparticles (AgNPs) could accumulate in the central nervous system (CNS) and induce neurotoxicity for their widespread use in industry and medicine. Mitochondria are vulnerable to toxicity of AgNPs, however, their role in the neurotoxicity remains unclear. This study aimed to evaluate AgNPs-induced synaptic degeneration in mouse hippocampal neurons (at a dose of 12-120 mg/kg BW via intravenous injection), and to further investigate mechanism of mitophagy, mitochondrial biogenesis process in the neurotoxicity. The results indicated that AgNPs accumulated in mouse hippocampal neurons and induced neurological deficits of learning and memory, which involved in synaptic degeneration accompanied with mitochondrial damage. Mechanistically, AgNPs exposure increased protein expression of PTEN-induced kinase 1 (PINK1), Parkin and inhibited peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1α) protein expression, caused disturbed mitophagy and mitochondrial biogenesis. AgNPs also induced synaptic damage by increasing the protein expression of synaptophysin and decreasing PSD95, MAP2 protein expression. AgNPs exposure even promoted protein expression of amyloid precursor protein (APP) using in amyloid-ß (Aß) cleavage. Furthermore, AgNPs induced hippocampal neuronal synaptic degeneration, mitophagy and mitochondrial biogenesis is dependent on particle-specific AgNPs rather than released silver ions. Our research could provide insights into the regulatory mechanisms of AgNPs-induced neurotoxicity. This study will shed the light of neurotoxicological evaluation of nanoparticles and possible early warning of biomedical applications.

A positive feedback loop between LINC01605 and NF-κB pathway promotes tumor growth in nasopharyngeal carcinoma.

zong non-coding RNAs (lncRNAs) have been identified as crucial effector in modulating the progression of assorted malignancies. In our study, the main aim was to unveil the role and the underlying regulatory mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in nasopharyngeal carcinoma (NPC). RT-qPCR analysis results suggested that LINC01605 was upregulated in NPC cells. According to the results of function experiments, LINC01605 promoted NPC cell proliferation and impeded cell apoptosis. The oncogenic role of LINC01605 in NPC was further validated by animal experiments. Additionally, we verified that LINC01605 regulated Ikbkb expression to promote the nuclear translocation of p65 and thereby activated the NF-κB pathway in NPC cells. Mechanism experiments further suggested that LINC01605 could regulate Ikbkb expression via sponging miR-942-5p. Moreover, LINC01605 recruited IGF2BP2 to stabilize ubiquitin-specific protease 3 (USP3) mRNA and thereby enhanced the stability of IkB subunit beta (IKKß) protein. In addition, p65 acted as a transcription activator to upregulate LINC01605 in NPC cells. In conclusion, this study demonstrated a positive feedback loop between LINC01605 and the NF-κB signalling pathway that promoted NPC cell growth, thus providing new insights to better understand NPC. [Figure: see text].

Degradation of CP4-EPSPS with a Psychrophilic Bacterium Stenotrophomonas maltophilia 780.

CP4-EPSPS (Agrobacterium sp. strain CP4 5-enolpyruvylshikimate-3-phosphate synthase) protein showed remarkable thermostability and was highly resistant to proteases, such as trypsin. In order to eliminate the pollution of CP4-EPSPS from the accumulated straws to the surrounding environment during the winter, the present study investigated the extracellular proteases of 21 psychrophilic strains isolated from the south polar region. The results indicated that Stenotrophomonas maltophilia 780 was able to degrade CP4-EPSPS at 18 °C efficiently. Further study indicated that it was able to grow in the extract of Roundup Ready soybean at 18 °C, with CP4-EPSPS degraded to an undetectable level within 72 h. The extracellular proteases of Stenotrophomonas maltophilia 780 are thermo-sensitive, with an optimal temperature of 65 °C. The genomic sequencing result indicated that this strain had more than a hundred putative protease and peptidase coding genes, which may explain its high capability in decomposing CP4-EPSPS.