Establishment of a RAA-CRISPR Cas12a based diagnostic method for peste des petits ruminants virus N gene and M gene.

Peste des petis ruminants (PPR) is an acute, highly contagious fatal disease affecting both domestic and wild small ruminants, caused by Morbillivirus caprinae (also known as peste des petis ruminants virus (PPRV)). Herein, a rapid method based on recombinase aided amplification-clustered regularly interspaced short palindromic repeats-Cas12a (RAA-CRISPR Cas12a) to detect PPRV was developed. CRISPR RNAs and RAA primers for PPRV-N (nucleocapsid) and PPRV-M (matrix) fragments were designed. The reaction system was constructed following screening and optimization. Detection could be completed within in 50 minutes at 37°C. Detection of gradient dilutions of plasmids carrying of PPRV N and M gene fragments indicated a minimum limit of detection of 10 copies/µL. There were no cross-reactions with related viruses and all tested lineages of PPRV were detected successfully. The method also showed good repeatability. The detection of clinical samples (previously detected using reverse transcription polymerase chain reaction (RT-PCR)) indicated good consistency between the RAA-CRISPR Cas12a method and RT-PCR. Thus, the RAA-CRISPR Cas12a method for rapid PPRV diagnosis has strong specificity, high sensitivity, and stable repeatability. Moreover, the results can be observed visually under blue or UV light or using lateral flow strips without complex instruments.

Predicting Braess's paradox of power grids using graph neural networks.

As an increasing number of renewable energy generators are integrated into the electrical grid, the necessity to add new transmission lines to facilitate power transfer and ensure grid stability becomes paramount. However, the addition of new transmission lines to the existing grid topology can lead to the emergence of Braess's paradox or even trigger grid failures. Hence, predicting where to add transmission lines to guarantee stable grid operation is of utmost importance. In this context, we employ deep learning to address this challenge and propose a graph neural network-based method for predicting Braess's paradox in electrical grids, framing the problem of adding new transmission lines causing Braess's paradox as a graph classification task. Taking into consideration the topological and electrical attributes of the grid, we select node features such as degree, closeness centrality, and power values. This approach assists the model in better understanding the relationships between nodes, enhancing the model's representational capabilities. Furthermore, we apply layered adaptive weighting to the output of the graph isomorphism network to emphasize the significance of hierarchical information that has a greater impact on the output, thus improving the model's generalization across electrical grids of varying scales. Experimental results on the IEEE 39, IEEE 57, and IEEE 118 standard test systems demonstrate the efficiency of the proposed method, achieving prediction accuracies of 93.8%, 88.8%, and 88.1%, respectively. Model visualization and ablation studies further validate the effectiveness of this approach.

CXCL6 promotes the progression of NAFLD through regulation of PPARα.

An increasing number of studies have shown that Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity, insulin resistance, dyslipidemia, hypertension and metabolic syndrome, but its specific pathogenesis remains unclear. By analyzing GEO database, we found CXCL6 was upregulated in liver tissues of patients with NAFLD. We also confirmed with qPCR that CXCL6 is highly expressed in serum of patients with NAFLD. To identify the underlying impact of CXCL6 on NAFLD, we established animal and cell models of NAFLD. Similarly, we confirmed by qPCR and Western blot that CXCL6 was upregulated in the NAFLD model in vitro and vivo. After transfecting NAFLD cells with siRNA targeting CXCL6 (si-CXCL6), a series of functional experiments were carried out, and these data indicated that the inhibition of CXCL6 reduced intracellular lipid deposition, decreased AST, ALT and TG level, facilitate cell proliferation and suppress their apoptosis. Furthermore, western blot and qPCR analyses displayed that the suppression of CXCL6 could raise the PPARα expression, but PPAR α inhibitor, GW6471 could partially counteract this effect. What's more, Oil Red O staining, biochemical analyzer and TG detection kit revealed that GW6471 could reverse the inhibitory effect of si-CXCL6 on NAFLD. In summary, we provide convincing evidence that CXCL6 is markedly elevated in NAFLD, and the CXCL6/PPARα regulatory network mediates disease progression of NAFLD.

Tetrandrine (TET) inhibits African swine fever virus entry into cells by blocking the PI3K/Akt pathway.

African Swine Fever Virus (ASFV) infection causes an acute and highly contagious disease in swine, resulting in significant economic losses and societal harm worldwide. Currently, there are no effective vaccines or antiviral drugs available for ASFV. Tetrandrine (TET) is extracted from the traditional Chinese herb Stephania tetrandrae, possesses diverse biological functions such as anti-inflammatory, anti-tumor, and antiviral activities. The study comprehensively evaluated the anti-ASFV effect of TET and validated it through biological assays. The dose-dependent inhibition of TET against ASFV was confirmed and a novel mechanism of TET's anti-ASFV activity was elucidated. TET effectively inhibits ASFV during internalization by blocking macropinocytosis through the inhibition of the PI3K/Akt pathway. The specific inhibitor LY294002, targeting the PI3K/Akt pathway, exhibits similar antiviral activity against ASFV as TET. Furthermore, the inhibitory effect of TET against other viruses such as Lumpy Skin Disease Virus (LSDV) and Porcine Epidemic Diarrhea Virus (PEDV) was also identified. Our findings suggest that TET effectively inhibits ASFV and reveal the potential for broad-spectrum antiviral drugs targeting the PI3K/Akt pathway.

LINC00115 promotes gastric cancer partly by the miR-212-5p/ATPAF1 axis.

LncRNAs are known to be key regulators in the initiation and development of diverse cancers. Whether LINC00115 is involved in the regulation of gastric cancer (GC) progression remains unclear. Here, we aimed to show the function of LINC00115 in GC. RT-qPCR was used to measure gene expression in GC tissues and cells. Colony formation, EdU, TUNEL, and wound healing assays were used to analyze cellular processes in GC. The in vivo GC xenograft model was established. We observed that LINC00115 was highly expressed in GC. Functionally, silencing LINC00115 inhibited GC cell proliferation, and migration but facilitated GC apoptosis. Mechanistically, LINC00115 sponged miR-212-5p, while miR-212-5p targeted ATPAF1 in GC cells. Rescue assays showed ATPAF1 overexpression countervailed the inhibitory role of LINC00115 depletion in GC progression in vitro and in vivo. Overall, LINC00115 promoted GC progression by upregulating ATPAF1 via miR-212-5p.

Population genetics of Camellia granthamiana, an endangered plant species with extremely small populations in China.

Introduction: Camellia, the largest genus of Theaceae, is well-known for having high economic values. Camellia granthamiana demonstrates large beautiful flowers with some primitive characters, such as multiple large and persistent bracteoles and sepals, was listed as Vulnerable species on the IUCN Red List. Methods: In this study, we investigated all possible records of the species, and sampled four natural populations and five cultivated individuals. By applying shallow-genome sequencing for nine individuals and RAD-seq sequencing for all the sampled 77 individuals, we investigated population genetic diversity and population structure of the species. Results and discussion: The results showed that the population sampled from Fengkai, previously identified as C. albogigias, possessed different plastid genome from other species possibly due to plastid capture; the species possesses strong population structure possibly due to the effect of isolation by distance, habitat fragmentation, and self-crossing tendency of the species, whose effective population size declined quickly in the past 4,000 years. Nevertheless, C. granthamiana maintains a medium level of genetic diversity within population, and significant differentiation was observed among the four investigated populations, it is anticipated that more populations are expected to be found and all these extant populations should be taken into instant protection.

Deep Learner System Based on Focal Color Retinal Fundus Images to Assist in Diagnosis.

Retinal diseases are a serious and widespread ophthalmic disease that seriously affects patients' vision and quality of life. With the aging of the population and the change in lifestyle, the incidence rate of retinal diseases has increased year by year. However, traditional diagnostic methods often require experienced doctors to analyze and judge fundus images, which carries the risk of subjectivity and misdiagnosis. This paper will analyze an intelligent medical system based on focal retinal image-aided diagnosis and use a convolutional neural network (CNN) to recognize, classify, and detect hard exudates (HEs) in fundus images (FIs). The research results indicate that under the same other conditions, the accuracy, recall, and precision of the system in diagnosing five types of patients with pathological changes under color retinal FIs range from 86.4% to 98.6%. Under conventional retinopathy FIs, the accuracy, recall, and accuracy of the system in diagnosing five types of patients ranged from 70.1% to 85%. The results show that the application of focus color retinal FIs in the intelligent medical system has high accuracy and reliability for the early detection and diagnosis of diabetic retinopathy and has important clinical applications.

A Dynamic-Memory Event-Triggered Protocol to Multiarea Power Systems With Semi-Markov Jumping Parameter.

This work deals with the dynamic-memory event-triggered-based load frequency control issue for interconnected multiarea power systems (IMAPSs) associated with random abrupt variations and deception attacks. To facilitate the transient faults, a semi-Markov process is addressed to model the dynamic behavior of IMAPSs. In order to modulate transmission frequency, a novel area-dependent dynamic-memory event-triggered protocol (DMETP) is scheduled by resorting to a set of the historically released packets (HRPs), which ensures better dynamic performance. From the viewpoint of the defender, the randomly occurring deception attack is taken into account, which is regulated by a Bernoulli-distributed scalar. Benefitting from the DMETP scheduling, a novel framework of the memory-based asynchronous control strategy is formulated, in which the hidden semi-Markov model is adopted to reveal the mode mismatches. Based on the Lyapunov theory, sufficient conditions are established to ensure the stochastic stability of the resulting systems. In the end, the simulation result is presented to reveal the efficiency of the proposed dynamic-memory event-triggered-based approach.

School bullying among Chinese third to fifth grade primary school students in a cross-sectional study: The protective effect of psychological resilience.

School bullying is a major concern for school-aged youth and has great impacts on children's health and well-being, and an increasing number of school bullying cases have been reported in China. Many studies have indicated that psychological resilience may have a well-established association with school bullying. However, only a limited number of studies have explored this association, especially among primary school students. The present study aimed to investigate the relationship between school bullying and psychological resilience among primary school students from a Chinese city. The participants were 6,011 primary school students aged 7-14 years who were recruited in a cross-sectional survey in Luzhou, China. The statistical significance of differences between groups was tested using the χ2 test or t test. Binary logistic regression analyses were conducted to explore the association between psychological resilience and school bullying. The incidence rates of bullies and victims were 30.00% (1803/6011; 95% CI: 28.84%-31.16%) and 69.89% (4201/6011; 95% CI: 68.73%-71.05%), respectively. Psychological resilience was a protective factor of school bullying among primary school students (for bullying perpetrators, OR = 0.76, 95%CI:0.62-0.93, and for bully victims OR = 0.74, 95%CI:0.61-0.90), especially among female students (for bullying perpetrators, OR = 0.63, 95%CI: 0.47-0.85, and for bully victims, OR = 0.69, 95%CI: 0.53-0.90). School bullying among primary school students in Luzhou City was highly prevalent. High levels of psychological resilience might be a protective factor in preventing primary students from being involved in school bullying, especially among females.

Psychological Resilience May Be Related to Students' Responses to Victims of School Bullying: A Cross-Sectional Study of Chinese Grade 3-5 Primary School Students.

BACKGROUND: School bullying is a major public health problem with a large impact on children's health. There is an increasing number of cases of school bullying reported in China. Studies have shown that the health consequences of different ways of responding to school bullying may be quite different and that psychological resilience is also closely related to aggressive behaviors. However, there has been little research on whether individuals with different psychological resilience levels respond differently. OBJECTIVE: To explore the relationship between responses to school bullying and psychological resilience, which may provide new ideas and strategies to better prevent and intervene in school bullying. METHODS: A random sample of 5425 primary school students aged 7-14 years were recruited in Luzhou, China. All students completed a questionnaire anonymously. The statistical significance of differences between groups was tested using the χ2 test or t test. Binary logistic regression was conducted to explore the relationship between responses and psychological resilience. RESULTS: Over two-thirds of primary school students in this study reported experiencing bullying in the past year. The rate of positive responses among victims was 69.10% (2596/3757, 95% CI: 67.62~70.58%). There was a positive relationship between psychological resilience and positive responses. This relationship was observed for all victims (OR = 1.605, 95% CI: 1.254~2.055), especially male victims (OR = 2.300, 95% CI: 1.624~3.259). CONCLUSIONS: There was a positive relationship between primary school bullying responses and psychological resilience among victims, with differences by sex. Therefore, increasing students' level of psychological resilience, possibly by improving their responses, is important for preventing school bullying. Meanwhile, effective interventions for school bullying should be developed from multiple perspectives, particularly sex, bullying roles, and psychological resilience.

Epigenetic drug screen identified IOX1 as an inhibitor of Th17-mediated inflammation through targeting TET2.

BACKGROUND: Targeting helper T cells, especially Th17 cells, has become a plausible therapy for many autoimmune diseases. METHODS: Using an in vitro culture system, we screened an epigenetics compound library for inhibitors of IFN-γ and IL-17 expression in murine Th1 and Th17 cultures. FINDINGS: This identified IOX1 as an effective suppressor of IL-17 expression in both murine and human CD4+ T cells. Furthermore, we found that IOX1 suppresses Il17a expression directly by targeting TET2 activity on its promoter in Th17 cells. Using established pre-clinical models of intraocular inflammation, treatment with IOX1 in vivo reduced the migration/infiltration of Th17 cells into the site of inflammation and tissue damage. INTERPRETATION: These results provide evidence of the strong potential for IOX1 as a viable therapy for inflammatory diseases, in particular of the eye. FUNDING: This study was supported by the National Key Research and Development Program of China 2021YFA1101200 (2021YFA1101204) to LW and XW; the National Natural Science Foundation of China 81900844 to XH and 82171041 to LW; the China Postdoctoral Science Foundation 2021M700776 and the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine 20221373 to YZ; and the National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS (National Health Service) Foundation Trust and University College London Institute of Ophthalmology, UK (DAC, LPS, PJPL, MS, ADD and RWJL). The views expressed are those of the authors and not necessarily those of the NIHR or the UK's Department of Health and Social Care.

Low-density lipoprotein particles in atherosclerosis.

Among the diseases causing human death, cardiovascular disease (CVD) remains number one according to the World Health Organization report in 2021. It is known that atherosclerosis is the pathological basis of CVD. Low-density lipoprotein (LDL) plays a pivotal role in the initiation and progression of atherosclerotic CVD (ASCVD). LDL cholesterol (LDL-C) is the traditional biological marker of LDL. However, large numbers of patients who have achieved the recommended LDL-C goals still have ASCVD risk. In multiple prospective studies, LDL particle (LDL-P) is reported to be more accurate in predicting CVD risk than LDL-C. LDL-Ps differ in size, density and chemical composition. Numerous clinical studies have proved that the atherogenic mechanisms of LDL-Ps are determined not only by LDL number and size but also by LDL modifications. Of note, small dense LDL (sdLDL) particles possess stronger atherogenic ability compared with large and intermediate LDL subfractions. Besides, oxidized LDL (ox-LDL) is another risk factor in atherosclerosis. Among the traditional lipid-lowering drugs, statins induce dramatic reductions in LDL-C and LDL-P to a lesser extend. Recently, proprotein convertase subtilsin/kexin type 9 inhibitors (PCSK9i) have been demonstrated to be effective in lowering the levels of LDL-C, LDL-P, as well as CVD events. In this article, we will make a short review of LDL metabolism, discuss the discordance between LDL-C and LDL-P, outline the atherogenic mechanisms of action of LDL by focusing on sdLDL and ox-LDL, summarize the methods used for measurement of LDL subclasses, and conclude the advances in LDL-lowering therapies using statins and PCSK9i.

Chip Pad Inspection Method Based on an Improved YOLOv5 Algorithm.

Chip pad inspection is of great practical importance for chip alignment inspection and correction. It is one of the key technologies for automated chip inspection in semiconductor manufacturing. When applying deep learning methods for chip pad inspection, the main problem to be solved is how to ensure the accuracy of small target pad detection and, at the same time, achieve a lightweight inspection model. The attention mechanism is widely used to improve the accuracy of small target detection by finding the attention region of the network. However, conventional attention mechanisms capture feature information locally, which makes it difficult to effectively improve the detection efficiency of small targets from complex backgrounds in target detection tasks. In this paper, an OCAM (Object Convolution Attention Module) attention module is proposed to build long-range dependencies between channel features and position features by constructing feature contextual relationships to enhance the correlation between features. By adding the OCAM attention module to the feature extraction layer of the YOLOv5 network, the detection performance of chip pads is effectively improved. In addition, a design guideline for the attention layer is proposed in the paper. The attention layer is adjusted by network scaling to avoid network characterization bottlenecks, balance network parameters, and network detection performance, and reduce the hardware device requirements for the improved YOLOv5 network in practical scenarios. Extensive experiments on chip pad datasets, VOC datasets, and COCO datasets show that the approach in this paper is more general and superior to several state-of-the-art methods.

Cuticular lipids and associated gene expression analysis under NaCl stress in Thellungiella salsuginea.

Cuticular lipids, including wax and cutin, protect plants against external environmental stress. The relationship between the cuticle properties and salt tolerance is not clear. In this article, photosynthetic and physiological characteristics related to water use and cuticle permeability were assessed in the leaves of Thellungiella salsuginea under NaCl stress. The chemical composition of wax and cutin monomers, and the expression of cuticle-associated genes were also analyzed. The results showed that the net photosynthetic rate and stomatal conductance in the leaves of T. salsuginea decreased, and the water use efficiency increased with increasing NaCl concentration. Salt stress caused a significant increase in total wax, but total cutin monomers only increased under high salt. Transcriptome sequencing and lipid metabolism pathway analysis were performed on rosette leaves of T. salsuginea after 24 h of NaCl treatment. We analyzed the expression of 42 genes involved in cuticle lipid metabolism, and found that most of them exhibited higher expression levels at 0.15 mol L-1 NaCl, but lower expression levels at 0.3 mol L-1 NaCl. The expression of 12 of these genes was further detected by qRT-PCR after 1 week of NaCl treatment: most of them were upregulated both under low and high NaCl stress. Hence, we speculate that the cuticle acts as an adaptive trait in T. salsuginea in salty environments.

Inhibition of p38 MAPK increases the sensitivity of 5-fluorouracil-resistant SW480 human colon cancer cells to noscapine.

A major cause of treatment failure in advanced colon cancer is resistance to chemotherapy. p38 mitogen-activated protein kinase (MAPK) has been associated with cellular apoptosis and plays an important role in multidrug resistance (MDR) in cancer cells. In the present study the effect of p38 MAPK on the sensitivity of 5-fluorouracil (5-FU)-resistant SW480 (SW480/5-FU) human colon cancer cells to noscapine was investigated. Following p38 MAPK interference, the inhibitory effect of noscapine on cell viability and proliferation was increased in the SW480/5-FU cells and there was also a decrease in the expression level of minichromosome maintenance proteins, recombinant Ki-67 and proliferating cell nuclear antigen. Inhibition of p38 MAPK also enhanced noscapine-induced G1-phase cell cycle arrest in the SW480/5-FU cells and there was also a decrease in the protein and mRNA expression level of cyclin D, cyclin E and cyclin-dependent kinase 2, and an increase in the expression level of P57. Furthermore, p38 MAPK interference increased noscapine-induced apoptosis of the SW480/5-FU cells and there was an increase in the protein and mRNA expression level of caspases-3 and 8 and Bax, and decreased Bcl-2 expression level. The sensitivity of the SW480/5-FU cells to noscapine was also increased following p38 MAPK interference, as demonstrated by MDR inhibition via decreased Akt activity and reduced protein expression level of the MDR proteins P-glycoprotein, multidrug resistance protein 1 and ATP-binding cassette G2. These observations indicated that inhibition of p38 MAPK increased the sensitivity of the SW480/5-FU cells to noscapine by suppressing proliferation, induction of cell cycle arrest and apoptosis, and reversal of MDR in the SW480/5-FU cells.

Epigenetic Modifications and Therapy in Uveitis.

Uveitis is a sight-threatening intraocular inflammation, and the exact pathogenesis of uveitis is not yet clear. Recent studies, including multiple genome-wide association studies (GWASs), have identified genetic variations associated with the onset and progression of different types of uveitis, such as Vogt-Koyanagi-Harada (VKH) disease and Behcet's disease (BD). However, epigenetic regulation has been shown to play key roles in the immunoregulation of uveitis, and epigenetic therapies are promising treatments for intraocular inflammation. In this review, we summarize recent advances in identifying epigenetic programs that cooperate with the physiology of intraocular immune responses and the pathology of intraocular inflammation. These attempts to understand the epigenetic mechanisms of uveitis may provide hope for the future development of epigenetic therapies for these devastating intraocular inflammatory conditions.

Metagenomic Analysis Reveals the Heterogeneity of Conjunctival Microbiota Dysbiosis in Dry Eye Disease.

Background: Dry eye disease (DED) is a multifactorial inflammatory disease of the ocular surface. It is hypothesized that dysbiosis of the conjunctival microbiota contributes to the development of DED. However, species-level compositions of the conjunctival microbiota in DED and the potential dysbiosis involving microorganisms other than bacteria remain largely uncharacterized. Methods: We collected conjunctival impression samples from a cohort of 95 individuals, including 47 patients with DED and 48 healthy subjects. We examined the conjunctival microbiota of these samples using shotgun metagenomic sequencing and analyzed microbial dysbiosis in DED at the species level. Results: The conjunctival microbiota in DED exhibited a decreased α-diversity and an increased inter-individual variation. The α-diversity of female patients with DED was higher than that of male patients. Despite a decreased prevalence in DED, 23 microbial species were identified to show abnormally high abundance in DED samples positive for the species. Among these species, a fungal species Malassezia globosa was enriched female patients. In addition, distinct patterns of associations with disease status were observed for different species of the same genus. For DED subtypes, Staphylococcus aureus and S. capitis were associated with meibomian gland dysfunction (MGD), whereas S. hominis was enriched in patients solely with aqueous tear deficiency (ATD). The microbiota of patients with a mixed type of diagnosis was more similar to MGD patients than ATD patients. Conclusion: We demonstrated that the conjunctival microbiota dysbiosis in DED is characterized by significant heterogeneity. Microbial signatures may offer novel insights into the complicated etiology of DED and potentially promote the development of personalized treatment for DED in the future.