Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and immune characteristics of molecular subtypes related to protein glycosylation in Alzheimer’s disease

Background Protein glycosylation has been confirmed to be involved in the pathological mechanisms of Alzheimer’s disease (AD); however, there is still a lack of systematic analysis of the immune processes mediated by protein glycosylation-related genes (PGRGs) in AD. Materials and methods Transcriptomic data of AD patients were obtained from the Gene Expression Omnibus database and divided into training and verification datasets. The core PGRGs of the training set were identified by weighted gene co-expression network analysis, and protein glycosylation-related subtypes in AD were identified based on k-means unsupervised clustering. Protein glycosylation scores and neuroinflammatory levels of different subtypes were compared, and functional enrichment analysis and drug prediction were performed based on the differentially expressed genes (DEGs) between the subtypes. A random forest model was used to select important DEGs as diagnostic markers between subtypes, and a line chart model was constructed and verified in other datasets. We evaluated the differences in immune cell infiltration between the subtypes through the single-sample gene set enrichment analysis, analyzed the correlation between core diagnostic markers and immune cells, and explored the expression regulation network of the core diagnostic markers. Results Eight core PGRGs were differentially expressed between the training set and control samples. AD was divided into two subtypes with significantly different biological processes, such as vesicle-mediated transport in synapses and neuroactive ligand-receptor interactions. The high protein glycosylation subtype had a higher level of neuroinflammation. Riluzole and sulfasalazine were found to have potential clinical value in this subtype. A reliable construction line chart model was constructed based on nine diagnostic markers, and SERPINA3 was identified as the core diagnostic marker. There were significant differences in immune cell infiltration between the two subtypes. SERPINA3 was found to be closely related to immune cells, and the expression of SERPINA3 in AD was found to be regulated by a competing endogenous RNA network that involves eight long non-coding RNAs and seven microRNAs. Conclusion Protein glycosylation and its corresponding immune process play an important role in the occurrence and development of AD. Understanding the role of PGRGs in AD may provide a new potential therapeutic target for AD.
Mental health problems of preschool children during the COVID-19 home quarantine: A cross-sectional study in Shanghai, China

Objective As the coronavirus disease 2019 (COVID-19) pandemic spread across Shanghai, China, in late February 2022 and protective measures to mitigate its impact were enacted, this study aimed to estimate how home quarantine affected the mental health of preschool children in Shanghai, China and explore the association between lifestyle factors and mental health during this special period. Methods A cross-sectional online survey of 2,110 preschool students from Shanghai, China, was conducted during May 20–25,2022. Preschooler’ mental health (Strengths and Difficulties Questionnaire, SDQ) and daily activities were reported by parents. Results The sample involved 2,110 children with a mean age of 4.65 years [standard deviation (SD): 0.91, range: 3–6 years]. Boys and children whose mother’s education level were college and high school had higher rate of mental health problems. Boys had significantly higher rates of peer problems and prosocial behaviors than girls. The 3-year-old group had significantly higher rates of prosocial behaviors than other groups. As compared to the Shanghai norm and the SDQ results of preschool children in Shanghai in 2019 (SH2019), there were a significant decrease in emotional symptoms score, as well as a significant increase in conduct problems score. Additionally, peer problems score significantly increased compared to SH2019. Decreased time spent on daily sleep was associated with the increased risk for preschoolers’ mental health problems. Conclusion There was an increase in the frequency of emotional and behavioral problems, especially regarding conduct problems and peer problems, in preschool children during the COVID-19 home quarantine in Shanghai, China. Boys, younger preschool children and children whose mother’s education level were college and high school may be especially vulnerable to emotional and behavioral problems. It was also found that decreased time spent on sleep may aggravate preschool children’s mental health problems. It may be beneficial to differentiate and focus on conducting psychoeducation and implementing psycho-behavioral interventions to solve these issues.
Sodium cantharidate promotes autophagy in breast cancer cells by inhibiting the PI3K–Akt–mTOR signaling pathway

Sodium cantharidate (SCA) is a derivative of cantharidin obtained by its reaction with alkali. Studies have shown that it inhibits the occurrence and progression of several cancers. However, therapeutic effects of SCA on breast cancer are less well studied. This study aimed to clarify the effect of SCA on breast cancer cells and its mechanism, and to provide a scientific basis for the clinical use of SCA for the treatment of breast cancer. The results of cell counting kit-8, colony formation assay, and 5-ethynyl-2′-deoxyuridine staining showed that SCA inhibited breast cancer cell proliferation. Wound-healing and transwell assays demonstrated that SCA inhibited the migration and invasion of breast cancer cells. Transmission electron microscopy revealed that SCA induced autophagy in breast cancer cells. RNA sequencing technology showed that SCA significantly regulated the phosphoinositide 3-kinase–Akt–mammalian target of rapamycin (PI3K–Akt–mTOR) pathway, which was further verified using western blotting. The inducing effect of SCA on breast cancer autophagy was reversed by the mTOR activator MHY1485. In addition, subcutaneous xenograft experiments confirmed that SCA significantly inhibited tumor growth in vivo. Hematoxylin-eosin, TdT-mediated dUTP nick-end labeling, and immunohistochemical staining indicated that SCA induced tumor cell autophagy and apoptosis in nude mice without causing organ damage. In summary, we found that SCA promoted breast cancer cell apoptosis by inhibiting the PI3K–Akt–mTOR pathway and inducing autophagy. Graphical Abstract
Digital gene expression profiling of the transcriptional response to Sclerotinia sclerotiorum and its antagonistic bacterium Bacillus amyloliquefaciens in soybean

Soybean Sclerotinia stem rot caused by Sclerotinia sclerotiorum is a common disease in soybean, and effective biological control is urgently needed. We have previously confirmed that Bacillus amyloliquefaciens can effectively antagonize S. sclerotiorum in a plate competition experiment and a soybean seedling inoculation experiment. In this study, the mechanisms underlying plant death caused by S. sclerotiorum and soybean resistance to S. sclerotiorum induced by B. amyloliquefaciens were evaluated. The stems of potted soybean seedlings were inoculated with S. sclerotiorum (Gm-Ss), B. amyloliquefaciens (Gm-Ba), and their combination (Gm-Ba-Ss), using scratch treatments as a control, followed by dual RNA sequencing and bioinformatics analyses. Global gene expression levels in the Gm-Ss treatment were much lower than those in the Gm-Ba, Gm-Ba-Ss, and Gm groups, suggesting that S. sclerotiorum strongly inhibited global gene expression in soybean. In a pairwise comparison of Gm-Ss vs. Gm, 19983 differentially expressed genes (DEGs) were identified. Down-regulated DEGs were involved in various KEGG pathways, including ko01110 (biosynthesis of secondary metabolites), ko01100 (metabolic pathways), ko01120 (microbial metabolism in diverse environments), ko00500 (starch and sucrose metabolism), and ko04075 (plant hormone signal transmission), suggesting that S. sclerotiorum inoculation had a serious negative effect on soybean metabolism. In Gm-Ba vs. Gm, 13091 DEGs were identified, and these DEGs were significantly enriched in ko03010 (ribosome) and ko03008 (ribosome biogenesis in eucaryotes). Our results suggest that B. amyloliquefaciens increases the expression of genes encoding the ribosomal subunit, promotes cell wall biogenesis, and induces systemic resistance. S. sclerotiorum strongly inhibited metabolism in soybean, inhibited the synthesis of the cytoskeleton, and induced the up-regulation of programmed death and senescence-related genes via an ethylene signal transduction pathway. These results improve our understanding of S. sclerotiorum-induced plant death and soybean resistance to S. sclerotiorum induced by B. amyloliquefaciens and may contribute to the improvement of strategies to avoid yield losses.
Chromosome-level assembly of the Phytophthora agathidicida genome reveals adaptation in effector gene families

Phytophthora species are notorious plant pathogens, with some causing devastating tree diseases that threaten the survival of their host species. One such example is Phytophthora agathidicida, the causal agent of kauri dieback – a root and trunk rot disease that kills the ancient, iconic and culturally significant tree species, Agathis australis (New Zealand kauri). A deeper understanding of how Phytophthora pathogens infect their hosts and cause disease is critical for the development of effective treatments. Such an understanding can be gained by interrogating pathogen genomes for effector genes, which are involved in virulence or pathogenicity. Although genome sequencing has become more affordable, the complete assembly of Phytophthora genomes has been problematic, particularly for those with a high abundance of repetitive sequences. Therefore, effector genes located in repetitive regions could be truncated or missed in a fragmented genome assembly. Using a combination of long-read PacBio sequences, chromatin conformation capture (Hi-C) and Illumina short reads, we assembled the P. agathidicida genome into ten complete chromosomes, with a genome size of 57 Mb including 34% repeats. This is the first Phytophthora genome assembled to chromosome level and it reveals a high level of syntenic conservation with the complete genome of Peronospora effusa, the only other completely assembled genome sequence of an oomycete. All P. agathidicida chromosomes have clearly defined centromeres and contain candidate effector genes such as RXLRs and CRNs, but in different proportions, reflecting the presence of gene family clusters. Candidate effector genes are predominantly found in gene-poor, repeat-rich regions of the genome, and in some cases showed a high degree of duplication. Analysis of candidate RXLR effector genes that occur in multicopy gene families indicated half of them were not expressed in planta. Candidate CRN effector gene families showed evidence of transposon-mediated recombination leading to new combinations of protein domains, both within and between chromosomes. Further analysis of this complete genome assembly will help inform new methods of disease control against P. agathidicida and other Phytophthora species, ultimately helping decipher how Phytophthora pathogens have evolved to shape their effector repertoires and how they might adapt in the future.
Improving productivity of Sesbania pea in saline soils by enhancing antioxidant capacity with optimum application of nitrogen and phosphate combination

Salinity stress is one of the major constraints to plant growth and crop production. Optimum fertilizer management is essential for promoting crop growth and productivity in saline soils. A field experiment was conducted to study the effects of nitrogen and phosphate combination on sesbania pea (Sesbania cannabina (Retz.) Poir. ) growth and associated physiology in saline soils. Three N rates (N1: 240 kg·ha-1, N2: 360 kg·ha-1, N3: 480 kg·ha-1) and two P rates (P1: 120 kg·ha-1, P2:180 kg·ha-1) were arranged in this study using a RCBD with 3 replicates. The application of N and P fertilizers significantly improved plant growth and associated physiological traits of sesbania pea. Plant height (P=0.0001), fresh biomass weight (P=0.0006), dry biomass weight (P=0.0006), relative growth rate (RGR) (P=0.005), chlorophyll (P=0.002), peroxidase (POD) (P=0.0003), catalase (CAT) (P=0.0001), superoxide dismutase (SOD) (P=0.0001) and soluble protein (P=0.0053) were significantly increased, and the maximum values were consistently produced under N2P2 combination at each growth stage. On the contrary, malondialdehyde (MDA) was prominently decreased by N and P fertilizer application (P=0.0029), and the lowest values were all produced under N2P2 combination. The highest values of plant height, fresh biomass weight and dry biomass weight were recorded on the 163rd day after seeding (DAS). The highest RGR and MDA content were determined on the 141st DAS. The highest chlorophyll content, CAT and SOD activity, and soluble protein content were recorded on the 110th DAS, and the highest POD activity was at 47 DAS. This study suggested that the optimum N and P fertilizer combination was N2P2 (360 kg·hm-2 N + 180 kg·hm-2 P), which was superior in promoting growth and biomass yield with enhanced antioxidant capacity of sesbania pea in saline soils.
AI-boosted CRISPR-Cas13a and total internal reflection fluorescence microscopy system for SARS-CoV-2 detection

Integrating artificial intelligence with SARS-CoV-2 diagnostics can help in the timely execution of pandemic control and monitoring plans. To improve the efficiency of the diagnostic process, this study aims to classify fluorescent images via traditional machine learning and deep learning-based transfer learning. A previous study reported a CRISPR-Cas13a system combined with total internal reflection fluorescence microscopy (TIRFM) to detect the existence and concentrations of SARS-CoV-2 by fluorescent images. However, the lack of professional software and excessive manual labor hinder the practicability of the system. Here, we construct a fluorescent image dataset and develop an AI-boosted CRISPR-Cas13a and total internal reflection fluorescence microscopy system for the rapid diagnosis of SARS-CoV-2. Our study proposes Fluorescent Images Classification Transfer learning based on DenseNet-121 (FICTransDense), an approach that uses TIRF images (before and after sample introduction, respectively) for preprocessing, including outlier exclusion and setting and division preprocessing (i.e., SDP). Classification results indicate that the FICTransDense and Decision Tree algorithms outperform other approaches on the SDP dataset. Most of the algorithms benefit from the proposed SDP technique in terms of Accuracy, Recall, F1 Score, and Precision. The use of AI-boosted CRISPR-Cas13a and TIRFM systems facilitates rapid monitoring and diagnosis of SARS-CoV-2.
The more engaging, the more enjoyable? Age matters in predicting perceived enjoyment with different Facebook activities

Drawing upon uses and gratifications perspectives and socioemotional selectivity theory, this study examined the differences in the use of Facebook features among younger, middle-aged, and older adults. Furthermore, it explored the association between Facebook activities and users’ perceived enjoyment for different age groups. An online survey was conducted with 647 Facebook users in the United States. An exploratory factor analysis identified four types of Facebook activities: broadcasting, directed communication, content consumption, and information regulation. The results revealed that younger users’ broadcasting, content consumption, and information regulation activities substantially differed from those of older users. In addition, broadcasting and content consumption activities were more popular among younger users and more predictive of their enjoyment. Directed communication was more powerful in predicting middle-aged and older users’ enjoyment. However, younger and middle-aged users’ engagement with information regulation activities was negatively related to their enjoyment of Facebook. The study findings provide more nuanced knowledge regarding user experiences on social media platforms among specified age groups and practical insights into the improvement of social media by addressing their different needs.
Forsythiaside B ameliorates coagulopathies in a rat model of sepsis through inhibition of the formation of PAD4-dependent neutrophil extracellular traps

Forsythiaside B (FTB) is one of the main components of Forsythia suspensa (Thunb.) Vahl and exerts anti-inflammatory and anti-oxidative effects. However, its mechanism of action as a treatment for sepsis remains unclear. In this study, we developed a rat model of sepsis using cecal ligation and puncture (CLP) to investigate the effects of FTB on sepsis-associated coagulopathies. Using rats with sepsis, we investigated the effects of FTB on neutrophil extracellular trap (NETs) formation and peptidylarginine deiminase 4 (PAD4) expression in neutrophils. NET (DNase1) and PAD4 (Cl-amidine) inhibitors were used to further investigate whether FTB mitigates sepsis-associated coagulopathies by inhibiting PAD4-dependent NETs production. Our results showed that treatment with FTB increased the survival rate, ameliorated the CLP-induced inflammatory response and multiple organ dysfunction, and reduced CLP-induced pathological changes. FTB also alleviated the associated coagulopathies. Additionally, we demonstrated that treatment with FTB inhibited NETs formation and downregulated PAD4 expression in peripheral neutrophils. The effects of FTB on coagulopathies were similar to those of monotherapy with NET or PAD4 inhibitors. In conclusion, our study confirmed that FTB can alleviate coagulopathies in rats with sepsis. The underlying mechanism of FTB’s effect consists in inhibition of PAD4-dependent NETs formation.
Constant installation of present orientation and safety (CIPOS) - subjective and physiological effects of an ultrashort-term intervention combining both stabilizing and confrontational elements

Objectives Constant Installation of Present Orientation and Safety (CIPOS) is a Eye Movements Desensitization and Reprocessing (EMDR)-derived technique, which is often used to prepare for the treatment of post-traumatic stress disorder (PTSD). It differs from the latter by involving cyclically recurring exercises in reorientation to the present, interspersed between brief periods of exposure to the traumatic material. While EMDR is well established as a therapeutic method, the efficacy and mechanisms of action of CIPOS have not been investigated so far. In this pilot study, an experimental setting was used to record the subjective and physiological effects of the CIPOS intervention compared to a control condition with pure mental exposition. Methods The study was performed on 30 healthy volunteers aged from 20 to 30 years. Distress was induced using audio files of subjectively stressful situations. Subjective distress was measured via the Subjective Units of Distress Scale (SUD), while physiological indicators (noise-induced startle reflex, skin conductance level) were used as measures for objective stress. For each condition, pre- and post-intervention comparisons were calculated. Results In both groups, startle reflex potentiation and mean skin conductance level significantly decreased. In the group with CIPOS intervention, but not in the control group, a significant decrease in the SUD value was found. Conclusion and significance The results show that the CIPOS technique is as effective as pure mental exposition in reducing physiological stress. In addition, a superiority in reducing subjective distress (indicating a simplified reassessment of the stressful material) was found compared to pure mental exposition. Possible explanations of these effects are discussed.
Nanoparticles targeting hematopoietic stem and progenitor cells: Multimodal carriers for the treatment of hematological diseases

Modern-day hematopoietic stem cell (HSC) therapies, such as gene therapy, modify autologous HSCs prior to re-infusion into myelo-conditioned patients and hold great promise for treatment of hematological disorders. While this approach has been successful in numerous clinical trials, it relies on transplantation of ex vivo modified patient HSCs, which presents several limitations. It is a costly and time-consuming procedure, which includes only few patients so far, and ex vivo culturing negatively impacts on the viability and stem cell-properties of HSCs. If viral vectors are used, this carries the additional risk of insertional mutagenesis. A therapy delivered to HSCs in vivo, with minimal disturbance of the HSC niche, could offer great opportunities for novel treatments that aim to reverse disease symptoms for hematopoietic disorders and could bring safe, effective and affordable genetic therapies to all parts of the world. However, substantial unmet needs exist with respect to the in vivo delivery of therapeutics to HSCs. In the last decade, in particular with the development of gene editing technologies such as CRISPR/Cas9, nanoparticles (NPs) have become an emerging platform to facilitate the manipulation of cells and organs. By employing surface modification strategies, different types of NPs can be designed to target specific tissues and cell types in vivo. HSCs are particularly difficult to target due to the lack of unique cell surface markers that can be utilized for cell-specific delivery of therapeutics, and their shielded localization in the bone marrow (BM). Recent advances in NP technology and genetic engineering have resulted in the development of advanced nanocarriers that can deliver therapeutics and imaging agents to hematopoietic stem- and progenitor cells (HSPCs) in the BM niche. In this review we provide a comprehensive overview of NP-based approaches targeting HSPCs to control and monitor HSPC activity in vitro and in vivo, and we discuss the potential of NPs for the treatment of malignant and non-malignant hematological disorders, with a specific focus on the delivery of gene editing tools.
How well does CLIP understand texture?

We investigate how well does CLIP understand texture in natural images described by natural language. To this end we analyze CLIP’s ability to: (1) perform zero-shot learning on various texture and material classification datasets; (2) represent compositional properties of texture such as red dots or yellow stripes on the Describable Texture in Detail ( DTD 2 ) dataset; and (3) aid fine-grained categorization of birds in photographs described by color and texture of their body parts.
Residual Carbon in Oxygen–Neon White Dwarfs and Its Implications for Accretion-induced Collapse

We explore the effects of the residual present in oxygen–neon white dwarfs (ONe WDs) on their evolution toward accretion-induced collapse (AIC). We produce a set of ONe WD models using Modules for Experiments in Stellar Astrophysics (MESA) and illustrate how the amount and location of the residual carbon depends on the initial mass of the star and assumptions about rotation and convective overshooting. We find a wide range of possible mass fractions roughly ranging from 0.1% to 10%. Convection and thermohaline mixing that occurs as the ONe WDs cool leads to nearly homogeneous interior compositions by the time that AIC would occur. We evolve these ONe WD models and some toy WD models toward AIC and find that regardless of the carbon fraction, the occurrence of Urca-process cooling due to implies that the models are unlikely to reach carbon ignition before electron captures on occur. Difficulties associated with modeling electron-capture-driven convective regions in these ONe WDs prevent us from evolving our MESA models all the way to thermonuclear oxygen ignition and the onset of collapse. Thus, firm conclusions about the effect of carbon on the final fates of these objects await improved modeling. However, it is clear that the inclusion of residual carbon can shift the evolution from that previously described in the literature and should be included in future models.