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Soil salinization is a common environmental problem that seriously threatens crop yield and food security, especially through its impact on seed germination. Nanoparticle priming, an emerging seed treatment method, is receiving increasing attention in improving crop yield and stress resistance. This study used alfalfa seeds as materials to explore the potential benefits of cerium oxide nanoparticle (CeO2NP) priming to promote seed germination and improve salt tolerance. CeO2NPs at concentrations up to 500 mg/L were able to significantly alleviate salt stress in alfalfa seeds (200 mM), with 50 mg/L of CeO2NP having the best effect, significantly (P< 0.05) increasing germination potential (from 4.0% to 51.3%), germination rate (from 10.0% to 62.7%), root length (from 8.3 cm to 23.1 cm), and seedling length (from 9.8 cm to 13.7 cm). Priming treatment significantly (P< 0.05) increased seed water absorption by removing seed hardness and also reducing abscisic acid and jasmonic acid contents to relieve seed dormancy. CeO2NP priming increased α-amylase activity and osmoregulatory substance level, decreased reactive oxygen species and malonaldehyde contents and relative conductivity, and increased catalase enzyme activity. Seed priming regulated carotenoid, zeatin, and plant hormone signal transduction pathways, among other metabolic pathways, while CeO2NP priming additionally promoted the enrichment of α-linolenic acid and diterpenoid hormone metabolic pathways under salt stress. In addition, CeO2NPs enhanced α-amylase activity (by 6.55%) in vitro. The optimal tested concentration (50 mg/L) of CeO2NPs was able to improve the seed vigor, enhance the activity of α-amylase, regulate the osmotic level and endogenous hormone levels, and improve the salt tolerance of alfalfa seeds. This study demonstrates the efficacy of a simple seed treatment strategy that can improve crop stress resistance, which is of great importance for reducing agricultural costs and promoting sustainable agricultural development.

Soil salinization is a common environmental problem that seriously threatens crop yield and food security, especially through its impact on seed germination. Nanoparticle priming, an emerging seed treatment method, is receiving increasing attention in improving crop yield and stress resistance. This study used alfalfa seeds as materials to explore the potential benefits of cerium oxide nanoparticle (CeO2NP) priming to promote seed germination and improve salt tolerance. CeO2NPs at concentrations up to 500 mg/L were able to significantly alleviate salt stress in alfalfa seeds (200 mM), with 50 mg/L of CeO2NP having the best effect, significantly (P< 0.05) increasing germination potential (from 4.0% to 51.3%), germination rate (from 10.0% to 62.7%), root length (from 8.3 cm to 23.1 cm), and seedling length (from 9.8 cm to 13.7 cm). Priming treatment significantly (P< 0.05) increased seed water absorption by removing seed hardness and also reducing abscisic acid and jasmonic acid contents to relieve seed dormancy. CeO2NP priming increased α-amylase activity and osmoregulatory substance level, decreased reactive oxygen species and malonaldehyde contents and relative conductivity, and increased catalase enzyme activity. Seed priming regulated carotenoid, zeatin, and plant hormone signal transduction pathways, among other metabolic pathways, while CeO2NP priming additionally promoted the enrichment of α-linolenic acid and diterpenoid hormone metabolic pathways under salt stress. In addition, CeO2NPs enhanced α-amylase activity (by 6.55%) in vitro. The optimal tested concentration (50 mg/L) of CeO2NPs was able to improve the seed vigor, enhance the activity of α-amylase, regulate the osmotic level and endogenous hormone levels, and improve the salt tolerance of alfalfa seeds. This study demonstrates the efficacy of a simple seed treatment strategy that can improve crop stress resistance, which is of great importance for reducing agricultural costs and promoting sustainable agricultural development. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) is a common inherited retinal disease characterized by progressive degeneration of the retina, leading to night blindness, progressive vision loss, and constriction of the visual field. Previously, we established a human induced pluripotent stem cell line (CSUASOi006-A) from a RP patient carrying heterozygous PRPF8 (c.C5792T) mutation. Here, we corrected the mutation sites in PRPF8 (c.C5792T) using an adenine base editor and then generated an isogenic control (CSUASOi006-A-1), which is a valuable cell resource for research of RP.

PRPF6, located on chromosome 20, is required for the formation of the spliceosome. Mutations in the PRPF6 gene can lead to retinitis pigmentosa (RP), a common inherited retinal disease characterized by progressive degeneration of retinal pigment epithelium and photoreceptors. Here, we generated an induced pluripotent stem cell (iPSC) line carrying the PRPF6 c.2699 G > A mutation using CRISPR/Cas9 technology, which will provide a valuable resource for RP pathogenesis and treatment research.

X-linked retinoschisis (XLRS) is a common retinal genetic disease that occurs in juvenile males and causes progressive visual impairment. This presents a schisis in the macula or peripheral retina of bilateral eyes, which has no effective treatment. Here, we introduced the RS1 (c.C304T, p.R102W) mutation into a normal induced pluripotent stem (iPS) cell line using CRISPR/Cas9 technology. This missense mutation was consistent with that observed in the XLRS patient-derived iPS cell line (CSUASOi001-A). Conclusively, establishing a directed gene mutation cell line (CSUi007-A) provides a useful cell resource to investigate XLRS pathogenesis.

ABSTRACTProphages, which are an existing form of temperate phages that integrate into host genomes, have been found extensively present in diverse bacterial species. The human gut microbiome, characterized by its complexity, dynamism, and interconnectivity among multiple species, remains inadequately understood in terms of the global landscape of bacterial prophages. Here, we analyzed 43,942 human gut-derived bacterial genomes (439 species of 12 phyla) and identified 105,613 prophage regions in ~ 92% of them. 16254 complete prophages were distributed in ~ 24% of bacteria, indicating an extremely uneven prophage distribution across various species within the human gut. Among all identified prophages, ~4% possessed cross-genera (2–20 genera) integration capacity, while ~ 17% displayed broad infection host ranges (targeting 2–35 genera). Functional gene annotation revealed that antibiotic-resistance genes and toxin-related genes were detected in ~ 2.5% and ~ 5.8% of all prophages, respectively. Furthermore, through sequence alignments between our obtained prophages and publicly available human gut phageome contigs, we have observed that ~ 72% of non-redundant prophages are previously unreported genomes, and they illuminate ~ 6.5–9.5% of the individual intestinal “viral dark matter”. Our study represents the first comprehensive depiction of human gut-derived prophages, provides a substantial collection of reference sequences for forthcoming human gut phageome-related investigations, and potentially enables better risk assessment of prophage dissemination.

Abstract Background X-linked juvenile retinoschisis (XLRS) is an inherited disease caused by RS1 gene mutation, which leads to retinal splitting and visual impairment. The mechanism of RS1-associated retinal degeneration is not fully understood. Besides, animal models of XLRS have limitations in the study of XLRS. Here, we used human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) to investigate the disease mechanisms and potential treatments for XLRS. Methods hiPSCs reprogrammed from peripheral blood mononuclear cells of two RS1 mutant (E72K) XLRS patients were differentiated into ROs. Subsequently, we explored whether RS1 mutation could affect RO development and explore the effectiveness of RS1 gene augmentation therapy. Results ROs derived from RS1 (E72K) mutation hiPSCs exhibited a developmental delay in the photoreceptor, retinoschisin (RS1) deficiency, and altered spontaneous activity compared with control ROs. Furthermore, the delays in development were associated with decreased expression of rod-specific precursor markers (NRL) and photoreceptor-specific markers (RCVRN). Adeno-associated virus (AAV)-mediated gene augmentation with RS1 at the photoreceptor immature stage rescued the rod photoreceptor developmental delay in ROs with the RS1 (E72K) mutation. Conclusions The RS1 (E72K) mutation results in the photoreceptor development delay in ROs and can be partially rescued by the RS1 gene augmentation therapy.

Abstract Inherited retinal diseases (IRDs) can induce severe sight-threatening retinal degeneration and impose a considerable economic burden on patients and society, making efforts to cure blindness imperative. Transgenic animals mimicking human genetic diseases have long been used as a primary research tool to decipher the underlying pathogenesis, but there are still some obvious limitations. As an alternative strategy, patient-derived induced pluripotent stem cells (iPSCs), particularly three-dimensional (3D) organoid technology, are considered a promising platform for modeling different forms of IRDs, including retinitis pigmentosa, Leber congenital amaurosis, X-linked recessive retinoschisis, Batten disease, achromatopsia, and best vitelliform macular dystrophy. Here, this paper focuses on the status of patient-derived iPSCs and organoids in IRDs in recent years concerning disease modeling and therapeutic exploration, along with potential challenges for translating laboratory research to clinical application. Finally, the importance of human iPSCs and organoids in combination with emerging technologies such as multi-omics integration analysis, 3D bioprinting, or microfluidic chip platform are highlighted. Patient-derived retinal organoids may be a preferred choice for more accurately uncovering the mechanisms of human retinal diseases and will contribute to clinical practice.

X-linked retinoschisis (XLRS) is one of the most common retinal genetic diseases with progressive visual impairment in childhood affecting males. It is manifested with macular and/or peripheral schisis in neural retinas with no effective treatment. Previously, we successfully generated a human-induced pluripotent stem cell (iPSC) line from an XLRS patient carrying the hemizygous RS1 c. 304C > T (p.R102W) mutation. Here, we corrected the c.304C > T mutation in the RS1 gene using CRISPR/Cas9 technology to generate an isogenic control. This cell line is valuable for the study of XLRS.

Retinitis pigmentosa (RP) is one of the most common inherited retinal diseases characterized by nyctalopia, progressive vision loss and visual field contraction. we previously generated an induced pluripotent stem cell line (CSUASOi004-A) from a RP patient with heterozygous PRPF6 c.2699 G>A (p.R900H) mutation. Here we corrected the PRPF6 c.2699 G>A mutation genetically using CRISPR/Cas9 technology to generate an isogenic control (CSUASOi004-A-1), which can provide a valuable resource in the research of the disease.

Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes, and the leading cause of preventable blindness in working-aged people. Here, we generated an induced pluripotent stem (iPS) cell line using blood-derived cells from a patient with DR. Peripheral blood mononuclear cells (PBMCs) were reprogrammed with Sendai virus.

Suspended spheroid culture using ultralow attachment plates (ULAPs) is reported to effect corneal fibroblast reprogramming. Polydimethylsiloxane (PDMS), with hydrophobic and soft substrate properties, facilitates adherent spheroid formation that promotes cellular physical reprogramming into stem-like cells without using transcription factors. However, it is still unknown whether the biophysical properties of PDMS have the same effect on adult human corneal keratocyte reprogramming. Here, PDMS and essential 8 (E8) medium were utilized to culture keratocyte spheroids and fibroblast spheroids, and the reprogramming results were compared. We provide insights into the probable mechanisms of the PDMS effect on spheroids. qPCR analysis showed that the expression of some stem cell marker genes (OCT4, NANOG, SOX2, KLF4, CMYC, ABCG2 and PAX6) was significantly greater in keratocyte spheroids than in fibroblast spheroids. The endogenous level of stemness transcription factors (OCT4, NANOG, SOX2, KLF4 and CMYC) was higher in keratocytes than in fibroblasts. Immunofluorescence staining revealed Klf4, Nanog, Sox2, ABCG2 and Pax6 were positively stained in adherent 3D spheroids but weakly or negatively stained in adherent 2D cells. Furthermore, OCT4, NANOG, SOX2, KLF4, HNK1, ABCG2 and PAX6 gene expression was significantly higher in adherent 3D spheroids than in adherent 2D cells. Meanwhile, SOX2, ABCG2 and PAX6 were more upregulated in adherent 3D spheroids than in suspended 3D spheroids. The RNA-seq analysis suggested that regulation of the actin cytoskeleton, TGFβ/BMP and HIF-1 signaling pathways induced changes in mechanotransduction, the mesenchymal-to-epithelial transition and hypoxia, which might be responsible for the effect of PDMS on facilitating reprogramming. In conclusion, compared to corneal fibroblasts, keratocytes were more susceptible to reprogramming due to higher levels of endogenous stemness transcription factors. Spheroid culture of keratocytes using PDMS had a positive impact on promoting the expression of some stem cell markers. PDMS, as a substrate to form spheroids, was better able to promote reprogramming than ULAPs. These results indicated that the physiological cells and culture conditions herein enhance reprogramming. Therefore, adherent spheroid culture of keratocytes using PDMS is a promising strategy to more safely promote reprogramming, suggesting its potential application for developing clinical implants in tissue engineering and regenerative medicine.

Short-term load forecasting (STLF) has a significant role in reliable operation and efficient scheduling of power systems. However, it is still a major challenge to accurately predict power load due to social and natural factors, such as temperature, humidity, holidays and weekends, etc. Therefore, it is very important for the efficient feature selection and extraction of input data to improve the accuracy of STLF. In this paper, a novel hybrid model based on empirical mode decomposition (EMD), a one-dimensional convolutional neural network (1D-CNN), a temporal convolutional network (TCN), a self-attention mechanism (SAM), and a long short-term memory network (LSTM) is proposed to fully decompose the input data and mine the in-depth features to improve the accuracy of load forecasting. Firstly, the original load sequence was decomposed into a number of sub-series by the EMD, and the Pearson correlation coefficient method (PCC) was applied for analyzing the correlation between the sub-series with the original load data. Secondly, to achieve the relationships between load series and external factors during an hour scale and the correlations among these data points, a strategy based on the 1D-CNN and TCN is proposed to comprehensively refine the feature extraction. The SAM was introduced to further enhance the key feature information. Finally, the feature matrix was fed into the long short-term memory (LSTM) for STLF. According to experimental results employing the North American New England Control Area (ISO-NE-CA) dataset, the proposed model is more accurate than 1D-CNN, LSTM, TCN, 1D-CNN–LSTM, and TCN–LSTM models. The proposed model outperforms the 1D-CNN, LSTM, TCN, 1D-CNN–LSTM, and TCN–LSTM by 21.88%, 51.62%, 36.44%, 42.75%, 16.67% and 40.48%, respectively, in terms of the mean absolute percentage error.