A SCYL2 gene from Oryza sativa is involved in phytosterol accumulation and regulates plant growth and salt stress.

Rice is a crucial food for humans due to its high nutritional value. Phytosterols, essential components of the plant membrane lipid bilayer, play a vital role in plant growth and contribute significantly to lipid-lowering, antitumor, and immunomodulation processes. In this study, SCY1-like protein kinases 2 (SCYL2) was found to be closely related to the accumulation of phytosterols. The levels of campesterol, stigmasterol, and ß-sitosterol significantly increased in transgenic rice seeds, husks, and leaves, whereas there was a considerable reduction in scyl2 plants. Subsequent investigations revealed the crucial role of SCYL2 in plant development. Mutations in this gene led to stunted plant growth while overexpressing OsSCYL2 in Arabidopsis and rice resulted in larger leaves, taller plants, and accelerated development. When subjected to salt stress, Arabidopsis plants overexpressed OsSCYL2 showed significantly higher germination rates than wild-type plants. Similarly, transgenic rice seedlings displayed better growth than both ZH11 and mutant plants, exhibiting lower malondialdehyde (MDA) content and higher peroxidase (POD), and catalase (CAT) activities. Conversely, scyl2 plants exhibited more yellow leaves or even death. These findings suggested that OsSCYL2 proteins might be involved in phytosterols synthesis and play an important role during plant growth and development. This study provides a theoretical basis for developing functional rice.

Genome-Wide Identification of Vascular Plant One-Zinc-Finger Gene Family in Six Cucurbitaceae Species and the Role of CmoVOZ2 in Salt and Drought Stress Tolerance.

As a plant-specific transcription factor, the vascular plant one-zinc-finger (VOZ) plays a crucial role in regulating various biological processes. In this study, a total of 17 VOZ genes in the Cucurbitaceae family were investigated using various bioinformatics methods. The 17 VOZ genes in Cucurbitaceae are distributed across 16 chromosomes. Based on the affinity of VOZ proteins to AtVOZ proteins, these 17 proteins were categorized into two groups: group I encompassed eight VOZ members, while group II comprised nine VOZ members. The expression profiles of CmoVOZs under various hormonal and abiotic stresses indicated that these genes were induced differentially by JA, ABA, GA, salt, and drought stress. Subsequently, CmoVOZ1 and CmoVOZ2 were found to be transcriptionally active, with the CmoVOZ2 protein being located mainly in the nucleus. Further experiments revealed that yeast cells expressing CmoVOZ2 gene showed increased tolerance to salt stress and drought stress. These results suggest that the VOZ gene family is not only important for plant growth and development but also that this mechanism may be universal across yeast and plants.

Overexpression of the OsFes1A increased the phytosterols content and enhanced drought and salt stress tolerance in Arabidopsis.

MAIN CONCLUSION: Overexpression of the rice gene, OsFes1A, increased phytosterol content and drought and salt stress tolerance in Arabidopsis. Phytosterols are key components of the phospholipid bilayer membrane and regulate various processes of plant growth and response to biotic and abiotic stresses. In this study, it was demonstrated that the overexpression of OsFes1A (Hsp70 nucleotide exchange factor Fes1) increased phytosterols content and enhanced tolerance to salt and drought stress in Arabidopsis. In transgenic plants, the average content of campesterol was 17.6% higher than that of WT, and the average content of ß-sitosterol reached 923.75 µg/g, with an increase of 1.33-fold. In fes1a seeds, the contents of campesterol and ß-sitosterol reduced by 20% and 10.93%, respectively. In OsFes1A transgenic seeds, the contents of campesterol and ß-sitosterol increased by 1.38-fold and 1.25-fold respectively. Furthermore, the germination rate of transgenic Arabidopsis was significantly higher than WT under stress (salt, ABA, and drought treatment). Under salt stress, transgenic plants accumulated a lower MDA content, higher chlorophyll content, and POD activity relative to the wild type, while the mutants showed the opposite pattern Our study found multiple other functions of OsFes1A beyond the defined role of Fes1 in regulating Hsp70, contributing to the better understanding of the essential roles of Fes1 in plants. Meanwhile, it provides the theoretical basis for developing high phytosterol crop varieties.

Mechanism of Yishen Tonglong Decoction inhibiting TLR4/p38 MAPK/NF-κB signaling pathway against prostate cancer via upregulating miR-145-5p / 数字中医药（英文）

@#【Objective】 To investigate the mechanism of Yishen Tonglong Decoction (益肾通癃汤, YSTLD) inhibiting the toll-like receptor 4/p38 mitogen activated protein kinases/nuclear factor kappa-B (TLR4/p38 MAPK/NF-κB) signaling pathway against prostate cancer by up-regulating miR-145-5p. 【Methods】 miRNA microarray technology was used to detect the changes of miRNA expression profile in prostate cancer PC-3 cells treated with YSTLD, and miRNAs with marked differences in miRNA microarray results were screened and validated by real-time polymerase chain reaction (qRT-PCR). Lentiviral transfection of miR-145-5p into prostate cancer PC-3 cells, Cell Counting Kit-8 (CCK8) assay, and scratch assay were adopted to detect the effects of miR-145-5p on prostate cancer PC-3 cell proliferation and migration. qRT-PCR and Western blot were employed to detect the effects of miR-145-5p on TLR4/p38 MAPK/NF-κB signaling pathway and the expression levels of apoptosis-related genes caspase3, tumor necrosis factor-α (TNF-α), Bax, and Bcl-2. qRT-PCR and Western blot were used to detect the effects of serum containing YSTLD on miR-145-5p, TLR4/p38 MAPK/NF-κB signaling pathway, and the expression levels of apoptosis-related genes caspase3, TNF-α, Bax, and Bcl-2. 【Results】 The expression levels of 35 miRNAs in prostate cancer PC-3 cells treated with YSTLD were significantly different from those in the control group, with miR-145-5p being the most significantly different; qRT-PCR validation revealed that the miR-145-5p levels in prostate cancer PC-3 cells treated with YSTLD were significantly higher than those in the DMSO control group (P < 0.05). After lentiviral transfection of miR-145-5p into prostate cancer PC-3 cells, miR-145-5p was found to inhibit the proliferation and migration of prostate cancer PC-3 cells. Overexpression of miR-145-5p up-regulated expression levels of caspase3, TNF-α, and Bax mRNA, and down-regulated expression levels of p38 MAPK, p65 NF-κB, and Bcl-2 mRNA in prostate cancer PC-3 cells (P < 0.05), while up-regulated caspase3 protein expression levels in prostate cancer PC-3 cells and down-regulated expression levels of TLR4, p38 MAPK, and p65 NF-κB protein (P < 0.05). Serum containing YSTLD could up-regulate the expression levels of caspase3, TNF-α, and Bax mRNA, and down-regulate the mRNA expression levels of p38 MAPK, p65 NF-κB, Bcl-2, and TNF receptor-associated factor 1 (TRAF1) in prostate cancer PC-3 cells after intervening prostate cancer PC-3 cells (P < 0.05). Simultaneously, it up-regulated the expression levels of caspase3 protein and down-regulated the protein expression levels of TLR4, p38 MARK, p65 NF-κB, and TRAF1 in prostate cancer PC-3 cells (P < 0.05). 【Conclusion】 YSTLD can promote apoptosis of prostate cancer PC-3 cells by up-regulating the expression level of miR-145-5p and inhibiting TLR4/p38 MAPK/NF-κB signaling pathway, which may be an important mechanism of YSTLD against prostate cancer.

Associations between Sex and Risk Factors for Predicting Chronic Kidney Disease.

Gender is an important risk factor in predicting chronic kidney disease (CKD); however, it is under-researched. The purpose of this study was to examine whether gender differences affect the risk factors of early CKD prediction. This study used data from 19,270 adult health screenings, including 5101 with CKD, to screen for 11 independent variables selected as risk factors and to test for the significant effects of statistical Chi-square test variables, using seven machine learning techniques to train the predictive models. Performance indicators included classification accuracy, sensitivity, specificity, and precision. Unbalanced category issues were addressed using three extraction methods: manual sampling, the synthetic minority oversampling technique, and SpreadSubsample. The Chi-square test revealed statistically significant results (p < 0.001) for gender, age, red blood cell count in urine, urine protein (PRO) content, and the PRO-to-urinary creatinine ratio. In terms of classifier prediction performance, the manual extraction method, logistic regression, exhibited the highest average prediction accuracy rate (0.8053) for men, whereas the manual extraction method, linear discriminant analysis, demonstrated the highest average prediction accuracy rate (0.8485) for women. The clinical features of a normal or abnormal PRO-to-urinary creatinine ratio indicated that PRO ratio, age, and urine red blood cell count are the most important risk factors with which to predict CKD in both genders. As a result, this study proposes a prediction model with acceptable prediction accuracy. The model supports doctors in diagnosis and treatment and achieves the goal of early detection and treatment. Based on the evidence-based medicine, machine learning methods are used to develop predictive model in this study. The model has proven to support the prediction of early clinical risk of CKD as much as possible to improve the efficacy and quality of clinical decision making.

LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of prostate cancer via up-regulating PD-L1.

BACKGROUND: We focused on the KCNQ1OT1/miR-15a/PD-L1 axis and explored its significance in regulating immune evasion and malignant behaviors of prostate cancer (PC) cells. METHODS: The expression levels of KCNQ1OT1, miR-15a, PD-L1, and CD8 in cells or tissues were examined by RT-qPCR, western blot or immunohistochemistry (IHC) assays. The direct regulations between KCNQ1OT1, miR-15a and PD-L1 were validated by luciferase reporter assay. PC cells were co-cultured with CD8+ T cells to study the immune evasion. Proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, wound healing and Transwell assays, respectively. The cytotoxicity of CD8+ T cells was determined by LDH cytotoxicity Kit. Epithelial-mesenchymal transition (EMT) and Ras/ERK signaling markers were evaluated by western blot. RESULTS: KCNQ1OT1, PD-L1 and CD8 were increased, while miR-15a was decreased in PC tissues. MiR-15a directly bound to the 3'-UTR of PD-L1 and inhibited the expression of PD-L1. Overexpressing miR-15a in PC cells was sufficient to promote cytotoxicity and proliferation, while inhibit apoptosis of CD8+ T cells, and also suppressed viability, migration, invasion and EMT while promoted apoptosis of PC cells. The above anti-tumor effects of miR-15a were reversed by overexpressing PD-L1. KCNQ1OT1 sponged miR-15a and released its inhibition on PD-L1. Functionally, KCNQ1OT1 in PC cells was essential for suppressing the cytotoxicity of CD8+ T cells and maintaining multiple malignant phenotypes of PC cells. The Ras/ERK signaling was suppressed after overexpressing miR-15a or knocking down KCNQ1OT1. CONCLUSIONS: LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.

Garcinone D, a natural xanthone promotes C17.2 neural stem cell proliferation: Possible involvement of STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway.

Garcinia mangostana L. (Mangosteen) has been used to treat various pathological conditions, including inflammation and urinary tract infections. Here, we observed that garcinone D, a natural xanthone from mangosteen, promoted the proliferation of C17.2 neural progenitor cells and also resulted in a larger percentage of cells in S phase compared with the control group. Moreover, garcinone D increased the protein levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and Cyclin D1 in concentration- and time- dependent manners. Garcinone D also increased the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in concentration- and time- dependent manners, and inhibiting Nrf2 activation by brusatol could partly reverse garcinone D-induced C17.2 cell proliferation. Taken together, it is the first time to show that garcinone D promotes the proliferation of C17.2 neural stem cells, which may involve the STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway. It would provide new inspiration to develop garcinone D as a lead compound to promote the proliferation of endogenous neural stem cells (NSCs).