Quantitative evaluation and mechanism analysis of soil chemical factors affecting rice yield in saline-sodic paddy fields.

Salinization and sodication have become an important abiotic stress affecting soil fertility and crop production in the western of the Songnen Plain in Northeast China. And rice cultivation is considered as one of the most effective biological methods to reclaim saline-sodic soils and ensure food security. However, it is difficult to select the optimal measures to regulate rice growth for increasing yield, because the independent and comprehensive influences of the soil limitation factors on rice yield are not quantitatively evaluated. In this study, the hierarchical partitioning (HP) and the structural equation model (SEM) were used to quantitatively evaluate the influences of salinization parameters, salt ion concentrations and soil nutrients to identify the dominant limitation factors and obstacle mechanism for rice yield. The results showed that soil pH was the key index in salinization parameters, [CO32- + HCO3-] was the key index in salt ion concentrations and available nitrogen (AN) was the key index in soil nutrients to impact rice yield, which independent influences reached 53.7 %, 45.4 % (negative) and 53.2 % (positive), respectively. Soil pH was determined by [CO32- + HCO3-], and the negative effect of alkali stress on rice yield mainly caused by [CO32- + HCO3-] was greater than that of salt stress mainly caused by [Na+] in saline-sodic paddy fields. Among the soil chemical factors, soil pH and AN were the most important explanatory variables of rice yield in saline-sodic paddy fields, which standardized total effects were - 0.32 and 0.40, respectively. Furthermore, the AN showed a more significant negative correlation with soil pH and a higher yield-increasing potential in severe saline-sodic soils (9 ≤ pH < 10) than that in moderate saline-sodic soils (8 ≤ pH < 9). Therefore, decreasing [CO32- + HCO3-] and increasing the content of AN are key to improve rice yield in saline-sodic paddy fields.

Distribution, development, and identity of retinal ganglion cells labeled in the Sert-Cre reporter mouse.

The mouse retina contains over 40 types of retinal ganglion cells (RGCs) that differ in morphology, function, or gene expression. RGCs also differ by whether their axons target the brain.s ipsilateral or contralateral hemisphere. Contralaterally projecting RGCs (contraRGCs) are widespread in mouse retina, whereas ipsilateral projecting RGCs (ipsiRGCs) are confined to the ventro-temporal (VT) crescent of retina. In this study, we employed the Sert-Cre transgenic line, which had been reported to selectively label ipsiRGCs, to study ipsiRGCs during development. Although the number of Cre-expressing ipsiRGCs did not significantly increase with postnatal age, the region of retina that they occupied did, and by adulthood represented ~30% of the retinal surface. Unexpectedly, genetic ablation of Sert-Cre cells failed to fully disrupt ipsilateral projecting retinal axons, suggesting that not all ipsiRGCs generated Cre in Sert-Cre mice. To test this hypothesis, we retrogradely labeled ipsiRGCs in Sert-Cre mice which revealed that not all ipsiRGCs are labeled in Sert-Cre mice and a small population of contraRGCs flanking the VT crescent generates Cre in this line. These results do not negate the usefulness of the Sert-Cre mouse but do raise important caveats to the interpretation of such studies.

Comprehensive phytohormone metabolomic and transcriptomic analysis of tobacco (Nicotiana tabacum) infected by tomato spotted wilt virus (TSWV).

Tomato spotted wilt virus (TSWV) is ranked among the top 10 most destructive viruses globally. It results in abnormal leaf growth, stunting, and even death, significantly affecting crop yield and quality. Phytohormones play a crucial role in regulating plant-virus interactions. However, there is still limited research on the effect of TSWV on phytohormone levels, particularly growth hormones and genes involved in the phytohormone pathway. In our study, we combined phytohormone metabolomics and transcriptomics to examine the impact of TSWV infection on phytohormone content and gene expression profile. Metabolomic results showed that 41 metabolites, including major phytohormones and their precursors and derivatives were significantly altered after 14 days of TSWV inoculation tobacco plants cvK326, with 31 being significantly increased and 10 significantly reduced. Specifically, the levels of abscisic acid (ABA) and jasmonoyl-isoleucine (JA-Ile) were significantly reduced. The levels of indole-3-acetic acid (IAA) have remained unchanged. However, the levels of cytokinin isopentenyladenine (iP) and salicylic acid (SA) significantly increased. The transcriptome analysis revealed 2,746 genes with significant changes in expression. Out of these, 1,072 genes were significantly downregulated, while 1,674 genes were significantly upregulated. Among them, genes involved in ABA synthesis and signaling pathways, such as 9-cis-epoxycarotenoid dioxygenase (NCED), protein phosphatase 2C (PP2C), serine/threonine-protein kinase (SnRK2), and abscisic acid responsive element binding factor (ABF), exhibited significant downregulation. Additionally, expression of the lipoxygenase gene LOX, Jasmonate ZIM domain-containing protein gene JAZ, and transcription factor gene MYC were significantly down-regulated. In the cytokinin pathway, while there were no significant changes in the expression of the cytokinin synthesis genes, a significant downregulation of transcriptionally active factor type-B response regulators (type-B RRs) was observed. In terms of SA synthesis and signaling pathways, the isochorismate synthase gene ICS1 and the pathogenesis-related gene PR1 were significantly upregulated. These results can strengthen the theoretical foundation for understanding the interaction between TSWV and tobacco and provide new insights for the future prevention and control of TSWV.

Retinal input is required for the maintenance of neuronal laminae in the ventral lateral geniculate nucleus.

Retinal ganglion cell (RGC) axons provide direct input into several nuclei of the mouse visual thalamus, including the dorsal lateral geniculate nucleus (dLGN), which is important for classical image-forming vision, and the ventral lateral geniculate nucleus (vLGN), which is associated with non-image-forming vision. Through both activity- and morphogen-dependent mechanisms, retinal inputs play important roles in the development of dLGN, including the refinement of retinal projections, morphological development of thalamocortical relay cells (TRCs), the timing of corticogeniculate innervation, and the recruitment of inhibitory interneurons from progenitor zones. In contrast, little is known about the role of retinal inputs in the development of vLGN. Grossly, vLGN is divided into two domains, the retinorecipient external vLGN (vLGNe) and the non-retinorecipient internal vLGN (vLGNi). We previously found that vLGNe consists of transcriptionally distinct GABAergic subtypes that are distributed into at least four adjacent laminae. At present, it remains unclear whether retinal inputs influence the development of these cell-specific neuronal laminae in vLGNe. Here, we elucidated the developmental timeline for the formation and maintenance of these laminae in the mouse vLGNe and results indicate that these laminae are specified at or before birth, well before eye-opening and the emergence of experience-dependent visual activity. We observed that mutant mice without retinal inputs have a normal laminar distribution of GABAergic cells at birth; however, after the first week of postnatal development, these mutants exhibited a dramatic disruption in the laminar organization of inhibitory neurons and clear boundaries between vLGNe and vLGNi. Overall, our results show that while the formation of cell type-specific layers in vLGNe does not depend on RGC inputs, retinal signals are critical for their maintenance.

Effect of grape pomace supplement on growth performance, gastrointestinal microbiota, and methane production in Tan lambs.

Grape pomace (GP), a by-product in wine production, is nutritious and can be used as a feed ingredient for ruminants; however, its role in shaping sheep gastrointestinal tract (GIT) microbiota is unclear. We conducted a controlled trial using a randomized block design with 10 Tan lambs fed a control diet (CD) and 10 Tan lambs fed a pelleted diet containing 8% GP (dry matter basis) for 46 days. Rumen, jejunum, cecum, and colon bacterial and archaeal composition were identified by 16S rRNA gene sequencing. Dry matter intake (DMI) was greater (p < 0.05) in the GP than CD group; however, there was no difference in average daily gain (ADG, p < 0.05) and feed conversion ratio (FCR, p < 0.05) between the two groups. The GP group had a greater abundance of Prevotella 1 and Prevotella 7 in the rumen; of Sharpe, Ruminococcaceae 2, and [Ruminococcus] gauvreauii group in the jejunum; of Ruminococcaceae UCG-014 and Romboutsia in the cecum, and Prevotella UCG-001 in the colon; but lesser Rikenellaceae RC9 gut group in the rumen and cecum, and Ruminococcaceae UCG-005 and Ruminococcaceae UCG-010 in the colon than the CD group. The pathways of carbohydrate metabolism, such as L-rhamnose degradation in the rumen, starch and glycogen degradation in the jejunum, galactose degradation in the cecum, and mixed acid fermentation and mannan degradation in the colon were up-graded; whereas, the pathways of tricarboxylic acid (TCA) cycle VIII, and pyruvate fermentation to acetone in the rumen and colon were down-graded with GP. The archaeal incomplete reductive TCA cycle was enriched in the rumen, jejunum, and colon; whereas, the methanogenesis from H2 and CO2, the cofactors of methanogenesis, including coenzyme M, coenzyme B, and factor 420 biosynthesis were decreased in the colon. The study concluded that a diet including GP at 8% DM did not affect ADG or FCR in Tan lambs. However, there were some potential benefits, such as enhancing propionate production by microbiota and pathways in the GIT, promoting B-vitamin production in the rumen, facilitating starch degradation and amino acid biosynthesis in the jejunum, and reducing methanogenesis in the colon.

EGCG-LYS Fibrils-Mediated CircMAP2K2 Silencing Decreases the Proliferation and Metastasis Ability of Gastric Cancer Cells in Vitro and in Vivo.

Aberrant expression of circular RNAs (circRNAs) has been reported to play an important biological regulatory role in gastric cancer (GC). For the purpose of silencing cancer-related genes, a new approach for cancer treatment using nanocarriers to deliver siRNA has been proposed. In this study, abundantly expressed circMAP2K2 (hsa_circRNA_102415) is identified in GC cells. CircMAP2K2 regulates the PCBP1/GPX1 axis through proteasome-mediated degradation, which further mediates the activation of the AKT/GSK3ß/epithelial-to-mesenchymal transition (EMT) signaling pathway and enhances the proliferation and metastatic ability of GC cells. To establish novel GC treatment, epigallocatechin-3-gallate-lysozyme (EGCG-LYS) fibrils are synthesized, and in vitro experiments demonstrate that EGCG-LYS has a higher siRNA delivery efficiency than Lipofectamine 2000 (lipo2000), which effectively silences the expression of circMAP2K2. Further studies show that EGCG-LYS carrying siRNA can successfully achieve lysosome escape, which allows it to be located in the cytoplasm to achieve post-transcriptional gene silencing. In addition, EGCG-LYS carrying si-circMAP2K2 has good circulating stability, excellent biosafety and antitumor ability in vivo. The EGCG-LYS fibrils delivery system provides a new tool and approach for the treatment of GC.

Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape.

Background: Numerous studies have substantiated the association between aging and the progression of malignant tumors in humans, notably prostate cancer (PCa). Nevertheless, to the best of our knowledge, no studies have comprehensively elucidated the intricate characteristics of the aging microenvironment (AME) in PCa. Methods: AME regulatory patterns were determined using the NMF algorithm. Then an ageing microenvironment index (AMI) was constructed, with excellent prognostic and immunotherapy prediction ability, and its' clinical relevance was surveyed through spatial transcriptomics. Further, the drug response was analysed using the Genomics of Drug Sensitivity in Cancer (GDSC), the Connectivity Map (CMap) and CellMiner database for patients with PCa. Finally, the AME was studied using in vitro and vivo experiments. Results: Three different AME regulatory patterns were identified across 813 PCa patients, associated with distinct clinical prognosis and physiological pathways. Based on the AMI, patients with PCa were divided into the high-score and low-score subsets. Higher AMI score was significantly infiltrated with more immune cells, higher rate of biochemical recurrence (BCR) and worse response to immunotherapy, antiandrogen therapy and chemotherapy in PCa. In addition, we found that the combination of bicalutamide and embelin was capable of suppressing tumor growth of PCa. Besides, as the main components of AMI, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: AME regulation is significantly associated with the diversity and complexity of TME. Quantitative evaluation of the AME regulatory patterns may provide promising novel molecular markers for individualised therapy in PCa.

Hsa_circ_0057105 modulates a balance of epithelial-mesenchymal transition and ferroptosis vulnerability in renal cell carcinoma.

BACKGROUND: The incidence of renal cell carcinoma (RCC) has increased in recent years. Metastatic RCC is common and remains a major cause of mortality. A regulatory role for circular RNAs (circRNAs) in the occurrence and progression of RCC has been identified, but their function, molecular mechanisms, and potential clinical applications remain poorly understood. METHODS: High-throughput RNA sequencing was used to explore the differential expression of circRNAs and their related pathways in RCC patients. Transwell and CCK-8 assays were used to assess the function of hsa_circ_0057105 in RCC cells. The clinical relevance of hsa_circ_0057105 was evaluated in a cohort of RCC patients. The hsa_circ_0057105 regulatory axis was defined using RNA pull-down, luciferase reporter assays, and fluorescence in situ hybridization assays, and the in vivo effect of hsa_circ_0057105 was validated using animal experiments. RESULTS: Single-sample gene set enrichment analysis and correlation analysis of RNA-seq data showed that hsa_circ_0057105 was potentially oncogenic and may serve to regulate epithelial-mesenchymal transition (EMT) activation in RCC. Hsa_circ_0057105 expression was associated with advanced TNM stages and was an independent prognostic factor for poor RCC patient survival. Phenotypic studies show that hsa_circ_0057105 can enhance the migration and invasion abilities of RCC cells. Further, hsa_circ_0057105 was shown to inhibit the expression of miR-577, a miRNA that regulated the expression of both COL1A1, which induced EMT activation, and VDAC2, which modulated ferroptosis sensitivity. The dual regulatory roles of hsa_circ_0057105 on EMT and ferroptosis sensitivity were verified using rescue experiments. Animal studies confirmed that hsa_circ_0057105 increased the metastatic ability and ferroptosis sensitivity of RCC cells in vivo. CONCLUSIONS: In RCC, hsa_circ_0057105 regulates COL1A1 and VDAC2 expression through its sponge effect on miR-577, acting like a 'double-edged sword'. These findings provide new insight into the relationship between EMT and ferroptosis in RCC and provide potential biomarkers for RCC surveillance and treatment.

Effect of dietary Agriophyllum squarrosum on average daily gain, meat quality and muscle fatty acids in growing Tan lambs.

The herb A. squarrosum is reputed to possess medicinal properties for humans, and has the potential to be a feed resource for livestock. We hypothesized that this herb would improve the meat quality of lambs. To test this hypothesis, 24 Tan ewe-lambs (27.7 ± 0.45 kg) were offered diets containing 0 (CON), 100 (AS100), 200 (AS200) and 300 (AS300) g A. squarrosum/kg DM, and average daily gain, carcass traits, blood metabolites, meat quality and fatty acid profiles were determined. Drip loss % and cooking loss % decreased with the AS100 and AS200 diets (P < 0.05). Dietary A. squarrosum reduced muscle fiber area and diameter and increased density of the meat (P < 0.05), which indicated that the meat was more tender. The concentrations of C10:0 and C18:1n-9 t were 1ower and of C17:0 and C18:3n-3 were greater in the AS200 and AS300 treatments than CON (P < 0.05). Our results suggest that feeding lambs up to 200 g/kg DM of A. squarrosum can increase the water-holding capacity and L* value of meat without compromising growth. Further research is needed to determine the optimal level.

LZTFL1 inhibits kidney tumor cell growth by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway.

LZTFL1 is a tumor suppressor located in chromosomal region 3p21.3 that is deleted frequently and early in various cancer types including the kidney cancer. However, its role in kidney tumorigenesis remains unknown. Here we hypothesized a tumor suppressive function of LZTFL1 in clear cell renal cell carcinoma (ccRCC) and its mechanism of action based on extensive bioinformatics analysis of patients' tumor data and validated it using both gain- and loss-functional studies in kidney tumor cell lines and patient-derive xenograft (PDX) model systems. Our studies indicated that LZTFL1 inhibits kidney tumor cell proliferation by destabilizing AKT through ZNRF1-mediated ubiquitin proteosome pathway and inducing cell cycle arrest at G1. Clinically, we found that LZTFL1 is frequently deleted in ccRCC. Downregulation of LZTFL1 is associated with a poor ccRCC outcome and may be used as prognostic maker. Furthermore, we show that overexpression of LZTFL1 in PDX via lentiviral delivery suppressed PDX growth, suggesting that re-expression of LZTFL1 may be a therapeutic strategy against ccRCC.

Therapeutic targeting of histone lysine demethylase KDM4B blocks the growth of castration-resistant prostate cancer.

Epigenetics is an emerging mechanism for tumorigenesis. Treatment that targets epigenetic regulators is becoming an attractive strategy for cancer therapy. The role of epigenetic therapy in prostate cancer (PCa) remains elusive. Previously we demonstrated that upregulation of histone lysine demethylase KDM4B correlated with the appearance of castration resistant prostate cancer (CRPC) and identified a small molecular inhibitor of KDM4B, B3. In this study, we further investigated the role of KDM4B in promoting PCa progression and tested the efficacy of B3 using clinically relevant PCa models including PCa cell line LNCaP and 22Rv1 and xenografts derived from these cell lines. In loss and gain-functional studies of KDM4B in PCa cells, we found that overexpression of KDM4B in LNCaP cells enhanced its tumorigenicity whereas knockdown of KDM4B in 22Rv1 cells reduced tumor growth in castrated mice. B3 suppressed the growth of 22Rv1 xenografts and sensitized tumor to anti-androgen receptor (AR) antagonist enzalutamide inhibition. B3 also inhibited 22Rv1 tumor growth synergistically with rapamycin, leading to cell apoptosis. Comparative transcriptomic analysis performed on KDM4B knockdown and B3-treated 22Rv1 cells revealed that B3 inhibited both H3K9me3 and H3K27me3 demethylase activities. Our studies establish KDM4B as a target for CRPC and B3 as a potential therapeutic agent. B3 as monotherapy or in combination with other anti-PCa therapeutics offers proof of principle for the clinical translation of epigenetic therapy targeting KDMs for CRPC patients.

Supplementing Diets with Agriophyllum squarrosum Reduced Blood Lipids, Enhanced Immunity and Anti-Inflammatory Capacities, and Mediated Lipid Metabolism in Tan Lambs.

Agriophyllum squarrosum (sand rice), a widespread desert plant, possesses anti-hyperglycemic and anti-inflammatory properties, and has been used in traditional Chinese medicine for many years. However, its effects on ruminants are unknown. To fill this gap, we examined the effects of A. squarrosum on the immune and anti-inflammatory responses of lambs. A total of 23, 6-month-old Tan ewe-lambs (27.6 ± 0.47 kg) were divided into four groups and offered a basic diet (C­control), or a diet that contained 10%, 20%, or 30% A. squarrosum, on a dry matter basis, for 128 days. Serum concentrations of total cholesterol were lower (p = 0.004) in the 30% supplemented lambs than controls, while concentrations of high-density lipoprotein cholesterol were lower (p = 0.006) in the 10% and 20%, but not in 30% supplemented lambs than controls. Serum-cortisol concentrations were lower (p = 0.012) in the 30% supplemented lambs and free fatty acid concentrations were higher in the 10% and 20% supplemented lambs than in control lambs (p < 0.001). Supplementation with A. squarrosum decreased (p < 0.05) the area of adipocytes in subcutaneous adipose tissue, but there was no difference between the 20% and 30% diets. Conversely, the area in visceral adipose tissue (VAT) increased (p < 0.05), especially for the 10% and 20% supplemented diets. Supplementation with A. squarrosum also enriched immune and anti-inflammatory related and lipid and glucose-metabolic pathways and associated differentially expressed gene expressions in adipose tissue. A total of 10 differential triacylglycerol, 34 differential phosphatidylcholines and seven differential phosphatidylethanolamines decreased in the diet with 30% supplementation, when compared to the other diets. Finally, adipocyte-differentiation genes, and immune and inflammatory response-related gene expression levels decreased in lamb adipocytes cultured with an aqueous A. squarrosum extract. In conclusion, supplementing lamb diets with A. squarrosum reduced blood lipids, enhanced immunity and anti-inflammatory capacities, and mediated lipid metabolism in adipose tissue and adipocytes of Tan lambs. A level of approximately 10% is recommended, but further research is required to determine the precise optimal level.

CircNTNG1 inhibits renal cell carcinoma progression via HOXA5-mediated epigenetic silencing of Slug.

BACKGROUND: Recent studies have identified that circular RNAs (circRNAs) have an important role in cancer via their well-recognized sponge effect on miRNAs, which regulates a large variety of cancer-related genes. However, only a few circRNAs have been well-studied in renal cell carcinoma (RCC) and their regulatory function remains largely elusive. METHODS: Bioinformatics approaches were used to characterize the differentially expressed circRNAs in our own circRNA-sequencing dataset, as well as two public circRNA microarray datasets. CircNTNG1 (hsa_circ_0002286) was identified as a potential tumor-suppressing circRNA. Transwell assay and CCK-8 assay were used to assess phenotypic changes. RNA pull-down, luciferase reporter assays and FISH experiment were used to confirm the interactions among circNTNG1, miR-19b-3p, and HOXA5 mRNA. GSEA was performed to explore the downstream pathway regulated by HOXA5. Immunoblotting, chromatin immunoprecipitation, and methylated DNA immunoprecipitation were used to study the mechanism of HOXA5. RESULTS: In all three circRNA datasets, circNTNG1, which was frequently deleted in RCC, showed significantly low expression in the tumor group. The basic properties of circNTNG1 were characterized, and phenotype studies also demonstrated the inhibitory effect of circNTNG1 on RCC cell aggressiveness. Clinically, circNTNG1 expression was associated with RCC stage and Fuhrman grade, and it also served as an independent predictive factor for both OS and RFS of RCC patients. Next, the sponge effect of circNTNG1 on miR-19b-3p and the inhibition of HOXA5 by miR-19b-3p were validated. GSEA analysis indicated that HOXA5 could inactivate the epithelial-mesenchymal transition (EMT) process, and this inactivation was mediated by HOXA5-induced SNAI2 (Slug) downregulation. Finally, it was confirmed that the Slug downregulation was caused by HOXA5, along with the DNA methyltransferase DNMT3A, binding to its promoter region and increasing the methylation level. CONCLUSIONS: Based on the experimental data, in RCC, circNTNG1/miR-19b-3p/HOXA5 axis can regulate the epigenetic silencing of Slug, thus interfering EMT and metastasis of RCC. Together, our findings provide potential biomarkers and novel therapeutic targets for future study in RCC.

Dietary Supplementation of Fruit from Nitraria tangutorum Improved Immunity and Abundance of Beneficial Ruminal Bacteria in Hu Sheep.

The fruit of Nitraria tangutorum (FNT) is reputed to possess medicinal properties; however, its effect on sheep (Ovis aries) is unknown. The aim of this study was to fill this gap. In a 3 × 3 Latin square design, six 12-month-old rumen-fistulated Hu rams (56.2 ± 8.26 kg; mean ± SD) were penned individually and offered one of three levels of FNT, namely, 0 g/d (control; CON), 16 g/d (N16), and 48 g/d (N48). The concentration of serum immunoglobulin G increased linearly (p = 0.03) with an increasing intake of FNT. The serum concentration of ß-hydroxybutyrate in the N48 group was lower than in the CON group (p = 0.01) and decreased linearly with increasing FNT (p = 0.001). The concentration of serum lactate dehydrogenase tended to decrease (p = 0.07) linearly with an increase in FNT intake, while the concentration of glucose did not differ among groups (p = 0.14) but displayed a quadratic curve with an increase in FNT (p = 0.05). The rumen concentration of lipase decreased linearly with increasing FNT (p = 0.04). The rumen fermentation variables were not affected by FNT. The FNT intake increased the abundance of beneficial ruminal bacteria, such as Lachnoclostridium, Rhodocyclaceae, and Candidatus Arthromitus. Prevotella, Rikenellaceae_RC9_gut_group, Ruminococcus, Olsenella, Lachnospiraceae_NK3A20_group, and Quinella were the dominant bacterial genera in all treatments. We conclude that FNT can improve immunity and increase the relative abundance of beneficial ruminal bacteria in sheep.

lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma.

Invasion and metastasis of melanoma are a series of complicated biological events regulated by multiple factors. The coregulation of many molecules involved in the development and progression of melanoma contributes to invasion and migration. mGluR1 is a metabotropic glutamate receptor that is overexpressed in melanocytes and is sufficient to induce melanoma. In our study, we found that mGluR1 was obviously increased in melanoma. Furthermore, we found that miR-129-5p could directly target and regulate mGluR1 mRNA, which was significantly reduced in A375 cells. Overexpression of miR-129-5p inhibited cell migration, invasion and clonal formation. lncRNA-AC130710 directly targeted and suppressed miR-129-5p in A375 cells. Downregulation of lncRNA-AC130710 suppressed the levels of mGluR1 mRNA by promoting miR-129-5p expression and further inhibiting migration, invasion and colony formation in A375 cells, which was associated with the activation of the PKCα-MAPK signaling pathway. Taken together, our study showed that the lncRNA-AC130710/miR-129-5p/mGluR1 axis plays an important role in the invasion and metastasis of melanoma.

The Combination of Red and Blue Light, Radiofrequency and Intense Pulsed Light for the Treatment of Facial Postacne Erythema.

Introduction: Postacne erythema, also referred to as postinflammatory erythema, is a common sequela in acne patients. At present, there is no specific treatment for postacne erythema, and some treatment drugs can even aggravate facial erythema. Objective: Our research sought to evaluate the efficacy of a combination therapy of LED red and blue light, radiofrequency (RF) and intense pulsed light (IPL) for the treatment of postacne erythema. Methods: Patients were treated with red and blue light for 2 weeks, followed by RF for 4 treatments over 8 weeks. Finally, patients were treated with intense pulsed light for 16 weeks. Therapeutic outcomes were evaluated by erythema index, postacne erythema severity grading and clinical photography. Results: After 3 stages of treatment, the percentage of excellent subjects was 79.2%, the percentage of good subjects was 17.2%, and the total effective rate was 96.4%. The mean erythema index decreased from 496.17±79.11 to 89.32±81.58 (p<0.01) after treatment. The postacne erythema lesions were rated clear in 22.4%, faint erythema in 74.4%, dull red in 2.8% and deep red only in 0.4% of subjects after three-stage treatments. Conclusion: Our results show that the combination of red and blue light therapy, RF therapy and IPL therapy is more effective than other treatments reported for facial postacne erythema.

m6A-immune-related lncRNA prognostic signature for predicting immune landscape and prognosis of bladder cancer.

BACKGROUND: N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity. METHODS: Bladder cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan-Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated. RESULTS: Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan-Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib. CONCLUSIONS: An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.

High-Resolution Imaging of Human Cancer Proteins Using Microprocessor Materials.

Mutations in tumor suppressor genes, such as Tumor Protein 53 (TP53), are heavily implicated in aggressive cancers giving rise to gain- and loss-of-function phenotypes. While individual domains of the p53 protein have been studied extensively, structural information for full-length p53 remains incomplete. Functionalized microprocessor chips (microchips) with properties amenable to electron microscopy permitted us to visualize complete p53 assemblies for the first time. The new structures revealed p53 in an inactive dimeric state independent of DNA binding. Residues located at the protein-protein interface corresponded with modification sites in cancer-related hot spots. Changes in these regions may amplify the toxic effects of clinical mutations. Taken together, these results contribute advances in technology and imaging approaches to decode native protein models in different states of activation.