A ratiometric fluorescent dark box and smartphone integrated portable sensing platform based on hydrogen bonding induction for on-site determination of enrofloxacin.

Enrofloxacin (ENR) residues in animal-derived food and water threaten human health. Simple, low-cost and on-site detection methods are urgently needed. Blue emitting carbon quantum dots (CQDs) and orange rhodamine B (RhB) were used as recognition and reference signals, respectively, to construct a ratiometric fluorescence sensor. After the addition of ENR, the color of the sensor changed from orange to blue because hydrogen bonding induced a considerable increase in CQDs fluorescence. Based on this mechanism, a simple and low cost on-site portable sensing platform was constructed, which integrated a stable UV light strip and a smartphone with voice-controlled phototaking function and an RGB app. The t-test results of spiked ENR recoveries for diluted milk, honey and drinking water revealed no significant differences between the ratiometric fluorescent sensor and portable sensing platform. Thus, this portable sensing platform provides a novel strategy for on-site quantification of quinolone antibiotics in foodstuffs and environmental water.

Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia.

An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.

High-yield porphyrin production through metabolic engineering and biocatalysis.

Porphyrins and their derivatives find extensive applications in medicine, food, energy and materials. In this study, we produced porphyrin compounds by combining Rhodobacter sphaeroides as an efficient cell factory with enzymatic catalysis. Genome-wide CRISPRi-based screening in R. sphaeroides identifies hemN as a target for improved coproporphyrin III (CPIII) production, and exploiting phosphorylation of PrrA further improves the production of bioactive CPIII to 16.5 g L-1 by fed-batch fermentation. Subsequent screening and engineering high-activity metal chelatases and coproheme decarboxylase results in the synthesis of various metalloporphyrins, including heme and the anti-tumor agent zincphyrin. After pilot-scale fermentation (200 L) and setting up the purification process for CPIII (purity >95%), we scaled up the production of heme and zincphyrin through enzymatic catalysis in a 5-L bioreactor, with CPIII achieving respective enzyme conversion rates of 63% and 98% and yielding 10.8 g L-1 and 21.3 g L-1, respectively. Our strategy offers a solution for high-yield bioproduction of heme and other valuable porphyrins with substantial industrial and medical applications.

Phosphorylated transcription factor PuHB40 mediates ROS-dependent anthocyanin biosynthesis in pear exposed to high light.

Plants are increasingly vulnerable to environmental stresses because of global warming and climate change. Stress-induced reactive oxygen species (ROS) accumulation results in plant cell damage and even cell death. Anthocyanins are important antioxidants that scavenge ROS to maintain ROS homeostasis. However, the mechanism underlying ROS-induced anthocyanin accumulation is unclear. In this study, we determined that the HD-Zip I family member transcription factor PuHB40 mediates ROS-dependent anthocyanin biosynthesis under high-light stress in pear (Pyrus ussuriensis). Specifically, PuHB40 induces the PuMYB123-like-PubHLH3 transcription factor complex for anthocyanin biosynthesis. PuHB40-mediated transcriptional activation depends on its phosphorylation level, which is regulated by protein phosphatase PP2A. Elevated ROS content maintains high PuHB40 phosphorylation levels, while also enhancing PuHB40-induced PuMYB123-like transcription by decreasing PuPP2AA2 expression, ultimately leading to increased anthocyanin biosynthesis. Our study reveals a pathway regulating ROS-induced anthocyanin biosynthesis in pear, further clarifying the mechanism underlying abiotic stress-induced anthocyanin biosynthesis, which may have implications for improving plant stress tolerance.

Ac2-26 reduced the liver injury after cardiopulmonary bypass in rats via AKT1/GSK3ß/eNOS pathway.

OBJECTIVE: About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB. METHODS: A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated. RESULTS: Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3ß and eNOS, and this promotion was inhibited by the shRNA. CONCLUSION: The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3ß/eNOS.

Distribution and ecological risk assessment of antibiotics in different freshwater aquaculture ponds in a typical agricultural plain, China.

Freshwater aquaculture serves as a significant focal point for antibiotic contamination, yet understanding antibiotic distribution across different aquaculture models and stages remains limited. This study evaluated antibiotic pollution in three distinct freshwater aquaculture models: rice-crayfish coculture, fish aquaculture, and crab-crayfish aquaculture, during various aquaculture stages. Of the 33 target antibiotics, 16 antibiotics were detected, with the total concentrations ranging from 111.81 ng/L to 15,949.05 ng/L in water and 10.11 ng/g to 8986.30 ng/g in sediment. Among these antibiotics, erythromycin and lomefloxacin are prohibited for use in Chinese aquaculture. Dominant antibiotics in water included lincomycin, enrofloxacin, and enoxacin, whereas in sediment, oxytetracycline and erythromycin were predominant. Notably, lincomycin emerged as a dominant antibiotic in aquaculture for the first time. The concentrations of these dominant antibiotics were high compared to other aquaculture settings and exhibited elevated ecological risk. Critical periods for antibiotic contamination in water and sediment were found to be incongruent, occurring during the rainy season in July for water and the dry season in October for sediment. Notably, the rice-crayfish coculture model exerts a good effect in reducing antibiotic pollution. Overall, these findings offer valuable evidence for the healthful and sustainable advancement of aquaculture.

A mathematical framework for understanding the spontaneous emergence of complexity applicable to growing multicellular systems.

In embryonic development and organogenesis, cells sharing identical genetic codes acquire diverse gene expression states in a highly reproducible spatial distribution, crucial for multicellular formation and quantifiable through positional information. To understand the spontaneous growth of complexity, we constructed a one-dimensional division-decision model, simulating the growth of cells with identical genetic networks from a single cell. Our findings highlight the pivotal role of cell division in providing positional cues, escorting the system toward states rich in information. Moreover, we pinpointed lateral inhibition as a critical mechanism translating spatial contacts into gene expression. Our model demonstrates that the spatial arrangement resulting from cell division, combined with cell lineages, imparts positional information, specifying multiple cell states with increased complexity-illustrated through examples in C.elegans. This study constitutes a foundational step in comprehending developmental intricacies, paving the way for future quantitative formulations to construct synthetic multicellular patterns.

Pt─O Bond Accelerated Cu0/Cu+ Activity for Boosting Low-Energy Bipolar Hydrogen Production.

To address the imperative challenge of producing hydrogen in a low-energy consumption electrocatalytic system, this study emphasizes the utilization of thermodynamically favorable biomass oxidation for achieving energy-efficient hydrogen generation. This research integrates ultralow PtO2-loaded flower-like nanosheets (denoted as PtO2@Cu2O/Cu FNs) with Cu0/Cu+ pairs and Pt─O bonds, thereby yielding substantial enhancement in both hydrogen evolution reaction (HER, -0.042 VRHE at 10 mA cm-2) and furfural oxidation reaction (FFOR, 0.09 VRHE at 10 mA cm-2). As validated by DFT calculations, the dual built-in electric field (BIEF) is elucidated as the driving force behind the enhanced activities, in which Pt─O bonds expedite the HER, while Cu+/Cu0 promotes low-potential FFOR. By coupling the FFOR and HER together, the resulting bipolar-hydrogen production system requires a low power input (0.5072 kWh per m3) for producing H2. The system can generate bipolar hydrogen and high value-added furoic acid, significantly enhancing hydrogen production efficiency and concurrently mitigating energy consumption.

USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer.

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.

RNA binding protein Lin28B promotes chronic myeloid leukemia blast crisis by transcriptionally upregulating miR-181d.

The blast crisis (BC) of chronic myeloid leukemia (CML) has poor efficacy against existing treatments and extremely short survival. However, the molecular mechanism of CML-chronic phase (CP) transformation to CML-BC is not yet fully understood. Here, we show that Lin28B, a RNA binding protein, acted as an activator enhancing the transformation to CML-BC by mediating excessive cell proliferation. The level of Lin28B expression was apparently elevated in CML-BC patients compared with newly diagnosed CML-CP patients. The overexpression of Lin28B promoted the proliferation of leukemia cells. Mechanistically, we identified Lin28B as a DNA binding protein by binding to the promoter region of miR-181d and upregulating its expression, which inhibited the expression of Programmed cell death 4 (PDCD4) by binding to the PDCD4 3'UTR region, thereby enhancing the proliferation of CML cells. Overall, the "Lin28B-miR-181d-PDCD4" regulatory axis promoted CML blast crisis. Implications: Our findings highlight the oncogenic role of Lin28B in CML blast crisis, acting as a DNA binding protein which transcriptionally upregulates miR-181d expression.

Atorvastatin ameliorates diabetic nephropathy through inhibiting oxidative stress and ferroptosis signaling.

Clinically, statins have long been used for the prevention and treatment of chronic renal diseases, however, the underlying mechanisms are not fully elucidated. The present study investigated the effects of atorvastatin on diabetes renal injury and ferroptosis signaling. A mouse model of diabetes was established by the intraperitoneal injection of streptozotocin (50 mg/kg/day) plus a high fat diet with or without atorvastatin treatment. Diabetes mice manifested increased plasma glucose and lipid profile, proteinuria, renal injury and fibrosis, atorvastatin significantly lowered plasma lipid profile, proteinuria, renal injury in diabetes mice. Atorvastatin reduced renal reactive oxygen species (ROS), iron accumulation and renal expression of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), transferrin receptor 1 (TFR1), and increased renal expression of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor (NRF2) and ferritin heavy chain (FTH) in diabetes mice. Consistent with the findings in vivo, atorvastatin prevented high glucose-induced ROS formation and Fe2+ accumulation, an increase in the expression of 4-HNE, MDA and TFR1, and a decrease in cell viability and the expression of NRF2, GPX4 and FTH in HK2 cells. Atorvastatin also reversed ferroptosis inducer erastin-induced ROS production, intracellular Fe2+ accumulation and the changes in the expression of above-mentioned ferroptosis signaling molecules in HK2 cells. In addition, atorvastatin alleviated high glucose- or erastin-induced mitochondria injury. Ferroptosis inhibitor ferrostatin-1 and antioxidant N-acetylcysteine (NAC) equally reversed the expression of high glucose-induced ferroptosis signaling molecules. Our data support the notion that statins can inhibit diabetes-induced renal oxidative stress and ferroptosis, which may contribute to statins protection of diabetic nephropathy.

Dormant carbohydrate reserves enhance pecan tree spring freeze tolerance: controlled environment observations.

Pecan (Carya illinoensis), an economically important deciduous tree, bears commercially valuable nutritional nuts. Spring freezes in April can severely injure pecan buds, decreasing bloom, and fruit set. This study determined how low temperatures affect pecan buds/flowers at different growth stages in several pecan scion/rootstock combinations. This study focused on three pecan scion/rootstock combinations: Pawnee/Peruque (PP), Kanza/Giles (KG), and Maramec/Colby (MC), grown at the Cimarron Valley Research Station, Perkins, Oklahoma. Branches at three different growth stages, i.e., outer bud scale shed, one week after bud break, and early bloom stages were collected from PP, MC, and KG. Branches were held in a Conviron E8 freezing unit at 4 temperatures (-2, 0, 2, and 4°C) for 4 and 8 hours; A total of 8 treatments. One sample set was kept as an untreated control. After 2-3 weeks, branch samples from all the temperature treatments were observed and categorized into two groups. Group one with number of branches had healthy buds/formation of healthy leaves/flowers and group two with number of dead branches. The carbohydrate content reserved from dormant was analyzed using an Anthrone reagent. Visual observations and carbohydrate analyses revealed differences in damage and carbohydrate content among the scion/rootstock combinations, low-temperature treatments, and growth stages. The MC combination had minimum visual damage to leaves, buds, and flowers and significantly lower soluble sugars and starch in bark phloem as well as significantly lower soluble sugars in woody tissue xylem. The KG combination had maximum visual damage and significantly higher soluble sugars and starches in the bark, and soluble sugars in the woody tissues. These results indicate the MC combination is more tolerant to spring freeze damage at all three growth stages compared to the other two pecan scion/rootstock combinations. The results also demonstrate the MC combination is using more non-structural carbohydrates, soluble sugars and starches, suggesting this is a possible mechanism in its freeze tolerance.

Frailty index and risk of delirium in hospitalized patients: a two-sample Mendelian randomization study.

Objective: Observational studies suggest that the frailty index (FI) is closely related to delirium, but the relationship between them is still uncertain due to the influence of various confounding factors. Therefore, two-sample Mendelian randomization (MR) was used to explore the causal relationship between the FI and delirium risk. Methods: This study obtained pooled statistics for the FI and delirium from two of the most extensive genome-wide association studies. To make the results more robust and reliable, supplementary analyses were performed using several robust analytical methods (inverse-variance weighting, MR-Egger regression, and weighted median). In addition, this study used the MR-Egger intercept test, Cochran's Q test, funnel plots and the leave-one-out method to evaluate the pleiotropy and heterogeneity among the abovementioned genetic variation instrumental variables. Results: Frailty might increase the relative risk of delirium, as shown by IVW (OR = 1.849, 95% CI 0.027∼2.067, P = 0.044), weighted median (OR = 1.726, 95% CI -0.178∼2.664, P = 0.083), MR-Egger regression (OR = 1.768, 95% CI -3.08∼6.171, P = 0.525) and leave-one-out sensitivity analysis (P = 0.058). Although the WME method and MR-Egger regression analysis showed no statistically significant causal relationship between the FI and the risk of delirium, the direction of the causal effect was consistent with the IVW method. Conclusion: There is a notable correlation between a higher FI and an elevated risk of delirium. This indicates that healthcare providers should take proactive measures to prevent delirium in hospitalized patients with a higher FI.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury.

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.

Role of NLRP3 inflammasome in central nervous system diseases.

The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.

Geochemical Characteristics and Origin of Sinian-Cambrian Natural Gas in Penglai Gas Area, Sichuan Basin.

The Sichuan Basin in southern China is well-known for its large natural gas resource potential stored in Sinian-Cambrian systems. Recently, high-yield industrial gas flow has been discovered from the Dengying Formation (Sinian System) and Canglangpu Formation (Cambrian System) in the Penglai gas area, preluding the multilayer stereoscopic exploration in Sichuan Basin. However, the origin of the natural gas and its preserving mechanics is still debated, and thus, in this study the geochemical characteristics of the natural gas are systematically analyzed, based on the data from gas composition and hydrocarbon isotope of a series of local wells. On this basis, the geochemical characteristics of natural gas in different regions and layers are compared, and the reasons for these differences from the origin and influencing factors are analyzed. The results show the following: (1) The natural gas of the Penglai gas field is dry gas dominated by CH4, and the Sinian Dengying Formation gas has lower C2H6 content, larger dryness coefficient, heavier δ13C, and lighter δ2HCH4 than the Cambrian gas, which is associated with the high proportion of hydrocarbons from the high-maturity Dengying source rocks. (2) The natural gas from some wells in the lower part of the structure is characterized by high H2S content and low CH4 content, and heavy δ13C in the components, which seems to be affected by the thermochemical sulfate reduction (TSR) effect. (3) The natural gas from the Penglai gas area has a relatively low maturity, which appears to be attributed to the continuous sealing ability of the caprock, which can preserve both the early generated gas and the late thermal-cracked gas.

Comprehensive Numerical Evaluation of CO2 Huff-n-Puff in an Offshore Tight Oil Reservoir: A Case Study in Bohai Bay Area, China.

Many reports have presented that in tight formation, the flow mechanism differs from a conventional reservoir, such as molecular diffusion, Pre-Darcy flow behavior, and stress sensitivity. However, for CO2 Huff-n-Puff development, it is a challenge to synthetically research these mechanisms. Considering the above flow mechanisms and offshore engineering background, the development plan optimization becomes a key issue. In this paper, a self-developed simulator that satisfies research needs is introduced. Then, based on experimental results, the simulation is launched to analyze the effects of CO2 diffusion, Huff-n-Puff period, and permeability heterogeneity. The results indicate that molecular diffusion makes a positive contribution to the oil recovery factor. Additionally, for offshore reservoirs, limited to the development cost and CO2 facilities corrosion, when the total Huff-n-Puff time is constant, the ratio of 0.5-1.0 between the Huff period and the Puff period in every cycle performs better. Finally, the greater heterogeneity in permeability is much more favorable for the CO2 Huff-n-Puff because of more intensive transport processes in formation. These different scenarios can increase the understanding of the CO2 Huff-n-Puff in tight oil offshore reservoirs.

Disulfidptosis-Related LncRNA Signatures for Prognostic Prediction in Kidney Renal Clear Cell Carcinoma.

INTRODUCTION BACKGROUND: Disulfidptosis is a prevalent apoptotic mechanism, intrinsically linked to cancer prognosis. However, the specific involvement of disulfidptosis-related long non-coding RNA (DRLncRNAs) in Kidney renal clear cell carcinoma (KIRC) remains incompletely understood. This study aims to elucidate the potential prognostic significance of disulfidptosis-related LncRNAs in KIRC. MATERIALS AND METHODS: Expression profiles and clinical data of KIRC patients were retrieved from the TCGA database to discern differentially expressed DRLncRNAs correlated with overall survival. Cox univariate analysis, Lasso Regression, and Cox multivariate analysis were used to construct a clinical prediction model. RESULTS: Six signatures, namely FAM83C.AS1, AC136475.2, AC121338.2, AC026401.3, AC254562.3, and AC000050.2, were established to evaluate overall survival (OS) in the context of Kidney renal clear cell carcinoma (KIRC) in this study. Survival analysis and ROC curves demonstrated the strong predictive performance of the associated signature. The nomogram exhibited accurate prognostic predictions for overall patient survival, offering substantial clinical utility. Gene set enrichment analysis revealed that risk signals were enriched in various immune-related pathways. Furthermore, the risk features exhibited significant correlations with immune cells, immune function, immune cell infiltration, and immune checkpoints. CONCLUSION: This study has unveiled, for the first time, six disulfdptosis-related LncRNA signatures, laying a solid foundation for enhanced and precise prognostic predictions in KIRC.

5mC modification of steroid hormone biosynthesis-related genes orchestrates feminization of channel catfish induced by high-temperature.

To elucidate the mechanism behind channel catfish feminization induced by high temperature, gonad samples were collected from XY pseudo-females and wild-type females and subjected to high-throughput sequencing for Whole-Genome-Bisulfite-Seq (WGBS) and transcriptome sequencing (RNA-Seq). The analysis revealed 50 differentially methylated genes between wild-type females and XY pseudo-females, identified through the analysis of KEGG pathways and GO enrichment in the promoter of the genome and differentially methylated regions (DMRs). Among these genes, multiple differential methylation sites observed within the srd5a2 gene. Repeatability tests confirmed 7 differential methylation sites in the srd5a2 gene in XY pseudo-females compared to normal males, with 1 specific differential methylation site (16608174) distinguishing XY pseudo-females from normal females. Interestingly, the expression of these genes in the transcriptome showed no difference between wild-type females and XY pseudo-females. Our study concluded that methylation of the srd5a2 gene sequence leads to decreased expression, which inhibits testosterone synthesis while promoting the synthesis of 17ß-estradiol from testosterone. This underscores the significance of the srd5a2 gene in the sexual differentiation of channel catfish, as indicated by the ipu00140 KEGG pathway analysis.

Shikonin-loaded PLGA nanoparticles: A promising strategy for psoriasis treatment.

Psoriasis is an inflammation-based skin illness marked by aggravated proliferation of epidermal cells. Shikonin is a natural naphthoquinone obtained from Arnebiae radix. It exerts anti-inflammatory and immunosuppressive effects. However, the poor water solubility and low bioavailability of shikonin limit its application. In this study, shikosin-loaded PLGA nanoparticle hydrogel was prepared and used to deliver the drug to the epidermis of psoriasis mice through local administration. The results demonstrated that shikosin-loaded PLGA nanoparticles inhibited HaCaT cell multiplication, increased drug uptake, and induced apoptosis of HaCaT cells. Results from Western blotting assays indicated that shikosin down-regulated the protein expressions of p65 and p-p65. Furthermore, shikonin mitigated psoriasis and decreased the concentrations of inflammation-inducing cytokines, i.e., IL17A, IL-17F, IL-22, IL-1ß, and TNF-α. Taken together, these results suggest that shikonin-PLGA nanoparticles loaded in hydrogel system possess promising therapeutic potential for psoriasis.