Clinical significance of prognostic nutritional index (PNI)-monocyte-to-lymphocyte ratio (MLR)-platelet (PLT) score on postoperative outcomes in non-metastatic clear cell renal cell carcinoma.

BACKGROUND: Prognositic nutritional index (PNI), monocyte-to-lymphocyte ratio (MLR) and platelet (PLT) are associated with tumor survival in many human malignancies. Whereas, no study combined PNI-MLR-PLT score and indicated its predictive significance on the prognosis of patients with non-metastatic clear cell renal cell carcinoma (ccRCC). METHODS: In this study, we retrospectively collected the clinicopathological characteristics and prognostic data from 164 cases of non-metastatic ccRCC and aimed to determine the clinical significance of PNI-MLR-PLT score on patients' outcomes after surgery. The optimal cut-off values of PNI (PNI > 47.40 vs PNI < 47.40), MLR (MLR > 0.31 vs MLR < 0.31) and PLT (PLT > 245 vs PLT < 245) were identified with relative operating characteristic (ROC) curve analysis. The PNI-MLR-PLT score system was established by the value of three indexes, each indication was assigned a score of 0 or 1. Overall survival (OS) and metastasis-free survival (MFS) were analyzed using Kaplan-Meier estimate and Cox regression models. RESULTS: The mean follow-up period was 85.67 months. Eight (5.0%) patients died, 4 (2.0%) relapsed, and 7 (4.0%) developed metastasis after surgery. The 3-year OS and MFS rates were 98.2% and 97.6%, and the 5-year OS and MFS rates were both 90.2%. Our results suggested that PNI-MLR-PLT score negatively correlated with pathological T stage and tumor grade. Survival outcomes revealed that lower PNI-MLR-PLT score is associated with inferior OS (P < 0.001) and MFS (P < 0.001) after surgery. Subgroup analysis regarding pathological T stage, tumor grade and surgical modalities obtained consistent results. univariable and multivariable Cox analysis showed that high PNI-MLR-PLT score was the independent protective factor of tumor survival in non-metastatic ccRCC patients. CONCLUSIONS: Our data suggested that PNI-MLR-PLT score could serve as a promising independent prognostic factor in patients with non-metastatic ccRCC.

Performance on desulfurization and denitrification of one-step produced activated carbon for purification of sintering flue gas.

An innovative one-step process for activated carbon production from low-rank coal is proposed in this research by applying oxidized pellets as activator. The new process can realize synchronous production of the activated carbon and direct reduction iron through combination of carbonization and activation of low-rank coal in one step while no solid wastes were discharged. The desulfurization and denitrification performance of the obtained activated carbon was also evaluated on the simulative sintering flue gas in comparison with one type of commercial activated carbon. The results indicated that a superior activated carbon with high specific surface area of 370.42 m2 g-1, iodine sorption value of 695.13 mg g-1, compressive strength of 315 N·per-1and abrasive resistance of 96.61%, can be prepared under suitable conditions of activation temperature at 850 °C for 140 min with C/Fe mass ratio of 2.5. Meanwhile, the direct reduction iron has a metallization ratio of 88.31%. The activated carbon has a preferable desulfurization performance with the breakthrough sulfur capacity of 5.463 mg/g and breakthrough time of 46.33 min, and single denitrification performance with the breakthrough nitric capacity of 1.935 mg/g and breakthrough time of 90.17 min at flue gas temperature of 80 °C, airspeed ratio of 8370 h-1, gas flow of 1.8 m3/h, and oxygen concentration of 16%. The denitrification of activated carbon in the simultaneous desulfurization and denitrification process can be improved by catalytic reduction via the transformation from NO to N2. The good results show that this process has a bright future with high technical and economic feasibility.

Identification and characterization of mRNAs and lncRNAs of a barley shrunken endosperm mutant using RNA-seq.

Barley shrunken endosperm mutants have been extensively reported. However, knowledge of the underlying molecular mechanisms of these mutants remains limited. Here, a pair of near isogenic lines (normal endosperm: Bowman and shrunken endosperm: sex1) was subjected to transcriptome analysis to identify mRNAs and lncRNAs related to endosperm development to further dissect its mechanism of molecular regulation. A total of 2123 (1140 up- and 983 down-regulated) unique differentially expressed genes (DEGs) were detected. Functional analyses showed that these DEGs were mainly involved in starch and sucrose metabolism, biosynthesis of secondary metabolites, and plant hormone signal transduction. A total of 343 unique target genes were identified for 57 differentially expressed lncRNAs (DE lncRNAs). These DE lncRNAs were mainly involved in glycerophospholipid metabolism, starch and sucrose metabolism, hormone signal transduction, and stress response. In addition, key lncRNAs were identified by constructing a co-expression network of the target genes of DE lncRNAs. Transcriptome results suggested that mRNA and lncRNA played a critical role in endosperm development. The shrunken endosperm in barley seems to be closely related to plant hormone signal transduction, starch and sucrose metabolism, and cell apoptosis. This study provides a foundation for fine mapping, elucidates the molecular mechanism of shrunken endosperm mutants, and also provides a reference for further studies of lncRNAs during the grain development of plants.

Quantitative trait loci for seeding root traits and the relationships between root and agronomic traits in common wheat.

A completely developed and vigorous root system can provide a stable platform for aboveground plant organs. To identify loci controlling root traits that could be used in wheat (Triticum aestivum L.) breeding, 199 recombinant inbred lines were used to measure and analyze eight root traits. A total of 18 quantitative trait loci (QTL) located on chromosomes 1A, 2A, 2B, 2D, 4B, 4D, 6A, 7A, and 7B were identified. The phenotypic variation explained by these 18 QTL ranged from 3.27% to 11.75%, and the logarithm of odds scores ranged from 2.50 to 6.58. A comparison of physical intervals indicated several new QTL for root traits were identified. In addition, significant correlations between root and agronomic traits were detected and discussed. The results presented in this study, along with those of previous reports, suggest that chromosomes 2 and 7 likely play important roles in the growth and development of wheat roots.

Identification and validation of a novel major QTL for all-stage stripe rust resistance on 1BL in the winter wheat line 20828.

KEY MESSAGE: A major, likely novel stripe rust resistance QTL for all-stage resistance on chromosome arm 1BL identified in a 1.76-cM interval using a saturated linkage map was validated in four populations with different genetic backgrounds. Stripe rust is a globally important disease of wheat. Identification and utilization of new resistance genes are essential for breeding resistant cultivars. Wheat line 20828 has exhibited high levels of stripe rust resistance for over a decade. However, the genetics of stripe rust resistance in this line has not been studied. A set of 199 recombinant inbred lines (RILs) were developed from a cross between 20828 and a susceptible cultivar Chuannong 16. The RIL population was genotyped with the Wheat55K SNP (single nucleotide polymorphism) array and SSR (simple sequence repeat) markers and evaluated in four environments with current predominant Puccinia striiformis f. sp. tritici t races including CYR32, CYR33 and CYR34. Four stable QTL were located on chromosomes 1B (2 QTL), 4A and 6A. Among them, the major QTL, QYr.sicau-1B.1 (LOD = 23-28, PVE = 16-39%), was localized to a 1.76-cM interval flanked by SSR markers Xwmc216 and Xwmc156 on chromosome 1BL. Eight resistance genes were previously identified in the physical interval of QYr.sicau-1B.1. Compared with previous studies, QYr.sicau-1B.1 is a new gene for resistant to stripe rust. It was further verified by analysis of the closely linked SSR markers Xwmc216 and Xwmc156 in four other populations with different genetic backgrounds. QYr.sicau-1B.1 reduced the stripe rust disease index by up to 82.8%. Three minor stable QTL (located on chromosomes 1B, 4A and 6A, respectively) also added to the resistance level of QYr.sicau-1B.1. Our results provide valuable information for further fine mapping and cloning as well as molecular-assisted breeding with QYr.sicau-1B.1.

A 55 K SNP array-based genetic map and its utilization in QTL mapping for productive tiller number in common wheat.

KEY MESSAGE: A high-density genetic map constructed with a wheat 55 K SNP array was highly consistent with the physical map of this species and it facilitated the identification of a novel major QTL for productive tiller number. Productive tiller number (PTN) plays a key role in wheat grain yield. In this study, a recombinant inbred line population with 199 lines derived from a cross between '20828' and 'Chuannong16' was used to construct a high-density genetic map using wheat 55 K single nucleotide polymorphism (SNP) array. The constructed genetic map contains 12,109 SNP markers spanning 3021.04 cM across the 21 wheat chromosomes. The orders of the genetic and physical positions of these markers are generally in agreement, and they also match well with those based on the 660 K SNP array from which the one used in this study was derived. The ratios of SNPs located in each of the wheat deletion bins were similar among the wheat 9 K, 55 K, 90 K, 660 K and 820 K SNP arrays. Based on the constructed maps, a novel major quantitative trait locus QPtn.sau-4B for PTN was detected across multi-environments in a 0.55 cM interval on 4B and it explained 17.23-45.46% of the phenotypic variance. Twenty common genes in the physical interval between the flanking markers were identified on chromosome 4B of 'Chinese Spring' and wild emmer. These results indicate that wheat 55 K SNP array could be an ideal tool in primary mapping of target genes and the identification of QPtn.sau-4B laid a foundation for the following fine mapping and cloning work.

Green synthesis of selenium nanoparticles with extract of hawthorn fruit induced HepG2 cells apoptosis.

CONTEXT: Selenium nanoparticles (SeNPs) have attracted worldwide attention due to their unique properties and potential bioactivities. Considering that hawthorn is both a traditional medicine and a common edible food, hawthorn fruit extract (HE) was chosen as a reductant to prepare SeNPs. OBJECTIVE: SeNPs were synthesized by using an aqueous HE as a reductant and stabilizer. The antitumor activities and potential mechanisms of SeNPs were explored by using a series of cellular assays. MATERIALS AND METHODS: The HE mediated SeNPs (HE-SeNPs) were examined using various characterisation methods. The cytotoxicity was measured against HepG2 cells after treated with 0, 5, 10 and 20 µg/mL of HE-SeNPs for 24 h. Annexin V-FITC/PI staining analysis was performed to observe the apoptosis of HepG2 cells. Additionally, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels were evaluated. Finally, the protein expression levels of caspase-9 and Bcl-2 were identified by Western blot. RESULTS: The mono-dispersed and stable SeNPs were prepared with an average size of 113 nm. HE-SeNPs showed obvious antitumor activities towards HepG2 cells with an IC50 of 19.22 ± 5.3 µg/mL. Results from flow cytometry revealed that both early and total apoptosis rates increased after treating with HE-SeNPs. After cells were treated with various concentrations of HE-SeNPs (5, 10 and 20 µg/mL) for 24 h, the total rate increased to 7.3 ± 0.5, 9.7 ± 1.7 and 19.2 ± 1.6%, respectively. Meanwhile, treatment of HE-SeNPs up-regulated intracellular ROS levels and reduced the MMP. In addition, HE-SeNPs induced the up-regulation of caspase-9 and down-regulation of Bcl-2. DISCUSSION AND CONCLUSIONS: HE-SeNPs induced intracellular oxidative stress and mitochondrial dysfunction to initiate HepG2 cell apoptosis through the mitochondrial pathway. Therefore, HE-SeNPs may be a candidate for further evaluation as a chemotherapeutic agent for human liver cancer.

Wireless Sensor System Based on Organohydrogel Ionic Skin for Physiological Activity Monitoring.

Supermolecular hydrogel ionic skin (i-skin) linked with smartphones has attracted widespread attention in physiological activity detection due to its good stability in complex scenarios. However, the low ionic conductivity, inferior mechanical properties, poor contact adhesion, and insufficient freeze resistance of most used hydrogels limit their practical application in flexible electronics. Herein, a novel multifunctional poly(vinyl alcohol)-based conductive organohydrogel (PCEL5.0%) with a supermolecular structure was constructed by innovatively employing sodium carboxymethyl cellulose (CMC-Na) as reinforcement material, ethylene glycol as antifreeze, and lithium chloride as a water retaining agent. Thanks to the synergistic effect of these components, the PCEL5.0% organohydrogel shows excellent performance in terms of ionic conductivity (1.61 S m-1), mechanical properties (tensile strength of 70.38 kPa and elongation at break of 537.84%), interfacial adhesion (1.06 kPa to pig skin), frost resistance (-50.4 °C), water retention (67.1% at 22% relative humidity), and remoldability. The resultant PCEL5.0%-based i-skin delivers satisfactory sensitivity (GF = 1.38) with fast response (348 ms) and high precision under different deformations and low temperature (-25 °C). Significantly, the wireless sensor system based on the PCEL5.0% organohydrogel i-skin can transmit signals from physiological activities and sign language to a smartphone by Bluetooth technology and dynamically displays the status of these movements. The organohydrogel i-skin shows great potential in diverse fields of physiological activity detection, human-computer interaction, and rehabilitation medicine.

The first structure of human Golm1 coiled coil domain reveals an unexpected tetramer and highlights its structural diversity.

Golgi membrane protein 1 (Golm1), a transmembrane protein with diverse subcellular localizations, has garnered significant attention in recent years due to its strong association with the development and progression of liver diseases and numerous cancers. Interestingly, although Golm1 is a membrane protein, the C-terminal of Golm1, which contains a coiled coil domain and a flexible acid region, can also be detected in the plasma of patients with various liver diseases. Notably, the coiled coil domain of serum Golm1 is postulated to play a pivotal role in physiological and pathological functions. However, little is currently known about the structure of this coiled coil domain and the full-length protein, which may limit our understanding of Golm1. Therefore, this study aims to address this gap in knowledge and reports the first crystal structure of the coiled coil domain of Golm1 at a resolution of 2.28 Å. Meanwhile, we have also confirmed that the Golm1 coiled coil domain in solution can form tetramer. Our results reveal that Golm1 can form a novel tetrameric structure that differs from the previous reported dimeric structure Golm1 could assemble, which may provide novel insights into the diversity of physiological functions and pathological roles.

DNA methylation-mediated phenylpropane and starch metabolism causes male poplars to be more tolerant to nitrogen deficiency than females.

Nitrogen (N) is an essential nutrient for plant growth and development. Dioecious plants, especially perennial plants, are often faced with a shortage of N supply in nature. Poplar is one of the most important dioecious and perennials species. Due to the different ecological functions, female and male poplars adopt different adaptation strategies to N limitation. However, the regulation in epigenetic mechanism is poorly understood on sexes. Here, the integrative analysis of whole-genome bisulfite sequencing (WGBS), RNA sequencing, and plant physiological analysis on female and male Populus cathayana were performed. We found that N deficiency reprograms methylation in both sexes, and the CG and CHH methylation types played critical roles in female and male poplars, respectively. Induced by DNA methylation, N-deficient males had a stronger phenylpropanoid synthesis pathway and less anthocyanin accumulation than females, which not only strengthened the N cycle but also reduced the defense cost of males. In addition, compared with male poplars, females accumulated more starch to expend excess energy under N limited condition. Additionally, DNA methylation also mediated hormone signalling involved in anthocyanin synthesis and starch metabolism. Therefore, our study reveals new molecular evidences that male poplars are more tolerant to N deficiency than females, which provides a reference for ecological adaptability of forest trees.

Hexaploid Salix rehderiana is more suitable for remediating lead contamination than diploids, especially male plants.

Willows are promising candidates for phytoremediation, but the lead (Pb) phytoremediation potential of different willow ploidy and sex has not yet been exploited. In this study, the Pb uptake, translocation and detoxification capacities of hexaploid and diploid, female and male Salix rehderiana were investigated. The results showed that Pb treatment inhibited biomass accumulation and gas exchange, caused ultrastructural and oxidative damage, and induced antioxidant, phytohormonal and transcriptional regulation in S. rehderiana. Absorbed Pb was mainly accumulated in the roots with restricted root-to-shoot transport. Despite lower biomass, greater transpiration, phytohormonal and transcriptional regulation indicated that hexaploid S. rehderiana had higher tissue Pb concentration, total accumulated Pb amount (4.39 mg, 6.19 mg, 6.60 mg and 10.83 mg in diploid and hexaploid females and males, respectively) as well as bioconcentration factors and translocation factors (0.412, 0.593, 0.921 and 1.320 for bioconcentration factors in roots, and 0.029, 0.032, 0.035 and 0.047 for translocation factors in diploid and hexaploid females and males, respectively) than diploids. Higher soil urease and acid phosphatase activities also favored hexaploids to use more available N and P than diploids in Pb-contaminated soils. Additionally, hexaploid S. rehderiana had stronger antioxidant, phytohormonal and transcriptional responses, and displayed less morphological and ultrastructural damage than diploids after Pb treatment, suggesting that hexaploids have greater Pb uptake, translocation and detoxification capacities than diploids. Moreover, S. rehderiana males had greater Pb uptake and translocation abilities, as well as stronger antioxidant, phytohormonal, and transcriptional regulation mediated Pb detoxification capacities than females. Therefore, hexaploid S. rehderiana are superior to diploids, and males are better than females in Pb phytoremediation. This study provides novel and valuable insights for selecting better willow materials to mitigate Pb contamination.

Clean Preparation of Formed Coke from Semi-coke by the Carbonated Consolidation Process.

In order to address the low thermal efficiency of low-rank coal combustion and the accompanying serious environmental issues, formed coke was prepared using a carbonization consolidation method with low-rank coal semi-coke. The test for briquetting and carbonation consolidation conditions revealed that the optimal parameters were a briquetting pressure of 93.63 MPa, moisture content of 16%, Ca(OH)2 binder amount of 10%, and a CO2 concentration of 30% at 20 °C. Under these conditions and a carbonation consolidation time of 60 min, high-quality formed coke was produced, exhibiting a compressive strength of 1256.2 N/a, redrying strength of 286.2 N/a, and a dropping strength of 10.6 number/a. The combustion characteristics of the prepared formed coke were investigated, revealing that ignition temperatures (345.39 °C), burnout temperatures (495.57 °C), and peak of the maximum weight loss rate temperatures (437.93 °C) are slightly higher than those of bituminous coal. The low calorific value of the briquette was 20.4 MJ/kg. During the combustion process, the emission concentrations of SO2, NOX, and solid particles from the formed coke were significantly lower than those of bituminous coal, indicating that it is a cleaner energy source. Moreover, adding Ca(OH)2 effectively reduced SO2 emissions and achieved sulfur fixation and emission reduction.

Research on the Impact of Intercustomer Social Support on Customer Engagement Behaviors in Virtual Brand Communities.

Customer engagement behavior is a key factor in promoting the sustainable growth of virtual brand communities. Despite the extensive research on the antecedents of customer engagement behaviors, the influence of intercustomer social support remains a neglected area in the context of virtual brand communities. Based on a total of 293 valid questionnaires collected via an online survey, a structural equation model and hierarchical regression analysis are used to examine the effects of intercustomer social support (informational/emotional support) on customer engagement behaviors (customer-oriented/community-oriented engagement behaviors) in virtual brand communities, as well as consider the mediating role of self-efficacy and the moderating role of interdependent self-construal in the above relationships. The empirical finding shows that informational/emotional support significantly affects customer-oriented and community-oriented engagement behaviors. Self-efficacy plays a mediating role in the relationship between informational/emotional support and customer-oriented/community-oriented engagement behaviors. Interdependent self-construal positively moderates the relationship between informational/emotional support and customer-oriented engagement behaviors and positively moderates the relationship between informational support and community-oriented engagement behaviors. This article provides a more comprehensive understanding of the relationships between intercustomer social support and customer engagement behaviors in the context of virtual brand communities, and improves the existing customer engagement behaviors management practices that are beneficial for the companies.

Integrated DNA methylation, transcriptome and physiological analyses reveal new insights into superiority of poplars formed by interspecific grafting.

Plant grafting has a long history and it is extensively employed to improve plant performance. In our previous research, reciprocal grafts of Populus cathayana Rehder (C) and Populus deltoides Bart. Ex Marsh (D) were generated. The results showed that interspecific grafting combinations (scion/rootstock: C/D and D/C) grew better than intraspecific grafting combinations (C/C and D/D). To further understand differences in molecular mechanisms between interspecific and intraspecific grafting, we performed an integrated analysis, including bisulfite sequencing, RNA sequencing and measurements of physiological indicators, to investigate leaves of different grafting combinations. We found that the difference at the genome-wide methylation level was greater in D/C vs D/D than in C/D vs C/C, but no difference was detected at the transcription level in D/C vs D/D. Furthermore, the grafting superiority of D/C vs D/D was not as strong as that of C/D vs C/C. These results may be associated with the different methylation forms, mCHH (71.76%) and mCG (57.16%), that accounted for the highest percentages in C/D vs C/C and D/C vs D/D, respectively. In addition, the interspecific grafting superiority was found mainly related to the process of photosynthesis, phytohormone signal transduction, biosynthesis of secondary metabolites, cell wall and transcriptional regulation based on both physiological and molecular results. Overall, the results indicated that the physiological and molecular phenotypes of grafted plants are affected by the interaction between scion and rootstock. Thus, our study provides a theoretical basis for developing suitable scion-rootstock combinations for grafted plants.

Enhanced adsorption of NO onto activated carbon by gas pre-magnetization.

The NO removal efficiency was relatively low in the traditional activated carbon adsorption process. In this work, a gas pre-magnetization and activated carbon adsorption process was developed to enhance the adsorption of NO onto activated carbon. In this innovative and green process, the mixed gas was magnetized in the external magnetic field and then absorbed by activated carbon. The results indicated that the maximal removal rate of NO could be increased from 75.0% to 89.5%, and the NO adsorption capacity of commercial activated carbon in one hour elevated from 2.28 to 2.60 mg/g when the magnetic induction intensity of external magnetic field increased from 0 T to 2 T. The strengthening mechanism of the gas pre-magnetization was investigated. It was found that magnetic field could elevate the oxidation rate of NO by 11.4% and thus promote the physical adsorption of NO onto activated carbon. External magnetic field could increase the reaction activity of NO and promote the chemical reaction between NO and some functional groups (CO, CO and COOH) on the activated carbon and thus promote the chemisorption process of NO.

Development and validation of a predictive model for diagnosing prostate cancer after transperineal prostate biopsy.

Objective: This study aimed to develop and validate a nomogram to predict the probability of prostate cancer (PCa) after transperineal prostate biopsy by combining patient clinical information and biomarkers. Methods: First, we retrospectively collected the clinicopathologic data from 475 patients who underwent prostate biopsy at our hospital between January 2019 to August 2021. Univariate and multivariate logistic regression analyses were used to select risk factors. Then, we established the nomogram prediction model based on the risk factors. The model performance was assessed by receiver operating characteristic (ROC) curves, calibration plots and the Hosmer-Lemeshow test. Decision curve analysis (DCA) was used to evaluate the net benefit of the model at different threshold probabilities. The model was validated in an independent cohort of 197 patients between September 2021 and June 2022. Results: The univariate and multivariate logistic regression analyses based on the development cohort indicated that the model should include the following factors: age (OR = 1.056, p = 0.001), NEUT (OR = 0.787, p = 0.008), HPR (OR = 0.139, p < 0.001), free/total (f/T) PSA (OR = 0.013, p = 0.015), and PI-RADS (OR = 3.356, p < 0.001). The calibration curve revealed great agreement. The internal nomogram validation showed that the C-index was 0.851 (95% CI 0.809-0.894). Additionally, the AUC was 0.851 (95% CI 0.809-0.894), and the Hosmer-Lemeshow test result presented p = 0.143 > 0.05. Finally, according to decision curve analysis, the model was clinically beneficial. Conclusion: Herein, we provided a nomogram combining patients' clinical data with biomarkers to help diagnose prostate cancers.

Selenium nanoparticles coupling with Astragalus Polysaccharides exert their cytotoxicities in MCF-7 cells by inhibiting autophagy and promoting apoptosis.

BACKGROUND: Astragalus Polysaccharides (APS) had been reported to exhibit antitumor activities. Given that nanoparticles possessed unique advantages in cancer treatment, APS was used as the modifier to prepare gold, silver and selenium nanoparticles (APS-Au, APS-Ag and APS-Se NPs) in the present study. METHODS: The three nanoparticles were synthesized via a green approach and characterized by DLS, TEM, XRD, FT-IR and UV-Vis. The inhibitory effects of these nanoparticles on various tumor cells proliferation were examined by MTT assay in vitro. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and the expression of apoptosis and autophagy-related proteins were also detected. RESULTS: Among these, APS-Se NPs displayed the most potent antitumor activities against MCF-7 cells in vitro. Flow cytometric analysis suggested that after cells were exposed to elevated concentrations of APS-Se NPs (10, 20 and 40 µmol/L), the rate of apoptosis was increasing (16.63 ± 0.89, 38.60 ± 3.46 and 44.38 ± 2.62%, respectively). Further analysis by immunofluorescence revealed an increase in intracellular ROS and a loss of MMP. This was accompanied by increased LC3-I to LC3-II conversion. Also, western blot analysis demonstrated that the ratios of Bax/Bcl-2 and cleaved caspase9/caspase 9 rose, and LC3-II and p62 protein levels increased. The addition of chloroquine, an inhibitor of autophagy, further enhanced protein expression of p62 and LC3-II. CONCLUSION: APS-Se NPs exerted their cytotoxic activity in MCF-7 cells by blocking autophagy and facilitating mitochondrial pathway-mediated apoptosis.

JNK Signaling Promotes Bladder Cancer Immune Escape by Regulating METTL3-Mediated m6A Modification of PD-L1 mRNA.

The RNA N6-methyladenosine (m6A) writer methyltransferase-like 3 (METTL3) is upregulated in many types of cancer and promotes cancer progression by increasing expression of several oncogenes. Therefore, a better understanding of the mechanisms regulating METTL3 expression and the key targets of METTL3 in cancer cells could provide new therapeutic targets. In this study, we found that activated JNK signaling is associated with increased METTL3 expression in bladder cancer. Knockdown of JNK1 or administration of a JNK inhibitor impaired the binding of c-Jun with the METTL3 promoter, thereby decreasing the expression of METTL3 and global RNA m6A levels. Moreover, RNA m6A sequencing indicated enrichment of m6A in the 3'-UTR of immune checkpoint PD-L1 mRNA, which could be recognized by the m6A reader IGF2BP1 to mediate RNA stability and expression levels of PD-L1. Inhibition of JNK signaling suppressed m6A abundance in PD-L1 mRNA, leading to decreased PD-L1 expression. Functionally, METTL3 was essential for bladder cancer cells to resist the cytotoxicity of CD8+ T cells by regulating PD-L1 expression. Additionally, JNK signaling contributed to tumor immune escape in a METTL3-dependent manner both in vitro and in vivo. These data reveal the JNK/METTL3 axis as a mechanism of aberrant m6A modification and immune regulation in bladder cancer. SIGNIFICANCE: The identification of a novel m6A-dependent mechanism underlying immune system evasion by bladder cancer cells reveals JNK signaling as a potential target for bladder cancer immunotherapy.

Sex-biased genes and metabolites explain morphologically sexual dimorphism and reproductive costs in Salix paraplesia catkins.

Dioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions. As reproductive organs, unisexual flowers have different reproductive roles and exhibit conspicuous sexual dimorphism. To date, little is known about the temporal variations in and molecular mechanisms underlying the morphology and reproductive costs of dioecious flowers. We investigated male and female flowers of Salix paraplesia in three flowering stages before pollination (the early, blooming and late stages) via transcriptional sequencing as well as metabolite content and phenotypic analysis. We found that a large number of sex-biased genes, rather than sex-limited genes, were responsible for sexual dimorphism in S. paraplesia flowers and that the variation in gene expression in male flowers intensified this situation throughout flower development. The temporal dynamics of sex-biased genes derived from changes in reproductive function during the different flowering stages. Sexually differentiated metabolites related to respiration and flavonoid biosynthesis exhibited the same bias directions as the sex-biased genes. These sex-biased genes were involved mainly in signal transduction, photosynthesis, respiration, cell proliferation, phytochrome biosynthesis, and phenol metabolism; therefore, they resulted in more biomass accumulation and higher energy consumption in male catkins. Our results indicated that sex-biased gene expression in S. paraplesia flowers is associated with different reproductive investments in unisexual flowers; male flowers require a greater reproductive investment to meet their higher biomass accumulation and energy consumption needs.

Autophagy deficiency promotes M1 macrophage polarization to exacerbate acute liver injury via ATG5 repression during aging.

Aging disrupts the maintenance of liver homeostasis, which impairs hepatocyte regeneration and aggravates acute liver injury (ALI), ultimately leading to the development of acute liver failure (ALF), a systemic inflammatory response, and even death. Macrophages influence the progression and outcome of ALI through the innate immune system. However, it is still unclear how macrophages regulate ALI during aging. The variation in macrophage autophagy with aging and the influence on macrophage polarization and cytokine release were assessed in BMDMs in vitro. Then, after BMDMs subjected to several treatments were intravenously or intraperitoneally injected into mice, thioacetamide (TAA)-induced ALI (TAA-ALI) was established, and its effects on inflammation, injury, and mortality were assessed. We found that aging aggravated the liver injury, along with increases in the levels of proinflammatory mediators, presenting a senescence-associated secretory phenotype (SASP), which promoted macrophage polarization to the M1 phenotype. In addition, autophagy levels decreased significantly in aged mice, which was ascribed to ATG5 repression during aging. Notably, enhancing autophagy levels in aged BMDMs restored macrophage polarization to that observed under young conditions. Finally, autophagy restoration in aged BMDMs enhanced the protective effect against TAA-ALI, similar to M2 macrophages induced by IL-4. Overall, we demonstrated that the influence of aging on macrophage polarization is an important aggravating factor in TAA-ALI, and the autophagy in macrophages is associated with the aging phenotype.