Early recurrence as a pivotal event in nasopharyngeal carcinoma: identifying predictors and key molecular signals for survivors.

PURPOSE: The duration of response to treatment is a significant prognostic indicator, with early recurrence (ER) often predicting poorer survival outcomes in nasopharyngeal carcinoma (NPC) survivors. This study seeks to elucidate the factors contributing to the onset of ER following radiotherapy in NPC survivors. METHODS: This investigation encompassed 2,789 newly diagnosed NPC patients who underwent radical intensity-modulated radiotherapy. Ordinal logistic regression analysis was employed to evaluate the independent predictors of earlier recurrence. A machine learning-based prediction model of NPC recurrence patterns was developed. Tumorous RNA-sequencing (in-house cohort: N = 192) and biological tipping point analysis were utilized to infer potential molecular mechanisms associated with ER. RESULTS: Our results demonstrated that ER within 24 months post-initial treatment was the optimal time frame for identifying early malignant progression in NPC survivors. The ER cohort (150 of 2,789, 5.38%) exhibited a notably short median overall survival of 48.6 months. Multivariate analyses revealed that male gender, T4 stage, local or regional residual disease, detectable pre- and post-radiotherapy EBV DNA, and the absence of induction chemotherapy were significant predictors of earlier recurrence. The machine learning-based predictive model further underscored the importance of tumor-related factors in NPC recurrence. Moreover, ER emerged as a pivotal stage in NPC progression, with 15 critical transition signals identified potentially associated with the negative modulation of the immune response. CONCLUSIONS: Our comprehensive analysis of NPC recurrence patterns has unveiled insights into the key factors driving ER and provided novel insights into potential early warning biomarkers and the mechanisms underlying NPC progression.

Machine learning-driven prognostic analysis of cuproptosis and disulfidptosis-related lncRNAs in clear cell renal cell carcinoma: a step towards precision oncology.

Cuproptosis and disulfidptosis, recently discovered mechanisms of cell death, have demonstrated that differential expression of key genes and long non-coding RNAs (lncRNAs) profoundly influences tumor development and affects their drug sensitivity. Clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer, presently lacks research utilizing cuproptosis and disulfidptosis-related lncRNAs (CDRLRs) as prognostic markers. In this study, we analyzed RNA-seq data, clinical information, and mutation data from The Cancer Genome Atlas (TCGA) on ccRCC and cross-referenced it with known cuproptosis and disulfidptosis-related genes (CDRGs). Using the LASSO machine learning algorithm, we identified four CDRLRs-ACVR2B-AS1, AC095055.1, AL161782.1, and MANEA-DT-that are strongly associated with prognosis and used them to construct a prognostic risk model. To verify the model's reliability and validate these four CDRLRs as significant prognostic factors, we performed dataset grouping validation, followed by RT-qPCR and external database validation for differential expression and prognosis of CDRLRs in ccRCC. Gene function and pathway analysis were conducted using Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) for high- and low-risk groups. Additionally, we have analyzed the tumor mutation burden (TMB) and the immune microenvironment (TME), employing the oncoPredict and Immunophenoscore (IPS) algorithms to assess the sensitivity of diverse risk categories to targeted therapeutics and immunosuppressants. Our predominant objective is to refine prognostic predictions for patients with ccRCC and inform treatment decisions by conducting an exhaustive study on cuproptosis and disulfidptosis.

The effect of parental psychological control on children's peer interactions in China: the moderating role of teachers' emotional support.

Background: Peer interactions are critical to young children's social development, and proximal-system has a direct influence on personal growth. The study aims to analyze the relationship between parental psychological control and young children's peer interactions, as well as the moderating role of teachers' emotional support in this association. Methods: A total of 241 children aged 3-6 years, alongside their parents, and 27 teachers, participated in the study. Teachers reported children's peer interactions whilst parents reported their psychological control. The level of teachers' emotional support was co-coded by two researchers. Results: The results of the study indicated that parental psychological control was significantly and negatively related to young children's peer interactions; teachers' emotional support was significantly and positively related to young children's peer interactions; the cross-level moderating effect validates our hypothesis that teachers' emotional support has a moderating effect between parental psychological control and young children's peer interactions, buffering the impact of parental psychological control on young children's peer interactions. Conclusion: These findings expand our comprehension of the association between parental psychological control, teachers' emotional support, and young children's peer interactions, and provide guidance for integrating the components of the proximal system and devising interventions to establish a home-school harmony environment that fosters children's social development.

Immune-related risk prognostic model for clear cell renal cell carcinoma: Implications for immunotherapy.

Clear cell renal cell carcinoma (ccRCC) is associated with complex immune interactions. We conducted a comprehensive analysis of immune-related differentially expressed genes in patients with ccRCC using data from The Cancer Genome Atlas and ImmPort databases. The immune-related differentially expressed genes underwent functional and pathway enrichment analysis, followed by COX regression combined with LASSO regression to construct an immune-related risk prognostic model. The model comprised 4 IRGs: CLDN4, SEMA3G, CAT, and UCN. Patients were stratified into high-risk and low-risk groups based on the median risk score, and the overall survival rate of the high-risk group was significantly lower than that of the low-risk group, confirming the reliability of the model from various perspectives. Further comparison of immune infiltration, tumor mutation load, and immunophenoscore (IPS) comparison between the 2 groups indicates that the high-risk group could potentially demonstrate a heightened sensitivity towards immunotherapy checkpoints PD-1, CTLA-4, IL-6, and LAG3 in ccRCC patients. The proposed model not only applies to ccRCC but also shows potential in developing into a prognostic model for renal cancer, thus introducing a novel approach for personalized immunotherapy in ccRCC.

Effect of Adding Fermented Proso Millet Bran Dietary Fiber on Micro-Structural, Physicochemical, and Digestive Properties of Gluten-Free Proso Millet-Based Dough and Cake.

The increasing demand for functional foods has pushed the food industry to produce fiber-enriched products. In this study, rheological, microstructural, physicochemical, and functional characteristics were investigated for whole proso millet dough and cake, fortified with fermented proso millet bran dietary fiber flour (F-DF). Results showed that proso millet flour is less absorbent and stable than the control group. Adding proso millet flour and F-DF reduced the elasticity of the dough and increased its hardness, but had no significant effect on viscosity, cohesion, and resilience. The microstructure analysis exhibited an unformed continuous network formation in proso millet dough. Analyses suggested that proso millet flour combined with the fermented dietary fiber group had significantly higher total phenol content (0.46 GAE mg/g), DPPH• scavenging activity (66.84%), and ABTS•+ scavenging activity (87.01%) than did the other group. In addition, F-DF led to a significant reduction in the predicted released glucose contents of reformulated cakes. In summary, cakes prepared with the involvement of whole proso millet flour and F-DF exhibited less adverse sensory impact and possessed the potential to decrease postprandial blood glucose levels resulting purely from cake consumption.

A Mixed-Reality-Based Unknown Space Navigation Method of a Flexible Manipulator.

A hyper-redundant flexible manipulator is characterized by high degree(s) of freedom (DoF), flexibility, and environmental adaptability. It has been used for missions in complex and unknown spaces, such as debris rescue and pipeline inspection, where the manipulator is not intelligent enough to face complex situations. Therefore, human intervention is required to assist in decision-making and control. In this paper, we designed an interactive navigation method based on mixed reality (MR) of a hyper-redundant flexible manipulator in an unknown space. A novel teleoperation system frame is put forward. An MR-based interface was developed to provide a virtual model of the remote workspace and virtual interactive interface, allowing the operator to observe the real-time situation from a third perspective and issue commands to the manipulator. As for environmental modeling, a simultaneous localization and mapping (SLAM) algorithm based on an RGB-D camera is applied. Additionally, a path-finding and obstacle avoidance method based on artificial potential field (APF) is introduced to ensure that the manipulator can move automatically under the artificial command in the remote space without collision. The results of the simulations and experiments validate that the system exhibits good real-time performance, accuracy, security, and user-friendliness.

Changes in the Microbial Communities of Tiger Frog (Rana tigrina) Meat during Refrigerated Storage.

ABSTRACT: Microbial activity is the major cause of the spoilage of aquatic meat products during storage. This study investigated the changes of the microbial compositions of the tiger frog (Rana tigrina) meat stored aerobically at 4°C for 12 days using 16S rRNA amplicon high-throughput sequencing analysis. The microbial diversity and species richness of the frog meat were abundant at the initial phase of storage but decreased substantially with prolongation of the storage time. Proteobacteria was the prevalent phylum identified from the frog meat, with a relative abundance of 40.29% at day 0 increasing to 96.77% at day 6 and 95.41% at day 12. At the genus level, Shewanella, Pseudomonas, and Acinetobacter were the three dominant genera in the spoiled samples and contributed to frog meat spoilage. Their proportions were 41.67, 28.48, and 5.94% at day 6 and 29.94, 23.48, and 18.44% at day 12, respectively. The present study is conducive to understanding the pattern and process of frog meat spoilage during refrigeration and could be used to develop efficient control measures to mitigate the predominant psychrotrophic spoilers in aerobically stored frog meat.

Effect of chlorine dioxide and phosphates on the quality of tiger frog (Rana tigrina) meat during 4 °C storage.

Tiger frog (Rana tigrina) meat is extremely perishable. This study investigated the antimicrobial efficacy of chlorine dioxide (ClO2 ) on frog meat, optimized the formulation of a phosphate-based enhancement solution by response surface methodology (RSM), and determined the quality parameters (i.e., total aerobic counts [TAC], pH, drip loss, cooking loss, color measurements, shear force, total volatile basic nitrogen [TVB-N], and thiobarbituric acid-reactive substances [TBARS]) of refrigerated frog meat pretreated with ClO2 and the optimized blend of phosphates. Treatments of frog meat with 35 and 70 ppm ClO2 for 3, 5, and 10 min achieved a 0.7-, 0.9- and 0.9-, and 0.8-, 1.4- and 1.6-log CFU/g reduction of TAC, respectively, indicating the antimicrobial efficacy of ClO2 was concentration- and time-dependent with such that higher concentrations and/or longer exposure time achieved greater bacterial reductions. The concentrations of the phosphates, including sodium tripolyphosphate (STPP), sodium pyrophosphate (SPP), and sodium hexametaphosphate (SHMP), were optimized as the formula of 0.3% STPP and 0.45% SPP obtaining the highest water retention of the frog meat. After washed with 70 ppm ClO2 for 10 min and subsequently soaked with 0.3% STPP and 0.45% SPP for 30 min, the frog meat stored at 4 °C shown significantly (P < 0.05) lower TAC (<4.4 log CFU/g) and higher water holding capacity during the whole storage of 12 days, compared to the control. Results indicated that the two-step process may be applicable to slow down deterioration and maintain quality frog meat during refrigeration. PRACTICAL APPLICATION: This research provides a means to slow down deterioration, maintain quality frog meat, and improve stability during refrigeration. Refrigerated frog meat products, which are preferred by consumers with juicier and more tender texture compared to the frozen-thawed meat, could be developed by the frog industry based on the data from this study.

Identification and bioinformatic analysis of Aux/IAA family based on transcriptome data of Bletilla striata.

Auxin/Indole-3-Acetic Acid (Aux/IAA) genes are involved in auxin signaling pathway and play an important role in plant growth and development. However, many studies focus on Aux/IAA gene families and much less known in Bletilla striata. In this study, a total of 27 Aux/IAA genes (BsIAA1-27) were cloned from the transcriptome of Bletilla striata. Based on a phylogenetic analysis of the Aux/IAA protein sequences from B. striata, Arabidopsis thaliana and Dendrobium officinale, the Aux/IAA genes of B. striata (BsIAAs) were categorized into 2 subfamilies and 9 groups. While BsIAAs were more closer to those of D. officinale compared to A. thaliana. EST-SSR marker mining test showed that 4 markers could be stably amplified with obvious polymorphisms among 4 landraces. Our results suggested that BsIAAs were involved in the process of tuber development and provided insights into functional roles of Aux/IAA genes in B. striata and other plants.

Concentrations, properties, and health risk of PM2.5 in the Tianjin City subway system.

A campaign was conducted to assess and compare the personal exposure in L3 of Tianjin subway, focusing on PM2.5 levels, chemical compositions, morphology analysis, as well as the health risk of heavy metal in PM2.5. The results indicated that the average concentration of the PM2.5 was 151.43 µg/m3 inside the train of the subway during rush hours. PM2.5 concentrations inside car under the ground are higher than those on the ground, and PM2.5 concentrations on the platform are higher than those inside car. Regarding metal concentrations, the highest element in PM2.5 samples was Fe; the level of which is 17.55 µg/m3. OC is a major component of PM2.5 in Tianjin subway. Secondary organic carbon is the formation of gaseous organic pollutants in subway. SEM-EDX and TEM-EDX exhibit the presence of individual particle with a large metal content in the subway samples. For small Fe metal particles, iron oxide can be formed easily. With regard to their sources, Fe-containing particles are generated mainly from mechanical wear and friction processes at the rail-wheel-brake interfaces. The non-carcinogenic risk to metals Cr, Ni, Cu, Zn and Pb, and carcinogenic hazard of Cr and Ni were all below the acceptable level in L3 of Tianjin subway.

Enhanced anti-tumor efficacy of aspirin combined with triptolide in cervical cancer cells.

BACKGROUND: The non-steroidal anti-inflammatory drug (NSAID) aspirin (acetylsalicylic acid) is an inhibitor of cyclooxygenase enzymes. Recent studies have shown that aspirin could be used as an anti-tumor drug. Triptolide, the major compound extracted from the Chinese herb Tripteryglum wilfordii Hook.f, has now been shown that it can inhibit tumor growth. The aim of this study was to analyze the anti-tumor efficiency of aspirin and triptolide in cervical cancer cells. METHODS: Viability of cervical cancer cell lines was assessed by the MTT method at various concentrations of aspirin and triptolide. Siha and HeLa cell apoptotic analysis was performed by flow cytometry. Real time-PCR and Western Blotting were used to analyze the expression of Bcl-2/Bax, Cyclin D1 and p16. RESULTS: Viability in the combination group was significantly decreased as compared with either drug used alone. Expression change of Bcl-2/Bax, CyclinD1 and p16 appeared to play an important role in the synergistic killing effect on cervical cancer cell apoptosis. CONCLUSION: Aspirin and triptolide combination treatment may have synergistic anti-tumor effects on cervical cancer cells.

Biosynthesis and thermal properties of PHBV produced from levulinic acid by Ralstonia eutropha.

Levulinic acid (LA) can be cost-effectively produced from a vast array of renewable carbohydrate-containing biomaterials. LA could facilitate the commercialization of the polymer poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) and PHBV-based products as carbon substrates. Therefore, this paper focused on the production of PHBV by Ralstonia eutropha with LA for hydroxyvalerate (HV) production, which plays an important role in enhancing the thermal properties of PHBV. Accordingly, the HV content of PHBV varied from 0-40.9% at different concentrations of LA. Stimulation of cell growth and PHBV accumulation were observed when 2-6 g L(-1) LA was supplied to the culture. The optimal nitrogen sources were determined to be 0.5 g L(-1) ammonium chloride and 2 g L(-1) casein peptone. It was determined that the optimal pH for cell growth and PHBV accumulation was 7.0. When the cultivation was performed in large scale (2 L fermenter) with a low DO concentration of 30% and a pH of 7.0, a high maximum dry cell weight of 15.53 g L(-1) with a PHBV concentration of 12.61 g L(-1) (53.9% HV), up to 81.2% of the dry cell weight, was obtained. The melting point of PHBV found to be decreased as the fraction of HV present in the polymer increased, which resulted in an improvement in the ductility and flexibility of the polymer. The results of this study will improve the understanding of the PHBV accumulation and production by R. eutropha and will be valuable for the industrial production of biosynthesized polymers.

Production and characterization of a novel bioflocculant from Bacillus licheniformis.

A bacterium producing an extracellular bioflocculant was isolated from contaminated LB medium and identified as Bacillus licheniformis by 16S rRNA gene sequencing and its biochemical/physiological characteristics. The optimum culture conditions for flocculant production were an initial medium pH of 7.2 and an inoculum size of 4% (vol/vol). The maximum flocculating activity (700 U/ml) was obtained after cultivation at 37 degrees C for 48 h. Chemical analyses of the purified bioflocculant revealed that it was a proteoglycan composed of 89% carbohydrate and 11% protein (wt/wt). The mass ratio of neutral sugar, amino sugar, and uronic acid was measured at 7.9:4:1. Infrared spectrometry further indicated the presence of carboxyl, hydroxyl, and amino groups, typical of heteropolysaccharide. The average mass of the bioflocculant was calculated to be 1.76 x 10(6) Da. Scanning electron microscopy (SEM) images of the bioflocculant showed an irregular structure with netted texture. Its efficient flocculation capabilities suggest potential applications in industry.