Vacancy Suppression and Resonant Level Rendering Extraordinary Power Factor in Sn0.99In0.01Te/Tourmaline Composite.

SnTe, as a potential medium-temperature thermoelectric material, reaches a maximum power factor (PF) usually above 750 K, which is not conducive to continuous high-power output in practical applications. In this study, PF is maintained at high values between 18.5 and 25 µW cm-1 K-2 for Sn0.99In0.01Te-x wt% tourmaline samples within the temperature range of 323 to 873 K, driving the highest PFeng of 1.2 W m-1 K-1 and PFave of 22.5 µW cm-1 K-2, over 2.5 times that of pristine SnTe. Such an extraordinary PF is attributed to the synergy of resonant levels and Sn vacancy suppression. Specifically, the Seebeck coefficient increases dramatically, reaching 88 µV K-1 at room temperature. Meanwhile, by Sn vacancy suppression, carrier concentration, and mobility are optimized to ≈1019 cm-3 and 740 cm2 V-1 s-1, respectively. With the tourmaline compositing, Sn vacancies are further suppressed and the thermal conductivity simultaneously decreases, with the minimum lattice thermal conductivity of 0.9 W m-1 K-1. Finally, the zT value ≈0.8 is obtained in the Sn0.99In0.01Te sample. The peak of the power output density reaches 0.89 W cm-2 at a temperature difference of 600 K. Such SnTe alloys with high and "temperature-independent" PF will offer an option for realizing high output power in thermoelectric devices.

Prognostic value of postoperative anti-thyroglobulin antibody in patients with differentiated thyroid cancer.

Purpose: Postoperative thyroglobulin (Tg) generally serves as a biomarker to monitor the recurrence or persistence of differentiated thyroid cancer (DTC), whereas it constrains to interference from anti-thyroglobulin antibody (TgAb). This study aimed to determine the value of postoperative TgAb as a surrogate for monitoring tumor status in DTCs with positive TgAb after successful radioactive iodine (RAI) remnant ablation. Methods: We retrospectively enrolled DTC patients with positive (≥40 IU/mL, Roche) postoperative TgAb measurements. An index of TgAb change (ΔTgAb) was defined to describe the TgAb decrease rate. DTC status was defined as either no evidence of disease (NED) or persistent/recurrent disease (PRD). Univariate and multivariate binary logistic analyses were used to identify the independent risk factors of PRD. Receiver operating characteristic (ROC) curves were performed to determine the optimal cutoff values of each risk factor, and DeLong's test was conducted to compare their predictive powers. Kaplan-Meier curves were used to assess the impact of different TgAb trends in the first year on progression-free survival. Results: Of the 232 patients enrolled, the median diagnosis age was 34 years (range, 18-62 years), with a male-to-female ratio of 1:4.66 (41/191). Among them, after a median follow-up of 44 months (range, 4-128 months),183 (78.87%) patients were evaluated as NED, while the other 49 (21.12%) had either persistent (n = 25) or recurrent disease (n = 24). Multivariate regression showed that ΔTgAb (P < 0.001) and lymph node metastasis (LNM) rate (P = 0.009) were independently relevant to the presence of PRD, with optimal cutoff values of 47.0% and 35.1%, respectively. It is important to note that there is a high negative predictive value (96.93%) of ΔTgAb with the cutoff of 47.0%. DeLong's test showed that ΔTgAb alone and the combination of ΔTgAb and LNM rate were significantly greater than the isolated LNM rate (both P < 0.001) in predicting NED, while there was no statistical difference of the predictive power between ΔTgAb and the combination (P = 0.203). Additionally, patients with ΔTgAb >47.0% had longer progression-free survival than those with ΔTgAb ≤47.0% (not reached vs. 50 months, P < 0.001), and those with ΔTgAb >47.0% or negative conversion within the first year after RAI ablation had longer progression-free survival. Conclusion: Our study suggested that ΔTgAb could serve as a valuable indicator of disease status in DTC patients with positive TgAb. A ΔTgAb of >47.0% is conducive to identify those with NED and may help to obviate their overtreatment. The decrease rate and negative conversion of TgAb in the first year were good predictors of disease-free survival in patients.

Mixed acid treatment for removal of green macroalgae from Neopyropia aquaculture nets: Field experiment in the Subei Shoal, China.

To develop an effective method to eliminate green macroalgae attached to Neopyropia aquaculture nets, we explored the influence of mixed acid solution on the photosynthetic fluorescence characteristics of Ulva spp. (green macroalgae) and Neopyropia yezoensis (red macroalgae) from Dafeng and Rudong aquaculture areas in Jiangsu Province, China. Treatment with mixed acid solution (0.0475 % hydrochloric acid:citric acid (pH 2.0) at a ratio of 4:3) for 60 s caused death of Ulva spp., but did not affect N. yezoensis. Additionally, a mixed acid solution effectively eliminated green macroalgae from Neopyropia aquaculture rafts and the marine environment remained unaffected. Hence, the application of mixed acid solution treatment has demonstrated significant efficacy in eradicating green macroalgae adhered to Neopyropia aquaculture rafts, thus presenting a promising strategy for mitigating green macroalgae proliferation in Neopyropia aquaculture areas and curbing their contribution to green tides.

Leaching characteristics of nutrients in food waste digestate-derived biochar.

Food waste anaerobic digestion requires proper utilization of solid digestate, and pyrolysis emerges as an effective method to produce nutrient-rich biochar. This study investigated the leaching characteristics and speciation changes of nutrients in food waste digestate (FWD)-derived biochar pyrolyzed at 350 °C (BC350), 450 °C (BC450), and 550 °C (BC550). BC350 featured inorganic nitrogen, while BC450 and BC550 contained elevated organic nitrogen. Nitrogen, potassium, and dissolved organic carbon were released via a quick surface wash-off process. Polyphosphates prevailed in BC350 and leached through a fast diffusion-controlled process. BC450 and BC550 were dominated by Ca/Mg orthophosphates and released via a slow dissolution-controlled process. Leachates from BC450 and BC550 stimulated the shoot length of wheat seeds. After 5 leaching cycles, there were more aromatic dissolved organics, and BC450 and BC550 exhibited higher abundance of C-N and O-P-O. Overall, pyrolysis of FWD at 450 °C and 550 °C shows potential in producing slow-release biochar fertilizers for resource recycling.

Overwintering and summer survival of Ulva prolifera in sediments: Indoor simulation of temperature impacts.

Green tides, a globally prevalent marine ecological anomaly observed in coastal regions, have received substantial attention. However, there is limited research on the burial of Ulva prolifera in sediments during the late stages of green tide outbreaks. This study investigates the effect of temperature on U. prolifera buried in sediment over 30 days. The measurements included the length, biomass, relative growth rate, chlorophyll composition and maximum quantum yield (Fv/Fm) of PS II at different stages. The results indicate that at -20 °C, numerous seedlings emerged after 14 days of recovery culture, suggesting the release of spores or gametes; survival was possible from -2 °C to 15 °C; but at 20 °C and 30 °C, all U. prolifera died. The U. prolifera buried in sediment during the late stage of green tide outbreaks may serve as one of the sources for the subsequent year's green tide eruption. This research provides insights into the origins of green tide outbreaks in the southern Yellow Sea.

Performance of wood waste biochar and food waste compost in a pilot-scale sustainable drainage system for stormwater treatment.

Sustainable drainage system (SuDS) for stormwater reclamation has the potential to alleviate the water scarcity and environmental pollution issues. Laboratory studies have demonstrated that the capacity of SuDS to treat stormwater can be improved by integrating biochar and compost in the filter media, whereas their performance in scaled-up applications is less reported. This study examines the effectiveness of a pilot-scale SuDS, bioswale followed by bioretention, amended with wood waste biochar (1, 2, and 4 wt.%) and food waste compost (2 and 4 wt.%) to simultaneously remove multiple pollutants including nutrients, heavy metals, and trace organics from the simulated stormwater. Our results confirmed that SuDS modified with both biochar (2 wt.%) and compost (2 wt.%) displayed superior water quality improvement. The system exhibited high removal efficiency (> 70%) for total phosphorus and major metal species including Ni, Pb, Cd, Cr, Cu, and Zn. Total suspended solids concentration was approaching the detection limit in the effluent, thereby confirming its capability to reduce turbidity and particle-associated pollutants from stormwater. Co-application of biochar and compost also moderately immobilized trace organic contaminants such as 2,4-dichlorophenoxyacetic acid, diuron, and atrazine at field-relevant concentrations. Moreover, the soil amendments amplified the activities of enzymes including ß-D-cellobiosidase and urease, suggesting that the improved soil conditions and health of microbial communities could possibly increase phyto and bioremediation of contaminants accumulated in the filter media. Overall, our pilot-scale demonstration confirmed that the co-application of biochar and compost in SuDS can provide a variety of benefits for soil/plant health and water quality.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer.

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied. Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS. Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041). Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Early Structural, Biochemical, and Metabolic Responses to Anlotinib in Patients With Progressive Radioactive Iodine Refractory Differentiated Thyroid Cancer.

OBJECTIVE: We aimed to assess the early efficacy of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer at the structural, biochemical, and metabolic levels. METHODS: Ten eligible patients were prospectively enrolled to receive anlotinib. Their responses were assessed at 6 weeks. Apart from the structural response according to Response Evaluation Criteria in Solid Tumors version 1.1, the biochemical response was assessed by serum thyroglobulin (Tg), and the metabolic response was assessed by 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) according to the European Organization for Research and Treatment of Cancer criteria. A safety profile was recorded. RESULTS: Structurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9-27.5) to 17.0 mm (IQR, 14.1-23.7) (P < .001), and the average shrinkage rate was -15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in 8 measurable patients. The 18F-FDG PET/CT-mapped glucose metabolic response was not quite comparable to the structural response, with 90% of the patients having controlled disease (30% partial metabolic response + 60% stable metabolic disease), whereas 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, whereas grade 3 AEs occurred only in hypertension. CONCLUSION: Anlotinib is generally well tolerated and can bring early disease control within the initial 6 weeks of treatment. The sharp biochemical response suggests Tg to be an early sensitive biomarker to anlotinib, whereas the heterogeneous metabolic response might play a complementary role.

Mechanisms of harmful effects of Microcystis aeruginosa on a brackish water organism Moina mongolica based on physiological and transcriptomic responses.

To investigate the detrimental impacts of cyanobacterial bloom, specifically Microcystis aeruginosa, on brackish water ecosystems, the study used Moina mongolica, a cladoceran species, as the test organism. In a chronic toxicology experiment, the survival and reproductive rates of M. mongolica were assessed under M. aeruginosa stress. It was observed that the survival rate of M. mongolica fed with M. aeruginosa significantly decreased with time and their reproduction rate dropped to zero, while the control group remained maintained stable and normal reproduction. To further explore the underlying molecular mechanisms of the effects of M. aeruginosa on M. mongolica, we conducted a transcriptomic analysis on newly hatched M. mongolica cultured under different food conditions for 24 h. The results revealed significant expression differences in 572 genes, with 233 genes significantly up-regulated and 339 genes significantly down-regulated. Functional analysis of these differentially expressed genes identified six categories of physiological functional changes, including nutrition and metabolism, oxidative phosphorylation, neuroimmunology, cuticle and molting, reproduction, and programmed cell death. Based on these findings, we outlined the basic mechanisms of microcystin toxicity. The discovery provides critical insights into the mechanisms of Microcystis toxicity on organisms and explores the response mechanisms of cladocerans under the stress of Microcystis.

Agarose amplification based sequencing characterization cell-free RNA in preimplantation spent embryo medium.

BACKGROUND: The cell-free RNA (cf-RNA) of spent embryo medium (SEM) has aroused a concern of academic and clinical researchers for its potential use in non-invasive embryo screening. However, comprehensive characterization of cf-RNA from SEM still presents significant technical challenges, primarily due to the limited volume of SEM. Hence, there is urgently need to a small input liquid volume and ultralow amount of cf-RNA library preparation method to unbiased cf-RNA sequencing from SEM. (75) RESULT: Here, we report a high sensitivity agarose amplification-based cf-RNA sequencing method (SEM-Acf) for human preimplantation SEM cf-RNA analysis. It is a cf-RNA sequencing library preparation method by adding agarose amplification. The agarose amplification sensitivity (0.005 pg) and efficiency (105.35 %) were increased than that of without agarose addition (0.45 pg and 96.06 %) by âˆ¼ 90 fold and 9.29 %, respectively. Compared with SMART sequencing (SMART-seq), the correlation of gene expression was stronger in different SEM samples by using SEM-Acf. The cf-RNA number of detected and coverage uniformity of 3' end were significantly increased. The proportion of 5' end adenine, alternative splicing events and short fragments (<400 bp) were increased. It is also found that 4-mer end motifs of cf-RNA fragments was significantly differences between different embryonic stage by day3 spent cleavage medium and day5/6 spent blastocyst medium. (141) SIGNIFICANCE: This study established an efficient SEM amplification and library preparation method. Additionally, we successfully described the characterizations of SEM cf-RNA in preimplantation embryo using SEM-Acf, including expression features and fragment lengths. SEM-Acf facilitates the exploration of cf-RNA as a noninvasive embryo screening biomarker, and opens up potential clinical utilities of small input liquid volume and ultralow amount cf-RNA sequencing. (59).

Combustion properties and pollutant analysis of coal-blended bio-heavy oil fuel.

Excessive carbon-dioxide emissions drive global climate change and environmental challenges. Integrating renewable biomass fuels with coal in power units is crucial for achieving low-carbon emission reductions. Coal blending with bio-heavy oil enhances the combustion calorific value of the fuel, improves combustion characteristics, and decreases pollutant emissions. This study found that bio-heavy oil with low sulfur (0.073%), low nitrogen (0.18%), low ash, and high oxygen (11.005%) content exhibits excellent fuel performance, which can be attributed to the abundant oxygen-containing functional groups (such as C[double bond, length as m-dash]O) in the alcohols, aldehydes, and ketones present in bio-heavy oil. Additionally, the residual moisture in coal-blended bio-heavy oil reduces the fuel's calorific value. The calorific value increases with a higher proportion of blended bio-heavy oil (28.1, 28.9, 32.1, 34.7, 40.6 MJ kg-1). Experiments on combustion flame shooting reveal that the combustion time of bio-heavy oils is significantly shorter than that of coal. As the proportion of blended bio-heavy oil increases, the flame height increases. Coal blending with bio-heavy oil involves three stages: water evaporation, volatile-matter decomposition, fixed-carbon combustion and mineral decomposition. This advances the combustion process and improves coal's ignition performance. Furthermore, the amount of gaseous pollutants (sulfur dioxide and nitrogen dioxide) in coal mixed with bio-heavy oil is relatively low, which is in alignment with the green environmental protection guidelines. The blending of coal with biomass fuel holds significant practical and strategic importance for developing high-efficiency, low-carbon, coal power units.

The analysis of segmental lordosis restored by oblique lumbar interbody fusion and related factors: building up preoperative predicting model.

BACKGROUND: Oblique lumbar interbody fusion (OLIF) procedures have the potential to increase the segmental lordosis by inserting lordotic cages, however, the amount of segmental lordosis (SL) changes can vary and is likely influenced by several factors, such as patient characteristics, radiographic parameters, and surgical techniques. The objective of this study was to analyze the impact of related factors on the amount of SL changes in OLIF procedures and to build up predictive model for SL changes. METHODS: This is a retrospective study involving prospectively enrolled patients. A total of 119 patients with 174 segments undergoing OLIF procedure were included and analyzed. The lordotic cages used in all cases had 6-degree angle. Radiographic parameters including preoperative and postoperative segmental disc angle (SDA, preSDA and postSDA), SDA changes on flexion-extension views (ΔSDA-FE), CageLocation and CageInclination were measured by two observers. Interobserver reliability of measurements were ensured by analysis of interclass correlation coefficient (ICC > 0.75). Pearson correlation coefficient analysis and multivariate linear regression were employed to identify factors related to SDA changes and to build up predictive model for SDA changes. RESULTS: The average change of segmental disc angle (ΔSDA, postSDA-preSDA) was 3.9° ± 4.8° (95% confidence interval [CI]: 3.1°-4.6°) with preSDA 5.3° ± 5.0°. ΔSDA was 10.8° ± 3.2° with negative preSDA (kyphotic), 5.0° ± 3.7° with preSDA ranging from 0° to 6°, and 1.0° ± 4.1° with preSDA> 6°. Correlation analysis revealed a significant negative correlation between ΔSDA and preSDA (r = - 0.713, P < 0.001), CageLocation (r = - 0.183, P = 0.016) and ΔSDA-FE (r = - 0.153, P = 0.044). In the multivariate linear regression, preSDA and CageLocation were included in the predictive model, resulting in minimal adjusted R2 change (0.017) by including CageLocation. Therefore, the recommended predictive model was ΔSDA = 7.9-0.8 × preSDA with acceptable fit. (adjusted R2 = 0.508, n = 174, P < 0.001). CONCLUSIONS: The restoration of segmental lordosis through OLIF largely depends on the preoperative segmental lordosis. The predictive model, which utilized preoperative segmental lordosis, facilitates preoperative planning for corrective surgery using the OLIF procedure.

Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer.

Cell-free RNA (cfRNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cfRNA isolation technologies due to the low abundance and instability of cfRNA. Here, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids (containing cfRNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework (MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cfRNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cfRNA in serum from patients with liver cancer was described and a cfRNA signature with six cfRNAs was identified to diagnose liver cancer with high diagnostic efficiency (area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.

High-throughput identification of meat ingredients in adulterated foods based on centrifugal integrated purification-CRISPR array.

Rapid, accurate, and sensitive analytical methods for the detection of food fraud are now an urgent requirement in the global food industry to ensure food quality. In response to this demand, a centrifugal integrated purification-CRISPR array for meat adulteration (CIPAM) was established. In detail, CIPAM system combines microneedles for DNA extraction and RAA-CRISPR/Cas12a integrated into a centrifugal microfluidic chip for the detection of meat adulteration. The RAA-CRISPR/Cas12a reaction reagents were pre-embedded into the different reaction chambers on the microfluidic chip to achieve the streamline of operations, markedly simplifying the detection process. The whole reaction was completed within 30 min with a detection limit of 0.1 % (w/w) in pig, chicken, duck, and lamb products. Referring to the results of the standard method, CIPAM system achieved 100 % accuracy. The automatic multiplex detection process implemented in the developed CIPAM system met the needs of food regulatory authorities.

AEBP1 promotes papillary thyroid cancer progression by activating BMP4 signaling.

Papillary thyroid cancer (PTC) is the most prevalent endocrine cancer worldwide. Approximately 30 % of PTC patients will progress into the advanced or metastatic stage and have a relatively poor prognosis. It is well known that epithelial-mesenchymal transition (EMT) plays a pivotal role in thyroid cancer metastasis, resistance to therapy, and recurrence. Clarifying the molecular mechanisms of EMT in PTC progression will help develop the targeted therapy of PTC. The aberrant expression of some transcription factors (TFs) participated in many pathological processes of cancers including EMT. In this study, by performing bioinformatics analysis, adipocyte enhancer-binding protein 1 (AEBP1) was screened as a pivotal TF that promoted EMT and tumor progression in PTC. In vitro experiments indicated that knockout of AEBP1 can inhibit the growth and invasion of PTC cells and reduce the expression of EMT markers including N-cadherin, TWIST1, and ZEB2. In the xenograft model, knockout of AEBP1 inhibited the growth and lung metastasis of PTC cells. By performing RNA-sequencing, dual-luciferase reporter assay, and chromatin immunoprecipitation assay, Bone morphogenetic protein 4 (BMP4) was identified as a downstream target of AEBP1. Over-expression of BMP4 can rescue the inhibitory effects of AEBP1 knockout on the growth, invasion, and EMT phenotype of PTC cells. In conclusion, these findings demonstrated that AEBP1 plays a critical role in PTC progression by regulating BMP4 expression and the AEBP1-BMP4 axis may present novel therapeutic targets for PTC treatment.

Characterizing Genetic Alterations Related to Radioiodine Avidity in Metastatic Thyroid Cancer.

CONTEXT: Patients with differentiated thyroid cancer (DTC) with distant metastasis (DM) are usually not recognized as radioactive iodine (RAI)-refractory DTC in a timely manner. The elucidation of genetic features related to RAI uptake patterns may shed light on the early recognition of RAI-refractory DTC. OBJECTIVE: This work aimed to elucidate the underlying molecular features behind different RAI uptake patterns. METHODS: A total of 214 patients with DM-DTC were retrospectively included in the analysis. RAI uptake patterns were defined as initially RAI refractory (I-RAIR) and initially RAI avid (I-RAIA) according to the first post-treatment scan, then I-RAIA was further divided into continually RAIA (C-RAIA), partly RAIR (P-RAIR), and gradually RAIR (G-RAIR) according to subsequent scans. The molecular subtype groups-BRAFV600E mutated, RAS mutated, fusions, and others-were classified according to main driver genes status. RESULTS: BRAF, TERT promoter, and TP53 mutations are more frequently detected in the I-RAIR pattern while RET fusions and RAS mutations are more frequent in the I-RAIA pattern. A late-hit mutation including TERT, TP53, or PIK3CA is more common in I-RAIR than that in I-RAIA (50.0% vs 26.9%, P = .001), particularly for those with RAS mutations in the I-RAIR group, always accompanied by TERT promoter. Isolated RET fusions accounts for 10% of I-RAIR. When compared among driver gene groups, BRAFV600E-mutated tumors have a higher rate of the I-RAIR pattern (64.4%) than RAS-mutated (4.5%, P < .001) and fusion-positive (20.7%, P < .001) tumors. In I-RAIA subgroups, BRAFV600E-mutated tumors have lower prevalence of the C-RAIA pattern than those with RAS mutation or fusions. CONCLUSION: Patients with the I-RAIR pattern predominantly featured mutations of the BRAF and/or TERT promoter, of which RAS mutations were usually accompanied by late-hit mutations, while fusions mostly occurred alone.

Fusion Oncogenes in Patients With Locally Advanced or Distant Metastatic Differentiated Thyroid Cancer.

CONTEXT: Fusion oncogenes are involved in the underlying pathology of advanced differentiated thyroid cancer (DTC), and even the cause of radioactive iodine (RAI)-refractoriness. OBJECTIVE: We aimed to investigation between fusion oncogenes and clinicopathological characteristics involving a large-scale cohort of patients with advanced DTC. METHODS: We collected 278 tumor samples from patients with locally advanced (N1b or T4) or distant metastatic DTC. Targeted next-generation sequencing with a 26-gene ThyroLead panel was performed on these samples. RESULTS: Fusion oncogenes accounted for 29.86% of the samples (72 rearrangement during transfection (RET) fusions, 7 neurotrophic tropomyosin receptor kinase (NTRK) fusions, 4 anaplastic lymphoma kinase (ALK) fusions) and occurred more frequently in pediatric patients than in their adult counterparts (P = .003, OR 2.411, 95% CI 1.329-4.311) in our cohort. DTCs with fusion oncogenes appeared to have a more advanced American Joint Committee on Cancer (AJCC)_N and AJCC_M stage (P = .0002, OR 15.47, 95% CI 2.54-160.9, and P = .016, OR 2.35, 95% CI 1.18-4.81) than those without. DTCs with fusion oncogenes were associated with pediatric radioactive iodine (RAI) refractoriness compared with those without fusion oncogenes (P = .017, OR 4.85, 95% CI 1.29-15.19). However, in adult DTCs, those with fusion oncogenes were less likely to be associated with RAI refractoriness than those without (P = .029, OR 0.50, 95% CI 0.27-0.95), owing to a high occurrence of the TERT mutation, which was the most prominent genetic risk factor for RAI refractoriness in multivariate logistic regression analysis (P < .001, OR 7.36, 95% CI 3.14-17.27). CONCLUSION: Fusion oncogenes were more prevalent in pediatric DTCs than in their adult counterparts and were associated with pediatric RAI refractoriness, while in adult DTCs, TERT mutation was the dominant genetic contributor to RAI refractoriness rather than fusion oncogenes.

The role of peroxisome proliferator-activated receptors in the regulation of bile acid metabolism.

Bile acids are synthesized from cholesterol in the liver. Dysregulation of bile acid homeostasis, characterized by excessive accumulation in the liver, gallbladder and blood, can lead to hepatocellular damage and the development of cholestatic liver disease. Nuclear receptors play a crucial role in the control of bile acid metabolism by efficiently regulating bile acid synthesis and transport in the liver. Among these receptors, peroxisome proliferator-activated receptor (PPAR), a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily, controls the expression of genes involved in adipogenesis, lipid metabolism, inflammation and glucose homeostasis and has emerged as a potential therapeutic target for the treatment of the metabolic syndrome in the past two decades. Emerging evidence suggests that PPAR activation holds promise as a therapeutic target for cholestatic liver disease, as it affects both bile acid production and transport. This review provides a comprehensive overview of recent advances in elucidating the role of PPAR in the regulation of bile acid metabolism, highlighting the current position of PPAR agonists in the treatment of primary biliary cholangitis. By summarizing the specific regulatory effects of PPAR on bile acids, this review contributes to the exploration of novel therapeutic strategies for cholestatic liver diseases.

Revolutionizing early-stage green tide monitoring: eDNA metabarcoding insights into Ulva prolifera and microecology in the South Yellow Sea.

Green tides, characterized by excessive Ulva prolifera blooms, pose significant ecological and economic challenges, especially in the South Yellow Sea. We successfully employed 18S environmental DNA (eDNA) metabarcoding to detect Ulva prolifera micropropagules, confirming the technique's reliability and introducing a rapid green tide monitoring method. Our investigation revealed notable disparities in the eukaryotic microbial community composition within Ulva prolifera habitats across different regions. Particularly, during the early stages of the South Yellow Sea green tide outbreak, potential interactions emerged between Ulva prolifera micropropagules and certain previously undocumented microorganisms from neighboring waters. These findings enhance our comprehension of early-stage green tide ecosystem dynamics, underscoring the value of merging advanced molecular techniques with conventional ecological methods to gain a comprehensive understanding of the impact of green tide on the local ecosystem. Overall, our study advances our understanding of green tide dynamics, offering novel avenues for control, ecological restoration, and essential scientific support for sustainable marine conservation and management.

Mulberry leaf supplementation inhibits skatole deposition by regulating gut microbiota and upregulating liver cytochrome P450 1A1 expression in finishing pigs.

Skatole, a strong fecal odor substance, is generated through microbial degradation of tryptophan in the animal hindgut. It easily accumulates in adipose tissue and affects meat quality. In this study, the effect of mulberry leaf supplementation on skatole in finishing pigs was studied. In a 35-day trial, 20 finishing pigs (barrows and gilts) were fed with a basal diet or basal diet with 6% mulberry leaves. Growth performance of the pigs (n = 10) was automatically recorded by a performance-testing feeder system and 8 pigs in each treatment were slaughtered and sampled for the remaining tests. Skatole and short-chain fatty acids were detected using HPLC and gas chromatography, respectively. Fecal microbiota were analyzed using 16S rRNA gene sequencing. The metabolomics analysis of feces and serum was performed with UHPLC-MS/MS. The major cytochrome P450 (CYP) enzymes that catalyze skatole degradation in the liver were tested by using RT-PCR and Western blot. Effects of major bioactive compounds in mulberry leaves on the CYP genes were verified in the hepatic cell line HepG2 in an in vitro test (n = 3). In finishing pigs, mulberry leaf supplementation had no significant effect on the average daily gain, average daily feed intake, and feed conversion ratio (P > 0.05), but reduced skatole levels in feces, serum, and backfat (P < 0.05), and increased acetic acid levels in feces (P = 0.027). Mulberry leaf supplementation decreased the relative abundance of the skatole-producing bacteria Megasphaera and Olsenella (P < 0.05). Indole-3-acetic acid, the intermediate that is essential for skatole production, was significantly reduced in feces by mulberry leaf supplementation (P < 0.05) and was positively correlated with skatole content in feces (P = 0.004). In pigs treated with mulberry leaves, liver CYP1A1 expression was increased (P < 0.05) and was negatively correlated with skatole content in backfat (P = 0.045). The in vitro test demonstrated that mulberry leaf polyphenols and polysaccharides could directly stimulate CYP1A1 expression in hepatic cells. These findings suggest that mulberry leaf supplementation reduces skatole production and deposition in finishing pigs by regulating the gut microbiota and promoting skatole degradation in liver.