A new strategy of using low-dose caffeic acid carbon nanodots for high resistance to poorly differentiated human papillary thyroid cancer.

Thyroid cancer is one of the most common endocrine malignancies in clinical practice. Traditional surgery and radioactive iodine ablation have poor treatment results for poorly differentiated thyroid cancer, and there is a risk of metastasis and recurrence. In this study, caffeic acid, a natural herbal extract with certain biological activity, has been as precursor to prepare new caffeic acid carbon nanodots via a one-step hydrothermal method. The caffeic acid carbon nanodots retains part of the structure and biological activity of caffeic acid, and have good biocompatibility, water solubility and stability. The construction of the carbon nanodots could effectively improve their bio-absorption rate and the efficacy. In vitro cell experiments showed that low-dose caffeic acid carbon nanodots had a significant inhibitory effect on poorly differentiated papillary thyroid carcinoma BCPAP cells. At low concentrations of 16 µg/mL, the inhibition rate of human thyroid cancer cells BCPAP was ~ 79%. The anti-tumor mechanism was predicted and verified by transcriptome, real-time quantitative PCR and western blot experiments. The caffeic acid carbon nanodots showed to simultaneously downregulate the expression of KRAS, p-BRAF, p-MEK1 and p-ERK1/2, the four continuous key proteins in a MAPK classical signaling pathway. In vivo experiments further confirmed the caffeic acid carbon nanodots could significantly inhibit the tumorigenicity of xenografts in papillary thyroid carcinoma at quite low doses. This piece of work provides a new nanomedicine and therapeutic strategy for highly resistant poorly differentiated papillary thyroid carcinoma.

Using multi-omics to explore the genetic causal relationship between colorectal cancer and heart failure in gastrointestinal tumors.

Background: Heart failure (HF) and colorectal cancer are significant public health concerns with substantial morbidity and mortality. Previous studies have indicated a close association between HF and various tumors, including colorectal cancer. Further understanding the potential causal relationship between them could provide insights into their shared pathophysiological mechanisms and inform strategies for prevention and treatment. Methods: This study employed a bidirectional Mendelian randomization (MR) approach using genetic variants from large genome-wide association studies (GWAS) as instrumental variables (IVs). The inverse-variance weighted (IVW) method was employed for the MR analysis. Meta-analyses of IVW results from discovery and validation cohorts were performed to enhance the power of detecting causal effects. Sensitivity analyses, including heterogeneity analysis and tests for horizontal pleiotropy, were conducted to test the robustness of the conclusions. Results: Results from the discovery cohort suggest HF is associated with an approximately 30% increased risk of colorectal cancer (OR 1.32, 95% CI 1.03-1.69, P=0.025), although this finding did not reach statistical significance in the validation cohort (OR 1.19, 95% CI 0.97-1.46, P=0.090). However, meta-analysis supports HF as a potential risk factor for colorectal cancer (Pooled OR 1.24, 95% CI 1.06-1.25, P=0.007). Reverse MR analysis found no evidence of colorectal cancer increasing HF risk (Pooled OR 1.03, 95% CI 0.99-1.07, P=0.121). Sensitivity analyses (all P>0.05) indicate robustness against heterogeneity and horizontal pleiotropy. Conclusion: This comprehensive bidirectional MR study provides genetic evidence supporting a causal link between HF and colorectal cancer. The insights gained enhance understanding of their interconnectedness and may guide future research and clinical practices aimed at mitigating their risks through targeted interventions.

Growth characteristics of early-stage (IA) lung adenocarcinoma and its value in predicting lymph node metastasis.

BACKGROUND: We aim to compare the differences in growth characteristics between part-solid and solid lung adenocarcinoma, and to investigate the value of volume doubling time (VDT) or mass doubling time (MDT) in predicting lymph node (LN) metastasis and preoperative evaluation in patients of early-stage (IA) non-small cell lung cancer (NSCLC). METHOD: We reviewed 8,653 cases of surgically resected stage IA lung adenocarcinoma between 2018 and 2022, with two follow-up visits at least 3 months apart, comparing diameter, volume, and mass growth of pSN and SN. VDT and MDT calculations for nodules with a volume change of at least 25%. Univariable or multivariable analysis was used to identify the risk factors. The area under the curve (AUC) for the receiver operating characteristic (ROC) curves was used to evaluate the diagnostic value. RESULTS: A total of 144 patients were included 114 with solid nodules (SN) and 25 with part-solid nodules (pSN). During the follow-up period, the mean VDTt and MDTt of SN were shorter than those of pSN, 337 vs. 541 days (p = 0.005), 298 vs. 458 days (p = 0.018), respectively. Without considering the ground-glass component, the mean VDTc and MDTc of SN were shorter than the solid component of pSN, 337 vs. 498 days (p = 0.004) and 298 vs. 453 days (p = 0.003), respectively. 27 nodules were clinically and pathologically diagnosed as N1/N2. Logistic regression identified initial diameter (p < 0.001), consolidation increase (p = 0.019), volume increase (p = 0.020), mass increase (p = 0.021), VDTt (p = 0.002), and MDTt (p = 0.004) were independent factors for LN metastasis. The ROC curves showed that the AUC for VDTt was 0.860 (95% CI, 0.778-0.943; p < 0.001) and for MDTt was 0.848 (95% CI, 0.759-0.936; p < 0.001). CONCLUSIONS: Our study showed significant differences in the growth characteristics of pSN and SN, and the application of VDT and MDT could be a valid predictor LN metastasis in patients with early-stage NSCLC.

Proposal of Modified Lung-RADS in Assessing Pulmonary Nodules of Patients with Previous Malignancies: A Primary Study.

BACKGROUND: In addition to the diameters of pulmonary nodules, the number and morphology of blood vessels in pure ground-glass nodules (pGGNs) were closely related to the occurrence of lung cancer. Moreover, the benign and malignant signs of nodules were also valuable for the identification of nodules. Based on these two points, we tried to revise Lung-RADS 2022 and proposed our Modified Lung-RADS. The aim of the study was to verify the diagnostic performance of Modified Lung-RADS for pulmonary solid nodules (SNs) and pure ground-glass nodules (pGGNs) in patients with previous malignancies. METHODS: The chest CT and clinical data of patients with prior cancer who underwent pulmonary nodulectomies from 1 January 2018 to 30 November 2021 were enrolled according to inclusion and exclusion criteria. A total of 240 patients with 293 pulmonary nodules were included in this study. In contrast with the original version, the risk classification of pGGNs based on the GGN-vascular relationships (GVRs), and the SNs without burrs and with benign signs, could be downgraded to category 2. The sensitivity, specificity, and agreement rate of the original Lung-RADS 2022 and Modified Lung-RADS for pGGNs and SNs were calculated and compared. RESULTS: Compared with the original version, the sensitivity and agreement rate of the Modified version for pGGNs increased from 0 and 23.33% to 97.10% and 92.22%, respectively, while the specificity decreased from 100% to 76.19%. As regards SNs, the specificity and agreement rate of the Modified version increased from 44.44% to 75.00% (p < 0.05) and 88.67% to 94.09% (p = 0.052), respectively, while the sensitivity was unchanged (98.20%). CONCLUSIONS: In general, the diagnostic efficiency of Modified Lung-RADS was superior to that of the original version, and Modified Lung-RADS could be a preliminary attempt to improve Lung-RADS 2022.

The influence of different previous cancer histories on the diagnostic efficacy of Lung Imaging Reporting and Data System.

Background: For lung cancer screening in patients with previous malignant tumors, Lung Imaging Reporting and Data System (Lung-RADS) and other lung cancer screening tools are controversial in terms of requirements for the previous cancer history. This study investigated the effect of the length and type of malignancy history on the diagnostic efficacy of Lung Imaging Reporting and Data System (Lung-RADS) 2022 in pulmonary nodules (PNs). Methods: Chest computed tomography and clinical data of PNs in patients with a history of cancer who underwent surgical resection in The First Affiliated Hospital of Chongqing Medical University from January 1, 2018, to November 30, 2021, were retrospectively collected and evaluated based on Lung-RADS. All PNs were divided into 2 groups: the prior lung cancer (PLC) and the prior extrapulmonary cancer (PEPC) groups. Each group was divided into the ≥5 years and <5 years groups based on the duration of cancer history. The diagnostic agreement of Lung-RADS was evaluated based on the pathological diagnosis of nodules after operation. The diagnostic agreement rate (AR) of Lung-RADS and the composition ratios of different types between different groups were calculated and compared. Results: A total of 451 patients with 565 PNs were included in this study. These patients were divided into the PLC group (<5 years: 135 cases, 175 PNs; ≥5 years: 9 cases, 12 PNs) and the PEPC group (<5 years: 219 cases, 278 PNs; ≥5 years: 88 cases, 100 PNs). The diagnostic AR of partial solid nodules (93.0%; 95% CI: 88.7-97.2%) and solid nodules (88.1%; 95% CI: 84.1-92.1%) was close (P=0.13), while both were higher than that of the pure ground-glass nodules (24.0%; 95% CI: 17.5-30.4%; all P values <0.001). Within 5 years, the composition ratio of PNs and the diagnostic AR (PLC: 58.9%, 95% CI: 51.5-66.2%; PEPC: 76.6%, 95% CI: 71.6-81.6%) between the PLC and PEPC groups were all different (all P values <0.001), and the others [composition ratio of PNs & the diagnostic AR: PLC (≥5 years) vs. PEPC (≥5 years); PLC (<5 years) vs. PLC (≥5 years); PEPC (<5 years) vs. PEPC (≥5 years)] were similar (all P values >0.05; range: 0.10-0.93). Conclusions: The length of prior cancer history may affect the diagnostic agreement of Lung-RADS, especially for patients with prior lung cancer within 5 years.

Correlations Between Inflammatory Cell Infiltration and Relative Density and the Boundary Manifestation of Pulmonary Non-Neoplastic Ground Glass Nodules.

Purpose: To investigate the influence factors for the various boundary manifestations of pulmonary non-neoplastic ground glass nodules (GGNs) on computed tomography (CT). Materials and Methods: From January 2015 to March 2022, a total of 280 patients with 318 non-neoplastic GGNs were enrolled. The correlations between degree of inflammatory cell infiltration and relative density (ΔCT) and the boundary manifestations of lesions were evaluated, respectively. Results: Nongranulomatous nodules (283, 89.0%) with fibrous tissue proliferation and/or inflammatory cells as the predominant pathological findings were the most common non-neoplastic GGNs, followed by granulomatous nodules (28, 8.8%). Among nongranulomatous GGNs, cases with more and less/no inflammatory cells were 15 (10.9%) and 122 (89.1%) in 137 well-defined ones with smooth margin, 16 (24.6%) and 49 (75.4%) in 65 well-defined ones with coarse margin, 43 (91.5%) and 4 (8.5%) in 47 ill-defined ones with higher ΔCT (>151HU), and 4 (11.8%) and 30 (88.2%) in 34 ill-defined ones with lower ΔCT (< 151HU). The proportion of cases with more inflammatory cells in well-defined nodules was similar to that in ill-defined ones with lower ΔCT (P = 0.587) but significantly lower than that in ill-defined ones with higher ΔCT (P < 0.001). Among the granulomatous nodules, ill-defined cases with higher ΔCT (16, 57.1%) were the most common, and they (7/8, 87.5%) frequently had changes during short-term follow-up. Conclusion: Nongranulomatous nodules are the most common non-neoplastic GGNs, their diverse boundary manifestations closely correlate with degree of inflammatory cell infiltration and density difference.

Multiple caleosins have overlapping functions in oil accumulation and embryo development.

Caleosins are lipid droplet- and endoplasmic reticulum-associated proteins. To investigate their functions in oil accumulation, expression levels of caleosins in developing seeds of Arabidopsis thaliana were examined and four seed-expressed caleosins (CLO1, CLO2, CLO4, and CLO6) were identified. The four single mutants showed similar minor changes of fatty acid composition in seeds. Two double mutants (clo1 clo2 and clo1×clo2) demonstrated distinct changes of fatty acid composition, a 16-23% decrease of oil content, and a 10-13% decrease of seed weight. Moreover, a 40% decrease of oil content, further fatty acid changes, and misshapen membranes of smaller lipid droplets were found in seeds of quadruple CLO RNAi lines. Notably, ~40% of quadruple CLO RNAi T1 seeds failed to germinate, and deformed embryos and seedlings were also observed. Complementation experiments showed that CLO1 rescued the phenotype of clo1 clo2. Overexpression of CLO1 in seedlings and BY2 cells increased triacylglycerol content up to 73.6%. Transcriptome analysis of clo1 clo2 developing seeds showed that expression levels of some genes related to lipid, embryo development, calcium signaling, and stress responses were affected. Together, these results suggest that the major seed-expressed caleosins have overlapping functions in oil accumulation and show pleiotropic effects on embryo development.

ABA-INSENSITIVE 3 with or without FUSCA3 highly up-regulates lipid droplet proteins and activates oil accumulation.

ABA-INSENSITIVE 3 (ABI3) has long been known for activation of storage protein accumulation. A role of ABI3 on oil accumulation was previously suggested based on a decrease of oil content in seeds of abi3 mutant. However, this conclusion could not exclude possibilities of indirect or pleiotropic effects, such as through mutual regulatory interactions with FUSCA3 (FUS3), an activator of oil accumulation. To identify that ABI3 functions independent of the effects of related seed transcription factors, we expressed ABI3 under the control of an inducible promoter in tobacco BY2 cells and Arabidopsis rosette leaves. Inducible expression of ABI3 activated oil accumulation in these non-seed cells, demonstrating a general role of ABI3 in regulation of oil biosynthesis. Further expressing ABI3 in rosette leaves of fus3 knockout mutant still caused up to 3-fold greater triacylglycerol accumulation, indicating ABI3 can activate lipid accumulation independently of FUS3. Transcriptome analysis revealed that LIPID DROPLET PROTEIN (LDP) genes, including OLEOSINs and CALEOSINs, were up-regulated up to 1000-fold by ABI3 in the absence of FUS3, while the expression of WRINKLED1 was doubled. Taken together, our results provide genetic evidence that ABI3 activates oil accumulation with or without FUS3, most likely through up-regulating LDPs and WRINKLED1.

1,8-cineole alleviates bisphenol A-induced apoptosis and necroptosis in bursa of Fabricius in chicken through regulating oxidative stress and PI3K/AKT pathway.

Bisphenol A (BPA), an important chemical raw material, is now a ubiquitous environmental contaminant. As an endocrine disruptor similar to estrogen, BPA increases the risk of various metabolic and chronic diseases. BPA has immunotoxicity to humans and animals. 1,8-cineole (CIN) is a plant-derived monoterpene with antioxidant and antiapoptosis actions. However, there are no reports about whether CIN could antagonize the BPA-induced apoptosis and necroptosis in bursa of Fabricius (BF) of chicken. This study was to elucidate the ameliorative mechanism of CIN on the apoptosis and necroptosis in BF induced by BPA. 120 broilers (1-day-old) were randomly divided into four groups: control group, CIN group, CIN and BPA co-treatment group, and BPA group. TUNEL analysis results, histopathological variations, and the overexpression of proapoptosis biomakers (Caspase 3, Bax, Cyt-c, and p53) and necroptosis pathway-related factors (RIPK1, RIPK3, MLKL, and FADD) indicated that BPA exposure induced the apoptosis and necroptosis in chicken BF. Moreover, BPA treatment elevated the levels of oxidative stress indexes (MDA, iNOS, and NO) and weaken antioxidases activity (SOD, GPx, and CAT) and total antioxidant capacity in chicken BF. BPA administration also lessened the expression of PI3K and AKT and promoted HSPs (HSP27, HSP40, HSP60, and HSP70) activation. whereas CIN supplementation prominently mitigated BPA-caused these changes and the apoptosis and necroptosis damages. In brief, this study illuminated that CIN could protect the chicken BF against BPA-induced apoptosis and necroptosis through restraining oxidative stress and activating PI3K/AKT pathway.

WRINKLED1 homologs highly and functionally express in oil-rich endosperms of oat and castor.

Oat (Avena sativa) and castor (Ricinus communis) accumulate a large amount of lipids in their endosperms, however the molecular mechanism remains unknown. In this study, differences in oil regulators between oat and wheat (Triticum aestivum) as well as common features between oat and castor were tested by analyzing their transcriptomes with further q-PCR analysis. Results indicated that WRINKLED1 (WRI1) homologs and their target genes highly expressed in the endosperms of oat and castor, but not in the starchy endosperms of wheat. Expression pattern of WRI1s was in agreement with that of oil accumulation. Three AsWRI1s (AsWRI1a, AsWRI1b and AsWRI1c) and one RcWRI1 were identified in the endosperms of oat and castor, respectively. AsWRI1c lacks VYL motif, which is different from the other three WRI1s. Expressions of these four WRI1s all complemented the phenotypes of Arabidopsis wri1-1 mutant. Overexpression of these WRI1s in Arabidopsis and tobacco BY2 cells increased oil contents of seeds and total fatty acids of the cells, respectively. Moreover, this overexpression also resulted in up-regulations of WRI1 target genes, such as PKp-ß1. Taken together, our results suggest that high and functional expression of WRI1 play a key role in the oil-rich endosperms and the VYL motif is dispensable for WRI1 function.

The Effect of Interleukin 38 on Inflammation-induced Corneal Neovascularization.

BACKGROUND: Angiogenesis is tightly linked to inflammation. Cytokines of interleukin 1 (IL-1) family are key mediators in modulating inflammatory responses. METHODS: In this study, we examined the role of IL-38, a member of the IL-1 family, in mediating inflammation-induced angiogenesis. RESULTS: The results showed that the angiogenesis was attenuated by topical administration of IL-38 to the injured corneas in a mouse model of alkali-induced corneal neovascularization (CNV). Further study showed that the expression of inflammatory cytokines TNF-α, IL-6, IL-8 and IL-1ß was decreased in the IL-38-treated corneas. Moreover, the angiogenic activities including the proliferation, migration and tube formation of human retinal endothelial cells were reduced by IL-38 treatment in vitro. CONCLUSION: The data indicate that IL-38 modulates inflammation-induced angiogenesis.

Investigation of Plant Species with Identified Seed Oil Fatty Acids in Chinese Literature and Analysis of Five Unsurveyed Chinese Endemic Species.

Diverse fatty acid structures from different plant species are important renewable resources for industrial raw materials and as liquid fuels with high energy density. Because of its immense geographical and topographical variations, China is a country with enormous diversity of plant species, including large numbers of plants endemic to China. The richness of this resource of species provides a wide range of fatty acids in seeds or other tissues, many of which have been identified by Chinese scientists. However, in the past, most publications describing analysis of these plants were written in Chinese, making access for researchers from other countries difficult. In this study, we investigated reports on seed and fruit oil fatty acids as described in Chinese literature. Six books and more than one thousand papers were collected and the identified fatty acids and relevant plant species were summarized. In total, about 240 fatty acids from almost 1,500 plant species were identified from available Chinese literature. Only about one third of these species were retrieved in the PhyloFAdb and SOFA online databases of plant fatty acids. By referring to a summary of plant species endemic to China, 277 Chinese endemic species from 68 families have been surveyed for seed fatty acids. These account for <2% of total Angiosperm species endemic to China indicating the scope of species yet to be surveyed. To discover additional new fatty acid structures that might benefit society, it is important in the future to study oilseed fatty acids of the many other Chinese endemic plants. As an example, seeds of five unsurveyed species were collected and their fatty acids were analyzed. Ricinoleic acid was detected for the first time in the Salicaceae family.

Disruption of secondary wall cellulose biosynthesis alters cadmium translocation and tolerance in rice plants.

Tricheary elements (TEs), wrapped by secondary cell wall, play essential roles in water, mineral, and nutrient transduction. Cadmium (Cd) is a toxic heavy metal that is absorbed by roots and transported to shoot, leaves, and grains through vascular systems in plants. As rice is a major source of Cd intake, many efforts have been made to establish 'low-Cd rice'. However, no links have been found between cellulose biosynthesis and cadmium accumulation. We report here a rice brittle culm13 mutant, resulting from a novel missense mutation (E101K) [corrected] in the N-terminus of cellulose synthase subunit 9 (CESA9). Except for the abnormal mechanical strength, the mutant plants are morphologically indistinguishable from the wild-type plants. Transmission electron microscopy (TEM) and chemical analyses showed a slight reduction in secondary wall thickness and 22% decrease in cellulose content in bc13 plants. Moreover, this mutation unexpectedly confers the mutant plants Cd tolerance due to less Cd accumulation in leaves. Expression analysis of the genes required for Cd uptake and transport revealed complicated alterations after applying Cd to wild-type and bc13. The mutants were further found to have altered vascular structure. More importantly, Cd concentration in the xylem saps from the bc13 plants was significantly lower than that from the wild-type. Combining the analyses of CESA9 gene expression and Cd content retention in the cell-wall residues, we conclude that CESA9(E101K) [corrected] mutation alters cell-wall properties in the conducting tissues, which consequently affects Cd translocation efficiency that largely contributes to the low Cd accumulation in the mutant plants.