Development and validation of a stromal-immune signature to predict prognosis in intrahepatic cholangiocarcinoma.

BACKGROUNDS/AIMS: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. METHODS: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. RESULTS: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. CONCLUSION: We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Identification of mechanism of the oncogenic role of FGFR1 in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the thyroid. Fibroblast growth factor receptor 1 (FGFR1) is highly expressed in PTC and works as an oncogenic protein in this disease. In this report, we wanted to uncover a new mechanism that drives overexpression of FGFR1 in PTC. Analysis of FGFR1 expression in clinical specimens and PTC cells revealed that FGFR1 expression was enhanced in PTC. Using siRNA/shRNA silencing experiments, we found that FGFR1 downregulation impeded PTC cell growth, invasion, and migration and promoted apoptosis in vitro, as well as suppressed tumor growth in vivo. Bioinformatic analyses predicted the potential USP7-FGFR1 interplay and the potential binding between YY1 and the FGFR1 promoter. The mechanism study found that USP7 stabilized FGFR1 protein via deubiquitination, and YY1 could promote the transcription of FGFR1. Our rescue experiments showed that FGFR1 re-expression had a counteracting effect on USP7 downregulation-imposed in vitro alterations of cell functions and in vivo suppression of xenograft growth. In conclusion, our study identifies the deubiquitinating enzyme USP7 and the oncogenic transcription factor YY1 as potent inducers of FGFR1 overexpression. Designing inhibitors targeting FGFR1 or its upstream inducers USP7 and YY1 may be foreseen as a promising strategy to control PTC development.

Distribution, risk evaluation, and source allocation of cesium and strontium in surface soil in a mining city.

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.

Seasonal dynamics of the microbiota and nutritional composition in bee bread from Apis cerana and Apis mellifera colonies.

Bee bread is a product of honeybees, which collect and ferment pollen, that contains highly nutritious and easily digestible active substances. However, its nutritional composition varies significantly with fermentation strains and seasonal changes. To unveil the patterns of microbial community and nutritional component changes in bee bread across seasons, we employed high-throughput techniques to assess the diversity of bacteria and fungi in bee bread. The results indicated that the compositions of bacteria and fungi in bee bread undergo significant seasonal variation, with noticeable changes in the microbial diversity of bee bread from different bee species. Subsequently, metabolomic analysis revealed high activity of glycerophospholipid metabolism in bee bread. Furthermore, our analysis identifaied noteworthy differences in nutritional components, including pH values, sugar content, and free amino acid levels, in bee bread across different seasons.

CRISPR/Cas9-mediated ebony knockout causes melanin pigmentation and prevents moth Eclosion in Ectropis grisescens.

Ectropis grisescens (Lepidoptera: Geometridae) is a destructive tea pest in China. Mimesis, characterized by changing body color, is an important trait of E. grisescens larvae. Hence, identifying melanin pathway-related genes may contribute to developing new pest control strategies. In the present study, we cloned Egebony, a gene potentially involved in melanin pigmentation in E. grisescens, and subsequently conducted CRISPR/Cas9-mediated targeted mutagenesis of Egebony to analyze its role in pigmentation and development. At the larvae, prepupae, and pupae stages, Egebony-knockout individuals exhibited darker pigmentation than the wild-type. However, Egebony knockout did not impact the colors of sclerotized appendants, including ocelli, setae, and claws. While mutant pupae could successfully develop into moths, they were unable to emerge from the puparium. Notably, embryo hatchability and larval survival of mutants remained normal. Further investigation indicated that mutant pupae exhibited significantly stronger shearing force than the wild-type, with the pigmented layer of mutant pupae appearing darker and thicker. Collectively, these results suggest that the loss of Egebony might increase the rigidity of the puparium and prevent moth eclosion. This study provides new insights into understanding the function and diversification of ebony in insect development and identifies a lethal gene that can be manipulated for developing effective pest control strategies.

Role of sodium/iodide symporter overexpression in inhibiting thyroid cancer cell invasion and stem cell maintenance by inhibiting the ß-catenin/LEF-1 pathway.

Background: In thyroid cancers, a reduction in the expression of the sodium/iodide symporter (NIS) is observed concomitant with a diminution in cancer cell differentiation. The ß-catenin/LEF-1 pathway emerges as a crucial regulatory pathway influencing the functional expression of NIS in human thyroid cancer cells. Further research is required to comprehensively elucidate the role of NIS overexpression in impeding the progression of thyroid cancer cells. Methods: Human papillary thyroid carcinoma (PTC) cell lines, specifically PTC-1 and KTC-1, were subjected to Scratch and Transwell assays, colony formation, and tumor sphere formation tests to investigate invasion and migration, focusing on the impact of NIS overexpression. The assessment involved the use of western blot to analyze the expression levels of ß-catenin, NIS, CD133, SRY-related HMG box2 (Sox2), lymphoid enhancer-binding factor 1 (LEF-1), NANOG, octamer-binding transcription factor 4 (Oct4), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), and epithelial cellular adhesion molecule (EpCAM). Statistical analysis was conducted using SPSS version 20.0, and the graphs were developed using GraphPad Prism 7 (GraphPad Software, Inc.). Results: Our observations revealed that Nthy-ori-3-1 cell lines exhibited notably higher average expression levels of NIS, yet significantly lower levels of LEF-1 and ß-catenin compared to PTC-1 and KTC-1 cell lines. Furthermore, the overexpression of ß-catenin resulted in reduced binding of LEF-1 to NIF promotion but concurrently increased the expression of NIS. The downregulation of NIS markedly enhanced the expression of ALDH1A1, CD133, OCT4, Nanog, SOX2, and EpCam-all of which are targets within the Wnt/ß-catenin signaling pathway. Conversely, the upregulation of NIS suppressed the expression of these proteins. Moreover, cells treated with ß-catenin activators demonstrated an increased capability to form more spheroids and displayed heightened aggressiveness. Conversely, the NIS overexpression (OE) group exhibited suppressed abilities in invasion and colony formation. Conclusion: Thyroid cancer cells exhibit diminished expression of NIS, and the invasion and maintenance of stem cells in thyroid cancer cells were hindered by NIS OE through the inhibition of the ß-catenin/LEF-1 pathway. Further research is warranted to comprehensively assess this outcome, which holds promise as a potential targeted treatment for thyroid cancer.

Uncovering the Importance of Ligand Mobility on Cellular Uptake of Nanoparticles: Insights from Experimental, Computational, and Theoretical Investigations.

The cellular uptake of nanoparticles (NPs) by biological cells is an important and fundamental process in drug delivery. Previous studies reveal that the physicochemical properties of nanoparticles as well as those of functionalized ligands can both critically affect the uptake behaviors. However, the effect of the conjugation strategy (i.e., the "bond" between the ligand and the NP) on the cellular uptake is overlooked and remains largely elusive. Here, by taking the broadly employed gold nanoparticle as an example, we comprehensively assessed the relationship between the conjugation strategy and uptake behaviors by introducing three ligands with the same functional terminal but different anchoring sites. As revealed by in vitro cell experiments and multiscale molecular simulations, the uptake efficiency of gold NPs was positively correlated with the strength of the "bond" and more specifically the ligand mobility on the NP surface. Moreover, we validated the results presented above by proposing a thermodynamic theory for the wrapping of NPs with mobile ligands. Further, we also showed that the endocytic pathway of NPs was highly dependent on ligand mobility. Overall, this study uncovered a vital role of conjugation strategy in the cellular uptake and may provide useful guidelines for tailoring the biobehaviors of nanoparticles.

Visible-Light-Driven NO Release from Postmodified MOFs via Photoinduced Electron Transfer for Antibacterial Application.

Photoresponsive nitric oxide (NO)-releasing materials (NORMs) enable the spatiotemporal delivery of NO to facilitate their potential applications in physiological conditions. Here two novel metal-organic frameworks (MOFs)-based photoactive NORMs achieved by the incorporation of prefunctionalized NO donors into the photosensitive Fe-MOFs via a postmodification strategy is reported. The modified Fe-MOFs display superior photoactivity of NO release when exposed to visible light (up to 720 nm). Significantly, the visible-light-driven NO release properties are further corroborated by their efficient antibacterial performance.

Gut microbiota-driven regulation of queen bee ovarian metabolism.

With the global prevalence of Varroa mites, more and more beekeepers resort to confining the queen bee in a queen cage to control mite infestation or to breed superior and robust queen bees. However, the impact of such practices on the queen bee remains largely unknown. Therefore, we subjected the queen bees to a 21-day egg-laying restriction treatment (from the egg stage to the emergence of adult worker bees) and analyzed the queen bees' ovarian metabolites and gut microbiota after 21 days, aiming to assess the queen bees' quality and assist beekeepers in better hive management. Our findings revealed a significant reduction in the relative expression levels of Vg and Hex110 genes in the ovaries of egg laying-restricted queen bees compared to unrestricted egg-laying queens. The diversity of gut microbiota in the queen bee exhibited a notable decrease, accompanied by corresponding changes in the core bacteria of the microbial community, the relative abundance of Lactobacillus and Bifidobacterium increased from 22.34% to 53.14% (P = 0.01) and from 0.053% to 0.580% (P = 0.04), respectively. The relative abundance of Bombella decreased from 25.85% to 1.720% (P = 0.002). Following egg-laying restriction, the activity of the queen bee's ovaries decreased, while the metabolism of glycerophospholipids remained or stored more lipid molecules, awaiting environmental changes for the queen bee to resume egg laying promptly. Furthermore, we observed that Bombella in the queen bee's gut may regulate the queen's ovarian metabolism through tryptophan metabolism. These findings provide novel insights into the interplay among queen egg laying, gut microbiota, and ovarian metabolism. IMPORTANCE With Varroa mite infestation, beekeepers often confine the queen bee in cages for control or breeding. However, the impact on the queen bee is largely unknown. We evaluated queen bee quality by restricting egg laying and analyzing ovarian metabolites and gut microbiota. In this study, we provided a comprehensive explanation of the expression of ovarian genes, the diversity of gut microbiota, and changes in ovarian metabolism in the queen bee. Through integrated analysis of the queen bee's gut microbiota and ovarian metabolism, we discovered that the gut microbiota can regulate the queen bee's ovarian metabolism. These findings provide valuable insights into the interplay among egg laying, gut microbiota, and the reproductive health of the queen bee. Understanding these relationships can contribute to the development of better strategies for Varroa mite control and queen bee breeding.

Vanadium mobilization and redistribution during mineral transformation of vanadium-titanium magnetite tailings with different weathering degrees.

Due to the long-term open stockpile, the release of vanadium (V) from V-containing tailings will cause continuous V pollution in the mining area. Previous studies on the concentration and speciation of V primarily focused on surface tailings at a regional scale. However, the mobilization and redistribution of V within the tailing profile during the mineral transformation of tailings remain unclear. Herein, a series of concentrations of V(V) (0-200 mg L-1) solutions were added to the vanadium­titanium magnetite tailings at different depths separately to simulate the redistribution of dissolved V released from tailings in the solid phase of tailings. During the 56-day incubation, the concentrations of aqueous V in the surface tailings were significantly lower than those in the deep tailings under the same level of V(V) treatment, indicating that the shallow tailings had a stronger immobilization capacity for V than the deep tailings. Morphological analysis and color overlays of the elements demonstrated that most of V was immobilized into the tailings and adsorbed or precipitated by the Fe (hydr)oxides in the tailings in 200 mg L-1 V(V) treatment. This portion of V mainly occurred in acid-soluble and reducible fractions in the tailings after a 7-day incubation, accounting for >71.7 % of the total V. However, these two factions of V with high bioavailability were gradually mineralized over time and transferred to residual V, which is difficult to move and has low bioavailability. Mineral phase analysis revealed that additional V(V) favored the formation of melanovanadite (Ca2V8O20·10H2O) and chromium vanadium oxide (Cr2V4O13) in the tailings. This study reveals that the dissolved V influenced the fractionation and redistribution of solid-phase V during tailing weathering, improving the understanding of the geochemical processes of V in tailing profiles and providing important guidance for the management of V-containing tailings.

Assessment of hepatic fat content and prediction of myocardial fibrosis in athletes by using proton density fat fraction sequence.

PURPOSE: To explore the characteristics of the hepatic fat content in athletes, and predict late gadolinium enhancement (LGE) based on magnetic resonance imaging-proton density fat fraction (MRI-PDFF). MATERIAL AND METHODS: From March 2020 to March 2021, 233 amateur athletes and 42 healthy sedentary controls were prospectively recruited. The liver fat content of four regions of interest (ROIs 1-4), the mean liver fat fraction (FF), cardiac function, and myocardium LGE were recorded, respectively. The values of ROIs 1-4 and FF were compared between athletes and controls. According to the liver fat content threshold for distinguishing athletes and controls, the cutoff total exercise time that induced a change in liver fat was obtained. The correlations among the liver fat content, cardiac function, and other parameters were analyzed. Moreover, the liver fat content was used to predict myocardium LGE by logistic regression. RESULTS: There were significant differences for the values of ROI 1, ROI 3, ROI 4, and FF between athletes and controls (allp< 0.05). The cutoff total exercise time for inducing a change in the liver fat content was 1680 h (area under the curve [AUC] = 0.593, specificity = 83.3,p< 0.05). Blood indexes, cardiac function, and basic clinical parameters were related to liver fat content (allp< 0.05). The prediction model for LGE had an AUC value of 0.829 for the receiver operator characteristic curve. CONCLUSION: MRI-PDFF could assess liver fat content and predict cardiac fibrosis in athletes for risk stratification and follow-up.

Nongenetic and genetic predictors of haemodynamic instability induced by propofol and opioids: A retrospective clinical study.

AIM: Propofol and opioids are commonly used in anaesthesia, but are highly susceptible to haemodynamic instability, thereby threatening the patient's surgical safety and prognosis. The purpose of this study was to investigate the predictors of haemodynamic instability and establish its predictive model. METHODS: A total of 150 Chinese patients undergoing thyroid or breast surgery participated in the study, with target-controlled infusion concentrations of propofol, opioids dosage, heart rate (HR), mean arterial pressure (MAP) and Narcotrend Index recorded at key points throughout the procedure. The Agena MassARRAY system was used to genotype candidate single nucleotide polymorphisms related to pharmacodynamics and pharmacokinetics of propofol and opioids. RESULTS: Among nongenetic factors, baseline HR (R = -.579, P < .001) and baseline MAP (R = -.725, P < .001) had a significant effect on the haemodynamic instability. Among genetic factors, the CT/CC genotype of GABRB1 rs4694846 (95% confidence interval [CI]: -11.309 to -3.155), AA/AG of OPRM1 rs1799971 (95%CI: 0.773 to 10.290), AA of CES2 rs8192925 (95%CI: 1.842 to 9.090) were associated with higher HR instability; the AA/GG genotype of NR1I2 rs6438550 (95%CI: 0.351 to 7.761), AA of BDNF rs2049046 (95%CI: -9.039 to -0.640) and GG of GABBR2 rs1167768 (95%CI: -10.146 to -1.740) were associated with higher MAP instability. The predictive models of HR and MAP fluctuations were developed, accounting for 45.0 and 59.2% of variations, respectively. CONCLUSION: We found that cardiovascular fundamentals and genetic variants of GABRB1, GABBR2, OPRM1, BDNF, CES2 and NR1I2 are associated with cardiovascular susceptibility, which can provide a reference for haemodynamic management in clinical anaesthesia.

Dynamic assessment of coronary artery during different cardiac cycle in patients with coronary artery disease using coronary CT angiography.

INTRODUCTION: To evaluate the effect of the cardiac cycle for the coronary artery opening and coronary stenosis at the plaque to determine the phase of measuring maximum diameters required for coronary artery disease (CAD). METHODS: This retrospective study assessed data for 208 consecutive patients who underwent coronary computed tomography angiography (CTA). The cross-sectional area and diameters of the opening of the left main coronary artery (LM), left anterior descending branch (LAD), left circumflex branch (LCX) and right coronary artery (RCA), the stenosis rate of involved vessels were measured in 10 cardiac cycles. And all their dynamic changes were estimated by the linear mixed model. The relationship between stenosis rate and opening orifice were analyzed by monofactorial variance. RESULTS: The opening parameters and stenosis rate of the four main coronary arteries varied within the cardiac cycle (p < .05). The maximum opening area occurred at the 45%-55% phase; The range of stenosis rate varied approximately 11%-14% and the maximum stenosis rate was at the 65% phase. The degree of vascular stenosis for LM, LAD and LCX were not associated with their corresponding opening diameters, but were positively intercorrelation with each other. CONCLUSION: For patients with CAD, the maximum coronary artery stenosis rate were at 65% phase and the maximum value of coronary artery opening were at 45%-55% phase, which were chosen for the appropriate measurement and evaluation by CTA.

Age-associated proteostasis collapse.

Healthy cells utilize a series of protein quality regulatory networks to maintain the integrity and functionality of their proteome, named as protein homeostasis (proteostasis). However, the phenomenon of proteostasis collapse, including the destruction of the balance between protein synthesis, folding and degradation, are common with aging. The main causes of age-associated proteostasis collapse are as follows: (1) the decline in transcriptional activation of stress response related pathways, (2) the reduction of proteasome and autophagy activity, and (3) ribosome pausing during translation. In addition, proteostasis is regulated mainly through chaperones, proteasomes, and autophagy systems of proteostasis network in aging. This paper mainly reviews the causes of age-associated proteostasis collapse and the pathways of proteostasis regulation, which may open the way to explore aging studies and solve aging problems.

Short and long-term prognosis of admission hyperglycemia in patients with and without diabetes after acute myocardial infarction: a retrospective cohort study.

OBJECTIVE: Admission hyperglycemia is associated with poor prognosis in patients with acute myocardial infarction (AMI), but the effects of baseline diabetes status on this association remain elusive. We aim to investigate the impact of admission hyperglycemia on short and long-term outcomes in diabetic and non-diabetic AMI patients. METHODS: In this retrospective cohort study, 3330 patients with regard to first-time AMI between July 2012 and July 2020 were identified. Participants were divided into two groups according to diabetes status (1060 diabetic patients and 2270 non-diabetic patients). Thereafter, they were divided into four groups according to diabetes status-specific cutoff values of fasting blood glucose (FBG) identified by restricted cubic spline. Short-term outcomes included in-hospital death and cardiac complications. Long-term outcomes were all-cause mortality and major adverse cardiovascular events (MACE). Inverse probability of treatment weighting (IPTW) was conducted to adjust for baseline differences among the groups, followed by a weighted Cox proportional hazards regression analysis to calculate hazard ratios and 95% confidence intervals for all-cause mortality associated with each FBG category. Subgroup analysis and sensitivity analysis were performed to test the robustness of our findings. RESULTS: During a median follow-up of 3.2 years, 837 patients died. There was a significant interaction between diabetes status and FBG levels for all-cause mortality during long-term follow-up (p-interaction < 0.001). Moreover, restricted cubic spline curves for the association between FBG and all-cause mortality followed a J shape in patients with diabetes and a non-linear in patients without diabetes. Kaplan-Meier analysis demonstrated greater survival in non-hyperglycemia patients compared to hyperglycemia patients for both diabetic and non-diabetic patients groups. Survival of hyperglycemia patients without diabetes greater than in hyperglycemia patients with diabetes. In the weighted Multivariable cox analysis, admission hyperglycemia predicted higher short and long-term mortality. Subgroup analysis and sensitivity analysis showed the robustness of the results. CONCLUSIONS: The inflection points of FBG level for poor prognosis were 5.60 mmol/L for patients without diabetes and 10.60 mmol/L for patients with diabetes. Admission hyperglycemia was identified as an independent predictor of worse short and long-term outcomes in AMI patients, with or without diabetes. These findings should be explored further.

Comparison and correlation study of synovial ultrasound indices and serum VEGF in rheumatoid wrist arthritis before and after treatment.

OBJECTIVE: Rheumatoid wrist arthritis is a chronic autoimmune disease, resulting in joint deformity and functional impairment. We aimed to compare the wrist synovial ultrasound indices and serum vascular endothelial growth factor (VEGF) level in patients with RA before and after treatment, and to explore the correlation between the two. METHODS: Forty patients with RA in wrist underwent ultrasound examination to determine wrist synovial thickness, synovial blood flow grade, and synovial artery resistive index (RI) before and after treatment. The serum level of VEGF was detected by enzyme-linked immunosorbent assay. Correlation between synovial ultrasound indices and serum VEGF level was assessed. RESULTS: Pre-treatment synovial thickness, synovial artery RI, and serum VEGF level were 8.60 ± 2.82 mm, 0.62 ± 0.07, and 419.49 ± 19.27 pg/mL, respectively. The corresponding post-treatment levels were 4.05 ± 1.89 mm, 0.83 ± 0.10, and 199.30 ± 16.18 pg/mL. Pre-treatment distribution of synovial blood flow grades was as follows: grade 0, nil; grade I, 1 case; grade II, 17 cases; grade III, 22 cases. The post-treatment distribution was as follows: grade 0, 6 cases; grade I, 23 cases; grade II, 11 cases; and grade III, nil. There were significant differences between pre- and post-treatment wrist synovial thickness, artery RI, and blood flow grading. Wrist synovial thickness and synovial blood flow grade showed a strong positive correlation with serum VEGF level (P < 0.01). There was strong negative correlation between wrist synovial artery RI and serum VEGF level (P < 0.01). CONCLUSION: The strong correlation between wrist synovial ultrasound indicators and serum VEGF may be clinically useful for diagnosis and therapy.

Formaldehyde recognition through aminal formation in a luminescent metal-organic framework.

Two isostructural pillar-layer MOFs (JNU-105 and JNU-105-(NH2)2) have been successfully synthesized. JNU-105-(NH2)2 exhibits a red-shifted luminescence "turn on" for formaldehyde without the interference from other VOCs and a detection limit of 1.87 ppb. In situ single-crystal transformation studies confirm the aminal formation on the pillar linker, which was attributed to the exclusive luminescence response toward formaldehyde.

Methylation-mediated expression of SPARC is correlated with tumor progression and poor prognosis of breast cancer.

Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the formation and progression of tumors. DNA methylation has become increasingly recognized as a frequent event of epigenetic alterations and one of the primary mechanisms of gene inactivation. The study aims to investigate the status of DNA methylation and the biofunction of SPARC in breast cancer. The qRT-PCR, BGS, and MSP methods were respectively employed to measure the relative mRNA expression levels and methylation status of SPARC. Additionally, the effects of SPARC on cell proliferation, migration, and invasion were examined in SPARC overexpression and knockdown cells. Immunohistochemical staining and western blot assay were used to examine the protein expression of genes. The expression levels of SPARC were found to be higher in breast cancer tissues and most breast cancer cells. The expression levels of SPARC in MDA-MB-231 and MCF-7 cells were significantly reversed by 5-Aza-dC treatment. Furthermore, the high expression and promoter DNA hypomethylation of SPARC were detected in triple-negative breast cancer tissues, while no expression changes of SPARC were found in luminal A breast cancer tissues. Overexpression of SPARC dramatically promoted MCF-7 cells migration and invasion, while knockdown of SPARC inhibited MDA-MB-231 cells migration and invasion. SPARC was involved in the epithelial-mesenchymal transition (EMT) process of breast cancer cells. The expression levels of mesenchymal markers N-cadherin, Vimentin, and ß-catenin were upregulated, while E-cadherin was downregulated in SPARC overexpressed breast cancer cells. Conversely, the expression levels of EMT-related genes demonstrated the opposite trend in SPARC knockdown cells. To conclude, high expression of SPARC regulated by promoter hypomethylation promotes breast cancer cells migration and invasion, thus SPARC may act as an oncogene and serve as a potential target for breast cancer therapy.

Research progress on lncRNAs in Alzheimer's disease.

Alzheimer's disease (AD) is the common neurodegenerative disease in the center never system and the typical dementia in old people. The major pathological changes of AD are the accumulation of amyloid-ß (Aß) plaques, neurofibrillary tangles, loss of cholinergic neurons, inflammation and metabolism dysfunction. However, the molecular mechanism leading to AD pathogenesis is not clear. More and more studies reported that long non-coding RNAs (lncRNAs) play important roles in AD. In this review, we briefly introduce the recent research progress on lncRNAs in AD, including their regulation of clearance of the Aß plaques, synaptic function, inflammation reaction and mitochondrial function, and thus providing the references for that lncRNAs can serve as a potential diagnostic biomarker and therapeutic target in AD.

Effects of spinetoram and glyphosate on physiological biomarkers and gut microbes in Bombus terrestris.

The sublethal effects of pesticide poisoning will have significant negative impacts on the foraging and learning of bees and bumblebees, so it has received widespread attention. However, little is known about the physiological effects of sublethal spinetoram and glyphosate exposure on bumblebees. We continuously exposed Bombus terrestris to sublethal (2.5 mg/L) spinetoram or glyphosate under controlled conditions for 10 days. The superoxide dismutase, glutathione-S-transferase, carboxylesterase, prophenoloxidase, α-amylase and protease activities, and changes in gut microbes were measured to understand the effects of sublethal pesticide exposure on the physiology and gut microbes of bumblebees. Sublethal pesticide exposure to significantly increased superoxide dismutase activity and significantly decreased gut α-amylase activity in bumblebees but had no significant effect on glutathione-S-transferase, carboxylesterase or gut protease activities. In addition, glyphosate increased the activity of prophenoloxidase. Interestingly, we observed that neither of the two pesticides had a significant effect on dominant gut bacteria, but glyphosate significantly altered the structure of the dominant gut fungal community, and reduced the relative abundance of Zygosaccharomyces associated with fat accumulation. These results suggest that sublethal spinetoram and glyphosate do not significantly affect the detoxification system of bumblebees, but may affect bumblebee health by inhibiting energy acquisition. Our results provide information on the sublethal effects of exposure to low concentrations of glyphosate and spinetoram on bumblebees in terms of physiology and gut microbes.