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Although tobacco smoking is a risk factor for lung adenocarcinoma (LUAD), the mechanisms by which tobacco smoking induces LUAD development remain elusive. Histone methylation levels in human bronchial epithelial cells have been reported to increase after exposure to cigarettes. In this study, we explored the mechanisms regulating histone methylation in LUAD in response to smoking. We found that the histone H3K9 methylation reader CBX3 was upregulated in current smokers with LUAD, and that CBX3 overexpression promoted LUAD progression. Functional enrichment analyses revealed that CBX3 regulated the activation of Rho GTPases in LUAD. We also found that by forming a complex with TRIM28, TRIM24, and RBBP4, CBX3 repressed the expression of ARHGAP24 and increased the amount of active Rac1 in LUAD cells. Collectively, these results suggest that smoking associated upregulation of CBX3 promotes LUAD progression by activating the ARHGAP24/Rac1 pathway. Hence, the CBX3/ARHGAP24/Rac1 axis may represent a promising therapeutic target in smoking-induced LUAD.

Mercury pollution in soil poses serious risks to human health through consumption of contaminated vegetables. We used a meta-analysis to examine the mercury enrichment ability of different vegetables and the main factors affecting mercury uptake. We drew the following conclusions. (1) Plants with a lower bioconcentration factor (BCF) include cowpea, long bean, and radish, whereas plants with a higher BCF include green pepper, spinach, cabbage, and Chinese cabbage. (2) Leaf and cucurbit have the highest and lowest capacity, respectively, for mercury enrichment. (3) When soil pH is <6.5, mercury level uptake by the plant increases, whereas it decreases when the pH is >7.5, meaning that increased soil pH reduces mercury uptake in soil. (4) When soil organic matter (SOM) is lower than 20 g/kg, tuber plants have the highest and eggplant has the lowest mercury adsorption capacity, respectively. When SOM is 20–30 g/kg, cucurbit has the lowest and leaf the highest adsorption capacity, respectively. When SOM is higher than 30 g/kg, however, eggplant has the highest mercury adsorption capacity, but there were no significant differences among the five types of vegetables. We argue that this meta-analysis aids in selecting vegetables suitable for absorption of heavy metals from polluted soil.

Renal cell carcinoma (RCC) is a malignant tumor of the kidneys. Approximately 70% of RCC cases are clear cell renal cell carcinoma with von Hippel–Lindau (VHL) gene mutation and activation of the vascular endothelial growth factor (VEGF) pathway. Tyrosine kinase inhibitors (TKIs) targeting VEGF have emerged as promising agents for RCC treatment. Apart from primary resistance, acquired resistance to TKIs after initial tumor regression is common in RCC. Recently, immune checkpoint inhibition, including PD‐1/PD‐L1 blockade, alone or in combination with TKIs has improved the overall survival of patients with RCC. Ribonucleotide reductase subunit M2 (RRM2) has been reported in many types of cancer and has been implicated in tumor progression. However, the role of RRM2 in TKIs resistance in RCC remains unclear. In this study, the authors have demonstrated that RRM2 is upregulated in sunitinib‐resistant RCC cells and patient tissues. They also find that RRM2 stabilizes ANXA1 and activates the AKT pathway independent of its ribonucleotide reductase activity, promoting sunitinib resistance in RCC. Moreover, RRM2 regulated antitumor immune responses, and knockdown of RRM2 enhance the anti‐tumor efficiency of PD‐1 blockade in renal cancer. Collectively, these results suggest that aberrantly expressed RRM2 may be a promising therapeutic target for RCC. RRM2 overexpression plays a key role in sunitinib resistance in patients with renal cell carcinoma and that RRM2 competes with UBE3A to prevent ANXA1 degradation. The up‐regulated ANXA1 activates AKT signaling pathway to regulate the sensitivity to sunitinib and PD‐1 blockade in renal cancer cells.

Bladder cancer is one of the most lethal cancers in the world. Despite the continuous development of medical technologies and therapeutic strategies, the overall survival rate of bladder cancer has not changed significantly. Targeted therapy is a new promising method for bladder cancer treatment. Thus, an in-depth study of the molecular mechanism of the occurrence and development of bladder cancer is urgently needed to identify novel therapeutic candidates for bladder cancer. Here, bioinformatics analysis demonstrated that RNF26 was one of the risk factors for bladder cancer. Then, we showed that RNF26 is abnormally upregulated in bladder cancer cells and tissues and that higher RNF26 expression is an unfavorable prognostic factor for bladder cancer. Moreover, we found that RNF26 promotes bladder cancer progression. In addition, we showed that RNF26 expression is promoted by FOXM1 at the transcriptional level through MuvB complex. The upregulated RNF26 in turn degrades p57 (CDKN1C) to regulate the cell cycle process. Collectively, we uncovered a novel FOXM1/RNF26/p57 axis that modulates the cell cycle process and enhances the progression of bladder cancer. Thus, the FOXM1/RNF26/p57 signaling axis could be a candidate target for the treatment of bladder cancer.

The brown planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), a major pest of rice in Asia, is able to successfully puncture sieve tubes in rice with its piercing stylet and then to ingest phloem sap. How BPH manages to continuously feed on rice remains unclear. Here, we cloned the gene NlSEF1 , which is highly expressed in the salivary glands of BPH. The NlSEF1 protein has EF-hand Ca 2+ -binding activity and can be secreted into rice plants when BPH feed. Infestation of rice by BPH nymphs whose NlSEF1 was knocked down elicited higher levels of Ca 2+ and H 2 O 2 but not jasmonic acid, jasmonoyl-isoleucine (JA-Ile) and SA in rice than did infestation by control nymphs; Consistently, wounding plus the recombination protein NlSEF1 suppressed the production of H 2 O 2 in rice. Bioassays revealed that NlSEF1 -knockdown BPH nymphs had a higher mortality rate and lower feeding capacity on rice than control nymphs. These results indicate that the salivary protein in BPH, NlSEF1, functions as an effector and plays important roles in interactions between BPH and rice by mediating the plant’s defense responses.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma and has the highest mortality rate. For metastatic RCC, systemic drug therapy is the most important method in addition to surgical tumor reduction. In recent years, tyrosine kinase inhibitors (TKIs) targeting the angiogenesis have been applied to treat ccRCC and achieved profound therapeutic effects. It has been reported that most patients receiving antiangiogenic therapy will develop resistance within 15 months. The mechanism of resistance to targeted therapy is extremely complex and has not been clarified. Ovarian tumor-associated protease domain-containing proteins (OTUDs) belonging to DUBs play a critical role in the tumorigenesis of solid tumors. However, the specific role of OTUDs in ccRCC is still elusive. Here, we investigated the clinicopathological role of OTUD family members in ccRCC. We demonstrated that OTUD1 was downregulated in renal cancer and involved in the poor prognosis of renal cancer. Then, we showed that OTUD1 inhibits cancer cell growth. Moreover, analysis of OTUD1 RNA-seq data indicated that OTUD1 inhibition triggers the AKT and NF-kappa B pathways in renal cancer cells. Furthermore, OTUD1 interacts with PTEN and regulates its stability. Subsequently, we revealed that downregulation of OTUD1 contributes to the sensitivity of renal cancer cells to TKIs, and this effect was blocked by TNF/NF-kappa B inhibitors and AKT inhibitors. Thus, we identified that the OTUD1-PTEN axis suppresses tumor growth and regulates the resistance of renal cancer to TKIs.

Background Extracellular vesicle (EV) biomarkers have promising diagnosis and screening capacity for several cancers, but the diagnostic value for pancreatic cancer (PC) is controversial. The aim of our study was to review the diagnostic performance of EV biomarkers for PC. Methods We performed a systematic review of PubMed, Medline, and Web Of Science databases from inception to 18 Feb 2022. We identified studies reporting the diagnostic performance of EV biomarkers for PC and summarized the information of sensitivity, specificity, area under the curve (AUC), or receiver operator characteristic (ROC) curve) in according to a pre-designed data collection form. Pooled sensitivity and specificity was calculated using a random-effect model. Results We identified 39 studies, including 2037 PC patients and 1632 noncancerous, seven of which were conducted independent validation tests. Seventeen studies emphasized on EV RNAs, sixteen on EV proteins, and sixteen on biomarker panels. MiR-10b, miR-21, and GPC1 were the most frequently reported RNA and protein for PC diagnosis. For individual RNAs and proteins, the pooled sensitivity and specificity were 79% (95% CI: 77–81%) and 87% (95% CI: 85–89%), 72% (95% CI: 69–74%) and 77% (95% CI: 74–80%), respectively. the pooled sensitivity and specificity of EV RNA combined with protein panels were 84% (95% CI: 81–86%) and 89% (95% CI: 86–91%), respectively. Surprisingly, for early stage (stage I and II) PC EV biomarkers showed excellent diagnostic performance with the sensitivity of 90% (95% CI: 87–93%) and the specificity of 94% (95% CI: 92–95%). Both in sensitivity and subgroup analyses, we did not observe notable difference in pooled sensitivity and specificity. Studies might be limited by the isolation and detection techniques of EVs to a certain extent. Conclusions EV biomarkers showed appealing diagnostic preference for PC, especially for early stage PC. Solving the deficiency of technologies of isolation and detection EVs has important implications for application these novel noninvasive biomarkers in clinical practice.

Emerging evidence has shown the potential of oral microbiota as a noninvasive diagnostic tool in gastrointestinal (GI) cancer. PubMed, Web of Science, and Embase were systematically searched for eligible studies published until May 31, 2019. Of the 17 included studies published between 2011 and 2019, five kinds of GI cancer, including colorectal cancer (n=6), pancreatic cancer (n=5), gastric cancer (n=4), esophageal cancer (n=2) and liver cancer (n=1), were reported. Generally, the diagnostic performance of the multi-bacteria model for GI cancer was strong with the best area under the receiver operator characteristic curve (AUC) exceeding 0.90, but only one study had a validation phase. Pathogens involved in periodontal disease, such as and , were linked to various kinds of GI cancer. Besides, more oral bacteria significantly differed between cases with upper digestive cancer and healthy controls when compared to colorectal cancer (the most common form of lower digestive cancer), probably indicating a different mechanism due to anatomical and physiological differences in the digestive tract. Oral microbiota changes were associated with risk of various kinds of GI cancer, which could be considered as a potential tool for early prediction and prevention of GI cancer, but validation based on a large population, reproducible protocols for oral microbiota research and oral-gut microbiota transmission patterns are required to be resolved in further studies.

The brown planthopper (BPH), Nilaparvata lugens (Stål), a destructive rice pest in Asia, can quickly overcome rice resistance by evolving new virulent populations. Herbivore saliva plays an important role in plant-herbivore interactions, including in plant defense and herbivore virulence. However, thus far little is known about BPH saliva at the molecular level, especially its role in virulence and BPH-rice interaction. Using cDNA amplification in combination with Illumina short-read sequencing technology, we sequenced the salivary-gland transcriptomes of two BPH populations with different virulence; the populations were derived from rice variety TN1 (TN1 population) and Mudgo (M population). In total, 37,666 and 38,451 unigenes were generated from the salivary glands of these populations, respectively. When combined, a total of 43,312 unigenes were obtained, about 18 times more than the number of expressed sequence tags previously identified from these glands. Gene ontology annotations and KEGG orthology classifications indicated that genes related to metabolism, binding and transport were significantly active in the salivary glands. A total of 352 genes were predicted to encode secretory proteins, and some might play important roles in BPH feeding and BPH-rice interactions. Comparative analysis of the transcriptomes of the two populations revealed that the genes related to 'metabolism,' 'digestion and absorption,' and 'salivary secretion' might be associated with virulence. Moreover, 67 genes encoding putative secreted proteins were differentially expressed between the two populations, suggesting these genes may contribute to the change in virulence. This study was the first to compare the salivary-gland transcriptomes of two BPH populations having different virulence traits and to find genes that may be related to this difference. Our data provide a rich molecular resource for future functional studies on salivary glands and will be useful for elucidating the molecular mechanisms underlying BPH feeding and virulence differences.

Objective This study aims to quantitatively compare segment-specific disc kinematics, height changes, and strain patterns in the lumbar spine between patients with chronic low back pain (CLBP) and asymptomatic controls during weight-bearing flexion-extension, before and after fatigue loading. Methods A total of 29 patients with CLBP and 24 asymptomatic controls were included. All participants underwent dual fluoroscopic imaging system (DFIS) and computed tomography (CT) imaging. Weight-bearing kinematic sequences from maximum extension to approximately 45° flexion were captured pre- and post-fatigue. A validated geometric deformation model based on supine CT scans was used to quantify intervertebral kinematics from L1 to S1. Disc height variations and strain (axial and shear) were computed using computational morphometry and kinematic correspondence tracking. Statistical analyses included paired and independent t-tests for within- and between-group comparisons, with significance set at p  < 0.05. Results Computational morphometry revealed distinct degenerative features associated with CLBP. Compared with controls, L4/5 discs in CLBP patients showed significantly reduced baseline height ( p  < 0.05), which may indicate a predisposition to early degeneration. At L5/S1, disc height was significantly reduced after fatigue loading across all postures in the CLBP group ( p  < 0.01), a change not observed in controls. Strain analysis demonstrated segment-dependent alterations in mechanical behavior. During flexion, both groups exhibited posterior tensile and anterior compressive strains from L4 to S1. However, after fatigue, CLBP patients developed a distinct strain pattern at L5/S1, characterized by high compressive strain and reduced shear strain. More broadly, fatigue loading in CLBP patients led to impaired shear strain dissipation and accumulation of compressive strain within the L4–S1 segments. In contrast, the upper lumbar segments (L1–L3) in both groups maintained physiological strain gradients that were unaffected by fatigue. Conclusions This study provides in vivo evidence of fatigue-induced biomechanical alterations in the L4–S1 discs of CLBP patients, marked by increased compressive strain and reduced capacity for shear strain redistribution. The preserved biomechanical behavior in the upper lumbar segments underscores the particular vulnerability of the lumbosacral junction to mechanical deficits. These findings support the value of segment-specific biomechanical assessment for identifying early degenerative changes and inform the development of targeted load-management strategies in CLBP. However, further research is needed to account for potential confounding variables and to validate these observations in larger cohorts. Trial registration Chinese Clinical Trial Registry Registration number ChiCTR2000036039. Registered 21 August 2020.