This study aimed to explore the role of lncRNA RPPH1 in hepatocellular carcinoma. The expression of RPPH1 and miR-122 was determined by Real-time PCR. Cell proliferation and colony formation assays were employed to monitor cell growth in vitro. Wound healing and Transwell assays were applied to detect cell migration and invasion. A dual-luciferase reporter assay was used to verify the interaction between RPPH1 and miR-122. The in vivo function of RPPH1 was illustrated by xenograft tumor models. The results showed that the expression of RPPH1 was markedly upregulated in human HCC specimens and cell lines compared to normal controls. However, the trend of miR-122 was the opposite. RPPH1 facilitates the proliferation, migration, and invasion of HCC cells and synchronously suppresses cell apoptosis. The dual-luciferase assay confirmed the relationship between RPPH1 and miR-122. Rescue experiments showed that RPPH1 acted as a competing endogenous RNA (ceRNA) by sponging miR-122 in HCC cells. Moreover, RPPH1 positively regulated the expression of Wnt1 and its downstream targets through miR-122. Our study demonstrates for the first time that RPPH1 promotes HCC progression via the miR-122/Wnt1/β-catenin axis, which may represent a valuable therapeutic target for patients with HCC.

Clear cell renal cell carcinoma (ccRCC) is a fatal cancer of the urinary system. Long non-coding RNAs (lncRNAs) act as competitive endogenous RNAs (ceRNAs) involving the ccRCC progression. However, the relationship between the ceRNA network and immune signature is largely unknown. In this study, the ccRCC-related gene expression profiles retrieved from the TCGA database were used first to identify the differentially expressed genes through differential gene expression analysis and weighted gene co-expression network analysis. The interaction among differentially expressed lncRNAs, miRNAs, and mRNAs were matched using public databases. As a result, a ceRNA network was developed that contained 144 lncRNAs, 23 miRNAs, as well as 62 mRNAs. Four of 144 lncRNAs including LINC00943, SRD5A3-AS1, LINC02345, and U62317.3 were identified through LASSO regression and Cox regression analyses, and were used to create a prognostic risk model. Then, the ccRCC samples were divided into the high- and low-risk groups depending on their risk scores. ROC curves, Kaplan-Meier survival analysis, and the survival risk plots indicated that the predictive performance of our developed risk model was accurate. Moreover, the CIBERSORT algorithm was used to measure the infiltration levels of immune cells in the ccRCC samples. The further genomic analysis illustrated a positive correlation between most immune checkpoint blockade-related genes and the risk score. In conclusion, the present findings effectually contribute to the comprehensive understanding of the ccRCC pathogenesis, and may offer a reference for developing novel therapeutic and prognostic biomarkers.

Long noncoding RNAs (lncRNAs) play a central role in the pathogenesis of various tumors, including hepatocellular carcinoma (HCC). TMPO antisense RNA 1 (TMPO-AS1) has been reported in many tumors. Nevertheless, the underlying mechanism whereby TMPO-AS1 influences HCC remains unclear. Our research aimed to reveal the molecular mechanism governing the function of TMPO-AS1 in HCC.

Indoor microbial exposure is associated with asthma, but the health effects of indoor metabolites and chemicals have not been comprehensively assessed.

Bone cancer pain (BCP) is severe chronic pain caused by tumor metastasis to the bones, often resulting in significant skeletal remodeling and fractures. Currently, there is no curative treatment. Therefore, insight into the underlying mechanisms could guide the development of mechanism-based therapeutic strategies for BCP. We speculated that Rac1/PAK1 signaling plays a critical role in the development of BCP. Tumor cells implantation (TCI) into the tibial cavity resulted in bone cancer-associated mechanical allodynia. Golgi staining revealed changes in the excitatory synaptic structure of WDR (Wide-dynamic range) neurons in the spinal cord, including increased postsynaptic density (PSD) length and thickness, and width of the cleft. Behavioral and western blotting test revealed that the development and persistence of pain correlated with Rac1/PAK1 signaling activation in primary sensory neurons. Intrathecal injection of NSC23766, a Rac1 inhibitor, reduced the persistence of BCP as well as reversed the remodeling of dendrites. Therefore, we concluded that activation of the Rac1/PAK1 signaling pathway in the spinal cord plays an important role in the development of BCP through remodeling of dendritic spines. Modulation of the Rac1/PAK1 pathway may be a potential strategy for BCP treatment.

Hepatitis B virus (HBV) infection has been associated with an increased risk of a few malignancies. However, the prognostic impact of HBV infection remains unclear in cervical cancer.

To explore the factors affecting the prognosis of cervical cancer (CC), and to construct and evaluate predictive nomograms to guide individualized clinical treatment.

Reactive oxidative species (ROS) production-driven ferroptosis plays a role in acute kidney injury (AKI). However, its exact molecular mechanism is poorly understood. Scavenger receptor CD36 has important roles in oxidizing lipids, lipid accumulation, metabolic syndrome, and insulin resistance in chronic kidney disease, but its roles remain unexplored in AKI. The present study investigated the role and mechanism of CD36 in regulating proximal tubular cell ferroptosis and AKI. The expression of CD36 was found to be significantly up-regulated in AKI renal tissues and correlated with renal function, which might serve as an independent biomarker for AKI patients. Moreover, in adult mice subjected to AKI, deletion of CD36 (CD36-/-) induced tubular cell ROS accumulation, ferroptosis activation, and renal injury. Mechanistically, combining LC-MS/MS, co-IP, and ubiquitination analyses revealed that CD36 could specifically bind to ferroptosis suppressor protein 1 (FSP1) and regulate its ubiquitination at sites K16 and K24, leading to FSP1 degradation and progression of ferroptosis in AKI. The present results emphasize a novel mechanism of CD36 in cisplatin-induced AKI. The discovery of the special CD36 roles in promoting ferroptosis and AKI development by regulating the ubiquitination of FSP1 in proximal tubular cells may be potential therapeutic targets for AKI. Moreover, CD36 may play a key role in the progression of AKI. Therefore, targeting CD36 may provide a promising treatment option for AKI.

The collagen from jellyfish has many beneficial effects, including antioxidant, anti-inflammatory and immune-modulatory activities. However, whether jellyfish collagen hydrolysate (JCH) has any effects on high-fat diet-induced obesity remains unknown. Consequently, we in the present study orally administrated JCH in high-fat diet-fed mice to explore its effects on body weight gain, inflammatory and oxidative status, and cecum microbe composition. The results showed that oral administration of JCH prevented the body weight gain in high-fat diet-treated mice. Meanwhile, glucose, triglycerides, and total cholesterol level in serum were maintained by JCH administration. Furthermore, JCH administration alleviated oxidative stress by increasing the GSH content and decreasing the level reactive oxygen species in the liver and improved inflammatory response by decreasing the expression of TNF-α, IL-1β, and IL-8 gene in the liver and ileum. Importantly, JCH administration helps recover the alteration of microbiota composition induced by high-fat diet, and the genus Romboutsia may critically involve in the beneficial effects of JCH administration. In conclusion, our results indicated that JCH could be potentially used for the prevention and treatment of diet-induced obesity.

This study aims to explore the association between coffee consumption and the prevalence of hearing loss in American adults based on a national population-based survey.

Exposure to cadmium (Cd) can affect neurodevelopment and results in increased potential of developing neurodegenerative diseases during the early developmental stage of organisms, but the mechanisms through which exposure to environmentally relevant concentrations of Cd lead to developmental neurotoxicity remain unclear. Although we know that microbial community fixations overlap with the neurodevelopmental window during early development and that Cd-induced neurodevelopmental toxicity may be related to the disruption of microorganisms during early development, information on the effects of exposure to environmentally relevant Cd concentrations on gut microbiota disruption and neurodevelopment is scarce. Therefore, we established a model of zebrafish exposed to Cd (5 µg/L) to observe the changes in the gut microbiota, SCFAs, and free fatty acid receptor 2 (FFAR2) in zebrafish larvae exposed to Cd for 7 days. Our results indicated that there were significant changes in the gut microbial composition due to the exposure to Cd in zebrafish larvae. At the genus level, there were decreases in the relative abundances of Phascolarctobacterium, Candidatus Saccharimonas, and Blautia in the Cd group. Our analysis revealed that the acetic acid concentration was decreased (p > 0.05) while the isobutyric acid concentration was increased (p < 0.05). Further correlation analysis indicated a positive correlation between the content of acetic acid and the relative abundances of Phascolarctobacterium and Candidatus Saccharimonas (R = 0.842, p < 0.01; R = 0.767, p < 0.01), and a negative correlation between that of isobutyric acid and the relative abundance of Blautia glucerasea (R = -0.673, p < 0.05). FFAR2 needs to be activated by SCFAs to exert physiological effects, and acetic acid is its main ligand. The FFAR2 expression and the acetic acid concentration were decreased in the Cd group. We speculate that FFAR2 may be implicated in the regulatory mechanism of the gut-brain axis in Cd-induced neurodevelopmental toxicity.

Background: Previous studies have demonstrated the embryotoxicity and fetotoxicity of thallium (Tl). However, the effects of prenatal exposure to Tl on birth weight and placental weight and the mediating role of placental weight in the association of Tl with birth weight remain unclear. Methods: We recruited 2,748 participants from the ongoing Prenatal Environment and Offspring Health Cohort (PEOH Cohort) study, which was initiated in 2016 in Guangzhou, China. The Tl concentrations in maternal urine samples collected during the first and third trimester were determined by inductively coupled plasma mass spectrometry. Birth weight and placental weight were extracted from maternal medical records. Results: Pregnant women exposed to the highest tertile of Tl in the first trimester (β = -42.7 g, 95% CI: -82.3, -3.1 g) and third trimester (β = -50.6 g, 95% CI: -99.0, -2.3 g) had babies with lower birth weights than those exposed to the lowest tertile. We also found significant negative associations of exposure to Tl concentrations in the first and third trimester with placental weight. Mediation analyses showed that 50.3% (95% CI: 15.9, 79.2%) and 33.5% (95% CI: 1.3, 80.3%) of the effects of Tl exposure in the first and third trimester on birth weight were mediated by decreased placental weight. Conclusion: Our results suggest that prenatal exposure to Tl is negatively associated with birth weight and that this association may be mediated by decreased placental weight.

Metal exposures have been inconsistently related to the risk of hyperuricemia, and limited research has investigated the interaction between obesity and metals in hyperuricemia. To explore their associations and interaction effects, 3300 participants were enrolled from 11 districts within 1 province in China, and the blood concentrations of 13 metals were measured to assess internal exposure. Multivariable logistic regression, restricted cubic spline (RCS), Bayesian kernel machine regression (BKMR), and interaction analysis were applied in the single- and multi-metal models. In single-metal models, five metals (V, Cr, Mn, Co, and Zn) were positively associated with hyperuricemia in males, but V was negatively associated with hyperuricemia in females. Following the multi-metal logistic regression, the multivariate-adjusted odds ratios (95% confidence intervals) of hyperuricemia were 1.7 (1.18, 2.45) for Cr and 1.76 (1.26, 2.46) for Co in males, and 0.68 (0.47, 0.99) for V in females. For V and Co, RCS models revealed wavy and inverted V-shaped negative associations with female hyperuricemia risk. The BKMR models showed a significant joint effect of multiple metals on hyperuricemia when the concentrations of five metals were at or above their 55th percentile compared to their median values, and V, Cr, Mn, and Co were major contributors to the combined effect. A potential interaction between Cr and obesity and Zn and obesity in increasing the risk of hyperuricemia was observed. Our results suggest that higher levels of Cr and Co may increase male hyperuricemia risk, while higher levels of V may decrease female hyperuricemia risk. Therefore, the management of metal exposure in the environment and diet should be improved to prevent hyperuricemia.

Renal denervation (RDN) was still performed without any intra-procedural method for nerve mapping. Whether renal nerve stimulation (RNS) is an efficient way to identify renal autonomic innervation and optimize the strategy for RDN remain to be worthy for further exploration.

Sexual swear words are frequently used and considered vulgar and controversial in Chinese. The study of attitude is not only an important part of the study of swear words, but is also an important way for predicting their use. To date, few independent studies have been conducted on Chinese sexual swear words; those that have been conducted mostly focus on language ontology rather than language use. The studies have mainly used qualitative research methods, with a lack of empirical analysis and use of measurement tools. It is feasible and necessary to study college students as the object of sexual swear words because of the prevalence of "Zu'an culture" and the abuse of sexual swear words. Based on the current research status of Chinese swear words and the context of using swear words on campus, this paper combines the research of linguistic differences in swearing, psychological theories, and social science measurement theories and uses SPSS and Mplus statistical software to develop Chinese college students' attitudes toward Sexual Swear Words Scale. The participants consist of students from Zhejiang Normal University and other universities. A total of 262 college students participated in the preliminary test. Through item analysis and exploratory factor analysis, the formal scale was formed. A total of 608 college students were formally tested, and confirmatory factor analysis, reliability, and validity tests were carried out to produce the final scale. The scale contains three subscales: Cognition (17 items), Affection (17 items), and Behavior Tendency (15 items). The results show that each subscale model fits well, has good reliability and validity, and can be used as an important tool to measure attitudes of Chinese college students toward sexual swear words.

The prevalence of hyperuricemia (HUA) is gradually increasing worldwide. HUA is closely related to diabetes, but the relationship between HUA and pancreatic β-cells function in the population is unclear. The purpose of this article is to investigate the association between pancreatic β-cells and HUA.

The gold standard for confirming bacterial infections is culture-positive, which has a long sample-to-result turnaround time and poor sensitivity for unculturable and fastidious pathogens; therefore, it is hard to guide early, targeted antimicrobial therapy and reduce overuse of broad-spectrum antibiotics. Nanopore targeted sequencing (NTS) is reported to be advantageous in detection speed and range over culture in prior published reports. However, investigation of the clinical performance of NTS is deficient at present. Thus, we assessed the feasibility of NTS for the first time with cohort and systematic comparisons with traditional culture assays and PCR followed by Sanger sequencing. This retrospective study was performed on 472 samples, including 6 specimen types from 436 patients, to evaluate the clinical performance of NTS designed for identifying the microbial composition of various infections. Of these samples, 86.7% were found to be NTS positive, which was significantly higher than culture-positive (26.7%). A total of 425 significant human opportunistic bacteria and fungi detected by NTS were selected to go through validation with PCR followed by Sanger sequencing. The average accuracy rate was 85.2% (maximum 100% created by Cryptococcus neoformans, the last one 66.7% provided by both Staphylococcus haemolyticus and Moraxella osloensis, minimum 0% produced by Burkholderia cepacia). The accuracy rate also varied with sample type; the highest accuracy rate was found in pleural and ascites fluid (95.8%) followed by bronchoalveolar lavage fluid (88.7%), urine (86.8%), and wound secretions (85.0%), while the lowest was present in cerebrospinal fluid (58.8%). NTS had a diagnostic sensitivity of 94.5% and specificity of 31.8%. The positive and negative predictive values of NTS were 79.9% and 66.7%, respectively. For diagnosis of infectious diseases, the sensitivity was greatly increased by 56.7% in NTS compared with culture (94.5% vs 37.8%). Therefore, NTS can accurately detect the causative pathogens in infectious samples, particularly in pleural and ascites fluid, bronchoalveolar lavage fluid, urine, and wound secretions, with a short turnaround time of 8-14 h, and might innovatively contribute to personalizing antibiotic treatments for individuals with standardized protocols in clinical practices. IMPORTANCE Nanopore targeted sequencing (NTS) is reported to be advantageous in detection speed and range over culture in prior published reports. Investigation of the clinical performance of NTS is deficient at present. In our study, cohort and systematic comparisons among three assays (culture, NTS, and Sanger sequencing) were analyzed retrospectively for the first time. We found that NTS undoubtedly has incomparable advantages in accurately detecting the causative pathogens in infectious samples, particularly in pleural and ascites fluid, bronchoalveolar lavage fluid, urine, and wound secretions, with a short turnaround time of 8-14 h. For sterile specimens like blood and cerebrospinal fluid (CSF), the NTS outcomes should be validated using other nucleic acid based detection technology. Overall, NTS might innovatively contribute to guiding early, targeted antimicrobial therapy with lower cost and reduce overuse of broad-spectrum antibiotics.

Ischemia and reperfusion (I/R) injury is a common cause of hepatocyte injury and liver dysfunction during liver transplantation, but its mechanism is needed further explored. We aimed to investigate whether STING pathway activation is involved in the liver I/R and further determine the role of the microRNA(miR)-24-3p in liver I/R injury in mice. Our data showed that STING mRNA level was negatively related with miR-24-3p in livers of I/R-treated mice. Next, we identified that STING could be bound by miR-24-3p by bioinformatic and luciferase report assay. Moreover, downregulation of STING alleviated the protein expression of p-IRF3 and the serum level of inflammatory factor and aminotransferase in I/R mice model. Furthermore, transfection of I/R treated mice with exogenous miR-24-3p significantly inhibited the protein expression of STING and p-IRF3 in liver, and attenuated serum inflammatory cytokines release, as well as the dysfunction and apoptosis of liver in I/R model in vivo. This study suggests that miR-24-3p may ameliorate inflammatory response and cellular apoptosis in hepatic I/R process by targeting STING, which might be a potential therapeutic target for preventing liver I/R development and progression.

Hepatic ischemia-reperfusion (IR) injury can cause serious liver damage, leading to liver dysfunction after liver surgery, which is associated with NF-κB-mediated inflammation. The K63-linked auto-polyubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6) is essential for the activation of NF-κB. Here, we found that OTU domain-containing protein 4 (OTUD4), a deubiquitinating enzyme (DUB), interacts with TRAF6 and decreases the K63 auto-polyubiquitination of TRAF6. In addition, the data showed that NF-κB activation was impaired and inflammatory factor levels were reduced after overexpressing OTUD4 in a hypoxia/reoxygenation (HR) model and a hepatic IR model. Additionally, the liver inflammatory response and tissue damage were ameliorated in mice overexpressing OTUD4.Taken together, these results show that OTUD4 can negatively regulate NF-κB activation by suppressing the K63-linked ubiquitination of TRAF6, thus alleviating hepatic ischemia-reperfusion injury.

The effects of deep neuromuscular block (DNMB) on chronic postsurgical pain (CPSP) have not been conclusively determined. Moreover, a limited number of studies have examined the impact of DNMB on long-term recovery quality after spinal surgery. We investigated the impact of DNMB on CPSP and the quality of long-term recovery in patients who had been subjected to spinal surgery.