Invasion and metastasis of hepatocellular carcinoma (HCC) is still an important reason for poor prognosis. LincRNA ZNF529-AS1 is a recently identified tumour-associated molecule that is ...differentially expressed in a variety of tumours, but its role in HCC is still unclear. This study investigated the expression and function of ZNF529-AS1 in HCC and explored the prognostic significance of ZNF529-AS1 in HCC.
Based on HCC information in TCGA and other databases, the relationship between the expression of ZNF529-AS1 and clinicopathological characteristics of HCC was analysed by the Wilcoxon signed-rank test and logistic regression. The relationship between ZNF529-AS1 and HCC prognosis was evaluated by Kaplan‒Meier and Cox regression analyses. The cellular function and signalling pathways involved in ZNF529-AS1 were analysed by GO and KEGG enrichment analysis. The relationship between ZNF529-AS1 and immunological signatures in the HCC tumour microenvironment was analysed by the ssGSEA algorithm and CIBERSORT algorithm. HCC cell invasion and migration were investigated by the Transwell assay. Gene and protein expression were detected by PCR and western blot analysis, respectively.
ZNF529-AS1 was differentially expressed in various types of tumours and was highly expressed in HCC. The expression of ZNF529-AS1 was closely correlated with the age, sex, T stage, M stage and pathological grade of HCC patients. Univariate and multivariate analyses showed that ZNF529-AS1 was significantly associated with poor prognosis of HCC patients and could be an independent prognostic indicator of HCC. Immunological analysis showed that the expression of ZNF529-AS1 was correlated with the abundance and immune function of various immune cells. Knockdown of ZNF529-AS1 in HCC cells inhibited cell invasion and migration and inhibited the expression of FBXO31.
ZNF529-AS1 could be a new prognostic marker for HCC. FBXO31 may be the downstream target of ZNF529-AS1 in HCC.
•Nitrate has a dual effect on sediment phosphorus release in shallow lakes•Nitrate can reduce sediment phosphorus release through oxidation•Nitrate can promote phosphorus release by stimulating ...phytoplankton growth•Alkaline phosphatase secreted by phytoplankton explains the phosphorus release•The effects of nitrate loading on sediment phosphorus release are dose-dependent
Phosphorus (P) release from sediment is a key process affecting the effectiveness of eutrophication mitigation. We hypothesized that high nitrate (NO3−) input may have dual effect on sediment P release: reduce the sediment P release by improving the oxidation of sediment or promote P release by stimulating the growth of phytoplankton and increase the decomposition rates and oxygen consumption at the sediment water interface. To test the effect of different NO3− concentrations, we conducted a three-month experiment in 15 cement tanks (1 m3), with five targeted concentrations of NO3−: control, 2 mg L−1, 5 mg L−1, 10 mg L−1, and 15 mg L−1. The results showed that: i) when NO3− was maintained at high levels: NO3−≥5–7 mg L−1 (range of median values), there was no effect of NO3− on net P release from the sediment, likely because the positive effects of NO3− (increasing oxidation) was counteracted by a promotion of phytoplankton growth. ii) after NO3− addition was terminated NO3− dropped sharply to a low level (NO3−≤0.4 mg L−1), followed by a minor P release in the low N treatments but a significant P release in the high N treatments, which likely reflect that the inhibition effect of NO3− on P release decreased, while the promotion effects at high NO3− concentrations continued. The results thus supported our hypotheses of a dual effect on sediment P release and suggest dose-dependent effect of NO3− loading on stimulating P release from the sediment, being clear at high NO3− exceeding 5–7 mg L−1.
Display omitted
Taxi ridesharing can be of significant social and environmental benefit, e.g. by saving energy consumption and satisfying people's commute needs. Despite the great potential, taxi ridesharing, ...especially with dynamic queries, is not well studied. In this paper, we formally define the dynamic ridesharing problem and propose a large-scale taxi ridesharing service. It efficiently serves real-time requests sent by taxi users and generates ridesharing schedules that reduce the total travel distance significantly. In our method, we first propose a taxi searching algorithm using a spatio-temporal index to quickly retrieve candidate taxis that are likely to satisfy a user query. A scheduling algorithm is then proposed. It checks each candidate taxi and inserts the query's trip into the schedule of the taxi which satisfies the query with minimum additional incurred travel distance. To tackle the heavy computational load, a lazy shortest path calculation strategy is devised to speed up the scheduling algorithm. We evaluated our service using a GPS trajectory dataset generated by over 33,000 taxis during a period of 3 months. By learning the spatio-temporal distributions of real user queries from this dataset, we built an experimental platform that simulates user real behaviours in taking a taxi. Tested on this platform with extensive experiments, our approach demonstrated its efficiency, effectiveness, and scalability. For example, our proposed service serves 25% additional taxi users while saving 13% travel distance compared with no-ridesharing (when the ratio of the number of queries to that of taxis is 6).
Flexible hydrogel sensors have expanded the applications of electronic devices due to their suitable mechanical properties and excellent biocompatibility. However, conventionally synthesized reduced ...graphene oxide (rGO) encounters limitations in reduction degree and dispersion, restricting the conductivity of graphene hydrogels and impeding the development of high-sensitivity flexible sensors. Moreover, hydrogels are susceptible to inflammation and bacterial infections, jeopardizing sensor stability over time. Thus, the challenge persists in designing conductive hydrogels that encompass high sensitivity, antibacterial efficacy, and anti-oxidative capabilities. In this study, GO was modified and reduced via a heparin-polydopamine (Hep-PDA) complex, yielding well-reduced and uniformly dispersed Hep-PDA-rGO nanosheets. Consequently, a hydrogel utilizing Hep-PDA-rGO was synthesized, showcasing commendable conductivity (3.63 S/m) and sensor performance, effectively applied in real-time motion monitoring. Notably, the hydrogel's attributes extend to facilitating chronic diabetic wound healing. It maintained a suitable inflammatory environment credited to its potent antibacterial and antioxidative properties, while its inherent conductivity promoted angiogenesis. The multifunctional nature of this hydrogel highlight its potential not only as an epidermal sensor but also as a promising dressing candidate for chronic wound treatment.
To define the efficacy of venetoclax with extended follow-up and identify clinical or biological treatment effect modifiers, updated data for previously treated patients with chronic lymphocytic ...leukemia (CLL) or small lymphocytic lymphoma (SLL) enrolled in 4 early-phase trials were pooled. Rates of response, complete remission (CR/CRi), and undetectable minimal residual disease (U-MRD) were analyzed for all patients (n = 436) and for those patients who were planned to receive 400 mg/day monotherapy (n = 347). Univariate and multiple regression analyses were performed to identify the pretreatment factors associated with response rates and duration of response (DoR). Objective responses were documented in 75% of all patients, including 22% CR/CRi. Overall, 27% and 16% of the patients achieved U-MRD in blood and marrow, respectively. Estimated median progression-free survival (PFS), DoR, and time to progression were 30.2, 38.4, and 36.9 months, respectively. Similar efficacy outcomes were observed within the 400 mg/day monotherapy subset. For those who achieved CR/CRi, the 3-year PFS estimate was 83%. DoR was superior for patients achieving CR/CRi or U-MRD in landmark analyses. In multiple regression analyses, bulky lymphadenopathy (≥5 cm) and refractoriness to B-cell receptor inhibitor (BCRi) therapy were significantly associated with lower CR rate and shorter DoR. Fewer prior therapies were associated with higher CR rate, but not DoR. Chromosome 17p deletion and/or TP53 mutation and NOTCH1 mutation were consistently associated with shorter DoR, but not probability of response. Thus, both pretreatment factors and depth of response correlated with DoR with venetoclax. Patients without bulky lymphadenopathy, BCRi-refractory CLL, or an adverse mutation profile had the most durable benefit.
•Patients with relapsed CLL achieving complete remission or undetectable MRD on venetoclax treatment have the most durable responses.•Less durable responses are associated with bulky adenopathy, TP53 aberrations, NOTCH1 mutations, and prior refractoriness to BCRis.
Display omitted
Gastric cancer (GC) is one of the most common tumors worldwide and the leading cause of tumor-related mortality. Endoscopy and serological tumor marker testing are currently the main methods of GC ...screening, and treatment relies on surgical resection or chemotherapy. However, traditional examination and treatment methods are more harmful to patients and less sensitive and accurate. A minimally invasive method to respond to GC early screening, prognosis monitoring, treatment efficacy, and drug resistance situations is urgently needed. As a result, liquid biopsy techniques have received much attention in the clinical application of GC. The non-invasive liquid biopsy technique requires fewer samples, is reproducible, and can guide individualized patient treatment by monitoring patients' molecular-level changes in real-time. In this review, we introduced the clinical applications of circulating tumor cells, circulating free DNA, circulating tumor DNA, non-coding RNAs, exosomes, and proteins, which are the primary markers in liquid biopsy technology in GC. We also discuss the current limitations and future trends of liquid biopsy technology as applied to early clinical biopsy technology.
In this paper, an adaptive fuzzy fault-tolerant control (FTC) scheme is proposed for active seat suspension systems. The addressed system contains electromagnetic actuator faults. In addition, the ...constraints of the displacements of the car seat, active suspension, and wheel, their vertical vibration speeds and current intensity are included. In the control design, since the systems have dynamic characteristics of complexities and spring non-linearities, the fuzzy logic systems are utilized to approximate the unknown nonlinear dynamics. By the aid of Barrier Lyapunov functions and based on the adaptive backstepping recursive design algorithm, a novel adaptive fuzzy FTC scheme is formulated. When the electromagnetic actuator fails, the developed control scheme can guarantee that all the vertical vibration states are stable. Eventually, the effectiveness of the presented control method is offered to illustrate by a random road surface.
Gastric cancer (GC) is one of the most common malignant tumors globally and the third leading cause of cancer-related death. Currently, the sensitivity and specificity of diagnostic markers for GC ...are low, so it is urgent to find new biomarkers with higher sensitivity and specificity. tRNA-derived small RNAs are a kind of small non-coding RNAs derived from tRNAs. It is abundant in cancer cells and body fluids. Our goal is to find the differentially expressed tRNA-derived small RNAs in GC to explore their potential as a GC biomarker.
Quantitative real-time PCR was used to detect the expression level of hsa_tsr016141. The molecular characteristics of hsa_tsr016141 were verified by agarose gel electrophoresis, Sanger sequencing, Actinomycin D Assay, and Nuclear and Cytoplasmic RNA Separation Assay. The diagnostic efficiency of hsa_tsr016141 was analyzed through receiver operating characteristic.
The expression level of hsa_tsr016141 in GC tissues and serum was significantly increased. The serum expression level showed a gradient change between GC patients, gastritis patients, and healthy donors and was positively correlated with the degree of lymph node metastasis and tumor grade. ROC analysis showed that the serum expression level of hsa_tsr016141 could significantly distinguish GC patients from healthy donors or gastritis patients. Besides, the expression level of hsa_tsr016141 in GC patients decreased significantly after the operation (P<0.0001).
Serum hsa_tsr016141 has good stability and specificity and can be used for dynamic monitoring of GC patients, suggesting that serum hsa_tsr016141 can be a novel biomarker for GC diagnosis and postoperative monitoring.
Patients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with ...acceptable side-effect profiles are needed for this patient population.
In this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo. We randomly assigned 220 patients with decreased renal function, previous therapy-induced myelosuppression, or major coexisting illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily. The primary end point was progression-free survival. At the first prespecified interim analysis, the study was stopped early on the recommendation of the data and safety monitoring board owing to overwhelming efficacy.
The median progression-free survival was 5.5 months in the placebo group and was not reached in the idelalisib group (hazard ratio for progression or death in the idelalisib group, 0.15; P<0.001). Patients receiving idelalisib versus those receiving placebo had improved rates of overall response (81% vs. 13%; odds ratio, 29.92; P<0.001) and overall survival at 12 months (92% vs. 80%; hazard ratio for death, 0.28; P=0.02). Serious adverse events occurred in 40% of the patients receiving idelalisib and rituximab and in 35% of those receiving placebo and rituximab.
The combination of idelalisib and rituximab, as compared with placebo and rituximab, significantly improved progression-free survival, response rate, and overall survival among patients with relapsed CLL who were less able to undergo chemotherapy. (Funded by Gilead; ClinicalTrials.gov number, NCT01539512.).
Ibrutinib increases the risk of atrial fibrillation (AF), but the associated risk factors are not clearly defined. We performed retrospective review of ibrutinib-treated patients in a large academic ...practice to identify risk factors for new-onset AF. Variables with p-values <.05 in logrank analysis were included as pairs in two-variable Cox regression. Of the 168 patients treated with ibrutinib, 60.7% had chronic lymphocytic leukemia/small lymphocytic lymphoma and 39.3% other histologies. The incidence of AF was 11.9% after a median 154-day ibrutinib exposure. Only heart failure (hazard ratio, 95% confidence interval; 14.1, 5.3-37.2) and left atrial abnormality on electrocardiogram (5.4, 1.9-15.4) were independently significant in paired Cox regression. Eighty-seven percent of patients with HF satisfied Framingham clinical criteria. As structural heart disease is a strong risk factor for incident AF, we emphasize the importance of baseline electrocardiogram, recommend baseline clinical screening for HF and, in specific instances, a baseline echocardiogram.
PDF
