YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance.

OBJECTIVE: Gastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib's effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1's connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1. DESIGN: Utilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments. RESULTS: Higher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1's role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues. CONCLUSIONS: Our findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes.

Identification of a novel Calpain-2-SRC feed-back loop as necessity for ß-Catenin accumulation and signaling activation in hepatocellular carcinoma.

Rapid progression is the major cause of the poor prognosis of hepatocellular carcinoma (HCC); however, the underlying mechanism remained unclear. Here, we found Calpain-2 (CAPN2), a well-established protease that accelerates tumor progression in several malignancies, is overexpressed in HCC and acts as an independent predictor for poor outcomes. Furthermore, CAPN2 promoted the proliferation and invasion of HCC, and showed a positive correlation with the levels of invasion-related markers. Mechanistically, a novel CAPN2-SRC positive regulatory loop was identified upstream of ß-catenin to prevent its ubiquitination and degradation, and subsequently promoted HCC progression: CAPN2 could proteolyze PTP1B to form a truncation of approximately 42 kDa with increased phosphatase activity, resulting in reduced SRC Y530 phosphorylation and increased SRC kinase activity; meanwhile, CAPN2 itself was a bone fide substrate of SRC that was primarily phosphorylated at Y625 by SRC and exhibited increased proteolysis activity upon phosphorylation. Interestingly, the CAPN2-SRC loop could not only restrain most of cytoplasmic ß-catenin degradation by inhibiting GSK3ß pathway, but also prevented TRIM33-induced nuclear ß-catenin degradation even in ß-catenin-mutant cells. Present study identified a CAPN2-SRC positive loop responsible for intracellular ß-catenin accumulation and signaling activation, and targeting CAPN2 protease activity might be a promising approach for preventing HCC progression.

Associations among Audiometric, Doppler Hydroacoustic, and Subjective Outcomes of Venous Pulsatile Tinnitus.

OBJECTIVE: Venous pulsatile tinnitus (PT) has received increasing attention recently. As analyses of psychophysical and neuropsychological dimensions of venous PT are lacking, this study aimed to quantitatively and qualitatively investigate the correlation among audiometric, hydroacoustic, and subjective outcomes in patients with PT. METHODS: Fifty-five venous PT patients, with or without sigmoid sinus wall anomalies (SSWAs), were subdivided into SSWAs (n = 30) and non-SSWAs (n = 25) groups. Audiometric and hemodynamic evaluations were assessed. Questionnaires including the Tinnitus Handicap Inventory, Hospital Anxiety and Depression Scale (HADS), and Athens Insomnia Scale (AIS) were deployed to evaluate the psychological impacts of PT. RESULTS: Among 55 subjects, PT frequency-related pure-tone audiometry (PTA) was significantly different between ipsilesional non-PT frequency-related PTA (p < 0.01), ipsilateral jugular vein compression PTA (p < 0.01), and contralesional ear PTA (p < 0.01). In contrast with the pulsatility index and flow velocity, bilateral EOET and flow volume were significantly different (p < 0.01). Of the 3 questionnaire types, there was a strong correlation between HADS anxiety and AIS scores (r = 0.658, p < 0.01). The duration of PT was not correlated with subjective outcomes, and there was no statistical significance found among audiometric, hemodynamic, and subjective outcomes between SSWAs and non-SSWAs groups. CONCLUSIONS: (1) The duration of PT was irrelevant to the increase of PTA. (2) Venous PT is the perception of vascular flow sound, in which hydroacoustic characteristics can be highly independent. (3) Anxiety, depression, and sleep disorders commonly prevail among PT patients.

CircRNA UBAP2 serves as a sponge of miR-1294 to increase tumorigenesis in hepatocellular carcinoma through regulating c-Myc expression.

Circular RNAs (circRNAs) are a class of regulatory RNAs with complex roles in healthy and diseased tissues. However, the oncogenic role of circRNAs in hepatocellular carcinoma (HCC) remains poorly understood, including the mechanisms by which the circular ubiquitin-binding associated protein 2 (circUBAP2) contributes to tumorigenesis. We analyzed the expression of circUBAP2 in 20 paired samples of HCC and healthy tissue as well as in seven HCC cell lines via quantitative real-time polymerase chain reaction. Functional experiments, such as CCK8 viability assays, colony formation assays, wound healing, transwell assays and flow cytometry, were conducted to assess the effects of circUBAP2 in vitro. To further elucidate the mechanisms by which circUBAP2 acts, we conducted dual-luciferase assays, western blots, RNA pull-down assays and rescue experiments. CircUBAP2 was highly upregulated in most HCC tissues and was associated with poor prognosis. HCC patients with high circUBAP2 expression had greater vascular invasion and worse differentiation. Functionally, circUBAP2 overexpression enhanced HCC cell proliferation, migration and invasion and inhibited apoptosis. Furthermore, we found that circUBAP2 upregulated c-Myc expression by sponging miR-1294, thus contributing to hepatocarcinogenesis. Inhibiting circUBAP2 expression in HCC attenuated the oncogenic effects of c-Myc. These findings suggest that circUBAP2 promotes HCC growth and metastasis. CircUBAP2 may have value as an independent prognostic biomarker or as a new target for the treatment of HCC.

Hydroacoustic analysis and extraluminal compression surgical insights of venous pulsatile tinnitus.

OBJECTIVE: This study aimed to quantitatively and qualitatively evaluate the hydroacoustic changes from "presence" to "disappearance" of pulsatile tinnitus (PT) with the extraluminal compression surgical technique. The recent issues of concern pertaining to the hydroacoustic characteristics of sigmoid sinus wall anomalies and distal transverse sinus stenosis (dTSS) were discussed. METHODS: This study was based on a retrospective case series. Seventy-seven patients with PT and transverse-sigmoid sinus enlargement with or without transverse-sigmoid sinus junction anomalies and transverse sinus stenosis (TSS) who had undergone extraluminal compression surgery under local anesthesia were included. Management of intractable intraoperative challenges and techniques for reversal extraluminal compression were introduced. Anatomical measurements, intraoperative color-coded Doppler ultrasonography, spectro-temporal analysis, and computational fluid dynamics were employed to analyze the hydroacoustic characteristics of PT. RESULTS: The efficacy of the extraluminal compression technique was evident with the significant reduction in peak turbulent kinetic energy, vorticity, and mean pressure gradient at the transverse-sigmoid junction, resulting in over 20% reduction in PT amplitude. dTSS is a common finding in patients with PT exhibiting transverse-sigmoid sinus enlargement. Patients with dTSS presented with significant differences in hemodynamic characteristics as compared to those without. Linear regression analysis showed that the flow disturbance (turbulent kinetic energy and vorticity) was closely associated with the degree of dTSS, whereas the flow amplitude was not related to the degree or location of TSS. Low-pulsatory vortex flow at the transverse-sigmoid junction was visualized during an intraoperative color-coded Doppler examination, and the displayed low-frequency PT sound corresponded to the patients' subjective perception of PT. CONCLUSION: (1) A reduction of over 20% of the flow-induced noise is the therapeutic goal of extraluminal compression technique. Since reductions in the magnitude of hemodynamic parameters, including turbulent kinetic energy, vorticity, and mean pressure gradient, render the flow-induced noise inaudible, besides sigmoid sinus wall anomalies, it is likely that PT develops from the aggregation of flow-based pathologies. (2) Although dTSS and diverticulum may greatly affect the hemodynamics at the transverse-sigmoid junction, in contrast to dehiscence, dTSS and diverticulum may not be the limiting factors for PT development.

Recent Advances in Energy Conversion Applications of Carbon Dots: From Optoelectronic Devices to Electrocatalysis.

Exploitation and utilization of sustainable energy sources has increasingly become the common theme of global social development, which has promoted tremendous development of energy conversion devices/technologies. Owing to excellent and unique optical/electrical properties, carbon dots (CDs) have attracted extensive research interest for numerous energy conversion applications. Strong absorption, downconversion photoluminescence, electron acceptor/donor characteristics, and excellent electron conductivity endow CDs with enormous potential for applications in optoelectronic devices. Furthermore, excellent electron transfers/transport capacities and easily manipulable structural defects of CDs offer distinct advantages for electrocatalytic applications. Recent advances in CD-based energy conversion applications, including optoelectronic devices such as light-emitting diodes and solar cells, and electrocatalytic reactions including the hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, and carbon dioxide reduction reaction, are summarized. Finally, current challenges and future prospects for CD-based energy conversion applications are proposed, highlighting the importance of controllable structural design and modifications.

Meta-Analysis of the Effect of the Clinical Pathway Applied to Patients with Endoscopic Sinus Surgery in China.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common diseases in China. The incidence of CRS in the Chinese urban population is between 5 and 15%. It is difficult to cure with traditional surgery. Endoscopic sinus surgery is the first choice for the treatment of CRS. Compared with developed countries, the development of the clinical pathway of endoscopic sinus surgery in China is still unclear. OBJECTIVES: The aim is to explore whether the clinical pathway of endonasal sinus surgery is better than the traditional one in the Chinese population. METHODS: We searched PubMed, Embase, the Cochrane Library, Web of Science, ClinicalTrials.gov, SinoMed, China National Knowledge Internet, Wanfang database of Chinese Journals, and VIP database of Chinese Journals. The last retrieval date was August 24, 2018. Review Manager 5.3 software was used for comprehensive quantification data analysis. RESULTS: Fourteen papers involving 1,882 patients were included in this study. The results showed that compared with the traditional pathway, the clinical pathway can effectively shorten the average number of hospitalization days (mean difference, MD = -2.00, 95% CI: -2.50, -1.49). In total, 10 of the 14 papers, with a total of 1,500 patients, proved that the clinical pathway can effectively reduce the hospitalization costs of patients (standard mean difference, SMD = -3.15, 95% CI: -4.20, -2.10); 11 of the 14 papers, with a total of 1,488 patients, proved that the clinical pathway can effectively improve patients' knowledge of health (95% CI:1.03, 1.09); and 7 of the 14 papers, with a total of 810 patients, proved that the clinical pathway can effectively improve patient satisfaction (95% CI:1.10, 1.20). CONCLUSIONS: Our systematic review and meta-analysis support the use of the clinical pathway in patients with endoscopic sinus surgery in China.

Analyzing polymeric matrix for fabrication of a biodegradable microneedle array to enhance transdermal delivery.

Traditional drug delivery systems, using invasive, transdermal, and oral routes, are limited by various factors, such as the digestive system environment, skin protection, and sensory nerve stimulation. To improve the drug delivery system, we fabricated a polysaccharide-based, dissolvable microneedle-based array, which combines the advantages of both invasive and transdermal delivery systems, and promises to be an innovative solution for minimally invasive drug delivery. In this study, we designed a reusable aluminum mold that greatly improved the efficiency and convenience of microneedle fabrication. Physical characterization of the polysaccharides, individual or mixed at different ratios, was performed to identify a suitable molecule to fabricate the dissolvable microneedle. We used a vacuum deposition-based micro-molding method at low temperature to fabricate the model. Using a series of checkpoints from material into product, a systematic feedback mechanism was built into the "all-in-one" fabrication step, which helped to improve production yields. The physical properties of the fabricated microneedle were assessed. The cytotoxicity analysis and animal testing of the microneedle demonstrated the safety and compatibility of the microneedle, and the successful penetration and effective release of a model protein.

Tribochemical mechanism of amorphous silica asperities in aqueous environment: a reactive molecular dynamics study.

Reactive molecular dynamics (ReaxFF) simulations are used to explore the atomic-level tribochemical mechanism of amorphous silica (a-SiO2) in a nanoscale, single-asperity contact in an aqueous environment. These sliding simulations are performed in both a phosphoric acid solution and in pure water under different normal pressures. The results show that tribochemical processes have profound consequences on tribological performance. Water molecules could help avoid direct adhesive interaction between a-SiO2 surfaces in pure water under low normal load. However, formation and rupture of interfacial siloxane bonds are obviously observed under higher normal load. In phosphoric acid solution, polymerization of phosphoric acid molecules occurs, yielding oligomers under lower load, and tribochemical reactions between the molecules and the sliding surfaces could enhance wear under higher load. The bridging oxygen atoms in silica play an important role in the formation of interfacial covalent bonds, and hydrogen is found to have a weakening effect on these bonds, resulting in the rupture during shear-related loading. This work sheds light on tribochemical reactions as a mechanism for lubrication and wear in water-based or other tribological systems.

A protein concentration measurement system using a flexural plate-wave frequency-shift readout technique.

A protein concentration measurement system with two-port flexural plate-wave (FPW) biosensors using a frequency-shift readout technique is presented in this paper. The proposed frequency-shift readout method employs a peak detecting scheme to measure the amount of resonant frequency shift. The proposed system is composed of a linear frequency generator, a pair of peak detectors, two registers, and a subtractor. The frequency sweep range of the linear frequency generator is limited to 2 MHz to 10 MHz according to the characteristics of the FPW biosensors. The proposed frequency-shift readout circuit is carried out on silicon using a standard 0.18 µm CMOS technology. The sensitivity of the peak detectors is measured to be 10 mV. The power consumption of the proposed protein concentration measurement system is 48 mW given a 0.1 MHz system clock.

[Analysis of the spatial and temporal characteristics of measles patients younger than 1 year old in Shandong province].

OBJECTIVE: To explore the spatial and temporal characteristics of measles patients younger than 1 year old in Shandong province. METHODS: A total of 5309 cases of measles, whose patients were younger than 1 year old in Shandong province between year 1999 and 2008 were collected. The epidemic features of measles were described, and the annual infant incidence was calculated. Software ArcGIS9.3 was applied to draw the spatial map of the disease, and the software GeoDa0.95i-beta was adopted to analyze the spatial autocorrelation. RESULTS: The incidence among infants younger than 1 year old reported in Shandong province rose from 23.45/100 000 (206 cases) in 1999 to 269.60/100 000 (2791 cases) in 2008.5309 cases covered all month-aged infants under 1 year old, except 12 months old. Most patients (3494 cases) aged between 6 - 9 months old; especially the infants around 8 months old, accounting for 20.7% (1100/5309). The epidemic peak was between March and May, accounting for 45.5% (2414/5309). The spatial and temporal distribution features showed an up and down temporal trend and an increase from east to west in spatial trend. The global Moran's I values of measles incidence among infants in Shandong province were 0.346, 0.150, 0.396, 0.213, 0.477, 0.354 and 0.331 in year 1999, 2001 - 2002, 2005 - 2008 (P < 0.01) and 0.076 in year 2004 (P < 0.05). The local spatial autocorrelation analysis showed that southwest and northwest districts of Shandong were highly clustered districts of measles. CONCLUSION: In Shandong, the measles incidence among infants younger than 1 year old rose obviously; especially the infants aged between 6-9 months age. The epidemic peak was between March and May. A positive spatial correlation was found, the disease showed a distinct regional distribution feature, and a cluster district was found.

[PAH sources in road runoff system in Beijing].

In this study, road runoff, rainwater, ground sediment and roadside tree water samples were collected from three types of roads in Beijing in 2006. The samples were analyzed for polycyclic aromatic hydrocarbons (PAHs). The average PAH concentrations in each media in May-June were generally higher than those in July-August. Factor analysis indicated that PAHs in road runoff were mainly from ground sediment, and rainwater and roadside tree water also had certain influence to road runoff. Multiple regression analysis indicated that PAHs in ground sediment and road runoff mainly come from vehicular emission at the vehicle way and branch road, and at the bicycle way, the contributions of vehicular emission and coal combustion were equal. PAHs in rain were mainly from coal/oil combustion, and PAHs in roadside tree water were dominated by vehicular emission source.

[Residue level of HCHs in chicken].

The concentrations of hexachlorocyclohexane isomers (HCHs) in muscle, skin, liver, stomach, heart, eggs, feed and feces of chicken from a poultry farm were determined by GC-ECD. The residue level of total HCHs (SigmaHCHs) in muscle, skin, liver, stomach and heart were (0.35 +/- 0.37), (3.91 +/- 2.52), (1.78 +/- 1.26), (1.00 +/- 0.85), (1.35 +/- 0.75) ng/g (wet weight), while the lipid normalized concentrations were (64.3 +/- 171), (19.6 +/- 7.33), (64.9 +/- 27.2), (74.5 +/- 74.1), (17.8 +/- 4.42) ng/g, respectively,which are far lower than the Maximum Residue Limits for Food in China. Among all tissue samples, the highest lipid-normalized concentration was observed in the liver and no significant differences were observed among other organs. delta-HCH was the predominant isomer in chicken feed, stomach and faces, while beta-HCH owned the highest concentration in all other samples. beta-HCH was enriched in muscle, skin, liver, stomach and heart, while alpha-HCH and delta-HCH were also enriched in liver. Significant difference was revealed between male and female chicken in terms of bioaccumulation, indicating higher bioaccumulation ability of the former.