Nanofluidic Membrane-Assisted Organic Electrochemical Transistors for Bioinspired Gustatory Sensation Based on Selective Cation Transport.

Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

Glutathione-activated biotin-targeted dual-modal imaging probe with improved PDT/PTT synergistic therapy.

BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

Immobilization of multilayer sodium alginate/polysaccharide antibacterial material composite beads as glufosinate controlled release matrices.

To find a new way to slow down the release of glufosinate (GA) pesticide and to solve the susceptibility to decomposition by soil microorganisms, a series of novel antibacterial polysaccharide-based sustained release beads (PSRB) were prepared. The PSRB was prepared by immobilization of GA loaded polysaccharide-based chitosan quaternary ammonium salt (PS-HACC) microcapsules in the core and layers of the multilayer sodium alginate beads. The PSRB was characterized by FI-IR spectroscopy, XRD, SEM, and BET to reveal their composition and surface morphology. The optimal conditions of the slow release beads were as follows, the concentration of Ca2+, pH, temperature and the coating layer number was 0.1 mol/L, 7, 25 °Cand 3, respectively. The kinetic study showed that the slow release of PSRB was in accordance with the Higuchi kinetic model, and the FI-IR and XRD analyses revealed that the PS-HACC and GA were successfully cross-linked to the PSRB. BET showed that PSRB were greater than PSRB3 at surface area, pore volume and pore size. Inhibition circles experiments demonstrated that WPSRB3 has good antibacterial activity. The weed control in soybean with PSRB3 application is perfect and the weed control cycle is long. Therefore, this technology can provide a potential way to control GA release, improve utilization efficiency, reduce pesticide use and environmental pollution, and at the same time, provide a potential way to achieve ecological agriculture.

[Distribution Characteristics and Source Analysis of Carbonaceous Aerosols Before and After the Spring Festival in the Guanzhong Plain].

The spatio-temporal variation characteristics and potential sources of carbonaceous aerosols in the Guanzhong Plain during the Spring Festival in 2023 were analyzed using inverse distance weighting spatial interpolation （IDW）, secondary organic carbon （SOC） estimation, and potential source contribution factor analysis （PSCF）, with the OC and EC in the PM2.5 of five cities： Xi'an, Baoji, Xianyang, Weinan, and Tongchuan as the research objects. The results showed that in terms of time distribution, ρ（OC） was as follows： after the Spring Festival [（18.6 ±11.0） µg·m-3] > during the Spring Festival [（16.2 ±15.1） µg·m-3] > before the Spring Festival [（10.0 ±8.3） µg·m-3], and ρ（EC） was as follows： after the Spring Festival [（2.2 ±1.2） µg·m-3] > during the Spring Festival [（1.7 ±1.5） µg·m-3] > before the Spring Festival [（1.4 ±1.1） µg·m-3], which indicated that OC and EC concentrations were the most severe after the Spring Festival. In terms of spatial distribution, ρ（OC） was as follows： Xianyang [（21.4 ±17.3） µg·m-3] > Baoji [（15.8 ±12.8） µg·m-3] > Xi'an [（13.6 ±11.3） µg·m-3] > Weinan [（11.6 ±9.1） µg·m-3] > Tongchuan [（10.0 ±8.3） µg·m-3], and ρ（EC） was as follows： Xianyang [（2.1 ±1.4） µg·m-3] > Weinan [（1.8 ±1.4） µg·m-3] > Xi'an [（1.8 ±1.2） µg·m-3] > Tongchuan [（1.6 ±1.4） µg·m-3] > Baoji [（1.2 ±0.9） µg·m-3]. Overall, Xianyang had the most severe PM2.5 and carbon aerosol pollution, whereas Tongchuan had the least pollution. IDW results showed that the high-value center of OC and EC concentration [ρ（OC） > 27.3 µg·m-3, ρ（EC） > 2.9 µg·m-3] was in the middle of the plain, the low-value center of OC and EC concentration [ρ（OC） <7.0 µg·m-3, ρ（EC） < 1.0 µg·m-3] was in the northern plain, and the distribution of OC was higher in the west and lower in the east, whereas the distribution of EC was higher in the east and lower in the west. The proportion of SOC in OC was as follows： after the Spring Festival （51.7%） > during the Spring Festival （41.1%） > before the Spring Festival （36.8%）. The SOC/OC values of each city and the contribution rate of SOC of each city to the Guanzhong Plain indicated that Tongchuan, Baoji, and Xianyang were greatly affected by the secondary conversion of organic carbon. The correlation of OC and EC before, during, and after the Spring Festival （r = 0.85, r = 0.98, and r = 0.94, respectively） indicated a high degree of homology between them. Carbonaceous aerosols had a certain correlation with humidity and wind speed before and during the Spring Festival but had a weak correlation with meteorological factors after the Spring Festival. Carbonaceous aerosols generally were strongly correlated with CO and NO2, and the correlation was strongest after the Spring Festival, whereas the correlation with SO2 was strongest during the Spring Festival. The potential source areas of carbonaceous aerosols in the five cities were mainly concentrated in the local and surrounding areas of southern Gansu, northern Shaanxi, and southern Shaanxi. They were also affected by long-distance transportation from the northwest before the Spring Festival.

Exploring a maize-derived dietary fiber-phenolic acid complex with prebiotic effects.

The structural, functional, and prebiotic properties of three maize-derived cell wall dietary fiber-phenolic acid complexes (CWDFPC1, CWDFPC2, and CWDFPC3) were investigated. The results showed that all three CWDFPCs had similar proximate composition and XRD pattern (type I). However, there were significant differences in the phytochemical profiles of their phenolic compounds (PC). Although the testa was the primary source of bound PC (BPC) in all three CWDFPCs, CWDFPC2 had the highest BPC content (15.41 mg GAE/g) and exhibited the greatest antioxidant activity in vitro (DPPH and ABTS assays). The water holding capacity of CWDFPC1 (6.53 g/g) and CWDFPC3 (6.86 g/g) was higher than CWDFPC2 (4.84 g/g), and three CWDFPCs had similar nitrite ion adsorption capacity, bile adsorption capacity, and cation-exchange capacity. After 48 h of in vitro fecal fermentation, CWDFPC2 produced more short-chain fatty acids (46.33 mM) compared to CWDFPC1 and CWDFPC3 (40.26 mM and 44.20 mM, respectively).

Inhibiting NF-κB inducing kinase improved the motor performance of ALS animal model.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a typical neurodegenerative disorder typically characterized by inflammation activation. However, the relationship between non-canonical NF-κB (ncNF-κB) pathway activation and ALS progression is not clear. METHODS: We tested the ncNF-κB pathway in the ALS animal model including hSOD1-G93A transgenic mice and TBK1 deletion mice.We treated age-matched SOD1-G93A mice with B022 (a NIK inhibitor) to investigate the role of NIK in the ALS animal model. We also established a new mice model by crossing SOD1-G93A mice with NIK+/- mice to further evaluate the interrelationship between the NIK and the disease progression in ALS animal model. RESULTS: In this study, we found the ncNF-κB pathway was activated in SOD1-G93A animal model and TBK1 deletion model. Inhibition of NIK activity by small molecule B022 significantly improved the motor performance of the ALS animal model. However, NIK deletion enhanced the mutant SOD1 toxicity by inflammatory infiltration. CONCLUSION: TBK1 deletion and mutant SOD1 shared the common pathological feature possibly via effects on NIK activation and inhibitor of NIK could be a novel strategy for treating ALS.

Association of late-life blood pressure change with cerebral small vessel disease in the MIND-China study.

OBJECTIVES: This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). METHODS: This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. RESULT: The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. CONCLUSIONS: CSVDs are associated with increased exposure to elevated BP later in life.

Iron metabolism biomarkers and mortality risk in U.S. patients with congestive heart failure: NHANES 1999-2018 analysis.

BACKGROUND AND AIMS: Iron deficiency is a major public health concern. We aimed to assess the predictive capability of 4 iron metabolism biomarkers for all-cause and cardiovascular disease-specific mortality in U.S. patients with congestive heart failure (CHF). METHODS AND RESULTS: 1904 CHF patients aged ≥20 years were enrolled from NHANES, 1999-2000 to 2017-2018. All analyses were weighted to provide nationally representative estimates. Among 1905 CHF patients, mean age was 71 years, and 1024 (53.8%), 459 (24.1%), 206 (10.8%), and 216 (11.3%) were Non-Hispanic Black, Non-Hispanic White, Hispanic-Mexican American, and Hispanic-Other Hispanic, respectively. During follow-ups, 1080 deaths occurred. Median follow-up time was 5.08 years. Per-unit increase in natural-logarithmic-transformed iron and transferrin saturation decreased all-cause mortality risk separately by 33.0% (adjusted hazard ratio: 0.670, 95% confidence interval: 0.563 to 0.797, P < 0.001) and 32.6% (0.674, 0.495 to 0.917, 0.013), and per-unit increase in transferrin receptor increased mortality risk by 33.7% (1.337, 1.104 to 1.618, 0.004). Two derivates from 3 significant iron biomarkers were generated - transferrin receptor to natural-logarithmic-transformed iron ratio (TRI) and transferrin receptor to natural-logarithmic-transformed transferrin saturation ratio (TRTS), which were significantly associated with all-cause mortality, with per-unit increase corresponding to 2.692- and 1.655-fold increased all-cause mortality risk (P: 0.003 and 0.023). Only iron and TRTS were associated with the significant risk of cardiovascular disease-specific mortality (P: 0.004 and 0.017). CONCLUSIONS: Our findings identified 3 iron metabolism biomarkers that were individually, significantly, and independently associated with all-cause mortality in patients with CHF, and importantly 2 derivates generated exhibited stronger predictive capability.

Exosomal Hsp27 protein are associated with heart failure in STZ-induced type 1 diabetic rats.

The researchers evaluated cardiac function by measuring the left ventricular ejection fraction and fractional shortening. Plasma samples were collected to measure the levels of EVs and Hsp27. The presence and levels of Hsp27 within the EVs were analyzed. The researchers observed the protective effect of Hsp27-overexpressed BMSC exosomes on heart failure in the rats. The levels of plasma EVs were lower in these rats compared to the control rats. Additionally, the EVs derived from the plasma of the rats with STZ-induced type 1 diabetes contained lower levels of Hsp27. The overexpression of Hsp27 in BMSCs effectively improved heart failure induced by STZ in the rats. The results of this study suggest that EVs and their cargo, specifically Hsp27, play a role in the development of heart failure in individuals with type 1 diabetes.

Study on the impact of comprehensive geriatric assessment on anxiety and depression in chronic obstructive pulmonary disease patients.

BACKGROUND: Psychological factors such as anxiety and depression will not only aggravate the symptoms of chronic obstructive pulmonary disease (COPD) patients and reduce the quality of life of patients, but also affect the treatment effect and long-term prognosis. Therefore, it is of great significance to explore the clinical application of senile comprehensive assessment in the treatment of COPD and its influence on psychological factors such as anxiety and depression. AIM: To explore the clinical application of comprehensive geriatric assessment in COPD care and its impact on anxiety and depression in elderly patents. METHODS: In this retrospective study, 60 patients with COPD who were hospitalized in our hospital from 2019 to 2020 were randomly divided into two groups with 30 patients in each group. The control group was given routine nursing, and the observation group was given comprehensive assessment. Clinical symptoms, quality of life [COPD assessment test (CAT) score], anxiety and depression Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD) were compared between the two groups. RESULTS: CAT scores in the observation group decreased from an average of 24.5 points at admission to an average of 18.3 points at discharge, and in the control group from an average of 24.7 points at admission to an average of 18.3 points at discharge. The average score was 22.1 (P < 0.05). In the observation group, HAMA scores decreased from 14.2 points at admission to 8.6 points at discharge, and HAMD scores decreased from 13.8 points at admission to 7.4 points at discharge. The mean HAMD scores in the control group decreased from an average of 14.5 at admission to an average of 12.3 at discharge, and from an average of 14.1 at admission to an average of 11.8 at discharge. CONCLUSION: The application of comprehensive geriatric assessment in COPD care has a significant effect on improving patients' clinical symptoms and quality of life, and can effectively reduce patients' anxiety and depression.

Clinical implications of persistent joint pain after gout flare.

OBJECTIVES: A subset of gout patients developed persistent joint pain after flares. Analysis of this clinical phenomenon may shed further light on the factors related to worsening gout and even provide clues to its pathogenesis. METHODS: We analyzed the clinical, laboratory, and ultrasound data of gout patients to explore the associations of these data with persistent joint pain after gout flares. RESULTS: A total of 1029 gout patients were included: 182 (17.7%) patients with persistent joint pain and 847 (82.3%) patients with nonpersistent joint pain. Patients with persistent joint pain had more total involved joints, more gout flares in the past year, and more joints with simultaneous gout flares (P<0.01). Among the ultrasound-detected lesions, patients with persistent joint pain had a higher incidence of tophus (36.4% vs. 21.1%) and bone erosion (18.6% vs. 8.6%) (P<0.05). Higher UA and lower TBil were found in patients with persistent joint pain (P<0.001). Hypertension (54.9% vs. 38.7%) and metabolic syndrome (58.8% vs. 46.4%) were both more frequent in patients with persistent joint pain (P<0.05). TBil was negatively correlated with the incidence of persistent joint pain (P<0.001, r=-0.190), UA values (P<0.001, r=-0.125), and metabolic syndrome scores (P<0.001, r=-0.192). A correlation curve was fitted using LOESS (locally weighted region). CONCLUSION: Persistent joint pain after gout flares is a marker of increased disease burden in gout. The significance of the level of total bilirubin for the exacerbation of gout deserves further study.

Unified calibration of D-dimer can improve the uniformity of different detection systems.

Background: D-dimer at a low level is important evidence for excluding the onset and progression of thrombosis. It is readily detectable and yields rapid results, although significant variability exists among different detection systems. Our study aims to enhance the consistency across various detection systems. Methods: Twelve detection systems were included in our study. We sought to address this inconsistency by using various calibrators (two supplied by manufacturers and two comprising pooled human plasma diluted with different diluents) to standardize D-dimer measurements. We categorized the data into three groups according to D-dimer concentration levels: low (≤0.5 mg/L), medium (>0.5 mg/L - <3 mg/L), and high (≥3 mg/L). We then analyzed the data focusing on range, consistency, comparability, negative coincidence rate, and false negative rate. Results: Calibrating with pooled human plasma led to narrower result ranges in the low and medium groups (P < 0.05). In the low group, consistency improved from weak to strong (ICC 0.4-0.7, P﹤0.05), while it remained excellent in the other groups and overall (ICCï¹¥0.75, P﹤0.05). The percentage of pairwise comparability increased in both the low and high groups. Additionally, there was an increase in the negative coincidence rate. Conclusion: These findings demonstrate that uniform calibration of D-dimer can significantly enhance the consistency of results across different detection systems.

The antioxidant effects of butylated hydroxytoluene on cryopreserved goat sperm from a proteomic perspective.

At present, there are few reports about the proteomics changes provoked by butylated hydroxytoluene (BHT) supplementation on cryopreserved semen in mammals. Thus, we aimed to evaluate the effects of different concentrations of BHT on goat sperm and to investigate the proteomics changes of adding BHT to cryopreserved goat (Capra hircus) sperm. Firstly, semen samples were collected from four goats, and frozen in the basic extenders containing different concentrations of BHT (0.5 mM, 1.0 mM, 2.0 mM) and a control without BHT, respectively. After thawing, the protective effects of dose-dependent replenished BHT to the freezing medium on post-thaw sperm motility, integrities of plasma membrane and acrosome, reactive oxygen species levels were confirmed, with 0.5 mM BHT being the best (B group) as compared to the control (without BHT, C group). Afterwards, TMT-based quantitative proteomic technique was performed to profile proteome of the goat sperm between C group and B group. Parallel reaction monitoring was used to confirm reliability of the data. Overall, 2,476 proteins were identified and quantified via this approach. Comparing the C and B groups directly (C vs. B), there were 17 differentially abundant proteins (DAPs) po-tentially associated with sperm characteristics and functions were identified, wherein three were upregulated and 14 were downregulated, respectively. GO annotation analysis demonstrated the potential involvement of the identified DAPs in metabolic process, multi-organism process, reproduction, reproductive process, and cellular process. KEGG enrichment analysis further indicated their potential roles in renin-angiotensin system and glutathione metabolism pathways. Together, this novel study clearly shows that BHT can effectively improve quality parameters and fertility potential of post-thawed goat sperm at the optimal concentration, and its cryoprotection may be realized through regulation of sperm metabolism and antioxidative capability from the perspective of sperm proteomic modification.

Development of a genome atlas for discriminating benign, preinvasive, and invasive lung nodules.

To tackle misdiagnosis in lung cancer screening with low-dose computed tomography (LDCT), we aimed to compile a genome atlas for differentiating benign, preinvasive, and invasive lung nodules and characterize their molecular pathogenesis. We collected 432 lung nodule tissue samples from Chinese patients, spanning benign, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA). We performed comprehensive sequencing, examining somatic variants, gene expressions, and methylation levels. Our findings uncovered EGFR and TP53 mutations as key drivers in - early lung cancer development, with EGFR mutation frequency increasing with disease progression. Both EGFR mutations and EGF/EGFR hypo-methylation activated the EGFR pathway, fueling cancer growth. Transcriptome analysis identified four lung nodule subtypes (G1-4) with distinct molecular features and immune cell infiltrations: EGFR-driven G1, EGFR/TP53 co-mutation G2, inflamed G3, stem-like G4. Estrogen/androgen response was associated with the EGFR pathway, proposing a new therapy combining tyrosine kinase inhibitors with antiestrogens. Preinvasive nodules exhibited stem cell pathway enrichment, potentially hindering invasion. Epigenetic regulation of various genes was essential for lung cancer initiation and development. This study provides insights into the molecular mechanism of neoplastic progression and identifies potential diagnostic biomarkers and therapeutic targets for lung cancer.

Development and validation of a diagnostic model for cerebral small vessel disease among rural older adults in China.

Objectives: Cerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults. Methods: This study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis. Results: The model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67-0.76) in the training set and 0.69 (95% CI, 0.63-0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50-90% in the training set, and 65-98% in the validation set. Conclusion: A model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.

SntB Affects Growth to Regulate Infecting Potential in Penicillium italicum.

Penicillium italicum, a major postharvest pathogen, causes blue mold rot in citrus fruits through the deployment of various virulence factors. Recent studies highlight the role of the epigenetic reader, SntB, in modulating the pathogenicity of phytopathogenic fungi. Our research revealed that the deletion of the SntB gene in P. italicum led to significant phenotypic alterations, including delayed mycelial growth, reduced spore production, and decreased utilization of sucrose. Additionally, the mutant strain exhibited increased sensitivity to pH fluctuations and elevated iron and calcium ion stress, culminating in reduced virulence on Gannan Novel oranges. Ultrastructural analyses disclosed notable disruptions in cell membrane integrity, disorganization within the cellular matrix, and signs of autophagy. Transcriptomic data further indicated a pronounced upregulation of hydrolytic enzymes, oxidoreductases, and transport proteins, suggesting a heightened energy demand. The observed phenomena were consistent with a carbon starvation response potentially triggering apoptotic pathways, including iron-dependent cell death. These findings collectively underscored the pivotal role of SntB in maintaining the pathogenic traits of P. italicum, proposing that targeting PiSntB could offer a new avenue for controlling citrus fungal infections and subsequent fruit decay.

An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression.

BACKGROUND: Enhancers are important gene regulatory elements that promote the expression of critical genes in development and disease. Aberrant enhancer can modulate cancer risk and activate oncogenes that lead to the occurrence of various cancers. However, the underlying mechanism of most enhancers in cancer remains unclear. Here, we aim to explore the function and mechanism of a crucial enhancer in melanoma. METHODS: Multi-omics data were applied to identify an enhancer (enh17) involved in melanoma progression. To evaluate the function of enh17, CRISPR/Cas9 technology were applied to knockout enh17 in melanoma cell line A375. RNA-seq, ChIP-seq and Hi-C data analysis integrated with luciferase reporter assay were performed to identify the potential target gene of enh17. Functional experiments were conducted to further validate the function of the target gene ETV4. Multi-omics data integrated with CUT&Tag sequencing were performed to validate the binding profile of the inferred transcription factor STAT3. RESULTS: An enhancer, named enh17 here, was found to be aberrantly activated and involved in melanoma progression. CRISPR/Cas9-mediated deletion of enh17 inhibited cell proliferation, migration, and tumor growth of melanoma both in vitro and in vivo. Mechanistically, we identified ETV4 as a target gene regulated by enh17, and functional experiments further support ETV4 as a target gene that is involved in cancer-associated phenotypes. In addition, STAT3 acts as a transcription factor binding with enh17 to regulate the transcription of ETV4. CONCLUSIONS: Our findings revealed that enh17 plays an oncogenic role and promotes tumor progression in melanoma, and its transcriptional regulatory mechanisms were fully elucidated, which may open a promising window for melanoma prevention and treatment.

Stable Vortex Solitons Sustained by Localized Gain in a Cubic Medium.

We propose a simple dissipative system with purely cubic defocusing nonlinearity and nonuniform linear gain that can support stable localized dissipative vortex solitons with high topological charges without the utilization of competing nonlinearities and nonlinear gain or losses. Localization of such solitons is achieved due to an intriguing mechanism when defocusing nonlinearity stimulates energy flow from the ringlike region with linear gain to the periphery of the medium where energy is absorbed due to linear background losses. Vortex solitons bifurcate from linear gain-guided vortical modes with eigenvalues depending on topological charges that become purely real only at specific gain amplitudes. Increasing gain amplitude leads to transverse expansion of vortex solitons, but simultaneously it usually also leads to stability enhancement. Increasing background losses allows creation of stable vortex solitons with high topological charges that are usually prone to instabilities in conservative and dissipative systems. Propagation of the perturbed unstable vortex solitons in this system reveals unusual dynamical regimes, when instead of decay or breakup, the initial state transforms into stable vortex solitons with lower or sometimes even with higher topological charge. Our results suggest an efficient mechanism for the formation of nonlinear excited vortex-carrying states with suppressed destructive azimuthal modulational instabilities in a simple setting relevant to a wide class of systems, including polaritonic systems, structured microcavities, and lasers.

Alpha-fetoprotein and APRI as predictive markers for patients with Type C hepatitis B-related acute-on-chronic liver failure: a retrospective study.

BACKGROUND: Type C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF. METHOD: Patients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model. RESULTS: A total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH-ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (<-9.07) survived longer. CONCLUSIONS: A new prognostic scoring system for patients with type C HBV-ACLF based on seven routine indices was established in our study and can accurately predict short-term mortality and might be used to guide clinical management.