HYENA detects oncogenes activated by distal enhancers in cancer.

Somatic structural variations (SVs) in cancer can shuffle DNA content in the genome, relocate regulatory elements, and alter genome organization. Enhancer hijacking occurs when SVs relocate distal enhancers to activate proto-oncogenes. However, most enhancer hijacking studies have only focused on protein-coding genes. Here, we develop a computational algorithm 'HYENA' to identify candidate oncogenes (both protein-coding and non-coding) activated by enhancer hijacking based on tumor whole-genome and transcriptome sequencing data. HYENA detects genes whose elevated expression is associated with somatic SVs by using a rank-based regression model. We systematically analyze 1146 tumors across 25 types of adult tumors and identify a total of 108 candidate oncogenes including many non-coding genes. A long non-coding RNA TOB1-AS1 is activated by various types of SVs in 10% of pancreatic cancers through altered 3-dimensional genome structure. We find that high expression of TOB1-AS1 can promote cell invasion and metastasis. Our study highlights the contribution of genetic alterations in non-coding regions to tumorigenesis and tumor progression.

SFyNCS detects oncogenic fusions involving non-coding sequences in cancer.

Fusion genes are well-known cancer drivers. However, most known oncogenic fusions are protein-coding, and very few involve non-coding sequences due to lack of suitable detection tools. We develop SFyNCS to detect fusions of both protein-coding genes and non-coding sequences from transcriptomic sequencing data. The main advantage of this study is that we use somatic structural variations detected from genomic data to validate fusions detected from transcriptomic data. This allows us to comprehensively evaluate various fusion detection and filtering strategies and parameters. We show that SFyNCS has superior sensitivity and specificity over existing algorithms through extensive benchmarking in cancer cell lines and patient samples. We then apply SFyNCS to 9565 tumor samples across 33 tumor types in The Cancer Genome Atlas cohort and detect a total of 165,139 fusions. Among them, 72% of the fusions involve non-coding sequences. We find a long non-coding RNA to recurrently fuse with various oncogenes in 3% of prostate cancers. In addition, we discover fusions involving two non-coding RNAs in 32% of dedifferentiated liposarcomas and experimentally validated the oncogenic functions in mouse model.

Tetra-Ln3+-Implanted Tellurotungstates Covalently Modified by dl-Malic Acid: Proton Conduction and Photochromic Properties.

Three unique dl-malic acid covalently modified tetra-Ln3+-implanted tellurotungstates [H2(CH3)2]9NaH9[Ln4(H2O)14W6O13(OH)5(Mal)2(B-α-TeW9O33)4]·48H2O [Ln = La3+ (1), Ce3+ (2), Pr3+ (3); H3Mal = dl-malic acid] were fabricated by reacting Na2TeO3, Na2WO4·2H2O, Mal, and LnCl3·6H2O with dimethylamine hydrochloride in an aqueous solution. The most prominent architectural feature of these compounds is the covalent connection mode of an organic ligand and a polyoxometallate backbone, which is relatively rare in the realm of polyoxotungstates. The tetrameric polyanion can be deemed as four [TeW9O33]8- fragments fused together via an intriguing hexanuclearity [W6O13(OH)5(Mal)2Ln4(H2O)14]13+ cluster. Impedance measurements manifest that all three complexes display splendid proton conduction properties, with an exceptional conductivity for 2 up to 2.48 × 10-2 S·cm-1 under 85 °C and 95% relative humidity. Moreover, compounds 1 and 3 exhibited fast reversible photochromic properties with allochroic half-life periods t1/2 of 1.046 and 0.544 min, respectively.

Evaluating the reliability of the lateral femoral condyle measuring methods by different modalities for patients with lateral patellar dislocation.

BACKGROUND: A variety of measurement methods and imaging modalities are in use to quantify the morphology of lateral femoral condyle (LFC), but the most reliable method remains elusive in patients with lateral patellar dislocation (LPD). The purpose of this study was to determine the intra- and inter-observer reliability of different measurement methods for evaluating the morphology of LFC on different imaging modalities in patients with LPD. METHODS: Seventy-three patients with LPD were included. Four parameters for quantifying the morphology of LFC were retrospectively measured by three observers on MRI, sagittal CT image, conventional radiograph (CR), and three-dimensional CT (3D-CT). The intra-class correlation coefficient was calculated to determine the intra- and inter-observer reliability. Bland-Altman analysis was conducted to identify the bias between observers. RESULTS: The lateral femoral condyle index (LFCI) showed better intra- and inter-observer reliability on MRI and 3D-CT than on CR and sagittal CT images. The mean difference in the LFCI between observers was lowest on 3D-CT (0.047), higher on MRI (0.053), and highest on sagittal CT images (0.062). The LFCI was associated with the lateral femoral condyle ratio (ρ = 0.422, P = 0.022), lateral condyle index (r = 0.413, P = 0.037), and lateral femoral condyle distance (r = 0.459, P = 0.014). The LFCI could be reliably measured by MRI and 3D-CT. CONCLUSION: The LFCI could be reliably measured by MRI and 3D-CT. The LFCI was associated with both the height and length of LFC and could serve as a comprehensive parameter for quantifying the morphology of LFC in patients with LPD.

Experience from transport teams on interhospital transfer of patients with extracorporeal membrane oxygenation support: A qualitative study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) can be a life-saving treatment for patients requiring advanced cardiopulmonary support. Several ECMO centres offer interhospital transport (ECMO IHT) services that involve establishing ECMO teams to initiate ECMO at referring hospitals and then transfer patients to ECMO centres. ECMO IHT is often high risk and complex. Understanding the experience of transport team members is crucial to ensure patient safety and promote quality improvement. AIM: To explore the experiences of transport teams performing ECMO IHT. STUDY DESIGN: A descriptive qualitative methodology was adopted. RESULTS: Thirteen health care professionals who have performed ECMO IHT at a general hospital in China agreed to be interviewed and enrolled in this study. Two investigators conducted face-to-face individual interviews in September-November 2022. All interviews were audio-recorded, transcribed verbatim and analysed using inductive thematic analysis. Three main themes and nine sub-themes were developed: (1) practicing with good organizational management (conducting training programs, cultivating the spirit of good teamwork and developing a standardized transport procedure), (2) dedicated to ensuring patient safety (adequate preparation and regular checking to reduce risk, accurate evaluation to avoid futility and maintaining communication to increase safety) and (3) having confidence despite being uneasy (feeling stressed is common, facing insecurity in transport settings and gaining confidence through practice). CONCLUSIONS: Health care professionals must adequately prepare and assess ECMO IHT to ensure patient safety. Supportive measures should be taken to ensure team members' health and improve patient safety. Good communication and teamwork could improve this challenging task. Further research is required for training programs and establishing standardized transport procedures. RELEVANCE TO CLINICAL PRACTICE: This study presents multi-professional perspectives on the experience of performing ECMO IHT to help management identify what needs to be further developed. With the increasing number of ECMO IHT, promoting its standardization is warranted.

Two Tetra-Nuclear Ln-Substituted Prazine Dicarboxylic Acid-Functionalized Selenotungstates with Catalytic Oxidation of Thioether Properties.

Two two-dimensional Ln-substituted prazine dicarboxylic acid-functionalized selenotungstates Na3H9[(H2N(CH3)2]2{(Se4W27O100)[Ln4(H2O)8(Hpzdc)2(pzdc)]}·26H2O [Ln = Nd (1) and Ce (2)]; H2pzdc = 2,3-pyrazine dicarboxylic acid) have been synthesized by one-pot self-assembly strategy, in which the basic polyanion [Se4W27O100]22-was composed of two [SeW8O31]10- fragments, a [SeW9O33]8- segment and an intriguing {SeO} group, simultaneously tetra-nuclear Ln3+ ions with H2pzdc pendants were embedded. Compounds 1 and 2 showed excellent catalytic oxidation of thioether properties within a short time (20 min) with high 100% conversion and 98.9% selectivity. In addition, the pioneering Ln-substituted selenotungstates were used as catalysts to degrade sulfur mustard simulant 2-chloroethyl ethyl sulfide at room temperature with 99% conversion and 100% selectivity. The chemical kinetic experiment studies revealed that the catalytic reaction was in compliance with the first-order reaction, and the kinetic half-life (t1/2) values were 3.814 and 3.849 min, respectively.

Health-related quality of life assessment instruments for extracorporeal membrane oxygenation survivors: A scoping review.

BACKGROUND AND OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been successfully and widely used in adult patients for the past 5 years. About 50% of these patients can survive and are discharged from hospitals. Health-related quality of life (HRQOL) is crucial for evaluating survived ECMO patients. This scoping review aims to identify instruments commonly used to measure HRQOL of ECMO survivors and give pertinent instrument characteristics. METHODS: A systematic search was conducted in PubMed, Web of Science, EMBASE (OVID), MEDLINE (OVID), CINAHL (EBSCO), Cochrane Library, and three Chinese databases from January 2012 to December 2021. Two reviewers independently reviewed publication selection and data extraction. RESULTS: Twenty-nine studies met the inclusion criteria. Most studies (93%) were cross-sectional, and the median (or average) follow-up time ranged from 3 months to 9 years. Two prospective studies (7%) followed patients longitudinally until 1 year after discharge. ECMO survivors had poorer long-term HRQOL than the general population. However, it is comparable to or better than patients with other critical or chronic illnesses. Identified HRQOL assessment instruments show four generic HRQOL instruments, one disease-specific HRQOL instrument, and nineteen single-dimensional instruments. Seven instruments were used in more than three articles. SF-36 (86.2%), IES/IES-R (41.4%), and HADS (37.9%) were the most frequently used instruments. CONCLUSION: The timing, frequency, and tools for HRQOL assessment of ECMO survivors are variable. No ECMO-specific HRQOL instrument was developed and validated. Further studies on assessment instruments are warranted. Research is also needed to identify interventions that may enhance HRQOL in ECMO survivors.

Identification and preparation of selenium-containing peptides from selenium-enriched Pleurotus eryngii and their protective effect on lead-induced oxidative damage in NCTC1469 hepatocytes.

BACKGROUND: Lead (Pb) is a highly toxic and persistent substance that easily accumulates in living organisms, eliciting cellular toxicity and oxidative stress. Some selenium-containing proteins and peptides prepared from plant extracts are beneficial for protecting the body's health and resisting external disturbances. In the present study, selenium-containing peptide species were prepared from selenium-enriched Pleurotus eryngii protein hydrolysates and to evaluate the benefits of selenium-containing peptides on Pb-induced oxidative stress in NCTC1469 hepatocytes. RESULTS: Trypsin was selected as primary enzyme to hydrolyze the selenium-enriched protein (SPH). The optimal hydrolysis conditions were: hydrolysis time, 1.5 h; initial pH 8.0. The SPH was digested by trypsin and then purified by ultrafiltration, gel filtration chromatography and reversed-phase HPLC to obtain the selenium-containing peptides SPH-I-2. Furthermore, SPH-I-2 was analyzed and a number of total 12 selenium-containing peptides were identified by liquid chromatography-tandem mass spectroscopy. The NCTC1469 cell culture study showed that selenium-containing peptides were capable of reducing reactive oxygen species levels and regulating the Keap1/Nrf2 pathway by upregulating Nrf2, HO-1, GCLC, GCLM and NQO1 genes and downregulating Keap1 genes. Moreover, selenium-containing peptides were also able to suppress Pb-induced elevated levels of nitric oxide (NO), lactate dehydrogenase (LDH), malondialdehyde (MDA), increase antioxidant enzyme activity and alleviate cell apoptosis. CONCLUSION: The present study indicated that the selenium-containing peptides could protect cells from Pb2+ -induced oxidative stress. © 2023 Society of Chemical Industry.

Terahertz hybrid optical-plasmonic modes: tunable resonant frequency, narrow linewidth, and strong local field enhancement.

Hybrid optical-plasmonic modes have the characteristics of low loss and small mode volume, which will result in the strong localization and enhancement of electromagnetic field. Such advantages of hybrid optical-plasmonic mode are important for the enhancement of light-matter interactions. Here, terahertz (THz) hybrid modes of Fabry-Perot resonances (FPRs) and spoof surface plasmon polaritons (SSPPs) in the modified Otto scheme are investigated both in theoretical and experimental aspects. The device structure is composed of a metal grating silicon waveguide (MGSW) and a metal slit grating (MSG). The two components are vertically stacked with a variable air gap between them. The THz hybrid modes are originated from the far-field coupling of the FPRs and the SSPP supported by the air gap and the MSG, respectively. By changing the thickness of the air gap, the resonant frequency of the FPR-SSPP modes can be tuned in a frequency range of about 0.1 THz. An anti-crossing behavior between two reflection dips corresponding to the guided-mode resonance in the MGSW and the FPR-SSPP mode is observed, which leads to the narrowing of the reflection dips in the anti-crossing region. Numerical simulations show that at the resonant frequencies of FPR-SSPP mode, there is a huge volume-averaged electromagnetic energy enhancement of about 1600 times in the grooves of the MSG, which is around 8.7 times larger than that induced by the SSPP directly launched by free-space electromagnetic field. The hybrid FPR-SSPP modes can be used to construct THz sensors and detectors with high sensitivity.

Duration of an acute moderate-intensity exercise session affects approach bias toward high-calorie food among individuals with obesity.

Obesity is partly driven by unhealthy eating behaviors underpinned by an approach bias toward high-calorie food. Although exercise is a useful strategy for weight loss among individuals with obesity, whether exercise modulates this approach bias is unclear. This study assessed whether the duration of an acute moderate-intensity exercise altered the approach bias toward high-calorie food among individuals with obesity. In total, 24 individuals with obesity were included in this study with a randomized, counterbalanced, crossover design. Participants completed three sessions of 30, 45, or 60 min of moderate-intensity exercise (40%-59% of heart rate reserve) on an elliptical trainer or completed a control rest session for 55 min. Food approach bias was evaluated using a joystick-based approach-avoidance task immediately before and after each session. Two-way repeated-measures analysis of variance was used to analyze the data. We found that compared with that before exercise, the approach bias score toward high-calorie food was significantly decreased only in the 45-min exercise session (p = .015) and that this score was also significantly lower than that after both the 60-min exercise session (p = .002) and the control session (p = .024). These findings suggest a dose-response relationship between exercise duration and approach bias, with 45 min of moderate-intensity exercise being an effective strategy for decreasing the approach bias toward high-calorie food among individuals with obesity.

Mafenide derivatives inhibit neuroinflammation in Alzheimer's disease by regulating pyroptosis.

The main mechanism of pyroptosis is Caspase-1-mediated GSDMD cleavage, and GSDMD is also the executive protein of pyroptosis. Our previous study has shown that mafenide can inhibit pyroptosis by inhibiting the GSDMD-Asp275 site to suppress cleavage. In this study, sulfonamide was used as the parent nucleus structure to synthesize sulfa-4 and sulfa-20. Screening of drug activity in the pyroptosis model of BV2 and iBMDM cell lines revealed the efficacy of five compounds were superior to mafenide, which exerted a better inhibitory effect on the occurrence of pyroptosis. For in vivo assay, Sulfa-4 and Sulfa-22 were intervened in the neuroinflammation APP/PS1 mice. As a result, the administration of Sulfa-4 and Sulfa-22 could significantly inhibit the activation of microglia, decrease the expression of inflammatory factors in the central nervous system and simultaneously suppress the production of p30-GSDMD as well as the expression of upstream NLRP3 inflammasome and Caspase-1 protein. Immunoprecipitation and Biotin-labelled assay confirmed the targeted binding relationship of Sulfa-4 and Sulfa-22 with GSDMD protein in the iBMDM model in vitro. In this study, we investigated a new type inhibitor of GSDMD cleavage, which exerted a good inhibitory effect on pyroptosis and provided new references for the development of inflammatory drugs in the future.

Excitation of graphene surface plasmons polaritons by guided-mode resonances with high efficiency.

An Otto-like configuration for the excitation of graphene surface plasmon polaritons (GSPPs) is proposed. The configuration is composed of a metallic grating-dielectric-waveguide structure and a monolayer graphene with a subwavelength vacuum gap between them. The evanescent field located at the bottom surface of the dielectric waveguide corresponding to grating-coupled guided-mode resonances (GMRs) is utilized to efficiently excite the highly confined GSPPs. The finite difference time domain method is used to investigate the behaviors of the GMR-GSPP hybrid modes. The dispersion relations of GMRs and GSPPs are calculated and the numerical results further identify the excitation of GMR-GSPP hybrid modes. By changing the gap between the graphene layer and the bottom of the dielectric waveguide and the Fermi energy of graphene, the resonant frequencies of GMR-GSPP hybrid modes can be continuously tuned. When the optimized excitation condition is satisfied, the maximum energy enhancement factor in the gap can reach about 500 at the resonant frequencies. The proposed structure can be used to realize highly sensitive, compatible with planar fabrication technology, and electrically (mechanically) tunable sensors.

Multiband and broadband active controllable terahertz absorption in dual-side grating-gate graphene field-effect transistors.

We show that the even order ungated modes can be excited under normal incidence while the odd order ungated modes cannot in traditional single-side grating-gate graphene field-effect transistors. The odd order ungated modes will suppress the excitation efficiency of the gated modes. In order to realize multiband detection by effectively exciting the higher order gated modes, the frequency of the 1st order ungated mode should be tuned up, which can be realized by shortening the length of the ungated region. We propose to use the dual-side grating-gate structure to shorten the length of the ungated region. Gated mode up to 21st order can be realized in complementary dual-side grating-gate structure. The ultra-multiband absorption can be actively controlled to cover 1.06-10 THz when the graphene Fermi energy is tuned from 0.2 eV to 0.6 eV. Even order gated modes will be excited by gradually overlapping the two grating layers because of the break of symmetry. Broadband detection from 0.1-8.2 THz can be realized by the effective excitation and overlap of the odd and even order gated modes.

Metal-graphene hybridized plasmon induced transparency in the terahertz frequencies.

In this work, metal-graphene hybridized plasmon induced transparency (PIT) is systematically studied in the proposed simple metal/dielectric/graphene system. The PIT effect is the result of the coupling between the bright dipolar modes excited in the graphene regions under the shorter metallic bars and the dark quadrupolar modes excited in the graphene regions under the longer metallic bars. The coupled Lorentz oscillator model is used to help explain the physical origin of the PIT effect. Other than being tuned by the distance and the lateral displacement of the orthogonal metallic bars, the coupling efficiency can be further enhanced by the in-phase coupling or quenched by the out-of-phase coupling between the adjacent unit cells. Reduced barrier thickness will result in the enhancement of the coupling strengths and the scaling down of the device. Finally, we show that the PIT window can be actively tuned by changing the Fermi energy of graphene. The proposed structure has potential applications in actively tunable THz modulators, sensors and filters.

Post-stroke cognitive impairment: exploring molecular mechanisms and omics biomarkers for early identification and intervention.

Post-stroke cognitive impairment (PSCI) is a major stroke consequence that has a severe impact on patients' quality of life and survival rate. For this reason, it is especially crucial to identify and intervene early in high-risk groups during the acute phase of stroke. Currently, there are no reliable and efficient techniques for the early diagnosis, appropriate evaluation, or prognostication of PSCI. Instead, plenty of biomarkers in stroke patients have progressively been linked to cognitive impairment in recent years. High-throughput omics techniques that generate large amounts of data and process it to a high quality have been used to screen and identify biomarkers of PSCI in order to investigate the molecular mechanisms of the disease. These techniques include metabolomics, which explores dynamic changes in the organism, gut microbiomics, which studies host-microbe interactions, genomics, which elucidates deeper disease mechanisms, transcriptomics and proteomics, which describe gene expression and regulation. We looked through electronic databases like PubMed, the Cochrane Library, Embase, Web of Science, and common databases for each omics to find biomarkers that might be connected to the pathophysiology of PSCI. As all, we found 34 studies: 14 in the field of metabolomics, 5 in the field of gut microbiomics, 5 in the field of genomics, 4 in the field of transcriptomics, and 7 in the field of proteomics. We discovered that neuroinflammation, oxidative stress, and atherosclerosis may be the primary causes of PSCI development, and that metabolomics may play a role in the molecular mechanisms of PSCI. In this study, we summarized the existing issues across omics technologies and discuss the latest discoveries of PSCI biomarkers in the context of omics, with the goal of investigating the molecular causes of post-stroke cognitive impairment. We also discuss the potential therapeutic utility of omics platforms for PSCI mechanisms, diagnosis, and intervention in order to promote the area's advancement towards precision PSCI treatment.

HYENA detects oncogenes activated by distal enhancers in cancer.

Somatic structural variations (SVs) in cancer can shuffle DNA content in the genome, relocate regulatory elements, and alter genome organization. Enhancer hijacking occurs when SVs relocate distal enhancers to activate proto-oncogenes. However, most enhancer hijacking studies have only focused on protein-coding genes. Here, we develop a computational algorithm "HYENA" to identify candidate oncogenes (both protein-coding and non-coding) activated by enhancer hijacking based on tumor whole-genome and transcriptome sequencing data. HYENA detects genes whose elevated expression is associated with somatic SVs by using a rank-based regression model. We systematically analyze 1,146 tumors across 25 types of adult tumors and identify a total of 108 candidate oncogenes including many non-coding genes. A long non-coding RNA TOB1-AS1 is activated by various types of SVs in 10% of pancreatic cancers through altered 3-dimensional genome structure. We find that high expression of TOB1-AS1 can promote cell invasion and metastasis. Our study highlights the contribution of genetic alterations in non-coding regions to tumorigenesis and tumor progression.

The absorption tunability and enhanced electromagnetic coupling of terahertz-plasmons in grating-gate AlN/GaN plasmonic device.

This paper describes the dynamic interaction between plasmons in a two dimensional electron gas system under electrical tuning to the high density regime in AlN/GaN high electron mobility transistor. The results demonstrate an enhanced resonance when the two plasmons are commonly excited, during which the potentially splitting phenomenon of such resonance is explored in detail. An asymmetrical plasmon possess wide frequency tunability has also been demonstrated in the AlN/GaN system, on the contrary, the results also indicate a finite tunable regime of symmetrical-plasmons as limited by the coupling strength between such plasmons. For the devices with narrow gate-fingers, significant near-field enhancement can be obtained due to the strong cavity pumping of electromagnetic energy. These properties may have important applications including high-responsivity quantum-dot detection systems, THz modulator etc.

Individualized folic acid supplementation based on MTHFR and MTRR gene polymorphisms reduces the risk of gestational diabetes mellitus in a Chinese population.

OBJECTIVE: Folic acid (FA) may contribute to the development of gestational diabetes mellitus (GDM), but available studies are inconsistent. We studied the genotype distribution and allele frequencies of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C, and methionine synthase reductase (MTRR) A66G polymorphisms in pregnant Chinese women and compared the effects of individualized and traditional FA supplementation on GDM. METHODS: In this retrospective study, genotype distribution and allele frequencies in 968 pregnant women were tested. FA metabolism was tested by dividing patients into four groups, each of which was supplemented with different doses of FA at different times. Pregnancy complications were followed up and compared to 1940 pregnant women traditionally supplemented with FA in the same hospital as a control group. RESULTS: The allele frequencies were 63.3% (C) and 36.7% (T) for MTHFR C677T, 79.3% (A) and 20.7% (C) for MTHFR A1298C and 75.0% (A) and 25.0% (G) for MTRR A66G. The incidence of GDM after FA supplementation was significantly lower in the case group compared to the control group, especially in high-risk pregnancies. CONCLUSION: Using genetic polymorphisms to elucidate FA metabolism in pregnant women and providing appropriate FA supplementation can be effective in reducing GDM, especially in high-risk groups.

SFyNCS detects oncogenic fusions involving non-coding sequences in cancer.

Fusion genes are well-known cancer drivers. However, very few known oncogenic fusions involve non-coding sequences. We develop SFyNCS with superior performance to detect fusions of both protein-coding genes and non-coding sequences from transcriptomic sequencing data. We validate fusions using somatic structural variations detected from the genomes. This allows us to comprehensively evaluate various fusion detection and filtering strategies and parameters. We detect 165,139 fusions in 9,565 tumor samples across 33 tumor types in the Cancer Genome Atlas cohort. Among them, 72% of the fusions involve non-coding sequences and many are recurrent. We discover two long non-coding RNAs recurrently fused with various partner genes in 32% of dedifferentiated liposarcomas and experimentally validated the oncogenic functions in mouse model.