DiSignAtlas: an atlas of human and mouse disease signatures based on bulk and single-cell transcriptomics.

Molecular signatures are usually sets of biomolecules that can serve as diagnostic, prognostic, predictive, or therapeutic markers for a specific disease. Omics data derived from various high-throughput molecular biology technologies offer global, unbiased and appropriately comparable data, which can be used to identify such molecular signatures. To address the need for comprehensive disease signatures, DiSignAtlas (http://www.inbirg.com/disignatlas/) was developed to provide transcriptomics-based signatures for a wide range of diseases. A total of 181 434 transcriptome profiles were manually curated from studies involving 1836 nonredundant disease types in humans and mice. Then, 10 306 comparison datasets comprising both disease and control samples, including 328 single-cell RNA sequencing datasets, were established. Furthermore, a total of 3 775 317 differentially expressed genes in humans and 1 723 674 in mice were identified as disease signatures by analysing transcriptome profiles using commonly used pipelines. In addition to providing multiple methods for the retrieval of disease signatures, DiSignAtlas provides downstream functional enrichment analysis, cell type analysis and signature correlation analysis between diseases or species when available. Moreover, multiple analytical and comparison tools for disease signatures are available. DiSignAtlas is expected to become a valuable resource for both bioscientists and bioinformaticians engaged in translational research.

A comfort analysis of AR glasses on physical load during long-term wearing.

The present study investigated the effect of the physical load of augmented reality (AR) glasses on subjective assessments for an extended duration of a video viewing task. Ninety-six subjects were recruited for this test and were divided by spectacle use, sex, age, and body mass index (BMI). Four glasses frame weights were assessed. To investigate their effectiveness, a novel prototype adopting three design interventions, (1) adjustable frame width, (2) ergonomic temples, and (3) fixed centre of gravity, was designed with regard to subjective discomfort ratings (nose, ear, and overall). Subjective discomfort in all regions was significantly increased with increasing physical load on the nose. In addition, non-spectacle users, women, older users, and participants in the middle BMI category reported higher discomfort than other groups. This finding could have important implications for the ergonomic design of AR glasses and could help to identify design considerations relevant to the emerging wearable display industry. Practitioner summary: This research aims to explore the influence of the physical load of augmented reality (AR) glasses. It found that discomfort was increased with added nose load. Non-spectacle users, women, older users, and participants in the middle BMI category were more sensitive to discomfort. The results have important implications for glasses-type wearables' design.

In-ear earphone design-oriented pressure sensitivity evaluation on the external ear.

This study aimed to explore the pressure sensitivity of the external ear that can be the basis for adapting the pressure distribution on the concha for in-ear earphone design. Overall, 30 participants were included in this study, where an electronic mechanical algometer with a stepping motor was used to apply constant pressure. Before the experiment, the customised concha shell models of the participants were positioned in the ear perpendicular to the concha surface. Furthermore, the pressure discomfort threshold (PDT), moderate pressure discomfort (MPD), and maximum pressure threshold (MPT) in eight regions of the ear were recorded. This study's results indicate that the four regions of the external ear are less sensitive to pressure than those of the other regions. Additionally, women had higher pressure sensitivity values in the external ear. Therefore, this study's findings could have important implications for earphone designs and evaluating discomfort conditions in the external ear. Practitioner summary: This study explores the pressure sensitivity threshold (PDT, MPD, and MPT) on the external ear and the relevant implications for in-ear earphone design. Interestingly, regions closer to the bone structure were less sensitive to pressure, and men could tolerate greater pressure on the external ear than women.

Acidophilic partial nitrification (pH<6) facilitates ultra-efficient short-flow nitrogen transformation: Experimental validation and genomic insights.

Partial nitrification (PN) represents an energy-efficient bioprocess; however, it often confronts challenges such as unstable nitrite accumulation, nitrite oxidizing bacteria shocks, and slow reaction rate. This study established an acidophilic PN with self-sustained pH as low as 5.36. Over 120-day monitoring, nitrite accumulation rate (NAR) was stabilized at more than 97.9 %, and an ultra-high ammonia oxidation rate of 0.81 kg/m3·d was achieved. Notably, least NAR of 77.8 % persisted even under accidental nitrite oxidizing bacteria invasion, aeration delay, alkalinity fluctuations, and cooling shocks. During processing, despite detrimental effects on bacterial diversity, there was a discernible increase in acid-tolerant bacteria responsible for nitrification. Candidatus Nitrosoglobus, gradually dominated in nitrifying guild (2.15 %), with the substantially reduction or disappearance of typical nitrifying microorganisms. Acidobacteriota, a key player in nitrogen cycling of soil, significantly increased from 0.45 % to 9.98 %, and its associated nitrogen metabolism genes showed a substantial 215 % rise. AmoB emerged as the most critical functional gene influencing acidophilic PN, exhibiting significantly higher unit gene expression than other nitrification genes. Blockade tricarboxylic acid cycle, DNA damage, and presence of free nitrous acid exert substantial effects on nitrite-oxidizing bacteria (NOB), serving as internal driving forces for acidophilic PN. This highlights the reliable potential for shortening nitrogen transformation process.

Unraveling the intrinsic mechanism behind the retention of arsenic in the co-gasification of coal and sewage sludge: Focus on the role of Ca and Fe compounds.

Minimizing the emission of arsenic (As) is one of the urgent problems during co-gasification of Shenmu coal (SM) and sewage sludge (SS). The intrinsic mechanism of As retention was obtained by analyzing the effect of different SM addition ratios on the As form transformation during co-gasification at 1000 °C under CO2 atmosphere. The results showed that the addition of SM effectively promoted the enrichment of As in the co-gasified residues. Especially, the best As retention rate of 65.71% was achieved with the 70 wt% addition ratio of SM. The addition of SM promoted the adsorption and chemical oxidation of As(III) to the less toxic As(V) through the coupling of Ca and Fe compounds in the co-gasified residues. XRD and XPS results indicated that Fe2O3 adsorbed As2O3(g) after partial conversion to Fe3O4 by the Boudouard reaction, while part of As2O3 was oxidized to As2O5 by lattice oxygen. Finally, the generated As2O5 was successively trapped by CaO and Fe2O3 to form stable Ca3(AsO4)2 and FeAsO4. HRTEM and TEM analysis comprehensively proved that As(III) was stabilized by the lattice cage of CaAl2Si2O8. In conclusion, the co-oxidation of Ca and Fe compounds and lattice stabilization simultaneously played a crucial role in the retention of As2O3(g) during co-gasification.

Accessing Benzoazepine Derivatives via Photoinduced Radical Relay Formal [5 + 2] Reaction of Amide/Alkyne Enabled by Palladium Catalysis.

A novel class of alkyne-tethered amides facilitates an unprecedented photoinduced palladium-catalyzed radical relay formal [5 + 2] reaction. This innovative strategy allows for the rapid construction of diverse fused benzoazepine structures, yielding structurally novel and compelling compounds. With a broad substrate scope and excellent functional group tolerance, the methodology synthesizes biologically active compounds. Notably, the resulting tricyclic benzo[b]azepines offer diversification opportunities through simple transformations. DFT calculations elucidate a seven-membered ring closure mechanism involving the alkenyl radical and Pd(I) rebound alongside a concerted metalation-deprotonation (CMD) process.

Ergonomic Design and Assessment of an Improved Handle for a Laparoscopic Dissector Based on 3D Anthropometry.

Laparoscopic surgery (LS) has been shown to provide great benefits to patients compared with open surgery. However, surgeons experience discomfort, low-efficiency, and even musculoskeletal disorders (MSDs) because of the poor ergonomic design of laparoscopic instruments. A methodology for the ergonomic design of laparoscopic dissector handles considering three-dimensional (3D) hand anthropometry and dynamic hand positions was addressed in this research. Two types of hand positions for grasping and stretching were scanned from 21 volunteers using a high-resolution 3D scanner. The 3D anthropometric data were extracted from these 3D hand pose models and used to design an improved handle (IH) that provides additional support for the thumb, a better fit to the purlicue, and a more flexible grasp for the index finger. Thirty subjects were invited to evaluate the IH in terms of muscular effort, goniometric study of motion, and efficiency and effectiveness during four trials of a laparoscopic training task. Questionnaires provided subjective parameters for ergonomic assessment. Positive results included less muscle load in the trapezius as well as significant but small angular differences in the upper limb. No significant reduction in the trial time and no increased percentage of the achievement were observed between the IH and the commercial handle (CH). Improved intuitiveness, comfort, precision, stability, and overall satisfaction were reported. IH provides significant ergonomic advantages in laparoscopic training tasks, demonstrating that the proposed methodology based on 3D anthropometry is a powerful tool for the handle design of laparoscopic dissectors and other surgical instruments.

IL-17 promotes melanoma through TRAF2 as a scaffold protein recruiting PIAS2 and ELAVL1 to induce EPHA5.

An abnormal immune response induces melanoma development. IL-17 and the classical downstream signal STAT1 are associated with melanoma development. TRAF2 also mediates the downstream signaling of IL-17; however, its role in IL-17-stimulated melanoma remains unclear. Bioinformatic analysis revealed that TRAF2 can bind to PIAS2 (a SUMO E3 ligase), ELAVL1 (an RNA-binding protein), and EPHA5 (an ephrin receptor of the tyrosine kinase family). To elucidate the IL-17 downstream signal, the IL-17 receptor (R), STAT1, TRAF2, PIAS2, ELAVL1, and EPHA5 were knocked down before melanoma cells were treated with recombinant IL-17A protein. Co-immunoprecipitation and RNA immunoprecipitation were conducted to determine the interaction of TRAF2 with PIAS2, ELAVL1, and EPHA5 proteins, as well as the interaction of ELAVL1 protein with EPHA5 mRNA. STAT1 knockdown suppressed the proliferation and invasion triggered by IL-17A, but the suppressive effects were much weaker than those caused by IL-17R knockdown. This implies that another nonclassical signal mediates IL-17 effects. IL-17A induces TRAF2 recruitment of ELAVL1, PIAS2, and EPHA5 proteins. We speculated that ELAVL1 bound to the AU-rich elements in the 3' untranslated region of the EPHA5 mRNA, thereby enhancing mRNA stability. Furthermore, PIAS2 induced EPHA5 SUMOylation, which suppressed EPHA5 ubiquitination and degradation. Through pre- and post-translational regulation, IL-17A induced EPHA5 expression in melanoma, and EPHA5 knockdown markedly suppressed IL-17A-induced proliferation and invasion. This study revealed a non-classical signaling mechanism responsible for the effects of IL-17 in melanoma.

Photoinduced Nitrogen-to-Alkyl Radical Relay Heck Reaction of o-Alkylbenzamides with Vinyl Arenes by Palladium Catalysis.

Here, a palladium-catalyzed photoinduced N-to-alkyl radical relay Heck reaction of o-alkylbenzamides at benzylic sites with vinyl arenes is described. The reaction employs neither exogeneous photosensitizers nor external oxidants. It is proposed to proceed via a N-to-alkyl hybrid palladium-radical mechanism which occurs under mild conditions that are compatible with a wide range of functional groups. The products are easily transformed to azepinone derivatives, which are prevalent in pharmaceuticals and natural products.

Aryl-to-alkyl radical relay Heck reaction of amides with vinyl arenes.

A palladium-catalyzed aryl-to-alkyl radical relay Heck reaction of amides at α-C(sp3)-H sites with vinyl arenes is described. This process displays a broad substrate scope with respect to both amide and alkene components and provides access to a diverse class of more complex molecules. The reaction is proposed to proceed via a hybrid palladium-radical mechanism. The core of the strategy is that the fast oxidative addition of aryl iodide and fast 1,5-HAT overcome the slow oxidative addition of alkyl halides, and the photoexcitation effect suppresses the undesired ß-H elimination. It is anticipated that this approach would inspire the discovery of new palladium-catalyzed alkyl-Heck methods.

[Eco-physiological functions of soil microbial biofilms: A review]. / åœŸå£¤å¾®ç”Ÿç‰©è†œç”Ÿç†ç”Ÿæ€åŠŸèƒ½ç ”ç©¶è¿›å±•.

Soil microbial biofilms (SMBs) are a biological community of soil bacteria and their accumulative extracellular polymeric substances (EPS), which are the initial status and the most important components of biological soil crusts. SMBs, as the most common mode of soil bacterium survival, not only greatly contribute to the survival of free-living cells, but also stick to soil particles and roots, performing a variety of important ecological functions. Based on the structure and composition analysis of SMBs, we gave a summary of eco-physiological functions of SMBs involving soil quality and plant health. SMBs have higher metabolic activity than free-living cells. It promotes EPS secretion and organic turnover, which is important for soil fertility, pollutant decomposition, and aggregate formation. SMBs help improve plant nutrient utilization and stress resistance through the synergy of microorganisms, promotion of plant growth, promoting substance secretion and immobilization of EPS. In the future, it will be critical to uncover the micro-mechanisms underlying SMBs' eco-physiological functions and to screen functional soil bacterium strains.

Stability of the recombinant anti­erbB2 scFv­Fc­interleukin­2 fusion protein and its inhibition of HER2­overexpressing tumor cells.

The anti­erbB2 scFv­Fc­IL­2 fusion protein (HFI) is the basis for development of a novel targeted anticancer drug, in particular for the treatment of HER2­positive cancer patients. HFI was fused with the anti­erbB2 antibody and human IL­2 by genetic engineering technology and by antibody targeting characteristics of HFI. IL­2 was recruited to target cells to block HER2 signaling, inhibit or kill tumor cells, improve the immune capacity, reduce the dose of antibody and IL­2 synergy. In order to analyse HFI drug ability, HFI plasmid stability was verified by HFI expression of the trend of volume changes. Additionally, HFI could easily precipitate and had progressive characteristics and thus, the buffer system of the additive phosphate­citric acid buffer, arginine, Triton X­100 or Tween­80, the establishment of a microfiltration, ion exchange, affinity chromatography and gel filtration chromatography­based purification process were explored. HFI samples were obtained according to the requirements of purity, activity and homogeneity. In vivo, HFI significantly delayed HER2 overexpression of non­small cell lung cancer (Calu­3) in human non­small cell lung cancer xenografts in nude mice, and the inhibition rate was more than 60% (P<0.05) in the group treated with 1 mg/kg the HFI dose; HFI significantly inhibited HER2 expression of breast cancer (FVB/neu) transgenic mouse tumor growth in 1 mg/kg of the HFI dose group, and in the following treatment the 400 mm3 tumors disappeared completely. Combined with other HFI test data analysis, HFI not only has good prospects, but also laid the foundation for the development of antibody­cytokine fusion protein­like drugs.