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Abstract Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

Abstract Background The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. Methods A multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. Results Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. Conclusions We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand. Graphical Abstract

Abstract Marine oil exploration is important yet greatly increases the risk of oil leakage, which will result in severe environment pollution and economic losses. It is an urgent need to develop effective underoil adhesives. However, realizing underoil adhesion is even harder than those underwater, due to the stubborn attachment of a highly viscous oil layer on target surface. Here, inspired by endocytosis, a tough gel tape composed of zwitterionic polymer network and zwitterionic surfactants is developed. The amphiphilic surfactants can form micelle to capture the oil droplets and transport them from the interface to gel via electrostatic attraction of polymer backbone, mimicking the endocytosis and achieving robust underoil adhesion. Benefiting from the oil‐resistance of polymer backbone, the gel further realizes a combination of i) long‐term adhesion with high durability, ii) repeated adhesion in oil, and iii) renewable adhesion efficiency after exhausted use. The tape exhibits an ultra‐high adhesive toughness of 2446.86 J m−2 to stainless steel in silicone oil after 30 days' oil‐exposure; such value of adhesive toughness surpasses many of those achieved in underwater adhesion and is greater than underoil adhesion performance of commercial tape. The strategy illustrated here will motivate the design of sustainable and efficient adhesives for wet environments.

Objectives: Neuregulin 1 (NRG1) is a risk gene for schizophrenia and involved in neurodevelopment and synaptic plasticity. Polymorphisms in NRG1 may affect psychotic symptoms in schizophrenia. This study investigated the effects of the single nucleotide polymorphism (SNP) rs6982890 on peripheral plasma NRG1 immunoreactivity, clinical symptoms and cognitive functions in schizophrenia patients. Material and methods: We recruited subjects from the Han population of northern China from 2010 to 2022. We first genotyped and analyzed 6 NRG1 SNPS in 1304 patients with schizophrenia and 871 healthy controls. Then, 91 patients with schizophrenia and 40 healthy controls were selected to detect the peripheral plasma NRG1 immunoreactivity by ELISA. Among them, 84 patients were divided into rs6982890 genotypes to analyze the correlation between NRG1 immunoreactivity and clinical symptoms. Results: Rs6982890 allelic frequencies were statistically significant between patients and controls. Baseline peripheral plasma NRG1 immunoreactivity in patients were significantly lower than controls. NRG1 immunoreactivity in patients were significantly increased after 8 weeks of antipsychotic treatment and significantly correlated with clinical symptoms and cognitive function. Genotyping of patients with SNP rs6982890 indicated NRG1 immunoreactivity in CC genotype increased significantly after treatment, while CT genotype had no significant change. Baseline NRG1 immunoreactivity with the CT genotype were significantly higher than CC genotype. Conclusions: NRG1 SNP rs6982890 is significantly associated with schizophrenia in the Han population of northern China, and it may affect the effect of antipsychotic drug treatment by regulating the peripheral plasma NRG1 immunoreactivity.

Abstract Background Urban ecological health is crucial for the long-term sustainable development of watershed. Accurately evaluating the health level of the ecological environment helps to develop reasonable strategies for ecological environment restoration and resource management. This paper constructed a comprehensive evaluation index system based on the Pressure-State-Response (PSR) framework and evaluated the ecological health of eleven administrative regions in the Wei River Basin (WRB), northwest China in 1980, 2000, and 2020 using an evaluation model established by fuzzy mathematics. Further, obstacle degrees were used to quantify the contribution of pressure, state, and response modules, as well as individual indicators to ecological health. Results The comprehensive evaluation system constructed based on the PSR framework could effectively reflect the ecological health conditions of different regions in the WRB. During the study period, the ecological health went through a process of first deterioration and then improvement. By 2020, the ecological health of seven administrative regions reached healthy levels. The state module was the main obstacle module of the PSR framework to the ecological health of the most regions. The population density (P1), patch density of construction land (S5), comprehensive elasticity index (S8), soil erosion index (R1), and per capital GDP (R3) were the most crucial individual indicators affecting the ecological health. For different cities, the main obstacle factors varied. In economically developed cities, the limiting effect of P1 was more significant, while in economically underdeveloped cities, the limiting effect of R3 was stronger. Conclusions In response to the special natural environment and socio-economic conditions of arid and semi-arid areas in the WRB, an ecological health evaluation index system suitable for the characteristics of the basin was constructed. The results indicated that, to improve the levels of urban ecological health, it is necessary to restore the natural ecological environment and control population size while accelerating economic construction. Our results can provide scientific support for the ecological health evaluation and protection of the WRB and even the arid and semi-arid areas in northwest China.

RationaleRelapse to drug use is a major clinical challenge in the treatment of addictive disorders, including psychostimulant use and may be exacerbated by reduced sensitivity to natural, non-drug reward. Given the relatively limited set of outcomes, and short withdrawal time in rodent studies, we conducted a more detailed assessment of the response to natural rewards in methamphetamine (METH) naive versus exposed monkeys during long-term abstinence.MethodsThis study introduced an improved sucrose preference test (iSPT) to assess natural reward seeking and consumption in monkeys with long-term abstinence after methamphetamine (METH) use. The test was administered to sixteen naive monkeys and five METH exposed monkeys that had been abstinent for at least 3 months.ResultsMETH exposed monkeys showed a lower sucrose preference score in both the iSPT (z = -2.10, p = 0.036) and the sucrose preference test (z = -2.61, p = 0.009). The sucrose preference score was significantly correlated with the latency of the establishment of stable sucrose-preference (r = -0.76, df = 46, p < 0.001) but not with the other variables. Furthermore, water-sucrose switch latency and switch times were significantly negatively correlated (r = -0.50, df = 20, p = 0.02).ConclusionThese results show reductions in natural reward consumption during long-term methamphetamine abstinence.

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation. Imaging studies confirmed that the helmet consistently targets the primary motor cortex (M1) with a margin of error less than 1 mm. Evaluations of stimulation efficacy revealed high resolution and stability. Additionally, physiological evaluations under propofol anesthesia showed that the helmet effectively facilitated the generation of recruitment curves for motor area, confirming successful neuromodulation. Collectively, our findings present a straightforward and effective method for achieving consistent and precise NIBS targeting in awake NHPs, potentially advancing both basic neuroscience research and the development of clinical neuromodulation therapies.

Abstract Over the past century, the field of antibody discovery has undergone significant evolution, excluding the current exploration stage of artificial intelligence‐based antibody generation and the often overlooked non‐animal sourced antibody discovery, which typically requires mature in vitro affinity and the selection of high‐quality antigen formulations. This journey has traversed various stages, from methods involving serum‐based antibody acquisition, the isolation of B cells capable of perpetual antibody production through hybridoma technology, to the in‐depth exploration of genetic material using the phage display system, and the current stage involving diverse single B cell screening techniques. Additionally, the emergence of machine learning has brought impressive scientific and technological breakthroughs across research domains, proving to be a powerful application in the field of antibody discovery. However, each technique comes with its limitations, such as variability and control challenges in serum‐based acquisition, lengthy and difficult hybridoma‐derived antibody development, potential limitations in sequence and epitope diversity due to immunization biases in phage display techniques, and costly single B cell screening. Protein mass spectrometry sequencing, with shorter acquisition time and lower costs, is seen as a shortcut by diagnostic companies, impacting traditional antibody development. In diagnostic antibody development, methodological differences in downstream assays and the impact of constant regions outside the Fv core are often neglected. This paper deeply analyzes challenges, proposing innovative strategies for the next generation of diagnostic antibody development. Aimed at moving closer to the gold standard of antibody discovery, these strategies enhance the competitiveness of diagnostic reagent products.

Host remodeling of decellularized extracellular matrix (dECM) material through the appropriate involvement of immune cells is essential for achieving functional organ/tissue regeneration. As many studies have focused on the role of macrophages, only few have evaluated the role of regulatory T cells (Tregs) in dECM remodeling. In this study, we used a mouse model of traumatic muscle injury to determine the role of Tregs in the constructive remodeling of vascular-derived dECM. According to the results, a certain number of Tregs could be recruited after dECM implantation. Notably, using anti-CD25 to reduce the number of Tregs recruited by the dECM was significantly detrimental to material remodeling based on a significant reduction in the number of M2 macrophages. In addition, collagen and elastic fibers, which maintain the integrity and mechanical properties of the material, rapidly degraded during the early stages of implantation. In contrast, the use of CD28-SA antibodies to increase the number of Tregs recruited by dECM promoted constructive remodeling, resulting in a decreased inflammatory response at the material edge, thinning of the surrounding fibrous connective tissue, uniform infiltration of host cells, and significantly improved tissue remodeling scores. The number of M2 macrophages increased whereas that of M1 macrophages decreased. Moreover, Treg-conditioned medium further enhanced material-induced M2 macrophage polarization in vitro. Overall, Treg is an important cell type that influences constructive remodeling of the dECM. Such findings contribute to the design of next-generation biomaterials to optimize the remodeling and regeneration of dECM materials.

Abstract The interrelated side reactions and dendrites growth severely destabilize the electrode/electrolyte interfaces, resulting in the difficult application of aqueous Zn ion batteries (AZIBs). Hydrophobic protective layer possesses natural inhibition ability for side reactions. However, the conventional protective layer with plane structure is difficult to attain joint regulation of side reaction and Zn nucleation. Herein, a novel three‐dimensional (3D) electrically conductive and hydrophobic (3DECH) interface is elaborated to enable stable Zn anode. The as‐prepared 3DECH interface presents a uniform 3D morphology with hydrophobic property, large specific surface area, abundant zincophilic sites, and excellent electroconductivity. Therefore, the 3DECH interface achieves uniform nucleation and dendrite‐free deposition from synergetic benefits: (1) increased nucleation sites and reduced local current density through the special 3D structure and (2) uniform electric potential distribution and rapid Zn2+ transport due to the electroconductive alloy chemistry, thus coupling the hydrophobic property to obtain a highly reversible Zn anode. Consequently, the modified anode achieves a superior coulombic efficiency of 99.88% over 3500 cycles, and the pouch cells using modified anode and LiMn2O4 (LMO) cathode retain a capacity of 84 mAh g−1 after 700 cycles at a reasonable depth discharge of 36%, without dendrite piercing and “dead Zn.”

Superhydrophobic surfaces have been extensively utilized due to their high hydrophobicity and anti-icing properties. Inspired by the shape of a cross flower, research has utilized circular arc curves and Bessel curves to design a cross flower structure model. Using 3D modeling software for modeling and 3D printing technology to prepare biomimetic microstructures in structural design. The structural shape of the microstructure before and after spray coating was detected using ultra depth of field and laser confocal microscopy. Using Ultra-Ever Dry as a low surface energy substance to alter the wettability of microstructure surfaces. Through surface wettability tests, droplet freezing, and droplet impact tests, the cross shaped biomimetic structure designed by the Bessel curve has a maximum droplet freezing time of 4193 s and a minimum droplet impact time of 9.81 ms. The experimental results indicate that the cross shaped biomimetic structure has good hydrophobicity and broad application prospects.

Integrating deformable mirrors within the optical train of an adaptive telescope was one of the major innovations in astronomical observation technology, distinguished by its high optical throughput, reduced optical surfaces, and the incorporation of the deformable mirror. Typically, voice-coil actuators are used, which require additional position sensors, internal control electronics, and cooling systems, leading to a very complex structure. Piezoelectric deformable secondary mirror technologies were proposed to overcome these problems. Recently, a high-order piezoelectric deformable secondary mirror has been developed and installed on the 1.8-m telescope at Lijiang Observatory in China to make it an adaptive telescope. The system consists of a 241-actuator piezoelectric deformable secondary mirror, a 192-sub-aperture Shack-Hartmann wavefront sensor, and a multi-core-based real-time controller. The actuator spacing of the PDSM measures 19.3 mm, equivalent to approximately 12.6 cm when mapped onto the primary mirror, significantly less than the voice-coil-based adaptive telescopes such as LBT, Magellan and VLT. As a result, stellar images with Strehl ratios above 0.49 in the R band have been obtained. To our knowledge, these are the highest R band images captured by an adaptive telescope with deformable secondary mirrors. Here, we report the system description and on-sky performance of this adaptive telescope.

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), stands out as one of the most devastating epidemics impacting wheat production worldwide. Resistant wheat varieties had swiftly been overcome due to the emergence of new virulent Pst strains. Effectors secreted by Pst interfere with plant immunity, and verification of their biological function is extremely important for controlling wheat stripe rust. In this study, we identified an effector, Pst-18220, from Puccinia striiformis f. sp. tritici (Pst), which was induced during the early infection stage of Pst. Silencing the expression of Pst-18220 through virus-mediated host-induced gene silencing (HIGS) resulted in a decreased number of rust pustules. In Nicotiana benthamiana, it significantly suppressed cell death induced by Pseudomonas syringae pv. tomato (Pto) DC3000. In Arabidopsis, plants with stable overexpression of Pst-18220 showed increased susceptibility to Pto DC3000, accompanied by a decrease in the expression level of pattern-triggered immunity (PTI)/effector-triggered immunity (ETI)-related genes, namely, AtPCRK1, AtPCRK2, and AtBIK1. These results emphasize the significant role of the Pst candidate effector, Pst-18220, in rust pathogenicity and the suppression of plant defense mechanisms. This broadens our understanding of effectors without any known motif.

Abstract In clinics, hepcidin levels are elevated in various anemia‐related conditions, particularly in iron‐refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron‐refractory anemia, the potential effect of hypoxia and pharmacologically‐mimetic drug FG‐4592 (Roxadustat) are evaluated, a hypoxia‐inducible factor (HIF)‐prolyl hydroxylase (PHD) inhibitor, on mouse models of iron‐refractory iron‐deficiency anemia (IRIDA), anemia of inflammation and 5‐fluorouracil‐induced chemotherapy‐related anemia. The potent protective effects of both hypoxia and FG‐4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG‐4592 could stabilize duodenal Hif2α, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin‐activated anemias. Moreover, duodenal Hif2α overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2α knockout in the gut significantly delays the recovery from 5‐fluorouracil‐induced anemia, which can not be rescued by FG‐4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia‐related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia.

Abstract Purpose To evaluate the effectiveness of a discourse-based psychological intervention on perioperative anxiety, pain and life satisfaction of patients with AIS. Methods Between April 2018 and February 2021, 116 consecutive patients with AIS undergoing corrective surgery were enrolled in this study, including 51 with personalized psychological intervention (intervention group, IG) and 65 without (control group, CG). After propensity score matching (PSM), patient characteristics, perioperative scores of anxiety and life satisfaction, measured by values of Generalized Anxiety Disorder 7-item Scale (GAD-7) and Life Satisfaction Index Z scale (LSIZ), were recorded. Mixed linear models were used to estimate the influence of intervention group and time of measurement, as well as their interactions, in anxiety and life satisfaction. Data on post-surgical pain in both groups was also collected and analyzed. Results After PSM, a total of 90 patients (IG, n = 45; CG, n = 45) were enrolled in this study, and the 2 groups were comparable in patients’ demographic and baseline characteristics. There were no pre-intervention between-group differences in the degree of anxiety (IG: 3.98 ± 3.27 vs. CG: 3.93 ± 3.20, p = .948, Cohen’s d = 0.015), and life satisfaction (IG: 6.56 ± 1.70 vs. CG: 6.67 ± 2.09, p = .783, Cohen’s d = -0.058). After surgery, participants in both IG and CG showed improved the levels of anxiety (GAD-7: IG 2.18 ± 1.21; CG 2.87 ± 2.00) and life satisfaction (LSIZ: IG 9.84 ± 2.09; CG 9.02 ± 2.15). A stratified analysis of patients with generalized anxiety disorder showed improved anxiety (GAD-7: IG 3.50 ± 1.22 vs. CG 6.80 ± 2.05, p = .017, Cohen’s d = -1.956) and lower pain level (VAS: IG 4.50 ± 1.76 vs. CG 7.00 ± 1.00, p = .017, Cohen’s d = -1.747) in the IG than the CG after surgery. Conclusions Discourse-based psychological intervention before surgery can improve perioperative anxiety and life satisfaction, and postoperative painful condition, especially for patients with high-leveled pre-surgical anxiety.

Zirconia (ZrO2) is a ceramic material with high-temperature resistance and good insulating properties. Herein, for the first time, the surface of ZrO2 was modified with docosanoic acid (DCA) to improve its self-cleaning and hydrophobic properties. This surface modification transformed the surface of ZrO2 from hydrophilic to superhydrophobic. A two-step spraying method was used to prepare the superhydrophobic surface of ZrO2 by sequentially applying a primer and a topcoat. The primer was a solution configured using an epoxy resin as the adhesive and polyamide as the curing agent, while the topcoat was a modified ZrO2 solution. The superhydrophobic surface of ZrO2 exhibited a contact angle of 154° and a sliding angle of 4°. Scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and other analytical techniques were used to characterize the prepared zirconia particles and their surfaces. Moreover, results from surface self-cleaning and droplet freezing tests showed that DCA-modified ZrO2 can be well combined, and its coatings show good self-cleaning and anti-icing properties on TA2 bases.

ABSTRACTMetallic lattice structures based on triply periodic minimum surfaces (TPMS) have attracted extensive attention for their potential application in lightweight and energy absorption. The underlying phenomena, mechanisms and modelling under the crushing responses from quasi-static to shock conditions still remain to be revealed. This work systematically investigates the mechanical behaviour of graded additively Schoen-F-RD (FRD) lattice structures under various loading rates. Under dynamic compression, FRD lattices exhibit the ability to withstand larger densification strains at higher plateau strengths, thus, holding enhanced energy absorption capabilities. At medium strain rates, it is the rate-dependence of lattice base material dominates in the strength enhancement, while, at higher strain rates, the role of inertia effect becomes notable. Furthermore, an empirical formula is introduced to predict the shock stress responses. Finally, constitutive models with strain-rates are proposed for the uniform and graded lattices. These findings can provide excellent guidance on the design of energy-absorbing structures.

In clinical practice, it is frequently observed that cardiac and psychological disorders frequently co-occur, leading to the emergence of a field known as cardiovascular disease with depression. Depression, in particular, poses a remarkable risk for the evolution of cardiovascular disease and intimately relates to adverse cardiovascular outcomes and mortality. Moreover, individuals who are depressed exhibit a higher susceptibility to developing cardiovascular disease compared to those in good health. Patients diagnosed with cardiovascular disease with depression disease face a heightened risk of mortality within a 5-year timeframe, and their prognosis remains unsatisfactory even after receiving treatment targeting a single disorder, with a notable recurrence rate. Psychological interventions in conjunction with medications are commonly employed in clinical settings for treating patients with cardiovascular disease and depression diseases, albeit with limited effectiveness and unfavorable prognosis. Traditional Chinese medicine (TCM), such as Shuangxinfang, Chaihujialonggumuli, and Yixin Ningshen Tablet, etc., have been reported and have Therapeutic effects in patients with cardiovascular disease combined with depression. Despite numerous articles documenting a notable association between heart disease and depression, there exists a dearth of studies elucidating the precise pathogenesis and target of action for cardiovascular disease with depression diseases. This article endeavors to consolidate the epidemiological data, potential pathogenic mechanisms, and available treatment modalities for cardiovascular disease with depression diseases. Its primary objective is to unveil plausible co-morbid mechanisms and suitable treatment approaches, thereby offering novel insights for the prevention, diagnosis, and management of cardiovascular disease with depression diseases.

Background Brain-derived neurotrophic factor (BDNF) is known to prevent methamphetamine (METH)-induced neurotoxicity and plays a role in various stages of METH addiction. However, there is a lack of research with longitudinal design on changes in plasma BDNF levels in active METH-dependent individuals.Aims The aim of the study was to investigate changes in BDNF levels during METH self-administration in monkeys.Methods This study measured plasma BDNF levels in three male rhesus monkeys with continuous METH exposure and four male control rhesus monkeys without METH exposure. Changes in plasma BDNF levels were then assessed longitudinally during 40 sessions of METH self-administration in the three monkeys.Results Repeated METH exposure decreased plasma BDNF levels. Additionally, plasma BDNF decreased with long-term rather than short-term accumulation of METH during METH self-administration.Conclusions These findings may indicate that the changes in peripheral BDNF may reflect the quantity of accumulative METH intake during a frequent drug use period.

Abstract Background N4-acetylcytidine (ac4C) as a significant RNA modification has been reported to maintain the stability of mRNA and to regulate the translation process. However, the roles of both ac4C and its ‘writer’ protein N-acetyltransferase 10 (NAT10) played in the disease especially colorectal cancer (CRC) are unclear. At this point, we discover the underlying mechanism of NAT10 modulating the progression of CRC via mRNA ac4C modification. Methods The clinical significance of NAT10 was explored based on the TCGA and GEO data sets and the 80 CRC patients cohort of our hospital. qRT-PCR, dot blot, WB, and IHC were performed to detect the level of NAT10 and ac4C modification in CRC tissues and matched adjacent tissues. CCK-8, colony formation, transwell assay, mouse xenograft, and other in vivo and in vitro experiments were conducted to probe the biological functions of NAT10. The potential mechanisms of NAT10 in CRC were clarified by RNA-seq, RIP-seq, acRIP-seq, luciferase reporter assays, etc. Results The levels of NAT10 and ac4C modification were significantly upregulated. Also, the high expression of NAT10 had important clinical values like poor prognosis, lymph node metastasis, distant metastasis, etc. Furthermore, the in vitro experiments showed that NAT10 could inhibit apoptosis and enhance the proliferation, migration, and invasion of CRC cells and also arrest them in the G2/M phase. The in vivo experiments discovered that NAT10 could promote tumor growth and liver/lung metastasis. In terms of mechanism, NAT10 could mediate the stability of KIF23 mRNA by binding to its mRNA 3’UTR region and up-regulating its mRNA ac4c modification. And then the protein level of KIF23 was elevated to activate the Wnt/β-catenin pathway and more β-catenin was transported into the nucleus which led to the CRC progression. Besides, the inhibitor of NAT10, remodelin, was applied in vitro and vivo which showed an inhibitory effect on the CRC cells. Conclusions NAT10 promotes the CRC progression through the NAT10/KIF23/GSK-3β/β-catenin axis and its expression is mediated by GSK-3β which forms a feedback loop. Our findings provide a potential prognosis or therapeutic target for CRC and remodelin deserves more attention. Graphical Abstract

Abstract Background Estrogen receptor β (ERβ) is the major ER subtype in hepatic stellate cells (HSCs). Previously we reported phytoestrogen calycosin suppressed liver fibrosis progression and inhibited HSC-T6 cell functions, suggesting the effects may be related to ERβ. Here, we explore the effect of overexpressed ERβ on human HSCs and the role of ERβ in pharmacological action of calycosin. Methods LX-2 cells were transfected with lentivirus to overexpress ERβ. In the presence or absence of overexpressed ERβ, the effects of ERβ and calycosin on proliferation, migration, activation, collagen production and degradation of TGF-β1-induced LX-2 cells and the role of ERβ in the inhibition effect of calycosin were investigated. LX-2 cells overexpressed with ERβ or treated with ER non-selective antagonist ICI182,780 were used to investigate the regulation of ERβ on JAK2/STAT3 signaling pathway. CCK-8 method was used to screen effective doses of calycosin and investigate cell proliferation. The cell migration was detected by transwell chamber assay. The expression of α-SMA was detected by immunofluorescence and western blot. The protein expressions of Col-I, MMP1, TIMP1, JAK2, p-JAK2, STAT3 and p-STAT3 were detected by western blot. Results ERβ overexpressed lentivirus was successfully transfected into LX-2 cells with high efficiency. Overexpressed ERβ or calycosin alone inhibited the TGF-β1-induced LX-2 cell proliferation and migration, downregulated the protein expressions of α-SMA, Col-I, TIMP-1, p-STAT3 and upregulated MMP-1. Both overexpressed ERβ and calycosin had no significant effect on JAK2, p-JAK2 and STAT3 expressions. ERβ overexpression further enhanced the above effects of calycosin. However, after the cells were treated with ICI182,780, downregulation of STAT3 phosphorylation induced by calycosin was reversed. Conclusions ERβ mediated the inhibition of major functions of LX-2 cell possibly by inhibiting the phosphorylation of STAT3, and was an important pathway through which calycosin exerted anti-liver fibrosis effect. Graphical Abstract

With the advancement of sensor technology, distributed processing technology, and wireless communication, Visual Sensor Networks (VSNs) are widely used. However, VSNs also have flaws such as poor data synchronization, limited node resources, and complicated node management. Thus, this paper proposes a sensor placement optimization method to save network resources and facilitate management. First, some necessary models are established, including the sensor model, the space model, the coverage model, and the reconstruction error model, and a dimensionality reduction search method is proposed. Next, following the creation of a multi-objective optimization function to balance reconstruction error and coverage, a clever optimization algorithm that combines the benefits of Genetic Algorithms (GA) and Particle Swarm Optimization (PSO) is applied. Finally, comparison studies validate the methodology presented in this paper, and the combined algorithm can enhance optimization effect while relatively reducing running time. In addition, a sensor coverage method for large-range target space with obstacles is discussed.

Abstract Cancer-associated fibroblasts (CAFs) are the most abundant stromal components in the tumor microenvironment (TME) and closely involved in tumor progression. However, the precise biological functions and molecular mechanisms of CAFs in the TME have yet to be understood. Here, we demonstrate that WEE2-AS1 is highly expressed in the CAF-derived small extracellular vesicles (sEVs). Moreover, WEE2-AS1 is markedly higher in plasma sEVs of CRC patients than in healthy subjects and its high level predicts advanced pathological staging and poor survival. Then, we conducted a series of in vitro and in vivo experiments. Elevated expression of WEE2-AS1 in sEVs increases CRC cell proliferation in vitro. Importantly, aberrant CAF-sEVsWEE2-AS1 leads to tumor formation and progression in BALB/c nude mice and promotes AOM/DSS-induced tumorigenesis. Mechanistically, WEE2-AS1 functions as a modular scaffold for the MOB1A and E3 ubiquitin-protein ligase praja2 complexes, leading to MOB1A degradation via the ubiquitin-proteasome pathway. The Hippo pathway is then inhibited and more YAP are transported into the nucleus, where they activate downstream gene transcription. Together, our data reveal that CAF-sEVsWEE2-AS1 interacts with MOB1A, promotes degradation of MOB1A, inhibits the Hippo pathway, and facilitates the growth of CRC cells. Hence, exosomal WEE2-AS1 may be a promising therapeutic target and circulating biomarker for CRC diagnosis and prognosis.

Primary malignant melanoma of the lung (PMML) is an extremely rare and refractory tumor, and its diagnosis is a significant challenge. The current study presents the case of a 62-year-old man who presented to the Department of Cardiothoracic Surgery (Lishui Municipal Central Hospital, Lishui, China) with chest tightness and fatigue for 3 months. Chest computed tomography (CT) revealed a 1.5- × 1.9-cm mass with irregular borders and heterogenous density located in the right lower lung lobe. Contrast-enhanced CT revealed slight enhancement of the mass, but there was no clear evidence of malignancy. Positron emission tomography (PET)/CT revealed a defined-margin mass, with slightly high uptake (standardized uptake value [SUV]: 3.6). The patient underwent video-assisted thoracoscopic surgery (VATS), and the final diagnosis was PMML on the basis of the results of the pathological examination. The patient received four courses of immunotherapy after the operation, and eventually declined further immunotherapy owing to the high cost. The patient was followed-up for 1 year without metastasis or recurrence.

Anoikis and epithelial-mesenchymal transition (EMT) are significant phenomena occurring in distant metastasis of colon adenocarcinoma (COAD). A comprehensive understanding of their crosstalk and the identification of key genes are vital for treating the distant metastasis of COAD. The objective of this study was to design and validate accurate prognostic predictors for COAD patients based on the anoikis and EMT processes. We obtained gene signatures from various databases and performed univariate and multivariate Cox regression analyses, principal component analysis (PCA). The COAD patients were categorized into the worst prognosis group, the Anoikis Potential Index (API) Low + EMT Potential Index (EPI) High group and the others group. Then we utilized gene set enrichment analysis (GSEA) to identify differentially expressed genes and to establish a prognostic risk model. The model classified patients into high- or low-risk groups, with patients in the high-risk group displaying worse survival status. A nomogram was established to predict overall survival rates, demonstrating high specificity and sensitivity. Additionally, we connected the risk model to the tumor microenvironment (TME) using single-sample GSEA and the MCP counter tool, as well as evaluated the sensitivity to common chemotherapeutic drugs, such as Gefitinib and Gemcitabine. Lastly, cell and tissue experiments suggested a positive correlation among anoikis resistance, EMT, and liver/lung metastasis of COAD. This is the first study to comprehensively analyze the crosstalk between anoikis and EMT and offers new therapeutic targets for COAD metastasis patients.

BackgroundDisease control is a primary treatment goal for patients with chronic rhinosinusitis (CRS). This study aims to summarize the evaluation parameters of disease control and then identify predictors of poorly controlled CRS.MethodsA systematic review of the literature was performed on PubMed, Google Scholar, Scopus, and Cochrane databases to identify studies relating to disease control in CRS.ResultsThe concept of disease control in patients with CRS involved the longitudinal assessment of the disease state and was also an important goal of treatment. As a metric of the disease state, the disease control reflected the ability to keep disease manifestations within certain limits, the efficacy after treatment, and the impact on quality of life. Validated measurements, such as EPOS2012 criteria, EPOS2020 criteria, Sinus Control Test, and patient/physician-reported global level of CRS control, have been utilized in clinical practice. These existing disease control instruments incorporated various disease manifestations and categorized patients into two (well-controlled and poor-controlled), three (uncontrolled, partly controlled, and controlled), or five (not at all, a little, somewhat, very, and completely) control categories. Eosinophilia, high computerized tomography score, bilateral sinonasal disease, asthma, allergic rhinitis, female gender, aspirin intolerance, revision surgery, low serum amyloid A, and specific T cell subtype would predict poorly controlled CRS.ConclusionThe concept of disease control and its application were gradually developed in patients with CRS. The existing disease control instruments demonstrated a lack of uniformity regarding the controlled criteria and included parameters.

Virtualization technology represented through Virtual Machines (VMs) is recognized as a key infrastructure in cloud computing. This technology is developing rapidly and cloud data centers face challenges such as Virtual Machine Placement (VMP) for energy efficiency. VMP is defined as the efficient allocation of VMs to Host Machines (HMs) to achieve various objectives such as reducing energy consumption, load balancing and avoid Service Level Agreement Violations (SLAV). In this paper, VMP is addressed using a Deep Reinforcement Learning (DRL) based strategy to determine the best mapping between VMs and HMs. We present VMP-A3C, an effective strategy to solve VMP using Asynchronous Advantage Actor-Critic (A3C) algorithm as a new DRL approach. VMP-A3C aims at load balancing in HMs without SLAV, where energy consumption is reduced as much as possible. VMP-A3C learns to dynamically consolidate VMs using migration techniques to a minimum number of HMs. We believe that there is scope for improvements in shutting down little-workload HMs through VMs migration. The effectiveness of the proposed algorithm has been evaluated from various aspects such as the deployment rate, energy consumption, SLAV, the number of shutdown HMs and the number of migrated VMs. The main difference in terms of energy consumption and the number of required HMs between VMP-A3C and the best existing state-of-the-art method is 2.54% and 7.14%, respectively.

Computing-in-Memory (CIM) is a novel computing architecture that enormously improves energy efficiency and reduces computing latency by avoiding frequent data movement between the computation and memory units. Currently, digital CIM is regarded as more suitable for high-precision operations represented in floating-point arithmetic, as it is not limited by the bit width of ADC/DAC in analog CIM. However, the development of DCIM still faces two problems: On the one hand, mainstream SRAM-based DCIM memory cells introduce large area overheads, which contain at least six transistors per cell. On the other hand, existing DCIM solutions can only support the computing precision up to FP32, failing to meet the demands of high-accuracy application scenarios. To overcome these problems, this work designs a novel SOT-MRAM-based digital CIM macro (MDCIM) with higher area/energy efficiency and achieves double-precision floating-point (FP64) computation with a modified fused multiply–accumulate (FMA) module. The proposed design is synthesized with a 55 nm CMOS technology node, achieving 0.62 mW power consumption, 26.9 GOPS/W, and 0.332 GOPS/mm2 energy efficiency at 150 MHz with 1.08 V supply. Circuit level simulation results show that the MDCIM can achieve higher area utilization compared to previous SRAM-based CIM designs.

Abstract Wearables and bioelectronics rely on breathable interface devices with bioaffinity, biocompatibility, and smart functionality for interactions between beings and things and the surrounding environment. Elastic fibers/fabrics with mechanical adaptivity to various deformations and complex substrates, are promising to act as fillers, carriers, substrates, dressings, and scaffolds in the construction of biointerfaces for the human body, skins, organs, and plants, realizing functions such as energy exchange, sensing, perception, augmented virtuality, health monitoring, disease diagnosis, and intervention therapy. This review summarizes and highlights the latest breakthroughs of elastic fibers/fabrics for wearables and bioelectronics, aiming to offer insights into elasticity mechanisms, production methods, and electrical components integration strategies with fibers/fabrics, presenting a profile of elastic fibers/fabrics for energy management, sensors, e‐skins, thermal management, personal protection, wound healing, biosensing, and drug delivery. The trans‐disciplinary application of elastic fibers/fabrics from wearables to biomedicine provides important inspiration for technology transplantation and function integration to adapt different application systems. As a discussion platform, here the main challenges and possible solutions in the field are proposed, hopefully can provide guidance for promoting the development of elastic e‐textiles in consideration of the trade‐off between mechanical/electrical performance, industrial‐scale production, diverse environmental adaptivity, and multiscenario on‐spot applications.

Land resources are closely intertwined with human survival, making it crucial to explore the spatiotemporal changes and driving forces of land use. In this study, the Yan River Basin in the Loess Plateau was selected as the study area. The Mann–Kendall trend test, Pettitt’s test, landscape pattern indices, and other methods were employed to explore characteristics and driving factors of land use change from 1990 to 2020. The results indicate that: (1) The areas of forest and impervious showed a significant increasing trend and suddenly changed in 2004. Change-point years for the area of cropland and grassland were 2005 and 1999, respectively. The main transition of land use types was from cropland to grassland and from grassland to forest. (2) Patches showed a trend towards regularization and simplification, indicating the strengthening of human activities’ impact on spatial patterns. (3) Both social and natural factors jointly influenced land use change in the Yan River Basin. The Grain for Green (GfG) project was the main driving factor in accelerating land use transformation. This study aims to provide a basis for the scientific management of land resources and serve as an example for related research on land use change in the Loess Plateau.

Abstract Background Recent studies have investigated the role of circular RNAs (circRNAs) as significant regulatory factors in multiple cancer progression. Nevertheless, the biological functions of circRNAs and the underlying mechanisms by which they regulate colorectal cancer (CRC) progression remain unclear. Methods A novel circRNA (circ-GALNT16) was identified by microarray and qRT-PCR. A series of in vitro and in vivo phenotype experiments were performed to investigate the role of circ-GALNT16 in CRC. The FISH, RNA pulldown assay, RIP assay, RNA sequencing, coimmunoprecipitation, and ChIP were performed to investigate the molecular mechanisms of circ-GALNT16 in CRC progression. Results Circ-GALNT16 was downregulated in CRC and was negatively correlated with poor prognosis. Circ-GALNT16 suppressed the proliferation and metastatic ability of CRC cells in vitro and in vivo. Mechanistically, circ-GALNT16 could bind to the KH3 domain of heterogeneous nuclear ribonucleoprotein K (hnRNPK), which promoted the SUMOylation of hnRNPK. Additionally, circ-GALNT16 could enhance the formation of the hnRNPK-p53 complex by facilitating the SUMOylation of hnRNPK. RNA sequencing assay identified serpin family E member 1 as the target gene of circ-GALNT16 at the transcriptional level. Rescue assays revealed that circ-GALNT16 regulated the expression of Serpine1 by inhibiting the deSUMOylation of hnRNPK mediated by SUMO-specific peptidase 2 and then regulating the sequence-specific DNA binding ability of the hnRNPK-p53 transcriptional complex. Conclusions Circ-GALNT16 suppressed CRC progression by inhibiting Serpine1 expression through regulating the sequence-specific DNA binding ability of the SENP2-mediated hnRNPK-p53 transcriptional complex and might function as a biomarker and therapeutic target for CRC.

N7-Methylguanosine (m7G) modifications are a common type of posttranscriptional RNA modifications. Its function in the tumor microenvironment (TME) has garnered widespread focus in the past few years. Long non-coding RNAs (lncRNAs) played an essential part in tumor development and are closely associated with the tumor immune microenvironment. In this study, we employed a comprehensive bioinformatics approach to develop an m7G-associated lncRNA prognostic model based on the colon adenocarcinoma (COAD) database from The Cancer Genome Atlas (TCGA) database. Pearson’s correlation analysis was performed to identify m7G-related lncRNAs. Differential gene expression analysis was used to screen lncRNAs. Then, we gained 88 differentially expressed m7G-related lncRNAs. Univariate Cox analysis and Lasso regression analysis were performed to build an eight-m7G-related-lncRNA (ELFN1-AS1, GABPB1-AS1, SNHG7, GS1-124K5.4, ZEB1-AS1, PCAT6, C1RL-AS1, MCM3AP-AS1) risk model. Consensus clustering analysis was applied to identify the m7G-related lncRNA subtypes. We also verified the risk prediction effect of a gene signature in the GSE17536 test set (177 patients). A nomogram was constructed to predict overall survival rates. Furthermore, we analyzed differentially expressed genes (DEGs) between high-risk and low-risk groups. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted with the analyzed DEGs. At last, single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, MCP-COUNTER, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithms were utilized to discover the relationship between the risk model and the TME. Consequently, the m7G-related lncRNA risk model for COAD patients could be a viable prognostic tool and treatment target.

Inflammatory bowel diseases (IBDs), including Crohn’s disease (CD) and ulcerative colitis (UC), have become a global health problem with a rapid growth of incidence in newly industrialized countries. Observational studies have recognized associations between blood lipid traits and IBDs, but the causality still remains unclear. To determine the causal effects of blood lipid traits, including triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) on IBDs, two-sample Mendelian randomization (MR) analyses were conducted using the summary-level genome-wide association study (GWAS) statistics of blood lipid traits and IBDs. Our univariable MR using multiplicative random-effect inverse-variance weight (IVW) method identified TC (OR: 0.674; 95% CI: 0.554, 0.820; p < 0.00625) and LDL-C (OR: 0.685; 95% CI: 0.546, 0.858; p < 0.00625) as protective factors of UC. The result of our multivariable MR analysis further provided suggestive evidence of the protective effect of TC on UC risk (OR: 0.147; 95% CI: 0.025, 0.883; p < 0.05). Finally, our MR-BMA analysis prioritized TG (MIP: 0.336; θ^MACE: −0.025; PP: 0.31; θ^λ: −0.072) and HDL-C (MIP: 0.254; θ^MACE: −0.011; PP: 0.232; θ^λ: −0.04) for CD and TC (MIP: 0.721; θ^MACE: −0.257; PP: 0.648; θ^λ: −0.356) and LDL-C (MIP: 0.31; θ^MACE: −0.095; PP: 0.256; θ^λ: −0.344) for UC as the top-ranked protective factors. In conclusion, the causal effect of TC for UC prevention was robust across all of our MR approaches, which provide the first evidence that genetically determined TC is causally associated with reduced risk of UC. The finding of this study provides important insights into the metabolic regulation of IBDs and potential metabolites targeting strategies for IBDs intervention.

Arc sag is an important parameter in the design and operation and maintenance of transmission lines and is directly related to the safety and reliability of grid operation. The current arc sag measurement method is inefficient and costly, which makes it difficult to meet the engineering demand for fast inspection of transmission lines. In view of this, this paper proposes an automatic spacer bar segmentation algorithm, CM-Mask-RCNN, that combines the CAB attention mechanism and MHSA self-attention mechanism, which automatically extracts the spacer bars and calculates the center coordinates, and combines classical algorithms such as beam method leveling, spatial front rendezvous, and spatial curve fitting, based on UAV inspection video data, to realize arc sag measurement with a low cost and high efficiency. It is experimentally verified that the CM-Mask-RCNN algorithm proposed in this paper achieves an AP index of 73.40% on the self-built dataset, which is better than the Yolact++, U-net, and Mask-RCNN algorithms. In addition, it is also verified that the adopted approach of fusing CAB and MHSA attention mechanisms can effectively improve the segmentation performance of the model, and this combination improves the model performance more significantly compared with other attention mechanisms, with an AP improvement of 2.24%. The algorithm in this paper was used to perform arc sag measurement experiments on 10 different transmission lines, and the measurement errors are all within ±2.5%, with an average error of −0.11, which verifies the effectiveness of the arc sag measurement method proposed in this paper for transmission lines.

Abstract Colorectal cancer (CRC) is one of the most common cancers around the world and endangers human health seriously. Liver metastasis is an important factor affecting the long-term prognosis of CRC and the specific mechanism of CRLM (colorectal cancer with liver metastasis) is not fully understood. LZTS1 has been found dysregulated in many cancers, especially in CRC. Theories suggested that hypermethylation of the promoter regions of LZTS1 was responsible for LZTS1 abnormal expression in multiple malignant tumors. Although the role of LZTS1 in CRC cell proliferation has been reported, its role in CRLM remains unclear. Numerous studies reported Long non-coding RNA (lncRNA) could regulate the gene expression level by regulating gene methylation status in many tumors. However, whether there were lncRNAs could change the methylation status of LZTS1 or not in CRLM was unknown. In this study, we aimed to investigate whether there are lncRNAs can regulate the expression of LZTS1 through affecting DNA methylation in CRLM. We found that upregulated Lnc-LALC in CRC was negatively correlated with LZTS1 expression, and Lnc-LALC could regulate LZTS1 expression in both mRNA and protein level in our study. Functionally, Lnc-LALC enhanced the CRC cells metastasis ability in vitro and vivo through inhibiting the expression of LZTS1. Furthermore, the precise mechanisms exploration showed that lnc-LALC could recruit DNA methyltransferases (DNMTs) to the LZTS1 promoter by combining with Enhancer of zeste homolog 2(EZH2) and then altered the expression of LZTS1 via DNMTs-mediated DNA methylation. Collectively, our data demonstrated the important role of Lnc-LALC/ LZTS1 axis in CRLM development.

Triboelectric nanogenerators (TENGs) are an emerging technology capable of converting the ambient mechanical energy into electricity, promising for complete utilization of the distributed energy to improve the quality of human life. However, realizing material innovation for good trade‐off between the high triboelectric output and environment friendliness remains huge challenge, but it is of great importance for sustainable development of TENGs. Cellulose is a typical natural polymer that promises to address the challenge. Herein, the sustainable TENGs that originate from cellulose and potentially back to the natural world are focused on, realizing on‐spot TENGs. First, the sources, forms, morphologies, structures, and modifications of cellulose are systematically summarized, indicating the commercial and noncommercial cellulose materials’ potential for TENGs’ application. Second, the dominating additive properties of cellulose such as hydrophobicity, self‐cleaning, corrosion resistance, optical transparency, electrical conductivity, and degradability are introduced, which can effectively steer the development of TENGs. Thereafter, the TENGs with tailorable functions enabled by less‐refined cellulose and various physical/chemical modified cellulose are reviewed, as well as plants‐supported on‐spot TENGs with environment adaptivity and transient property, embracing a sustainable future of versatile cellulose to adapt the distributed network of multiscenario TENGs for energy management and information communication.

Abstract Background Acute spinal cord injury (SCI) could cause mainly two types of pathological sequelae, the primary mechanical injury, and the secondary injury. The macrophage in SCI are skewed toward the M1 phenotype that might cause the failure to post-SCI repair. Methods SCI model was established in Balb/c mice, and the changes in macrophage phenotypes after SCI were monitored. Bioinformatic analyses were performed to select factors that might regulate macrophage polarization after SCI. Mouse bone marrow-derived macrophages (BMDMs) were isolated, identified, and induced for M1 or M2 polarization; the effects of lncRNA guanylate binding protein-9 (lncGBP9) and suppressor of cytokine signaling 3 (SOCS3) on macrophages polarization were examined in vitro and in vivo. The predicted miR-34a binding to lncGBP9 and SOCS3 was validated; the dynamic effects of lncGBP9 and miR-34a on SOCS3, signal transducer and activator of transcription 1 (STAT1)/STAT6 signaling, and macrophage polarization were examined. Finally, we investigated whether STAT6 could bind the miR-34a promoter to activate its transcription. Results In SCI Balb/c mice, macrophage skewing toward M1 phenotypes was observed after SCI. In M1 macrophages, lncGBP9 silencing significantly decreased p-STAT1 and SOCS3 expression and protein levels, as well as the production of Interleukin (IL)-6 and IL-12; in M2 macrophages, lncGBP9 overexpression increased SOCS3 mRNA expression and protein levels while suppressed p-STAT6 levels and the production of IL-10 and transforming growth factor-beta 1 (TGF-β1), indicating that lncGBP9 overexpression promotes the M1 polarization of macrophages. In lncGBP9-silenced SCI mice, the M2 polarization was promoted on day 28 after the operation, further indicating that lncGBP9 silencing revised the predominance of M1 phenotype at the late stage of secondary injury after SCI, therefore improving the repair after SCI. IncGBP9 competed with SOCS3 for miR-34a binding to counteract miR-34a-mediated suppression on SOCS3 and then modulated STAT1/STAT6 signaling and the polarization of macrophages. STAT6 bound the promoter of miR-34a to activate its transcription. Conclusions In macrophages, lncGBP9 sponges miR-34a to rescue SOCS3 expression, therefore modulating macrophage polarization through STAT1/STAT6 signaling. STAT6 bound the promoter of miR-34a to activate its transcription, thus forming two different regulatory loops to modulate the phenotype of macrophages after SCI.

Aiming at the fault diagnosis accuracy of rolling bearings is not high enough, and unknown faults cannot be correctly identified. A priority elimination (PE) method is proposed in this paper. First, the priority diagnosis sequence of faults was determined by comparing the ratios of the inter-class distance to the intra-class distance for all faults. Then, the model training and fault diagnosis were carried out in order of the priority sequence, and the samples of the fault that had been identified were eliminated from the data set until all faults were diagnosed. For the diagnosis model, the stacked sparse auto-encoder network (SSAE) was selected to extract the features of the vibration signal. The extreme gradient boosting algorithm (XGBoost) was chosen to identify the fault type. Finally, the method was tested and verified by experimental data and compared with classical algorithms. Research results indicate the following: (1) with the addition of PE based on SSAE-XGBoost, the fault diagnosis accuracy can be improved from 96.3% to 99.27%, which is higher than other methods; (2) for the test set with the samples of unknown faults, the diagnosis accuracy of SSAE-XGBoost with PE can reach 92.34%, which is nearly 6% higher than that without PE and is also obviously higher than other classical fault diagnosis methods with or without PE. The PE method can not only improve the diagnosis accuracy of faults but also identify unknown faults, which provides a new method and way for fault diagnosis.

Abstract Background Though circular RNAs, new non‐coding RNA classes have demonstrated that they have an essential role in the initiation as well as development of CRC (colorectal cancer), whereas in CRC the function and mechanism of hsa_circ_0001666 are less known. Methods Hsa_circ_0001666 was identified by bioinformatics analysis of a circRNA microarray from the GEO database, and its expression in both CRC cell lines and tissues was analysed. A series of in vitro along with in vivo experiments were carried out for exploring the hsa_circ_0001666 functions, including transwell, wound healing, flow cytometry, colony formation, Edu, CCK‐8, soft agar colony formation, tumor xenografts and lung/liver metastasis in mice. RNA pull‐down, RIP (RNA immunoprecipitation), luciferase reporter assay, FISH (fluorescence in situ hybridization) and rescue experiments were used for determining the correlation among hsa_circ_0001666, miR‐576‐5p and PCDH10. Results Hsa_circ_0001666 was downregulated in both CRC cell lines along with tumour tissues. A higher expression level of hsa_circ_0001666 indicated a better clinical prognosis in patients with CRC. Hsa_circ_0001666 knockdown significantly supported CRC cell proliferation along with invasion and inhibited cell apoptosis in vitro. Hsa_circ_0001666 knockdown accelerated the CRC growth and metastasis in vivo. Moreover, the mechanistic study showed that hsa_circ_0001666, acting as ‘ceRNA’ of miR‐576‐5p, prevented PCDH10 downregulation, as well as suppressed EMT and stemness of CRC cells, and the Wnt/β‐catenin signalling pathway. Inhibiting miR‐576‐5p or overexpressing PCDH10 could reverse phenotypic changes caused by knocking down of hsa_circ_0001666. Conclusions Hsa_circ_0001666 suppresses CRC progression through the miR‐576‐5p/PCDH10 axis and may provide a new insight for the diagnosis and treatment of CRC.

Background: Emerging evidence suggests that inflammatory response biomarkers are predictive factors that can improve the accuracy of colorectal cancer (CRC) prognoses. We aimed to evaluate the prognostic significance of C-reactive protein (CRP), the Glasgow Prognostic Score (GPS), and the CRP-to-albumin ratio (CAR) in CRC.Methods: Overall, 307 stage I–III CRC patients and 72 colorectal liver metastases (CRLM) patients were enrolled between October 2013 and September 2019. We investigated the correlation between the pretreatment CRP, GPS, and CAR and the clinicopathological characteristics. The Cox proportional hazards model was used for univariate or multivariate analysis to assess potential prognostic factors. A receiver operating characteristic (ROC) curve was constructed to evaluate the predictive value of each prognostic score. We established CRC survival nomograms based on the prognostic scores of inflammation.Results: The optimal cutoff levels for the CAR for overall survival (OS) in all CRC patients, stage I–III CRC patients, and CRLM patients were 0.16, 0.14, and 0.25, respectively. Kaplan–Meier analysis and log-rank tests demonstrated that patients with high CRP, CAR, and GPS had poorer OS in CRC, both in the cohorts of stage I–III patients and CRLM patients. In the different cohorts of CRC patients, the area under the ROC curve (AUC) of these three markers were all high. Multivariate analysis indicated that the location of the primary tumor, pathological differentiation, and pretreatment carcinoembryonic antigen (CEA), CRP, GPS, and CAR were independent prognostic factors for OS in stage I–III patients and that CRP, GPS, and CAR were independent prognostic factors for OS in CRLM patients. The predictors in the prediction nomograms included the pretreatment CRP, GPS, and CAR.Conclusions: CRP, GPS, and CAR have independent prognostic values in patients with CRC. Furthermore, the survival nomograms based on CRP, GPS, and CAR can provide more valuable clinical significance.

Abstract Background The mitogen‐activated protein kinase (MAPK) pathway is highly associated with the progression and metastasis of various solid tumours. MAPK14, a core molecule of the MAPK pathway, plays vital roles in the colorectal cancer (CRC). Recent studies have shown that circRNAs can affect tumour progression by encoding peptides. However, little is known regarding the potential protein translated from circMAPK14 and whether it plays a role in the carcinogenesis of colorectal cancer. Methods The RNA level and translatable potential of circMAPK14 in CRC was verified using qRT‐PCR and public databases. RNase R digestion assay, qRT‐PCR, sanger sequencing and FISH assays were utilised to verify the circular characteristics and subcellular localisation of circMAPK14. The suppressive role of circMAPK14 on the progression and metastasis of CRC was verified in vivo and in vitro. LC/MS analysis combined with western blotting demonstrated the presence and relative expression of circMAPK14‐175aa. The underlying mechanism of circMAPK14‐175aa action to inhibit CRC was identified by co‐IP analysis. The binding of U2AF2 within the flanking introns of circMAPK14 was evaluated by RNA pull‐down assay and RIP assay. Ultimately, luciferase reporter gene assays and ChIP assays confirmed that FOXC1 suppressed transcription of U2AF2 by binding to the U2AF2 promoter in the –400 bp to –100 bp region. Results We identified that hsa_circ_0131663 (termed circMAPK14) showed significantly decreased expression level in cells and tissue samples of CRC, and was primarily localised in the cytoplasm. A series of function experiments demonstrated that circMAPK14 influenced CRC progression and metastasis by encoding a peptide of 175 amino acids (termed circMAPK14‐175aa). We also found that circMAPK14‐175aa reduced nuclear translocation of MAPK14 by competitively binding to MKK6, thus facilitating ubiquitin‐mediated degradation of FOXC1. Moreover, we described a positive feedback loop in CRC in which elevated FOXC1 expression was caused by reduced circMAPK14‐175aa expression. This, in turn, decreased circMAPK14 biogenesis by suppressing U2AF2 transcription. Conclusion In summary, we reported for the first time that circMAPK14 functioned as a tumour‐suppressor by encoding circMAPK14‐175aa, which blocked the progression and metastasis of colorectal cancer.

Aim: The role of plasma heat shock protein 90 alpha (HSP90α) in colorectal cancer patients remains unclear. This study aimed to evaluate the relationship between HSP90α and the occurrence and development of colorectal cancer through diagnosis and prognosis value.Methods: 635 colorectal cancer patients and 295 healthy controls were recruited. The HSP90α was measured by using the ELISA kit in all objects and the immune cells and common biomarkers as CEA, AFP, CA125, CA153 and CA199 were measured in all colorectal cancer patients. The relationship between plasma HSP90α with clinical features, common tumor markers and immune cells were also conducted. The survival analysis endpoint was progression-free survival (PFS).Results: The levels of plasma HSP90α were significantly higher in colorectal cancer patients compared to healthy controls [51.4 (ng/ml) vs. 43.7 (ng/ml), p < 0.001]. In additional, the levels of plasma HSP90α were associated with gender and disease progress as stage, lymphatic and distant metastasis. Furthermore, plasma HSP90α was closed correlation with CEA, CA125, CA199 and percentage of B cells. However, the initial expression level of plasma HSP90α failed to show a prognostic value for progression-free survival in colorectal cancer.Conclusion: The plasma Hsp90α was remarkable higher in colorectal cancer and correlated with common tumor biomarkers and immune cells. Plasma Hsp90α levels were associated with disease progress but a poor diagnosis performance and also failed to show a prognostic value in colorectal cancer.

Supercapacitors are an important part of the hybrid energy storage system for electric vehicles (EVs.) They not only protect the battery, but also improve the starting performance, acceleration performance, and regenerative braking performance of the EVs. Accurate modeling and state of charge (SOC) estimation of supercapacitors are essential for reliability, resilience, and safety in hybrid energy storage system operations. In this paper, a fractional order dynamic equivalent circuit model of the supercapacitor is proposed. Through the parameter identification and the experimental analysis, it is proved that the fractional equivalent circuit has better precision. Furthermore, the SOC estimation method of particle filter and Kalman filter is investigated, and a method of estimating supercapacitor SOC is proposed by combining the particle filter and the fractional Kalman filter. The validation results prove that the proposed method has better accuracy and real-time performance based on the fractional order.

Polymer matrix composites (PMCs) have been widely used in aero industry because of its low density and high strength-to-weight ratio. However, the application of PMCs is still limited by poor abrasion resistance, weak oxidation resistance and low operation temperature. In this study, Cu (Al)/NiCrAlY/YSZ triple layer coating system was deposited on glass fiber reinforced polyimide matrix composites (FPM) by means of High Velocity Oxygen Fuel (HVOF) for metallic coatings and Atmospheric Plasma Spraying (APS) for YSZ coating. The influences of different bond coats and different thickness of the top coat on the thermal shock resistance and thermal ablation resistance of the coating system was investigated. Compared with Al particle, Cu particle has a high density and correspondingly a high kinetic energy during spraying by HVOF, resulting in a high bonding strength between the Cu coating and FPM substrate. In the thermal shock test, the coating Cu/NiCrAlY/YSZ has a much longer lifetime than the coating Al/NiCrAlY/YSZ. After high-speed impact on the substrate, there is a great compressive stress at the interface, which makes a plastic deformation to the substrate, and the particles are closely embedded into the substrate to form a strong mechanical interlock. The coating system consisting of 50 μm Cu, 50 μm NiCrAlY, and 200 μm 8YSZ exhibited the best thermal shock resistance, thermal ablation resistance and bonding strength. The increase of the top coat thickness will lead to the increase of residual stress and the decrease of bonding strength. The failure mechanism of the coating is mainly attributed to the residual stress in the deposition process and the thermal stress caused by thermal expansion mismatch.

Myocardial ischemia is a high-risk disease among middle-aged and senior individuals. After thrombolytic therapy, heart tissue can potentially suffer further damage, which is called myocardial ischemia-reperfusion injury (MIRI). At present, the treatment methods and drugs for MIRI are scarce and cannot meet the current clinical needs. The mechanism of MIRI involves the interaction of multiple factors, and the current research hotspots mainly include oxidative stress, inflammation, calcium overload, energy metabolism disorders, pyroptosis, and ferroptosis. Traditional Chinese medicine (TCM) has multiple targets and few toxic side effects; clinical preparations containing Panax ginseng C. A. Mey., Panax notoginseng (Burk.) F. H. Chen, Aralia chinensis L., cardioprotection, and other Chinese herbal medicines have been used to treat patients with coronary heart disease, angina pectoris, and other cardiovascular diseases. Studies have shown that saponins are the main active substances in TCMs containing Panax ginseng C. A. Mey., Panax notoginseng (Burk.) F. H. Chen, Aralia chinensis L., and Radix astragali. In the present review, we sorted the saponin components with anti-MIRI effects and their regulatory mechanisms. Each saponin can play a cardioprotective role via multiple mechanisms, and the signaling pathways involved in different saponins are not the same. We found that more active saponins in Panax ginseng C. A. Mey. are mainly dammar-type structures and have a strong regulatory effect on energy metabolism. The highly active saponin components of Aralia chinensis L. are oleanolic acid structures, which have significant regulatory effects on calcium homeostasis. Therefore, saponins in Chinese herbal medicine provide a broad application prospect for the development of highly effective and low-toxicity anti-MIRI drugs.

Abstract Background Long noncoding RNAs (lncRNAs) have emerged as key regulators in multiple cancers, including colorectal cancer (CRC). However, the biological functions and molecular mechanisms underlying most lncRNAs in CRC remain largely unknown. Methods A novel lncRNA (TCONS_00012883) was identified using RNA sequencing. The level of TCONS_00012883 expression in CRC was analyzed by qRT‐PCR. The biological functions of TCONS_00012883 in CRC were investigated by a series of in vitro and in vivo experiments: CCK8, colony formation, EdU, flow cytometric assays, transwell assays, and mouse xenograft. The molecular mechanisms of TCONS_00012883 were demonstrated by RNA pulldown, mass spectrometry analysis, RIP, coimmunoprecipitation, RNA sequencing, chromatin immunoprecipitation, and rescue experiments. Results Elevated expression of TCONS_00012883 was confirmed in CRC and positively associated with a poor prognosis. Functionally, gain‐ and loss‐of‐function assays indicated that TCONS_00012883 promoted proliferation and metastasis of CRC cell lines in vitro and in vivo. Mechanistically, RNA pulldown and mass spectrometry analysis showed that DEAD‐box helicase 3 (DDX3) was the protein partner of TCONS_00012883. Furthermore, RNA sequencing assay revealed that matrix metallopeptidase 1 (MMP1) was the downstream of TCONS_00012883. Intriguingly, we found that transcription factor (YY1) could serve as a bridge between TCONS_00012883, DDX3, and MMP1. Conclusions TCONS_00012883 significantly promoted CRC progression via the DDX3/YY1/MMP1 axis, and thus, may act as a major role in diagnosis and therapy of CRC.

Hybrid energy storage system has been widely studied as an important technology for electric vehicles. Since the hybrid energy storage system is a nonlinear and complex system, the modeling of the system and the high-precision nonlinear control strategy are technical difficulties for research. The establishment of a high-precision mathematical model of the hybrid energy storage system is the basis for the study of high-quality nonlinear control algorithms. Fortunately, the theory of fractional calculus can help build accurate mathematical models of hybrid energy storage systems. In order to obtain the high-quality nonlinear control strategy of this complex system, this paper, respectively, carried out fractional-order modeling and analysis on the three basic equivalent working states of the hybrid energy storage system of electric vehicles. Among them, the fractional-order average state space model is carried out for the equivalent Buck and Boost mode. Also, the steady-state analysis of the equivalent Dual-Boost mode is carried out by combining the fractional-order calculus theory with the equivalent small parameter variable method. Finally, the effectiveness and precision of the fractional-order model are proved by simulation and experiment.

DNA damage response (DDR) is essential for maintaining genome stability and protecting cells from tumorigenesis. Ubiquitin and ubiquitin-like modifications play an important role in DDR, from signaling DNA damage to mediating DNA repair. In this report, we found that the E3 ligase ring finger protein 126 (RNF126) was recruited to UV laser micro-irradiation-induced stripes in a RNF8-dependent manner. RNF126 directly interacted with and ubiquitinated another E3 ligase, RNF168. Overexpression of wild type RNF126, but not catalytically-inactive mutant RNF126 (CC229/232AA), diminished ubiquitination of H2A histone family member X (H2AX), and subsequent bleomycin-induced focus formation of total ubiquitin FK2, TP53-binding protein 1 (53BP1), and receptor-associated protein 80 (RAP80). Interestingly, both RNF126 overexpression and RNF126 downregulation compromised homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs). Taken together, our findings demonstrate that RNF126 negatively regulates RNF168 function in DDR and its appropriate cellular expression levels are essential for HR-mediated DSB repair. Keywords: DNA repair, DNA damage response, Ubiquitination, RNF126, RNF8, RNF168