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Abstract Background Cisplatin (DDP) is one of the most effective anticancer drugs, commonly used to treat advanced ovarian cancer (OC). However, DDP has significant limitations of platinum-based drugs, including chemical resistance and high-dose toxic side effects. Traditional Chinese medicines (TCMs) often presented in the form of formula, in which the herb pair was the basic unit. Scutellaria barbata D.Don and Hedyotis diffusa Willd (SB-HD) are famous TCMs herb pair that have been shown to help treat multiple types of cancers. However, the synergistic effects and mechanism of combination of SB-HD and DDP to enhance DDP chemosensitivity in OC are still unknown. Results In vitro, we found that the optimal proportion of SB-HD to inhibit the proliferation of OC cells was 2:1, SB-HD and DDP were shown to synergistically reduce the viability of OC cells, inhibit the colony formation, promote cell cycle arrest and apoptosis, as well as inhibit cell migration and invasion. In vivo, combination treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice and reduced the toxic side effects of DDP. Mechanistically, SB-HD and DDP combination treatment significantly promoted oxidative stress response, decreased MMP, inhibited ATP production, decreased ROS levels and increased SOD activity, increased the expression of NRF2, HO-1, ATG5 and LC3, decreased the expression of p62 and FTH1 both in OC cells and tumor tissue of mice. Inhibitor 3-MA (Methyladenine, autophagy inhibitor) and Fer-1 (Ferrostatin-1, iron ion inhibitor) can effectively reverse the expression changes of the key target proteins, but not ZnPP (Zinc protoporphyrin, HO-1 inhibitor). Through bioinformatics analysis, it was found that the abnormal expression level of NRF2 and FTH1 mRNA has a high prognostic value, at the same time, the other four key proteins respectively or interacting with NRF2 and FTH1, also play important roles in the occurrence and development of OC. Conclusion Our findings uncover a synergistic effect of SB-HD and DDP against OC through modulating oxidative stress via NRF2-FTH1 autophagic degradation pathway, which may provide an important theoretical foundation for the use of SB-HD and a new strategy for enhancing DDP chemosensitivity as well as reducing toxic side effects.

Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as a critical suppressor through transcriptomic sequencing and metastasis correlation screening. In UM, hypoxia-induced VM and metastasis are markedly exacerbated by UBE2G2 knockdown and significantly alleviated by its overexpression. Mechanistically, UBE2G2 directly binds to galectin 3 binding protein (LGALS3BP) and forms a complex with the E3 ubiquitin ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue. Furthermore, UBE2G2 inhibits oncogenic phenotypes by inactivating intracellular PI3K/AKT signaling and reprogramming the tumor microenvironment. Therefore, targeting intercellular and intracellular molecular mechanisms of the hypoxia–UBE2G2–LGALS3BP axis may contribute to developing various therapeutic strategies for UM.

Abstract New proteasomes are produced to accommodate increases in cellular catabolic demand and prevent the accumulation of cytotoxic proteins. Formation of the proteasomal 20S core complex relies on the function of the five chaperones PAC1-4 and POMP. Here, to understand how these chaperones facilitate proteasome assembly, we tagged the endogenous chaperones using CRISPR/Cas gene editing and examined the chaperone-bound complexes by cryo-EM. We observe an early α-ring intermediate subcomplex that is stabilized by PAC1-4, which transitions to β-ring assembly upon dissociation of PAC3/PAC4 and rearrangement of the PAC1 N-terminal tail. Completion of the β-ring and dimerization of half-proteasomes repositions critical lysine K33 to trigger cleavage of the β pro-peptides, leading to the concerted dissociation of POMP and PAC1/PAC2 to yield mature 20S proteasomes. This study reveals structural insights into critical points along the assembly pathway of the human proteasome and provides a molecular blueprint for 20S biogenesis.

BackgroundPatients with bipolar disorder (BD) frequently exhibit cognitive impairments. However, the association between childhood trauma as a risk factor for BD and cognitive deficits remains ambiguous.ObjectiveTo investigate the relationship between childhood trauma and cognitive function among patients with BD.MethodsThe study included 90 patients with BD and 94 healthy controls (HC). Childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ), and cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The relationships between childhood trauma and cognitive function.ResultsIn BD group, childhood abuse and neglect were more prevalent than in HC group. Mood stabilizer use was positively associated with language abilities, while antipsychotic use negatively impacted attention. Emotional abuse predicted impaired immediate memory, with the number of episodes and valproate dosage negatively correlating with total RBANS scores, whereas education and mood stabilizer use showed positive correlations.ConclusionsThe incidence of childhood trauma was higher among BD than HC, and different types of childhood trauma had varying effects on different aspects of cognition. These studies will deepen the understanding of the complexity of BD and support the development of more effective treatment methods.

Objectives To assess the knowledge, attitude and practice (KAP) of patients with type A aortic dissection (AD) or their relatives regarding postoperative management.Design Cross-sectional study.Setting The participants were recruited from three hospitals between October 2022 and February 2023.Participants Patients diagnosed with type A AD or their relatives.Interventions No interventions were administered. A structured questionnaire was used to gather the demographic and KAP data from the participants.Primary and secondary outcome measures The outcome measures included the levels of KAP regarding postoperative management.Results A total of 483 participants were included. They exhibited poor knowledge (15.52±7.67, possible score: 0–32), positive attitude (31.10±5.86, possible score: 9–45) and poor practice (21.96±4.83, possible score: 8–40) towards postoperative management. The multivariable logistic analysis showed that knowledge scores (OR=1.09, 95% CI 1.05 to 1.12, p

The randomness, fluctuation and uncertainty of wind power brings great challenges to the dispatch and control of the power system. In order to raise the economy of hydro and wind power optimal dispatch, a stochastic optimal dispatching model considering the uncertainty of wind power in both time and power dimensions is proposed. The versatile distribution is used to describe the uncertainty of wind power in different power-time intervals, providing foundation for positive and negative reserves of hydro power. Moreover, to solve the multi-objective stochastic optimal dispatching model, the twin delayed deep deterministic policy gradient (TD3) algorithm is utilized, which can avoid falling into local optimum and has stronger search ability when dealing with high-dimensional multi-objective optimization problem. Simulations in a wind farm and hydro power station of western China show that the proposed model can accurately describe the uncertainty of wind power, and TD3 algorithm can find the global optimal solution more effectively than the traditional intelligent algorithms and other deep reinforcement learning algorithms.

Background Neutrophil extracellular traps (NETs) are produced by polymorphonuclear neutrophils (PMNs) stimulated by interleukin-17 (IL-17) and tumor necrosis factor α (TNF-α). However, the level and role of NETs in oral lichen planus (OLP) remain poorly understood. Objective This study aimed to investigate the expression of NETs in OLP and explore the correlation between NETs and the levels of IL-17 and TNF-α. Methods The expression and distribution of NET-related proteins in tissue samples from each group were assessed using hematoxylin-eosin (HE) staining and immunofluorescence (IF). Additionally, the expression of NET-related proteins in peripheral blood samples from each group was evaluated using cell IF technique and fluorescence spectrophotometry. The relative formation level of NETs in each group was determined by fluorescence spectrophotometry via plasma co-culture. Furthermore, the levels of inflammatory cytokines IL-17 and TNF-α in plasma and culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA). Results NET-related proteins were located in the subepithelial and lamina propria layers of OLP lesions. OLP had significantly higher expression of NET-related proteins in lesion tissues and peripheral blood compared to the healthy control (HC) group (p < 0.05). The rate of NETs formation in the erosive-stage OLP (EOLP) group was significantly higher than that in the HC group (p < 0.05), in contrast, no significant increase was observed in the non-erosive OLP (NEOLP) group (p > 0.05). Furthermore, the levels of IL-17 and TNF-α in the EOLP group were significantly elevated compared to those in the NEOLP group and HC group (p < 0.05), while the levels in the NEOLP group did not significantly differ from those in the HC group (p > 0.05). The rate of NETs formation showed a positive correlation with the levels of IL-17 and TNF-α in plasma. Conclusion The expression of NET-related proteins was upregulated in OLP lesion tissues and peripheral blood. Elevated levels of IL-17 and TNF-α in peripheral blood plasma positively correlated with the rate of NETs formation, suggesting that IL-17 and TNF-α mediate the formation of NETs in OLP patients, and may thereby contribute to the development of OLP.

Abstract The performance of superconducting quantum circuits for quantum computing has advanced tremendously in recent decades; however, a comprehensive understanding of relaxation mechanisms does not yet exist. In this work, we utilize a multimode approach to characterizing energy losses in superconducting quantum circuits, with the goals of predicting device performance and improving coherence through materials, process, and circuit design optimization. Using this approach, we measure significant reductions in surface and bulk dielectric losses by employing a tantalum-based materials platform and annealed sapphire substrates. With this knowledge we predict the relaxation times of aluminum- and tantalum-based transmon qubits, and find that they are consistent with experimental results. We additionally optimize device geometry to maximize coherence within a coaxial tunnel architecture, and realize on-chip quantum memories with single-photon Ramsey times of 2.0 − 2.7 ms, limited by their energy relaxation times of 1.0 − 1.4 ms. These results demonstrate an advancement towards a more modular and compact coaxial circuit architecture for bosonic qubits with reproducibly high coherence.

Abstract In two-dimensional chiral metal-halide perovskites, chiral organic spacers endow structural and optical chirality to the metal-halide sublattice, enabling exquisite control of light, charge, and electron spin. The chiroptical properties of metal-halide perovskites have been measured by transmissive circular dichroism spectroscopy, which necessitates thin-film samples. Here, by developing a reflection-based approach, we characterize the intrinsic, circular polarization-dependent complex refractive index for a prototypical two-dimensional chiral lead-bromide perovskite and report large circular dichroism for single crystals. Comparison with ab initio theory reveals the large circular dichroism arises from the inorganic sublattice rather than the chiral ligand and is an excitonic phenomenon driven by electron-hole exchange interactions, which breaks the degeneracy of transitions between Rashba-Dresselhaus-split bands, resulting in a Cotton effect. Our study suggests that previous data for spin-coated films largely underestimate the optical chirality and provides quantitative insights into the intrinsic optical properties of chiral perovskites for chiroptical and spintronic applications.

Background: Prolonged circulatory arrest time is an independent risk factor for postoperative adverse events of type A aortic dissection (TAAD) surgery. Further reduction of the circulatory arrest time is essential to improve surgical outcomes. This study aimed to evaluate the safety and effectiveness of the novel Sutureless Integrated Stented (SIS) graft prosthesis in an animal experiment. Materials and methods: Straight type of the SIS graft prosthesis was implanted into the descending aorta of 10 adult male sheep, and the use of the device was scored on a scale of 1–10. Aortic digital subtraction angiography (DSA) was performed at 4, 14, and 26 weeks to investigate the prostheses. After 26 weeks, the animals were sacrificed for histological analysis. Results: The immediate success rate of the surgery was 100 %, and the overall mean score of the use of the device was 9.65 ± 0.99. Three animals died from non-device-related causes during follow-up. Aortic DSA showed filling defects in 5 animals. Histological analysis revealed that all prostheses were intact. Except for 2 early deaths, the other 8 prostheses were endothelialized with mild inflammation, foreign body reactions, and intimal fibrosis. The mean cross-sectional area of the sutureless region was reduced by 26.4 % (range, 1.3–39.1 %). Conclusions: The safety and effectiveness of the novel SIS graft prosthesis were acceptable, and the delivery system exhibited a promising performance. Using the SIS graft prosthesis in TAAD surgery was expected to simplify the procedures and shorten the circulatory arrest time. Further large-scale clinical trials are required to verify these findings.

Objective: To evaluate the efficacy of the fruits of the medicinal plant Forsythia suspensa (Thunb.) Vahl (FS), in treating inflammation-associated diseases through a meta-analysis of animal models, and also probe deeply into the signaling pathways underlying the progression of inflammation.Materials and methods: All data analyses were performed using Review Manager 5.3 and the results are presented as flow diagrams, risk-of-bias summaries, forest plots, and funnel plots. Summary estimates were calculated using a random- or fixed-effect model, depending on the value of I2.Results: Of the 710 records identified in the initial search, 11 were selected for the final meta-analysis. Each study extracted data from the model and treatment groups for analysis, and the results showed that FS alleviated the inflammatory cytokine levels in serum; oxidant indicator: reactive oxygen species; enzymes of liver function; endotoxin and regulatory cells in blood; and improved the antioxidant enzyme superoxide dismutase.Conclusion: FS effectively reversed the change in acute or chronic inflammation indicators in animal models, and the regulation of multiple channel proteins in inflammatory signaling pathways suggests that FS is a good potential drug for inflammatory disease drug therapy.

Abstract Osteoarthritis (OA) is a complicated disorder that is the most prevalent chronic degenerative joint disease nowadays. Pudilan Tablets (PDL) is a prominent traditional Chinese medicine formula used in clinical settings to treat chronic inflammatory illnesses. However, there is currently minimal fundamental research on PDL in the therapy of joint diseases. As a result, this study looked at the anti-inflammatory and anti-OA properties of PDL in vitro and in vivo, as well as the mechanism of PDL in the treatment of OA. We investigated the anti-OA properties of PDL in OA mice that were generated by monosodium iodoacetate (MIA). All animals were administered PDL (2 g/kg or 4 g/kg) or the positive control drug, indomethacin (150 mg/kg), once daily for a total of 28 days starting on the day of MIA injection. The CCK-8 assay was used to test the vitality of PDL-treated RAW264.7 cells in vitro. RAW264.7 cells that had been activated with lipopolysaccharide (LPS) were used to assess the anti-inflammatory properties of PDL. In the MIA-induced OA model mice, PDL reduced pain, decreased OA-induced cartilage damages and degradation, decreased production of pro-inflammatory cytokines in serum, and suppressed IL-1β, IL-6, and TNF-α mRNA expression levels in tibiofemoral joint. In RAW264.7 cells, PDL treatment prevented LPS-induced activation of the ERK/Akt signaling pathway and significantly decreased the levels of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α. In conclusion, these results suggest that PDL is involved in combating the development and progression of OA, exerts a powerful anti-inflammatory effect on the knee joint, and may be a promising candidate for the treatment of OA.

Rice (Oryza sativa L.), a crucial food crop that sustains over half the world’s population, is often hindered by salt stress during various growth stages, ultimately causing a decrease in yield. However, the specific mechanism of rice roots’ response to salt stress remains largely unknown. In this study, transcriptomics and lipidomics were used to analyze the changes in the lipid metabolism and gene expression profiles of rice roots in response to salt stress. The results showed that salt stress significantly inhibited rice roots’ growth and increased the roots’ MDA content. Furthermore, 1286 differentially expressed genes including 526 upregulated and 760 downregulated, were identified as responding to salt stress in rice roots. The lipidomic analysis revealed that the composition and unsaturation of membrane lipids were significantly altered. In total, 249 lipid molecules were differentially accumulated in rice roots as a response to salt stress. And most of the major phospholipids, such as phosphatidic acid (PA), phosphatidylcholine (PC), and phosphatidylserine (PS), as well as major sphingolipids including ceramide (Cer), phytoceramide (CerP), monohexose ceramide (Hex1Cer), and sphingosine (SPH), were significantly increased, while the triglyceride (TG) molecules decreased. These results suggested that rice roots mitigate salt stress by altering the fluidity and integrity of cell membranes. This study enhances our comprehension of salt stress, offering valuable insights into changes in the lipids and adaptive lipid remodeling in rice’s response to salt stress.

Abstract Over the past decades, superconducting qubits have emerged as one of the leading hardware platforms for realizing a quantum processor. Consequently, researchers have made significant effort to understand the loss channels that limit the coherence times of superconducting qubits. A major source of loss has been attributed to two level systems that are present at the material interfaces. It is recently shown that replacing the metal in the capacitor of a transmon with tantalum yields record relaxation and coherence times for superconducting qubits, motivating a detailed study of the tantalum surface. In this work, the chemical profile of the surface of tantalum films grown on c‐plane sapphire using variable energy X‐ray photoelectron spectroscopy (VEXPS) is studied. The different oxidation states of tantalum that are present in the native oxide resulting from exposure to air are identified, and their distribution through the depth of the film is measured. Furthermore, it is shown how the volume and depth distribution of these tantalum oxidation states can be altered by various chemical treatments. Correlating these measurements with detailed measurements of quantum devices may elucidate the underlying microscopic sources of loss.

Ti6Al4V is the most widely used materials in aerospace, medical, nuclear power and other fields. However, due to its unique properties such as low thermal conductivity, titanium alloy poses challenges in machining processes. Electrical discharge milling (EDM) is a machining method that utilizes the electrical corrosion phenomenon of pulsed spark discharge between two electrodes to remove materials, which is highly suitable for the machining of Ti6Al4V. This paper investigates a mixed powder EDM approach for titanium alloy using a graphene solution medium known for its green and sustainable characteristics. Compared to conventional deionized water medium processing which without powder particles, the material removal rate can be increased by 50%, the surface hardness after processing was 2.5 times higher than that of the substrate, the electrode wear rate could be reduced by 40%, the surface roughness values were reduced by more than 20%. Besides that, the micro-cracks and micro-pores on the workpiece surface can be significantly reduced. Subsequently, single factor experiments and orthogonal experiments were conducted using material removal rate, electrode wear rate, and surface roughness as process indicators. The influence of processing parameters on process indicators was investigated based on optimal selection method and analysis of variance (ANOVA). Finally, the optimized parameters in graphene solution mixed powder EDM for Ti6Al4V were obtained. When using the process combination A3B3C1D2, the maximum MRR can be obtained.

Background: Computational fluid dynamics (CFD) is a new medical method combining medicine and science. The aim of this study is to summarize and analyze the application of CFD in adult aortic diseases. Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search in the PubMed, Cochrane Library and Chinese databases identified 47 highly relevant articles. Studies were included if they assessed biomechanical markers and their potential association with progression or rupture of aortic aneurysms or dissections. Results: There are no randomized controlled trials to examine the direct relationship between all biomechanical parameters and aortic disease progression or rupture. Wall stress and peak wall rupture risk can predict the risk of aortic aneurysm rupture using biomechanics, which is more accurate than the prediction based on “diameter” alone. Areas with lower time averaged wall shear stress (TAWSS) and higher oscillatory shear index (OSI) are at risk for further aortic expansion or dissection. Higher relative residence time (RRT) area can predict platelet activation and thrombosis. In addition, pressure, flow field and other indicators can also roughly predict the risk of aortic disease progression. Conclusions: Contemporary evidence suggests that CFD can provide additional hemodynamic parameters, which have the potential to predict the progression of aortic lesions, the effect of surgical intervention, and prognosis.

Abstract A vital pursuit in solar energy research is to achieve high efficiency and long‐term stability in energy conversion devices. Coating or sandwiching an ultrathin layer of TiO2 onto active solar components has been demonstrated to be a remarkably effective and facile strategy to improve their stability. The TiO2 film acts as a protection layer and enhances solar energy conversion efficiency by passivating surface recombination sites or facilitating electron transport. To date, numerous efforts have been devoted to applying ultrathin TiO2 layers in various kinds of solar energy conversion devices. In this study, we review deposition techniques, characterization methods of the resulting ultrathin TiO2 layer, as well as its applications in dye‐sensitized solar cells, organic–inorganic hybrid solar cells, and photoelectrochemical cells.

The impact of chloride (Cl⁻) in heat-activated peroxydisulfate (PDS) and peroxymonosulfate (PMS) processes for benzotriazole (BTA) degradation was investigated. Results showed that 0.42 mM BTA could be degraded by PDS and PMS under 70 °C in presence and absence of Cl⁻. The PMS-mediated BTA degradation rate increased with increasing Cl⁻ concentration up to 1000 mg/L, while a further increase of Cl⁻ concentration decreased the BTA degradation rate. In contrast, Cl⁻ inhibited PDS-mediated BTA degradation at concentrations tested between 100 and 10,000 mg/L. Radical scavenging experiments indicated that BTA degradation was mainly driven by hydroxyl and sulfate radicals in PDS and PMS systems without Cl⁻. However, reactive chlorine species (RCS) significantly boosted the PMS system for BTA degradation in presence of Cl⁻. Variation in pH substantially influenced the PMS system, but not the PDS system, whether in presence and absence of Cl⁻. By LC-MS/MS analysis, forty-two transformation products (TPs) were identified resulting from BTA degradation. Based on the TPs, polymerization, hydroxylation, benzene ring-opening, and carboxylic acid formation were hypothesized to be the main degradation mechanisms in absence of Cl⁻, whereas chlorination, triazole ring-opening, and nitration were the additional degradation steps in presence of Cl⁻. These findings help understand the influence of Cl⁻ on BTA removal rate and degradation pathway in saline wastewater. Moreover, more chlorinated TPs were found in PMS/Cl⁻ system than in PDS/Cl⁻ system, which was also reflected in absorbable organic halides (AOX) and end-product toxicity analyses. The PMS/Cl⁻ process also produced other undesirable by-products, such as chlorates which were not detected in the PDS/Cl⁻ process. This shows that PDS and PMS-based advanced oxidation processes can notably differ in terms of toxic by-product formation. Thus, they need to be critically evaluated before applying for organic pollutant degradation under saline conditions.

Summary: Patients with myotonic dystrophy type I (DM1) demonstrate visuospatial dysfunction and impaired performance in tasks requiring recognition or memory of figures and objects. In DM1, CUG expansion RNAs inactivate the muscleblind-like (MBNL) proteins. We show that constitutive Mbnl2 inactivation in Mbnl2ΔE2/ΔE2 mice selectively impairs object recognition memory in the novel object recognition test. When exploring the context of a novel arena in which the objects are later encountered, the Mbnl2ΔE2/ΔE2 dorsal hippocampus responds with a lack of enrichment for learning and memory-related pathways, mounting instead transcriptome alterations predicted to impair growth and neuron viability. In Mbnl2ΔE2/ΔE2 mice, saturation effects may prevent deployment of a functionally relevant transcriptome response during novel context exploration. Post-novel context exploration alterations in genes implicated in tauopathy and dementia are observed in the Mbnl2ΔE2/ΔE2 dorsal hippocampus. Thus, MBNL2 inactivation in patients with DM1 may alter novel context processing in the dorsal hippocampus and impair object recognition memory.

Abstract Oral lichen planus (OLP) is a localized autoimmune disease of the oral mucosa, with an incidence of up to 2%. Although corticosteroids are the first-line treatment, they cause several adverse effects. Quercetin, a naturally occurring compound, has fewer side-effects and provides long-term benefits. Besides, it has powerful anti‑inflammatory activities. Here, we combined network pharmacology with experimental verification to predict and verify the key targets of quercetin against OLP. First, 66 quercetin-OLP common targets were analyzed from various databases. The protein–protein interaction (PPI) network was constructed. Topology analysis and MCODE cluster analysis of common targets were conducted to identify 12 key targets including TP53, IL-6 and IFN-γ and their connections. Gene functions and key signaling pathways, including reactive oxygen species metabolism, IL-17 pathway and AGE-RAGE pathway, were enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, in vitro experiments showed that quercetin interfered with Th1/Th2 balance by acting on IL-6 and IFN-γ to modulate the immune system in treating OLP. Quercetin considerably affected the apoptosis and migration of T lymphocytes in OLP patients. Our study reveals the potential therapeutic targets and signaling pathways of quercetin associated with OLP, and establishes the groundwork for future clinical applications.

Head and neck squamous cell carcinoma (HNSCC) has become a prevalent malignancy, and its incidence and mortality rate are increasing worldwide. Accumulating evidence has indicated that lipid metabolism-related genes (LMRGs) are involved in the occurrence and development of HNSCC. This study investigated the latent association of lipid metabolism with HNSCC and established a prognostic signature based on LMRGs. A prognostic risk model composed of eight differentially expressed LMRGs (PHYH, CYP4F8, INMT, ELOVL6, PLPP3, BCHE, TPTE, and STAR) was constructed through The Cancer Genome Atlas database. Then, ELOVL6 expression was validated in oral squamous cell carcinoma (OSCC), which is a common type of HNSCC, by immunohistochemical analysis. ELOVL6 expression in the OSCC II/III group was significantly higher than that in the other three groups (normal, dysplasia, and OSCC I), and OSCC patients with high ELOVL6 expression had poorer survival than those with low ELOVL6 expression. In summary, the LMRG-based prognostic feature had prognostic predictive capacity. ELOVL6 may be a potential prognostic factor for HNSCC patients.

In order to prevent pullorum disease and fowl typhoid in breeders, the use of oregano essential oil (OEO) was tested for the prevention and treatment of infections of multidrug-resistant Salmonella pullorum (SP) and Salmonella gallinarum (SG) in commercial Yellow-chicken breeders. In the challenge-protection experiment, commercial Hongguang-Black 1-day-old breeder chicks were randomly divided into four groups, including A (challenged, preventive dose), B (challenged, treatment dose), C (challenged, untreated), and D (unchallenged, untreated). Group A was supplemented with 200 μL/L OEO in the drinking water during the whole trial (1-35 days of age) and group B was supplemented with 400 μL/L OEO during 8–12 days of age, while groups C and D were kept as untreated controls. At 7 days of age, birds of groups A, B, and C were divided into two subgroups with equal number of birds (A1-A2, B1-B2, and C1-C2), and then subgroups A1, B1, and C1 were challenged with SP, while subgroups A2, B2, and C2 were challenged with SG. Clinical symptoms and death were observed and recorded daily. Every week during the experiment, serum antibodies against SP and SG of all the groups were detected by the plate agglutinate test (PAT). At the age of 35 days, all birds were weighed and necropsied, lesions were recorded and the challenging pathogens were isolated. The results showed that the positive rates of SP and SG isolation in groups A1, A2 and B1, B2 were significantly lower (P < 0.05) than those of groups C1 and C2, respectively, while groups A1 and A2 were slightly lower (P > 0.05) than those of groups B1 and B2. The average body weight (BW) of groups A1 and A2 were significantly higher (P < 0.05) than those of groups B1, B2 and C1, C2, respectively, but there was no significant difference (P > 0.05) with that of group D. The r-value between PAT positive and the recovery rates of Salmonella was 0.99, which means they are highly positively correlated. The results of this study demonstrated that the prevention dose (200μL/L) and the treatment dose (400 μL/L) of OEO supplemented in the drinking water could all effectively decrease infections of SP and SG and that the effect of the prevention was greater than that of the treatment and finally that the prevention could also significantly reduce the BW decline of birds challenged with SP and SG.

Climate warming are supposed to have irreversible effects on the biodiversity and ecosystem functions of grassland. Alpine meadow is the predominant ecosystem in Qinghai-Tibet Plateau, which has attracted much attention because of its sensitivity to global changes. However, there is still no unified understanding of the impact of warming on the relationship between diversity and productivity of alpine meadows. In this study, we conducted multi-gradient warming, used fiberglass open-top chambers (OTCs) to raise the temperature, based on the investigation of community structure and productivity, we evaluated the effect of field simulated warming on the relationship of species diversity-primary productivity. Our result showed that gradient warming reduced species richness, diversity and dominance, inhibited the accumulation of above-ground biomass (AGB) and below-ground biomass (BGB), which was more significant under higher warming (P

Sta Maria et al. use 2D MRI to study brains from mice deficient in Mbnl1 and/or Mbnl2 as these Muscleblind-like proteins are thought to play a role in Myotonic Dystrophy Type I (DM1). They show brain region-specific reductions in white and gray matter that could help to explain the variability in the brain structural alterations reported in DM1.

Coach emergency escape research is an effective measure to reduce casualties under serious vehicle fire accidents. A novel experiment method employing a wireless transducer was implemented and the head rotation speed, rotation moment and rotation duration were collected as the input variables for the classification and regression tree (CART) model. Based on this model, the classification result explicitly pointed out that the exit searching efficiency was evolving. By ignoring the last three unimportant factors from the Analytic Hierarchy Process (AHP), the ultimate Dynamic Bayesian Network (DBN) was built with the temporal part of the CART output and the time-independent part of the vehicle characteristics. Simulation showed that the most efficient exit searching period is the middle escape stage, which is 10 seconds after the emergency signal is triggered, and the escape probability clearly increases with the efficient exit searching. Furthermore, receiving emergency escape training contributes to a significant escape probability improvement of more than 10%. Compared with different failure modes, the emergency hammer layout and door reliability have a more significant influence on the escape probability improvement than aisle condition. Based on the simulation results, the escape probability will significantly drop below 0.55 if the emergency hammers, door, and aisle are all in a failure state.

Cluster of differentiation 47 (CD47)/signal regulatory protein alpha (SIRPα) is a negative innate immune checkpoint signaling pathway that restrains immunosurveillance and immune clearance, and thus has aroused wide interest in cancer immunotherapy. Blockade of the CD47/SIRPα signaling pathway shows remarkable antitumor effects in clinical trials. Currently, all inhibitors targeting CD47/SIRPα in clinical trials are biomacromolecules. The poor permeability and undesirable oral bioavailability of biomacromolecules have caused researchers to develop small-molecule CD47/SIRPα pathway inhibitors. This review will summarize the recent advances in CD47/SIRPα interactions, including crystal structures, peptides and small molecule inhibitors. In particular, we have employed computer-aided drug discovery (CADD) approaches to analyze all the published crystal structures and docking results of small molecule inhibitors of CD47/SIRPα, providing insight into the key interaction information to facilitate future development of small molecule CD47/SIRPα inhibitors.

Since the facts in the knowledge graph (KG) cannot be updated automatically over time, some facts have temporal conflicts. To discover and eliminate the temporal conflicts in the KG, this paper proposes a novel temporal conflict resolution method based on temporal KG embedding (named TeCre). Firstly, the predicate relation and timestamp information of time series are incorporated into the entity–relation embedding representation by leveraging the temporal KG embedding (KGE) method. Then, taking into account the chronological sequence of the evolution of the entity–relation representation over time, TeCre constrains the temporal relation in the KG according to the principles of time disjoint, time precedence, and time mutually exclusive constraints. Besides that, TeCre further considers the sequence vectorization of predicate relation to discover the temporal conflict facts in the KG. Finally, to eliminate the temporal conflict facts, TeCre deletes the tail entities of the temporal conflict facts, and employs the link prediction method to complete the missing tail entities according to the output of the score function based on the entity–relation embedding. Experimental results on four public datasets show that TeCre is significantly better than the state-of-the-art temporal KG conflict resolution model. The mean reciprocal ranking (MRR) and Hits@10 of TeCre are at least 5.46% and 3.2% higher than the baseline methods, respectively.

Grassland resources occupy an important place in the national economy. However, grasslands in alpine regions of China are severely degraded, and the effects of land-use types on species composition, soil nutrients, and ecosystem multifunctionality of degraded alpine grasslands are less certain. To ascertain the effects of main land-use types (no-tillage reseeding and fertilization) on species diversity and ecosystem multifunctionality in alpine grasslands, we investigated the changes in these factors by subjecting specified areas. Using a standardized field survey, we measured the cover, richness, and evenness of plants. At each site, we measured microbial diversity and twelve soil variables critical for maintaining ecosystem multifunctionality in alpine grasslands. The results showed that: (1) the Margalef, Shannon–Wiener, and Simpson indices of plant community, and fungal diversity indices increased significantly in no-tillage reseeding and fertilization; (2) at the phyla level, the relative abundances of Basidiomycota, Olpidiomycota, and Proteobacteria increased significantly in no-tillage reseeding and fertilization, as well as, at the genus level, those of Coniochaeta, Solirubrobacter, Pseudonocardia, and Microvirga; (3) the soil physicochemical properties (except the C:N of soil) increased significantly in no-tillage reseeding and fertilization; (4) correlation analysis showed that species diversity was mainly correlated with soil nutrients in control check, while it was mainly correlated with soil physical properties in no-tillage reseeding and fertilization; (5) linear regression analysis showed significant positive relationships between Margalef, Shannon–Wiener, and Simpson indices of plant community and ecosystem multifunctionality. In addition, ecosystem multifunctionality was positively related to Pielou, Shannon–Wiener, and Simpson indices of the fungal community and it was positively related to Pielou and Shannon–Wiener indices of bacterial community. These observations indicated that no-tillage reseeding and fertilization of degraded alpine grasslands had the potential to improve ecosystem functions in many ways.

China has achieved universal social health insurance coverage, but it is unclear whether this has alleviated the economic burden of disease for individuals. This was investigated in the present study by analyzing National Health Service Survey (2008–2018) data from Jiangsu province. Ordinary least squares and binary multivariate logistic regression of pooled cross-sectional data were carried out to evaluate the effect of universal health insurance coverage and other socioeconomic factors on the economic burden of disease. Total health expenses (THE) first increased and then decreased during the survey period while out-of-pocket health expenses (OOP) decreased except for urban residents, for whom OOP increased after 2013. Household catastrophic health expenditure (HCHE) was stable between 2008 and 2013 but increased after 2013. Social health insurance had a significant positive effect on the annual THE and OOP and a negative effect on HCHE, however, universal health insurance coverage could alleviated THE and the economic burden of disease on individuals (OOP) while it was insufficient to protect against the economic risk of diseases (HCHE), with greater benefits for urban as compared to rural residents. Other socioeconomic factors including age, marital status, education, income, and health status also influenced the economic burden of disease.

Objective:This meta-analysis and systematic review investigated whether partial thrombosed false lumen was a predictor for adverse events in uncomplicated Type B aortic dissection (TBAD).Methods:We performed the current systematic review of the medical literature according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The Newcastle-Ottawa Scale was used to evaluate the quality of individual studies. Search terms based on the MEDLINE database included “type B aortic dissection,” “false lumen” and “thrombosis.” The primary outcomes included mortality, intervention, and aortic growth.Results:Six studies were included in this systematic review, with a total number of 692 patients, including 197 patency (28.5%), 214 partial thrombosis (30.9%), and 281 complete thrombosis (40.6%). Due to the insufficient data for quantitative analysis, we only conducted a scoping review for mortality and intervention. For aortic growth, we conducted a meta-analysis based on Standardized Mean Difference (SMD). The SMD of PT vs. P by random effect model was −0.05 (random effect model) [95% confidence interval (CI), −0.39 to 0.29]. The 95% CI crossed with the null line of 0, indicating no significant difference. The SMD was 0.37 (fixed effects model) (95% CI, 0.03–0.71) and 0.70 (fixed effects model) (95% CI, 0.37–1.04) for PT vs. CT, and P vs. CT, respectively.Conclusions:Current researches on partial thrombosis of TBAD are inconsistent. Partial thrombosis is not associated with a faster aortic growth rate. Until more solid evidence is available, we do not recommend partial thrombosis as a surgical indication or high-risk profile for TBAD.Systematic Review Registration: Unique Identifier: CRD42019121912.

Multi-task learning (MTL) is a learning paradigm which can improve generalization performance by transferring knowledge among multiple tasks. Traditional collaborative filtering recommendation methods suffer from cold start, sparsity and scalability problems. The latest research has shown that applying side information of knowledge graph can not only solve the problems above, but also improve the accuracy of recommendation. However, existing multi-task methods for knowledge graph enhanced recommendation expose obvious issues of disclosing the private information of training samples. In order to solve these problems, we put forward a privacy-preserving multi-task framework for knowledge graph enhanced recommendation. In specific, Laplacian noise is added into the recommendation module to guarantee the privacy of sensitive data and knowledge graph is utilized to improve the accuracy of recommendation. Extensive experimental results on three datasets demonstrate that the proposed method can not only preserve the privacy of sensitive training data, but also have little effect on the prediction accuracy of the model.

ABSTRACT: A selected yeast fraction (SYF) was tested for the purpose of preventing pullorum disease and fowl typhoid in breeder chickens. In a challenge-protection experiment, commercial Three-Yellow breeder chicks were initially divided into groups A, B (challenged, treated), C (challenged, untreated), and D (unchallenged, untreated). The group A diet was supplemented with SYF and group B was supplemented with Acidipure via drinking water. At 7 D, birds of groups A, B, and C were divided into 2 equal subgroups (A1-A2, B1-B2, and C1-C2). Subgroups A1, B1, and C1 were challenged with Salmonella pullorum (SP), while subgroups A2, B2, and C2 were challenged with Salmonella gallinarum (SG). Clinical signs and mortality were recorded daily. At intervals, antibodies against SP and SG were detected by a plate agglutinate test (PAT). At 42 D, all birds were weighed and necropsied, lesions were recorded and challenge pathogens were isolated. Results showed that SP and SG isolation positive rates of groups A1-A2 were significantly lower (P < 0.05) than those of B1-B2 and C1-C2, respectively. The average body weight (BW) of groups A1-A2 was significantly higher (P < 0.05) than that of B1-B2 and C1-C2, respectively. In the field trial, chicks were randomly divided into 3 groups. Group 1 birds were fed a diet supplemented with SYF, group 2 diet was supplemented with Acidipure via drinking water, and group 3 was fed the same but un-supplemented diet as the control group. Antibodies against SP and SG were detected by PAT at 120 D. The antibodies positive rate of group 1 was significantly lower (P < 0.05) than those of groups 2 and 3, while no significant difference (P > 0.05) was found between groups 2 and 3. The results demonstrated that SYF supplementation could significantly decrease SP and SG infection rates, improve the BW of birds challenged with SP and SG, and was more effective than Acidipure via drinking water.

Long non-coding RNAs and microRNAs (miRNAs) have been reported to participate in the progression of non-small-cell lung cancer (NSCLC). Long intergenic non-protein-coding RNA 472 (LINC00472), miR-149-3p, and miR-4270 were found to be involved in tumor activities, suggesting potential roles in NSCLC. Thus, this study aimed to examine the ability of LINC00472 to influence the progression of NSCLC with the involvement of miR-149-3p and miR-4270. Initially, differentially expressed long non-coding RNAs (lncRNAs), downstream regulatory miRNAs, and genes related to NSCLC were identified. Next, the interaction among LINC00472, miR-149-3p and miR-4270, and KLLN and the p53-signaling pathway was determined. The effect of LINC00472 on the expression of E-cadherin, N-cadherin, and Vimentin was examined through gain-of-function and loss-of-function experiments. Lastly, the effects of LINC00472 on NSCLC tumor growth were assessed in vivo. LINC00472 and KLLN were found to exhibit low levels, while miR-149-3p and miR-4270 were highly expressed in NSCLC. In addition, the overexpression of LINC00472 was observed to upregulate KLLN and activate the p53-signaling pathway, which ultimately inhibited the invasion, migration, and EMT of NSCLC cells via miR-149-3p and miR-4270, corresponding to decreased N-cadherin and Vimentin and increased E-cadherin. The overexpression of LINC00472 exerted an inhibitory effect on tumor growth in vivo. Taken together, the key evidence suggests that the overexpression of LINC00472 can downregulate miR-149-3p and miR-4270 to upregulate KLLN and activate the p53-signaling pathway, thus inhibiting the development of NSCLC. This study highlights the potential of LINC00472 as a promising therapeutic target for NSCLC treatment. Keywords: long intergenic non-protein-coding RNA 472, microRNA-149-3p, microRNA-4270, KLLN, p53-signaling pathway, non-small-cell lung cancer, invasion, migration, epithelial-mesenchymal transition

Salmonella is capable of harming human and animal health, and its multidrug resistance (MDR) has always been a public health problem. In addition, antibiotic-free or antibiotic-reduced policies have been implemented in poultry production. Therefore, the search for antibiotic alternatives is more urgent than ever before. The aim of this study was to assess the antibacterial activity of star anise-cinnamon essential oil (SCEO) in vitro and its prophylactic effect against the infections of Salmonella pullorum, Salmonella give, and Salmonella kentucky in vivo. The results demonstrated that SCEO is effective against Salmonella pullorum, Salmonella give, and Salmonella kentucky in vitro. Supplementation with SCEO could significantly decrease the infections of Salmonella pullorum and Salmonella give, whereas it could slightly but not significantly decrease the infection of Salmonella kentucky, while also significantly alleviating the body weight (BW) loss caused by the infections of Salmonella pullorum, Salmonella give, and Salmonella kentucky in Yellow chickens. The SCEO had the best prophylactic effect against the infection of Salmonella give in Yellow chickens, followed by the infection of Salmonella pullorum and the infection of Salmonella kentucky. The SCEO, used as an antibiotic alternative, could be an effective prevention strategy against the infections of Salmonella pullorum, Salmonella give, and Salmonella kentucky in Yellow chickens.

Skeletal muscle injury is a common disease accompanied by inflammation, and its treatment still faces many challenges. The local inflammatory microenvironment can be modulated by a novel ROS-scavenging hydrogel (Gel) we constructed. And MSCs could differentiate into myoblasts and contribute to muscle tissue homeostasis and regeneration. Here, Gel loaded with mesenchymal stem cells (MSCs) (Gel@MSCs) was developed for repairing the injured skeletal muscle. Results showed that the Gel improved the survivability and enhanced the proliferation of MSCs (≈two-fold), and the Gel@MSCs inhibited the local inflammatory responses as it promoted polarization of M2 macrophages (increased from 5% to 17%), the mediator of the production of anti-inflammatory factors. Western blotting and qPCR revealed the Gel promoted the expression of proteins (≈two-fold) and genes (≈two to six-fold) related to myogenesis in MSCs. Histological assessment indicated that the Gel or MSCs promoted regeneration of skeletal muscle, and the efficacy was more significant at Gel@MSCs than MSCs alone. Finally, behavioral experiments confirmed that Gel@MSCs improved the motor function of injured mice. In short, the Gel@MSCs system we constructed presented a positive effect on reducing skeletal muscle damage and promoted skeletal muscle regeneration, which might be a novel treatment for such injuries.

Phillyrin is an effective lignan glycoside extracted from a traditional Chinese medicine Forsythia suspensa (Thunb.) Vahl (Oleaceae). It mainly exists in the roots, stems, leaves and fruits of the plant, with the highest content in the leaves. In terms of its medicinal application, there are a large number of experimental data proving its pharmacological effects in vitro and in animal models, such as anti-inflammatory, anti-obesity, anti-tumor, etc. Furthermore, pharmacokinetic experiments have also shown phillyrin’s high effectiveness and low toxicity. Despite more than one thousand studies in the literature on phillyrin retrievable from Web of Science, PubMed, and CNKI, few reviews on its pharmacological activities have been presented conclusively. In this paper, we aimed to summarize the pharmacological and pharmacokinetic characteristics of phillyrin from the current literature, focusing on its anti-inflammatory, anti-aging, antiviral, antibacterial, hepatoprotective and anti-cancer effects, hoping to come up with new insights for its application as well as future studies.

Energy wasted for heating the empty space of the entire building can be saved by passively heating the immediate environment around the human body. Here, the authors show a nanophotonic structure textile with tailored infrared property for passive personal heating using nanoporous metallized polyethylene.

Energy storage technology plays a significant role in the pursuit of the high-quality development of the electricity market. Many regions in China have issued policies and regulations of different intensities for promoting the popularization of the energy storage industry. Based on a variety of initial conditions of different regions, this paper explores the evolutionary process of electricity market players considering energy storage technology. The trilateral evolutionary game model is adopted to analyze the strategies of the power plant, the power grid, and the government. After assigning the model according to an actual situation, each equilibrium point corresponds to a real electricity market situation. The results indicate the following: (1) In the process of stabilizing, the role of “Advanced Imitators” leading the strategy of building energy storage changes between the power plant and the power grid. (2) In Eastern, Middle, and Southern China, the power plants and power grids on a greater-than-medium scale will choose to build energy storage without governmental regulations, due to the abundant net profit. (3) In the northeast of China, power plants with a medium-or-lower scale will choose not to build energy storage because of the relatively low on-grid price, and small power grids can make enough profits by operating energy storage facilities. (4) In Northern China, the large power plants and the medium power grids will choose to build energy storage due to the high electricity sale price and the resulting high profit. (5) In Western China, the small power plants and power grids cannot afford to build energy storage due to the low electricity price. The results lead to valuable policy suggestions for the local governments of China in promoting energy storage in the future. To meet the goal of energy storage popularization, regional electricity market plans need relevant policies based on its existing conditions, offering suitable external conditions for adding energy storage.

This paper presents a double loop controller for a 7-DoF automobile electrohydraulic active suspension via T-S fuzzy modelling technique. The outer loop controller employs a modified H-infinity feedback control based on a T-S fuzzy model to provide the actuation force needed to ensure better riding comfort and handling stability. The resulting optimizing problem is transformed into a linear matrix inequalities solution issue associated with stability analysis, suspension stroke limit, and force constraints. Integrating these via parallel distributed compensation method, the feedback gains are derived to render the suspension performance dependent on the perturbation size and improve the efficiency of active suspensions. Adaptive Robust Control (ARC) is then adopted in the inner loop design to deal with uncertain nonlinearities and improve tracking accuracy. The validity of improvements attained from this controller is demonstrated by comparing with conventional Backstepping control and a passive suspension on a 7-DoF simulation example. It is shown that the T-S fuzzy model based controller can achieve favourable suspension performance and energy conservation under both mild and malevolent road inputs.