Search

Abstract Objectives The capability of MR elastography (MRE) to differentiate fibrosis and inflammation, and to provide precise diagnoses is crucial, whereas the coexistence of fibrosis and inflammation may obscure the diagnostic accuracy. Methods In this retrospective study, from June 2020 to December 2022, chronic viral hepatitis patients who underwent multifrequency MRE (mMRE) were included in, and further divided into, training and validation cohorts. The hepatic viscoelastic parameters [shear wave speed (c) and loss angle (φ) of the complex shear modulus] were obtained from mMRE. The logistic regression and receiver operating characteristic (ROC) curves were generated to evaluate performance of viscoelastic parameters for fibrosis and inflammation. Results A total of 233 patients were assigned to training cohort and validation cohorts (mean age, 52 years ± 13 (SD); 51 women; training cohort, n = 170 (73%), and validation cohort, n = 63 (27%)). Liver c exhibited superior performance in detecting fibrosis with ROC (95% confidence interval) of ≥ S1 (0.96 (0.92–0.99)), ≥ S2 (0.86 (0.78–0.92)), ≥ S3 (0.89 (0.84–0.95)), and S4 (0.88 (0.83–0.93)). Similarly, φ was effective in diagnosing inflammation with ROC values of ≥ G2 (0.72 (0.63–0.81)), ≥ G3 (0.88 (0.83–0.94)), and G4 (0.92 (0.87–0.98)). And great predictive discrimination for fibrosis and inflammation were shown in validation cohort (all AUCs > 0.75). Conclusion The viscoelastic parameters derived from multifrequency MRE could realize simultaneous detection of hepatic fibrosis and inflammation. Critical relevance statement Fibrosis and inflammation coexist in chronic liver disease which obscures the diagnostic performance of MR elastography, whereas the viscoelastic parameters derived from multifrequency MR elastography could realize simultaneous detection of hepatic fibrosis and inflammation. Key points • Hepatic biomechanical parameters derived from multifrequency MR elastography could effectively detect fibrosis and inflammation. • Liver stiffness is useful for detecting fibrosis independent of inflammatory activity. • Fibrosis could affect the diagnostic efficacy of liver viscosity in inflammation, especially in early-grade of inflammation. Graphical Abstract

We propose a novel technique to search for axions with an optomechanical cavity filled with a material such as superfluid helium. Axion absorption converts a pump laser photon to a photon plus a phonon. The axion absorption rate is enhanced by the high occupation number of coherent photons or phonons in the cavity, allowing our proposal to largely overcome the extremely small axion coupling. The axion mass probed is set by the relative frequency of the photon produced in the final state and the Stokes mode. Because neither the axion mass nor momentum need to be matched to the physical size of the cavity, we can scale up the cavity size while maintaining access to a wide range of axion masses (up to a meV) complementary to other cavity proposals.

Abstract The effect of interpass temperature on the microstructure and pit nucleation behaviour in wire and arc additive manufacturing (WAAM) deposited ER316L stainless steel is investigated. Lowering the interpass temperature increases the ferrite content and decreases the sigma phase precipitation. Potentiostatic pulse measurements show that the WAAM ER316L pits develop predominantly near sigma phases and have higher pit density compared to a wrought 316L (UNS S31600). The pitting susceptibility of WAAM ER316L increases with increasing interpass temperature due to the precipitation of larger sigma phase enhancing the elemental segregation.

Abstract Corrosion performance of a multi-layered ER316LSi wall deposited using wire and arc additive manufacturing was studied in the as-deposited condition and after stress relief heat treatment at 900 °C, in 3.5 wt% NaCl solution. It was found that the heat treatment is not suitable for WAAM ER316LSi components due to the complete transformation of the delta ferrite into sigma decreasing the corrosion performance. The delta ferrite to sigma transformation during heat treatment was facilitated by the cyclic reheating of the part during deposition. The electrochemical response of as-deposited WAAM differed from a wrought alloy with similar composition and linked to microstructural differences: as-deposited WAAM had a higher pitting potential due to the absence of sulfide inclusions and increased metastable-like activity due to the presence of the secondary delta ferrite causing elemental segregation.

The nonlinear dynamics of the composite shaft rotor-bearing system are greatly affected by the orientation angle layer and its proportion of the ply, i.e., the ratio of the orientation angle layer in the laminate. This paper presents a nonlinear dynamic analysis of a composite rotor-bearing system with pedestal looseness that considers the nonlinear oil film force and the pedestal looseness. Nonlinear phenomena including periodic, quasi-periodic, and chaotic motions are analyzed. The analysis results indicate that the stiffness and damping coefficients of a composite shaft tube can be influenced strongly by the laminate parameters, which can in turn affect the instability speed of the rotor system. To enhance the oil film instability speed of the composite rotor system, it is essential to maximize the ratio of the small orientation angle layer or the ±45° layer. Additionally, increasing the ratio of the small orientation angle layers in the shaft tube leads to a higher rotational speed for loosening instability. The research results obtained in this paper have important theoretical value for the design of composite rotor-bearing systems.

Abstract We investigate the electroweak phase transition patterns for a recently proposed baryogenesis model with CP violation originated in the dark sector. The model includes a complex scalar singlet-Higgs boson portal, a U(1) l gauge lepton symmetry with a Z′ gauge boson portal and a fermionic dark matter particle. We find a novel thermal history of the scalar sector, featuring a Z 2 breaking singlet vacuum in the early Universe driven by a dark Yukawa coupling, that induces a one-step strongly first order electroweak phase transition. We explore the parameter space that generates the observed matter-antimatter asymmetry and dark matter relic abundance, while being consistent with constraints from electric dipole moment, collider searches, and dark matter direct detection bounds. The complex singlet can be produced via the Higgs portal and decays into Standard Model particles after traveling a certain distance. We explore the reach for long-lived singlet scalars at the 13 TeV Large Hadron Collider with L $$ \mathcal{L} $$ = 139 fb −1 and show its impact on the parameter space of the model. Setting aside currently unresolved theoretical uncertainties, we estimate the gravitational wave signatures detectable at future observatories.

Introduction: Corni Fructus (CF) is a Chinese herbal medicine used for medicinal and dietary purposes. It is available commercially in two main forms: raw CF (unprocessed CF) and wine-processed CF. Clinical observations have indicated that wine-processed CF exhibits superior hypoglycemic activity compared to its raw counterpart. However, the mechanisms responsible for this improvement are not well understood.Methods: To address this gap in knowledge, we conducted metabolomics analysis using ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS) to compare the chemical composition of raw CF and wine-processed CF. Subsequently, network analysis, along with immunofluorescence assays, was employed to elucidate the potential targets and mechanisms underlying the hypoglycemic effects of metabolites in CF.Results: Our results revealed significant compositional differences between raw CF and wine-processed CF, identifying 34 potential markers for distinguishing between the two forms of CF. Notably, wine processing led to a marked decrease in iridoid glycosides and flavonoid glycosides, which are abundant in raw CF. Network analysis predictions provided clues that eight compounds might serve as hypoglycemic metabolites of CF, and glucokinase (GCK) and adenylate cyclase (ADCYs) were speculated as possible key targets responsible for the hypoglycemic effects of CF. Immunofluorescence assays confirmed that oleanolic acid and ursolic acid, two bioactive compounds present in CF, significantly upregulated the expression of GCK and ADCYs in the HepG2 cell model.Discussion: These findings support the notion that CF exerted hypoglycemic activity via multiple components and targets, shedding light on the impact of processing methods on the chemical composition and hypoglycemic activity of Chinese herbal medicine.

An essential goal of the Higgs physics program at the LHC and beyond is to explore the nature of the Higgs potential and shed light on the mechanism of electroweak symmetry breaking. An important class of models alter the thermal history of electroweak symmetry breaking from the predictions of the Standard Model (SM). This paper reviews the existence of a region of parameter space where a strong first-order electroweak phase transition is compatible with exotic decays of the SM-like Higgs boson. A dedicated search for exotic Higgs decays can actively explore this framework at the Large Hadron Collider (LHC), while future exotic Higgs decay searches at the high-luminosity LHC and future Higgs factories will be vital to conclusively probe the scenario.

Abstract Background Resistance to ferroptosis, a regulated cell death caused by iron‐dependent excessive accumulation of lipid peroxides, has recently been linked to lung adenocarcinoma (LUAD). Intracellular antioxidant systems are required for protection against ferroptosis. The purpose of the present study was to investigate whether and how extracellular system desensitizes LUAD cells to ferroptosis. Methods Established human lung fibroblasts MRC‐5, WI38, and human LUAD H1650, PC9, H1975, H358, A549, and H1299 cell lines, tumor and matched normal adjacent tissues of LUAD, and plasma from healthy individuals and LUAD patients were used in this study. Immunohistochemistry and immunoblotting were used to analyze protein expression, and quantitative reverse transcription‐PCR was used to analyze mRNA expression. Cell viability, cell death, and the lipid reactive oxygen species generation were measured to evaluate the responses to ferroptosis. Exosomes were observed using transmission electron microscope. The localization of arachidonic acid (AA) was detected using click chemistry labeling followed by confocal microscopy. Interactions between RNAs and proteins were detected using RNA pull‐down, RNA immunoprecipitation and photoactivatable ribonucleoside‐enhanced crosslinking and immunoprecipitation methods. Proteomic analysis was used to investigate RNA‐regulated proteins, and metabolomic analysis was performed to analyze metabolites. Cell‐derived xenograft, patient‐derived xenograft, cell‐implanted intrapulmonary LUAD mouse models and plasma/tissue specimens from LUAD patients were used to validate the molecular mechanism. Results Plasma exosome from LUAD patients specifically reduced lipid peroxidation and desensitized LUAD cells to ferroptosis. A potential explanation is that exosomal circRNA_101093 (cir93) maintained an elevation in intracellular cir93 in LUAD to modulate AA, a poly‐unsaturated fatty acid critical for ferroptosis‐associated increased peroxidation in the plasma membrane. Mechanistically, cir93 interacted with and increased fatty acid‐binding protein 3 (FABP3), which transported AA and facilitated its reaction with taurine. Thus, global AA was reduced, whereas N‐arachidonoyl taurine (NAT, the product of AA and taurine) was induced. Notably, the role of NAT in suppressing AA incorporation into the plasma membrane was also revealed. In pre‐clinical in vivo models, reducing exosome improved ferroptosis‐based treatment. Conclusion Exosome and cir93 are essential for desensitizing LUAD cells to ferroptosis, and blocking exosome may be helpful for future LUAD treatment.

Abstract Yes-associated protein (YAP) activation is crucial for tumor formation and development, and its stability is regulated by ubiquitination. ISGylation is a type of ubiquitination like post-translational modification, whereas whether YAP is ISGylated and how ISGylation influences YAP ubiquitination-related function remains uncovered. In addition, YAP can activate glucose metabolism by activating the hexosamine biosynthesis pathway (HBP) and glycolysis, and generate a large number of intermediates to promote tumor proliferation. However, whether YAP stimulates the pentose phosphate pathway (PPP), another tumor-promoting glucose metabolism pathway, and the relationship between this stimulation and ISGylation needs further investigation. Here, we found that YAP was ISGylated and this ISGylation inhibited YAP ubiquitination, proteasome degradation, interaction with-beta-transducin repeat containing E3 ubiquitin-protein ligase (βTrCP) to promote YAP stability. However, ISGylation-induced pro-YAP effects were abolished by YAP K497R (K, lysine; R, arginine) mutation, suggesting K497 could be the major YAP ISGylation site. In addition, YAP ISGylation promoted cell viability, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) tumor formation. YAP ISGylation also increased downstream genes transcription, including one of the key enzymes of PPP, 6-phosphogluconolactonase (6PGL). Mechanistically, YAP promoted 6PGL transcription by simultaneously recruiting SMAD family member 2 (SMAD2) and TEA domain transcription factor 4 (TEAD4) binding to the 6PGL promoter to activate PPP. In clinical lung adenocarcinoma (LUAD) specimens, we found that YAP ISGylation degree was positively associated with 6PGL mRNA level, especially in high glucose LUAD tissues compared to low glucose LUAD tissues. Collectively, this study suggested that YAP ISGylation is critical for maintaining its stability and further activation of PPP. Targeting ISGylated YAP might be a new choice for hyperglycemia cancer treatment.

Abstract Background Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Patient prognosis is poor, and the existing therapeutic strategies for LUAD are far from satisfactory. Recently, targeting N6-methyladenosine (m6A) modification of RNA has been suggested as a potential strategy to impede tumor progression. However, the roles of m6A modification in LUAD tumorigenesis is unknown. Methods Global m6A levels and expressions of m6A writers, erasers and readers were evaluated by RNA methylation assay, dot blot, immunoblotting, immunohistochemistry and ELISA in human LUAD, mouse models and cell lines. Cell viability, 3D-spheroid generation, in vivo LUAD formation, experiments in cell- and patient-derived xenograft mice and survival analysis were conducted to explore the impact of m6A on LUAD. The RNA-protein interactions, translation, putative m6A sites and glycolysis were explored in the investigation of the mechanism underlying how m6A stimulates tumorigenesis. Results The elevation of global m6A level in most human LUAD specimens resulted from the combined upregulation of m6A writer methyltransferase 3 (METTL3) and downregulation of eraser alkB homolog 5 (ALKBH5). Elevated global m6A level was associated with a poor overall survival in LUAD patients. Reducing m6A levels by knocking out METTL3 and overexpressing ALKBH5 suppressed 3D-spheroid generation in LUAD cells and intra-pulmonary tumor formation in mice. Mechanistically, m6A-dependent stimulation of glycolysis and tumorigenesis occurred via enolase 1 (ENO1). ENO1 mRNA was m6A methylated at 359 A, which facilitated it’s binding with the m6A reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) and resulted in enhanced translation of ENO1. ENO1 positively correlated with METTL3 and global m6A levels, and negatively correlated with ALKBH5 in human LUAD. In addition, m6A-dependent elevation of ENO1 was associated with LUAD progression. In preclinical models, tumors with a higher global m6A level showed a more sensitive response to the inhibition of pan-methylation, glycolysis and ENO activity in LUAD. Conclusions The m6A-dependent stimulation of glycolysis and tumorigenesis in LUAD is at least partially orchestrated by the upregulation of METTL3, downregulation of ALKBH5, and stimulation of YTHDF1-mediated ENO1 translation. Blocking this mechanism may represent a potential treatment strategy for m6A-dependent LUAD.

Solanum nigrum L. (S. nigrum) and microbial agents are often used for the remediation of cadmium (Cd)-contaminated soil; however, no studies to date have examined the efficacy of using various microbial agents for enhancing the remediation efficiency of Cd-contaminated soil by S. nigrum. Here, we conducted greenhouse pot experiments to evaluate the efficacy of applying Bacillus megaterium (BM) along with citric acid (BM + CA), Glomus mosseae (BM + GM), and Piriformospora indica (BM + PI) on the ability of S. nigrum to remediate Cd-contaminated soil. The results showed that BM + GM significantly increased the Cd accumulation of each pot of S. nigrum by 104% compared with the control. Application of microbial agents changed the soil microbial communities. Redundancy analysis showed that the activities of Catalase (CAT) and urease (UE), soil organic matter, available N and total Cd were the main influencing factors. By constructing the microbial co-occurrence networks, the soil microbe was divided into four main Modules. BM + GM and BM + PI significantly increased the relative abundance of Module#1 and Module#3, respectively, when compared with the control. Additionally, Module#1 showed a significant positive correlation with translocation factor (TF), which could be regarded as the key microbial taxa. Further research found that Ascomycota, Glomeromycota, Proteobacteria, and Actinobacteria within Module#1 were also significantly correlated with TF, and these key species enriched in BM + GM. Overall, our findings indicate that the BM + GM treatment was the most effective for the remediation of Cd pollution. This treatment method may further affect the rhizosphere microbial community by affecting soil indicators, which might drive the formation of Module#1, thus greatly enhancing the Cd remediation capacity of S. nigrum.

A lack of promising targets leads to poor prognosis in patients with lung adenocarcinoma (LUAD). Therefore, it is urgent to identify novel therapeutic targets. The importance of the N6-methyladenosine (m6A) RNA modification has been demonstrated in various types of tumors; however, knowledge of m6A-related proteins in LUAD is still limited. Here, we found that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), an m6A reader protein, is highly expressed in LUAD and associated with poor prognosis. IGF2BP3 desensitizes ferroptosis (a new form of regulated cell death) in a manner dependent on its m6A reading domain and binding capacity to m6A-methylated mRNAs encoding anti-ferroptotic factors, including but not limited to glutathione peroxidase 4 (GPX4), solute carrier family 3 member 2 (SLC3A2), acyl-CoA synthetase long chain family member 3 (ACSL3), and ferritin heavy chain 1 (FTH1). After IGF2BP3 overexpression, expression levels and mRNA stabilities of these anti-ferroptotic factors were successfully sustained. Notably, significant correlations between SLC3A2, ACSL3, and IGF2BP3 were revealed in clinical LUAD specimens, further establishing the essential role of IGF2BP3 in desensitizing ferroptosis. Inducing ferroptosis has been gradually accepted as an alternative strategy to treat tumors. Thus, IGF2BP3 could be a potential target for the future development of new biomaterial-associated therapeutic anti-tumor drugs.

Abstract Background Lipid management is the first line of treatment for decreasing the incidence of cardiovascular events in patients with coronary heart disease (CHD), and a variety of indicators are used to evaluate lipid management. This work analyses the differences in LDL-C and apoB for lipid management evaluation, as well as explores the feasibility of skin cholesterol as a marker that can be measured non-invasively for lipid management. Methods The prospective study enrolled 121 patients who had been diagnosed with acute coronary syndrome (ACS) at the department of emergency medicine of the First Affiliated Hospital of the USTC from May 2020 to January 2021, and the patients were grouped into Group I (n=53) and Group II (n=68) according to whether they had comorbid hyperlipidemia and/or diabetes mellitus. All patients were administered 10 mg/day of rosuvastatin and observed for 12 weeks. Lipid management was assessed on the basis of LDL-C and apoB, and linear correlation models were employed to assess the relationship between changes in these well accepted markers to that of changes in skin cholesterol. Results Out of 121 patients with ACS, 53 patients (43.80 %) had combined hyperlipidemia and/or diabetes mellitus (Group I), while 68 patients (56.20 %) did not (Group II). Cardiovascular events occur at earlier ages in patients with CHD who are comorbid for hyperlipidemia and/or diabetes (P

In this paper, a N-rich B–N polymorph named as B20N24 is proposed through first-principles calculations. The stability of the B20N24 polymorph at ambient conditions is confirmed using the phonon dispersion spectra and the Born stability criteria. Electronic properties calculations show that B20N24 exhibits a semiconducting feature, with a 0.87 eV direct band gap derived from HSE06 functions, which is much lower than many other B–N polymorphs. Specifically, owing to its cage-like framework, B20N24 may be used in hydrogen storage at a capacity of ~6.8 wt.%. The B20N24 polymorph enriches the B–N system theoretically, and this polymorph is promising for use in electronic devices and hydrogen storage.

A pot experiment was performed to investigate the effects of Trichoderma harzianum on the root morphology of Malus hupehensis Rehd. seedlings and their soil environment under replant conditions. The experiment consisted of four treatments: continuously cropped soil (CK1), methyl bromide fumigation (CK2), carrier substrate control (T1), and T. harzianum fertilizer (T2). Plant growth parameters, soil phenolic acid content, abundance of soil microorganisms, and root respiration rate were measured. Compared with CK1, plant height, basal diameter, and fresh weight were 34.58%, 27.55%, and 32.91% greater in T2; 11.35%, 12.10%, and 18.33% greater in T1; and 54.34%, 57.64%, and 45.74% greater in CK2. These metrics were significantly higher in the CK2 treatment than in the other treatments. The second highest values were recorded in the T2 treatment. Differences in root architecture were consistent with differences in biomass. Application of T. harzianum fertilizer was associated with increases of 45.45%, 120.06%, 86.44%, and 268.29% in the activities of the antioxidant enzymes superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), respectively, and there was little difference between T2 and CK2. The contents of phlorizin and phloretin were 39.39% and 51.70% less in T2, respectively, and 17.85% and 18.14% less in T1, respectively, compared with CK1. Trichoderma harzianum fertilizer increased the abundance of bacteria and actinomycetes while decreasing that of fungi. The gene copy numbers of Fusarium oxysporum and Fusarium moniliforme were 64.30% and 49.35% less, respectively, in the T2 treatment. The fungus population and the gene copy number of Fusarium oxysporum and Fusarium moniliforme was the least in CK2 because of the good sterilization effect. The T. harzianum fertilizer showed satisfactory effects in promoting the root growth of M. hupehensis, increasing the root resistance, decreasing the soil phenolic acid content, and significantly reducing the gene copy number of F. oxysporum and F. moniliforme. In summary, T. harzianum fertilizer is an effective and green alternative for the prevention and control of apple replant disease (ARD).

Abstract Tribbles homolog 2 (TRIB2) is known to boost liver tumorigenesis via regulating Ubiquitin (Ub) proteasome system (UPS). At least two ways are involved, i.e., acts as an adaptor protein to modulate ubiquitination functions of certain ubiquitin E3 ligases (E3s) and reduces global Ub levels via increasing the proteolysis activity of proteasome. Recently, we have identified the role of TRIB2 to relieve oxidative damage via reducing the availability of Ub that is essential for the ubiquitination and subsequent degradation of Glutathione peroxidase 4 (GPX4). Although GPX4 is a critical antioxidant factor to protect against ferroptosis, the exact evidence showing that TRIB2 desensitizes ferroptosis is lacking. Also, whether such function is via E3 remains unclear. Here, we demonstrated that deletion of TRIB2 sensitized ferroptosis via lifting labile iron in liver cancer cells. By contrast, overexpression of TRIB2 led to the opposite outcome. We further demonstrated that transferrin receptor (TFRC) was required for TRIB2 to desensitize the cells to ferroptosis. Without TFRC, the labile iron pool could not be reduced by overexpressing TRIB2. We also found that beta-transducin repeat containing E3 ubiqutin protein ligase (βTrCP) was a genuine E3 for the ubiquitination of TFRC, and TRIB2 was unable to decline labile iron level once upon βTrCP was knocked out. In addition, we confirmed that the opposite effects on ferroptosis and ferroptosis-associated lipid reactive oxygen species (ROS) generation resulted from knockout and overexpression of TRIB2 were all indispensible of TFRC and βTrCP. Finally, we demonstrated that TRIB2 exclusively manipulated RSL3- and erastin-induced-ferroptosis independent of GPX4 and glutathione (GSH). In conclusion, we elucidated a novel role of TRIB2 to desensitize ferroptosis via E3 βTrCP, by which facilitates TFRC ubiquitiation and finally decreases labile iron in liver cancer cells.

Abstract Background Establishing a high-accuracy and non-invasive method is essential for evaluating cardiovascular disease. Skin cholesterol is a novel marker for assessing the risk of atherosclerosis and can be used as an independent risk factor of early assessment of atherosclerotic risk. Methods We propose a non-invasive skin cholesterol detection method based on absorption spectroscopy. Detection reagents specifically bind to skin cholesterol and react with indicator to produce colored products, the skin cholesterol content can be obtained through absorption spectrum information on colored products detected by non-invasive technology. Gas chromatography is used to measure cholesterol extracted from the skin to verify the accuracy and reliability of the non-invasive test method. A total of 342 subjects were divided into normal group (n = 115), disease group (n = 110) and risk group (n = 117). All subjects underwent non-invasive skin cholesterol test. The diagnostic accuracy of the measured value was analyzed by receiver-operating characteristic (ROC) curve. Results The proposed method is able to identify porcine skin containing gradient concentration of cholesterol. The values measured by non-invasive detection method were significantly correlated with gas chromatography measured results (r = 0.9074, n = 73, p

BackgroundDue to substantial comorbidities of major depressive disorder (MDD) and anxiety disorder (AN), these two disorders must be distinguished. Accurate identification and diagnosis facilitate effective and prompt treatment. EEG biomarkers are a potential research hotspot for neuropsychiatric diseases. The purpose of this study was to investigate the differences in EEG power spectrum at theta oscillations between patients with MDD and patients with AN.MethodsSpectral analysis was used to study 66 patients with MDD and 43 patients with AN. Participants wore 16-lead EEG caps to measure resting EEG signals. The EEG power spectrum was measured using the fast Fourier transform. Independent samples t-test was used to analyze the EEG power values of the two groups, and p < 0.05 was statistically significant.ResultsEEG power spectrum of the MDD group significantly differed from the AN group in the theta oscillation on 4–7 Hz at eight electrode points at F3, O2, T3, P3, P4, FP1, FP2, and F8.ConclusionParticipants with anxiety demonstrated reduced power in the prefrontal cortex, left temporal lobe, and right occipital regions. Confirmed by further studies, theta oscillations could be another biomarker that distinguishes MDD from AN.

Abstract Electroweak baryogenesis is an attractive mechanism to generate the baryon asymmetry of the Universe via a strong first order electroweak phase transition. We compare the phase transition patterns suggested by the vacuum structure at the critical temperatures, at which local minima are degenerate, with those obtained from computing the probability for nucleation via tunneling through the barrier separating local minima. Heuristically, nucleation becomes difficult if the barrier between the local minima is too high, or if the distance (in field space) between the minima is too large. As an example of a model exhibiting such behavior, we study the Next-to-Minimal Supersymmetric Standard Model, whose scalar sector contains two SU(2) doublets and one gauge singlet. We find that the calculation of the nucleation probabilities prefers different regions of parameter space for a strong first order electroweak phase transition than the calculation based solely on the critical temperatures. Our results demonstrate that analyzing only the vacuum structure via the critical temperatures can provide a misleading picture of the phase transition patterns, and, in turn, of the parameter space suitable for electroweak baryogenesis.

Computing directed Minimum Spanning Tree (DMST) is a fundamental problem in graph theory. It is applied in a wide spectrum of fields from computer network and communication protocol design to revenue maximization in social networks and syntactic parsing in Natural Language Processing. State-of-the-art solutions are online algorithms that compute DMST for a given graph and a root. For multi-query requirements, the online algorithm is inefficient. To overcome the drawbacks, in this paper, we propose an indexed approach that reuses the computation result to facilitate single and batch queries. We store all the potential edges of DMST in a hierarchical tree in O(n) space complexity. Furthermore, we answer the DMST query of any root in O(n) time complexity. Experimental results demonstrate that our approach can achieve a speedup of 2–3 orders of magnitude in query processing compared to the state-of-the-art while consuming O(n) index size.

The egg production of laying hens is crucial to breeding enterprises in the laying hen breeding industry. However, there is currently no systematic or accurate method to identify low-egg-production-laying hens in commercial farms, and the majority of these hens are identified by breeders based on their experience. In order to address this issue, we propose a method that is widely applicable and highly precise. First, breeders themselves separate low-egg-production-laying hens and normal-laying hens. Then, under a halogen lamp, hyperspectral images of the two different types of hens are captured via hyperspectral imaging equipment. The vertex component analysis (VCA) algorithm is used to extract the cockscomb end member spectrum to obtain the cockscomb spectral feature curves of low-egg-production-laying hens and normal ones. Next, fast continuous wavelet transform (FCWT) is employed to analyze the data of the feature curves in order to obtain the two-dimensional spectral feature image dataset. Finally, referring to the two-dimensional spectral image dataset of the low-egg-production-laying hens and normal ones, we developed a deep learning model based on a convolutional neural network (CNN). When we tested the model’s accuracy by using the prepared dataset, we found that it was 0.975 percent accurate. This outcome demonstrates our identification method, which combines hyperspectral imaging technology, an FCWT data analysis method, and a CNN deep learning model, and is highly effective and precise in laying-hen breeding plants. Furthermore, the attempt to use FCWT for the analysis and processing of hyperspectral data will have a significant impact on the research and application of hyperspectral technology in other fields due to its high efficiency and resolution characteristics for data signal analysis and processing.

Abstract Background Ferroptosis is the process of cell death triggered by lipid peroxides, and inhibition of glutathione (GSH) synthesis leads to ferroptosis. Liver cancer progression is closely linked to ferroptosis suppression. However, the mechanism by which inhibition of GSH synthesis suppresses potential ferroptosis of liver cancer cells and whether ferroptosis-related liver cancer biomarkers have a promising diagnostic value remain unknown. Methods Ribonucleotide reductase regulatory subunit M2 (RRM2) levels were measured using an enzyme linked immunosorbent assay (ELISA), quantitative RT-PCR (qPCR), immunoblotting (IB) and immunochemistry (IHC). Cell viability and cell death were measured by a CellTiter-Glo luminescent cell viability assay and staining with SYTOX Green followed by flow cytometry, respectively. Metabolites were measured using the indicated kits. The Interaction between glutathione synthetase (GSS) and RRM2 was measured using immunofluorescence (IF), co-immunoprecipitation (co-IP) and the proximal ligation assay (PLA). The diagnostic value was analyzed using the area under the receiver operating characteristic curve (AUC-ROC). Bioinformatics analysis was performed using the indicated database. Results RRM2 showed specifically elevated levels in liver cancer and inhibited ferroptosis by stimulating GSH synthesis via GSS. Mechanistically, phosphorylation of RRM2 at the Threonine 33 residue (T33) was maintained at normal levels to block the RRM2–GSS interaction and therefore protected RRM2 and GSS from further proteasome degradation. However, under ferroptotic stress, RRM2 was dephosphorylated at T33, thus the RRM2–GSS interaction was promoted. This resulted in the translocation of RRM2 and GSS to the proteasome for simultaneous degradation. Clinically, serum RRM2 was significantly associated with serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GT), albumin (ALB) and total bilirubin. The AUC-ROC for the combination of RRM2 with AFP was 0.947, with a sensitivity of 88.7% and a specificity of 97.0%, which indicates better diagnostic performance compared to either RRM2 or AFP alone. Conclusion RRM2 exerts an anti-ferroptotic role in liver cancer cells by sustaining GSH synthesis. Serum RRM2 will be useful as a biomarker to evaluate the degree to which ferroptosis is suppressed and improve diagnostic efficiency for liver cancer.

BackgroundMajor depressive disorder (MDD) with suicide attempts (SA) poses a significant public health issue. This study aims to identify neurobiological markers for MDD with SA on resting-state brain functional magnetic resonance imaging (rs-fMRI).MethodsFifty-one unmedicated adult MDD participants, 27 with SA on the Beck Scale for Suicidal Ideation and 24 without SA, underwent rs-fMRI scanning. A group of 30 healthy controls (HC) matched for age, gender, and education-level with MDD were chosen. A whole brain analysis of regional homogeneity (ReHo) was performed on subjects to identify regions where brain activity was associated with SA. Multiple comparison analysis was performed for ReHo. Pearson’s correlation analysis was performed between HAMD-SA scores and ReHo. The statistical significance level was set at p < 0.05.ResultsWe examined whether there were significant differences among the three groups in whole brain ReHo during resting state. Subjects with SA showed significant increase of ReHo in the right Cingulum Post in comparison with those without SA. Subjects with SA showed significant decrease of ReHo in the right Cingulate Gyrus/Precuneus in comparison with HC. The mean ReHo from the significant brain region was associated with HAMD-SA (item 3 of the HAMD) scores (r = 0.349, P = 0.012) but was not associated with HAMD-24 scores.ConclusionThese results indicate that SA is associated with altered resting-state brain activity. The pattern of elevated activity in the cingulum functioning may be related to SA. Identifying cingulum activity associated with SA may help to elucidate its pathogenesis and etiology.

Abstract This work investigates a simple, representative extension of the Standard Model with a real scalar singlet and spontaneous Z 2 breaking, which allows for a strongly first-order phase transition, as required by electroweak baryogenesis. We perform analytical and numerical calculations that systematically include one-loop thermal effects, Coleman-Weinberg corrections, and daisy resummation, as well as evaluation of bubble nucleation. We study the rich thermal history and identify the conditions for a strongly first-order electroweak phase transition with nearly degenerate extrema at zero temperature. This requires a light scalar with mass below 50 GeV. Exotic Higgs decays, as well as Higgs coupling precision measurements at the LHC and future collider facilities, will test this model. Additional information may be obtained from future collider constraints on the Higgs self-coupling. Gravitational-wave signals are typically too low to be probed by future gravitational wave experiments.

Background: The development of bacterial biofilm can cause severe chronic infections and antibiotic resistance. Therefore, it poses a significant threat to public health. Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa) are two major pathogens that can cause biofilm-associated infections, which leads to the urgent necessity of developing new agents with biofilm-forming inhibitory ability. Methods: A series of pyran derivatives were synthesized and characterized, and their in vitro anti-biofilm activity against S. aureus and P. aeruginosa were measured by minimal biofilm inhibitory concentration assay and FITC dye staining. The in vivo antibiofilm therapeutical effects were evaluated in S. aureus induced tissue cage infection mice model and P. aeruginosa induced urinary tract catheter infection rat model. Results: Several pyran derivatives showed the in vitro anti-biofilm activity against S. aureus and P. aeruginosa, and the activity of these compounds was not mediated through the accessory gene regulator (agr) quorum sensing system of S. aureus. One of these pyran derivatives, namely 2-amino-4-(2,6-dichlorophenyl)-3-cyano-5-oxo-4H,5H-pyrano[3,2c]chromene, exhibited significant inhibitory biofilm-formation activity in S. aureus tissue cage infection mice model and in the P. aeruginosa-infected urinary tract catheters of experimental rats. Conclusions: The data indicated that this pyran derivative is a possible lead compound that can be used for the development of novel anti-biofilm agents against S. aureus and P. aeruginosa infection. Keywords: Staphylococcus aureus, Pseudomonas aeruginosa, Biofilm, Quorum sensing system, Pyran derivative

ObjectiveMajor depression disorder (MDD) is a harmful disorder, and the pathological mechanism remains unclear. The primary pharmacotherapy regimen for MDD is selective serotonin reuptake inhibitors (SSRIs), but fewer than 40% of patients with MDD are in remission following initial treatment. Neuroimaging biomarkers of treatment efficacy can be used to guide personalized treatment in MDD. This study aims to determine if cortical thickness can be used as a predictor for SSRIs.MethodsA total of 126 first-episode, drug-naive MDD patients (MDDs) and 71 healthy controls (HCs) were enrolled in our study. Demographic data were collected according to the self-made case report form (CRF) at the baseline of all subjects. Magnetic resonance imaging (MRI) scanning was performed for all the participants at baseline, and all imaging was processed using the DPABISurf software. All MDDs were treated with SSRIs, and symptoms were assessed at both the baseline and 2 weeks using the 17-item Hamilton Rating Scale (HAMD-17). According to HAMD-17 total score improvement from baseline to the end of 2 weeks, the MDDs were divided into the non-responder group (defined as ≤ 20% HAMD-17 reduction) and responder group (defined as ≥50% HAMD-17 reduction). The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of MDDs' and HCs' cortical thickness for MDD. Correlation analysis was performed for the responder group and the non-responder group separately to identify the relationship between cortical thickness and SSRI treatment efficacy. To analyze whether cortical thickness was sufficient to differentiate responders and non-responders at baseline, we used ROC curve analysis.ResultsSignificant decreases were found in the cortical thickness of the right supplementary motor area (SMA) in MDDs at the baseline (corrected by the Monte Carlo permutation correction, cluster-wise significant threshold at p < 0.025 and vertex-wise threshold at p = 0.001), area under the curve (AUC) = 0.732 [95% confidence interval (CI) = 0.233–0.399]. In the responder group, the cortical thickness of the right SMA was significantly thinner than in the non-responder group at baseline. There was a negative correlation (r = −0.373, p = 0.044) between the cortical thickness of SMA (0 weeks) and HAMD-17 reductive rate (2 weeks) in the responder group. The results of ROC curve analyses of the responder and non-responder groups were AUC = 0.885 (95% CI = 0.803–0.968), sensitivity = 73.5%, and specificity = 96.6%, and the cutoff value was 0.701.ConclusionLower cortical thickness of the right SMA in MDD patients at the baseline may be a neuroimaging biomarker for MDD diagnosis, and a greater extent of thinner cortical thickness in the right SMA at baseline may predict improved SSRI treatment response. Our study shows the potential of cortical thickness as a possible biomarker that predicts a patient's clinical treatment response to SSRIs in MDD.

Abstract Background Ferroptosis, a form of regulated cell death, is an important topic in the field of cancer research. However, the signalling pathways and factors that sensitise tumour cells to ferroptosis remain elusive. Methods We determined the level of ferroptosis in cells by measuring cell death and lipid reactive oxygen species (ROS) production. The expression of RB1‐inducible coiled‐coil 1 (RB1CC1) and related proteins was analyzed by immunoblotting and immunohistochemistry. Immunofluorescence was used to determine the subcellular localization of RB1CC1. We investigated the mechanism of RB1CC1 nuclear translocation by constructing a series of RB1CC1 variants. To examine the ferroptosis‐ and RB1CC1‐dependent transcriptional program in tumour cells, chromatin immunoprecipitation sequencing was performed. To assess the effect of c‐Jun N‐terminal kinase (JNK) agonists on strenthening imidazole ketone erastin (IKE) therapy, we constructed cell‐derived xenograft mouse models. Mouse models of hepatocellular carcinoma to elucidate the importance of Rb1cc1 in IKE‐based therapy of liver tumourigenesis. Results RB1CC1 is upregulated by lipid ROS and that nuclear translocation of phosphorylation of RB1CC1 at Ser537 was essential for sensitising ferroptosis in tumour cells. Upon ferroptosis induction, nuclear RB1CC1 sharing forkhead box (FOX)‐binding motifs recruits elongator acetyltransferase complex subunit 3 (ELP3) to strengthen H4K12Ac histone modifications within enhancers linked to ferroptosis. This also stimulated transcription of ferroptosis‐associated genes, such as coiled‐coil–helix–coiled‐coil–helix domain containing 3 (CHCHD3), which enhanced mitochondrial function to elevate mitochondrial ROS early following induction of ferroptosis. FDA‐approved JNK activators reinforced RB1CC1 nuclear translocation and sensitised cells to ferroptosis, which strongly suggested that JNK is upstream of RB1CC1. Nuclear localisation of RB1CC1 correlated with lipid peroxidation in clinical lung cancer specimens. Rb1cc1 was essential for ferroptosis agonists to suppress liver tumourigenesis in mice. Conclusions Our findings indicate that RB1CC1‐associated signalling sensitises tumour cells to ferroptosis and that targeting RB1CC1 may be beneficial for tumour treatment.

Ferroptosis is an iron- and lipid peroxidation-dependent form of regulated cell death. The release of labile iron is one of the important factors affecting sensitivity to ferroptosis. Yes-associated protein (YAP) controls intracellular iron levels by affecting the transcription of ferritin heavy chain (FTH) and transferrin receptor (TFRC). However, whether YAP regulates iron metabolism through other target genes remains unknown. Here, we observed that the system Xc– inhibitor erastin inhibited the binding of the WW domain and PSY motif between YAP and transcription factor CP2 (TFCP2), and then suppressed the transcription of ferritin light chain (FTL) simultaneously mediated by YAP, TFCP2 and forkhead box A1 (FOXA1). Furthermore, inhibition of FTL expression abrogated ferroptosis-resistance in cells with sustained YAP expression. Unlike FTH, which exhibited first an increase and then a decrease in transcription, FTL transcription continued to decline after the addition of erastin, and a decrease in lysine acetyltransferase 5 (KAT5)-dependent acetylation of FTL was also observed. In lung adenocarcinoma (LUAD) tissues, lipid peroxidation and labile iron decreased, while YAP, TFCP2 and FTL increased compared to their adjacent normal tissues, and the lipid peroxidation marker 4-hydroxynonenal (4-HNE) was negatively correlated with the level of FTL or the degree of LUAD malignancy, but LUAD tissues with lower levels of 4-HNE showed a higher sensitivity to ferroptosis. In conclusion, the findings from this study indicated that the suppression of FTL transcription through the inhibition of the YAP-TFCP2-KAT5 complex could be another mechanism for elevating ferroptosis sensitivity and inducing cell death, and ferroptotic therapy is more likely to achieve better results in LUAD patients with a lower degree of lipid peroxidation.

Aims: Advanced glycation end products (AGEs) were reported to be correlated with the development of diabetes, as well as diabetic vascular complications. Therefore, this study aimed at investigating the association between AGEs and lower-extremity atherosclerotic disease (LEAD).Methods: A total of 1,013 type 2 diabetes patients were enrolled. LEAD was measured through color Doppler ultrasonography. The non-invasive skin autofluorescence method was performed for AGEs measurement. Considering that age plays an important role in both AGEs and LEAD, age-combined AGEs, i.e., AGEage index (define as AGEs × age/100) was used for related analysis.Results: The overall prevalence of LEAD was 48.9% (495/1,013). Patients with LEAD showed a significantly higher AGEage (p < 0.001), and the prevalence of LEAD increased with ascending AGEage levels (p for trend < 0.001). Logistic regression analysis revealed that AGEage was significantly positively associated with risk of LEAD, and the odds ratios of presence of LEAD across quartiles of AGEage were 1.00, 1.72 [95% confidence interval (CI) = 1.14–2.61], 2.72 (95% CI = 1.76–4.22), 4.29 (95% CI = 2.69–6.85) for multivariable-adjusted model (both p for trend < 0.001), respectively. The results were similar among patients of different sexes, body mass index, and with or without diabetes family history. Further, AGEage presented a better predictive value for LEAD than glycated hemoglobin A1c (HbA1c), with its sensitivity, specificity, and area under the curve of 75.5% (95% CI = 71.6–79.2%), 59.3% (95% CI = 54.9–63.6%), and 0.731 (0.703–0.758), respectively.Conclusion: AGEage, the non-invasive measured skin AGEs combined with age, seems to be a more promising approach than HbA1c in identifying patient at high risk of LEAD.

In this paper, the Layer-wise theory was improve based on the alternate characteristics of layer angle of composite hollow shaft. The ±φ i laminate was considered as the minimum mechanical analysis element, which can effectively simplify the stress coupling in mechanical analytical method. On this foundation, a 3-D analytical method of bending stiffness < EI > for thick-walled composite hollow shaft was derived. The CFRP hollow shaft specimens made of same dimensions but different laminate were used for bending test. Then, the bending stiffness calculated by theory of beams, 2-D analytical method, 3-D analytical model and experiment were compared. All the results show that the 3-D analytical model predicts the bending stiffness of thick-walled composite hollow shaft more precisely than the theory of beams and analytical method, and agree well with experimental results. And the 3-D analytical model can reflect the influence of stacking sequence on the bending stiffness of the composite hollow shaft.

The dynamics of cross-flow tubes were studied in consideration of initial axial load and distributed impacting constraints, modeled as cubic and trilinear spring constraints. The tubes were modeled as Euler–Bernoulli beams and supported at both ends, including the simply supported tube and clamped-clamped tube. The analytical model involves a time-delayed displacement term induced by the cross flow based on the quasi-steady theory. For simplicity, a single flexible supported beam in a rigid square array of cylinders was studied by using the damping-controlled mechanism. The mean extension of the tube was considered, and thus, it added another nonlinear term in the equation of motion. Results show that the tube loses stability by buckling and fluttering at various initial pressure loads and cross-flow velocities. An increase was observed for critical velocities and initial pressure loads. Chaotic oscillations were observed for the trilinear spring model. The distribution of the impacting forces was also calculated. Some of the fresh results obtained in the impact system are expected to be helpful in understanding and controlling the dynamic responses of fluid-conveying pipes.

CaCO3 nanoparticles are very suitable as intelligent carriers because of their ideal biocompatibility and biodegradability, especially their sensitivity to pH. In this paper, we use mesoporous CaCO3 nanoparticles as intelligent carrier, sodium alginate, and chitosan as alternating assembly materials, folic acid as target molecules, and exploit layer-by-layer assembly technology to achieve sensitive molecular targeting and pH response drug release. Mesoporous CaCO3 hybrid nanoparticles have high drug loading on doxorubicin. The effects of different pH values on drug release in vitro were studied by regulating simulated body fluids with different pH values. The cytotoxicity, targeting effect, and drug release of human cervical cancer cell line (HeLa) were studied by cell vitality and imaging experiments. All the evidence suggests that the smart mesoporous CaCO3 nanoparticles may be a potential clinical application platform for cancer therapy.

To guarantee a smooth in-orbit space gravitational wave detection for the Taiji mission, a semi-physical simulation test of inter-satellite laser interference is carried out. The semi-physical simulation test consists of three aspects: the establishment of the inter-satellite laser link, interferometry of the inter-satellite ranging, and simulation of the space environment. With the designed specifications for the semi-physical simulation platform, the test results for the inter-satellite laser interference can be obtained. Based on the semi-physical simulation test, the risks of inter-satellite laser interference technology can be mitigated, laying a solid foundation for the successful detection of in-orbit gravitational waves.

Natural polysaccharides and their metabolites’ short chain fatty acids (SCFAs) have attracted much attention. Recently, they have shown great potential in attenuating systemic inflammation activities, especially in inflammatory bowel disease (IBD). IBD is a complex pathological process and is related to epithelial damage and microbiota imbalance in the gut. Recent studies have indicated that natural polysaccharides could improve IBD recovery by different mechanisms. They could not only influence the ratio of intestine microbiota, but also regulate the secretion levels of immunity cytokines through multiple pathways, the latter including modulation of the TLR/MAPK/NF-κB signaling pathways and stimulation of G-protein-coupled receptors. Moreover, they could increase intestinal integrity and modulate oxidative stress. In this review, recent research about how natural polysaccharides impact the pathogenesis of IBD are summarized to prove the association between polysaccharides and disease recovery, which might contribute to the secretion of inflammatory cytokines, improve intestine epithelial damage, reduce oxidative stress, sustain the balanced microenvironment of the intestines, and finally lower the risk of IBD.

Advanced glycation end products (AGEs) are a complex and heterogeneous group of compounds that have been implicated in diabetes related complifications. Skin autofluorescence was recently introduced as an alternative tool for skin AGEs accumulation assessment in diabetes. Successful optical diagnosis of diabetes requires a rapid and accurate classification algorithm. In order to improve the performance of noninvasive and optical diagnosis of type 2 diabetes, support vector machines (SVM) algorithm was implemented for the classification of skin autofluorescence from diabetics and control subjects. Cross-validation and grid-optimization methods were employed to calculate the optimal parameters that maximize classification accuracy. Classification model was set up according to the training set and then verified by the testing set. The results show that radical basis function is the best choice in the four common kernels in SVM. Moreover, a diagnostic accuracy of 82.61%, a sensitivity of 69.57%, and a specificity of 95.65% for discriminating diabetics from control subjects were achieved using a mixed kernel function, which is based on liner kernel function and radical basis function. In comparison with fasting plasma glucose and HbA1c test, the classification method of skin autofluorescence spectrum based on SVM shows great potential in screening of diabetes.

The gravitational wave spacecraft is a complex multi-input multi-output dynamic system. The gravitational wave detection mission requires the spacecraft to achieve single spacecraft with two laser links and high-precision control. Establishing one spacecraftwith two laser links, compared to one spacecraft with a single laser link, requires an upgraded decoupling algorithmfor the link establishment. The decoupling algorithmwe designed reassigns the degrees of freedomand forces in the control loop to ensure sufficient degrees of freedomfor optical axis control. In addressing the distinct dynamic characteristics of different degrees of freedom, a transfer function compensation method is used in the decoupling process to furtherminimizemotion coupling. The open-loop frequency response of the systemis obtained through simulation. The upgraded decoupling algorithms effectively reduce the open-loop frequency response by 30 dB. The transfer function compensation method efficiently suppresses the coupling of low-frequency noise. [ABSTRACT FROM AUTHOR]

During a large-scale epidemic, a local healthcare system can be overwhelmed by a large number of infected and non-infected patients. To serve the infected and non-infected patients well with limited medical resources, effective emergency medical service planning should be conducted before the epidemic. In this study, we propose a two-stage stochastic programming model, which integrally deploys various types of emergency healthcare facilities before an epidemic and serves infected and non-infected patients dynamically at the deployed healthcare facilities during the epidemic. With the service equity of infected patients and various practical requirements of emergency medical services being explicitly considered, our model minimizes a weighted sum of the expected operation cost and the equity cost. We develop two comparison models and conduct a case study on Chengdu, a Chinese city influenced by the COVID-19 epidemic, to show the effectiveness and benefits of our proposed model. Sensitivity analyses are conducted to generate managerial insights and suggestions. Our study not only extends the existing emergency supply planning models but also can facilitate better practices of emergency medical service planning for large-scale epidemics. [ABSTRACT FROM AUTHOR]