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Abstract Autoimmunity underlies many painful disorders, such as enthesopathies, which localize to the enthesis. From infiltration of the synovium and axial skeleton by B cells, to disturbances in the ratio of M1/M2 enthesis macrophages, to CD8 + T cell mediated inflammation, autoimmune dysregulation is becoming increasingly well characterized in enthesopathies. Tissue resident B cells, macrophages, neutrophils, and T cells have also been localized in healthy human entheses. However, the potential developmental origins, presence, and role of immune cells (ICs) in enthesis development is not known. Here, we use single-cell RNA-sequencing analysis to describe IC subtypes present in the enthesis before, during, and after mineralization, and to infer regulatory interactions between ICs and mesenchymal cells (MCs). We report the presence of nine phenotypically distinct IC subtypes, including B cells, macrophages, neutrophils, and T cells. We find that specific IC subtypes may promote MC-proliferation and differentiation, and that MCs may regulate IC phenotype and autoimmunity. Our findings suggest that bidirectional regulatory interactions between ICs and MCs may be important to enthesis mineralization, and suggest that progenitor MCs have a unique ability to limit autoimmunity during development.

MicroRNA (miRNA) has garnered considerable attention due to its diagnostic capabilities, such as in hypoxic cognitive impairment and cancers. However, the existing miRNA detection methods are commonly criticized for the drawbacks of low sensitivity and false-positive detection derived from interfering molecules. Here, we provide a novel, sensitive and portable method for miRNA detection by combining target identification based cyclization of padlocks, immobilized primer-based signal amplification and a personal glucose meter. The proposed method exhibits several advantages, including precise identification of specific sites, exceptional sensitivity and instrument-free feature. These attributes hold great promise for the diagnosis and clinical investigation of various diseases, such as cancer and hypoxic cognitive impairment, enabling a deeper understanding of their pathological and physiological aspects.

BackgroundBell palsy (BP) is the most common cause of acute peripheral facial palsy which leads to functional and esthetic disturbances in patients and has a negative influence on daily living. Electroacupuncture (EA) has been considered an alternative treatment for improving facial function in patients with BP. However, there is no agreement on the preferred waveform type of the EA for treating BP.MethodsThis is a study protocol for a pilot randomized, two-arm, three-center, clinical trial at the Third Affiliated hospital of Zhejiang Chinese Medical University, the First Affiliated hospital of Zhejiang Chinese Medical University, and the Hangzhou First People’s Hospital. The trial began in November 2023 and is expected to end in December 2025. Sixty patients with BP whose electroneurography (ENoG) value is at least 20% and 60 patients with BP whose ENoG value is less than 20% will be randomly assigned to the low frequency continuous waveform group or the intermittent waveform group in a 1:1 ratio. Participants will receive 4 weeks of EA treatment and clinical assessments. The primary outcome is the change from baseline score of the Facial Nerve Grading System 2.0. The secondary outcomes include the change from baseline score of the Sunnybrook grading scale and the change from baseline amplitude of the compound muscle action potential of the affected side in the ENoG tests.DiscussionThis is the first study protocol to compare the treatment effect and safety of EA with low frequency continuous waveform and intermittent waveform for different severity groups of BP. This study will contribute to subsequent studies for exploring optimal EA parameters for BP treatment.Clinical trial registrationClinicalTrials.gov, NCT06063954.

Abstract Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture, which increases patient susceptibility to fragile fractures. The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles (EVs), which play crucial roles in both pathological and physiological contexts. EVs derived from various sources exert distinct effects on osteoporosis. Specifically, EVs released by osteoblasts, endothelial cells, myocytes, and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins, miRNAs, and cytokines. Conversely, EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation. Furthermore, the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising. Here, we review the current understanding of the impact of EVs on bone homeostasis, including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis. Furthermore, we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs. Finally, we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.

The genus Ganoderma is a widely used medicinal fungus in East Asia. The main medicinal components are triterpenoids, polyphenols, and polysaccharides. Bitterness is an important commercial trait for Ganoderma. White Lingzhi (G. leucocontextum) is less bitter. But the characteristics of its nutritional and medicinal ingredients are still unclear, which undoubtedly limits its commercialization. In this study, the medicinal ingredients of Lingzhi and white Lingzhi were extracted and quantified. The structure and antioxidant activities of purified polysaccharides were determined. At the same time, their nutritional differences were compared. White Lingzhi contains more medicinal ingredients and its polysaccharide is more active. The higher protein content may be one of the reasons for weaker bitterness in white Lingzhi. The nutritional and medicinal traits of white Lingzhi were described for the first time in this study, which provides fundamental knowledge to support the development of white Lingzhi.

Summary: Maternal-to-zygotic transition (MZT) is central to early embryogenesis. However, its underlying molecular mechanisms are still not well described. Here, we revealed the expression dynamics of 5,000 proteins across four stages of zebrafish embryos during MZT, representing one of the most systematic surveys of proteome landscape of the zebrafish embryos during MZT. Nearly 700 proteins were differentially expressed and were divided into six clusters according to their expression patterns. The proteome expression profiles accurately reflect the main events that happen during the MZT, i.e., zygotic genome activation (ZGA), clearance of maternal mRNAs, and initiation of cellular differentiation and organogenesis. MZT is modulated by many proteins at multiple levels in a collaborative fashion, i.e., transcription factors, histones, histone-modifying enzymes, RNA helicases, and P-body proteins. Significant discrepancies were discovered between zebrafish proteome and transcriptome profiles during the MZT. The proteome dynamics database will be a valuable resource for bettering our understanding of MZT.

Abstract Epithelial ovarian cancer (EOC) is universally acknowledged as a terrifying women killer for its high mortality. Recent research advances support that ferroptosis, an emerging iron-dependent type of regulated cell death (RCD) triggered by the excessive accumulation of lipid peroxides probably possesses extraordinary therapeutic potential in EOC therapy. Herein, we firstly provide a very concise introduction of ferroptosis. Special emphasis will be put on the ferroptosis’s vital role in EOC, primarily covering its role in tumorigenesis and progression of EOC, the capability of reversing chemotherapy resistance, and the research and development of related therapeutic strategies. Furthermore, the construction of ferroptosis-related prognostic prediction systems, and mechanisms of ferroptosis resistance in EOC are also discussed. Finally, we propose and highlight several important yet unanswered problems and some future research directions in this field.

Focusing water surface waves is a promising approach for enhancing wave power in clean energy harvesting. This study presents a novel method that simplifies the wave-scattering problems of large-scale three-dimensional (3D) focusing blocks by decomposing them into scattering problems of two-dimensional (2D) phase regulators. The phase lags of transmitted waves over such 2D structures of various heights and thicknesses are investigated using both linear potential flow theory and numerical simulations based on smoothed-particle hydrodynamics (SPH). Due to propagation path differences of a converging wave, our approach compensates for circular phase differences within a maximal collection angle by optimizing the geometries of 2D phase regulators. Based on this concept, we designed three types of submerged structures and tested them in a 3D numerical water tank. All three structures successfully converted monochromatic plane waves into circular waves, which then converged at the designated focal point. This study offers a potential method to enhance the collection efficiency of monochromatic and regular waves for wave energy converters.

Abstract Severe hypoxia would aggravate the acute kidney injury (AKI) in high-altitude areas and continuous renal replacement therapy (CRRT) has been used to treat critically ill patients with AKI. However, the characteristics and outcomes of CRRT in critically ill patients at AKI in high altitudes and the optimal timing of CRRT initiation remain unclear. 1124 patients were diagnosed with AKI and treated with CRRT in the ICU, comprising a high-altitude group (n = 648) and low-altitude group (n = 476). Compared with the low-altitude group, patients with AKI at high altitude showed longer CRRT (4.8 vs. 3.7, P = 0.036) and more rapid progression of AKI stages (P 0.05). Referring to the analysis of survival and kidney recovery curves, a higher mortality but a lower possibility of renal recovery was observed in the high-altitude group (P

Drought-induced protein 19 (Di19) is a Cys2/His2 zinc-finger protein that functions in plant growth and development and in tolerance to abiotic stresses. GmPUB21, an E3 ubiquitin ligase, negatively regulates drought and salinity response in soybean. We identified potential interaction target proteins of GmPUB21 by yeast two-hybrid cDNA library screening, GmDi19-5 as a candidate. Bimolecular fluorescence complementation and glutathionine-S-transferase pull-down assays confirmed the interaction between GmDi19-5 and GmPUB21. GmDi19-5 was induced by NaCl, drought, and abscisic acid (ABA) treatments. GmDi19-5 was expressed in the cytoplasm and nucleus. GmDi19-5 overexpression conferred hypersensitivity to drought and high salinity, whereas GmDi19-5 silencing increased drought and salinity tolerance. Transcripts of ABA- and stress response-associated genes including GmRAB18 and GmDREB2A were down-regulated in GmDi19-5-overexpressing plants under drought and salinity stresses. ABA decreased the protein level of GmDi19-5 in vivo, whereas GmPUB21 increased the decrease of GmDi19-5 after exogenous ABA application. The accumulation of GmPUB21 was also inhibited by GmDi19-5. We conclude that GmPUB21 and GmDi19-5 collaborate to regulate drought and salinity tolerance via an ABA-dependent pathway.

Vascular calcification (VC) is an accurate risk factor and predictor of adverse cardiovascular events; however, there is currently no effective therapy to specifically prevent VC progression. Capsaicin (Cap) is a bioactive alkaloid isolated from Capsicum annuum L., a traditional medicinal and edible plant that is beneficial for preventing cardiovascular diseases. However, the effect of Cap on VC remains unclear. This study aimed to explore the effects and related mechanisms of Cap on aortic calcification in a mouse and on Pi-induced calcification in vascular smooth muscle cells (VSMCs). First, we established a calcification mouse model with vitamin D3 and evaluated the effects of Cap on calcification mice using von Kossa staining, calcium content, and alkaline phosphatase activity tests. The results showed that Cap significantly improved calcification in mice. VSMCs were then cultured in 2.6 mM Na2HPO4 and 50 μg/mL ascorbic acid for 7 days to obtain a calcification model, and we investigated the effects and mechanisms of Cap on VSMCs calcification by assessing the changes of calcium deposition, calcium content, and subsequent VC biomarkers. These results showed that Cap alleviated VSMCs calcification by upregulating the expressions of TRPV1. Moreover, Cap reduced the expression of Wnt3a and β-catenin, whereas DKK1 antagonised the inhibitory effect of Cap on VSMC calcification. This study is the first to offer direct evidence that Cap inhibits the Wnt/β-catenin signaling pathway by upregulating the expression of the TRPV1 receptor, resulting in the decreased expression of Runx2 and BMP-2, thereby reducing VSMC calcification. Our study may provide novel strategies for preventing the progression of VC. This could serve as a theoretical basis for clinically treating VC with spicy foods.

The limitations of current drug-eluting stent technologies in selectively inhibiting vascular smooth muscle cell proliferation, which often leads to inflammation, call for innovative approaches in coronary artery disease treatment. In the present work, we propose a revolutionary solution: a three-in-one platform for vascular stents, combining arsenic trioxide (ATO) and tacrolimus (TAC) to address anti-proliferation, pro-endothelialization, and anti-inflammation aspects. Our findings demonstrate that the synergistic action of ATO and TAC effectively suppresses aberrant vascular smooth muscle cell proliferation and mitigates endothelial cell inflammation. Remarkably, the combination treatment of TAC/ATO enhances endothelial cell migration and adhesion abilities. Moreover, our TAC/ATO-eluting stent exhibits superior re-endothelialization and anti-restenosis effects in a rabbit and porcine stent implantation model. Both in vitro and in vivo results solidify the notion that the TAC/ATO-eluting stent ensures rapid re-endothelialization and significantly reduces the incidence of in-stent restenosis. Overall, this study represents a promising and novel multifunctional platform with immense potential in the therapy of coronary artery disease.

ObjectivePeer review frequently follows a process where reviewers first provide initial reviews, authors respond to these reviews, then reviewers update their reviews based on the authors' response. There is mixed evidence regarding whether this process is useful, including frequent anecdotal complaints that reviewers insufficiently update their scores. In this study, we aim to investigate whether reviewers anchor to their original scores when updating their reviews, which serves as a potential explanation for the lack of updates in reviewer scores.DesignWe design a novel randomized controlled trial to test if reviewers exhibit anchoring. In the experimental condition, participants initially see a flawed version of a paper that is corrected after they submit their initial review, while in the control condition, participants only see the correct version. We take various measures to ensure that in the absence of anchoring, reviewers in the experimental group should revise their scores to be identically distributed to the scores from the control group. Furthermore, we construct the reviewed paper to maximize the difference between the flawed and corrected versions, and employ deception to hide the true experiment purpose.ResultsOur randomized controlled trial consists of 108 researchers as participants. First, we find that our intervention was successful at creating a difference in perceived paper quality between the flawed and corrected versions: Using a permutation test with the Mann-Whitney U statistic, we find that the experimental group's initial scores are lower than the control group's scores in both the Evaluation category (Vargha-Delaney A = 0.64, p = 0.0096) and Overall score (A = 0.59, p = 0.058). Next, we test for anchoring by comparing the experimental group's revised scores with the control group's scores. We find no significant evidence of anchoring in either the Overall (A = 0.50, p = 0.61) or Evaluation category (A = 0.49, p = 0.61). The Mann-Whitney U represents the number of individual pairwise comparisons across groups in which the value from the specified group is stochastically greater, while the Vargha-Delaney A is the normalized version in [0, 1].

Abstract The emotional experience of the driver is influenced by the design of the in-vehicle interaction interface. User experience journey maps are commonly used by designers to reveal interface design pain points and refine user needs, and further studies are required to effectively characterize and quantify user emotional needs. This study provides a method for accurately presenting a driver’s emotional experience through a human–machine interface using Kansei engineering and user experience journey. Firstly, the semantic difference approach was used to match the relationship between user behavioral touchpoints and Kansei imagery words of the interface. And then the emotional quantification curve was built to generate an average value for Kansei imagery word evaluation. Finally, design pain points were identified and iterative design was carried out. A validation study was implemented to ensure the method’s validity. The study demonstrated that a quantitative map of user emotional experience could efficiently quantify and depict the findings of emotional quantification. This method enables designers to accurately recognize user needs while also facilitating product iterations.

We studied various fund investing options in the circular economy sector. We found that most circular economy mutual funds and exchange-traded funds charge higher fees and take higher risks than their benchmarks. However, they appear to have underperformed their benchmarks during their short existence so far. Most of these funds are rated as sustainable and low-carbon funds. Investors keen on circular economy startups may consider private equity/venture capital funds, but most of these funds are exclusive to institutional and accredited investors.

Atherosclerosis is a chronic inflammatory disease, occurring preferentially in bifurcation, branching, and bending of blood vessels exposed to disturbed flow. Disturbed flow in atheroprone areas activates elevated proteases, degrading elastin lamellae and collagenous matrix, resulting in endothelial dysfunction and vascular remodeling. As a mediator for extracellular matrix protein degradation, cathepsin K (CTSK) was directly regulated by hemodynamics and contributed to atherosclerosis. The mechanism of CTSK responding to disturbed flow and contributing to disturbed flow-induced atherosclerosis is unclear. In this study, the partial carotid ligation model of mice and in vitro disturbed shear stress model were constructed to explore the contribution and potential mechanism of CTSK in atherosclerosis. Our results indicated that CTSK elevated in the disturbed flow area in vivo and in vitro along with endothelial inflammation and atherogenesis. Additionally, the expression of integrin αvβ3 was upregulated in these atheroprone areas. We found that inhibition of the integrin αvβ3-cytoskeleton pathway could significantly block the activation of NF-κB and the expression of CTSK. Collectively, our findings unraveled that disturbed flow induces increased CTSK expression, and contributes to endothelial inflammation and vascular remodeling, leading to atherogenesis eventually. This study is helpful to provide new enlightenment for the therapy of atherosclerosis.

There is limited knowledge about the impact of circulating lipids and lipid-modifying drugs on pterygium development, with conflicting results reported. Our study aimed to address these questions by applying the Mendelian randomization (MR) approach. A two-step MR model was developed. In the first step, bidirectional two-sample MR was employed to establish the causal relationship between circulating lipids and pterygium risk. In the second step, drug-target MR analysis was conducted to assess the causal effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors on pterygium outcomes. Genetically predicted low-density lipoprotein cholesterol (LDL-c) levels were found to be significantly associated with an increased risk of pterygium (Inverse variance weighted [IVW] odds ratio [OR] = 2.227; P = 1.53 × 10–4). Similarly, higher total cholesterol (TC) levels exhibited a suggestive association with greater susceptibility to pterygium (IVW OR = 1.806; P = 1.70 × 10–3). Through drug-target MR, a positive causal association was noted between HMGCR-mediated LDL-c levels and pterygium (IVW OR = 6.999; P = 0.016), suggesting that statins may be effective in reducing pterygium risk. The present findings suggest that circulating TC and LDL-c are risk factors for pterygium. Additionally, the results indicate that HMGCR inhibitors, which lower LDL-c levels, have a potential protective effect on pterygium outcomes. Further research is warranted to elucidate the underlying mechanisms involved in pterygium pathogenesis, with a particular focus on cholesterol metabolism.

The oxidation of methane to formic acid or related oxygenates relies on efficient reaction with H2O2. Here, the authors report a TiO2-based catalyst to selectively form formic acid by using molecular O2 additives to avoid unwanted side reactions.

Tumour microenvironment profiling during colorectal cancer progression may enable the discovery of therapeutic targets. Here, single cell and spatial RNA sequencing of tumour and adjacent normal tissues reveals an interaction between FAP + fibroblasts and SPP1 + macrophages that could be disrupted as an immunotherapy strategy.

In this paper, we use the self-similar transformation and the modified potential well method to study the long time behaviors of solutions to the classical semilinear parabolic equation associated with critical Sobolev exponent in $\mathbb{R}^N$. Global existence and finite time blowup of solutions are proved when the initial energy is in three cases. When the initial energy is low or critical, we not only give a threshold result for the global existence and blowup of solutions, but also obtain the decay rate of the $L^2$ norm for global solutions. When the initial energy is high, sufficient conditions for the global existence and blowup of solutions are also provided. We extend the recent results which were obtained in [R. Ikehata, M. Ishiwata, T. Suzuki, Ann. Inst. H. Poincaré Anal. Non Linéaire 27(2010), No. 3, 877–900].

BackgroundBiopsy-based diagnosis is essential for maintaining kidney allograft longevity by ensuring prompt treatment for graft complications. Although histologic assessment remains the gold standard, it carries significant limitations such as subjective interpretation, suboptimal reproducibility, and imprecise quantitation of disease burden. It is hoped that molecular diagnostics could enhance the efficiency, accuracy, and reproducibility of traditional histologic methods.MethodsQuantitative label-free mass spectrometry analysis was performed on a set of formalin-fixed, paraffin-embedded (FFPE) biopsies from kidney transplant patients, including five samples each with diagnosis of T-cell-mediated rejection (TCMR), polyomavirus BK nephropathy (BKPyVN), and stable (STA) kidney function control tissue. Using the differential protein expression result as a classifier, three different machine learning algorithms were tested to build a molecular diagnostic model for TCMR.ResultsThe label-free proteomics method yielded 800-1350 proteins that could be quantified with high confidence per sample by single-shot measurements. Among these candidate proteins, 329 and 467 proteins were defined as differentially expressed proteins (DEPs) for TCMR in comparison with STA and BKPyVN, respectively. Comparing the FFPE quantitative proteomics data set obtained in this study using label-free method with a data set we previously reported using isobaric labeling technology, a classifier pool comprised of features from DEPs commonly quantified in both data sets, was generated for TCMR prediction. Leave-one-out cross-validation result demonstrated that the random forest (RF)-based model achieved the best predictive power. In a follow-up blind test using an independent sample set, the RF-based model yields 80% accuracy for TCMR and 100% for STA. When applying the established RF-based model to two public transcriptome datasets, 78.1%-82.9% sensitivity and 58.7%-64.4% specificity was achieved respectively.ConclusionsThis proof-of-principle study demonstrates the clinical feasibility of proteomics profiling for FFPE biopsies using an accurate, efficient, and cost-effective platform integrated of quantitative label-free mass spectrometry analysis with a machine learning-based diagnostic model. It costs less than 10 dollars per test.

Introduction: Atherosclerosis is the main cause of many cardiovascular diseases and contributes to morbidity and mortality worldwide. The formation of macrophage-derived foam cells plays a critical role in the early stage of atherosclerosis pathogenesis. Diterpenoids found in the flowers of Callicarpa rubella Lindl., a traditional Chinese medicine, have been reported to have anti-inflammatory activity. However, little is known about the effects of these diterpenoids on macrophage foam cell formation.Methods: A macrophage-derived foam cell formation model was established by treating RAW264.7 cells with oxidized low-density lipoprotein (ox-LDL) for 24 h. Oil red O staining were used to detect the intracellular lipids. The cholesterol efflux capacity was assayed by labeling cells with 22-NBD-cholesterol. Western blots and real-time PCRs were performed to quantify protein and mRNA expressions.Results: Two diterpenoid molecules, 14α-hydroxyisopimaric acid (C069002) and isopimaric acid (C069004), extracted from the flowers of Callicarpa rubella Lindl., significantly attenuated ox-LDL-induced foam cell formation in RAW264.7 macrophages. Further investigation showed that these two diterpenoids could promote cholesterol efflux from RAW264.7 macrophages to apolipoprotein A-I or high-density lipoproteins, which was associated with upregulated expression of ATP-binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα), and peroxisome proliferator-activated receptor-γ (PPARγ). Unexpectedly, the diterpenoids C069002 and C069004 failed to enhance the mRNA transcription of the ABCG1 gene in macrophage-derived foam cells induced by ox-LDL. To evaluate the effects of diterpenoids on macrophage foam cell formation and determine the underlying mechanism, two drugs (lovastatin and rosiglitazone) were used as positive controls. Although both drugs could reduce macrophage foam cell formation and promote cholesterol efflux, they each had distinctive abilities to modulate the expression of cholesterol efflux-related genes. In contrast to lovastatin, rosiglitazone showed a similar influence on the expression of cholesterol efflux-related genes (including ABCA1, LXRα, and PPARγ) as the diterpenoids regardless of the presence or absence of ox-LDL, implying a similar mechanism by which they may exert atheroprotective effects.Conclusion: Our research indicates that diterpenoids effectively inhibit ox-LDL-induced macrophage foam cell formation by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1 pathway. Further investigation of diterpenoids as potential drugs for the treatment of atherosclerosis is warranted.

Epithelial–mesenchymal transition (EMT) mediated by fluid shear stress (FSS) in the tumor microenvironment plays an important role in driving metastasis of the malignant tumor. As a mechanotransducer, Yes‐associated protein (YAP) is known to translocate into the nucleus to initiate transcription of genes involved in cell proliferation upon extracellular biophysical stimuli. Here, we showed that FSS facilitated cytoskeleton rearrangement in hepatocellular carcinoma cells, which led to the release of YAP from its binding partner, integrin β subunit, in the cytomembrane. Moreover, we found that upregulation of guanine nucleotide exchange factor (GEF)‐H1, a microtubule‐associated Rho GEF, is a critical step in the FSS‐induced translocation of YAP. Nuclear YAP activated the expression of the EMT‐regulating transcription factor SNAI1, but suppressed the expression of N6‐methyladenosine (m6A) modulators; together, this promoted the expression of EMT‐related genes. We also observed that FSS‐treated HepG2 cells showed markedly increased tumorigenesis and metastasis in vivo. Collectively, our findings unravel the underlying molecular processes by which FSS induces translocation of YAP from the cytomembrane to the nucleus, contributes to EMT and enhances metastasis in hepatocellular carcinoma.

The straightness error of guideways is one of the key indicators of an ultra-precision machine, which plays an important role in the machining accuracy of a workpiece. In order to measure the straightness error of a long-distance ultra-precision guideway accurately, a splicing measurement for the straightness error of a guideway using a high-precision flat mirror and displacement sensor was proposed in this paper, and the data splicing processing algorithm based on coordinate transformation was studied. Then, comparative experiments on a splicing measurement and direct measurement of the straightness error were carried out on a hydrostatic guideway grinder. The maximum difference between the two measurements was 0.3 μm, which was far less than the straightness error of 5.8 μm. The experiment demonstrated the correctness of the proposed splicing measurement method and data processing algorithm. To suppress the influence of the straightness error on machining accuracy, a straightness error compensation algorithm based on error rotation transformation and vertical axis position correction was proposed, and the grinding experiment of a plane optics with a size of 1400 mm × 500 mm was carried out. Without error compensation grinding, the flatness error of the element was 7.54 μm. After error compensation grinding, the flatness error was significantly reduced to 2.98 μm, which was less than the straightness errors of the guideways. These results demonstrated that the straightness error of the grinding machine had been well suppressed.

PurposeTo investigate the association between sleep quality and meibomian gland dropout characteristics in dry eye patients.MethodsThis cross-sectional study involved 172 dry eye patients with no history of conditions or factors that could confound dry eye disease (DED) and/or meibomian gland dropout. Participants underwent a comprehensive anterior eye assessment. The validated Athens Insomnia Scale (AIS) and Pittsburgh Sleep Quality Index (PSQI) were used to assess sleep quality. The measured outcomes were dry eye symptoms via the Ocular Surface Disease Index (OSDI), tear breakup time (TBUT), corneal fluorescein staining, meibomian gland function, and extent of meibomian gland dropout.ResultsOf the dry eye participants, 34.9% had severe meibomian gland dropout (SMD) and 41.3% of the subjects had poor sleep quality. Patients with poor sleep quality had greater Meibomian gland dropout while the sleep AIS and PSQI scores were significantly correlated with Meibomian gland dropout (r = 0.495, p < 0.001; r = 0.24, p = 0.002; respectively). SMD patients had worse scores on all components of the PSQI (all p < 0.001, corrected for age and sex). Use of sleep medication, poor habitual sleep efficiency, and sleep disturbance were particularly prevalent in SMD patients as compared to Non-severe meibomian gland dropout (NSMD) patients. Multivariate logistic regression analysis revealed that sleep quality was eventually associated with female gender (p = 0.042), OSDI (p = 0.004), TBUT (p = 0.036), and Meibomian gland dropout score (p < 0.001).ConclusionIt was found that greater meibomian gland dropout in poor sleep quality individuals is especially related to use of sleep medication, poor habitual sleep efficiency, and sleep disturbance. This finding suggests a need for long-term studies of anterior eye health in people with poor sleep quality.

Tenderness is an important characteristic of meat quality. Calpastatin and calpain play important roles in meat tenderization. However, it is not clear how phosphorylation affects the regulation of calpastatin on μ-calpain and, consequently, meat tenderness. Calpastatin with high and low phosphorylation levels were obtained in vitro corresponding to the treatments by protein kinase A (PKA) and alkaline phosphatase. Then, calpain was incubated with calpastatin with different phosphorylation levels, and the effect of calpastatin on calpain activity under different phosphorylation levels was analyzed. The results showed that PKA promoted the phosphorylation of calpastatin, and a high phosphorylation level was maintained during incubation. The degradation rate of μ-calpain in AP group was higher than that in the other groups, meaning there was lower inhibition of calpastatin on calpain activity. The degradation of calpastatin was lower and its structure was more stable after phosphorylation. One more serine 133 site of calpastatin was identified in PKA group compared with the other groups. Phosphorylation at serine 133 of calpastatin enhanced its inhibition on calpain activity by maintaining its structural stability, thus inhibiting the tenderization of meat.

In order to study the changes in invasive plant population characteristics under different nutrient addition treatments, this study used the native invasive species Pedicularis kansuensis, which is spreading in the Bayabulak alpine grassland, as the research object and conducted two consecutive years of field studies in which nutrients were added to plots. Changes in the P. kansuensis population’s invasive characteristics were monitored in 2020 and 2021 in four different nutrient-addition treatments, namely no-nutrients (control), low-nitrogen, high-nitrogen, and phosphorus treatments. The result showed that (1) nutrient addition had significant effects on P. kansuensis height and root/shoot ratio (p < 0.05); the time effect had significant effects on P. kansuensis height, coverage, abundance, aboveground biomass, and belowground biomass (p < 0.01), and the interaction between nutrient addition and time had a significant effect on P. kansuensis height (p < 0.01). (2) Nitrogen addition effectively inhibited the growth and the development of P. kansuensis, especially under high-nitrogen conditions in the second growing season, where the effect of height (2.50 cm), coverage (0.13%), richness (3 strains), aboveground biomass (0.21 g m−2), and belowground biomass (0.03 g m−2) was significant, with the P. kansuensis population almost disappearing by the end of the trial. (3) Phosphorus addition had no significant effect on the P. kansuensis population’s invasive characteristics. These results indicate that higher nitrogen addition could effectively slow the invasion of the P. kansuensis population, and the findings of this study could provide certain baseline data and scientific guidance for the effective control of the P. kansuensis invasion of the Bayabulak alpine grassland in the future as well as identify certain theoretical bases for the effect of nutrient addition on invasive plants overall.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death globally. Currently there is a lack of tumor-selective and efficacious therapies for hepatocellular carcinoma. β-Lapachone (ARQ761 in clinical form) selectively kill NADPH: quinone oxidoreductase 1 (NQO1)-overexpressing cancer cells. However, the effect of β-Lapachone on HCC is virtually unknown. In this study, we found that relatively high NQO1 and low catalase levels were observed in both clinical specimens collected from HCC patients and HCC tumors from the TCGA database. β-Lapachone treatment induced NQO1-selective killing of HCC cells and caused ROS formation and PARP1 hyperactivation, resulting in a significant decrease in NAD+ and ATP levels and a dramatic increase in double-strand break (DSB) lesions over time in vitro. Administration of β-Lapachone significantly inhibited tumor growth and prolonged survival in a mouse xenograft model in vivo. Our data suggest that NQO1 is an ideal potential biomarker, and relatively high NQO1:CAT ratios in HCC tumors but low ratios in normal tissues offer an optimal therapeutic window to use β-Lapachone. This study provides novel preclinical evidence for β-Lapachone as a new promising chemotherapeutic agent for use in NQO1-positive HCC patients.

Coronary stent placement inevitably causes mechanical damage to the endothelium, leading to endothelial denudation and in-stent restenosis (ISR). Re-endothelialization depends mainly on the migration of vascular endothelial cells (VECs) adjacent to the damaged intima, as well as the mobilization and adhesion of circulating VECs. To evaluate the combined contribution of VEC migration and adhesion to re-endothelialization under flow and the influence of stent, in vitro models were constructed to simulate various endothelial denudation scales (2 mm/5 mm/10 mm) and stent deployment depths (flat/groove/bulge). Our results showed that (1) in 2 mm flat/groove/bulge models, both VEC migration and adhesion combined completed the percentage of endothelial recovery about 27, 16, and 12%, and migration accounted for about 21, 15, and 7%, respectively. It was suggested that the flat and groove models were in favor of VEC migration. (2) With the augmentation of the injury scales (5 and 10 mm), the contribution of circulating VEC adhesion on endothelial repair increased. Taken together, endothelial restoration mainly depended on the migration of adjacent VECs when the injury scale was 2 mm. The adhered cells contributed to re-endothelialization in an injury scale-dependent way. This study is helpful to provide new enlightenment for surface modification of cardiovascular implants.

Background: Cancer-associated fibroblasts (CAFs) are of considerable importance in tumor progression by interacting with the tumor microenvironment. However, the hidden mechanism explaining how tumor cells interact with CAFs in the tumor mechanical microenvironment remains largely unknown. Methods: We highlighted exosomes as the mediator modulating the interaction between liver cancer cells and CAFs under mechanical conditions. The normal hepatic stellate cells LX2 were exposed to the medium or exosomes from the HepG2 cells with or without fluid shear stress subjection, and the CAFs activation markers were checked. To further explore the potential role of PI3K, which is active in liver fibrosis, the PI3K inhibitor was used. Results: The specific markers of CAFs, FAP, and α-SMA, increased in LX2 with subjection to the fluid shear stress-induced exosomes from HepG2 cells. In turn, the enriched IGF2 in the exosomes activated the IGF2-PI3K signaling pathway in LX2 cells. Conclusions: These findings reveal that fluid shear stress-induced liver cancer cells possess a stronger capacity to convert normal fibroblasts to CAFs than statically cultured liver cancer cells, and tumor-derived exosomes mediated the intercellular cross-talk between liver cancer cells and fibroblasts.

In this article we study the perturbed fractional Schrodinger equation involving oscillatory terms $$\displaylines{ (-\Delta)^{\alpha} u+u =Q(x)\Big(f(u)+\epsilon g(u)\Big), \quad x\in \mathbb{R}^N\cr u\geq 0, }$$ where $\alpha\in (0, 1)$ and $N> 2\alpha$, $(-\Delta)^{\alpha}$ stands for the fractional Laplacian, $Q: \mathbb{R}^N\to \mathbb{R}^N$ is a radial, positive potential, $f\in C([0, \infty), \mathbb{R})$ oscillates near the origin or at infinity and $g\in C([0, \infty), \mathbb{R})$ with $g(0)=0$. By using the variational method and the principle of symmetric criticality for non-smooth Szulkin-type functionals, we establish that: (1) the unperturbed problem, i.e. with $\epsilon=0$ has infinitely many solutions; (2) the number of distinct solutions becomes greater and greater when $| \epsilon|$ is smaller and smaller. Moreover, various properties of the solutions are also described in terms of the $L^{\infty}$- and $H^{\alpha}(\mathbb{R}^N)$-norms.

Lipogenesis in liver is highest in the postprandial state; insulin activates SREBP-1c, which transcriptionally activates genes involved in FA synthesis, whereas glucose activates carbohydrate-responsive element-binding protein (ChREBP), which activates both glycolysis and FA synthesis. Whether SREBP-1c and ChREBP act independently of one another is unknown. Here, we characterized mice with liver-specific deletion of ChREBP (L-Chrebp−/− mice). Hepatic ChREBP deficiency resulted in reduced mRNA levels of glycolytic and lipogenic enzymes, particularly in response to sucrose refeeding following fasting, a dietary regimen that elicits maximal lipogenesis. mRNA and protein levels of SREBP-1c, a master transcriptional regulator of lipogenesis, were also reduced in L-Chrebp−/− livers. Adeno-associated virus-mediated restoration of nuclear SREBP-1c in L-Chrebp−/− mice normalized expression of a subset of lipogenic genes, while not affecting glycolytic genes. Conversely, ChREBP overexpression alone failed to support expression of lipogenic genes in the livers of mice lacking active SREBPs as a result of Scap deficiency. Together, these data show that SREBP-1c and ChREBP are both required for coordinated induction of glycolytic and lipogenic mRNAs. Whereas SREBP-1c mediates insulin's induction of lipogenic genes, ChREBP mediates glucose's induction of both glycolytic and lipogenic genes. These overlapping, but distinct, actions ensure that the liver synthesizes FAs only when insulin and carbohydrates are both present.

The aim of this study was to investigate the effect of chilling rate (1.44, 22.2, and 32.4 °C/h) on the evolution of volatile and non-volatile compounds in raw lamb meat during refrigeration (1, 24, 72, and 120 h). Through orthogonal projection to latent structure-discriminant analysis, the calculation of odor activity values (OAV > 1) and taste activity values (TAV > 1) analysis, 1-octen-3-ol, (E, E)-2,4-decadienal, nonanal, hexanal, nona-3,5-dien-2-one, 2,3-octanedione, hexanoic acid, 1-nonen-4-ol, aspartate (Asp), Glutamic Acid (Glu), 5′-GMP, 5′-IMP, and 5′-AMP were regarded as differential flavor or taste compounds for raw meat undergone different chilling rates. With a rapid chilling rate at 24 h after slaughter, the contribution of 1-octen-3-ol decreased, but (E, E)-2,4-decadienal increased. Moreover, at 24 h post-mortem, the equivalent umami concentration of Asp, Glu, 5′-GMP, 5′-IMP and 5′-AMP in raw meat were significantly lower at a chilling rate of 1.44 °C/h than 32.4 °C/h (p < 0.05). Conclusively, under the rapid chilling rate, more fatty odor and umami compounds accumulated in 24 h aged meat.

The key aroma compounds in the pre- and postrigor roasted mutton were studied in this study. The results showed that 33 and 30 odorants were detected in the pre- and postrigor roasted mutton, respectively. Eight aroma compounds, including 3-methylbutanal, pentanal, hexanal, heptanal, octanal, nonanal, 1-octen-3-ol, and 2-pentylfuran, were confirmed as key odorants by aroma recombination and omission experiments. The aroma profiles of pre- and postrigor roasted mutton both presented great fatty, roasty, meaty, grassy, and sweet odors. Particularly, the concentrations of hexanal, heptanal, octanal, nonanal, 1-octen-3-ol, and 2-pentylfuran in postrigor roasted mutton were significantly higher (p < 0.05) than those in the prerigor roasted mutton. The postrigor back strap was more suitable for roasting than the prerigor back strap. The pre- and postrigor roasted mutton could be obviously discriminated based on the aroma compounds by orthogonal partial least squares discrimination analysis (OPLS-DA) and principal component analysis (PCA). Hexanal and 1-octen-3-ol might potential markers for the discrimination of the pre- and postrigor roasted mutton.

The visible and near-infrared spectroscopy (Vis/NIRS) models for sheep meat quality evaluation using only one type of meat cut are not suitable for other types. In this study, a novel portable Vis/NIRS system was used to simultaneously detect physicochemical properties (pH, color L*, a*, b*, cooking loss, and shear force) for different types of sheep meat cut, including silverside, back strap, oyster, fillet, thick flank, and tenderloin cuts. The results show that the predictive abilities for all parameters could be effectively improved by spectral preprocessing. The coefficient of determination (Rp2) and residual predictive deviation (RPD) of the optimal prediction models for pH, L*, a*, b*, cooking loss, and shear force were 0.79 and 3.50, 0.78 and 2.28, 0.68 and 2.46, 0.75 and 2.62, 0.77 and 2.19, and 0.83 and 2.81, respectively. The findings demonstrate that Vis/NIR spectroscopy is a useful tool for predicting the physicochemical properties of different types of meat cut.

This article concerns the existence of the least energy sign-changing solutions for the Schrodinger-Poisson system $$\displaylines{ -\Delta u+V(x)u+\lambda\phi(x)u=f(u),\quad \text{in } \mathbb{R}^3,\cr -\Delta\phi=u^2,\quad \text{in } \mathbb{R}^3. }$$ Because the so-called nonlocal term $\lambda\phi(x)u$ is involved in the system, the variational functional of the above system has totally different properties from the case of $\lambda=0$. By constraint variational method and quantitative deformation lemma, we prove that the above problem has one least energy sign-changing solution. Moreover, for any $\lambda>0$, we show that the energy of a sign-changing solution is strictly larger than twice of the ground state energy. Finally, we consider $\lambda$ as a parameter and study the convergence property of the least energy sign-changing solutions as $\lambda\searrow 0$.

Abstract Macrophage-dependent inflammatory response is considered a pivotal biological process that contributes to a host of diseases when aberrantly activated. The underlying epigenetic mechanism is not completely understood. We report here that MKL1 was both sufficient and necessary for p65-dependent pro-inflammatory transcriptional program in immortalized macrophages, in primary human and mouse macrophages, and in an animal model of systemic inflammation (endotoxic shock). Extensive chromatin immunoprecipitation (ChIP) profiling and ChIP-seq analyses revealed that MKL1 deficiency erased key histone modifications synonymous with transactivation on p65 target promoters. Specifically, MKL1 defined histone H3K4 trimethylation landscape for NF-κB dependent transcription. MKL1 recruited an H3K4 trimethyltransferase SET1 to the promoter regions of p65 target genes. There, our work has identified a novel modifier of p65-dependent pro-inflammatory transcription, which may serve as potential therapeutic targets in treating inflammation related diseases.

The excess of low-density lipoprotein (LDL) strongly promotes the accumulation of cholesterol on the arterial wall, which can easily lead to the atherosclerotic cardiovascular diseases (ACDs). It is a challenge on how to recognize and quantify the LDL with a simple and sensitive analytical technology. Herein, β-cyclodextrins (β-CDs), acting as molecular receptors, can bind with LDL to form stable inclusion complexes via the multiple interactions, including electrostatic, van der Waals forces, hydrogen bonding and hydrophobic interactions. With the combination of gold nanoparticles (Au NPs) and β-CDs, we developed an electrochemical sensor providing an excellent molecular recognition and sensing performance towards LDL detection. The LDL dynamic adsorption behavior on the surface of the β-CD-Au electrode was explored by electrochemical impedance spectroscopy (EIS), displaying that the electron-transfer resistance (Ret) values were proportional to the LDL (positively charged apolipoprotein B-100) concentrations. The β-CD-Au modified sensor exhibited a high selectivity and sensitivity (978 kΩ·µM−1) toward LDL, especially in ultra-low concentrations compared with the common interferers HDL and HSA. Due to its excellent molecular recognition performance, β-CD-Au can be used as a sensing material to monitor LDL in human blood for preventing ACDs in the future.

This study summarized the current development of wastewater recycling standards in China by analyzing published policies, existing national, industrial and local standards, as well as related activities in typical provinces. Meanwhile, further prospects for standardization in the area were also suggested in order to promote this industry.

In this article, we study the biharmonic elliptic problem with the secondnd Hessian $$\displaylines{ \Delta^2u =S_2(D^2u)+\lambda f(x) |u|^{p-1}u,\quad \text{in } \Omega \subset \mathbb{R}^3, \cr u =\frac{\partial u}{\partial n}=0, \quad \text{on } \partial\Omega, }$$ where $f(x)\in C(\bar{\Omega})$ is a sign-changing weight function. By using variational methods and some properties of the Nehari manifold, we prove that the biharmonic elliptic problem has at least two nontrivial solutions.

The Camellia oleifera oil industry is the economic mainstay in many high-poverty mountain regions of China, but the defatted seeds are currently discarded, leading to a waste of bioresources. In this work, a cost-effective technique was designed to isolate the flavonoid, saponins, and polysaccharides by ultrasonic-assisted acid-base alternative extraction. The activities of these compounds were evaluated by their DPPH and ABTS radical scavenging abilities in vitro and inflammatory inhibition in mice, and the economic efficiency was assessed. The optimal extraction conditions by response surface design were 1.6% HCl, water/seed ratio 16, extraction time 89 min, and ultrasonic power 310 W. The yields of the flavonoid, saponin, and polysaccharide were, respectively, 1.4 ± 0.2%, 6.7 ± 0.8%, and 22.5 ± 1.7%. The extracts could eliminate DPPH and ABTS radicals and alleviate inflammation with concentration dependence, and showed excellent capacity in the order of flavonoid ≥ saponin > polysaccharides. The residue after extraction was cellulose, with a yield of 63.0 ± 2.4%. The defatted seeds could produce a value of $11.35 per kilogram after production of the four valuable extracts, which would greatly increase the income in these high-poverty areas. This integrated extraction technique provides valuable recycling utilization of a typically discarded bioresource.

In this article, we consider three types of solutions in Orlicz spaces for the quasilinear elliptic problem $$ -\hbox{div}(a(|\nabla u|)\nabla u)=0. $$ By applying a comparison principle, we establish the relationships between viscosity supersolutions, weak supersolutions, and superharmonic functions.