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Abstract The motivational process of physical education (PE) in schools is significantly influenced by social factors, as demonstrated by a number of research based on self-determination theory (SDT). As a proximal factor affecting students’ learning motivation, the relatedness support of dancesport teachers plays a key role in promoting the learning motivation and sustainable development of dancesport students. This research aims to test the validity of the second-order model of perceived teacher relatedness support behavior (RSB) and investigate how students’ perceptions of their professional teachers directly or indirectly predicted their motivation to learn dancesport. To validate the relationship between the higher-order model and perceived teacher RSB among dancesport majors, this study used the structural equation modeling method for validation and 302 undergraduates majoring in dancesport participated in this investigation. The results showed that students’ perceived teacher relatedness support was positively related to intrinsic, integrated, identified, and introjected regulations during dancesport learning and negatively related to external regulation and amotivation. These findings revealed the importance of teacher RSB in dancesport. And this study provides a practical reference for improving the teaching effectiveness of dancesport in universities, promoting harmonious teacher-student relationships, and inspiring students’ learning motivation in dancesport. At the same time, it also lays a research foundation for the reform of dancesport teaching in universities and the system of dancesport talent training programs.

Abstract B-cell subsets in peripheral blood (PB) and tumor microenvironment (TME) were evaluated to determine myasthenia gravis (MG) severity in patients with thymoma-associated MG (TMG) and the distribution of B cells in type B TMG. The distribution of mature B cells, including Bm1–Bm5, CD19+ and CD20+ B cells and non-switched (NSMBCs) and switched (SMBCs) memory B cells, were determined in 79 patients with thymoma or TMG. Quantitative relationships between the T and TMG groups and the TMG-low and TMG-high subgroups were determined. NSMBCs and SMBCs were compared in TME and PB. Type B thymoma was more likely to develop into MG, with types B2 and B3 being especially associated with MG worsening. The percentage of CD19+ B cells in PB gradually increased, whereas the percentage of CD20+ B cells and the CD19/CD20 ratio were not altered. The (Bm2 + Bm2′)/(eBm5 + Bm5) index was significantly higher in the TMG-high than in thymoma group. The difference between SMBC/CD19+ and NSMBC/CD19+ B cell ratios was significantly lower in the thymoma than TMG group. NSMBCs assembled around tertiary lymphoid tissue in thymomas of patients with TMG. Few NSMBCs were observed in patients with thymoma alone, with these cells being diffusely distributed. MG severity in patients with TMG can be determined by measuring CD19+ B cells and Bm1-Bm5 in PB. The CD19/CD20 ratio is a marker of disease severity in TMG patients. Differences between NSMBCs and SMBCs in PB and TME of thymomas can synergistically determine MG severity in patients with TMG.

Abstract Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ADTC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Oxidative stress is recognized as a prominent factor contributing to follicular atresia and ovarian aging, which leads to decreased laying performance in hens. Reducing oxidative stress can improve ovarian function and prolong the laying period in poultry. This study investigates the impact of Pterostilbene (PTS), a natural antioxidant, on ovarian oxidative stress in low-laying chickens. Thirty-six Hy-Line White laying chickens were evenly divided into four groups and fed diets containing varying doses of PTS for 15 consecutive days. The results showed that dietary supplementation with PTS significantly increased the laying rate, with the most effective group exhibiting a remarkable 42.7% increase. Furthermore, PTS significantly enhanced the antioxidant capacity of aging laying hens, as evidenced by increased levels of glutathione, glutathione peroxidase, superoxide dismutase, catalase, and total antioxidant capacity in the ovaries, livers, and serum. Subsequent experiments revealed decreased expressions of Bax, Caspase-3, and γ-H2AX, along with an increased expression of BCL-2 in the ovaries and livers of laying hens. PTS supplementation also positively affects fat metabolism by reducing abdominal fat accumulation and promoting fat transfer from the liver to the ovary. To elucidate the mechanism underlying the effects of PTS on ovarian function, a series of in vitro experiments were conducted. These in vitro experiments revealed that PTS pretreatment restored the antioxidant capacity of D-galactose-induced small white follicles by upregulating SIRT1/Nrf2 expression. This protective effect was inhibited by EX-527, a specific inhibitor of SIRT1. These findings suggest that the natural antioxidant PTS has the potential to regulate cell apoptosis and fat metabolism in laying chickens by ameliorating oxidative stress, thereby enhancing laying performance.

Abstract Background The objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40–45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC. Methods The response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1β and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8+ T cells were performed using flow cytometry. Results Tumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8+ T cells. Experiments with both clinical samples and mice indicated that infiltration of IL-1β-driven MDSCs and inactivation of CD8+ T cells contribute to anti-PD-1 resistance in MSI-H/dMMR CRC. Conclusions CD8+ T cells and IL-1β were identified as the cell type and gene, respectively, with the highest correlation with anti-PD-1 resistance. Infiltration of IL-1β-driven MDSCs was a significant factor in anti-PD-1 resistance in CRC. IL-1β antagonists are expected to be developed as a new treatment for anti-PD-1 inhibitor resistance.

Aging is not only a key internal cause of age-related diseases in humans but also poses a threat to the productivity of farm animals with longer breeding cycles, such as laying chickens. Various measures were taken to prolong the laying period by reducing oxidative stress to improve poultry ovarian functions. Within the mitochondria, SIRT3, a member of the Sirtuin family, plays an important role in post-translational modifications and the regulation of protein activities involved in energy metabolism and oxidative response. This study aimed to investigate the alleviating effect of a bioactive lignan Honokiol (HKL) on oxidative stress in aging chicken ovaries in order to retard decline in egg production. The results showed that HKL treatment restored the abnormal balance between cell proliferation and apoptosis, and it enhanced the antioxidant capacity of the H2O2-induced small white follicles (SWFs) by activating the SIRT3/AMPK pathway. Moreover, HKL significantly increased total egg production, the number of yellow follicles, and the mRNA expression of yolk synthesis and deposition-related genes, serum estrogen, and antioxidant levels. These findings suggest that HKL holds promise in enhancing the egg productivity of aging laying chickens by promoting yolk deposition and reducing ovarian oxidative stress.

The cold chain supply chain of e-commerce has the characteristics of long chain, dispersed production, heterogeneous information sources, etc., which is easy to cause the upstream and downstream information of the supply chain to be broken and opaque. Traditional traceability data is stored in each node enterprise, and there are problems such as low cooperation trust and poor authenticity in the upstream and downstream data transmission process of the supply chain, resulting in consumers' trust crisis on the authenticity of traceability information. Blockchain traceability system through the establishment of multi-party participation, joint maintenance of distributed database, and the use of cryptography and consensus mechanism to establish trust relationships, with data can not be tampered with, sharing of high credibility. On the basis of stochastic Petri net theory, this study constructed a blockchain e-commerce cold chain traceability model centering on the actual application of blockchain technology in logistics traceability to improve the reliability and validity of e-commerce cold chain traceability. Correlation matrix and invariants were used to analyze the validity of the model, and an isomorphic Markov chain was constructed to analyze the effectiveness evolution of the model. This study aims to deepen the understanding of the cold chain traceability system of blockchain e-commerce from the three aspects of the best optimization link, the best synergism scale, and the adaptive ability of the system to provide reference for the improvement of cold chain traceability ability by blockchain technology.

For maintaining an effective fire resistance for in-wall service penetrations (e.g. pipe and cable systems) under fire conditions, firestop seals are used to be applied to thoroughly fill the installation gap between perimeter of penetrations and inner surface of wall/floor openings. Consistent with other building elements installed for fire resistive purposes, through-penetration firestopping systems are not specifically designed with any earthquake-damage considerations. However, evidence from global earthquakes have revealed a varying extent of damage could occur around where the firestopping material sits, caused by differential movements between penetrations and supporting assemblies. If the associated damage is not identified and remedied, the building is left vulnerable to fire attack in the rest of its service life. This issue is particularly important for seismically active countries, such as New Zealand, Japan and the USA. As part of new research to establish interdependencies between the performance of firestopping systems under earthquakes and in fires, this paper conducts a review of the literature on identifying the deficiencies in current knowledge of through-penetration firestopping systems as well as suggesting specific research needs to assess the quake-affected residual fire resistance of these systems.

Plain Language Summary Clinical trials in rheumatoid arthritis recruit too few patients from diverse ethnic backgrounds to be able to identify differences in treatment outcomes. In adults with moderate-to-severe active rheumatoid arthritis who do not tolerate or have responded poorly to other advanced treatments, the Janus kinase inhibitor filgotinib can be used alone or in combination with the immunosuppressant methotrexate. Using data from 4695 patients with rheumatoid arthritis from five previous clinical trials and two ongoing trial extensions, this paper examined the efficacy and safety of filgotinib in patients with rheumatoid arthritis across geographic locations worldwide. Patients were grouped by region: North America, South and Central America, Western Europe, Eastern Europe, East Asia, South and Southeast Asia, and Other (South Africa, New Zealand, Australia, and Israel). The efficacy of filgotinib in treating the symptoms of rheumatoid arthritis was assessed using several measures of disease activity, with changes in patient quality of life determined using a health assessment questionnaire. Safety data were reported as the rates of side effects experienced by patients. Across different geographic regions, no major differences in filgotinib treatment response were observed. Rheumatoid arthritis disease activity levels were consistently lower in patients receiving filgotinib than in patients receiving placebo. Across the regions examined, quality-of-life scores also improved to a greater degree in patients receiving filgotinib compared with placebo. The rates of side effects, including infections, were similar irrespective of region. The number of deaths was low, mostly resulting from cardiovascular events, infections, and malignancies. This study demonstrates that the efficacy and safety of filgotinib are consistent in patients with rheumatoid arthritis from a broad range of geographic regions and ethnic backgrounds.

With the increase in the age of laying chickens, the aging of follicles is accelerated, and the reproductive ability is decreased. Increased oxidative stress and mitochondrial malfunction are indispensable causes of ovarian aging. In this study, the physiological condition of prehierarchical small white follicles (SWFs) was compared between D280 high-producing chickens and D580 aging chickens, and the effect of a plant-derived flavonoid nobiletin (Nob), a natural antioxidant, on senescence of SWFs granulosa cells (SWF-GCs) was investigated. The results showed that Nob treatment activated cell autophagy by activating the AMP-activated protein kinase (AMPK) and Sirtuin-1 (SIRT1) pathways in D-galactose (D-gal)-generated senescent SWF-GCs, restoring the expression of proliferation-related mRNAs and proteins. In addition, the expression of inflammation-related protein NF-κB was significantly enhanced in aging GCs that were induced by D-gal. Nob supplementation significantly increased the antioxidant capacity and decreased the expression of several genes associated with cell apoptosis. Furthermore, Nob promoted activation of PINK1 and Parkin pathways for mitophagy and alleviated mitochondrial edema. Either the AMPK inhibitor dorsomorphin (Compound C) or SIRT1 inhibitor selisistat (EX-527) attenuated the effect of Nob on mitophagy. The protective effect of Nob on natural aging, GC proliferation, and elimination of the beneficial impact on energy regulation of naturally aging ovaries was diminished by inhibition of Nob-mediated autophagy. These data suggest that Nob treatment increases the expression of mitophagy-related proteins (PINK1 and Parkin) via the AMPK/SIRT1 pathways to prevent ovarian aging in the laying chickens.

Megacity regions where human activities are intensive are key areas for CVD prevention and control in China. Optimizing land-use patterns has been widely recognized as an important public health intervention. Ecological space, agricultural space, and construction space are three basic management objects in China’s new land-use management system. Given that most existing studies focused on a single type of land use, this study treats them as a whole and not only explores the impact of each type, but also systematically investigates the effects of the interactions between any two types of land use and the whole land-use pattern. Specifically, this study first constructs a hierarchical index system, then uses spatial error models (SEM) to explore the global associations between each index and age-standardized CVD mortality rates (ASMRs) and uses the multiple geographical weighted regression model (MGWR) to explore the spatial heterogeneity of factor effects. The possible association between land-use patterns and CVD mortality is then explored, and recommendations for policy formulation are provided. The analysis results show that the overall pattern of moderately decentralized and organically combined land use can control CVD mortality to a certain extent, but the specific influence mechanisms show significant differences according to different land-use types, relationships, and location conditions. First, in terms of single-type land-use distribution, the concentration of ecological space has positive health benefits, while a too high concentration of agricultural space has negative effects. Second, the combination of different types of land use has a significant association with CVD, in which the mixed layout of ecological and agricultural space helps to suppress CVD, while ecological and construction space need to be appropriately regularized and should not be too interspersed. Third, the same index may have different effects in different regions, suggesting that policy makers need to tailor their policies to local conditions.

Abstract Background To investigate the expression and biological functions of mitogen‐induced gene 6 (Mig‐6) in esophageal squamous cell carcinoma (ESCC). Methods The expression of Mig‐6 in ESCC tissues and normal esophageal epithelial tissues were measured by immunohistochemistry (IHC) assay. MTT test was applied to detect the proliferative ability of ESCC cells after Mig‐6 was upregulated by transfection. A fluid cytology assay was used to detect apoptosis of ESCC cells. Agilent whole human genome oligo microarray was used to screen different expressed genes and the possible signaling pathways which might be involved. Results The expression of Mig‐6 protein was lower in ESCC tissues compared to normal esophageal epithelial tissues. Mig‐6 could restrain the ESCC cell growth and induce cell apoptosis. PPAR, CAMs and MAPK signaling pathways might be involved. Conclusions Mig‐6 might be a new tumor suppressor gene and a possible target for the specific therapy of ESCC.

Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. Dexmedetomidine (DEX) has shown certain neuroprotective roles in ICH. Nevertheless, the details concerning the underlying molecular mechanism of DEX’s protective effects still need further elucidation. Herein, a model of ICH was established. The rats were randomly divided into the sham group, the ICH group, and the ICH + DEX group. Neurological outcomes, neuronal injury, and apoptosis were evaluated. Brain water content, Evans blue extravasation, and the expression of tight junction-associated proteins were also detected to assess the blood-brain barrier (BBB) integrity. Subsequently, the microglia/macrophage polarization state and inflammatory cytokine levels were observed. To further explore the underlying mechanism, NF-κB signaling pathway-associated proteins were detected. The results showed that DEX exerted neuroprotective effects against ICH-induced neurological deficits. DEX significantly increased the numbers of the surviving neurons and ameliorated neuronal cell loss and apoptosis in ICH. The rats that received the DEX displayed a lower level of brain water content and EB extravasation, moreover, ZO-1, occludin, and claudin-5 were markedly increased by DEX. Additionally, DEX facilitated M2 microglia/macrophage polarization, the M1-associated markers were reduced by DEX, while the M2-associated identification significantly increased. We found that DEX dramatically diminished pro-inflammatory cytokines expression, simultaneously promoting anti-inflammatory cytokines expression. DEX inhibited nuclear translocation of NF-κB in ICH rats. Our data suggest that DEX post-conditioning protects BBB integrity by modulating microglia/macrophage polarization via inhibiting the NF-κB signaling pathway in ICH.

Agricultural carbon emissions, which are the second largest source of greenhouse gas emissions in China, not only place great pressure on emission reduction but also seriously affect food security and sustainable development of agriculture. As farmers are the direct users of cultivated land and the main adopters of agricultural technology, their adoption behavior of low-carbon agricultural technology directly determines its promotion and subsequent emissions reduction. It is of great theoretical and practical significance to analyze farmers’ adoption behavior of low-carbon agricultural technology and their influencing factors. Based on social embeddedness theory and the survey data of 688 farmers in Jiangsu Province, this study applied a logistic model to analyze the impact of government support, farmers’ cognition, social capital, personal characteristics, and family characteristics on farmers’ adoption behavior of low-carbon agricultural technology. The results showed that (1) only 58.72% of farmers have adopted such a technology, which needs to be further improved; (2) government support and farmers’ cognition had significantly positive influences on farmers’ adoption behavior; (3) social capital is an important factor affecting farmers’ adoption decisions, where social trust, networks, and norms play a significant role in promoting the adoption of low-carbon agricultural technology; and (4) party membership and household-contracted farmland area also had positive influences on farmers’ adoption behavior of low-carbon technology. Therefore, to continue developing low-carbon agriculture, it is recommended to further strengthen government support, raise the price of low-carbon agricultural products, strengthen environmental supervision, and build a social embedded environment according to local conditions, and further improve farmers’ social trust, enrich social networks, improve social norms, and give full play to the guiding and exemplary role of social capital. Additionally, it is also recommended to reinforce education and training to raise farmers’ awareness regarding low-carbon agricultural technology, thereby guiding them to actively adopt these technologies.

Abstract Background The effects of thymectomy on late-onset non-thymomatous myasthenia gravis (NTMG) remain controversial. The objective of this study was to conduct a systematic review in order to answer two questions pertinent to late-onset NTMG: (1) do patients with late-onset NTMG experience the same effects from thymectomy as their early-onset counterparts? (2) Compared with conservative treatment, does thymectomy have any benefits for late-onset NTMG patients? Methods We searched the PubMed, EMBASE, and Cochrane Library databases for studies published from January 1, 1950 to March 10, 2021. Outcomes were measured via clinical stable remission/pharmacological remission (CSR/PR) and improvement rates. We used Stata software to analyze the data. Results We ultimately included a total of 12 observational articles representing the best evidence answering the questions of our study objective. Of these, nine studies, which included 896 patients overall (766 early-onset and 230 late-onset), compared postoperative outcomes between early- and late-onset NTMG. The remaining three articles, which included 216 patients (75 in the thymectomy group and 141 in the conservative-treatment group), compared thymectomy with conservative treatment for late-onset NTMG. The early- versus late-onset NTMG studies demonstrated that patients in the former category were 1.95× likelier than their late-onset counterparts to achieve clinical remission (odds ratio [OR] 1.95; 95% confidence interval [CI] 1.39–2.73; I 2 = 0%). No difference was seen in improvement or remission + improvement rates between these two groups. When comparing thymectomy with conservative treatments in late-onset NTMG patients, neither did we observe any difference in CSR/PR. Conclusion We found that late-onset NTMG patients had a lower chance of achieving CSR after thymectomy than early-onset patients. Thymectomy in late-onset NTMG also yielded no benefit to CSR or PR compared with conservative treatments. In late-onset NTMG patients, thymectomy should therefore be performed with caution, and the appropriate cutoff between early- and late-onset MG should be further explored in order to tailor and execute the proper therapeutic strategies.

Traumatic brain injury (TBI) is a complex injury with a multi-faceted recovery process. Long non-coding RNAs (lncRNAs) are demonstrated to be involved in central nervous system (CNS) disorders. However, the roles of lncRNAs in long-term neurological deficits post-TBI are poorly understood. The present study depicted the microarray’s lncRNA and messenger RNA (mRNA) profiles at 14 days in TBI mice hippocampi. LncRNA and mRNA microarray was used to identify differentially expressed genes. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to validate the microarray results. Bioinformatics analysis [including Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, lncRNA-mRNA co-expression network, and lncRNA-miRNA-mRNA network] were applied to explore the underlying mechanism. A total of 264 differentially expressed lncRNAs and 232 expressed mRNAs were identified (fold change > 1.5 and P-value < 0.05). Altered genes were enriched in inflammation, immune response, blood–brain barrier, glutamatergic neurological effects, and neuroactive ligand-receptor, which may be associated with TBI-induced pathophysiologic changes in the long-term neurological deficits. The lncRNAs-mRNAs co-expression network was generated for 74 lncRNA-mRNA pairs, most of which are positive correlations. The lncRNA-miRNA-mRNA interaction network included 12 lncRNAs, 59 miRNAs, and 25 mRNAs. Numerous significantly altered lncRNAs and mRNAs in mice hippocampi were enriched in inflammation and immune response. Furthermore, these dysregulated lncRNAs and mRNAs may be promising therapeutic targets to overcome obstacles in long-term recovery following TBI.

Background:Depressive disorder is the leading cause of disability and suicidality worldwide. Metabolites are considered indicators and regulators of depression. However, the pathophysiology of the prefrontal cortex (PFC) in depression remains unclear.MethodsA chronic unpredictable mild stress (CUMS) model and a maturation rodent model of depression was used to investigate metabolic changes in the PFC. Eighteen male Sprague-Dawley rats were randomly divided into CUMS and control groups. The sucrose preference test (SPT) and forced swimming test (FST) were employed to evaluate and record depression-associated behaviors and changes in body weight (BW). High-performance liquid chromatography–tandem mass spectrometry was applied to test metabolites in rat PFC. Furthermore, principal component analysis and orthogonal partial least-squares discriminant analysis were employed to identify differentially abundant metabolites. Metabolic pathways were analyzed using MetaboAnalyst. Finally, a metabolite-protein interaction network was established to illustrate the function of differential metabolites.ResultsSPT and FST results confirmed successful establishment of the CUMS-induced depression-like behavior model in rats. Five metabolites, including 1-methylnicotinamide, 3-methylhistidine, acetylcholine, glycerophospho-N-palmitoyl ethanolamine, α-D-mannose 1-phosphate, were identified as potential biomarkers of depression. Four pathways changed in the CUMS group. Metabolite-protein interaction analysis revealed that 10 pathways play roles in the metabolism of depression.ConclusionFive potential biomarkers were identified in the PFC and metabolite-protein interactions associated with metabolic pathophysiological processes were explored using the CUMS model. The results of this study will assist physicians and scientists in discovering potential diagnostic markers and novel therapeutic targets for depression.

Background KIT proto‐oncogene ligand (KITLG) is a pleiotropic factor which is found in diverse cancers and is involved in cell proliferation, differentiation, and survival. However, the value of KITLG in thymoma remains unclear. Methods A total of 121 thymoma samples from The Cancer Genome Atlas Thymoma (TCGA‐THYM) dataset were used to analyze KITLG related genome‐wide expression profiles, and microRNA profiles and methylation alterations and a GEO dataset‐GSE29695, including 37 samples was used as verification. For cell‐based studies, specific small interfering RNA targeting KITLG or a KITLG overexpression vector were used to clarify the changes of the MAPK pathway in an AB thymoma cell line Thy0517. Results Both datasets showed that high expression of KITLG was significantly associated with type A and AB thymoma. Through multiomic analysis of the TCGA‐THYM, it was found that with the high expression of KITLG, there were 220 upregulated and 72 downregulated genes at the mRNA level, 79 positive and 78 negative miRNAs, 28 hypermethylation and 163 hypomethylation regions. In the thymoma cell line Thy0517, it was found that the expression of GRB2 and the phosphorylation levels of BRAF, MEK1/2, and ERK1/2 in the MAPK pathway were positively correlated with the change in KITLG. Conclusions High expression of KITLG is a new hallmark of WHO type A and AB thymomas in which it might play a critical role through the activation of the MAPK signaling pathway. Additionally, it is hoped that KITLG will become a potential target for the diagnosis of type A and AB thymoma through further research in the future. Key points Significant findings of the study KIT proto‐oncogene ligand (KITLG) is a new hallmark of type A and AB thymomas which induce a series of aberrant alteration of mRNA, miRNA and DNA methylation. The expression of KITLG is significantly higher in type A and AB than other subtypes of thymoma. What this study adds KITLG activated the MAPK signaling pathway to promote type A and AB thymoma which might be a potential diagnostic biomarker or target.

Solitary fibrous tumor (SFT) is a rare clinical tumor, defined as a mesenchymal tumor of fibroblastic origin. A classic SFT is benign in most cases, but its clinical behavior is unpredictable. Lately, molecular analyses has discovered that almost all SFTs harbor an NAB2‐STAT6 fusion gene, which is considered specific to this tumor type. Recent studies have suggested that nuclear STAT6 immunoreactivity is a highly sensitive and specific marker of SFTs and can be helpful when diagnosis is inconclusive by conventional methods. We herein report the case of a rare malignant solitary fibrous tumor occurring in the mediastinal pleura. An 82‐year‐old Chinese man with intermittent breathlessness was referred to our hospital. Chest CT showed a significantly enhanced irregular huge soft tissue mass in the anterior mediastinal area. After radical resection, the immunohistochemistry staining results of the sample showed that STAT6 was negative. The final diagnosis was confirmed by qualitative endpoint reverse transcriptase‐polymerase chain reaction technique, showing positive NAB2ex4‐STAT6ex2 fusion.

BackgroundTransforaminal percutaneous endoscopic lumbar discectomy (PELD) is a widely used basic technique for lumbar disc herniation (LDH) with advantages including causing less trauma and fast recovery. The secure, efficient, and rapid enlargement of the intervertebral foramen is a key step in PELD procedures. However, the conventional multi-step trephine system for foraminoplasty involves complicated surgical procedures. In this study, we reported an improved one-step foraminoplasty via a large trephine with simplified surgical procedures, reduced radiation exposure, and shortened operative time.Methods70 LDH patients who underwent PELD were retrospectively reviewed in this study. The conventional multi-step trephine system was used for foraminoplasty in 35 patients in the multi-step (MS) group, and the single large trephine was used in the other 35 patients in the one-step (OS) group. Indicators including the operative time, the time to establish the working cannula, intraoperative fluoroscopy times, the radiation dose, and postoperative complications were compared between the MS and OS group.ResultsThe operative time and the time to establish the working cannula in the OS group was significantly shorter than that in the MS group (P < 0.01); intraoperative fluoroscopy times and the radiation dose in the OS group were significantly smaller than those in the MS group (P < 0.01). There was no statistical difference in the incidence of postoperative complications between the two groups (P > 0.05). The postoperative VAS scores and ODI scores (2 days and 3 months after the surgery) were significantly lower than the preoperative scores in both groups (P < 0.01), and there was no statistical difference in VAS scores or ODI scores between the two groups at the same time points (P > 0.05).ConclusionsThe one-step foraminoplasty via a single large trephine is an optimized technique evolving from the conventional multi-step foraminoplasty, showing significant superiority in simplified operation, shorted operative time, and reduced radiation exposure.

Background: Chaihu-Shugan-San is a classical prescription to treat depression. According to the traditional Chinese medicine (TCM) principle, the 2 decomposed recipes in Chaihu-Shugan-San exert synergistic effects, including Shu Gan (stagnated Gan-Qi dispersion) and Rou Gan (Gan nourishment to alleviate pain). However, the specific mechanism of Chaihu-Shugan-San on depression and its compatibility rule remain to be explored.Objective: We aimed to explore the anti-depression mechanisms and analyze the advantage of TCM compatibility of Chaihu-Shugan-San.Methods: The chronic unpredictable mild stress (CUMS) rat model was established. Antidepressant effects were evaluated by sucrose preference test (SPT), and forced swimming test (FST). Tandem Mass Tag (TMT)-based quantitative proteomics of the hippocampus was used to obtain differentially expressed proteins (DEPs). Bioinformatics analysis including Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) networks was utilized to study the DEPs connections. At last, the achieved key targets were verified by western blotting.Results: Chaihu-Shugan-San increased weight gain and food intake, as well as exhibited better therapeutic effects including enhanced sucrose preference and extended immobility time when compared with its decomposed recipes. Proteomics showed Chaihu-Shugan-San, Shu Gan, and Rou Gan regulated 110, 12, and 407 DEPs, respectively. Compared with Shu Gan or Rou Gan alone, the expression of 22 proteins was additionally changed by Chaihu-Shugan-San treatment, whereas the expression of 323 proteins whose expression was changed by Shu Gan or Rou Gan alone were not changed by Chaihu-Shugan-San treatment. Bioinformatics analysis demonstrated that Chaihu-Shugan-San affected neurotransmitter’s release and transmission cycle (e.g., γ-aminobutyric acid (GABA), glutamate, serotonin, norepinephrine, dopamine, and acetylcholine). GABA release pathway is also targeted by the 22 DEPs. Unexpectedly, only 2 pathways were enriched by the 323 DEPs: Metabolism and Cellular responses to external stimuli. Lastly, the expression of Gad2, Vamp2, and Pde2a was verified by western blotting.Conclusions: Chaihu-Shugan-San treats depression via multiple targets and pathways, which may include regulations of 110 DEPs and some neurotransmitter’s transmission cycle. Compared with Shu Gan and Rou Gan, the 22 Chaihu-Shugan-San advanced proteins and the affected GABA pathway may be the advantages of Chaihu-Shugan-San compatibility. This research offers data and theory support for the clinical application of Chaihu-Shugan-San.

BackgroundSevere traumatic brain injury (TBI) has become a global health problem and causes a vast worldwide societal burden. However, distinct mechanisms between acute and subacute stages have not been systemically revealed. The present study aimed to identify differentially expressed proteins in severe TBI from the acute to subacute phase.MethodsSixty Sprague Dawley (SD) rats were randomly divided into sham surgery and model groups. The severe TBI models were induced by the controlled cortical impact (CCI) method. We evaluated the neurological deficits through the modified neurological severity score (NSS). Meanwhile, H&E staining and immunofluorescence were performed to assess the injured brain tissues. The protein expressions of the hippocampus on the wounded side of CCI groups and the same side of Sham groups were analyzed by the tandem mass tag-based (TMT) quantitative proteomics on the third and fourteenth days. Then, using the gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and protein–protein interaction (PPI), the shared and stage-specific differentially expressed proteins (DEPs) were screened, analyzed, and visualized. Eventually, target proteins were further verified by Western blotting (WB).ResultsIn the severe TBI, the neurological deficits always exist from the acute stage to the subacute stage, and brain parenchyma was dramatically impaired in either period. Of the significant DEPs identified, 312 were unique to the acute phase, 76 were specific to the subacute phase, and 63 were shared in both. Of the 375 DEPs between Sham-a and CCI-a, 240 and 135 proteins were up-regulated and down-regulated, respectively. Of 139 DEPs, 84 proteins were upregulated, and 55 were downregulated in the Sham-s and CCI-s. Bioinformatics analysis revealed that the differential pathophysiology across both stages. One of the most critical shared pathways is the complement and coagulation cascades. Notably, three pathways associated with gastric acid secretion, insulin secretion, and thyroid hormone synthesis were only enriched in the acute phase. Amyotrophic lateral sclerosis (ALS) was significantly enriched in the subacute stage. WB experiments confirmed the reliability of the TMT quantitative proteomics results.ConclusionOur findings highlight the same and different pathological processes in the acute and subacute phases of severe TBI at the proteomic level. The results of potential protein biomarkers might facilitate the design of novel strategies to treat TBI.

As a predominant hormone in the reproductive axis, follicle-stimulating hormone (FSH) is known as the primary surviving factor for follicular growth. In this study, the alleviating effect of FSH on aging chicken granulosa cells (GCs) was investigated. Results showed that FSH activated mitophagy and relieved mitochondrial edema in D-gal-induced senescent GCs, which was evidenced by an increased number of mitophagosomes as well as increased mitochondria-light chain 3 (LC3) colocalization. Mitophagy activation was accompanied by the activation of the AMP-activated protein kinase (AMPK) signaling pathway. Furthermore, upregulated glycophagy was demonstrated by an increased interaction of starch-binding domain protein 1 (STBD1) with GABA type A receptor-associated protein-like 1 (GABARAPL1) in D-gal-induced senescent GCs. FSH treatment further promoted glycophagy, accompanied by PI3K/AKT activation. PI3K inhibitor LY294002 and AKT inhibitor GSK690693 attenuated the effect of FSH on glycophagy and glycolysis. The inhibition of FSH-mediated autophagy attenuated the protective effect of FSH on naturally aging GC proliferation and glycolysis. The simultaneous blockage of PI3K/AKT and AMPK signaling also abolished the positive effect of FSH on naturally senescent ovarian energy regulation. These data reveal that FSH prevents chicken ovarian aging by modulating glycophagy- and mitophagy-based energy metabolism through the PI3K/AKT and AMPK pathways.

Objective This analysis evaluated efficacy and safety of filgotinib, a Janus-associated kinase 1-preferential inhibitor, in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) with multiple poor prognostic factors (PPFs).Methods This was a post hoc analysis of the phase III, randomised, double-blind, active-controlled, FINCH 3 study (clinicaltrials.gov NCT02886728). Patients received once-daily oral filgotinib 200 or 100 mg plus once-weekly oral MTX ≤20 mg (FIL200 + MTX and FIL100 + MTX), filgotinib 200 mg monotherapy (FIL200), or oral MTX monotherapy (MTX-mono) for up to 52 weeks. PPFs investigated were seropositivity for rheumatoid factor or anticyclic citrullinated peptide antibodies, high-sensitivity C reactive protein (CRP) ≥4 mg/L, Disease Activity Score in 28 joints with CRP (DAS28(CRP)) >5.1, and presence of erosions. Filgotinib efficacy and safety in patients with all four PPFs at baseline were explored versus MTX-mono within this subgroup and compared informally with the overall population.Results Of 1249 patients in FINCH 3, 510 (40.8%) had all PPFs. Efficacy of FIL200 + MTX among these patients was comparable to the overall population, with higher rates of 20%/50%/70% improvement from baseline by American College of Rheumatology criteria, DAS28(CRP)

Infrared ocean ships detection still faces great challenges due to the low signal-to-noise ratio and low spatial resolution resulting in a severe lack of texture details for small infrared targets, as well as the distribution of the extremely multiscale ships. In this paper, we propose a CAA-YOLO to alleviate the problems. In this study, to highlight and preserve features of small targets, we apply a high-resolution feature layer (P2) to better use shallow details and the location information. In order to suppress the shallow noise of the P2 layer and further enhance the feature extraction capability, we introduce a TA module into the backbone. Moreover, we design a new feature fusion method to capture the long-range contextual information of small targets and propose a combined attention mechanism to enhance the ability of the feature fusion while suppressing the noise interference caused by the shallow feature layers. We conduct a detailed study of the algorithm based on a marine infrared dataset to verify the effectiveness of our algorithm, in which the AP and AR of small targets increase by 5.63% and 9.01%, respectively, and the mAP increases by 3.4% compared to that of YOLOv5.

Xuefu Zhuyu decoction (XFZYD) performs multiple functions for traumatic brain injury (TBI) treatment. However, its clinical application is limited by the incomplete exploration of targets and inadequate discussion of mechanisms. We aimed to investigate the metabolic alterations of XFZYD in acute and chronic stages of TBI. Sprague-Dawley rats were randomly divided into the sham, controlled cortical impact (CCI) and XFZYD group. Behavioral and histopathological tests were used to evaluate the neuroprotective effects. Coagulation assays were performed to assess safety. Moreover, we analyzed the metabolomic profiling of hippocampal samples with different time intervals after CCI by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Differential metabolites were screened by multivariate data analysis. To further uncover the association between candidate metabolites and biological interaction networks, we applied bioinformatics analysis using MetaboAnalyst 4.0, STITCH 5.0 and TCMSP. The potential mechanism was verified by ELISA and Western blot. XFZYD ameliorated neurological deficiencies post-CCI without impairing blood coagulation in the rat’s model. Seventeen and fourteen metabolites were filtered on d 3 and 21, respectively. Eleven of potential metabolites were common at these time points, involving two significant pathways (arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis). Gamma-aminobutyric acid (GABA) and the related pathways were specifically affected by XFZYD at the acute phase of TBI, while biosynthesis of amino acids was the major pathway influenced at the chronic phase. This study provides broad insights into the therapeutic effects of XFZYD in treating TBI through the whole phases.

Permafrost has been thawing faster due to climate change which would release greenhouse gases, change the hydrological regimes, affect buildings above, and so on. It is necessary to study the thawing process of frozen soil. A water-heat coupling model for frozen soil thawing is established on Darcy’s law and Heat Transfer in Porous Media interfaces in Comsol Multiphysics 5.5. Three curves of total liquid water volume, minimum temperature, and total heat flux in the thawing process are obtained from a numerical simulation. The distributions of liquid water, temperature, and pressure based on time are simulated too. The liquid water distribution is consistent with the total liquid water volume curve. The temperature distribution is confirmed by the minimum temperature and total heat flux curve. The pressure distribution represents ice in the frozen soil that generates negative pressure during the melting process. The numerical simulation research in this article deepens the understanding of the internal evolution in the process of frozen soil thawing and has a certain reference value for subsequent experimental research and related applications.

The β-carbolines in our diet, mainly including harman and norharman, are a group of biologically active, naturally occurring plant-derived alkaloids. Fragrant sesame seed oil is one of the most popular flavor edible oils in China. Considering that sesame seeds are roasted at 200–240 °C during the processing of flavor sesame seed oils, it is meaningful to investigate the levels of β-carboline compounds in various sesame seed oils. In this work, the levels of β-carbolines (harman and norharman) in different types of sesame seed oils in China (e.g., pressed fragrant sesame oil, ground fragrant sesame oil) have been determined systematically. The results showed that the levels of total β-carbolines in pressed fragrant sesame oils (700.5~2423.2 μg/kg) were higher than that in ground fragrant sesame oils (660.4~1171.7 μg/kg). Roasting sesame seeds at high temperatures (200–240 °C) led to higher levels of β-carbolines (660~2400 μg/kg) in fragrant sesame seed oils. In addition, the loss of tryptophan might be attributed to the formation of β-carbolines in sesame seeds during the roasting process. In general, fragrant sesame seed oils (pressed fragrant sesame oils, ground fragrant sesame oils) contain higher levels of β-carbolines due to the formation of harman and norharman during the roasting sesame seed process.

The β-carbolines, mainly including harman and norharman, are a group of naturally occurring, plant-derived alkaloids, and are also considered as nonpolar heterocyclic aromatic amines. Sesame seed oils contain a high level of β-carbolines (harman and norharman). In China, sesame seed oil blends are one of the most popular types of vegetable oils blends, which can be used as cooking oils or frying oils. Thus, it is meaningful to investigate the degradation of β-carbolines (harman and norharman) in sesame seed oil blends as frying oils during heating. In this work, the loss of harman and norharman in different types of sesame seed oil blends have been investigated. The results showed that the degradation of harman and norharman were dependent both on the type of oil blends, heating temperature and time. Harman and norharman were more degraded during heating (150 °C, 180 °C) in oleic acid-rich oil blends compared to polyunsaturated acid-rich oil blends. Mechanistic investigation suggested that the reduction in harman and norharman in oil blends during heating was mainly due to the oxidative degradation reaction between β-carbolines and lipid oxidation products. Therefore, the contents of β-carbolines (harman and norharman) in sesame seed oil blends when used as frying oils and heated can be decreased with prolonged cooking time.

Objectives We investigated the role of long non-coding (lnc) RNA-NEF (neighboring enhancer of FoxA2), a characterized oncogene in cancer biology, in postmenopausal osteoporosis and its diagnostic and prognostic value in this disease. Methods Expression of lncRNA-NEF in plasma was detected by RNA extraction and real-time quantitative PCR. The diagnostic value of lncRNA-NEF and interleukin (IL)-6 for postmenopausal osteoporosis was evaluated by receiver operating characteristic curve analysis, with postmenopausal osteoporosis patients as true positive cases and healthy volunteers as true negative cases. Results We showed that plasma lncRNA-NEF was downregulated and plasma IL-6 was upregulated in postmenopausal osteoporosis patients compared with healthy controls. Altered plasma levels of lncRNA-NEF and IL-6 separated postmenopausal osteoporosis patients from healthy controls, and lncRNA-NEF and IL-6 were inversely and significantly correlated in osteoporosis patients. Patients were divided into high (n = 68) and low lncRNA-NEF (n = 73) groups according to Youden’s index. Patients with high lncRNA-NEF levels required a significantly shorter treatment course and had a lower post-treatment recurrence rate. Conclusion We showed that lncRNA-NEF is downregulated in postmenopausal osteoporosis and is related to course of treatment and recurrence. The involvement of lncRNA-NEF in postmenopausal osteoporosis is likely related to IL-6.

The interfrontal bone (IF) is a minor skeletal trait residing between the frontal bones. IF is considered a quasi-continuous trait. Genetic and environmental factors appear to play roles in its development. The mechanism(s) underlying IF bone development are poorly understood. We sought to survey inbred strains of mice for the prevalence of IF and to perform QTL mapping studies. Archived mouse skulls from a mouse phenome project (MPP) were available for this study. 27 inbred strains were investigated with 6–20 mice examined for each strain. Skulls were viewed dorsally and the IF measured using a zoom stereomicroscope equipped with a calibrated reticle. A two generation cross between C3H/HeJ and C57BL/6J mice was performed to generate a panel of 468 F2 mice. F2 mice were phenotyped for presence or absence of IF bone and among mice with the IF bone maximum widths and lengths were measured. F2 mice were genotyped for 573 SNP markers informative between the two strains and subjected to linkage map construction and interval QTL mapping. Results: Strain dependent differences in the prevalence of IF bones were observed. Overall, 77.8% or 21/27, of the inbred strains examined had IF bones. Six strains (C3H/HeJ, MOLF/EiJ, NZW/LacJ, SPRET/EiJ, SWR/J, and WSB/EiJ) lack IF bones. Among the strains with IF bones, the prevalence ranged from 100% for C57BL/6J, C57/LJ, CBA/J, and NZB/B1NJ and down to 5% for strains such as CAST/Ei. QTL mapping for IF bone length and widths identifies for each trait one strong QTL detected on chromosome 14 along with several other significant QTLs on chromosomes 3, 4, 7, and 11. Strain dependent differences in IF will facilitate investigation of genetic factors contributing to IF development. IF bone formation may be a model to understand intrasutural bone formation.

Introduction: The association between the residential environment and emotional wellbeing (EWB) in older adults has received extensive attention from gerontologists, especially during the COVID-19 pandemic; however, the mediating mechanism of how residential environment affects emotional wellbeing has not been fully explored. This study examined the effects of the residential environment on EWB and the mediating role of health lifestyle., Methods: This study analyzed the survey data of 493 rural and 515 urban older adults from 2021 Chinese General Social Survey. General linear regression and structural equation models were used to examine the effects of residential environment and health lifestyle., Results: Urban participants exhibited clear advantages in EWB, residential environment, and physical activity. Residential environment significantly affected the EWB of older adults, and health lifestyle played a mediating role in this relationship. The residential environment and health lifestyle did not significantly affect EWB in rural participants., Discussion: This study revealed differences in the effects of health lifestyles and residential environments on EWB among older adults in rural and urban settings in China. This study provided empirical evidence of mental health disparities between older rural and urban Chinese residents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huijie, Haojun, Zhiping and Zhaoyu.)

Background: Currently, standard treatments for chronic hepatitis B such as nucleos(t)ide analogs (NAs), effectively reduce hepatitis B virus (HBV) loads but rarely result in a functional cure (defined as sustained HBsAg loss). We report the discovery of a novel, 4-pyridone compound, SAG-524, a potent and orally bioavailable small molecule inhibitor of HBV replication., Methods: The antiviral characteristics and selectivity of SAG-524 and its derivative compound against HBV were evaluated in HBV-infection assays and HBV-infected chimeric urokinase-type plasminogen activator/severe combined immunodeficiency mice with humanized livers (PXB mice), alone or in combination with entecavir. Toxicity studies were conducted in mice and monkeys., Results: SAG-524 reduced HBV-DNA (IC 50  = 0.92 nM) and HBsAg (IC 50  = 1.4 nM) in the supernatant of the HepG2.2.15 cells. SAG-524 selectively destabilized HBV-RNA via PAPD5, but not GAPDH or albumin mRNA, by shortening the poly(A) tail. PAPD5 may also be involved in HBV regulation via ELAVL1. In a study of HBV-infected PXB mice, SAG-524 produced potent reductions of serum HBsAg and HBcrAg, and the minimum effective dose was estimated to be 6 mg/kg/day. The combination therapy with entecavir greatly reduced HBsAg and cccDNA in the liver due to reduction of human hepatocytes with good tolerability. Administration of SAG-524 to monkeys, up to 1000 mg/kg/day for two weeks, led to no significant toxicity, as determined by blood tests and pathological images., Conclusions: We have identified SAG-524 as novel and orally bioavailable HBV-RNA destabilizers which can reduce HBsAg and HBV-DNA levels, and possibly contribute a functional cure., (© 2024. Japanese Society of Gastroenterology.)