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Shitong Su,1,2 Lianjing Liang,1 Lin Lü,1 Mingfeng Li,3 Xiaoling Zhang,4 Yongmei Jin,5 Wei Wei,1 Zhi Wan6 1Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Division of Head & Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Department of Cardiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 6Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Wei Wei, Chest Pain center, Department of Emergency Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of China, Email ww8075@126.com Zhi Wan, Rare Diseases Center, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of China, Email 456wz@163.comAbstract: Loeffler endocarditis, eosinophilic endocarditis or eosinophilic endomyocardial disease are conditions associated with hypereosinophilia and they affect the heart function. Loeffler endocarditis is a rare endomyocardial disorder thought to be caused by eosinophilic damage. The disorder is characterized by inflammatory infiltration, formation of thrombus within cardiovascular system, and ultimately fibrosis of the afflicted area. It can lead to multiple severe complications, including thromboembolic disease, thickening of fibrous tissue in the endocardium of ventricles, valve involvement, apical obliteration, and various heart disorders. Although early clinical intervention can lead to remission, the underlying mechanisms of the disorder remain unresolved. In the present article, we summarise the existing literature concerning Loeffler endocarditis based on PubMed, Web of Science, and other medical databases to conduct an in-depth review of the epidemiology, etiology, pathophysiological mechanisms, staging, diagnosis, treatment and prognosis of Loeffler endocarditis. Meanwhile, we provide novel patients data and clinical figures of Loeffler endocarditis to supplement the understanding of this cardiac disorder. The findings presented in this article provide a basis for further studies and can be used to improve management of the disorder.Keywords: Loeffler endocarditis, hypereosinophilia, eosinophils damage

In order to understand the change of water state and quality characteristics of longan during practical drying production and discover the pivotal drying stages, the dynamic changes of moisture content and state, color, 5-HMF, main nutritional and functional qualities, and antioxidant capacity were monitored through whole intermittent heat pump drying and equilibrium stages. The results showed that the moisture content of longan decreased rapidly during drying stages, and decreased slowly during the equilibrium stages. After through drying stage 2, the free water of longan was removed and transferred coupled with the immobilized water increased. With the drying and equilibrium progress going, the color, browning degree and 5-HMF of longan increased in a step manner, color changes were most significantly occurred in drying stage 3, and the content of 5-HMF was dramatically increased to 55.40 μg/g DW after drying stage 1. On the contrary, the total phenols, total flavonoids, total free amino acids were decreased in a step manner, and decreased to 35.23%, 41.05%, and 42.13% after drying stage 3, respectively, when compared with fresh sample. Moreover, the degradation of total free amino acids was mainly decreased in drying stage 1 and 3. According to antioxidant analysis, the antioxidant capacity of longan was mainly decreased in drying stage 2, which was in conformity with the change of total phenols. Overall, drying stage 1 and 3 were the key stages during the intermittent heat pump drying process, which affected quality characteristics of longan mostly.

Bioactive hydrogel materials have great potential for applications in bone tissue engineering. However, fabrication of functional hydrogels that mimic the natural bone extracellular matrix (ECM) remains a challenge, because they need to provide mechanical support and embody physiological cues for angiogenesis and osteogenesis. Inspired by the features of ECM, we constructed a dual-component composite hydrogel comprising interpenetrating polymer networks of gelatin methacryloyl (GelMA) and deoxyribonucleic acid (DNA). Within the composite hydrogel, the GelMA network serves as the backbone for mechanical and biological stability, whereas the DNA network realizes dynamic capabilities (e.g., stress relaxation), thereby promoting cell proliferation and osteogenic differentiation. Furthermore, functional aptamers (Apt19S and AptV) are readily attached to the DNA network to recruit bone marrow mesenchymal stem cells (BMSCs) and achieve sustained release of loaded vascular endothelial growth factor towards angiogenesis. Our results showed that the composite hydrogel could facilitate the adhesion of BMSCs, promote osteogenic differentiation by activating focal adhesion kinase (FAK)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/β-Catenin signaling pathway, and eventually enhance vascularized bone regeneration. This study shows that the multifunctional composite hydrogel of GelMA and DNA can successfully simulate the biological functions of natural bone ECM and has great potential for repairing bone defects.

Colorectal cancer (CRC) is the third most diagnosed cancer and the second deadliest cancer worldwide representing a major public health problem. In recent years, increasing evidence has shown that microRNA (miRNA) can control the expression of targeted human messenger RNA (mRNA) by reducing their abundance or translation, acting as oncogenes or tumor suppressors in various cancers, including CRC. Due to the significant up-regulation of oncogenic miRNAs in CRC, elucidating the underlying mechanism and identifying dysregulated miRNA targets may provide a basis for improving current therapeutic interventions. In this paper, we proposed Gra-CRC-miRTar, a pre-trained nucleotide-to-graph neural network framework, for identifying potential miRNA targets in CRC. Different from previous studies, we constructed two pre-trained models to encode RNA sequences and transformed them into de Bruijn graphs. We employed different graph neural networks to learn the latent representations. The embeddings generated from de Bruijn graphs were then fed into a Multilayer Perceptron (MLP) to perform the prediction tasks. Our extensive experiments show that Gra-CRC-miRTar achieves better performance than other deep learning algorithms and existing predictors. In addition, our analyses also successfully revealed 172 out of 201 functional interactions through experimentally validated miRNA-mRNA pairs in CRC. Collectively, our effort provides an accurate and efficient framework to identify potential miRNA targets in CRC, which can also be used to reveal miRNA target interactions in other malignancies, facilitating the development of novel therapeutics. The Gra-CRC-miRTar web server can be found at: http://gra-crc-mirtar.com/.

In this study, the change of Msalais quality and antioxidant capacity during storage were investigated. The experiments were carried out over a period of 9 months, and analyses were performed monthly. The results showed that the pH, total sugar, and alcohol content of Msalais during the storage period exhibited a decreasing trend, while the total acid content increased. The antioxidant capacity indicated that the contents of total phenols and flavonoids and the scavenging ability of Msalais for DPPH and ABTS decreased markedly with storage time, and stabilizing after 9 months of storage. Furthermore, a total of 27 aroma components, including alcohols, aldehydes, ketones, esters and acids, were detected. After 9 months of storage, the content of most aroma components in Msalais had changed. Among them, the values of the characteristic aroma ingredient phenylethyl alcohol decreased during storage. However, the contents of diisobutyl phthalate, hexadecanoic acid ethyl ester, and octadecanoic acid ethyl ester increased substantially with the following 9 months of storage time. Overall, during the storage process, alcohols, aldehydes and ketones continued to decrease, while esters and acids continued to increase; it was determined that within the 9 month storage period, the longer the storage time, the greater the difference. The obtained findings provide reference data for the optimization of Msalais storage.

AbstractContext The effect of the active ingredients in traditional Chinese medicines on the activity of cytochrome P450 enzymes (CYP450s) is a critical factor that should be considered in TCM prescriptions. Physcion, the major active ingredient of Rheum spp. (Polygonaceae), possesses wide pharmacological activities.Objectives The effect of physcion on CYP450 activity was investigated to provide a theoretical basis for use.Materials and methods The experiments were conducted in pooled human liver microsomes (HLMs). The activity of CYP450 isoforms was evaluated with corresponding substrates and probe reactions. Blank HLMs were set as negative controls, and typical inhibitors were employed as positive controls. The inhibition model was fitted with Lineweaver Burk plots. The concentration (0, 2.5, 5, 10, 25, 50 and 100 μM physcion) and time-dependent (0, 5, 10, 15 and 30 min) effects of physcion were also assessed.Results Physcion suppressed CYP2C9, 2D6 and 3A4 in a concentration-dependent manner with IC50 values of 7.44, 17.84 and 13.50 μM, respectively. The inhibition of CYP2C9 and 2D6 was competitive with the Ki values of 3.69 and 8.66 μM, respectively. The inhibition of CYP3A4 was non-competitive with a Ki value of 6.70 μM. Additionally, only the inhibition of CYP3A4 was time-dependent with the KI and Kinact parameters of 3.10 μM−1 and 0.049 min−1, respectively.Conclusions The inhibition of CYP450s by physcion should be considered in its clinical prescription, and the study design can be employed to evaluate the interaction of CYP450s with other herbs.

Abstract A discrete‐time full‐order sensorless control strategy for high‐speed interior permanent magnet synchronous motor (IPMSM) used in electric vehicle (EV) traction system is designed in this paper. While most speed and position observer (SPO) methods are developed in the continuous‐time domain, the presence of a unit‐time‐delay block existed in feedback loop and discretisation of the algorithm can lead to performance degradation during digital implementation. In this work, speed and angle are observed using the discrete‐time four‐order IPMSM model. A quadrature phase‐locked loop model with compensation is introduced, and its stability condition is established for the first time. Furthermore, to address the potential for sudden speed changes in vehicle applications, the parameter range is further refined to keep the estimation error within a specified range. The sliding mode observer is discretised and its stability is analysed using discrete Lyapunov theory. Additionally, the time sequence of interactive signals between SPO and field‐oriented control is thoroughly examined to ensure accurate time cycle. Finally, the proposed control strategy is validated and demonstrated through bench tests and real EV (LS6 of IM Motors) tests with a 190 kW IPMSM, which can improve the accuracy by 0.3 radians at 8000 rpm compared to traditional methods, and achieve stable control at 15,000 rpm on the test bench and at 120 kph with the EV.

The development of urbanization has fostered the rise of instrumental rationality and the decline of value rationality, leading to a diminishing sense of belonging among individuals in fast-paced urban life. As a result, rurality has become a core attraction for rural tourists. Research on rurality has emerged as a key topic in the fields of rural geography and rural tourism. However, relatively little research has focused on how to realize micro-level human-land interactions and achieve a subjective understanding of rurality in rural tourism destinations from a cognitive perspective. Schema theory offers a framework to explore this issue. Amid the confrontation and integration of modernity and provinciality, the rurality of rural World Heritage sites, by preserving the integrity and authenticity of traditional rural social structures, enhances tourists' local attachment and local experiences. This paper uses Hongcun, a rural World Heritage site, as a case study, introducing schema theory to explore the cognitive schema of rurality and its generation mechanism among tourists by conducting a grounded theory analysis of travel notes on Ctrip. Through open coding, axial coding, and selective coding, a model of rurality cognitive schema and its generation mechanism was constructed. The findings are as follows: 1) Tourists acquire a concrete schema of rurality through embodied experiences and behavioral interactions, which resonate with and enrich their existing schemas, facilitating schema integration across time and space; 2) The existing schema, shaped by cultural background and individual experience, serves as the foundation for tourists to form cognitive schemas. The local characteristics of traditional Chinese rural society and the traditional culture passed down through generations are embedded in individuals' existing schemas. Tourists' existing schemas interact with the rural tourism environment, engaging in both top-down and bottom-up cognitive processing through anticipation contrast, uniqueness contrast, feature association, and cross-temporal imagination. 3) The rural cognitive schema consists of four sub-schemas: the natural ecological schema, life schema, cultural schema, and place atmosphere schema. The natural ecological schema emphasizes tourists' perception of the interplay between rural nature and humanity. The life schema pertains to daily life scenes observed at the tourist destination, while the cultural schema refers to the local culture formed through the development and evolution of the destination. The place atmosphere schema captures the abstract perception and impression of the destination, formed through the interaction between tourists' embodied experiences and their existing schemas. The natural ecological schema provides the spatial foundation for both the life and cultural schemas, while the latter two exert external influences on the natural ecological schema, helping shape the rural area's natural and humanistic characteristics. The cultural schema informs and regulates the life schema, while the life schema simultaneously practices and reshapes the cultural schema. Together, these schemas, along with the place atmosphere schema, form a comprehensive cognitive network of rural nature. This study is significant for deepening the understanding of the connotation and formation mechanism of rurality, exploring human-local interaction from a microscopic perspective, and offering theoretical and practical guidance for the development of rural tourism through the mining of rurality and culture.

Abstract Using 7.33 fb −1 of e + e − collision data samples collected with the BESIII detector at center-of-mass energies between 4.128 and 4.226 GeV, we search for the radiative decay D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ for the first time. A hint of D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ is observed with a statistical significance of 2.5σ. The branching fraction of D s + → γρ 770 + $$ {D}_s^{+}\to \gamma \rho {(770)}^{+} $$ is measured to be (2.2 ± 0.9stat. ± 0.2syst. ) × 10 −4, corresponding to an upper limit of 6.1 × 10 −4 at the 90% confidence level.

Abstract Background DNA methylation is an epigenetic modification that plays an important role in animal and plant development. Among the diverse types of DNA methylation modifications, methylation of cytosines catalyzed by DNA cytosine methyltransferases (DNMTs) is the most common. Recently, we characterized DNA methyltransferase genes including HlDnmt1 and HlDnmt from the Asian longhorned tick, Haemaphysalis longicornis. However, the dynamic expression and functions of these DNMTs at different developmental stages and feeding statuses of the important vector tick H. longicornis remain unknown. Results The expression levels of HlDnmt1 and HlDnmt were significantly different at the four developmental stages: eggs, larvae, nymphs, and adults, with the highest expression levels observed in the larval stage. HlDnmt1 and HlDnmt showed different expression trends in the midguts, ovary, Malpighian tubules, and salivary glands of engorged adults, with the highest expression of HlDnmt1 observed in the ovary and the lowest in the midguts; HlDnmt expression was the highest in the midguts and the lowest in the Malpighian tubules. After RNA interference, the relative expression of HlDnmt1 and HlDnmt in H. longicornis decreased significantly, resulting in a significant decrease in the biting rate of H. longicornis. RNA-seq revealed that the differentially expressed genes were mainly enriched in the biological processes of peptide biosynthesis and the cell components of ribosomes. Molecular functions were mainly concentrated on oxidoreductase activity, ribosome structure composition, serine-type endopeptidase activity, molecular function regulators, and endopeptidase inhibitor activity. KEGG enrichment analysis showed that the differentially expressed genes were mainly enriched in autophagy and lysosome pathways, amino sugar and nucleotide sugar metabolism, glyceride metabolism, ribosomes, and other pathways. Conclusions HlDnmt1 and HlDnmt played an important role during development and feeding of H. longicornis, and their functions were potentially associated with lysosome pathways. These results provide basic knowledge for understanding the epigenetic regulation of the development of the tick H. longicornis, which sheds light on control strategies for ticks and tick-borne diseases.

Abstract The relationship between depression and severe non-alcoholic fatty liver disease (NAFLD) has not been clearly defined. We conducted a longitudinal cohort study and a two-sample Mendelian randomization (MR) analysis to assess the association of depression with severe NAFLD risk. We used individual data from the UK Biobank study with 481,181 participants, and summary data from published genome-wide association studies. The association between depression and severe NAFLD was assessed using Cox proportional hazards regression analysis. Two-sample MR for depression with NAFLD was conducted, the principal analysis employed the inverse variance weighted (IVW) approach. In the observational study, after a median follow-up of 13.46 years, 4,563 participants had severe NAFLD. In multivariable-adjusted model, participants with depression had an increased risk of severe NAFLD (hazards ratio:1.21, 95% confidence interval (CI):1.09–1.34), as compared to those without depression. In subgroup analyses, the association between depression and severe NAFLD risk was generally observed across different subgroups. For the MR, result also showed that genetically predicted depression was causally associated with a higher risk of NAFLD (odds ratio:1.55, 95%CI:1.10–2.19) in IVW. Our study revealed a prospective association of depression with severe NAFLD, thus potentially necessitating clinical monitoring of individuals with depression for severe NAFLD.

Abstract Colorectal cancer (CRC) development involves a series of molecular events that drive the progression from normal colorectal epithelium to adenoma and eventually to invasive carcinoma. While the involvement of extrachromosomal circular DNAs (ecDNAs) in cancer genome remodeling has been established, their specific roles in CRC formation remain unclear. Using Circle-Sequencing and whole transcriptomic sequencing, we comprehensively profile circular DNAs and transcriptomes in healthy individuals, colorectal adenoma, and CRC patients. Our delineate analyses characterize the key circular DNAs involved in oncogene expression through the normal-adenoma–carcinoma continuum and highlight that immune response-related pathways and cell cycle pathways, are the dominat events in CRC progression. Notably, chr8 ecDNA 64950741–114379093 exhibits robust up-regulation during CRC progression. Further validation in a new cohort of 50 CRC patients confirms the higher expression of chr8 ecDNA 64950741–114379093 and its strong correlation with poor prognosis. Thus, these findings provide unprecedented insights into the landscape of circular DNAs in CRC and highlights the potential of chr8 ecDNA 64950741–114379093 as a promising biomarker and therapeutic target for CRC management.

Abstract The close spatial and temporal connection between osteogenesis and angiogenesis around type H vasculature is referred as “osteogenesis-angiogenesis coupling”, which is one of the basic mechanisms of osteogenesis. Endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and their specific lineage constitute important cluster that participate in the regulation of osteogenesis and angiogenesis in bone microenvironment. However, the regulatory mechanism of osteogenesis-angiogenesis coupling under the condition of bone healing has not been unveiled. In this study, we demonstrated that the exosome derived from ECs (EC-exo) is an initiator of type H blood vessels formation, and EC-exo acts as a mediator in orchestrating osteogenesis-angiogenesis coupling by enhancing BMSC osteogenic differentiation and EC angiogenesis both in monolayer and stereoscopic co-culture system of primary human cells. The transcriptome array indicated that zinc finger and BTB domain containing 16 (ZBTB16) is a key gene in EC-exo-mediated osteogenesis, and ZBTB16 is indispensable in EC-exo-initiated osteogenesis-angiogenesis coupling. Mechanistically, EC-exo up-regulated the expression of ZBTB16 in BMSCs, thereby promoting osteoprogenitor phenotype transformation; the osteoprogenitors further promote ECs which constitute type H vessel (H-ECs) generation by activating HIF-1α pathway; and the H-ECs conversely promotes osteogenic differentiation of BMSCs. The crosstalk between BMSCs and ECs triggered by EC-exo constitutes a positive feedback loop that enhances osteogenesis-angiogenesis coupling. This study demonstrates that EC-exo can become an effective therapeutic tool to promote bone regeneration and repair. Graphical Abstract

Abstract Background For decades, KRAS has always been a huge challenge to the field of drug discovery for its significance in cancer progression as well as its difficulties in being targeted as an “undruggable” protein. KRAS regulates downstream signaling pathways through protein–protein interactions, whereas many interaction partners of KRAS remain unknown. Results We developed a workflow to computationally predict and experimentally validate the potential KRAS-interacting proteins based on the interaction mode of KRAS and its known binding partners. We extracted 17 KRAS-interacting motifs from all experimentally determined KRAS-containing protein complexes as queries to identify proteins containing fragments structurally similar to the queries in the human protein structure database using our in-house protein–protein interaction prediction method, PPI-Miner. Finally, out of the 78 predicted potential interacting proteins of KRAS, 10 were selected for experimental validation, including BRAF, a previously reported interacting protein, which served as the positive control in our validation experiments. Additionally, a known peptide that binds to KRAS, KRpep-2d, was also used as a positive control. The predicted interacting motifs of these 10 proteins were synthesized to perform biolayer interferometry assays, with 4 out of 10 exhibiting binding affinities to KRAS, and the strongest, GRB10, was selected for further validation. Additionally, the interaction between GRB10 (RA-PH domain) and KRAS was confirmed via immunofluorescence and co-immunoprecipitation. Conclusions These results demonstrate the effectiveness of our workflow in predicting potential interacting proteins for KRAS and deepen the understanding of KRAS-driven tumor mechanisms and the development of therapeutic strategies.

Abstract Background Spinal orthoses are commonly prescribed for adolescent idiopathic scoliosis (AIS), yet their three-dimensional correction was not fully understood. The amount of deformity control largely depends on the corrective forces applied, which remain empirically based due to a lack of consensus on optimal force application. This study investigated the effects of different corrective force directions exerted by spinal orthoses on patients with AIS. Methods A retrospective analysis was conducted on 78 subjects. The trunk was segmented into four quadrants using coronal and sagittal planes from a top-down perspective. Each left or right posterolateral quadrant (with 90°) was further subdivided into zones 1–4, from the sagittal to coronal planes. Based on the zone where the resultant corrective force direction fell, the subjects were categorized into Group 1 (zone 1), Group 2 (zone 2), Group 3 (zone 3), or Group 4 (zone 4). The direction of the corrective force was estimated using modified models of the subjects’ bodies, designed through a computer-aided design and manufacturing system integral to the orthosis fabrication process. The effects of corrective forces in different zones on scoliotic spine were assessed. Results Among the subjects, 3 were in Group 1, 17 in Group 2, 52 in Group 3, and 6 in Group 4. Due to the limited number of subjects, data from Groups 1 and 4 were not analysed. Groups 2 and 3 showed significant reductions in Cobb angle in the coronal plane and plane of maximum curvature (PMC) following orthosis fitting (p 5º in thoracic kyphosis (p 0.05) but was notably higher in Group 2 after orthosis fitting (p

Abstract This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.

Abstract Background The mechanisms by which tumor-derived factors remodel the microenvironment of target organs to facilitate cancer metastasis, especially organ-specific metastasis, remains obscure. Our previous studies have demonstrated that SPP1 plays a key role in promoting metastasis of hepatocellular carcinoma (HCC). However, the functional roles and mechanisms of tumor-derived SPP1 in shaping the pre-metastatic niche (PMN) and promoting lung-specific metastasis are unclear. Methods Orthotopic metastasis models, experimental metastasis models, CyTOF and flow cytometry were conducted to explore the function of SPP1 in shaping neutrophil-dominant PMN and promoting HCC lung metastasis. The main source of CXCL1 in lung tissues was investigated via fluorescence activated cell sorting and immunofluorescence staining. The expression of neutrophils and neutrophil extracellular traps (NETs) markers was detected in the lung metastatic lesions of HCC patients and mouse lung specimens. The therapeutic significance was explored via in vivo DNase I and CXCR2 inhibitor assays. Results SPP1 promoted HCC lung colonization and metastasis by modifying pulmonary PMN in various murine models, and plasma SPP1 levels were closely associated with lung metastasis in HCC patients. Mechanistically, SPP1 binded to CD44 on lung alveolar epithelial cells to produce CXCL1, thereby attracting and forming neutrophil-abundant PMN in the lung. The recruited neutrophils were activated by SPP1 and then formed NETs-dominant PMN to trap the disseminated tumor cells and promote metastatic colonization. Moreover, early intervention of SPP1-orchestrated PMN by co-targeting the CXCL1-CXCR2 axis and NETs formation could efficiently inhibit the lung metastasis of HCC. Conclusions Our study illustrates that HCC-lung host cell-neutrophil interactions play important roles in PMN formation and SPP1-induced HCC lung metastasis. Early intervention in SPP1-orchestrated PMN via CXCR2 inhibitor and DNase I is a potential therapeutic strategy to combat HCC lung metastasis.

Abstract Ruthenium (Ru) is widely recognized as a low-cost alternative to iridium as anode electrocatalyst in proton-exchange membrane water electrolyzers (PEMWE). However, the reported Ru-based catalysts usually only operate within tens of hours in PEMWE because of their intrinsically high reactivity of lattice oxygen that leads to irrepressible Ru leaching and structural collapse. Herein, we report a design concept by employing large-sized and acid-resistant lattice lead (Pb) as a second element to induce a pinning effect for effectively narrowing the moving channels of oxygen atoms, thereby lowering the reactivity of lattice oxygen in Ru oxides. The Pb-RuO2 catalyst presents a low overpotential of 188 ± 2 mV at 10 mA cm−2 and can sustain for over 1100 h in an acid medium with a negligible degradation rate of 19 μV h−1. Particularly, the Pb-RuO2-based PEMWE can operate for more than 250 h at 500 mA cm−2 with a low degradation rate of only 17 μV h−1. Experimental and theoretical calculation results reveal that Ru-O covalency is reduced due to the unique 6s−2p−4d orbital hybridization, which increases the loss energy of lattice oxygen and suppresses the over-oxidation of Ru for improved long-term stability in PEMWE.

Abstract ENO1, also called 2-phospho-D-glycerate hydrolase in cellular glycolysis, is an enzyme that converts 2-phosphoglycerate to phosphoenolpyruvate and plays an important role in the Warburg effect. In various tumors, ENO1 overexpression correlates with poor prognosis. ENO1 is a multifunctional oncoprotein that, when located on the cell surface, acts as a “moonlighting protein” to promote tumor invasion and metastasis. When located intracellularly, ENO1 facilitates glycolysis to dysregulate cellular energy and sustain tumor proliferation. Additionally, it promotes tumor progression by activating oncogenic signaling pathways. ENO1 is a tumor biomarker and represents a promising target for tumor therapy. This review summarizes recent advances from 2020 to 2024 in understanding the relationship between ENO1 and tumors and explores the latest targeted therapeutic strategies involving ENO1.

Abstract Using e + e − collision data collected by the BESIII detector at BEPCII corresponding to an integrated luminosity of 30 fb −1, we measure Born cross sections and effective form factors for the process e + e − → Ξ 0 Ξ ¯ 0 $$ {e}^{+}{e}^{-}\to {\Xi}^0{\overline{\Xi}}^0 $$ at forty-five center-of-mass energies between 3.51 and 4.95 GeV. The dressed cross section is fitted, assuming a power-law function plus a charmonium(-like) state, i.e., ψ(3770), ψ(4040), ψ(4160), ψ(4230), ψ(4360), ψ(4415) or ψ(4660). No significant charmonium(-like) state decaying into Ξ 0 Ξ ¯ 0 $$ {\Xi}^0{\overline{\Xi}}^0 $$ is observed. Upper limits at the 90% confidence level on the product of the branching fraction and the electronic partial width are provided for each decay. In addition, ratios of the Born cross sections and the effective form factors for e + e − → Ξ 0 Ξ ¯ 0 $$ {e}^{+}{e}^{-}\to {\Xi}^0{\overline{\Xi}}^0 $$ and e + e − → Ξ − Ξ ¯ + $$ {e}^{+}{e}^{-}\to {\Xi}^{-}{\overline{\Xi}}^{+} $$ are also presented to test isospin symmetry and the vector meson dominance model.

Abstract Background The benefits of low-pressure laparoscopic cholecystectomy (LPLC) in patients with cardiopulmonary comorbidities remain unclear. This study aimed to explore the feasibility and pulmonary effects of LPLC in patients with cardiopulmonary comorbidities. Methods This was a multicenter, parallel, double-blind, randomized controlled trial. Eligible patients included patients with cardiac or pulmonary comorbidities, who were randomly assigned (1:1) to undergo LPLC (10 mmHg) or standard-pressure laparoscopic cholecystectomy (SPLC) (14 mmHg). The primary outcome was postoperative partial pressure of carbon dioxide (CO2). Surgical safety variables, patient recovery, pulmonary function parameters, and surgeon comfort were also compared between groups. Results This study enrolled 144 participants, with 124 participants extracted for the final analysis (62 in LPLC and 62 in SPLC group, respectively). The median postoperative PaCO2 was similar in the LPLC (43.3 mmHg) and SPLC (43.0 mmHg) groups (p = 0.988). Pulmonary parameters including postoperative pH, PaCO2, HCO3, and lactate levels were similar between the two groups. Postoperative base excess was significantly higher in the LPLC group (− 0.6 mmol/L [− 6.9 ~ 7.5] vs. −1.9 mmol/L [− 6.6 ~ 5.4]; p = 0.031). There was no between-group difference regarding intraabdominal operative time, rate of intraoperative bile spillage, blood loss, surgeon comfort during surgery, and conversion rate. Moreover, postoperative major complication rates, the median time to the first flatus, postoperative hospital stay, or mean postoperative visual analog scale score for pain were similar in both groups. Conclusions This study found no reduction of partial pressure of CO2 with LPLC compared with SPLC for patients with cardiopulmonary comorbidities. LPLC with a pneumoperitoneum pressure of 10 mmHg may be safe and feasible for these patients when performed by experienced surgeons, although it does not improve pulmonary parameters. Registration The trial is retrospectively registered at ClinicalTrials.gov (NCT04670952) on December 17, 2020.

Abstract Diazotrophic cyanobacteria can fix nitrogen gas (N2) but are usually scarce in nitrogen-limited coastal waters, which poses an apparent ecological paradox. One hypothesis is that high salinities (> 10 g/L NaCl) may inhibit cyanobacterial N2 fixation. However, here we show that N2 fixation in a unicellular coastal cyanobacterium exclusively depends on sodium ions and is inhibited at low NaCl concentrations (

Abstract Orthopedic implants have faced challenges in treating bone defects due to various factors, including inadequate osseointegration, oxidative stress, bacterial infection, immunological rejection, and poor individualized treatment. These challenges profoundly affect both the results of treatment and patients' daily lives. There is great promise for the layer-by-layer (LbL) assembly method in tissue engineering. The method primarily relies on electrostatic attraction and entails the consecutive deposition of electrolyte complexes with opposite charges onto a substrate, leading to the formation of homogeneous single layers that can be quickly deposited to produce nanolayer films. LbL has attracted considerable interest as a coating technology because of its ease of production, cost-effectiveness, and capability to apply diverse biomaterial coatings without compromising the primary bio-functional properties of the substrate materials. This review will look into the fundamentals and evolution of LbL in orthopedics, provide an analysis of the chemical strategy used to prepare bone implants with LbL and introduce the application of LbL bone implants in orthopedics over recent years. Among the many potential uses of LbL, such as the implementation of sustained-release and programmed drug delivery, which in turn promotes the osseointegration and the development of new blood vessels, as well as antibacterial, antioxidant, and other similar applications. In addition, we offer a thorough examination of cell behavior and biomaterial interaction to facilitate the advancement of next-generation LbL films for tissue engineering.

Abstract Glioblastoma is one of the most common and aggressive primary brain tumors. The aberration of metabolism is the important character of GBM cells and is tightly related to the malignancy of GBM. We mainly verified the regulatory effects of KHDRBS1, SNORD51 and ZBED6 on pentose phosphate pathway and malignant biological behavior in glioblastoma cells, such as proliferation, migration and invasion. KHDRBS1 and SNORD51 were upregulated in GBM tissues and cells. But ZBED6 had opposite tendency in GBM tissues and cells. KHDRBS1 may improve the stability of SNORD51 by binding to SNORD51, thus elevating the expression of SNORD51. More importantly, SNORD51 can competitively bind to WDR33 with 3’UTR of ZBED6 pre-mRNA which can inhibit the 3’ end processing of ZBED6 pre-mRNA, thereby inhibiting the expression of ZBED6 mRNA. ZBED6 inhibited the transcription of G6PD by binding to the promoter region of G6PD. Therefore, the KHDRBS1/SNORD51/ZBED6 pathway performs an important part in regulating the pentose phosphate pathway to influence malignant biological behavior of GBM cells, providing new insights and potential targets for the treatment of GBM.

Abstract Background The objective was to evaluate the level of neutrophil extracellular traps (NETs) in patients with chronic kidney disease (CKD) and periodontitis, and to explore the relationship between NETs and both diseases. Methods 63 CKD and 40 non-CKD participants were recruited and underwent periodontal examination, among which 35 early CKD patients underwent periodontal therapy. The concentrations of NETs were determined by dsDNA assay in gingival crevicular fluid (GCF) and plasma, and by flow cytometry or immunofluorescence assay in blood and gingival tissues. The correlations between NETs and clinical parameters were analyzed. The influence of periodontal therapy on periodontitis, CKD and NETs concentrations was also evaluated. Results CKD patients had higher concentrations of NETs in plasma than non-CKD patients, and NETs concentrations were also increased in both GCF and plasma of patients with periodontitis than that of periodontally healthy patients. NETs concentrations were positively correlated with increased clinical parameters of CKD and periodontitis. The positive correlation between CKD and periodontitis was demonstrated. Moreover, periodontal therapy ameliorated periodontitis and CKD, and reduced NETs concentrations in GCF of patients. Conclusions This study revealed that NETs might be a possible bridge between periodontitis and CKD, and suggested the potential target for therapy.

Liying Lu,1,2 Mengdan Pang,1,2 Tingting Chen,1,2 Yingying Hu,1,2 Likai Chen,3 Xiaoyue Tao,1,2 Shangqin Chen,1,2 Jianghu Zhu,1,2 Mingchu Fang,1,2 XiaoLing Guo,1,4 Zhenlang Lin1,2,4 1Department of Pediatrics, The Second School of Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Perinatal Medicine of Wenzhou, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Elson S. Floyd College of Medicine at Washington State University, Spokane, WA, USA; 4Basic Medical Research Center, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: XiaoLing Guo; Zhenlang Lin, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +00-86-138-0668-9800, Fax +86-0577-88002198, Email guoxling@hotmail.com; linzhenlang@hotmail.comIntroduction: Neonatal hypoxic-ischemic encephalopathy (HIE), caused by perinatal asphyxia, is characterized by high morbidity and mortality, but there are still no effective therapeutic drugs. Mitochondrial biogenesis and apoptosis play key roles in the pathogenesis of HIE. Protopine (Pro), an isoquinoline alkaloid, has anti-apoptotic and neuro-protective effects. However, the protective roles of Pro on neonatal hypoxic-ischemic brain injury remain unclear.Methods: In this study, we established a CoCl2-induced PC12 cell model in vitro and a neonatal rat hypoxic-ischemic (HI) brain damage model in vivo to explore the neuro-protective effects of Pro and try to elucidate the potential mechanisms.Results: Our results showed that Pro significantly reduced cerebral infarct volume, alleviated brain edema, inhibited glia activation, improved mitochondrial biogenesis, relieved neuron cell loss, decreased cell apoptosis and reactive oxygen species (ROS) after HI damage. In addition, Pro intervention upregulated the levels of p-AMPK/AMPK and PGC1α as well as the downstream mitochondrial biogenesis related factors, such as nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM), but the AMPK inhibitor compound c (CC) could significantly reverse these effects of Pro.Discussion: Pro may exert neuroprotective effects on neonatal hypoxic-ischemic brain damage via activation of the AMPK/PGC1α pathway, suggesting that Pro may be a promising therapeutic candidate for HIE, and our study firstly demonstrate the neuro-protective roles of Pro in HIE models.Keywords: neonatal hypoxic-ischemic brain damage, protopine, reactive oxygen species, apoptosis, mitochondrial biogenesis

Introduction: The proportion of animal based foods in daily diet of consumers is constantly increasing, with chicken being highly favored due to its high protein and low fat characteristics. The consumption of chicken around the world is steadily increasing. Intramuscular fat (IMF) is a key indicator affecting meat quality. Object: High IMF content can contribute to improve the quality of chicken meat. The regulatory mechanism of IMF deposition in chicken is poorly understood, so its complete elucidation is essential to improve chicken meat quality. Method: Here, we performed whole genome resequencing on 516 yellow feather chickens and single-cell RNA sequencing on 3 63-day-old female JXY chickens. In addition, transcriptome sequencing techniques were also performed on breast muscle tissue of JXY chickens at different developmental stages. And 13C isotope tracing technique was applied. Results: In this study, a large-scale genetic analysis of an IMF-selected population and a control population identified fatty acid synthase (FASN) as a key gene for improving IMF content. Also, contrary to conventional view, de novo lipogenesis (DNL) was deemed to be an important contributor to IMF deposition. As expected, further analyses by isotope tracing and other techniques, confirmed that DNL mainly occurs in myocytes, contributing about 40% of the total fatty acids through the regulation of FASN, using the available FAs as substrates. Additionally, we also identified a relevant causal mutation in the FASN gene with effects on FA composition. Conclusion: These findings contribute to the understanding of fat metabolism in muscle tissue of poultry, and provide the feasible strategy for the production of high-quality chicken meat.

Consideration of irradiation effects is important for in-orbit operation and radiation protection in aerospace applications. The configuration of irradiation defects and their impact on deteriorating the carrier transport properties of CZT crystals need to be clarified. In this study, the microdefect evolution mechanism of CdZnTe (CZT) crystals under 10 MeV Chlorine (Cl) ion irradiation at flux of 1 × 1010∼1 × 1012 n·cm−2 are investigated. The stacking faults first appear in the CZT crystal at 4.5 × 10−4 displacement per atom (dpa), which are categorized into slip-type, gap-type and vacancy-type. In order to hinder the further expansion of stacking fault, S-shaped stacking fault dipole appears. When the dpa reaches 4.5 × 10−2, the local phase transition occurs in the damage zone to form CuPt-A ordered phase with ZnTe/CdTe periodic arrangement because the fluctuation in local composition and strain caused by cascade collisions. The deterioration of electric field distribution and charge collection caused by irradiation damage layer leads to the decrease of γ-ray detection ability. The energy resolution (ER) of the CZT detector for γ-ray can be maintained at 30.6% when the ion flux accumulates to 1 × 1012 n·cm−2, revealing high irradiation hardness. Consequently, these findings provide a theoretical basis for the radiation damage recovery of CZT detectors, further demonstrating that CZT crystals are the most competitive new generation of room-temperature nuclear radiation detection materials, and can provide radiation protection strategies for similar compound semiconductor materials.

Elucidating the inherent origins of the sluggish hydrogen evolution reaction (HER) kinetics in alkaline media and developing high-performance electrocatalysts are fundamental for the advances of conventional alkaline water electrolyzers and emerging anion exchange membrane (AEM) electrolyzers. Here we present a facile electrochemical modification strategy for the synthesis of bi-component Co–Mo(18%)/A-Co(OH)2 catalyst toward efficient HER catalysis in alkaline media. Porous Co–Mo alloys with adjustable Mo/Co atomic ratio are first prepared by H2-assisted cathodic electrodeposition. By virtue of the appropriate electronic structure and hydrogen binding energy, Co–Mo(18%) is the most HER active among the alloys and is further activated by a constant-current electrochemical modification process. Physical characterizations reveal the formation of amorphous Co(OH)2 nanoparticles on the surface. Electrokinetic analysis combined with theoretical calculations reveal that the in-situ formed Co(OH)2 can efficiently promote the water dissociation, resulting in accelerated Volmer-step kinetics. As a result, the Co–Mo(18%)/A-Co(OH)2 simultaneously achieves the optimization of the two factors dominating alkaline HER activity, i.e., water dissociation and hydrogen adsorption/desorption via the bifunctional synergy of the bi-components. The high HER activity (η10 of 47 ​mV at 10 ​mA ​cm−2) of Co–Mo(18%)/A-Co(OH)2 is close to benchmark Pt/C catalyst and comparable or superior to the most active non-noble metal catalysts.

The conventional pretreatment methods for mine water generally include coagulation, sedimentation (flotation), and filtration. However, large equipment footprint, long processing time and pollution from coagulants and flocculants have been limiting the further development of underground mine water treatment. In this light, we designed an underground mine water pretreatment device based on ultrasonic atomization for clarifying and pre-softening mine water so that the turbid mine water could be treated to meet the needs of underground production, firefighting, and dust reduction. We conducted indoor experiments on mine water clarification and pre-softening treatment using water and rock samples from the field mined-out area. The results show that: (1) This method can clarify black-gray turbid mine water with a large amount of solid impurities, effectively removing insoluble solid impurities in the water. (2) Ultrasonic atomization reduces the total hardness of the water by 72.24%. The milligram equivalent concentration of Ca2+ is reduced from 5.33 mg/L to 0.81 mg/L and the milligram equivalent concentration of Mg2+ drops from 5.23 mg/L to 2.13 mg/L, with little impact on pH. (3) The water from the mined-out area after ultrasonic atomization can meet the requirements of sprinkling in underground firefighting, spraying in dust reduction, the mining process of coal mining equipment, and the use of cooling water.

Pediatric intracranial germ cell tumors (GCT) are clinically rare but highly heterogeneous tumors, primarily occurring in children and adolescents. The treatment method depends on the tumor type. Pure germinoma can be cured with radiotherapy and chemotherapy, while mature teratomas can be cured with surgical resection. Non-germinomatous germ cell tumors (NGGCT) require comprehensive treatment. Current domestic and international guidelines or expert consensus recommend initial chemotherapy, followed by surgical resection for those not achieving complete remission. However, clinical practice has found that surgery risks increase after chemotherapy, leading some experts to advocate for direct surgery. Beijing Tiantan Hospital, Capital Medical University proposed a clinical diagnosis and treatment strategy for pediatric intracranial NGGCT (2023 Tiantan version), recommending joint evaluation by neurosurgeons and oncologists for individualized treatment to provide better treatment plans for children.

Abstract The branching fraction of D + → K S 0 π 0 e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e $$ is measured for the first time using 7.93 fb −1 of e + e − annihilation data collected at the center-of-mass energy s $$ \sqrt{s} $$ = 3.773 GeV with the BESIII detector operating at the BEPCII collider, and is determined to be B D + → K S 0 π 0 e + ν e = 0.881 ± 0.017 stat . ± 0.016 syst . % $$ \mathcal{B}\left({D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e\right)=\left(0.881\pm {0.017}_{\textrm{stat}.}\pm {0.016}_{\textrm{syst}.}\right)\% $$ . Based on an analysis of the D + → K S 0 π 0 e + ν e $$ {D}^{+}\to {K}_S^0{\pi}^0{e}^{+}{\nu}_e $$ decay dynamics, we observe the S-wave and P-wave components with fractions of f S-wave = (6.13 ± 0.27stat. ± 0.30syst. )% and f K ¯ ∗ 892 0 = 93.88 ± 0.27 stat . ± 0.29 syst . % $$ {f}_{{\overline{K}}^{\ast }{(892)}^0}=\left(93.88\pm {0.27}_{\textrm{stat}.}\pm {0.29}_{\textrm{syst}.}\right)\% $$ , respectively. From these results, we obtain the branching fractions B D + → K S 0 π 0 S − wave e + ν e = 5.41 ± 0.35 stat . ± 0.37 syst . × 10 − 4 $$ \mathcal{B}\left({D}^{+}\to {\left({K}_S^0{\pi}^0\right)}_{S-\textrm{wave}}{e}^{+}{\nu}_e\right)=\left(5.41\pm {0.35}_{\textrm{stat}.}\pm {0.37}_{\textrm{syst}.}\right)\times {10}^{-4} $$ and B D + → K ¯ ∗ 892 0 e + ν e = 4.97 ± 0.11 stat . ± 0.12 syst . % $$ \mathcal{B}\left({D}^{+}\to {\overline{K}}^{\ast }{(892)}^0{e}^{+}{\nu}_e\right)=\left(4.97\pm {0.11}_{\textrm{stat}.}\pm {0.12}_{\textrm{syst}.}\right)\% $$ . In addition, the hadronic form-factor ratios of D + → K ¯ ∗ 892 0 e + ν e $$ {D}^{+}\to {\overline{K}}^{\ast }{(892)}^0{e}^{+}{\nu}_e $$ at q 2 = 0, assuming a single-pole dominance parameterization, are determined to be r V = V 0 A 1 0 = 1.43 ± 0.07 stat . ± 0.03 syst . $$ {r}_V=\frac{V(0)}{A_1(0)}=1.43\pm {0.07}_{\textrm{stat}.}\pm {0.03}_{\textrm{syst}.} $$ and r 2 = A 2 0 A 1 0 = 0.72 ± 0.06 stat . ± 0.02 syst . $$ {r}_2=\frac{A_2(0)}{A_1(0)}=0.72\pm {0.06}_{\textrm{stat}.}\pm {0.02}_{\textrm{syst}.} $$ .

Abstract As a typical intangible cultural heritage, Toponymic Cultural Heritage (TCH) is rich in geographic information and semantic and physical connotations. In the context of the heritage conservation era, it is highly important to study the spatiotemporal distribution characteristics of toponymic cultural heritage and explore its historical and geographic influencing factors on the sustainable conservation and development of toponymic cultural heritage. However, most existing studies focus on the toponym cultural landscape, and less attention has been given to TCH. Therefore, on the basis of the data of 357 provincial TCH items in Jiangsu Province, this study investigated the spatiotemporal distribution characteristics and historical–geographical influencing factors of the TCH by using geospatial analysis methods, such as the average nearest neighbor, tyson polygon, kernel density estimation, standard deviational ellipse, and superposition coupling analysis, and proposed several strategies for adaptive reuse of TCH. The results show that (1) the TCHs of Jiangsu Province have a spatial distribution characteristic of "sparse in the north, scattered in the middle and dense in the south" and form a high-density agglomeration around the southern part of Jiangsu Province. In the distribution of cultural districts, the Jinling cultural district, the Wu cultural district, and the Huaiyang cultural district have the largest number of TCHs. (2) From the Pre-Qin period to the Ming and Qing Dynasties, TCHs, such as Nanjing, Yangzhou, Zhenjiang, Changzhou, and Suzhou, tended to merge in the southern part of Jiangsu. (3) In terms of type, the roads, streets and alleys of TCHs are the richest, and all types of TCHs are spatially clustered in the southern part of Jiangsu Province, which has a high level of urbanization, industrialization, and a superior geographic environment. (4) TCHs have spatial tendencies toward low altitudes and hydrophilicity, and relatively favorable natural geographical conditions provide a high-quality environment for TCHs in southern Jiangsu Province. Influenced by historical, humanistic, and geographical factors, TCH is unevenly developed spatially. As a historical population concentration area, an important political, economic, and cultural core area, and a center of gravity for cultural development, more TCH resources have survived in the southern part of Jiangsu Province. This study provides a new perspective for interpreting and recognizing TCH as a special intangible cultural heritage and can provide a reference for the sustainable conservation and development of TCH.

Xiaofen Xu,1,* Wumeng Jin,1,* Jingyi Song,1 Xuanming Hu,1 Lu Lu,2 Jida Zhang,1 Changfeng Hu1 1College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jida Zhang; Changfeng Hu, College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China, Email zhjd82@tom.com; zhudianzhuifeng@163.comBackground: Liver injury, such as nonalcoholic fatty liver disease, is a common symptom observed in patients with gout/hyperuricaemia. However, the exact mechanisms are still unclear. There is ongoing controversy about whether representative agents like colchicine and febuxostat, commonly used to manage gout, could also help prevent the liver injury. Liver plays a crucial role in uric acid (UA) production and lipid metabolism. Thus, the study aimed to investigate the aberrant lipid metabolism in the liver during injury and the effects of these drugs.Methods: An advanced multi-dimensional mass spectrometry-based shotgun lipidomics technology was employed for class-targeted lipid analysis of cellular lipidomes in hepatic tissue of a gouty model induced by a combination of monosodium urate crystals and high-fat diet with or without treatment with colchicine and febuxostat. Serum UA, blood urea nitrogen, creatinine, proinflammatory cytokines, expression of AMP-activated protein kinase protein, footpad histopathology, and footpad swelling and pain threshold of these mice were assessed to evaluate the progression of gout.Results: Lipidomics analysis clearly demonstrated that the ectopic fat accumulation as well as changes in fatty acyls composition in TAG pool, impaired mitochondrial function resulted by decreased tetra 18:2 cardiolipin, and reduced 4-hydroxyalkenal bioavailability in liver tissue could contribute to liver damage to the gouty model. Treatment with colchicine or febuxostat not only ameliorated gouty symptoms but also corrected these abnormal hepatic lipid metabolism patterns.Conclusion: This study shed light on underlying mechanism(s) for liver injury in gout/hyperuricaemia and suggested that administration of drugs like colchicine and febuxostat could prevent liver injury.Keywords: gout, hepatic lipidome, febuxostat, colchicine, inflammation

Abstract Background This study aimed to compare the diagnostic accuracy of four indicators, including waist-to-height ratio (WHTR), vascular adiposity index (VAI), TG/HDL-C, and BMI/HDL-C for metabolic syndrome (MS) in Chinese adults aged 40 years and above. Additionally, the study aimed to develop an efficient diagnostic model displayed by a nomogram based on individual’s BMI and circulating HDL-C level. Methods A cross-sectional study was conducted on 699 participants aged 40 years and above. Quartiles of BMI/HDL-C, TG/HDL-C, VAI, and WHTR were used as independent variables, and metabolic syndrome was used as the dependent variable. Logistic regression was conducted to explore the impact of each parameter on the risk of MS. The areas under the receiver operating characteristics were compared to determine the accuracy of the indicators in diagnosing MS in the participants. Logistic regression was run to construct the nomograms, and the performance of the nomogram was assessed by a calibration curve. Results MS subjects had higher levels of BMI, BFM, PBF, VFA, AMC, WC, SCR, TG, and insulin, but lower LDH and HDL-C levels than the subjects without MS. The BMI/HDL-C ratio was positively correlated with the prevalence of MS and its components. The final diagnostic model included five variables: gender, BFM, WC, TG, and BMI/HDL-C. The model showed good calibration and discrimination power with an AUC of 0.780. The cut-off value for the nomogram was 0.623 for diagnosing MS. Conclusions BMI/HDL-C ratio was an independent risk factor for MS in Chinese adults. BMI/HDL-C was significantly correlated with MS and its components. BMI/HDL-C was the most powerful diagnostic indicator compared to other indicators, including TG/HDL-C, VAI and WHTR for diagnosing MS. The nomogram drawn based on the diagnostic model provided a practical tool for diagnosing MS in Chinese adults.

Abstract Background Cerebral venous thrombosis (CVT) is a rare but serious condition that can lead to significant morbidity and mortality. Virchow’s triad elucidates the role of blood hypercoagulability, blood flow dynamics, and endothelial damage in the pathogenesis of CVT. Cerebral venous congestion (CVC) increases the risk of cerebral venous sinus thrombosis and can lead to recurrent episodes and residual symptoms. However, the precise mechanism by which blood congestion leads to thrombosis remains unclear. Our objective was to investigate the cellular and molecular alterations linked to CVC through analysis of the pathological morphology of venous sinus endothelial cells and transcriptomic profiling. Results This study demonstrated a remarkable correlation between CVC and the phenotypic transformation of endothelial cells from an anticoagulant to a procoagulant state. The findings revealed that cerebral venous stasis results in tortuous dilatation of the venous sinuses, with slow blood flow and elevated pressure in the sinuses and damaged endothelial cells of the retroglenoid and internal jugular vein ligation (JVL) rat model. Mechanistically, analysis of transcriptomic results of cerebral venous sinus endothelial cells showed significant activation of platelet activation, complement and coagulation cascades pathway in the JVL rats. Furthermore, the expression of von Willebrand factor (vWF) and coagulation factor VIII (F8) in the complement and coagulation cascades and Fgg and F2 in the platelet activation was increased in the cerebral venous sinuses of JVL rats than in sham rats, suggesting that endothelial cell injury in the venous sinus induced by CVC has a prothrombotic effect. In addition, endothelial cell damage accelerates coagulation and promotes platelet activation. Significantly, the concentrations of vWF, F2 and F8 in venous sinus blood of patients with internal jugular vein stenosis were higher than in their peripheral blood. Conclusion Collectively, our data suggest that CVC can induce endothelial cell damage, which then exhibits a procoagulant phenotype and ultimately increases the risk of CVT. This research contributes to our understanding of the pathophysiology of CVC associated with procoagulant factors and reexamines the components of Virchow’s triad in the context of CVC.

Abstract Objective To compare the levels of functional impairments, discomfort and satisfaction experienced by those treated with full-mouth customized lingual appliances (Lingual appliances), full-mouth self-ligating bracket (Labial appliances), or upper lingual and lower labial appliances (Mixed appliances) using questionnaires. Materials and methods Patients within one year of the end of treatment were included in the survey and given a questionnaire concerning different kinds of discomfort and difficulties during the treatment process. The questionnaires focused on the following aspects including speech difficulty, pain (lip, cheek or tongue), difficulty in chewing, difficulty in tooth brushing and overall aesthetics and comfortability. Ordinary one-way ANOVA Tukey’s multiple comparison tests and Kruskal–Wallis tests were employed to analyze the data. Results A total of 115 patients participated in the study. In terms of functional impairments and discomfort, the rate and degree of speech difficulty was significantly higher in the Lingual appliances Group than that in the Labial appliances Group. But there was no difference among the three groups for difficulty in chewing and tooth brushing. Both lingual and labial appliances caused a similar level of overall pain, however, those treated with lingual appliances experienced more tongue pain, and those treated with labial appliances experienced more cheek and lip pain. The most common sites of irritation were the tongue lateral and tongue tip in the Lingual appliances Group, tongue lateral and cheek in the Mixed appliances Group, and cheek and lower lip in the Labial appliances Group. In total, patients gave highest scores to mixed appliances for comfortability and lowest scores to labial appliances for aesthetics when it came to satisfaction. Conclusions Lingual and labial appliances caused similar level of overall pain. Taking into account the overall comfortability, aesthetics and cost, the mixed appliances may be suitable for some patients who have aesthetic and comfort pursuits.

Lifen Lu,1 Di Sheng,1 Xiaowei Xia,2 Guanghui Chen,3 Jiali Liang,4 Xiulan Shen,1 Gui Zheng1 1Department of Nursing, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Ministry of Health, the Third Hospital of Ninghai County, Ningbo, Zhejiang, People’s Republic of China; 3Ministry of Health, the Liangzhu Street Community Health Service Center, Yuhang District, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Nursing, the First People’s Hospital of Yuhang District, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiulan Shen; Gui Zheng, Department of Nursing, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Email shenxl@zju.edu.cn; zhenggui1119@zju.edu.cnAim: To investigate the emotional response of hospital staff to the Depression Anxiety Stress Scale-21 (DASS-21) over the COVID-19 pandemic and after the relaxation of prevention and control measures in Zhejiang Province, China, and identify influencing factors.Design: Multicenter online cross-sectional design.Methods: From January 10, 2023, to January 20, 2023, 1054 hospital employees in Zhejiang, China, were recruited using WeChat. Data was gathered via online, self-administered surveys. T-tests and one-way analyses of variance, Pearson’s correlation analysis, and multiple linear stepwise regression analyses were used to examine the data.Results: More than 90% of hospital employees were infected with COVID-19. Through regression analysis, the following variables were found to be independent predictors of emotional response to DASS-21: resilience (− 13.346, P < 0.0001), sleep (14.689, P < 0.0001), friend support (− 4.278, P < 0.0001), education level (2.699, P = 0.007), and marriage (− 2.214, P = 0.027). The emotional responses were not as severe as predicted, but they were still well above the Chinese norm. A longitudinal comparison of DASS-21 emotional responses with similar studies showed a parabolic downward trend over time.Conclusion: Our results identified education level, marriage, friend support, resilience, and sleep as independent predictors of emotional responses to the DASS-21 among hospital workers in this outbreak. Improving the mental resilience and sleep status of staff is a key target. Unmarried medical personnel with higher education should be given greater attention and support by management. In addition, there is still room for further improvement in the government and societal responses to similar outbreaks. The study also found a parabolic downward trend in DASS-21 emotional responses among hospital workers during the COVID-19 outbreak over time.Keywords: COVID-19, hospital staff, DASS-21 emotional response, influencing factors, trajectory of change

A method for the determination of trimetazidine and clomiphene in animal-derived foods was developed by mixed-mode reversed-phase strong cation exchange solid phase extraction cleanup followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Samples were extracted with 0.5% (V/V) formic acid in acetonitrile, and purified on a mixed-mode reversed phase strong cation exchange column (PRiME MCX). The chromatographic separation was performed on a Waters ACQUITY UPLC HSS T3 column by gradient elution using a mobile phase composed of acetonitrile and 0.1% formic acid. The analytes were detected in the positive ion mode using multiple reaction monitoring (MRM). Quantification was performed by the internal standard method. The results showed that good linearity was observed for trimetazidine and clomiphene in the concentration range of 0.3–100.0 ng/mL with determination coefficients (R2) > 0.999. The average recoveries of this method ranged from 93.4% to 112.1%, with relative standard deviations (RSDs) of 0.68%–4.81% (n = 6). The limit of detection (LOD) and the limit of quantitation (LOQ) were 0.1 and 0.3 μg/kg, respectively. The developed method is sensitive, stable, practical, and suitable for the determination of trimetazidine and clomiphene in animal-derived foods, which can provide effective technical support for food safety assurance for sports events.

Case presentation A 47-year-old Asian woman was admitted with worsening chest tightness and dyspnea for 10 days. Computed tomography (CT) showed changes in the trachea and segmental bronchi. Pulmonary function results suggestive of severe obstructive ventilatory dysfunction. Bronchoscopic findings showed the presence of multiple nodular lesions in the patient’s trachea and left and right main bronchi. Bronchoscopic biopsy, lymph node biopsy and bone marrow aspiration flow cytometry test results led to a definitive diagnosis of chronic lymphocytic leukemia (CLL), staged as Binet stage B and Rai stage 2.

Abstract Ensuring equitable access to health services is crucial for public welfare and social equity, and is a key objective of the United Nations’ Sustainable Development Goals (SDGs). However, existing datasets often define hospital accessibility using travel time to hospitals in geographic dimension only, without considering the supply (hospital capacity) and demand (population distribution) dynamics. To overcome this limitation, we developed and validated a national-scale 1 km map of both hospital travel time and hospital accessibility in China. We used the Gaussian two-step floating catchment area (Ga2SFCA) model to calculate hospital accessibility, incorporating hospital capacity and service population. Various file types and statistical indicators are provided, making the dataset highly accessible for non-specialists. The dataset fills the gap in publicly available nationwide hospital accessibility data for China and can serve as a critical tool in optimizing resource allocation and developing targeted strategies to improve healthcare equity.