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BACKGROUND: Cholangiocarcinoma (CHOL) is the second most common primary hepatic malignant tumor, following hepatocellular carcinoma (HCC). CHOL is highly aggressive and heterogeneous resulting in poor prognosis. The diagnosis and prognosis of CHOL has not improved in the past decade. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is reported to be associated with tumors, however, its role in CHOL has not been revealed. This study is mainly for exploring the prognostic values and potential function of ACSL4 in CHOL. METHODS: We investigated the expression level and prognostic value of ACSL4 in CHOL based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. TIMER2.0, TISIDB and CIBERSORT databases were utilized to assess the associations between ACSL4 and immune infiltration cells in CHOL. Single-cell sequencing data from GSE138709 was analyzed to study the expression of ACSL4 in different types of cells. ACSL4 co-expressed genes were analyzed by Linkedomics. Additionally, Western Blot, qPCR, EdU assay, CCK8 assay, transwell assay and wound healing assay were performed to further confirm the roles of ACSL4 in the pathogenesis of CHOL. RESULTS: We found that the level of ACSL4 was higher in CHOL and it was correlated with the diagnosis and prognosis of CHOL patients. Then, we observed that the infiltration level of immune cells was related to the level of ACSL4 in CHOL. Moreover, ACSL4 and its co-expressed genes were mainly enriched in metabolism-related pathway and ACSL4 is also a key pro-ferroptosis gene in CHOL. Finally, knockdown of ACSL4 could reverse the tumor-promoting effect of ACSL4 in CHOL. CONCLUSIONS: The current findings demonstrated ACSL4 may as a novel biomarker for CHOL patients, which might regulate immune microenvironment and metabolism resulting in poor prognosis.
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Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Prognóstico , Colangiocarcinoma/genética , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Noninvasive skin examination evolved rapidly in recent years, with multiphoton microscopy (MPM) and reflectance confocal microscopy (RCM) being used to image in-vivo skin at high resolution. The aim of this study is to compare the imaging clarity between the two techniques and measure the thickness of the epidermis in different body sites. We also measured the degree of skin aging with noninvasive tools. METHODS: Fifty-six volunteers were evaluated and measured at three different body sites, including the cheek, volar forearm, and back. We used RCM and MPM to evaluate the clarity of each skin layer, including stratum corneum, stratum granulosum, stratum spinosum, dermo-epidermal junction, and dermis. We measured epidermal thickness (ET) at the three body sites in individuals of different ages and genders. We assessed skin aging by the second harmonic to autofluorescence aging index of dermis (SAAID), and multiple linear regression was used to analyze the factors affecting SAAID. RESULTS: MPM had advantages in observation of stratum granulosum, collagen fiber, and elastic fiber (p < 0.001), but RCM provided better observation in dermo-epidermal junction layer (p < 0.001). The epidermis was thicker in the cheek area than the volar forearm and back in both RCM and MPM detection, and the average ET measured by MPM was lower than RCM. ET varied among the three body sites with significant differences (p < 0.05). ET was significantly lower at almost all sites in individuals above 40y (p < 0.05). SAAID decreased with age, and more rapidly in women. Cheeks have lower SAAID scores than other body sites. CONCLUSION: MPM and RCM provide noninvasive methods for imaging skin and each method has its own advantages. Epidermal thickness and SAAID correlated with age, gender, and different body sites. MPM could also assess the degree of skin aging, which could guide the clinical treatment of patients with diffferent ages and genders in the above body sites.
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Envelhecimento da Pele , Pele , Humanos , Feminino , Masculino , Microscopia Confocal/métodos , Pele/diagnóstico por imagem , Epiderme/diagnóstico por imagem , EnvelhecimentoRESUMO
Wenchang chickens, a native breed in the Hainan province of China, are famous for their meat quality and adaptability to tropical conditions. For effective management and conservation, in the present study, we systematically investigated the characteristics of genetic variations and runs of homozygosity (ROH) along the genome using re-sequenced whole-genome sequencing data from 235 Wenchang chickens. A total of 16,511,769 single nucleotide polymorphisms (SNPs) and 53,506 ROH segments were identified in all individuals, and the ROH of Wenchang chicken were mainly composed of short segments (0-1 megabases (Mb)). On average, 5.664% of the genome was located in ROH segments across the Wenchang chicken samples. According to several parameters, the genetic diversity of the Wenchang chicken was relatively high. The average inbreeding coefficient of Wenchang chickens based on FHOM, FGRM, and FROH was 0.060 ± 0.014, 0.561 ± 0.020, and 0.0566 ± 0.01, respectively. A total of 19 ROH islands containing 393 genes were detected on 9 different autosomes. Some of these genes were putatively associated with growth performance (AMY1a), stress resistance (THEMIS2, PIK3C2B), meat traits (MBTPS1, DLK1, and EPS8L2), and fat deposition (LANCL2, PPARγ). These findings provide a better understanding of the degree of inbreeding in Wenchang chickens and the hereditary basis of the characteristics shaped under selection. These results are valuable for the future breeding, conservation, and utilization of Wenchang and other chicken breeds.
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In 2016, the SOFA score was proposed as the main evaluation system for diagnosis in the definition of sepsis 3.0, and the SOFA score has become a new research focus in sepsis. Some people are skeptical about diagnosing sepsis using the SOFA score. Experts and scholars from different regions have proposed different, modified versions of SOFA score to make up for the related problems with the use of the SOFA score in the diagnosis of sepsis. While synthesizing the different improved versions of SOFA proposed by experts and scholars in various regions, this paper also summarizes the relevant definitions of sepsis put forward in recent years to build a clear, improved application framework of SOFA score. In addition, the comparison between machine learning and SOFA scores related to sepsis is described and discussed in the article. Taken together, by summarizing the application of the improved SOFA score proposed in recent years in the related definition of sepsis, we believe that the SOFA score is still an effective means of diagnosing sepsis, but in the process of the continuous refinement and development of sepsis in the future, the SOFA score needs to be further refined and improved to provide more accurate coping strategies for different patient populations or application directions regarding sepsis. Against the big data background, machine learning has immeasurable value and significance, but its future applications should add more humanistic references and assistance.
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The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the development of nucleic acid diagnosis technology. Several platforms with isothermal amplification methods have achieved sensitive and specific detection of SARS-CoV-2. However, they still suffer from complicated operations, delicate instruments, and unintuitive signal output modes. Here, a system consisting of CRISPR Cas12a-based biosensors and commercial pregnancy test strips (CRISPR-PTS) was established for the point-of-care testing of SARS-CoV-2. The target viral nucleic acids were finally reflected on the test strips through four steps, namely sample pretreatment, RT-RAA amplification, CRISPR Cas12a reaction, and separation-free hCG detection. This CRISPR-PTS assay possessed an outstanding sensitivity of as low as 1 copy per µL for SARS-CoV-2 detection and showed an excellent specificity in distinguishing the SARS-CoV-2 pseudovirus as well as other SARS-like viral clinical samples. In addition, the CRISPR-PTS assay performed well in practical applications, with 96.3% agreement versus RT-qPCR in spiked samples. With the advantages of low reagent cost, simple operation procedure, and visible signal output, CRISPR-PTS assay was expected to provide a strong supplement in the prevention and early diagnosis of infectious diseases in resource-limited situations.
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Chemotherapy based on molecular drugs remains the most frequently used approach for the therapy of tumors, however their poor specificity, severe side effects and tumor resistance often seriously hinder their applications. It is therefore desirable to develop a new, alternative therapeutic strategy for tumor treatment without traditional chemotherapeutic drugs. Herein, we report a drug-free tumor therapy approach involving spermine (SPM)-responsive intracellular biomineralization in tumor cells. In this work, we designed calcium carbonate (CaCO3) nanoparticles capped with folic acid and supramolecular peptides, which could target tumor cells and rapidly self-aggregate into micron-sized CaCO3 aggregates in SPM-overexpressed tumor cells. Due to the extended intracellular retention, CaCO3 aggregates could induce intracellular biomineralization and Ca2+ overload of tumor cell, leading to mitochondrial damage and cellular apoptosis, resulting in effective inhibition of tumor growth without serious side effects otherwise seen in conventional chemotherapy.
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Nanopartículas , Neoplasias , Humanos , Espermina/uso terapêutico , Biomineralização , Neoplasias/tratamento farmacológico , Portadores de Fármacos , Carbonato de Cálcio/químicaRESUMO
Podosphaera xanthii is a well-known obligate biotrophic pathogen that causes powdery mildew (PM) disease on cucurbitaceous plants and is one of the most important limiting factors for cucumber production worldwide. To better understand the avirulence effector proteins in this species that are known to be involved in host-pathogen interaction, the draft genome assembly of P. xanthii isolate YZU573 from cucumber leaves with symptoms of PM was obtained with a hybrid approach, combining nanopore long-read and llumina paired-end sequencing. The final P. xanthii YZU573 genome assembly of 152.7 Mb consists of 58 contigs, with an N50 value of 0.75 Mb and 6491 predicted protein-coding genes. The effector analysis using the whole-genome sequence information revealed a total of 87 putative effector candidates, and 65 of them had their analogs, whereas the remaining 22 were novel ones. The new P. xanthii genome provides valuable resources to better understand plant-microbe interaction in cucumber PM disease.
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BACKGROUND: Superficial basal cell carcinoma (SBCC) is the rare subtype of basal cell carcinoma (BCC). BCC occurs in exposed areas such as the head and face, SCBB prone to form in trunk. Due to the manifestation of erythema and desquamation, it is prone to misdiagnosed as Bowen's disease in clinica. MATERIALS AND METHODS: A 68-year-old female presented with coin-sized erythema located on the lower abdomen for 5 years. Histopathological examination was performed, and results informed the diagnosis of SBCC. Lesions were detected by dermoscopy, reflectance confocal microscopy (RCM) and multiphoton microscopy (MPM). RESULTS: Dermoscopy revealed yellow-red background with more dendritic and linear proliferating vessels and more blue-gray nonaggregated dots structures. RCM displayed streaming of stratum spinosum, tortuous dilated vessels, highlighted inflammatory cells, and medium refraction round and oval tumor cell masses. MPM showed epidermal cells in polar arrangement, increased cell spacing, disorganized stratum granulosum and elastic fibers are gathered in clusters. CONCLUSION: We described a case of SBCC detected by dermoscopy, RCM and MPM. Noninvasive imaging features may provide a potentially tools in recognition and differentiation of SBCC.
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Doença de Bowen , Carcinoma Basocelular , Neoplasias Cutâneas , Feminino , Humanos , Idoso , Neoplasias Cutâneas/patologia , Doença de Bowen/diagnóstico por imagem , Dermoscopia/métodos , Microscopia Confocal/métodos , Carcinoma Basocelular/patologia , EritemaRESUMO
Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.529 (Omicron) has rapidly become the dominant strain, with an unprecedented number of mutations within its spike gene. However, it remains unknown whether these variants have alterations in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies and entry inhibitors. In this study, we found that Omicron spike has evolved to escape neutralization by three-dose inactivated-vaccine-elicited immunity but remains sensitive to an angiotensin-converting enzyme 2 (ACE2) decoy receptor. Moreover, Omicron spike could use human ACE2 with a slightly increased efficiency while gaining a significantly increased binding affinity for a mouse ACE2 ortholog, which exhibits limited binding with wild-type (WT) spike. Furthermore, Omicron could infect wild-type C57BL/6 mice and cause histopathological changes in the lungs. Collectively, our results reveal that evasion of neutralization by vaccine-elicited antibodies and enhanced human and mouse ACE2 receptor engagement may contribute to the expanded host range and rapid spread of the Omicron variant. IMPORTANCE The recently emerged SARS-CoV-2 Omicron variant with numerous mutations in the spike protein has rapidly become the dominant strain, thereby raising concerns about the effectiveness of vaccines. Here, we found that the Omicron variant exhibits a reduced sensitivity to serum neutralizing activity induced by a three-dose inactivated vaccine but remains sensitive to entry inhibitors or an ACE2-Ig decoy receptor. Compared with the ancestor strain isolated in early 2020, the spike protein of Omicron utilizes the human ACE2 receptor with enhanced efficiency while gaining the ability to utilize mouse ACE2 for cell entry. Moreover, Omicron could infect wild-type mice and cause pathological changes in the lungs. These results reveal that antibody evasion, enhanced human ACE2 utilization, and an expanded host range may contribute to its rapid spread.
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COVID-19 , Evasão da Resposta Imune , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Enzima de Conversão de Angiotensina 2/genética , Especificidade de Hospedeiro , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
Dual- or multi-modality combination therapy has become one of the most effective strategies to overcome drug resistance in cancer therapy, and the optimized ratio of the therapeutic agents working on the tumor greatly affects the therapeutic outcomes. However, the absence of a facile method to optimize the ratio of therapeutic agents in nanomedicine has, at least in part, impaired the clinical potential of combination therapy. Herein, a new cucurbit[7]uril (CB[7])-conjugated hyaluronic acid (HA) based nanomedicine was developed, in which both chlorin e6 (Ce6) and oxaliplatin (OX) were co-loaded non-covalently at an optimized ratio via facile host-guest complexation, for optimal, combined photodynamic therapy (PDT)/chemotherapy. To maximize the therapeutic efficacy, a mitochondrial respiration inhibitor, atovaquone (Ato), was also loaded into the nanomedicine to limit consumption of oxygen by the solid tumor, sparing oxygen for more efficient PDT. Additionally, HA on the surface of nanomedicine allowed targeted delivery to cancer cells with over-expressed CD44 receptors (such as CT26 cell lines). Thus, this supramolecular nanomedicine platform with an optimal ratio of photosensitizer and chemotherapeutic agent not only provides an important new tool for enhanced PDT/chemotherapy of solid tumors, but also offers a CB[7]-based host-guest complexation strategy to facilely optimize the ratio of therapeutic agents for multi-modality nanomedicine. STATEMENT OF SIGNIFICANCE: Chemotherapy remains the most common modality for cancer treatment in clinical practice. Combination therapy by co-delivery of two or more therapeutic agents has been recognized as one of the most effective strategies to improve therapeutic outcome of cancer treatment. However, the ratio of loaded drugs could not be facilely optimized, which may greatly affect the combination efficiency and overall therapeutic outcome. Herein, we developed a hyaluronic acid based supramolecular nanomedicine with facile method to optimize the ratio of two therapeutic agents for improved therapeutic outcome. This supramolecular nanomedicine not only provides an important new tool for enhanced photodynamic therapy/chemotherapy of solid tumors, but also offers insights in using macrocyclic molecule-based host-guest complexation to facilely optimize the ratio of therapeutic agents in multi-modality nanomedicine.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Oxaliplatina , Nanomedicina , Ácido Hialurônico/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias/tratamento farmacológico , Porfirinas/farmacologia , Oxigênio , Linhagem Celular TumoralRESUMO
Marek's disease (MD) is a lymphoproliferative neoplastic disease caused by Marek's disease virus (MDV). Previous studies have showed that DNA methylation was involved in MD development, but systematic studies are still lacking. Herein, we performed whole genome bisulfite sequencing (WGBS) and RNA-seq in MDV-infected tumorous spleens (IN), noninfected spleens (NoIN), and survivor (SUR) spleens of chickens to identify the genes playing important roles in MD tumor transformation. We generated the first genome-wide DNA methylation profile of MDV-infected, noninfected, and survivor chickens. Combined the WGBS and RNA-Seq, we found that the expression of 25% differential expression genes (DEGs) were significantly correlated with methylation of CpG sites in their gene bodies or promoters. Further, we focused on the DEGs with differentially methylated regions (DMRs) on genes' body and promoter, and it showed the expression of 60% DEGs were significantly correlated with methylation of CpG sites in DMRs. Finally, we identified 8 genes, including CD4, CTLA4, DTL, HMGB1, LGMN, NUP210, RAD52, and ZAP70, and their expression was negatively correlated with methylation of DMRs in their promoters in both IN vs. NoIN and IN vs. SUR. These 8 genes showed specifically high expression in IN groups and clustered in module turquoise analyzed by WGCNA. Out of 8 genes, CD4 and HMGB1 were drop in QTLs associated with MD resistance. Thus, we overexpressed the 2 genes to simulate their high expression in the IN group and found they significantly promoted MDCC-MSB-1 cell proliferation, which revealed they might play promoting roles in MD tumorigenesis in IN due to their high expression induced by hypomethylation.
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Proteína HMGB1 , Herpesvirus Galináceo 2 , Doença de Marek , Neoplasias , Animais , Doença de Marek/genética , Galinhas/genética , Transcriptoma , Baço , Metilação de DNA , Proteína HMGB1/genética , Herpesvirus Galináceo 2/genética , Carcinogênese/genética , Neoplasias/veterináriaRESUMO
Despite of the high lethality of gallbladder cancer (GBC), little is known regarding molecular regulation of the tumor immunosuppressive microenvironment. Here, we determined tumor expression levels of YKL-40 and the molecular mechanisms by which YKL-40 regulates escape of anti-tumor immune surveillance. We found that elevated expression levels of YKL-40 in plasma and tissue were correlated with tumor size, stage IV and lymph node metastasis. Single cell transcriptome analysis revealed that YKL-40 was predominantly derived from M2-like subtype of infiltrating macrophages. Blockade of M2-like macrophage differentiation of THP-1 cells with YKL-40 shRNA resulted in reprogramming to M1-like macrophages and restricting tumor development. YKL-40 induced tumor cell expression and secretion of growth differentiation factor 15 (GDF15), thus coordinating to promote PD-L1 expression mediated by PI3K, AKT and/or Erk activation. Interestingly, extracellular GDF15 inhibited intracellular expression of GDF15 that suppressed PD-L1 expression. Thus, YKL-40 disrupted the balance of pro- and anti-PD-L1 regulation to enhance expression of PD-L1 and inhibition of T cell cytotoxicity, leading to tumor immune evasion. The data suggest that YKL-40 and GDF15 could serve as diagnostic biomarkers and immunotherapeutic targets for GBC.
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Neoplasias da Vesícula Biliar , Humanos , Antígeno B7-H1 , Linhagem Celular Tumoral , Proteína 1 Semelhante à Quitinase-3/metabolismo , Neoplasias da Vesícula Biliar/metabolismo , Fator 15 de Diferenciação de Crescimento/genética , Fator 15 de Diferenciação de Crescimento/metabolismo , Macrófagos/metabolismo , Evasão Tumoral , Microambiente TumoralRESUMO
Neuropilin 1 (NRP1), a non-tyrosine kinase receptor for several ligands, is highly expressed in many kinds of mesenchymal stem cells (MSCs), but its function is poorly understood. In this study, we explored the roles of full-length NRP1 and glycosaminoglycan (GAG)-modifiable NRP1 in adipogenesis in C3H10T1/2 cells. The expression of full-length NRP1 and GAG-modifiable NRP1 increased during adipogenic differentiation in C3H10T1/2 cells. NRP1 knockdown repressed adipogenesis while decreasing the levels of Akt and ERK1/2 phosphorylation. Moreover, the scaffold protein JIP4 was involved in adipogenesis in C3H10T1/2 cells by interacting with NRP1. Furthermore, overexpression of non-GAG-modifiable NRP1 mutant (S612A) greatly promoted adipogenic differentiation, accompanied by upregulation of the phosphorylated Akt and ERK1/2. Taken together, these results indicate that NRP1 is a key regulator that promotes adipogenesis in C3H10T1/2 cells by interacting with JIP4 and activating the Akt and ERK1/2 pathway. Non-GAG-modifiable NRP1 mutant (S612A) accelerates the process of adipogenic differentiation, suggesting that GAG glycosylation is a negative post-translational modification of NRP1 in adipogenic differentiation.
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Adipogenia , Células-Tronco Mesenquimais , Adipogenia/genética , Neuropilina-1/genética , Neuropilina-1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Diferenciação Celular/genética , Células-Tronco Mesenquimais/metabolismoRESUMO
A full understanding of the inactivated COVID-19 vaccine-mediated antibody responses to SARS-CoV-2 circulating variants will inform vaccine effectiveness and vaccination development strategies. Here, we offer insights into the inactivated vaccine-induced antibody responses after prime-boost vaccination at both the polyclonal and monoclonal levels. We characterized the VDJ sequence of 118 monoclonal antibodies (mAbs) and found that 20 neutralizing mAbs showed varied potency and breadth against a range of variants including XBB.1.5, BQ.1.1, and BN.1. Bispecific antibodies (bsAbs) based on nonoverlapping mAbs exhibited enhanced neutralizing potency and breadth against the most antibody-evasive strains, such as XBB.1.5, BQ.1.1, and BN.1. The passive transfer of mAbs or their bsAb effectively protected female hACE2 transgenic mice from challenge with an infectious Delta or Omicron BA.2 variant. The neutralization mechanisms of these antibodies were determined by structural characterization. Overall, a broad spectrum of potent and distinct neutralizing antibodies can be induced in individuals immunized with the SARS-CoV-2 inactivated vaccine BBIBP-CorV, suggesting the application potential of inactivated vaccines and these antibodies for preventing infection by SARS-CoV-2 circulating variants.
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Vacinas contra COVID-19 , COVID-19 , Feminino , Animais , Camundongos , Humanos , SARS-CoV-2/genética , COVID-19/prevenção & controle , Anticorpos Monoclonais , Anticorpos Neutralizantes , Camundongos Transgênicos , Vacinas de Produtos Inativados , Anticorpos AntiviraisRESUMO
The distal metastasis of tumor cells is viewed as a series of concurrent processes rather than a linear cascade of events. Accompanied with the progression of the primary tumor, a favorable microenvironment, refered as pre-metastatic niche, has been created in pre-metastatic organs and sites by primary tumors for subsequent metastases. The proposal of "pre-metastatic niche" theory brings fresh insight into our understanding of cancer metastasis. Myeloid-derived suppressor cells (MDSCs) are indispensable for the formation of pre-metastatic niche, which empower the niche to favor tumor cell colonization and promote metastasis. In this review, we aim to provide a comprehensive understanding of the regulation of pre-metastatic niche formation by MDSCs and to conceptualize the framework for understanding the related factors involved in cancer metastasis.
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Células Supressoras Mieloides , Neoplasias , Humanos , Células Supressoras Mieloides/patologia , Neoplasias/patologia , Microambiente Tumoral , Metástase NeoplásicaRESUMO
Trem2, a transmembrane protein that is simultaneously expressed in both bone marrow-derived and embryonic-derived liver-resident macrophages, plays a complex role in liver inflammation. The unique role of myeloid Trem2 in hepatic ischemia-reperfusion (IR) injury is not precisely understood. Our study showed that in the early stage of inflammation induction after IR, Deletion of myeloid Trem2 inhibited the induction of iNOS, MCP-1, and CXCL1/2, alleviated the accumulation of neutrophils and mitochondrial damage, and simultaneously decreased ROS formation. However, when inflammatory monocyte-macrophages gradually evolved into CD11bhiLy6Clow pro-resolution macrophages through a phenotypic switch, the story of Trem2 took a turn. Myeloid Trem2 in pro-resolution macrophages promotes phagocytosis of IR-accumulated apoptotic cells by controlling Rac1-related actin polymerization, thereby actively promoting the resolution of inflammation. This effect may be exercised to regulate the Cox2/PGE2 axis by Trem2, alone or synergistically with MerTK/Arg1. Importantly, when myeloid Trem2 was over-expressed, the phenotypic transition of monocytes from a pro-inflammatory to a resolution type was accelerated, whereas knockdown of myeloid Trem2 resulted in delayed upregulation of CX3CR1. Collectively, our findings suggest that myeloid Trem2 is involved in the cascade of IR inflammation in a two-sided capacity, with complex and heterogeneous roles at different stages, not only contributing to our understanding of sterile inflammatory immunity but also to better explore the regulatory strategies and intrinsic requirements of targeting Trem2 in the event of sterile liver injury.
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Macrófagos , Traumatismo por Reperfusão , Animais , Camundongos , Macrófagos/metabolismo , Fagocitose , Inflamação/genética , Inflamação/metabolismo , Traumatismo por Reperfusão/genética , Monócitos/metabolismo , Camundongos Endogâmicos C57BL , Glicoproteínas de Membrana/genética , Receptores Imunológicos/genéticaRESUMO
To address the issue of declining performance over time with manual uterine manipulation during minimally invasive gynecologic surgery, we propose a novel uterine manipulation robot that offers tireless, stable, and safer manipulation. This proposed robot consists of a 3-DoF remote center of motion (RCM) mechanism and a 3-DoF manipulation rod. The RCM mechanism uses a single-motor bilinear-guided design that allows for a wide range of pitch motion (-50 to 34 degrees) while maintaining a compact structure. The manipulation rod has a tip diameter of only 6 mm, allowing it to accommodate almost any patient's cervix. The 30-degree distal pitch motion and ± 45-degree distal roll motion of the instrument further improve uterine visualization. The tip of the rod can be opened into a T-shape to minimize damage to the uterus. Laboratory tests have revealed that our device has a highly precise mechanical RCM accuracy of 0.373mm and is capable of handling a maximum load of 500g. Furthermore, through clinical testing, the robot has been proven to offer improved manipulation and visualization of the uterus, making it a valuable addition to the surgical tools available to gynecologists.
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Purpose: The purpose of this study is to investigate whether the emotional labor of service employees affects customer service misbehavior and repurchase intention and to explore the mechanism and boundary conditions. Methods: We collected a total of 252 pairs of employee-customer valid matching data and used SPSS 24.0 and Mplus7.0 statistical analysis tools to perform statistical analysis and hypothesis testing. Results: The results showed that employees' surface acting has a significant positive impact on customer misbehavior and negative impact on repurchase intention via perceived face threat, while deep acting has a significant negative impact on customer misbehavior and positive impact on repurchase intention via perceived face threat. And customer face threat sensitivity not only moderates the relationship between service employee emotional labor and customer perceived face threat but also moderates the indirect effect of surface acting on customer misbehavior and repurchase intention via customer perceived face threat. Conclusion: Based on face theory, this study explained how and when emotional labor of service employees may affect customer service misbehavior and repurchase intention. These results contribute to the emotional labor and customer service misbehavior literature by introducing perceived face threat as an underlying mechanism and face threat sensitivity as a boundary condition. In addition, this study suggests that service-oriented enterprises should pay attention to the management and guidance of employees' emotional labor and try their best to let employees show deep acting rather than surface acting.
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Risk genes and abnormal brain structural indices of psychiatric disorders have been extensively studied. However, whether genetic risk influences brain structure in the general population has been rarely studied. The current study enrolled 483 young Chinese adults, calculated their polygenic risk scores (PRS) for psychiatric disorders based on Psychiatric Genomics Consortium GWAS results, and examined the association between PRSs and brain volume. We found that PRSs were associated with the volume of many brain regions, with differences between PRS for different disorder, calculated at different threshold, and calculated using European or East Asian ancestry. Of them, the PRS for Major Depressive Disorder based on European ancestry was positively associated with right temporal gyrus; the PRS for schizophrenia based on East Asian ancestry was negatively associated with right precentral and postcentral gyrus; the PRS for schizophrenia based on European ancestry was positively associated with right superior temporal gyrus. All these brain regions are critical for corresponding disorders. However, no significant associations were found between PRS for Autism Spectrum Disorder / Bipolar Disorder and brain volume; and the association between PRS for Attention Deficit Hyperactivity Disorder at different thresholds and brain volume was inconsistent. These findings suggest distinct brain mechanisms underlying different psychiatric disorders.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtorno Depressivo Maior , Adulto , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/genética , Encéfalo/diagnóstico por imagem , Fatores de Risco , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estudo de Associação Genômica Ampla/métodos , Predisposição Genética para Doença/genéticaRESUMO
Swelling is a very common phenomenon in organic substances. However, the swelling behaviors of inorganic substances had rarely been reported. In this study, a new type of swellable organic-inorganic hybrid polymer (PIL@CHT) was designed and successfully synthesized through free-radical copolymerization of polymerizable phosphonium ionic liquid monomer and vinyl-functionalized hydrotalcite (CHT). The swelling behaviors of PIL@CHT in various solvents with a wide range of Hansen solubility parameters (δT) were investigated, and PIL@CHT exhibited excellent swellable capacity in the solvents with δT > 24.4 MPa1/2. The swollen state of the hybrid PIL@CHT in water presented a network structure with a diameter of approximately 8-12 µm, and CHT particles were well dispersed to the channel of PIL. PIL@CHT was applied to catalyze the CO2-assisted hydration of propylene oxide (PO), in which a cascade reaction including the cycloaddition of CO2 and PO and the subsequent hydrolysis of propylene carbonate (PC) occurred. PIL@CHT, combining the active sites of PIL and CHT, synergistically catalyzed this cascade reaction and achieved a high yield (93.0%) and selectivity (98.2%) of 1,2-propanediol (1,2-MPG) under a low H2O/PO ratio of 1.5/1. Moreover, the catalyst could be recycled seven times without any significant loss of catalytic activities and had good substrate generality.