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BACKGROUND: Stellate ganglion block is a commonly used sympathetic nerve block technique that restores the balance of the sympathetic and vagal nervous systems of the body and inhibits sympathetic nerve activity. AIM: To analyze the effect of a stellate ganglion block combined with total diploma intravenous anesthesia on postoperative pain and immune function in patients undergoing laparoscopic radical gastric cancer (GC) surgery to provide a reference basis for the formulation of anesthesia protocols for radical GC surgery. METHODS: This study included 112 patients who underwent laparoscopic radical surgery for GC between January 2022 and March 2024. There was no restriction on sex. The patient grouping method used was a digital random table method, and the number of cases in each group was 56. The control group was administered total intravenous anesthesia, and the observation group compounded the stellate ganglion block according to the total intravenous anesthesia protocol. Postoperative hemodynamics, pain levels, and immune indices were compared between the groups. RESULTS: The heart rate and mean arterial pressure in the observation group after intubation were lower than those in the control group (P < 0.05). Pain levels were compared between the two groups at 2 hours, 12 hours, 24 hours, and 48 hours after surgery (P > 0.05). The number of CD3+, CD4+, and CD4+/CD8+ cells at the end of surgery was higher in the observation group than in the control group, and the number of CD8+ cells was lower in the observation group than in the control group (P < 0.05). There were no significant differences between the two groups in terms of propofol dosage, awakening time, extubation time, or postoperative adverse reactions (P > 0.05). CONCLUSION: The application of a stellate ganglion block combined with total intravenous anesthesia had no significant effect on postoperative pain levels in patients undergoing laparoscopic radical GC surgery. However, it can safely reduce the effect of surgery on the immune function of patients and is worth applying in clinical practice.
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The prevalence of avian-derived Escherichia coli (E. coli) carrying mcr-1 poses a significant threat to the development of the poultry industry and public health safety. Despite ongoing in-depth epidemiological research worldwide, a comprehensive macroscopic study based on genomics is still lacking. In response, this study collected 1104 genomic sequences of avian-derived mcr-1-positive E. coli (MCRPEC) from the NCBI public database, covering 31 countries. The majority of sequences originated from China (48.82â¯%), followed by the Netherlands (10.41â¯%). In terms of avian hosts, chicken accounted for the largest proportion (44.11â¯%), followed by gallus (24.09â¯%). Avian-derived MCRPEC also serves as a reservoir for other antibiotic resistance genes (ARGs), with 179 ARGs coexisting with mcr-1 identified. A total of 206 virulence-associated genes were also identified, revealing the pathogenic risks of MCRPEC. Pan-genome analysis revealed that avian-derived MCRPEC from different hosts, countries of origin, and serotypes exhibit minor SNP differences, indicating a high risk of cross-regional and cross-host transmission. The ST types of MCRPRC are diverse, with ST10 being the most prevalent (n=70). Spearman analysis showed a significant correlation between the number of ARGs and the insertion sequences (ISs) as well as plasmid replicon in ST10 strains. Furthermore, ST10 strains share a similar genetic basis with human-derived MCRPEC, suggesting the possibility of clonal dissemination. Pan-genome-wide association studies (pan-GWAS) indicated that the differential genes of MCRPEC from different countries and host sources are significantly different, mainly related to genes encoding type IV secretion systems and mobile genetic elements (MGEs). Plasmid mapping of showed that the prevalent plasmid types vary by country and host, with IncI2 and IncX4 being the main mcr-1-positive plasmids. Among the 12 identified mcr-1 genetic contexts with ISs, the Tn6330 transposon was the predominant carrier of mcr-1. In summary, the potential threat of avian-derived MCRPEC cannot be ignored, and long-term and comprehensive monitoring are essential.
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The herpesvirus UL51 protein is a multifunctional tegument protein involved in the regulation of multiple aspects of the viral life cycle. This article reviews the biological characteristics of the UL51 protein and its functions in herpesviruses, including participating in the maintenance of the viral assembly complex (cVAC) during viral assembly, affecting the production of mature viral particles and promoting primary and secondary envelopment, as well as its positive impact on viral cell-to-cell spread (CCS) through interactions with multiple viral proteins and its key role in the proliferation and pathogenicity of the virus in the later stage of infection. This paper discusses how the UL51 protein participates in the life cycle of herpesviruses and provides new ideas for further research on UL51 protein function.
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In cancer development and progression, the Hippo signaling pathway functions. The transcriptional enhanced associate domain (TEAD) stands out as a pivotal transcription factor within this pathway, and the suppression of TEAD represents a promising approach for cancer treatment. The primary aim of the study was to establish an analytical method for the concurrent quantification of a novel TEAD target inhibitor, BPI-460372, and its principal metabolites, BPI-460444 and BPI-460456, in human plasma. The chromatographic separation utilized a XSelect™ HSS C18 column (2.1 × 100 mm, 2.5 µm), while quantification was conducted on a SCIEX API 4000 mass spectrometer. 22 plasma samples were tested via the developed method. The calibration curve for BPI-460372 exhibited linearity from 2 to 2000 ng/mL, while its metabolites BPI-460444 and BPI-460456 had linearity between 1 and 1000 ng/mL (r > 0.99). The precision (RSD) was ≤ 17.1 %, and the accuracy (RE) fell within the range of -17.7 % to 15.0 %, all meeting acceptance criteria. The matrix effect was from 101.0 % to 105.8 %. The extraction recovery of analytes fell within the range of 96.8 % to 104.1 % with an RSD of less than 7.4 %. The developed method was effectively utilized in an advanced solid tumor patient, and the concentration trends of the three analytes in plasma were found to be largely consistent. The established analytical method showed great sensitivity, simplicity, accuracy, and reliability for the rapid and simultaneous analysis of the TEAD target inhibitor BPI-460372, alongside its major metabolites BPI-460444 and BPI-460456 in human plasma. This analytical method provided essential support for future clinical investigations and pharmacokinetic analysis.
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BACKGROUND: Hypertension, a worldwide cardiovascular issue, is known to result in significant damage to the left ventricle. Left ventricular hypertrophy refers to an increase in ventricular mass, which is not only the primary independent risk factor for cardiovascular disease onset but also independently related to the risk of death. OBJECTIVES: We sought to synthesize the existing literature on the occurrence and correlation between hypertension and left ventricular hypertrophy and the progress. METHODS: A scoping review was performed based on the methodological framework developed by Arksey & O'Malley. Search in the Pubmed database with no language restrictions, as of September 1, 2024. RESULTS: Of the 8110 articles retrieved, 110 were finally included. The selected articles were published between 1987 and 2024, with 55.5% (61/110) of the studies in the last five years and 14.5% (16/110) of 2024. The studies covered diagnosis, epidemiology, pathophysiology, prognosis, and treatment of hypertension with left ventricular hypertrophy. CONCLUSION: The literature reviewed suggests that studies on hypertension combined with left ventricular hypertrophy covered a variety of clinical progress, especially the clinical trial results of some new drugs that may bring great hope for treatment.
Continuous development of 3D echocardiographic technology may provide more accurate measurements; however, studies with the aim of establishing standard reference values remain in exploratory stages.The field of metabolomics offers a promising approach for studying biomarkers by detecting changes in metabolites associated with physiological or pathological processes induced by diseases. This avenue of research holds potential for the early diagnosis and assessment of LVH.Sodium-glucose co-transporter 2 (SGLT2) inhibitors and metformin are initially indicated for conditions other than left ventricular hypertrophy (LVH); however, emerging evidence suggests that these medications may possess potential clinical value in reversing LVH.
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Anti-Hipertensivos , Hipertensão , Hipertrofia Ventricular Esquerda , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/complicações , Anti-Hipertensivos/uso terapêutico , Prognóstico , Fatores de RiscoRESUMO
The purpose of this paper is to investigate the potential prebiotic properties and proliferation mechanism of fermented milk-derived peptides. In this study, fermented milk-derived polypeptides were obtained by extraction, separation, and purification. The purified peptides were used to culture fecal flora in vitro, and the relative abundance and composition of the flora were analyzed by high-throughput 16S rRNA sequencing technology. The results showed that peptides can promote the proliferation of beneficial bacteria Lactococcus in the intestine and inhibit the proliferation of harmful bacteria Escherichia coli-Shigella. The amino acid sequence of polypeptide components was determined and synthesized in vitro to verify the proliferation of intestinal flora; the proliferation mechanism of peptides on Lactococcus lactis was studied using non-targeted LC-MS metabolomics technology. Five important peptides with molecular weights of 1000-2000 Da were identified by LC-MS: GRP1 (LTEEEK), GRP2 (ENDAPSPVM*K), GRP3 (ITVDDK), GRP4 (EAM*APK) and GRP5 (LPPPEK). The results showed that the peptides could affect the arginine biosynthesis pathway and the amino sugar and nucleotide sugar metabolism of Lactococcus lactis. In addition, the peptides increased the expression of organic acids and their derivatives in Lactococcus lactis. This study provides a research basis for expanding the potential sources of new prebiotics and also opens up a new idea for discovering new prebiotics in vitro.
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This study presents a method utilizing solid-phase microextraction Arrow (SPME Arrow) combined with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for the selective detection of three veterinary drugs-thiabendazole, sulfamethazine, and clenbuterol-in milk and pork. Two-dimensional metal-organic framework nanosheets (2D-MOFs) were employed as coating materials for the SPME Arrow. Three types of 2D-MOFs (Ni, Mn, and Co based) were synthesized and characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, and a physical adsorption analyzer. The 2D-MOF coatings were fabricated using the electrospinning technique, with polyacrylonitrile (PAN) serving as the binder. Comparative analysis of the three 2D-MOF coatings revealed that 2D-Ni-MOF was the optimal coating material for the SPME Arrow. Optimization of the coating preparation conditions and SPME procedures included determining the optimal mass ratio of 2D-Ni-MOF to PAN, electrospinning time, and extraction and desorption parameters. Equilibrium extraction was achieved within 60 min, and desorption was completed within 30 min. Subsequently, the 2D-Ni-MOF-SPME Arrow-UPLC-Q-TOF-MS method was established and validated under optimal conditions, demonstrating high precision with inter-day precision ranging from 3.8 % to 9.5 % and intra-day precision ranging from 5.1 % to 11.5 %. The reusability study indicated that the extraction performance of the new SPME Arrow remained consistent after 90 adsorption-desorption cycles. The method exhibited linearity in milk and pork over the ranges of 0.002-5 µg L-1 and 0.01-5 µg L-1, respectively. The detection limits in milk and pork were 0.001-0.004 µg L-1 and 0.003-0.007 µg L-1, respectively. This method demonstrated excellent applicability for determining residues of the three veterinary drugs in milk and pork.
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Duck Tembusu virus (DTMUV) of the Orthoflavivirus genus poses a significant threat to waterfowl aquaculture. Nonstructural protein 1 (NS1), a multifunctional glycoprotein, exists in various oligomeric forms and performs diverse functions. The greasy finger (GF) region within NS1 of other flaviviruses has been shown to be a crucial component of the hydrophobic protrusion aiding in anchoring NS1 to the endoplasmic reticulum (ER). However, detailed studies on the role of the GF region in viral proliferation in vitro and the biological properties of NS1 remain scarce. A series of recombinant DTMUV (rDTMUV) with mutations in the GF region, including NS1-F158A, G159A, F160A, G161A, V162A, L163A, F160R, multipoint mutations (GF-4M), or regional deletions (ΔGF), were rescued using a DNA-based reverse genetics system. Only 5 rDTMUV variants (G159A, F160A, G161A, V162A, and L163A) could be rescued successfully, and these mutations were found to impair replication, reduce virulence, and decrease plaque size, as shown by growth kinetics, duck embryo virulence, and plaque assays, respectively. Upon examining NS1 expression by western blot, we discovered that secreted NS1 (sNS1) presented in large quantities in the supernatant of cells infected with rDTMUV-NS1-G159A, whereas intracellular NS1 was less abundant. These mutations also impacted the primary forms and secretion rates of NS1 in cases of overexpression by western blot and indirect ELISA. Exception for F160A and G161A, which showed decreased secretion rates, all other mutations increased sNS1 expression, with the most pronounced increase observed in F158A and ΔGF, and rDTMUV with these mutations can't be rescued. Co-localization studies of NS1 with the ER demonstrated that the ΔGF mutation attenuated NS1 anchoring to the ER, thereby inhibiting its intracellular residence and promoting secretion. Although these effects vary between flaviviruses, our data reveal that the GF region of NS1 is crucial for viral proliferation and NS1 secretion.
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The ongoing epidemic of flaviviruses worldwide has underscored the importance of studying flavivirus vector competence, considering their close association with mosquito vectors. Tembusu virus is an avian-related mosquito-borne flavivirus that has been an epidemic in China and Southeast Asia since 2010. However, the reason for the outbreak of Tembusu virus in 2010 remains unclear, and it is unknown whether changes in vector transmission played an essential role in this process. To address these questions, we conducted a study using Culex quinquefasciatus as a model for Tembusu virus infection, employing both oral infection and microinjection methods. Our findings confirmed that both vertical and venereal transmission collectively contribute to the cycle of Tembusu virus within the mosquito population, with persistent infections observed. Importantly, our data revealed that the prototypical Tembusu virus MM_1775 strain exhibited significantly greater infectivity and transmission rates in mosquitoes than did the duck Tembusu virus (CQW1 strain). Furthermore, we revealed that the viral E protein and 3' untranslated region are key elements responsible for these differences. In conclusion, our study sheds light on mosquito transmission of Tembusu virus and provides valuable insights into the factors influencing its infectivity and transmission rates. These findings contribute to a better understanding of Tembusu virus epidemiology and can potentially aid in the development of strategies to control its spread.
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Culex , Infecções por Flavivirus , Flavivirus , Mosquitos Vetores , Animais , Culex/virologia , Flavivirus/fisiologia , Infecções por Flavivirus/veterinária , Infecções por Flavivirus/transmissão , Infecções por Flavivirus/virologia , Mosquitos Vetores/virologia , FemininoRESUMO
Radioactive safety in nuclear facilities is of utmost importance. Prior to workers entering these areas, a 3D radiation field is needed for accurately estimating their exposure. Due to the complex relationship between radiation measurements and radiation fields, implementing neural networks is a promising approach for reconstruction. However, research on direct 3D radiation field reconstruction using neural networks is limited, and there is no standardized open-source dataset for training and evaluation. To address these issues, we created a simplified model of a nuclear facility and utilized the Monte Carlo program MCShield to simulate 3D radiation parameters. MCShield, which is mainly used for shielding calculations, has been verified for accuracy through benchmark tests. In addition, this paper proves the correctness of the MCShield program and the effectiveness of the AIS variance reduction method through calculations on the WinFrith Iron benchmark experiment and the NUREG/CR-6115 benchmark. The results show that the MCShield program as well as the AIS method can be used for dataset calculations.
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Probiotics are used in cheese fermentation to endow the product with unique functional properties, such as enhanced flavor and aroma development through proteolysis and lipolysis. In this study, two probiotic Lactobacillus strains, Lactobacillus plantarum A3 and Lactobacillus reuteri WQY-1, were selected to develop new probiotic cheeses in the form of single- and mixed-strain starters. The results demonstrated that the L. plantarum A3 single-strain group and the L. plantarum A3/L. reuteri WQY-1 mixed fermentation group exhibited superior product performance, particularly the release of functional hydrolysates during cheese ripening. Furthermore, Label-free quantitative proteomic analysis revealed 26 unique antioxidant peptides in the L. plantarum A3 single-strain group and 53 in the L. plantarum A3/L. reuteri WQY-1 mixed fermentation group. Among these, CMENSAEPEQSLACQCL (ß-lactoglobulin), CMENSAEPEQSLVCQCL (ß-lactoglobulin), and IQYVLSR (κ-casein) have been found to possess potential antioxidant properties both in vitro and in vivo. This confirmed that milk-derived protein peptides in cheese products exhibit potential antioxidant functions through the hydrolysis of probiotic strains.
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Antioxidantes , Queijo , Fermentação , Lactobacillus plantarum , Peptídeos , Probióticos , Queijo/microbiologia , Queijo/análise , Antioxidantes/metabolismo , Antioxidantes/química , Peptídeos/metabolismo , Peptídeos/química , Lactobacillus plantarum/metabolismo , Lactobacillus plantarum/química , Animais , Probióticos/metabolismo , Probióticos/química , Limosilactobacillus reuteri/metabolismo , Limosilactobacillus reuteri/química , Bovinos , Lactobacillus/metabolismo , CamundongosRESUMO
OBJECTIVES: To explore the associations of air pollutants and Air Quality Index (AQI) with risk of sudden sensorineural hearing loss (SSNHL) DESIGN: Cross-sectional study SETTING: Medical record data and local population data collected between 2014 and 2022 in Changshu, China were retrospectively reviewed. PARTICIPANTS: Adults aged 18 years and above who were diagnosed with SSNHL in Changshu No. 1 People's Hospital or Changshu No. 2 People's Hospital from the spring of 2014 to the fall of 2022 were included in the study. OUTCOME MEASURE: SSNHL was diagnosed by clinicians using the Chinese diagnostic criteria for SSNHL. RESULTS: Compared with those exposed to the lowest tertile of carbon monoxide (CO), the prevalence ratio for those exposed to middle and high tertiles of CO were 1.113 (95% CI 1.022 to 1.213) and 1.230 (95% CI 1.105 to 1.369), respectively. The risk of SSNHL was increased by 30.6% (95% CI 9.9% to 55.4%) per doubling increment of CO. No categorical association was found between ozone (O3) exposure and risk of SSNHL, however, an increased risk of 22.2% (0.8%-48.2%) was identified for each doubling of O3. No association was identified between other pollutants and AQI and risk of SSNHL. CONCLUSIONS: In this study, CO and O3 were associated with an increased risk of SSNHL in Changshu, China. Further studies are warranted to confirm our findings.
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Poluentes Atmosféricos , Poluição do Ar , Perda Auditiva Neurossensorial , Ozônio , Humanos , Estudos Transversais , Masculino , China/epidemiologia , Pessoa de Meia-Idade , Feminino , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/induzido quimicamente , Perda Auditiva Neurossensorial/etiologia , Adulto , Ozônio/efeitos adversos , Ozônio/análise , Estudos Retrospectivos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Idoso , Perda Auditiva Súbita/epidemiologia , Perda Auditiva Súbita/etiologia , Fatores de Risco , Monóxido de Carbono/efeitos adversos , Monóxido de Carbono/análise , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Material Particulado/análise , PrevalênciaRESUMO
Traditional villages hold significant historical and cultural value as the precious heritage of China's agricultural civilization. Currently, against the backdrop of increasing urbanization and rapid expansion of urban construction land, the spatial patterns of traditional villages across various regions in China are being encroached upon and damaged, with protection pressures growing daily. As one of the important cradles of Chinese civilization, the Lower Yangtze River Basin (LYRB) has traditional villages closely linked with its water systems, forming a unique human-land relationship and spatial distribution pattern. However, influenced by the rapid urbanization process, the spatial patterns of traditional villages in this region also face a crisis, and the contradiction between protection and development is becoming increasingly prominent. How to balance this contradiction and ensure the reasonable protection and sustainable development of traditional villages has become an urgent issue to address. Therefore, this study focuses on the LYRB. Using ArcGIS tools and combined with mathematical analysis methods, the spatial distribution characteristics and essential influencing factors of traditional villages in this area were screened and analyzed. The objective was to examine the spatial structural relationship between traditional villages, four water system types, and nine sub-basin units, intending to reveal the unique interdependence between the water system and traditional villages in this area. This would provide scientific support for the formulation of scientific conservation strategies. The research results show that: (1) Traditional villages in The LYRB form two core clusters spatially and exhibit substantial spatial accumulation; (2) Water system characteristics are the main factors affecting the distribution of traditional villages; (3) In the LYRB, the spatial distribution of the nine sub-basins is closely related to the spatial distribution of traditional villages, resulting in typical regional spatial differentiation of traditional villages in this area. This study is based on a watershed perspective, and the results highlight the importance of the water system network in the development of traditional villages, revealing a unique spatial dependency relationship between traditional villages and the water network in the LYRB. In order to ensure the comprehensive protection of the traditional village system in this region, it is essential to adhere to the fundamental principles that govern its spatial configuration. A tripartite collaborative protection system based on the watershed should be formulated from the perspective of the overall distribution relationship between the water network and the traditional villages. This system would serve to protect the overall landscape, the water network pattern, and the traditional villages. Establishing an overall pattern view of integrating the water system network and the traditional villages is essential.
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Duck hepatitis A virus type 1 (DHAV-1) is an important member of the Picornaviridae family that causes highly fatal hepatitis in ducklings. Since picornaviruses have small genomes with limited coding capacity, they must utilize host proteins for viral cap-independent translation and RNA replication. Here, we report the role of duck poly(rC)-binding protein 2 (PCBP2) in regulating the replication and translation of DHAV-1. During DHAV-1 infection, PCBP2 expression was upregulated. A biotinylated RNA pull-down assay revealed that PCBP2 positively regulates DHAV-1 translation through specific interactions with structural domains II and III of the DHAV-1 internal ribosome entry site (IRES). Further studies revealed that PCBP2 promotes DHAV-1 replication via an interaction of its KH1 domain (aa 1-92) with DHAV-1 3Dpol. Thus, our studies demonstrated the specific role of PCBP2 in regulating DHAV-1 translation and replication, revealing a novel mechanism by which hostâvirus interactions regulate viral translation and replication. These findings contribute to further understanding of the pathogenesis of picornavirus infections.
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Patos , Vírus da Hepatite do Pato , Infecções por Picornaviridae , Doenças das Aves Domésticas , Proteínas de Ligação a RNA , Replicação Viral , Animais , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Vírus da Hepatite do Pato/fisiologia , Vírus da Hepatite do Pato/genética , Doenças das Aves Domésticas/virologia , Infecções por Picornaviridae/veterinária , Infecções por Picornaviridae/virologia , Hepatite Viral Animal/virologia , Biossíntese de ProteínasRESUMO
Microglia-mediated neuroinflammation is critical in the pathogenesis of sepsis-associated encephalopathy(SAE). Identifying the key factors that inhibit microglia-mediated neuroinflammation holds promise as a potential target for preventing and treating SAE. Esketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been proposed to possess protective and therapeutic properties against neuroinflammatory disorders. This study provides evidence that the administration of Esketamine in SAE mice improves cognitive impairments and alleviates neuronal damage by inhibiting the microglia-mediated neuroinflammation. The BDNF receptor antagonist K252a was employed in both vivo and in vitro experiments. The findings indicate that K252a successfully counteracted the beneficial effects of Esketamine on microglia and cognitive behavior in mice with SAE. Consequently, these results suggest that Esketamine inhibits microglia-mediated neuroinflammation by activating the BDNF pathway, and mitigating neuronal damage and cognitive dysfunction associated with SAE.
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RATIONALE AND OBJECTIVES: The first-line treatment for prolactinoma is drug therapy with dopamine agonists (DAs). However, some patients with resistance to DA treatment should prioritize surgical treatment. Therefore, it is crucial to accurately identify the drug treatment response of prolactinoma before treatment. The present study was performed to determine the DA treatment response of prolactinoma using a clinical radiomic model that incorporated radiomic and clinical features before treatment. MATERIALS AND METHODS: In total, 255 patients diagnosed with prolactinoma were retrospectively divided to training and validation sets. An elastic net algorithm was used to screen the radiomic features, and a fusion radiomic model was established. A clinical radiomic model was then constructed to integrate the fusion radiomic model and the most important clinical features through multivariate logistic regression analysis for individual prediction. The calibration, discrimination, and clinical applicability of the established models were evaluated. 60 patients with prolactinoma from other centers were used to validate the performance of the constructed model. RESULTS: The fusion radiomic model was constructed from three significant radiomic features, and the area under the curve in the training set and validation set was 0.930 and 0.910, respectively. The clinical radiomic model was constructed using the radiomic model and three clinical features. The model exhibited good recognition and calibration abilities as evidenced by its area under the curve of 0.96, 0.92, and 0.92 in the training, validation, and external multicenter validation set, respectively. Analysis of the decision curve showed that the fusion radiomic model and clinical radiomic model had good clinical application value for DA treatment response prediction in patients with prolactinoma. CONCLUSION: Our clinical radiomic model demonstrated high sensitivity and excellent performance in predicting DA treatment response in prolactinoma. This model holds promise for the noninvasive development of individualized diagnosis and treatment strategies for patients with prolactinoma.
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Bacterial wilt caused by Ralstonia solanacearum is one of the most important diseases in solanaceous plants, including peppers. It generally tends to be more serious under warm-temperature and moist (WM) conditions than at moist room-temperature (RM) conditions. Although immunity mechanisms at room temperature have been intensively studied, the mechanisms underlying WM conditions remain poorly understood. Herein, the pepper cysteine protease CaZingipain2 was expressed and functionally characterized in pepper immunity against R. solanacearum at WM conditions and at room temperature. The results showed that CaZingipain2 localized to the nucleus and was upregulated at the transcript level in pepper plants upon R. solanacearum infection under WM conditions (RSWM). Virus-induced gene silencing of CaZingipain2 significantly increased the susceptibility of pepper plants to RSWM, and was coupled with the downregulation of CaPRP1 and CaMgst3, which are specifically related to pepper immunity against RSWM, according to our previous studies, while its overexpression significantly reduced the susceptibility of N. benethamiana plants to RSWM compared to that of wild-type plants. In addition, our data showed that CaZingipain2 also acts positively in pepper immunity against R. solanacearum infection at room temperature by upregulating the SA- and JA-responsive PR genes, including CaNPR1 and CaDEF1. All these results indicate that CaZingipain2 improves pepper immunity against R. solanacearum under WM conditions and at room temperature by regulating different PR genes.
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Previous studies by our group and others have highlighted the critical role of hyperinflammation in the pathogenicity of duck hepatitis A virus 1 (DHAV-1), an avian picornavirus that has caused significant devastation in the duck industry worldwide for decades. However, the precise mechanisms by which DHAV-1 infection regulates the inflammatory responses, particularly the production of IL-1ß, remain poorly understood. In this study, we demonstrate that DHAV-1 infection triggers NF-κB- and NLRP3 inflammasome-mediated IL-1ß production. Mechanistically, DHAV-1 infection, particularly its replication and translation, disrupts cellular homeostasis of Ca2+, K+, ROS and cathepsin, which act cooperatively as assembly signals for NLRP3 inflammasome activation. By screening DHAV-1-encoded proteins, we identified that the viroporin 2B dominates NF-κB as well as NLRP3 inflammasome activation. Mutation analysis revealed that I43 within the 2B protein is the key amino acid for Ca2+ mobilization and subsequent activation of NF-κB transcriptional activity and NLRP3 inflammasome. Moreover, DHAV-1 infection and the 2B protein activate the MAVS- and MyD88-NF-κB pathways by relay, providing the necessary priming signals for NLRP3 inflammasome activation. In summary, our findings elucidate a mechanism through which DHAV-1 triggers inflammatory responses via NF-κB/NLRP3 inflammasome activation, offering new perspectives on DHAV-1 pathogenesis and informing the development of targeted anti-DHAV-1 treatments.
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INTRODUCTION: The impact of cardiac function decline on major adverse limb events (MALE) following lower extremity revascularization (LER) in patients with peripheral arterial disease (PAD) has not been described. METHODS: The electronic records of patients undergoing LER for PAD in a single center were reviewed. Two transthoracic echocardiograms were captured, the first within 6 months of LER and the second on later follow-up (most recent to date). Patients were then divided into 2 groups: cardiac function decline (decrease in left ventricular ejection fraction ΔEF ≥10%) or stable cardiac function (reduction in ΔEF <10%, no change or improved EF). Patient characteristics and outcomes, including MALE, were compared. RESULTS: Of the 926 patients who underwent LER, 222 (24.0%) experienced a cardiac function decline, with 704 (76.0%) patients having stable cardiac function. Patients with cardiac function decline were more likely to have diabetes mellitus and heart failure than patients with stable cardiac function. There were no differences in the mode of revascularization (open vs. endovascular) between both groups. Patients with cardiac function decline demonstrated higher rates of periprocedural bleeding after initial LER. After a mean follow-up of 3 years, patients with cardiac function decline had higher mortality. However, Kaplan-Meier analysis revealed no difference in freedom from MALE or reintervention rates between the 2 groups. CONCLUSION: Patients with cardiac function decline after LER for PAD have increased mortality but no significant difference in limb outcomes compared to patients with stable cardiac function.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related disease severely affecting life quality with its prevalence rising as the population ages, yet there is still no effective treatment available. Cell therapy has emerged as a promising option for IPF, however, the absence of mature and stable animal models for IPF immunodeficiency hampers preclinical evaluations of human cell therapies, primarily due to rapid immune clearance of administered cells. This study aims to establish a reliable pulmonary fibrosis (PF) model in immunodeficient mice that supports autologous cell therapy and to investigate underlying mechanism. METHODS: We utilized thirty 5-week-old male NOD/SCID mice, categorizing them into three age groups: 12weeks, 32 weeks and 43 weeks, with 6 mice euthanized randomly from each cohort for lung tissue analysis. We assessed fibrosis using HE staining, Masson's trichrome staining, α-SMA immunohistochemistry and hydroxyproline content measurement. Further, ß-galactosidase staining and gene expression analysis of MMP9, TGF-ß1, TNF-α, IL-1ß, IL-6, IL-8, SOD1, SOD2, NRF2, SIRT1, and SIRT3 were performed. ELISA was employed to quantify protein levels of TNF-α, TGF-ß1, and IL-8. RESULTS: When comparing lung tissues from 32-week-old and 43-week-old mice to those from 12-week-old mice, we noted a marked increase in inflammatory infiltration, fibrosis severity, and hydroxyproline content, alongside elevated expression levels of α-SMA and MMP9. Notably, the degree of fibrosis intensified with age. Additionally, ß-galactosidase staining became more pronounced in older mice. Quantitative PCR analyses revealed age-related, increases in the expression of senescence markers (GLB1, P16, P21), and proinflammatory genes (TGF-ß1, TNF-α, IL-1ß, IL-6, and IL-8). Conversely, the expression of anti-oxidative stress-related genes (SOD1, SOD2, NRF2, SIRT1, and SIRT3) declined, showing statistically significant differences (*P < 0.05, **P < 0.01, ***P < 0.001). ELISA results corroborated these findings, indicating a progressive rise in the protein levels of TGF-ß1, TNF-α, and IL-8 as the mice aged. CONCLUSIONS: The findings suggest that NOD/SCID mice aged 32 weeks and 43 weeks effectively model pulmonary fibrosis in an elderly context, with the disease pathogenesis likely driven by age-associated inflammation and oxidative stress.