Gold nanoclusters cure implant infections by targeting biofilm.

The biofilm-mediated implant infections pose a huge threat to human health. It is urgent to explore strategies to reverse this situation. Herein, we design 3-amino-1,2,4-triazole-5-thiol (ATT)-modified gold nanoclusters (AGNCs) to realize biofilm-targeting and near-infrared (NIR)-II light-responsive antibiofilm therapy. The AGNCs can interact with the bacterial extracellular DNA through the formation of hydrogen bonds between the amine groups on the ATT and the hydroxyl groups on the DNA. The AGNCs show photothermal properties even at a low power density (0.5 W/cm2) for a short-time (5 min) irradiation, making them highly effective in eradicating the biofilm with a dispersion rate up to 90 %. In vivo infected catheter implantation model demonstrates an exceptional high ability of the AGNCs to eradicate approximately 90 % of the bacteria encased within the biofilms. Moreover, the AGNCs show no detectable toxicity or systemic effects in mice. Our study suggests the great potential of the AGNCs for long-term prevention and elimination of the biofilm-mediated infections.

Complete Chloroplast Genome of Alternanthera sessilis and Comparative Analysis with Its Congeneric Invasive Weed Alternanthera philoxeroides.

Alternanthera sessilis is considered the closest relative to the invasive weed Alternanthera philoxeroides in China, making it an important native species for studying the invasive mechanisms and adaptations of A. philoxeroides. Chloroplasts play a crucial role in a plant's environmental adaptation, with their genomes being pivotal in the evolution and adaptation of both invasive and related species. However, the chloroplast genome of A. sessilis has remained unknown until now. In this study, we sequenced and assembled the complete chloroplast genome of A. sessilis using high-throughput sequencing. The A. sessilis chloroplast genome is 151,935 base pairs long, comprising two inverted repeat regions, a large single copy region, and a small single copy region. This chloroplast genome contains 128 genes, including 8 rRNA-coding genes, 37 tRNA-coding genes, 4 pseudogenes, and 83 protein-coding genes. When compared to the chloroplast genome of the invasive weed A. philoxeroides and other Amaranthaceae species, we observed significant variations in the ccsA, ycf1, and ycf2 regions in the A. sessilis chloroplast genome. Moreover, two genes, ccsA and accD, were found to be undergoing rapid evolution due to positive selection pressure. The phylogenetic trees were constructed for the Amaranthaceae family, estimating the time of independent species formation between A. philoxeroides and A. sessilis to be approximately 3.5186-8.8242 million years ago. These findings provide a foundation for understanding the population variation within invasive species among the Alternanthera genus.

Acidic Environment-Responsive Metal Organic Framework-Mediated Dihydroartemisinin Delivery for Triggering Production of Reactive Oxygen Species in Drug-Resistant Lung Cancer.

Background: Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics has been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy and leading to notable side effects during the treatment. Purpose: We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable and targeted DHA release properties, leading to enhanced antitumor effects while reducing potential side effects. Methods: D-ZIF was prepared by one-pot synthesis method using methylimidazole (MIM), Zn(NO3)2•6H2O and DHA. We characterized the physical and chemical properties of D-ZIF by TEM, DLS, XRD, FT-IR, and TG. We measured the drug loading efficiency and the cumulative release of DHA in different pH conditions. We evaluated the cytotoxicity of D-ZIF on renal cell carcinoma (RCC786-O), glioma cells (U251), TAX-resistant human lung adenocarcinoma (A549-TAX) cells by CCK8 in vitro. We explored the possible antitumor mechanism of D-ZIF by Western blot. We evaluated the biocompatibility and hemolysis of D-ZIF and explored the in vivo antitumor efficiency in mice model by TUNEL testing and blood biomarker evaluations. Results: D-ZIF showed rhombic dodecahedral morphology with size of 129±7.2 nm and possessed a noticeable DHA encapsulation efficiency (72.9%). After 48 hours, D-ZIF released a cumulative 70.0% of the loaded DHA at pH 6.5, and only 42.1% at pH 7.4. The pH-triggered programmed release behavior of D-ZIF could enhance anticancer effect of DHA while minimizing side effects under normal physiological conditions. Compared with the free DHA group with 31.75% of A549-TAX cell apoptosis, the percentage of apoptotic cells was approximately 76.67% in the D-ZIF group. D-ZIF inhibited tumor growth by inducing tumor cell apoptosis through the mechanism of ROS production and regulation of Nrf2/HO-1 and P38 MAPK signaling pathways. D-ZIF showed potent effects in treating tumors with high safety in vivo. Conclusion: This pH-responsive release mechanism enhanced the targeting efficiency of DHA towards tumor cells, thereby increasing drug concentration in tumor sites with negligible side effects. Herein, D-ZIF holds great promise for curing cancers with minimal adverse effects.

Role of C/EBP Homologous Protein (CHOP) and Nupr1 Interaction in Endoplasmic Reticulum Stress-Induced Apoptosis of Lens Epithelial Cells.

Our study mainly analyzed the mechanism of C/EBP homologous protein (CHOP) and its interacting protein Nupr1 on endoplasmic reticulum stress (ERS) induced lens epithelial cells (LEC) apoptosis. Cell proliferation was detected by CCK-8. Apoptosis was detected by flow cytometry and TUNEL. Nupr1 expression was detected by RT-qPCR. The expressions of CHOP, Nupr1, apoptosis-related protein, and ERS-related protein were detected by Western blot. DCFH-DA probe was used to detect cell ROS. The SOD, GSH-PX, and MDA contents were detected by the kit. Co-IP was used to detect the interaction between CHOP and Nupr1. The morphology of the lens was detected by HE staining. The result shows that Tunicamycin (TU) can induce endoplasmic reticulum stress and apoptosis in LEC in a concentration-dependent manner. TU induction leads to the occurrence of CHOP nuclear translocation. Overexpression of CHOP can further enhance the inhibitory effect of TU on LEC proliferation and the promotion of apoptosis, while knockdown of CHOP has the opposite effect. CHOP and Nupr1 are interacting proteins, and knockdown of Nupr1 or addition of Nupr1 inhibitor ZZW-115 can reverse the effects of TU and overexpression of CHOP, respectively. It has been observed in animal experiments that treatment with oe-CHOP can further aggravate the pathological lesions of the rat lens, while ZZW-115 can reverse the effect of oe-CHOP to a certain extent and improve the lesions of the rat lens. Overall, CHOP interacts with Nupr1 to regulate apoptosis caused by ERS and mediate cataract progression in rats, and this study provides a new potential therapeutic target for the treatment of cataract.

Identification of Eleutherococcus senticosus NAC transcription factors and their mechanisms in mediating DNA methylation of EsFPS, EsSS, and EsSE promoters to regulate saponin synthesis.

BACKGROUND: The formation of pharmacologically active components in medicinal plants is significantly impacted by DNA methylation. However, the exact mechanisms through which DNA methylation regulates secondary metabolism remain incompletely understood. Research in model species has demonstrated that DNA methylation at the transcription factor binding site within functional gene promoters can impact the binding of transcription factors to target DNA, subsequently influencing gene expression. These findings suggest that the interaction between transcription factors and target DNA could be a significant mechanism through which DNA methylation regulates secondary metabolism in medicinal plants. RESULTS: This research conducted a comprehensive analysis of the NAC family in E. senticosus, encompassing genome-wide characterization and functional analysis. A total of 117 EsNAC genes were identified and phylogenetically divided into 15 subfamilies. Tandem duplications and chromosome segment duplications were found to be the primary replication modes of these genes. Motif 2 was identified as the core conserved motif of the genes, and the cis-acting elements, gene structures, and expression patterns of each EsNAC gene were different. EsJUB1, EsNAC047, EsNAC098, and EsNAC005 were significantly associated with the DNA methylation ratio in E. senticosus. These four genes were located in the nucleus or cytoplasm and exhibited transcriptional self-activation activity. DNA methylation in EsFPS, EsSS, and EsSE promoters significantly reduced their activity. The methyl groups added to cytosine directly hindered the binding of the promoters to EsJUB1, EsNAC047, EsNAC098, and EsNAC005 and altered the expression of EsFPS, EsSS, and EsSE genes, eventually leading to changes in saponin synthesis in E. senticosus. CONCLUSIONS: NAC transcription factors that are hindered from binding by methylated DNA are found in E. senticosus. The incapacity of these NACs to bind to the promoter of the methylated saponin synthase gene leads to subsequent alterations in gene expression and saponin synthesis. This research is the initial evidence showcasing the involvement of EsNAC in governing the impact of DNA methylation on saponin production in E. senticosus.

Expression and Clinical Significance of CLCA2 in Pan-Cancer

SUMMARY: The calcium-activated chloride channel (CLCA2) performs a vital function in the intricate process of tumorigenesis. Using a bioinformatics analysis system, we conducted a pan-cancer investigation on CLCA2 to explore its association with tumor prognosis and its involvement in immunology. In order to achieve this objective, we examined the prognostic significance and expression level of CLCA2 in multiple cancer types using the TIMER and Sangerbox databases. The analysis of protein interaction networks revealed proteins linked to CLCA2. To investigate the potential biological functions and enrichment pathways of CLCA2 in cancer, the SangerBox and GSCA databases were utilized. Furthermore, the expression of CLCA2 in different cancer subtypes was evaluated during the analysis. Various functional conditions of cancer cells were then compared with CLCA2 in the CancerSEA database. Using online tools like TISIDB and Assistant for Clinical Bioinformatics, the investigation explored the link between CLCA2 and immune subtypes. Additionally, it assessed immune cell infiltration as part of the analysis. In addition, the application of GDSA was employed to investigate the predictive significance of CLCA2 in relation to drug sensitivity. The research outcomes uncovered abnormal expression patterns of CLCA2 in diverse tumor categories, with its expression level demonstrating a correlation with distinct subtypes of tumors. Strong associations have been observed between enhanced patient survival rates and CLCA2 in specific tumor types. There is a noteworthy connection observed among diverse tumor types, immune cell infiltration, immune subtypes, and CLCA2. The enrichment analysis of KEGG indicates that there may exist a connection between the expression of CLCA2 and renin secretion, pancreatic secretion, as well as other pathways in pan-cancer. CLCA2 appears to primarily activate pathways such as EMT (epithelial-mesenchymal transition), RAS/MAPK, RTK, apoptosis, TSC/mTOR, and PI3K/ AKT in pan-cancer. On the other hand, it seems to inhibit pathways like cell cycle, DNA damage, hormone AR, and hormone ER. Through single-cell functional analysis, it has been confirmed that CLCA2 is associated with diverse cellular functional states, encompassing DNA repair, EMT, hypoxia, invasion, metastasis, and quiescence. Furthermore, a substantial correlation has been observed between the expression of CLCA2 and drug sensitivity towards bosutinib, tipifarnib-P1, as well as other therapeutic agents. This research affirms that various cancer types express CLCA2 and its involvement in tumor advancement and immune penetration. CLCA2 possesses the capability to function as a noteworthy biomarker and target for therapeutic intervention in diverse cancer forms.

El canal de cloruro activado por calcio (CLCA2) desempeña una función vital en el proceso de tumorigénesis. Utilizando un sistema de análisis bioinformático, llevamos a cabo una investigación pan-cáncer en CLCA2 para explorar su asociación con el pronóstico tumoral y su participación en la inmunología. Para lograr este objetivo, examinamos la importancia pronóstica y el nivel de expresión de CLCA2 en múltiples tipos de cáncer utilizando las bases de datos TIMER y Sangerbox. El análisis de las redes de interacción de proteínas reveló proteínas vinculadas a CLCA2. Para investigar las posibles funciones biológicas y las vías de enriquecimiento de CLCA2 en el cáncer, se utilizaron las bases de datos SangerBox y GSCA. Además, durante el análisis se evaluó la expresión de CLCA2 en diferentes subtipos de cáncer. Luego se compararon varias condiciones funcionales de las células cancerosas con CLCA2 en la base de datos CancerSEA. Utilizando herramientas en línea como TISIDB y Assistant for Clinical Bioinformatics, la investigación exploró el vínculo entre CLCA2 y los subtipos inmunes. Además, evaluó la infiltración de células inmunitarias como parte del análisis y se empleó la aplicación de GDSA para investigar la importancia predictiva de CLCA2 en relación con la sensibilidad al fármaco. Los resultados de la investigación descubrieron patrones de expresión anormales de CLCA2 en diversas categorías de tumores, y su nivel de expresión demuestra una correlación con distintos subtipos de tumores. Se han observado fuertes asociaciones entre mayores tasas de supervivencia de los pacientes y CLCA2 en tipos de tumores específicos. Se observa una conexión notable entre diversos tipos de tumores, infiltración de células inmunitarias, subtipos inmunitarios y CLCA2. El análisis de enriquecimiento de KEGG indica que puede existir una conexión entre la expresión de CLCA2 y la secreción de renina, la secreción pancreática y otras vías en el pancáncer. CLCA2 parece activar principalmente vías como EMT (transición epitelial-mesenquimatosa), RAS/MAPK, RTK, apoptosis, TSC/mTOR y PI3K/AKT en pan-cáncer. Por otro lado, parece inhibir vías como el ciclo celular, el daño del ADN, la hormona AR y la hormona ER. Mediante análisis funcional unicelular, se ha confirmado que CLCA2 está asociado con diversos estados funcionales celulares, que abarcan la reparación del ADN, la EMT, la hipoxia, la invasión, la metástasis y la inactividad. Además, se ha observado una correlación sustancial entre la expresión de CLCA2 y la sensibilidad al fármaco hacia bosutinib, tipifarnib-P1, así como a otros agentes terapéuticos. Esta investigación indica que varios tipos de cáncer expresan CLCA2 y su participación en el avance tumoral y la penetración inmune. CLCA2 posee la capacidad de funcionar como un biomarcador notable y como un objetivo para la intervención terapéutica en diversas formas de cáncer.

Assessment of central nervous system vasculitis in children based on high-resolution vascular wall imaging.

Objectives: Central nervous system vasculitis (CNSV) is a rare disease. High-resolution vessel wall imaging (HR-VWI) enables the identification of inflammatory changes within the vessel wall. Few studies have applied HR-VWI to assess CNSV in children. This study delves into the utility of HR-VWI for diagnosing and treating CNSV in children, with the aim of enhancing clinical diagnosis and efficacy evaluation. Methods: Imaging data were acquired from children who underwent HR-VWI examinations. The study meticulously analysed clinical data and laboratory tests to discern the characteristics and distribution patterns of diverse vasculitis forms. Results: In children, CNSV mainly involves medium vessels with grade 1 and 2 stenosis (grade 4 stenosis is rare), and the imaging features generally show centripetal and moderate enhancement, suggesting that this feature is specific for the diagnosis of CNSV. High-grade stenosis, concentric enhancement and strong enhancement of the vasculature indicate more severe disease activity. Remarkably, HR-VWI proved to be significantly more sensitive than magnetic resonance angiography in detecting CNSV. Among the 13 cases subjected to imaging review, 8 demonstrated a reduction or resolution of vessel wall inflammation. In contrast, five patients exhibited worsening inflammation in the vessel wall. HR-VWI demonstrated that changes in vessel wall inflammation were closely correlated with changes in brain parenchymal lesions and symptoms. Conclusion: This study underscores the diagnostic value of HR-VWI in CNSV assessment and treatment monitoring, offering a quantitative evaluation of CNSV in children.

Research Progress on Regulation of Immune Response by Tanshinones and Salvianolic Acids of Danshen (Salvia miltiorrhiza Bunge).

As one of the traditional Chinese herbs, Danshen (Salvia miltiorrhiza Bunge) has been widely studied and widely used in the treatment of cardiovascular, cerebrovascular, and other immune diseases. Tanshinones and salvianolic acids isolated from Danshen are considered to be the main components of its biological activity and pharmacology that play important roles in increasing the index of immune organs, regulating the number and function of immune cells, and releasing immunoreactive substances. Especially tanshinone IIA, cryptotanshinone, salvianolic acid B, and rosmarinic acid show good biological activity in treating rheumatoid arthritis, some immune-mediated inflammatory diseases, psoriasis, and inflammatory bowel disease. In order to understand their pharmacological effects and provide references for future research and clinical treatment, the regulation of immune response by tanshinones and salvianolic acids is summarized in detail in this paper. In addition, the challenges in their pharmacological development and the opportunities to exploit their clinical potential have been documented.

CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

A simple fabrication of liquid-like polydimethylsiloxane coating for resisting ice adhesion.

The rapid realization of efficient anti-icing coatings on diverse substrates is of vital value for practical applications. However, current approaches for rapid preparations of anti-icing coatings are still deficient regarding their surface universality and accessibility. Here, we report a simple processing approach to rapidly form icephobic liquid-like polydimethylsiloxane (PDMS) brushes on various substrates, including metals, ceramics, glass, and plastics. A poly(dimethylsiloxane), trimethoxysilane is applied as a reactant under the catalysis of a minimal amount of acid formed by hydrolysis of dichlorodimethylsilane. With such an advantage, this approach is approved to be applicable of coating metal surfaces with less corrosion. The distinctive flexibility of the PDMS chains provides a liquid-like property to the coating showing low contact angle hysteresis and ice adhesion strength. Notably, the ice adhesion strength remains similar across a wide temperature window, from -70 to -10 °C, with a value of 18.4 kPa. The PDMS brushes demonstrate perfect capability for resisting acid and alkali corrosions, ultra-violet degradation, and even tens of icing/deicing cycles. Moreover, the liquid-like coating can also form at supercooling conditions, such as -20 °C, and shows an outstanding anti-icing/deicing performance, which meets the in situ coating reformation requirement under extreme conditions when it is damaged. This instantly forming anti-icing material will benefit from resisting instantaneous ice accretion on surfaces under extremely cold conditions.

Immune-cell-mediated tissue engineering strategies for peripheral nerve injury and regeneration.

During the process of peripheral nerve repair, there are many complex pathological and physiological changes, including multi-cellular responses and various signaling molecules, and all these events establish a dynamic microenvironment for axon repair, regeneration, and target tissue/organ reinnervation. The immune system plays an indispensable role in the process of nerve repair and function recovery. An effective immune response not only involves innate-immune and adaptive-immune cells but also consists of chemokines and cytokines released by these immune cells. The elucidation of the orchestrated interplay of immune cells with nerve regeneration and functional restoration is meaningful for the exploration of therapeutic strategies. This review mainly enumerates the general immune cell response to peripheral nerve injury and focuses on their contributions to functional recovery. The tissue engineering-mediated strategies to regulate macrophages and T cells through physical and biochemical factors combined with scaffolds are discussed. The dynamic immune responses during peripheral nerve repair and immune-cell-mediated tissue engineering methods are presented, which provide a new insight and inspiration for immunomodulatory therapies in peripheral nerve regeneration.

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

Parthenolide alleviates microglia-mediated neuroinflammation via MAPK/TRIM31/NLRP3 signaling to ameliorate cognitive disorder.

BACKGROUND AND PURPOSE: Neuroinflammation, mainly mediated by microglia, is involved in the evolution of Alzheimer's disease (AD). Parthenolide (PTL) has diverse pharmacological effects such as anti-inflammatory and antioxidative stress. However, whether PTL can modulate microglia-mediated neuroinflammation to improve cognitive impairment in amyloid precursor protein/presenilin 1 (APP/PS1) mice is unclear. METHODS: LPS/IFN-γ-induced BV2 and HMC3 microglia were used for in vitro experiments; the roles of PTL on anti-inflammatory, anti-oxidative, phagocytic activity, and neuroprotection were assessed by inflammatory cytokines assays, dichlorodihydrofluorescein diacetate, phagocytosis, and cell counting kit-8 assays. Western blot and immunofluorescence（IF） were used to examine related molecular mechanisms. In vivo, IF and western blot were applied in LPS-treated wild-type (WT) mice and APP/PS1 mice models. The Morris water maze test was performed to evaluate the effects of PTL on cognitive disorders. RESULTS: In vitro, PTL dramatically suppressed proinflammatory cytokines IL-6, IL-1ß, and TNF-α release and increased IL-10 levels. Moreover, PTL decreased reactive oxygen species and restored microglial phagocytic activities via the AKT/MAPK/ NF-κB signaling pathway. Importantly, we discovered that PTL obviously enhanced TRIM31 expression and siTRIM31 elevated proinflammatory cytokine levels. Furthermore, we determined that the anti-inflammatory role of PTL was mostly TRIM31/NLRP3 signaling-dependent. In vivo, PTL alleviated microgliosis and astrogliosis in LPS-treated WT and APP/PS1 mice. Additionally, PTL significantly ameliorated memory and learning deficits in cognitive behaviors. CONCLUSIONS: PTL improved cognitive and behavioral dysfunction, inhibited neuroinflammation, and showed potent anti-neuroinflammatory activity and neuroprotective effects by improving the MAPK/TRIM31/NLRP3 axis. Our study emphasized the therapeutic potential of PTL for improving cognitive disorders during AD progression.

Mining of long non-coding RNAs with target genes in response to rust based on full-length transcriptome in Kentucky bluegrass.

Kentucky bluegrass (Poa pratensis L.) is an eminent turfgrass species with a complex genome, but it is sensitive to rust (Puccinia striiformis). The molecular mechanisms of Kentucky bluegrass in response to rust still remain unclear. This study aimed to elucidate differentially expressed lncRNAs (DELs) and genes (DEGs) for rust resistance based on the full-length transcriptome. First, we used single-molecule real-time sequencing technology to generate the full-length transcriptome of Kentucky bluegrass. A total of 33,541 unigenes with an average read length of 2,233 bp were obtained, which contained 220 lncRNAs and 1,604 transcription factors. Then, the comparative transcriptome between the mock-inoculated leaves and rust-infected leaves was analyzed using the full-length transcriptome as a reference genome. A total of 105 DELs were identified in response to rust infection. A total of 15,711 DEGs were detected (8,278 upregulated genes, 7,433 downregulated genes) and were enriched in plant hormone signal transduction and plant-pathogen interaction pathways. Additionally, through co-location and expression analysis, it was found that lncRNA56517, lncRNA53468, and lncRNA40596 were highly expressed in infected plants and upregulated the expression of target genes AUX/IAA, RPM1, and RPS2, respectively; meanwhile, lncRNA25980 decreased the expression level of target gene EIN3 after infection. The results suggest that these DEGs and DELs are important candidates for potentially breeding the rust-resistant Kentucky bluegrass.

Application of modern computer technology in classical genetics lab course--Development of a mobile, lightweight and high-precision batch identification system for genetic traits of Drosophila.

Drosophila is a crucial biological experimental teaching material extensively utilized in experimental teaching. In this experimental teaching, each student typically needs to manually identify hundreds of fruit flies and record multiple of each fly. This task involves substantial workload, and the classification standards can be inconsistent. To address this issue, we introduce a deep convolutional neural network that classifies the traits of every fruit fly, using a two-stage consisting of an object detector and a trait classifier. We propose a keypoint-assisted classification model with tailored training session for the trait classification task and significantly enhanced the model interpretability. Additionally, we've enhanced the RandAugment method to better fit the features of our task. The model is trained with progressive learning and adaptive regularization under limited computational resources. The final classification model, which utilizes MobileNetV3 as backbone, achieves an accuracy of 97.5%, 97.5% and 98% for the eyes, wings, gender tasks, respectively. After optimization, the model is highly lightweight, classifying 600 fruit fly traits from raw images in 10 seconds and having a size less than 5 MB. It can be easily deployed on any android device. The development of this system is conducive to promoting the experimental teaching, such as verifying genetic laws with Drosophila as the research object. It can also be used for scientific research involving a large number of Drosophila classifications, statistics and analyses.

Lindenane-Type Sesquiterpene Dimers Mitigate Lipopolysaccharide-Induced Inflammation by Inhibiting Toll-Like Receptor Signaling.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and trigger an inflammatory response via the myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter-inducing interferon-ß (TRIF)-dependent pathways. Lindenane type sesquiterpene dimers (LSDs) are characteristic metabolites of plants belonging to the genus Sarcandra (Chloranthaceae). The aim of this study was to evaluate the potential anti-inflammatory effects of the LSDs shizukaol D (1) and sarcandrolide E (2) on lipopolysaccharides (LPS)-stimulated RAW264.7 macrophages in vitro, and explore the underlying mechanisms. Both LSDs neutralized the LPS-induced morphological changes and production of nitric oxide (NO), as determined by CCK-8 assay and Griess assay, respectively. Furthermore, shizukaol D (1) and sarcandrolide E (2) downregulated interferon ß (IFNß), tumor necrosis factor α (TNFα) and interleukin-1ß (IL-1ß) mRNA levels as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibited the phosphorylation of nuclear factor kappa B p65 (p65), nuclear factor kappa-Bα (IκBα), Jun N-terminal kinase (JNK), extracellular regulated kinase (ERK), mitogen-activated protein kinase p38 (p38), MyD88, IL-1RI-associated protein kinase 1 (IRAK1), and transforming growth factor-ß-activated kinase 1 (TAK1) proteins in the Western blotting assay. In conclusion, LSDs can alleviate the inflammatory response by inhibiting the TLR/MyD88 signalling pathway.

Effects of RFRP­3 on an ovariectomized estrogen­primed rat model and HEC­1A human endometrial carcinoma cells.

The hypothalamic peptide gonadotropin inhibitory hormone (GnIH) is a relatively novel hypothalamic neuropeptide, identified in 2000. It can influence the hypothalamic-pituitary-gonadal axis and reproductive function through various neuroendocrine systems. The present study aimed to explore the effects and potential underlying molecular mechanism of RFamide-related peptide-3 (RFRP-3) injection on the uterine fluid protein profile of ovariectomized estrogen-primed (OEP) rats using proteomics. In addition, the possible effects of RFRP-3 on the viability and apoptosis of the human endometrial cancer cell line HEC-1A and associated molecular mechanism were investigated. The OEP rat model was established through injection with GnIH/RFRP-3 through the lateral ventricle. At 6 h after injection, the protein components of uterine fluid of rats in the experimental and control groups were analyzed using liquid chromatography (LC)-tandem mass spectrometry (MS/MS). Differentially expressed proteins (DEPs) were analyzed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interactions (PPI) were investigated using the STRING database. PPI networks were then established before hub proteins were selected using OmicsBean software. The expression of one of the hub proteins, Kras, was then detected using western blot analysis. Cell Counting Kit-8, Annexin V-FITC/PI, reverse transcription-quantitative PCR and western blotting were also performed to analyze cell viability and apoptosis. In total, 417 DEPs were obtained using LC-MS/MS, including 279 upregulated and 138 downregulated proteins. GO analysis revealed that the majority of the DEPs were secretory proteins. According to KEGG enrichment analysis, the DEPs found were generally involved in tumor-associated pathways. In particular, five hub proteins, namely G protein subunit α (Gna)13, Gnaq, Gnai3, Kras and MMP9, were obtained following PPI network analysis. Western blot analysis showed that expression of the hub protein Kras was downregulated following treatment with 10,000 ng/ml RFRP-3. RFRP-3 treatment (10,000 ng/ml) also suppressed HEC-1A cell viability, induced apoptosis, downregulated Bcl-2 and upregulated Bax protein expression, compared with those in the control group. In addition, compared with those in the control group, RFRP-3 significantly reduced the mRNA expression levels of PI3K, AKT and mTOR, while upregulating those of LC3-II. Compared with those in the control group, RFRP-3 significantly decreased the protein expression levels of PI3K, AKT, mTOR and p62, in addition to decreasing AKT phosphorylation. By contrast, RFRP-3 significantly increased the LC3-II/I ratio and G protein-coupled receptor 147 (GPR147) protein expression. In conclusion, the present data suggest that RFRP-3 can alter the protein expression profile of the uterine fluid of OEP rats by upregulating MMP9 expression whilst downregulating that of key hub proteins Gna13, GnaQ, Gnai3 and Kras. Furthermore, RFRP-3 can inhibit HEC-1A cell viability while promoting apoptosis. The underlying molecular mechanism may involve activation of GPR147 receptor by the direct binding of RFRP-3, which further downregulates the hub protein Kras to switch on the PI3K/AKT/mTOR pathway. This subsequently reduces the Bcl-2 expression and promotes Bax expression to induce autophagy.

Time-of-Flight Intracranial MRA at 3 T versus 5 T versus 7 T: Visualization of Distal Small Cerebral Arteries.

Background Three-dimensional (3D) time-of-flight (TOF) MR angiography (MRA) at 7 T has been reported to have high image quality for visualizing small perforating vessels. However, B1 inhomogeneity and more physiologic considerations limit its applications. Angiography at 5 T may provide another choice for intracranial vascular imaging. Purpose To evaluate the image quality and cerebrovascular visualization of 5-T 3D TOF MRA for visualizing intracranial small branch arteries. Materials and Methods Participants (healthy volunteers or participants with a history of ischemic stroke undergoing intracranial CT angiography or MRA for identifying steno-occlusive disease) were prospectively included from September 2021 to November 2021. Each participant underwent 3-T, 5-T, and 7-T 3D TOF MRA with use of customized MR protocols within 48 hours. Radiologist scoring from 0 (invisible) to 3 (excellent) and quantitative assessment were obtained to evaluate the image quality. The Friedman test was used for comparison of characteristics derived from 3 T, 5 T, and 7 T. Results A total of 12 participants (mean age ± SD, 38 years ± 9; nine men) were included. Visualizations of the distal arteries and small vessels at 5-T TOF MRA were significantly higher than those at 3 T (median score: 3.0 vs 2.0, all P < .001 for distal segments and lenticulostriate artery; median score: 2.0 vs 0, P < .001 for pontine artery). The total length of small vessel branches detected at 5 T was larger than that at 3 T (5.1 m ± 0.7 vs 1.9 m ± 0.4; P < .001). However, there was no evidence of a significant difference compared with 7 T in either the depiction of distal segments and small vessel branches (average median score, 2.5; all P > .05) or the quantitative measurements (total length, 5.6 m ± 0.5; P = .41). Conclusion Three-dimensional time-of-flight MR angiography at 5 T presented the capability to provide superior visualization of distal large arteries and small vessel branches (in terms of subjective and quantitative assessment) to 3 T and had image quality similar to 7 T. © RSNA, 2022 Online supplemental material is available for this article. An earlier incorrect version appeared online. This article was corrected on September 14, 2022.

Incorporating multiple magnetic resonance diffusion models to differentiate low- and high-grade adult gliomas: a machine learning approach.

Background: Accurate grading of gliomas is a challenge in imaging diagnosis. This study aimed to evaluate the performance of a machine learning (ML) approach based on multiparametric diffusion-weighted imaging (DWI) in differentiating low- and high-grade adult gliomas. Methods: A model was developed from an initial cohort containing 74 patients with pathology-confirmed gliomas, who underwent 3 tesla (3T) diffusion magnetic resonance imaging (MRI) with 21 b values. In all, 112 histogram features were extracted from 16 parameters derived from seven diffusion models [monoexponential, intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), fractional order calculus (FROC), continuous-time random walk (CTRW), stretched-exponential, and statistical]. Feature selection and model training were performed using five randomly permuted five-fold cross-validations. An internal test set (15 cases of the primary dataset) and an external cohort (n=55) imaged on a different scanner were used to validate the model. The diagnostic performance of the model was compared with that of a single DWI model and DWI radiomics using accuracy, sensitivity, specificity, and the area under the curve (AUC). Results: Seven significant multiparametric DWI features (two from the stretched-exponential and FROC models, and three from the CTRW model) were selected to construct the model. The multiparametric DWI model achieved the highest AUC (0.84, versus 0.71 for the single DWI model, P<0.05), an accuracy of 0.80 in the internal test, and both AUC and accuracy of 0.76 in the external test. Conclusions: Our multiparametric DWI model differentiated low- (LGG) from high-grade glioma (HGG) with better generalization performance than the established single DWI model. This result suggests that the application of an ML approach with multiple DWI models is feasible for the preoperative grading of gliomas.