Development and validation of nomogram models for predicting overall survival and cancer-specific survival in gastric cancer patients with liver metastases: a cohort study based on the SEER database.

OBJECTIVE: To establish nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of gastric cancer liver metastasis (GCLM) patients. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) database for 5,451 GCLM patients diagnosed between 2010 and 2015 were analyzed. The cohort was divided into a training set (3,815 cases) and an internal validation set (1,636 cases). External validation included 193 patients from the Fourth Hospital of Hebei Medical University and 171 patients from the People's Hospital of Shijiazhuang City, spanning 2016-2018. Multivariable Cox regression analysis identified eight independent prognostic factors for OS and CSS in GCLM patients, including age, histological type, grade, tumor size, surgery, chemotherapy, bone metastasis, and lung metastasis. Two nomogram models were developed based on these factors and evaluated using time-dependent receiver operating characteristic curve analysis, calibration curves, and decision curve analysis. RESULTS: Internal validation showed that the nomogram models outperformed the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system in predicting 1-year, 2-year, and 3-year OS and CSS in GCLM patients (1-year OS: 0.801 vs. 0.593, P < 0.001; 1-year CSS: 0.807 vs. 0.598, P < 0.001; 2-year OS: 0.803 vs. 0.630, P < 0.001; 2-year CSS: 0.802 vs. 0.633, P < 0.001; 3-year OS: 0.824 vs. 0.691, P < 0.001; 3-year CSS: 0.839 vs. 0.692, P < 0.001). CONCLUSION: This study developed and validated nomogram models using SEER database data to predict OS and CSS in GCLM patients. These models offer improved prognostic accuracy over traditional staging systems, aiding in clinical decision-making.

In situ electron generation through Fe/C supported sludge coupled with a counter-diffusion biofilm for electron-deficient wastewater treatment: Binding properties and catalytic competition mechanism of nitrate reductase.

A membrane-aerated biofilm-coupled Fe/C supported sludge system (MABR-Fe/C) was constructed to achieve in situ electron production for NO3--N reduction enhancement in different Fe/C loadings (10 g and 200 g). The anoxic environment formed in the MABR-Fe/C promoted a continual Fe2+release of Fe/C in 120 d operation (average Fe2+concentrations is 1.18 and 2.95 mg/L in MABR-Fe/C10 and MABR-Fe/C200, respectively). Metagenomics results suggested that the electrons generated from ongoing Fe2+ oxidation were transferred via the Quinone pool to EC 1.7.5.1 rather than EC 1.9.6.1 to complete the process of NO3--N reduction to NO2--N in Acidovorax, Ottowia, and Polaromonas. In the absence of organic matter, the NO3--N removal in MABR-Fe/C10 and MABR-Fe/C200 increased by 11.99 and 12.52 mg/L, respectively, compared to that in MABR. In the further NO2--N reduction, even if the minimum binding free energy (MBFE) was low, NO2--N in Acidovorax and Dechloromonas preferentially bind the Gln-residues for dissimilatory nitrate reduction (DNR) in the presence of Fe/C. Increasing Fe/C loading (MABR-Fe/C200) caused the formation of different residue binding sites, further enhancing the already dominant DNR. When DNR in MABR-Fe/C200 intensified, the TN in the effluent increased by 3.75 mg/L although the effluent NO3--N concentration was lower than that in MABR-Fe/C10. This study demonstrated a new MABR-Fe/C system for in situ electron generation to enhance biological nitrogen removal and analyzed the NO3--N reduction pathway and metabolic mechanism, thus providing new ideas for nitrogen removal in electron-deficient wastewater.

Nomogram models for predicting overall and cancer-specific survival in early-onset gastric cancer patients: a population-based cohort study.

To develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of early-onset gastric cancer (EOGC) patients. A total of 1077 EOGC patients from the Surveillance, Epidemiology, and End Results (SEER) database were included, and an additional 512 EOGC patients were recruited from the Fourth Hospital of Hebei Medical University, serving as an external test set. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Based on these factors, two nomogram models were established, and web-based calculators were developed. These models were validated using receiver operating characteristics (ROC) curve analysis, calibration curves, and decision curve analysis (DCA). Multivariate analysis identified gender, histological type, stage, N stage, tumor size, surgery, primary site, and lung metastasis as independent prognostic factors for OS and CSS in EOGC patients. Calibration curves and DCA curves demonstrated that the two constructed nomogram models exhibited good performance. These nomogram models demonstrated superior performance compared to the 7th edition of the AJCC tumor-node-metastasis (TNM) classification (internal validation set: 1-year OS: 0.831 vs 0.793, P = 0.072; 1-year CSS: 0.842 vs 0.816, P = 0.190; 3-year OS: 0.892 vs 0.857, P = 0.039; 3-year CSS: 0.887 vs 0.848, P = 0.018; 5-year OS: 0.906 vs 0.880, P = 0.133; 5-year CSS: 0.900 vs 0.876, P = 0.109). In conclusion, this study developed two nomogram models: one for predicting OS and the other for CSS of EOGC patients, offering valuable assistance to clinicians.

Clinical calculator based on CT and clinicopathologic characteristics predicts short-term prognosis following resection of microsatellite-stabilized diffuse gastric cancer.

PURPOSE: Although microsatellite stability/Epithelial-mesenchymal transition (MSS/EMT) subtypes have been reported in multiple cancer prognosis studies, strong confounding factors between MSS/EMT (usually with Lauren's diffuse phenotype) and diffuse gastric cancer (GC) may obscure the independent prognostic value of diffuse GC. Additionally, recent studies suggest a strong correlation between mural stratification based on CT and diffuse GC. This study aims to investigate potential prognostic factors of MSS diffuse GC using mural stratification and to develop a risk assessment model. METHODS: This retrospective study included 131 patients with MSS diffuse GC who underwent radical surgery. Univariate and multivariate Cox proportional hazards regression analysis was used to identify model predictors and construct a nomogram for overall survival (OS) and recurrence-free survival (RFS) risks. The model's performance was evaluated using ROC, accuracy, and C-index. Internal validation of the model was conducted using the bootstrap resampling method. RESULTS: Among 131 cases, 60 cases (45.8%) exhibited grade 2 mural stratification, which correlated with a poorer tumor prognosis and a more invasive phenotype. Furthermore, a nomogram for predicting OS and RFS prognosis was established based on multivariate results (age, extranodal invasion, mural stratification, and/or P53). The nomogram demonstrated excellent performance, with an AUC of 0.859 (95% CI 0.794-0.924) for OS and 0.859 (95% CI 0.789-0.929) for RFS. Internal validation using 1000 bootstrap samples yielded AUC values of 0.845 and 0.846 for OS and RFS, respectively. CONCLUSION: Grade 2 mural stratification based on CT imaging revealed a more aggressive invasive phenotype, characterized by increased LN metastasis, higher rates of peritoneal metastasis, and a poorer short-term prognosis. Furthermore, the CT phenotype-based nomogram demonstrates favorable discrimination and calibration, enabling convenient individual short-term prognostic evaluation following resection of MSS diffuse GC.

MicroRNA-431-5p inhibits angiogenesis, lymphangiogenesis, and lymph node metastasis by affecting TGF-ß1/SMAD2/3 signaling via ZEB1 in gastric cancer.

Accumulating evidence suggests that lymphangiogenesis plays a crucial role in lymphatic metastasis, leading to tumor immune tolerance. However, the specific mechanism remains unclear. In this study, miR-431-5p was markedly downregulated in both gastric cancer (GC) tissues and plasma exosomes, and its expression were correlated negatively with LN metastasis and poor prognosis. Mechanistically, miR-431-5p weakens the TGF-ß1/SMAD2/3 signaling pathway by targeting ZEB1, thereby suppressing the secretion of VEGF-A and ANG2, which in turn hinders angiogenesis, lymphangiogenesis, and lymph node (LN) metastasis in GC. Experiments using a popliteal LN metastasis model in BALB/c nude mice demonstrated that miR-431-5p significantly reduced popliteal LN metastasis. Additionally, miR-431-5p enhances the efficacy of anti-PD1 treatment, particularly when combined with galunisertib, anti-PD1 treatment showing a synergistic effect in inhibiting GC progression in C57BL/6 mice. Collectively, these findings suggest that miR-431-5p may modulate the TGF-ß1/SMAD2/3 pathways by targeting ZEB1 to impede GC progression, angiogenesis, and lymphangiogenesis, making it a promising therapeutic target for GC management.

Cobalt single-atom catalyst tailored ceramic membrane for selective removal of emerging organic contaminants.

Water reuse is an effective way to solve the issues of current wastewater increments and water resource scarcity. Ultrafiltration, a promising method for water reuse, has the characteristics of low energy consumption, easy operation, and high adaptability to coupling with other water treatment processes. However, emerging organic contaminants (EOCs) in municipal wastewater cannot be effectively intercepted by ultrafiltration, which poses significant challenges to the effluent quality and sustainability of ultrafiltration process. Here, we develop a cobalt single-atom catalyst-tailored ceramic membrane (Co1-NCNT-CM) in conjunction with an activated peroxymonosulfate (PMS) system, achieving excellent EOCs degradation and anti-fouling performance. An interfacial reaction mechanism effectively mitigates membrane fouling through a repulsive interaction with natural organic matter. The generation of singlet oxygen at the Co-N3-C active sites through a catalytic pathway (PMS→PMS∗→OH∗→O∗→OO∗→1O2) exhibits selective oxidation of phenols and sulfonamides, achieving >90% removal rates. Our findings elucidate a multi-layered functional architecture within the Co1-NCNT-CM/PMS system, responsible for its superior performance in organic decontamination and membrane maintenance during secondary effluent treatment. It highlights the power of integrating Co1-NCNT-CM/PMS systems in advanced wastewater treatment frameworks, specifically for targeted EOCs removal, heralding a new direction for sustainable water management.

In Situ-Derived N-Doped ZnO from ZIF-8 for Enhanced Ethanol Sensing in ZnO/MEMS Devices.

Microelectromechanical systems (MEMS) gas sensors have numerous advantages such as compact size, low power consumption, ease of integration, etc., while encountering challenges in sensitivity and high resistance because of their low sintering temperature. This work utilizes the in situ growth of Zeolitic Imidazolate Framework-8 (ZIF-8) followed by its conversion to N-doped ZnO. The results obtained from scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicate that the in situ derivation of ZIF-8 facilitates the adhesion of ZnO particles, forming an island-like structure and significantly reducing the interfaces between these particles. Furthermore, powder X-ray diffraction (XRD) analysis, elemental mapping, and X-ray photoelectron spectroscopy (XPS) analysis confirm the conversion of ZIF-8 to ZnO, the successful incorporation of N atoms into the ZnO lattice, and the creation of more oxygen vacancies. The ZIF-8-derived N-doped ZnO/MEMS sensor (ZIF (3)-ZnO/MEMS) exhibits remarkable gas sensitivity for ethanol detection. At an operating temperature of 290 °C, it delivers a substantial response value of 80 towards 25 ppm ethanol, a 13-fold enhancement compared with pristine ZnO/MEMS sensors. The sensor also exhibits an ultra-low theoretical detection limit of 11.5 ppb to ethanol, showcasing its excellent selectivity. The enhanced performance is attributed to the incorporation of N-doped ZnO, which generates abundant oxygen vacancies on the sensor's surface, leading to enhanced interaction with ethanol molecules. Additionally, a substantial two-order-of-magnitude decrease in the resistance of the gas-sensitive film is observed. Overall, this study provides valuable insights into the design and fabrication strategies applicable to high-performance MEMS gas sensors in a broader range of gas sensing.

Myosteatosis predicts postoperative complications and long-term survival in robotic gastrectomy for gastric cancer: A propensity score analysis.

BACKGROUND: Robotic gastrectomy is increasingly utilized for gastric cancer, but high morbidity remains a concern. Myosteatosis or low skeletal muscle density reflecting fatty infiltration, associates with complications after other cancer surgeries but has not been evaluated for robotic gastrectomy. METHODS: This retrospective study analysed 381 patients undergoing robotic gastrectomy for gastric cancer from September 2019 to October 2022. Myosteatosis was quantified on preoperative computed tomography (CT) images at lumbar 3 (L3). Propensity score matching addressed potential confounding between myosteatosis and non-myosteatosis groups. Outcomes were postoperative complications, 30 days mortality, 30 days readmissions and survival. RESULTS: Myosteatosis was present in 33.6% of patients. Myosteatosis associated with increased overall (47.7% vs. 26.5%, p < 0.001) and severe complications (12.4% vs. 4.9%, p < 0.001). After matching, myosteatosis remained associated with increased overall complications, major complications, intensive care unit (ICU) transfer and readmission (all p < 0.05). Myosteatosis independently predicted overall [odds ratio (OR) = 2.86, 95% confidence interval (CI): 1.57-5.20, p = 0.001] and severe complications (OR = 4.81, 95% CI: 1.51-15.27, p = 0.008). Myosteatosis also associated with reduced overall (85.0% vs. 93.2%, p = 0.015) and disease-free survival (80.3% vs. 88.4%, p=0.029). On multivariate analysis, myosteatosis independently predicted poorer survival [hazard ratio (HR) = 2.83, 95% CI: 1.32-6.08, p=0.012] and disease-free survival (HR = 1.83, 95% CI: 1.01-3.30, p=0.032). CONCLUSION: Preoperative CT-defined myosteatosis independently predicts increased postoperative complications and reduced long-term survival after robotic gastrectomy for gastric cancer. Assessing myosteatosis on staging CT could optimize preoperative risk stratification.

Distinct fibroblast subpopulations associated with bone, brain or intrapulmonary metastasis in advanced non-small-cell lung cancer.

BACKGROUND: Bone or brain metastases may develop in 20-40% of individuals with late-stage non-small-cell lung cancer (NSCLC), resulting in a median overall survival of only 4-6 months. However, the primary lung cancer tissue's distinctions between bone, brain and intrapulmonary metastases of NSCLC at the single-cell level have not been underexplored. METHODS: We conducted a comprehensive analysis of 14 tissue biopsy samples obtained from treatment-naïve advanced NSCLC patients with bone (n = 4), brain (n = 6) or intrapulmonary (n = 4) metastasis using single-cell sequencing originating from the lungs. Following quality control and the removal of doublets, a total of 80 084 cells were successfully captured. RESULTS: The most significant inter-group differences were observed in the fraction and function of fibroblasts. We identified three distinct cancer-associated fibroblast (CAF) subpopulations: myofibroblastic CAF (myCAF), inflammatory CAF (iCAF) and antigen-presenting CAF (apCAF). Notably, apCAF was prevalent in NSCLC with bone metastasis, while iCAF dominated in NSCLC with brain metastasis. Intercellular signalling network analysis revealed that apCAF may play a role in bone metastasis by activating signalling pathways associated with cancer stemness, such as SPP1-CD44 and SPP1-PTGER4. Conversely, iCAF was found to promote brain metastasis by activating invasion and metastasis-related molecules, such as MET hepatocyte growth factor. Furthermore, the interaction between CAFs and tumour cells influenced T-cell exhaustion and signalling pathways within the tumour microenvironment. CONCLUSIONS: This study unveils the direct interplay between tumour cells and CAFs in NSCLC with bone or brain metastasis and identifies potential therapeutic targets for inhibiting metastasis by disrupting these critical cell-cell interactions.

Impact of preoperative sarcopenia on postoperative complications and prognosis in patients undergoing robotic gastric cancer surgery: A propensity score matching study.

BACKGROUND: Sarcopenia, defined as decreased muscle mass and function, correlates with postoperative morbidity and mortality in cancer surgery. However, sarcopenia's impact specifically following robotic gastrectomy for gastric cancer has not been clearly defined. This study aimed to determine the influence of sarcopenia on short- and long-term clinical outcomes after robotic gastrectomy for gastric cancer. METHODS: This retrospective study analyzed 381 gastric cancer patients undergoing robotic gastrectomy. Sarcopenia was diagnosed by preoperative computed tomography (CT) body composition analysis. Propensity score matching created 147 pairs of sarcopenia and nonsarcopenia patients for comparison. Outcomes included postoperative complications, survival, inflammatory markers, length of stay, intensive care unit (ICU) transfer, and readmissions. RESULTS: Sarcopenia patients exhibited significantly higher rates of overall (53.7% versus 21.1%, P < 0.001), serious (12.9% versus 4.1%, P = 0.007), and grade III-IV complications compared to nonsarcopenia pairs after matching. Sarcopenia independently predicted reduced 3-years overall (HR = 2.53, 95% CI: 1.19-5.40, P = 0.016) and disease-free survival (HR = 1.99, 95% CI: 1.09-3.66, P = 0.026). Sarcopenia patients also showed heightened postoperative leukocyte, neutrophil, platelet, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and monocyte to lymphocyte ratio (MLR) levels alongside suppressed lymphocytes, monocytes, and neutrophil to lymphocyte ratio (NLR). CONCLUSION: Preoperative sarcopenia is correlated with increased postoperative complications and poorer long-term survival in gastric cancer patients undergoing robotic gastrectomy. Sarcopenia assessment can optimize preoperative risk stratification and perioperative management in this population.

eccDNA-pipe: an integrated pipeline for identification, analysis and visualization of extrachromosomal circular DNA from high-throughput sequencing data.

Extrachromosomal circular DNA (eccDNA) is currently attracting considerable attention from researchers due to its significant impact on tumor biogenesis. High-throughput sequencing (HTS) methods for eccDNA identification are continually evolving. However, an efficient pipeline for the integrative and comprehensive analysis of eccDNA obtained from HTS data is still lacking. Here, we introduce eccDNA-pipe, an accessible software package that offers a user-friendly pipeline for conducting eccDNA analysis starting from raw sequencing data. This dataset includes data from various sequencing techniques such as whole-genome sequencing (WGS), Circle-seq and Circulome-seq, obtained through short-read sequencing or long-read sequencing. eccDNA-pipe presents a comprehensive solution for both upstream and downstream analysis, encompassing quality control and eccDNA identification in upstream analysis and downstream tasks such as eccDNA length distribution analysis, differential analysis of genes enriched with eccDNA and visualization of eccDNA structures. Notably, eccDNA-pipe automatically generates high-quality publication-ready plots. In summary, eccDNA-pipe provides a comprehensive and user-friendly pipeline for customized analysis of eccDNA research.

Fully genotyping and screening of clinically important blood-group antigens by MALDI TOF mass spectrometry.

Several molecular biology methods are available for high-throughput blood typing. In this study, we aimed to build a high-throughput blood-group genetic screening system for high-frequency blood-group antigen-negative rare-blood groups in donors and patients. The amplification primers for all blood-type gene fragments involving the selected alleles were designed for detection. Single-base extend primers were also designed based on specific loci. DNA fragments were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) for the last nucleotide identification of amplification products in the extend step. The accuracy was verified by known samples. Thirty-six random samples were detected by serological tests and sequencing to verify the system stability. After verification, according to the collected known rare-blood-type samples, all the alleles designed to be detected matched with the validated single-nucleotide polymorphisms. The verification tests showed that all genotyping results of the random samples were in accordance with the findings of serotyping and sequencing. Then, 1258 random donor samples were screened by the built typing system after the verification. Three Fy(a-) and four s- were screened out in 1258 random blood samples. The multiple polymerase chain reaction-based MS detection system can be used in rare-blood-type screening with good accuracy and stability.

Remote Sensing Retrieval of Cloud Top Height Using Neural Networks and Data from Cloud-Aerosol Lidar with Orthogonal Polarization.

In order to enhance the retrieval accuracy of cloud top height (CTH) from MODIS data, neural network models were employed based on Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) data. Three types of methods were established using MODIS inputs: cloud parameters, calibrated radiance, and a combination of both. From a statistical standpoint, models with combination inputs demonstrated the best performance, followed by models with calibrated radiance inputs, while models relying solely on calibrated radiance had poorer applicability. This work found that cloud top pressure (CTP) and cloud top temperature played a crucial role in CTH retrieval from MODIS data. However, within the same type of models, there were slight differences in the retrieved results, and these differences were not dependent on the quantity of input parameters. Therefore, the model with fewer inputs using cloud parameters and calibrated radiance was recommended and employed for individual case studies. This model produced results closest to the actual cloud top structure of the typhoon and exhibited similar cloud distribution patterns when compared with the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) CTHs from a climatic statistical perspective. This suggests that the recommended model has good applicability and credibility in CTH retrieval from MODIS images. This work provides a method to improve accurate CTHs from MODIS data for better utilization.

Analysis of the uncertainty of the AIS-based bottom-up approach for estimating ship emissions.

Although the AIS-based bottom-up approach has become the dominant method for estimating ship emissions, there are still inherent uncertainties due to the numerous complex factors involved. This paper aims to investigate the development process of the AIS-based bottom-up approach and identify the primary sources of uncertainty by conducting a systematic review of 29 articles published since 2015. The result shows three sources of uncertainty for estimating ship emissions, i.e., the acquisition and processing of AIS data, ship characteristic information and engine load calculation, and the determination of emission factors. This paper suggests that the accuracy of ship emission inventories can be improved by enhancing the reliability of datasets, uniformly defining engine load calculation formulas, and making more extensive measurements of local emissions to provide substantial support for ship emissions management and facilitate the development of more effective emission reduction strategies.

Replacing traditional pretreatment in one-step UF with natural short-distance riverbank filtration: Continuous contaminants removal and TMP increase relief.

Scientists have been focusing on applying more natural processes instead of industrial chemicals in drinking water treatment to achieve the purpose of carbon emissions reduction. In this study, we shortened the infiltration range of riverbank filtration, a natural water purification process, to form the short-distance riverbank filtration (sRBF) which retained its ability in water quality improvement and barely influenced the groundwater environment, and integrated it with ultrafiltration (UF) to form a one-step sRBF-UF system. This naturalness-artificiality combination could realize stable contaminants removal and trans-membrane pressure (TMP) increase relief for over 30 days without dosing chemicals. Generally, both sRBF and UF played the important role in river water purification, and the interaction between them made the one-step sRBF-UF superior in long-term operation. The sRBF could efficiently remove contaminants (90 % turbidity, 60 % total nitrogen, 30 % ammonia nitrogen, and 25 % total organic carbon) and reduce the membrane fouling potential of river water under its optimum operation conditions, i.e., a hydraulic retention time of 48 h, an operation temperature of 20 °C, and a synergistic filter material of aquifer and riverbank soil. Synergistic adsorption, interception, and microbial biodegradation were proved to be the mechanisms of contaminants and foulants removal for sRBF. The sequential UF also participated in the reduction of impurities and especially played a role in intercepting microbial metabolism products and possibly leaked microorganisms from sRBF, assuring the safety of product water. To date, the one-step sRBF-UF was a new attempt to combine a natural process with an artificial one, and realized a good and stable product quality in long-term operation without doing industrial chemicals, which made it a promised alternative for water purification for cities alongside the river.

miR-223-3p Prevents Necroptotic Macrophage Death by Targeting Ripk3 in a Negative Feedback Loop and Consequently Ameliorates Advanced Atherosclerosis.

BACKGROUND: The formation of large necrotic cores results in vulnerable atherosclerotic plaques, which can lead to severe cardiovascular diseases. However, the specific regulatory mechanisms underlying the development of necrotic cores remain unclear. METHODS: To evaluate how the modes of lesional cell death are reprogrammed during the development of atherosclerosis, the expression levels of key proteins that are involved in the necroptotic, apoptotic, and pyroptotic pathways were compared between different stages of plaques in humans and mice. Luciferase assays and loss-of-function studies were performed to identify the microRNA-mediated regulatory mechanism that protects foamy macrophages from necroptotic cell death. The role of this mechanism in atherosclerosis was determined by using a knockout mouse model with perivascular drug administration and tail vein injection of microRNA inhibitors in Apoe-/- mice. RESULTS: Here, we demonstrate that the necroptotic, rather than the apoptotic or pyroptotic, pathway is more activated in advanced unstable plaques compared with stable plaques in both humans and mice, which closely correlates with necrotic core formation. The upregulated expression of Ripk3 (receptor-interacting protein kinase 3) promotes the C/EBPß (CCAAT/enhancer binding protein beta)-dependent transcription of the microRNA miR-223-3p, which conversely inhibits Ripk3 expression and forms a negative feedback loop to regulate the necroptosis of foamy macrophages. The knockout of the Mir223 gene in bone marrow cells accelerates atherosclerosis in Apoe-/- mice, but this effect can be rescued by Ripk3 deficiency or treatment with the necroptosis inhibitors necrostatin-1 and GSK-872. Like the Mir223 knockout, treating Apoe-/- mice with miR-223-3p inhibitors increases atherosclerosis. CONCLUSIONS: Our study suggests that miR-223-3p expression in macrophages protects against atherosclerotic plaque rupture by limiting the formation of necrotic cores, thus providing a potential microRNA therapeutic candidate for atherosclerosis.

A novel homozygous splice-site mutation of JK gene leads to Jk(a-b-) phenotype.

OBJECTIVES: This study aimed to investigate the molecular mechanism of the Jk(a-b-) phenotype in a Chinese transfusion patient. BACKGROUND: Many different mutation types relating to Jk(a-b-) phenotype have been reported. However, the splice-site mutation is relatively rare and the related functional verification is lacking. MATERIALS AND METHODS: In this study, the blood sample was collected from a transfusion patient with the Jk(a-b-) phenotype. Serotyping was performed using routine serological methods. The exons sequences and coding regions of the JK gene were amplified using polymerase chain reaction and directly sequenced. To perform a minigene splicing assay, the intronic mutation sequences were cloned into a pSPL3 splice reporting vector. The splicing reporter minigene assay was performed in HEK 293T cells. RESULTS: The Jk(a-b-) phenotype of the blood sample was identified through serological testing. Sequencing results revealed that the sample had a novel homozygous splice-site mutation JK*02N (NM_015865.7: c.663+3A>C). Further analysis, including cDNA sequencing and minigene splicing assay, confirmed that the novel splice-site mutation resulted in exon skipping. Interestingly, different numbers of exons being skipped were obtained by the two methods. CONCLUSION: This study revealed a novel homozygous splicing-site mutation associated with the Jk(a-b-) phenotype in Chinese population. Our results emphasise the importance of the in vitro functional method minigene splicing assay, while also acknowledging its potential limitations when compared to cDNA sequencing.

Overlooked flocs in electrocoagulation-based ultrafiltration systems: A new understanding of the structural interfacial properties.

An integrated ferrate-induced electrocoagulation-ultrafiltration (FECUF) process is proposed to cope with the growing demand for water treatment. Although flocs formed during the electrocoagulation (EC) process are useful for contaminant reduction and mitigation of membrane fouling, few studies have been focused on their structures and properties. Herein, we investigated the formation and structural transformations of flocs and their responses to organic matter, as well as the relationships between their interfacial properties and membrane fouling mitigation. It was found that ferrate contributed to the fast formation of flocs during the ferrate-induced electrocoagulation (FEC) process, which accelerated the FECUF process. Physicochemical analyses indicated that the flocs formed in the FEC process were mainly composed of Fe(III)-(hydr)oxides with abundant hydroxyl groups and poor crystallinity, which allowed complexation with NOM. Therefore, the mobilities of the NOM and the soluble coagulant ions were reduced. The responses of flocs to NOM suggested that the period of 0-20 min resulted in the most efficient NOM removal. In addition, two patterns revealed the relationships between the interfacial properties of the small colloidal particles (SCPs) and the membrane filtration performance: i) the decline in the initial flux was closely related to the composition (gel-type substances or metal-(hydr)oxides) of the SCPs and ii) the steady-state flux was influenced by the energy barrier between the SCPs. However, when the SCPs had the same composition, the interfacial properties influenced both the initial flux and the steady-state flux. This study provides an alternative FECUF process for intensive upgrades of centralized water treatment systems.

A single-cell landscape of pre- and post-menopausal high-grade serous ovarian cancer ascites.

High-grade serous ovarian cancer (HGSOC) is a hormone-related cancer with high mortality and poor prognosis. Based on the transcriptome of 57,444 cells in ascites from 10 patients with HGSOC (including 5 pre-menopausal and 5 post-menopausal patients), we identified 14 cell clusters which were further classified into 6 cell types, including T cells, B cells, NK cells, myeloid cells, epithelial cells, and stromal cells. We discovered an increased proportion of epithelial cells and a decreased proportion of T cells in pre-menopausal ascites compared with post-menopausal ascites. GO analysis revealed the pre-menopausal tumor microenvironments (TME) are closely associated with viral infection, while the post-menopausal TME are mostly related to the IL-17 immune pathway. SPP1/CD44-mediated crosstalk between myeloid cells and B cells, NK cells, and stromal cells mainly present in the pre-menopausal group, while SPP1/PTGER4 -mediated crosstalk between myeloid cells and epithelial cells mostly present in the post-menopausal group.

Electroacupuncture relieves chronic pain by promoting microglia M2 polarization in lumbar disc herniation rats.

Electroacupuncture has an effective analgesia on chronic pain caused by lumbar disc herniation (LDH) clinically, however, the underlying mechanism is unclear. In this study, we investigated whether electroacupuncture alleviated pain in LDH model rats by inducing spinal microglia M2 polarization. We established a noncompression LDH rat model by implanting autologous caudal nucleus pulposus into L5/L6 nerve root. Electroacupuncture (30 min/day) treatment on the ipsilateral side was started on the 8th postoperative day, once a day for consecutive 7 days. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were tested for pain behavior. Western blotting was used to detect the protein expression in lumbar enlargement (L5/L6). Immunofluorescence was used to detect iNOS+/Iba-1+ and Arg-1+/Iba-1+ and CB2R+/Iba-1+ in lumbar enlargement (L5/L6). We show that PWT and PWL decreased in the LDH group while Iba-1, iNOS, and TNF-α expression increased significantly in lumbar spinal dorsal horn (SDH) after LDH surgery, and revealing that microglia were activated and polarized towards proinflammatory M1 phenotype. Electroacupuncture treatment significantly increased PWT and PWL while reducing Iba-1, iNOS, and TNF-α expression, interestingly, Arg-1 and IL-10 expression were significantly increased. Moreover, electroacupuncture treatment led to CB2 receptors on microglia upregulation, while NF-κB and p-NF-κB expression in lumbar SDH downregulation. Our study indicated that electroacupuncture may reduce nociceptive hyperalgesia by inhibiting microglia activation and microglia M1 polarization and promoting microglia M2 polarization in lumbar SDH of LDH rats, which may be caused by the activation of CB2 receptors on microglia and inhibition of NF-κB pathway in lumbar SDH.