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JOURNAL/nrgr/04.03/01300535-202502000-00032/figure1/v/2024-05-28T214302Z/r/image-tiff Invasive inflammation and excessive scar formation are the main reasons for the difficulty in repairing nervous tissue after spinal cord injury. Microglia and astrocytes play key roles in the spinal cord injury micro-environment and share a close interaction. However, the mechanisms involved remain unclear. In this study, we found that after spinal cord injury, resting microglia (M0) were polarized into pro-inflammatory phenotypes (MG1 and MG3), while resting astrocytes were polarized into reactive and scar-forming phenotypes. The expression of growth arrest-specific 6 (Gas6) and its receptor Axl were significantly down-regulated in microglia and astrocytes after spinal cord injury. In vitro experiments showed that Gas6 had negative effects on the polarization of reactive astrocytes and pro-inflammatory microglia, and even inhibited the cross-regulation between them. We further demonstrated that Gas6 can inhibit the polarization of reactive astrocytes by suppressing the activation of the Yes-associated protein signaling pathway. This, in turn, inhibited the polarization of pro-inflammatory microglia by suppressing the activation of the nuclear factor-κB/p65 and Janus kinase/signal transducer and activator of transcription signaling pathways. In vivo experiments showed that Gas6 inhibited the polarization of pro-inflammatory microglia and reactive astrocytes in the injured spinal cord, thereby promoting tissue repair and motor function recovery. Overall, Gas6 may play a role in the treatment of spinal cord injury. It can inhibit the inflammatory pathway of microglia and polarization of astrocytes, attenuate the interaction between microglia and astrocytes in the inflammatory microenvironment, and thereby alleviate local inflammation and reduce scar formation in the spinal cord.
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This study aims to investigate the drug resistance, regulation mechanism of quorum sensing system, expression of related virulence genes, and epidemiological characteristics of carbapenem-resistant Pseudomonas aeruginosa (CRPA).In this study,Polymerase chain reaction amplification was performed to evaluate carbapenemase genes, oprD gene, quorum sensing system, and related virulence genes. Bacterial genotypes were analyzed using multilocus sequence typing and evolutionary analysis was conducted based on the goeBURST algorithm. The results demonstrated that a total of 47 CRPA strains were collected in this study, primarily from respiratory specimens in the ICU. Drug sensitivity results showed that the resistance rates of the 47 CRPA strains were highest for imipenem (97.87%). The loss of oprD may be the main factor contributing to carbapenem resistance in our hospital's CRPA strains.All isolates tested positive for the quorum sensing system genes lasI and rhlI/R, and the virulence gene lasB was detected in all isolates, while the algD gene was detected in 19.15% of the isolates. Among the 47 strains, 6 were untypeable, and the 41 strains with 28 different sequence types were clustered into three clonal complexes (BG1, BG2, and BG3).In conclusion, the CRPA isolates from our hospital exhibit high genetic diversity, with the deletion of the oprD gene possibly being the primary determinant of carbapenem resistance in Pseudomonas aeruginosa.Moreover, Las and RhI systems play a key role in quorum sensing signal system. Further research and development of drugs targeting quorum sensing signaling system may provide valuable guidance for the treatment of CRPA.
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Self-assembled monolayers (SAMs) have become pivotal in achieving high-performance perovskite solar cells (PSCs) and organic solar cells (OSCs) by significantly minimizing interfacial energy losses. In this study, we propose a co-adsorb (CA) strategy employing a novel small molecule, 2-chloro-5-(trifluoromethyl)isonicotinic acid (PyCA-3F), introducing at the buried interface between 2PACz and the perovskite/organic layers. This approach effectively diminishes 2PACz's aggregation, enhancing surface smoothness and increasing work function for the modified SAM layer, thereby providing a flattened buried interface with a favorable heterointerface for perovskite. The resultant improvements in crystallinity, minimized trap states, and augmented hole extraction and transfer capabilities have propelled power conversion efficiencies (PCEs) beyond 25% in PSCs with a p-i-n structure (certified at 24.68%). OSCs employing the CA strategy achieve remarkable PCEs of 19.51% based on PM1:PTQ10:m-BTP-PhC6 photoactive system. Notably, universal improvements have also been achieved for the other two popular OSC systems. After a 1000-hour maximal power point tracking, the encapsulated PSCs and OSCs retain approximately 90% and 80% of their initial PCEs, respectively. This work introduces a facile, rational, and effective method to enhance the performance of SAMs, realizing efficiency breakthroughs in both PSCs and OSCs with a favorable p-i-n device structure, along with improved operational stability.
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Colombia is well-positioned for the development of sustainable energy due to its abundance of natural resources, which include water, wind, and sun. Regulating the safe and sustainable use of offshore wind energy, which is considered non-conventional, is lacking in the nation, nonetheless. The development of offshore wind technology in Colombia shows potential to meet energy needs during dry hydrological conditions and El Niño/Southern Oscillation events when the hydroelectric system power supply is low. This study examines global initiatives that have encouraged nations to develop plans for cutting their CO2 emissions, stressing both their successes and shortcomings in putting offshore wind technology into practice. An examination of Colombia's renewable energy administrative framework finds a lack of data required to carry out offshore wind projects. Furthermore, a review of previous research on marine energy emphasizes how important it is to expand our knowledge of offshore wind generation. Although the majority of local renewable energy projects concentrate on terrestrial sources, an analysis of wind speed and wind power density in Colombia at different altitudes shows promising magnitudes and good trends.Digital finance plays a crucial role in this context by providing innovative funding mechanisms, enhancing financial accessibility, and reducing investment risks through improved financial technologies. These advancements support the mobilization of capital necessary for the development and expansion of offshore wind energy projects.As a result, the technical, economic, administrative, and legal data pertinent to renewable energy in Colombia is compiled in this study. It proposes to provide information to stakeholders involved in decision-making processes and promotes the possible installation of offshore wind farms in regions close to Colombia's Caribbean coast. Because of its plentiful resources, Colombia offers a great chance to implement offshore wind energy technology, which will lessen dependency on fossil fuels and provide a backup energy source in case of supply shortages. The integration of digital finance is key to unlocking the economic potential of these projects, ensuring sustainable and scalable energy solutions for the future.
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Tire wear particles (TWPs) have been an emerging threat to the soil ecosystem, while impact of the TWPs aging on soil microbial communities remains poorly understood. This study investigated the dynamic responses of soil microbial communities to the TWPs aging under both wet and flooded conditions. We found that different soil moisture conditions resulted in distinct microbial community structures. Soil bacteria were more sensitive to wet conditions, while soil fungi were more sensitive to flooded conditions. The family Symbiobacteraceae was predominant in the TWP-sphere under both wet and flooded conditions after 60â¯days, followed by Brevibacillaceae. Notably, we observed that TWPs input significantly increased nitrous oxide (N2O) emission from dryland soil. Several taxa including Cyanobacteriales, Blastocatellaceae and Pyrinomonadaceae were identified as TWP-biomarkers in soils and potentially played significant roles in N2O emissions from drylands. Their responses to the TWPs input correlated closely with changes in the relative abundance of genes involved in ammonia oxidation (amoA/B), nitrite reduction (nirS/K) and N2O reduction (nosZ) in drylands. Our results demonstrate that soil moisture-dependent TWP aging influences N2O emission by altering both the associated microbial communities and the relevant genes.
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The fluorescence collection from single atoms and emitters has been extensively utilized in quantum information and quantum optics research. Here, we investigated the collection efficiency of an objective lens by drawing an analogy between the free-space beam (FSB) and a waveguide mode. We explored how efficiency is influenced by their thermal motion within a dipole trap. Furthermore, we introduce an effective energy fraction ratio to quantify potential imperfections in the focusing of the objective lens. Our results provide valuable insights for optimizing the fluorescence collection in single-atom experiments and highlight the importance of considering realistic experimental conditions when estimating achievable efficiencies.
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Light and nitrogen availability are basic requirements for photosynthesis. Changing in light intensity and nitrogen concentration may require adaptive physiological and life process changes in phytoplankton cells. Our previous study demonstrated that two Thalassiosira species exhibited, respectively, distinctive physiological responses to light and nitrogen stresses. Transcriptomic analyses were employed to investigate the mechanisms behind the different physiological responses observed in two diatom species of the genus Thalassiosira. The results indicate that the congeneric species are different in their cellular responses to the same shifting light and nitrogen conditions. When conditions changed to high light with low nitrate (HLLN), the large-celled T. punctigera was photodamaged. Thus, the photosynthesis pathway and carbon fixation related genes were significantly down-regulated. In contrast, the small-celled T. pseudonana sacrificed cellular processes, especially amino acid metabolisms, to overcome the photodamage. When changing to high light with high nitrate (HLHN) conditions, the additional nitrogen appeared to compensate for the photodamage in the large-celled T. punctigera, with the tricarboxylic acid cycle (TCA cycle) and carbon fixation significantly boosted. Consequently, the growth rate of T. punctigera increased, which suggest that the larger-celled species is adapted for forming post-storm algal blooms. The impact of high light stress on the small-celled T. pseudonana was not mitigated by elevated nitrate levels, and photodamage persisted.
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In cross-country skiing, ski poles play a crucial role in technique, propulsion, and overall performance. The kinematic parameters of ski poles can provide valuable information about the skier's technique, which is of great significance for coaches and athletes seeking to improve their skiing performance. In this work, a new smart ski pole is proposed, which combines the uniaxial load cell and the inertial measurement unit (IMU), aiming to provide comprehensive data measurement functions more easily and to play an auxiliary role in training. The ski pole can collect data directly related to skiing technical actions, such as the skier's pole force, pole angle, inertia data, etc., and the system's design, based on wireless transmission, makes the system more convenient to provide comprehensive data acquisition functions, in order to achieve a more simple and efficient use experience. In this experiment, the characteristic data obtained from the ski poles during the Double Poling of three skiers were extracted and the sample t-test was conducted. The results showed that the three skiers had significant differences in pole force, pole angle, and pole time. Spearman correlation analysis was used to analyze the sports data of the people with good performance, and the results showed that the pole force and speed (r = 0.71) and pole support angle (r = 0.76) were significantly correlated. In addition, this study adopted the commonly used inertial sensor data for action recognition, combined with the load cell data as the input of the ski technical action recognition algorithm, and the recognition accuracy of five kinds of cross-country skiing technical actions (Diagonal Stride (DS), Double Poling (DP), Kick Double Poling (KDP), Two-stroke Glide (G2) and Five-stroke Glide (G5)) reached 99.5%, and the accuracy was significantly improved compared with similar recognition systems. Therefore, the equipment is expected to be a valuable training tool for coaches and athletes, helping them to better understand and improve their ski maneuver technique.
Subject(s)
Skiing , Skiing/physiology , Humans , Biomechanical Phenomena/physiology , Pattern Recognition, Automated/methods , Athletic Performance/physiologyABSTRACT
γ-polyglutamic acid (γ-PGA), as an environmentally sustainable material, is extensive applied in agriculture for enhancing water and fertilizer utilization efficiency, augmenting crop yield, and ameliorating soil conditions. However, the effect of γ-PGA in conjunction with sesame cake fertilizer on the soil environment remains uncertain.The aim of this study is to investigate the effect of γ-PGA on soil nutrients, water use efficiency (WUE) and nitrogen use efficiency (NUE), and maize yield across various levels of sesame cake fertilizer. Additionally, the study seeks to identify the optimal ratio to establish a theoretical and practical foundation for sustainable agricultural development and the promotion of ecological agriculture. Through field experiments, nine treatments were established, comprising three levels of sesame cake fertilizer application rates (B1 = 900 kg/hm2 for low fertility, B2 = 1100 kg/hm2 for medium fertility, and B3 = 1300 kg/hm2 for high fertility) and three levels of γ-PGA application rates (R1 = 200 kg/hm2, R2 = 400 kg/hm2, and R3 = 600 kg/hm2). The results can be outlined as follows: (1) When γ-PGA application rate increased, total nitrogen (TN) exhibited a synergistic effect under B1 treatment, but an antagonistic effect under B2 and B3 treatments. At the 6-leaf stage (V6), 12-leaf stage (V12), and tasseling stage (VT), available phosphorus (AP) exhibited antagonistic effects. However, at the filling stage (R2) and maturity stage (R6), AP in B1 and B2 treatments at various depths underwent partial transformation into a synergistic effect. The levels of available potassium exhibited a notable antagonistic effect, leading to a decrease in harvest index (HI). B2 treatment demonstrated superior results compared to the B1 and B3 treatments, with the highest levels observed under B2R1 treatment; (2) TN content in the 0-40 cm soil layer increased during the filling period, and it was uniformly distributed in the 40-60 cm soil layer. When the soil AP was located in the 0-60 cm soil layer, there was an increase in AP content during the mature period. Following the tasseling period, different treatments exhibited varying patterns of increase in response to the presence of potassium within the 0-60 cm soil layer. Consequently, in cases where the sesame cake fertilizer content is low, the interaction between γ-PGA can compensate for the deficiency of fertilizer, thereby enhancing water and nitrogen utilization efficiency. The optimal fertilization strategy for enhancing soil nutrient distribution, WUE and NUE, and yield is proposed to be the application of 1100 kg/hm2 sesame cake fertilizer and 200 kg/hm2 γ-PGA.
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Background: To evaluate the effectiveness of the surgical approach in patients with congenital heart disease and pulmonary hypertension (PH). Methods: This was a retrospective clinical review of patients with congenital heart disease and PH who underwent pulmonary artery banding (PAB) at our institution between January 2013 and January 2023. Results: We identified 219 patients (53.4% males) with a median age of 7 (4.0-15.0) months and a median weight of 6.8 (5.2-9.0) kg at the time of PAB. The median hospital stay was 7.0 (5.0-10.0) days. The in-hospital mortality rate was 4.6%. The median follow-up was 33.0 (17.0-61.0) months. Survival rates were 96.9 ± 2.5% at 60 months and 92.1 ± 6.9% at 120 months post-PAB. 43.8% of patients had a de-banding procedure, and 147 (79.0%) patients received a second-stage procedure (34.7% univentricular, 65.3% biventricular). The mortality rate between stages was 4.3%. 21 (9.6%) patients reached a third-stage procedure. The overall mortality rate was 9.1%. Conclusions: PAB is an acceptable strategy for patients with congenital heart disease complicated with PH. The results and outcomes of subsequent univentricular or biventricular procedures are generally good.
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Cholangiocarcinoma (CCA) is a rare type of digestive tract cancer originating from the epithelial cells of the liver and biliary tract. Current treatment modalities for CCA, such as chemotherapy and radiation therapy, have demonstrated limited efficacy in enhancing survival rates. Despite the revolutionary potential of immunotherapy in cancer management, its application in CCA remains restricted due to the minimal infiltration of immune cells in these tumors, rendering them cold and unresponsive to immune checkpoint inhibitors (ICIs). Cancer cells within cold tumors deploy various mechanisms for evading immune attack, thus impeding clinical management. Recently, combination immunotherapy has become increasingly essential to comprehend the mechanisms underlying cold tumors to enhance a deficient antitumor immune response. Therefore, a thorough understanding of the knowledge on the combination immunotherapy of cold CCA is imperative to leverage the benefits of immunotherapy in treating patients. Moreover, gut microbiota plays an essential role in the immunotherapeutic responses in CCA. In this review, we summarize the current concepts of immunotherapy in CCA and clarify the intricate dynamics within the tumor immune microenvironment (TIME) of CCA. We also delve into the evasion mechanisms employed by CCA tumors against the anti-tumor immune responses. The context of combination immunotherapies in igniting cold tumors of CCA and the critical function of gut microbiota in prompting immune responses have also been annotated. Furthermore, we have proposed future directions in the realm of CCA immunotherapy, aiming to improve the clinical prognosis of CCA patients.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Immunotherapy , Tumor Microenvironment , Humans , Cholangiocarcinoma/therapy , Cholangiocarcinoma/immunology , Cholangiocarcinoma/pathology , Tumor Microenvironment/immunology , Bile Duct Neoplasms/therapy , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/immunology , Immune Checkpoint Inhibitors/therapeutic use , Gastrointestinal MicrobiomeABSTRACT
PURPOSE: To confirm which method provides lower rate of recurrent instability and superior clinical outcomes. METHOD: We searched PubMed, Embase and Web of Science for the trials involving one intervention or both for patellar instability: medial patellofemoral ligament reconstruction (MPFLR) with and without tibial tubercle osteotomy (TTO). The postoperative Kujala score, Lysholm score, Tegner scores and the rate of recurrent instability (dislocation or subluxation) were analyzed as the primary clinical outcome parameters in a random or fixed effects meta-analysis. RESULTS: In total, 43 articles met inclusion criteria after full-text review. A total of 2046 patients were analyzed. The overall mean age was 20.3 years (range, 9.5-60.0 years), with a mean follow-up time of 3.2 years (range, 1-8 years). The mean Kujala scores in MPFLR and MPFLR + TTO were 89.04 and 84.44, respectively. There was significant difference in Kujala scores between MPFLR and MPFLR + TTO (MD = 4.60, 95%CI: 1.07-8.13; P = 0.01). The mean Lysholm scores in MPFLR and MPFLR + TTO were 90.59 and 88.14, respectively. There was no significant difference in Lysholm scores between MPFLR and MPFLR + TTO (MD = 2.45, 95%CI: -3.20-8.10; P = 0.40). The mean Tegner scores in MPFLR and MPFLR + TTO were 5.30 and 4.88, respectively. There was no significant difference in Tegner scores between MPFLR and MPFLR + TTO (MD = 0.42, 95%CI: -0.39-1.23; P = 0.31). At final follow-up, the rates of recurrent instability in MPFLR and MPFLR + TTO were 3% and 4%, respectively. There was no significant difference in the rates between MPFLR and MPFLR + TTO (OR = 0.99, 95%CI: 0.96-1.02; P = 0.4848). CONCLUSION: MPFLR and MPFLR + TTO are effective and reliable treatments in the setting of patellofemoral instability. MPFLR seems to show a better performance in functional outcomes than MPFLR + TTO. Moreover, their rates of recurrent instability are very low, and no significant difference exists.
Subject(s)
Joint Instability , Osteotomy , Patellofemoral Joint , Tibia , Humans , Osteotomy/methods , Joint Instability/surgery , Tibia/surgery , Patellofemoral Joint/surgery , Treatment Outcome , Plastic Surgery Procedures/methods , Adult , Patellar Dislocation/surgery , Young Adult , Patellar Ligament/surgery , Adolescent , Ligaments, Articular/surgery , RecurrenceABSTRACT
Mitochondrial pyruvate carrier (MPC) inhibitors promote the development of hair follicle stem cells without affecting normal cells, which is promising for the treatment of hair loss. Herein, a series of cyano-cinnamate derivatives of UK-5099 were designed and synthesized. All these new compounds have been tested for their ability to promote cellular lactate production in vitro. Compound 4i (LA content:0.322 µmol/106cell) showed better cellular lactate production activity than UK-5099 (LA content:0.185 µmol/106cell). Further compound 4i was also tested on shaved mice by topical treatment and promoted obvious hair growth on mice.
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Background: Bladder cancer (BC) is one of the most common malignancies of the urogenital system. This study assessed the nucleotide-binding oligomerization domain and leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) in BC as well as the effects of cryptotanshinone on changes in BC malignant behaviors and NLRP3 expression under a lipopolysaccharide (LPS)-induced inflammatory microenvironment. Methods: BC tissue specimens from 62 patients were collected for immunohistochemical detection of NLRP3 protein. BC and normal urothelial cell lines were cultured for the detection of NLRP3 mRNA and protein. Then, BC cells were pretreated with LPS to mimic the inflammatory tumor microenvironment. Next, these cells were incubated with a low or high dose of cryptotanshinone to assess its effects on tumor cell malignant behaviors as well as transfected with NLRP3 cDNA to confirm the role of NLRP3 in BC cells in vitro. Results: High NLRP3 expression was associated with larger tumor diameters (>2 cm), muscle invasion, and metastasis. The levels of NLRP3 mRNA and protein were greater in BC cells than in normal urothelial cells. LPS pretreatment significantly promoted NLRP3 and inflammatory cytokine expression in BC cells, and induced cell viability, migration, and invasion. However, cryptotanshinone was able to reduce the LPS-induced increase of NLRP3 and inflammatory cytokine expression as well as the BC cell malignant progression. NLRP3 overexpression using NLRP3 cDNA further promoted BC cell malignant progression after LPS stimulation and reversed cryptotanshinone-reduced LPS-induced BC cell malignant behaviors. Conclusion: NLRP3 might possess oncogenic activity in BC, and the antitumor activity of cryptotanshinone in BC in vitro might be related to its inhibition of NLRP3 expression.
Subject(s)
Lipopolysaccharides , NLR Family, Pyrin Domain-Containing 3 Protein , Phenanthrenes , Urinary Bladder Neoplasms , Humans , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/pathology , Phenanthrenes/pharmacology , Male , Cell Line, Tumor , Female , Middle Aged , Tumor Microenvironment/drug effects , Aged , Cell Movement/drug effects , Cell Survival/drug effects , Inflammation/metabolismABSTRACT
Breast cancer is one of the threatening malignant tumors with the highest mortality and incidence rate over the world. There are a lot of breast cancer patients dying every year due to the lack of effective and safe therapeutic drugs. Therefore, it is highly necessary to develop more effective drugs to overcome breast cancer. As a glycoside derivative of apigenin, cosmosiin is characterized by low toxicity, high water solubility, and wide distribution in nature. Additionally, cosmosiin has been shown to perform anti-tumor effects in cervical cancer, hepatocellular carcinoma and melanoma. However, its pharmacological effects on breast cancer and its mechanisms are still unknown. In our study, the anti-breast cancer effect and mechanism of cosmosiin were investigated by using breast cancer models in vivo and in vitro. The results showed that cosmosiin inhibited the proliferation, migration, and adhesion of breast cancer cells in vitro and suppressed the growth of tumor in vivo through binding with AhR and inhibiting it, thus regulating the downstream CYP1A1/AMPK/mTOR and PPARγ/Wnt/ß-catenin signaling pathways. Collectively, our findings have made contribution to the development of novel drugs against breast cancer by targeting AhR and provided a new direction for the research in the field of anti-breast cancer therapy.
Subject(s)
Breast Neoplasms , Cell Proliferation , Cytochrome P-450 CYP1A1 , PPAR gamma , Receptors, Aryl Hydrocarbon , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , PPAR gamma/metabolism , Animals , Receptors, Aryl Hydrocarbon/metabolism , Mice , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A1/genetics , Cell Proliferation/drug effects , Mice, Nude , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice, Inbred BALB C , Cell Movement/drug effects , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Xenograft Model Antitumor Assays , Wnt Signaling Pathway/drug effectsABSTRACT
(Hetero)arylated bicyclo[1.1.1]pentanes (BCPs) are important for the construction of complex druglike target molecules. Herein, we developed a method for light-induced, Cs2CO3-promoted homolytic cleavage of pyridinium C-N bonds for generating alkyl radicals from amino acid-derived Katritzky salts and use of the radicals for functionalization of [1.1.1]propellane to rapidly generate (hetero)arylated BCPs. The method features excellent functional group tolerance and a broad substrate scope and can be used to functionalize structurally complex natural products.
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Among the many adverse geological disasters, the surge water disaster in karst areas causes the greatest loss to underground engineering construction, so it is necessary to carry out relevant research on the management of surge water disaster in karst pipelines. This study presents the creation of an oily epoxy resin magnetic convergence grouting material (OEMS) specifically developed to prevent water infiltration in pipelines. A self-designed visual karst pipeline grouting simulation system was used to conduct an experimental study on the diffusion and plugging behavior of magnetic slurry grouting. A model was constructed to simulate the migration of a magnetic slurry in water inrush circumstances. The model is based on the theory of slurry diffusion and the concept of magnetic adsorption. The results suggest that:(i) The best performance in grouting sealing is achieved when the ratio of new OEMS epoxy resin A liquid to B liquid is 2:1, and the blending ratio of flyash and Fe3O4 powder falls between 25 and 55%. (ii) The primary and secondary correlations among the parameters that affect the rate of change in flow rate, plugging pressure, and slurry retention rate are as follows: Hydrodynamic velocity has the greatest correlation, followed by plugging length, Fe3O4 power ratio, and flyash mixture ratio. (iii) The validity of the model is verified by comparing empirical observations with calculated theoretical values.
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We establish an in vitro perfusion intestinal tissue bioreactor system tailored to study drug responses related to inflammatory bowel disease (IBD). The system includes key components including multiple human intestinal cell types (colonoids, myofibroblasts, and macrophages), a three-dimensional (3D) intestinal architecture, and fluid flow. Inclusion of myofibroblasts resulted in increased secretion of cytokines such as glypican-1 (GCP-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 1-α (IL-1α), whereas inclusion of macrophages resulted in increased secretion of monocyte chemoattractant proteins (MCPs) demonstrating a significant role of both stromal and immune cell types in intestinal inflammation. The system is responsive to drug treatments, as reflected in the reduction of pro-inflammatory cytokine production in tissue in some treatment scenarios. While future studies are needed to evaluate more nuanced responses in an IBD context, the present study demonstrates the ability to establish a 3D intestinal model with multiple relevant cell types and flow that is responsive to both inflammatory cues and various drug treatment options.