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1.
Int Immunopharmacol ; 136: 112330, 2024 May 31.
Article En | MEDLINE | ID: mdl-38823180

An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.

2.
Water Res ; 258: 121830, 2024 May 23.
Article En | MEDLINE | ID: mdl-38823285

Distance-decay (DD) equations can discern the biogeographical pattern of organisms and genes in a better way with advanced statistical methods. Here, we developed a data Compilation, Arrangement, and Statistics framework to advance quantile regression (QR) into the generation of DD equations for antibiotic resistance genes (ARGs) across various spatial scales using freshwater reservoirs as an illustration. We found that QR is superior at explaining dissemination potential of ARGs to the traditionally used least squares regression (LSR). This is because our model is based on the 'law of limiting factors', which reduces influence of unmeasured factors that reduce the efficacy of the LSR method. DD equations generated from the 99th QR model for ARGs were 'Sall = 90.03e-0.01Dall' in water and 'Sall = 92.31e-0.011Dall' in sediment. The 99th QR model was less impacted by uneven sample sizes, resulting in a better quantification of ARGs dissemination. Within an individual reservoir, the 99th QR model demonstrated that there is no dispersal limitation of ARGs at this smaller spatial scale. The QR method not only allows for construction of robust DD equations that better display dissemination of organisms and genes across ecosystems, but also provides new insights into the biogeography exhibited by key parameters, as well as the interactions between organisms and environment.

3.
Inflamm Res ; 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844678

BACKGROUND: We have previously shown that asthma-like airways inflammation may be induced by topical exposure to respiratory tract pathogens such as S. pneumoniae (SP) in concert with epithelial alarmins such as IL-33. Details of the pathogenesis of this murine surrogate remain however unexplored. METHODS: Airways inflammation was induced by repeated, intranasal exposure of Il-4-/-, Rag1-/- and Rag2-/-Il2rg-/- mice (in which B lymphocyte IgE switching, adaptive and innate immunity are respectively ablated) as well as wild type mice to inactivated SP, IL-33 or both. Airways pathological changes were analysed, and the subsets and functions of locally accumulated ILC2s investigated by single cell RNA sequencing and flow cytometry. RESULTS: In the presence of IL-33, repeated exposure of the airways to inactivated SP caused marked eosinophil- and neutrophil-rich inflammation and local accumulation of ILC2s, which was retained in the Il-4-/- and Rag1-/- deficient mice but abolished in the Rag2-/-Il2rg-/- mice, an effect partly reversed by adoptive transfer of ILC2s. Single cell sequencing analysis of ILC2s recruited following SP and IL-33 exposure revealed a Klrg1+Ly6a+subset, expressing particularly elevated quantities of the pro-inflammatory cytokine IL-6, type 2 cytokines (IL-5 and IL-13) and MHC class II molecules, promoting type 2 inflammation as well as involved in neutrophil-mediated inflammatory responses. CONCLUSION: Local accumulation of KLRG1+Ly6a+ ILC2s in the lung tissue is a critical aspect of the pathogenesis of airways eosinophilic and neutrophil-rich inflammation induced by repeated exposure to SP in the presence of the epithelial alarmin IL-33.

4.
J Cereb Blood Flow Metab ; : 271678X241251976, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38833561

Carotid atherosclerosis is a major cause of stroke. Hemodynamic forces, such as shear stress and oscillatory shear, play an important role in the initiation and progression of atherosclerosis. The alteration of the immune microenvironment is the fundamental pathological mechanism by which diverse external environmental factors impact the formation and progression of plaques. However, Current research on the relationship between hemodynamics and immunity in atherosclerosis still lack of comprehensive understanding. In this study, we combined computational fluid dynamics (CFD) and Mass cytometry (CyTOF) technologies to explore the changes in the immune microenvironment within plaques under different hemodynamic conditions. Our results indicated that neutrophils were enriched in adverse flow environments. M2-like CD163+CD86+ macrophages were predominantly enriched in high WSS and low OSI environments, while CD163-CD14+ macrophages were enriched in low WSS and high OSI environments. Functional analysis further revealed T cell pro-inflammatory activation and dysregulation in modulation, along with an imbalance in M1-like/M2-like macrophages, suggesting their potential involvement in the progression of atherosclerotic lesions mediated by adverse flow patterns. Our study elucidated the potential mechanisms by which hemodynamics regulated the immune microenvironment within plaques, providing intervention targets for future precision therapies.

5.
Respir Res ; 25(1): 230, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824593

BACKGROUND: Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma. METHODS: The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor. RESULTS: Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-ß1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression. CONCLUSIONS: Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.


Airway Remodeling , Amino Acid Oxidoreductases , Asthma , Ovalbumin , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Amino Acid Oxidoreductases/metabolism , Amino Acid Oxidoreductases/genetics , Amino Acid Oxidoreductases/biosynthesis , Ovalbumin/toxicity , Airway Remodeling/physiology , Proto-Oncogene Proteins c-akt/metabolism , Mice , Humans , Asthma/pathology , Asthma/metabolism , Asthma/enzymology , Asthma/genetics , Signal Transduction/physiology , Female , Mice, Inbred BALB C , Male , Epithelial-Mesenchymal Transition/physiology
6.
Sci Rep ; 14(1): 13197, 2024 Jun 08.
Article En | MEDLINE | ID: mdl-38851848

New urbanization (NU) and ecological welfare performance (EWP) play pivotal roles in achieving sustainable urban development, with both emphasizing social equity and environmental management. Exploring the coordinated relationship between EWP and NU is invaluable for understanding the symbiotic interplay between humans and nature. We constructed a framework to elucidate the coupling mechanism of EWP and NU from the perspective of systems theory. We quantified the levels of NU and EWP utilizing the entropy weighting method and the super-efficient SBM method, respectively. Furthermore, we assessed the degree of coupling coordination between the two using the coupling coordination degree model (CCDM). Spatial and temporal evolution analysis was conducted, and factors influencing the degree of coupling coordination between EWP and NU were explored through a spatial-temporal geographically-weighted regression model (GTWR). The results indicate: (1) During the study period, the average annual increase in EWP in the study area was 2.59%, with a narrowing relative gap between cities. Conversely, the average annual increase in the level of NU was 7.6%, with demographic and economic dimensions carrying the highest weights. (2) The type of coupling coordination between EWP and NU transitions from basic coordination to moderate coordination, with the development of EWP lagging behind that of NU. (3) City size demonstrates a positive yet diminishing trend on the coupling coordination level, with economic development exerting the greatest influence and exhibiting a "V" trend, while the impact of green technology innovation diminishes negatively. Additionally, regional disparities are significant, with city size exhibiting a negative impact in areas of high population density and low economic levels, and green technology innovation showing notable polarization characteristics in core cities. These findings serve as a foundation for fostering coordinated ecological development amid the rapid urbanization process of the Chengdu-Chongqing Economic Circle.

8.
Clin Transl Immunology ; 13(6): e1515, 2024.
Article En | MEDLINE | ID: mdl-38835955

Objectives: Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a subtype of lung carcinoma associated with the Epstein-Barr virus (EBV). The clinical predictive biomarkers of immune checkpoint blockade (ICB) in PLELC require further investigation. Methods: We prospectively analysed EBV levels in the blood and immune tumor biomarkers of 31 patients with ICB-treated PLELC. Viral EBNA-1 and BamHI-W DNA fragments in the plasma were quantified in parallel using quantitative polymerase chain reaction. Results: Progression-free survival (PFS) was significantly longer in EBNA-1 high or BamHI-W high groups. A longer PFS was also observed in patients with both high plasma EBNA-1 or BamHI-W and PD-L1 ≥ 1%. Intriguingly, the tumor mutational burden was inversely correlated with EBNA-1 and BamHI-W. Plasma EBV load was negatively associated with intratumoral CD8+ immune cell infiltration. Dynamic changes in plasma EBV DNA level were in accordance with the changes in tumor volume. An increase in EBV DNA levels during treatment indicated molecular progression that preceded the imaging progression by several months. Conclusions: Plasma EBV DNA could be a useful and easy-to-use biomarker for predicting the clinical activity of ICB in PLELC and could serve to monitor disease progression earlier than computed tomography imaging.

9.
Front Physiol ; 15: 1382982, 2024.
Article En | MEDLINE | ID: mdl-38860113

Objectives: To compare the inter-rectus distance (IRD), rectus abdominis thickness (RAT), and stiffness in women during pregnancy and postpartum and identify the risk and protective factors affecting diastasis recti abdominis (DRA). Materials and methods: A total of 171 pregnant women who volunteered to participate in this study were recruited. Using an ultrasonographic diagnostic instrument with shear wave elastography function, IRD, RAT and the Young's modulus of the rectus abdominis muscles were measured at 12 weeks, 37 weeks of pregnancy, and 6 weeks postpartum. Results: The IRD at 37 weeks was significantly higher than that at 12 weeks and then decreased at 6 weeks postpartum, but it was still higher than that at 12 weeks (p < 0.001). RAT and Young's modulus decreased significantly at 37 weeks compared with those at 12 weeks and then recovered at 6 weeks postpartum, but they were lower than those at 12 weeks (p < 0.001). IRD at 12 weeks was significantly higher in multiparae than in primiparae (p < 0.001). Moreover, positive correlation between the RAT and Young's modulus of rectus abdominis muscles at 12 and 37 weeks of gestation and 6 weeks postpartum (p < 0.001) was observed. Multiple linear regression analysis showed that the regression equation was significant (f = 24.856, p < 001). Conclusion: Our study identified differences in IRD, thickness and stiffness of the rectus abdominis muscle between early and advanced pregnancy and the postpartum period. The risk and protective factors of DRA may guide pregnant women's protection and treatment.

10.
IEEE Trans Med Imaging ; PP2024 Jun 11.
Article En | MEDLINE | ID: mdl-38861432

Estimation of the fractional flow reserve (FFR) pullback curve from invasive coronary imaging is important for the intraoperative guidance of coronary intervention. Machine/deep learning has been proven effective in FFR pullback curve estimation. However, the existing methods suffer from inadequate incorporation of intrinsic geometry associations and physics knowledge. In this paper, we propose a constraint-aware learning framework to improve the estimation of the FFR pullback curve from invasive coronary imaging. It incorporates both geometrical and physical constraints to approximate the relationships between the geometric structure and FFR values along the coronary artery centerline. Our method also leverages the power of synthetic data in model training to reduce the collection costs of clinical data. Moreover, to bridge the domain gap between synthetic and real data distributions when testing on real-world imaging data, we also employ a diffusion-driven test-time data adaptation method that preserves the knowledge learned in synthetic data. Specifically, this method learns a diffusion model of the synthetic data distribution and then projects real data to the synthetic data distribution at test time. Extensive experimental studies on a synthetic dataset and a real-world dataset of 382 patients covering three imaging modalities have shown the better performance of our method for FFR estimation of stenotic coronary arteries, compared with other machine/deep learning-based FFR estimation models and computational fluid dynamics-based model. The results also provide high agreement and correlation between the FFR predictions of our method and the invasively measured FFR values. The plausibility of FFR predictions along the coronary artery centerline is also validated.

11.
Nat Commun ; 15(1): 4992, 2024 Jun 11.
Article En | MEDLINE | ID: mdl-38862519

It has been previously shown that devices based on microbial biofilms can generate hydrovoltaic energy from water evaporation. However, the potential of hydrovoltaic energy as an energy source for microbial growth has remained unexplored. Here, we show that the electroautotrophic bacterium Rhodopseudomonas palustris can directly utilize evaporation-induced hydrovoltaic electrons for growth within biofilms through extracellular electron uptake, with a strong reliance on carbon fixation coupled with nitrate reduction. We obtained similar results with two other electroautotrophic bacterial species. Although the energy conversion efficiency for microbial growth based on hydrovoltaic energy is low compared to other processes such as photosynthesis, we hypothesize that hydrovoltaic energy may potentially contribute to microbial survival and growth in energy-limited environments, given the ubiquity of microbial biofilms and water evaporation conditions.


Biofilms , Rhodopseudomonas , Water , Biofilms/growth & development , Rhodopseudomonas/metabolism , Rhodopseudomonas/growth & development , Water/chemistry , Water/metabolism , Photosynthesis , Electrons , Carbon Cycle , Nitrates/metabolism , Bioelectric Energy Sources/microbiology
12.
Sci Rep ; 14(1): 11272, 2024 05 17.
Article En | MEDLINE | ID: mdl-38760392

Plyometric training (PT) is an effective training method for improving physical fitness among trained individuals; however, its impact on health-related physical fitness in untrained participants remains ambiguous. Therefore, this meta-analysis aimed to evaluate the effects of PT on health-related physical fitness among untrained participants. Six electronic databases (PubMed, CINAHL Plus, MEDLINE Complete, Web of Science Core Collection, SCOPUS, and SPORTDiscus) were systematically searched until March 2024. We included controlled trials that examined the effects of PT on health-related physical fitness indices in untrained participants. Twenty-one studies were eligible, including a total of 1263 participants. Our analyses revealed small to moderate effects of PT on body mass index, muscular strength, cardiorespiratory fitness, and flexibility (ES = 0.27-0.61; all p > 0.05). However, no significant effects were detected for body fat percentage and lean mass (ES = 0.21-0.41; all p > 0.05). In conclusion, the findings suggest that PT may be potentially effective in improving health-related physical fitness indices (i.e., body mass index, muscular strength, cardiorespiratory fitness, and flexibility) in untrained participants. However, the results should be interpreted cautiously due to data limitations in some fitness variables.


Body Mass Index , Cardiorespiratory Fitness , Muscle Strength , Physical Fitness , Plyometric Exercise , Humans , Physical Fitness/physiology , Muscle Strength/physiology , Plyometric Exercise/methods , Cardiorespiratory Fitness/physiology , Male , Female , Adult
13.
Carbohydr Polym ; 338: 122148, 2024 Aug 15.
Article En | MEDLINE | ID: mdl-38763731

Alginate-based materials present promising potential for emergency hemostasis due to their excellent properties, such as procoagulant capability, biocompatibility, low immunogenicity, and cost-effectiveness. However, the inherent deficiencies in water solubility and mechanical strength pose a threat to hemostatic efficiency. Here, we innovatively developed a macromolecular cross-linked alginate aerogel based on norbornene- and thiol-functionalized alginates through a combined thiol-ene cross-linking/freeze-drying process. The resulting aerogel features an interconnected macroporous structure with remarkable water-uptake capacity (approximately 9000 % in weight ratio), contributing to efficient blood absorption, while the enhanced mechanical strength of the aerogel ensures stability and durability during the hemostatic process. Comprehensive hemostasis-relevant assays demonstrated that the aerogel possessed outstanding coagulation capability, which is attributed to the synergistic impacts on concentrating effect, platelet enrichment, and intrinsic coagulation pathway. Upon application to in vivo uncontrolled hemorrhage models of tail amputation and hepatic injury, the aerogel demonstrated significantly superior performance compared to commercial alginate hemostatic agent, yielding reductions in clotting time and blood loss of up to 80 % and 85 %, respectively. Collectively, our work illustrated that the alginate porous aerogel overcomes the deficiencies of alginate materials while exhibiting exceptional performance in hemorrhage, rendering it an appealing candidate for rapid hemostasis.


Alginates , Gels , Hemostasis , Hemostatics , Alginates/chemistry , Animals , Hemostatics/chemistry , Hemostatics/pharmacology , Hemostasis/drug effects , Gels/chemistry , Porosity , Hemorrhage/drug therapy , Blood Coagulation/drug effects , Mice , Male , Cross-Linking Reagents/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
14.
Small ; : e2402529, 2024 May 20.
Article En | MEDLINE | ID: mdl-38767079

Unlocking CO2 capture potential remains a complex and challenging endeavor. Here, a blueprint is crafted for optimizing materials through CO2 capture and developing a synergistic hybridization strategy that involves synthesizing CO2-responsive hydrogels by integrating polymeric networks interpenetrated with polyethyleneimine (PEI) chains and inorganic CaCl2. Diverging from conventional CO2 absorbents, which typically serve a singular function in CO2 capture, these hybrid PEAC hydrogels additionally harness its presence to tune their optical and mechanical properties once interacting with CO2. Such synergistic functions entail two significant steps: (i) rapid CO2-fixing through PEI chains to generate abundant carbamic acid and carbamate species and (ii) mineralization via CaCl2 to induce the formation of CaCO3 micro-crystals within the hydrogel matrix. Due to the reversible bonding, the PEAC hydrogels enable the decoupling of CO2 through an acid fumigation treatment or a heating process, achieving dynamic CO2 capture-release cycles up to 8 times. Furthermore, the polyethyleneimine-acrylamide-calcium chloride (PEAC) hydrogel exhibits varying antibacterial attributes and high interfacial adhesive strength, which can be modulated by fine-tuning the compositions of PEI and CaCl2. This versatility underscores the promising potential of PEAC hydrogels, which not only unlocks CO2 capture capabilities but also offers opportunities in diverse biological and biomedical applications.

15.
Sci Rep ; 14(1): 10173, 2024 05 03.
Article En | MEDLINE | ID: mdl-38702351

This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.


Anti-Bacterial Agents , Meropenem , Microbial Sensitivity Tests , Shock, Septic , Humans , Meropenem/pharmacokinetics , Meropenem/administration & dosage , Meropenem/therapeutic use , Shock, Septic/drug therapy , Male , Female , Middle Aged , Aged , Prospective Studies , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Adult , Intestinal Perforation , Aged, 80 and over
16.
J Phys Chem B ; 128(19): 4751-4758, 2024 May 16.
Article En | MEDLINE | ID: mdl-38709975

The surface patterning in natural systems has exhibited appreciable functional advantages for life activities, which serve as inspiration for the design of artificial counterparts to achieve functions such as directional liquid transport at the nanoscale. Here, we propose a patterned two-dimensional (2D) in-plane heterostructure with a triangle-shaped hexagonal boron nitride (hBN) track embedded in graphene nanosheets, which can achieve unidirectional and self-propelled transport of nanodroplets carrying various biomolecules such as DNA, RNA, and peptides. Our extensive MD simulations show that the wettability gradient on the patterned heterostructure can drive the motion of nanodroplet with an instantaneous acceleration, which also permits long-distance transport (>100 nm) at the microsecond time scale. The different behaviors of various types of biomolecules have been further studied systematically within the transporting nanodroplets. These findings suggest that these specially designed, patterned heterostructures have the potential for spontaneous, directional transport of important biomolecules, which might be useful in biosensing, drug delivery, and biomedical nanodevices.


Boron Compounds , DNA , Graphite , Molecular Dynamics Simulation , Graphite/chemistry , DNA/chemistry , Boron Compounds/chemistry , Nanostructures/chemistry , RNA/chemistry , Peptides/chemistry , Wettability
17.
NPJ Precis Oncol ; 8(1): 100, 2024 May 13.
Article En | MEDLINE | ID: mdl-38740834

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

18.
Environ Technol ; : 1-14, 2024 May 15.
Article En | MEDLINE | ID: mdl-38748561

Sludge is an inevitable by-product of the sewage treatment process and its high moisture content poses significant challenges for its treatment and disposal. This study focuses on the technology of sludge deep dewatering using liquefied dimethyl ether (DME) and explores the relationship between operating parameters (DME/sludge ratio, extraction time and stirring speed) and the water content of the sludge after deep dewatering. After deep dewatering, the sludge's lower heating value (LHV) was significantly increased. The dehydrated filtrate is highly biodegradable and could be treated together with sewage. Based on the response surface method of central composite design, a second-order regression model of the above three variables and sludge water content as the response was established. Finally, the operating conditions diagram was drawn by target water content (36.96 wt.%) which meets the requirement of self-sustained incineration and model equation. This study provides a valuable perspective on sludge drying and fuelisation.

19.
Cancer Gene Ther ; 2024 May 15.
Article En | MEDLINE | ID: mdl-38750301

Immunosuppressive tumor microenvironment (TME) contributes to tumor progression and causes major obstacles for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism while its role in remodeling TME remains unclear. In this study, we reported that PGAM1 suppression in breast cancer (BC) cells led to a decrease in M2 polarization, migration, and interleukin-10 (IL-10) production of macrophages. PGAM1 regulation on CCL2 expression was essential to macrophage recruitment, which further mediated by activating JAK-STAT pathway. Additionally, the CCL2/CCR2 axis was observed to participate in PGAM1-mediated immunosuppression via regulating PD-1 expression in macrophages. Combined targeting of PGAM1 and the CCL2/CCR2 axis led to a reduction in tumor growth in vivo. Furthermore, clinical validation in BC tissues indicated a positive correlation between PGAM1, CCL2 and macrophage infiltration. Our study provides novel insights into the induction of immunosuppressive TME by PGAM1 and propose a new strategy for combination therapies targeting PGAM1 and macrophages in BC.

20.
Small ; : e2400879, 2024 May 15.
Article En | MEDLINE | ID: mdl-38751069

Misfolding and aggregation of amyloid peptides into ß-structure-rich fibrils represent pivotal pathological features in various neurodegenerative diseases, including Alzheimer's disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). The development of effective amyloid detectors and inhibitors for probing and preventing amyloid aggregation is crucial for diagnosing and treating debilitating diseases, yet it poses significant challenges. Here, an aggregation-induced emission (AIE) molecule of ROF2 with multifaceted functionalities as an amyloid probe and a screening tool for amyloid inhibitors using different biophysical, cellular, and worm assays, are reported. As an amyloid probe, ROF2 outperformed ThT, demonstrating its superior sensing capability in monitoring, detecting, and distinguishing amyloid aggregates of different sequences (Amyloid-ß, human islet amyloid polypeptide, or human calcitonin) and sizes (monomers, oligomers, or fibrils). More importantly, the utilization of ROF2 as a screening molecule to identify and repurpose cardiovascular drugs as amyloid inhibitors is introduced. These drugs exhibit potent amyloid inhibition properties, effectively preventing amyloid aggregation and reducing amyloid-induced cytotoxicity both in cells and nematode. The findings present a novel strategy to discovery AIE-based amyloid probes and to be used to repurpose amyloid inhibitors, expanding diagnostic and therapeutic options for neurodegenerative diseases while addressing vascular congestion and amyloid aggregation risks.

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