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1.
PLoS One ; 19(7): e0300516, 2024.
Article in English | MEDLINE | ID: mdl-39008493

ABSTRACT

To improve the accuracy of the Hami melon discrete element model, the parameters of the Hami melon seed discrete element model were calibrated by combining practical experiments and simulation tests. The basic physical parameters of Hami melon seeds were obtained through physical experiments, including triaxial size, 100-grain mass, moisture content, density, Poisson's ratio, Young's modulus, shear modulus, angle of repose, suspension speed and various contact parameters. Taking the repose angle of seed simulation as an index, the parameters of each simulation model were significantly screened by the Plackett-Burman test. The results showed that the recovery coefficient, static friction coefficient and rolling friction coefficient of Hami melon seeds had significant effects on repose angle. Based on the steepest climbing test and quadratic regression orthogonal rotation combination test, it was determined that the significant order of the influence of various contact parameters on the angle of repose was static friction coefficient, collision recovery coefficient, and rolling friction coefficient. The optimal parameter combination was obtained through the mathematical regression model between the angle of repose and various contact parameters, namely, the collision recovery coefficient of Hami melon seeds was 0.518, the static friction coefficient of Hami melon seeds was 0.585 and the rolling friction coefficient of Hami melon seeds was 0.337. Under this condition, three static seed-dropping experiments and dynamic rolling accumulation experiments were carried out. The average simulated angle of repose was 31.93°, and the relative error with the actual value was only 1.71%. The average simulated rolling accumulation angle was 51.98°, and the relative error with the actual value was only 1.92%.


Subject(s)
Cucurbitaceae , Seeds , Cucurbitaceae/physiology , Seeds/physiology , Calibration , Computer Simulation , Elastic Modulus , Models, Theoretical , Friction
2.
Nat Commun ; 15(1): 5874, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38997284

ABSTRACT

Mucus injury associated with goblet cell (GC) depletion constitutes an early event in inflammatory bowel disease (IBD). Using single-cell sequencing to detect critical events in mucus dysfunction, we discover that the Kazal-type serine protease inhibitor SPINK4 is dynamically regulated in colitic intestine in parallel with disease activities. Under chemically induced colitic conditions, the grim status in Spink4-conditional knockout mice is successfully rescued by recombinant murine SPINK4. Notably, its therapeutic potential is synergistic with existing TNF-α inhibitor infliximab in colitis treatment. Mechanistically, SPINK4 promotes GC differentiation using a Kazal-like motif to modulate EGFR-Wnt/ß-catenin and -Hippo pathways. Microbiota-derived diacylated lipoprotein Pam2CSK4 triggers SPINK4 production. We also show that monitoring SPINK4 in circulation is a reliable noninvasive technique to distinguish IBD patients from healthy controls and assess disease activity. Thus, SPINK4 serves as a serologic biomarker of IBD and has therapeutic potential for colitis via intrinsic EGFR activation in intestinal homeostasis.


Subject(s)
Colitis , Mice, Knockout , Animals , Colitis/genetics , Colitis/chemically induced , Colitis/pathology , Colitis/drug therapy , Colitis/metabolism , Humans , Mice , Goblet Cells/metabolism , Goblet Cells/pathology , Goblet Cells/drug effects , ErbB Receptors/metabolism , ErbB Receptors/genetics , ErbB Receptors/antagonists & inhibitors , Mice, Inbred C57BL , Serine Peptidase Inhibitors, Kazal Type/genetics , Serine Peptidase Inhibitors, Kazal Type/metabolism , Wnt Signaling Pathway/drug effects , Male , Inflammatory Bowel Diseases/genetics , Inflammatory Bowel Diseases/metabolism , Female , Disease Models, Animal , Biomarkers/blood , Biomarkers/metabolism , Cell Differentiation
3.
Nanomaterials (Basel) ; 14(13)2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38998685

ABSTRACT

With the swift advancement of wearable electronics and artificial intelligence, the integration of electronic devices with the human body has advanced significantly, leading to enhanced real-time health monitoring and remote disease diagnosis. Despite progress in developing stretchable materials with skin-like mechanical properties, there remains a need for materials that also exhibit high optical transparency. Supercapacitors, as promising energy storage devices, offer advantages such as portability, long cycle life, and rapid charge/discharge rates, but achieving high capacity, stretchability, and transparency simultaneously remains challenging. This study combines the stretchable, transparent polymer PEDOT:PSS with MnO2 nanoparticles to develop high-performance, stretchable, and transparent supercapacitors. PEDOT:PSS films were deposited on a PDMS substrate using a spin-coating method, followed by electrochemical deposition of MnO2 nanoparticles. This method ensured that the nanosized MnO2 particles were uniformly distributed, maintaining the transparency and stretchability of PEDOT:PSS. The resulting PEDOT:PSS/MnO2 nanoparticle electrodes were gathered into a symmetric device using a LiCl/PVA gel electrolyte, achieving an areal capacitance of 1.14 mF cm-2 at 71.2% transparency and maintaining 89.92% capacitance after 5000 cycles of 20% strain. This work presents a scalable and economical technique to manufacturing supercapacitors that combine high capacity, transparency, and mechanical stretchability, suggesting potential applications in wearable electronics.

4.
ACS Nano ; 18(28): 18729-18742, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38951993

ABSTRACT

The development of lithium metal batteries (LMBs) is severely hindered owing to the limited temperature window of the electrolyte, which renders uncontrolled side reactions, unstable electrolyte/electrode interface (EEI) formation, and sluggish desolvation kinetics for wide temperature operation condition. Herein, we developed an all-fluorinated electrolyte composed of lithium bis(trifluoromethane sulfonyl)imide, hexafluorobenzene (HFB), and fluoroethylene carbonate, which effectively regulates solvation structure toward a wide temperature of 160 °C (-50 to 110 °C). The introduction of thermostable HFB induces the generation of EEI with a high LiF ratio of 93%, which results in an inhibited side reaction and gas generation on EEI and enhanced interfacial ion transfer at extreme temperatures. Therefore, an unparalleled capacity retention of 88.3% after 400 cycles at 90 °C and an improved cycling performance at -50 °C can be achieved. Meanwhile, the practical 1.3 Ah-level pouch cell delivers high energy density of 307.13 Wh kg-1 at 60 °C and 277.99 Wh kg-1 at -30 °C after 50 cycles under lean E/C ratio of 2.7 g/Ah and low N/P ratio of 1.2. This work not only offers a viable strategy for wide-temperature-range electrolyte design but also promotes the practicalization of LMBs.

5.
Int J Surg ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954673

ABSTRACT

BACKGROUND: Normothermic iliac perfusion has been increasingly utilized for TAAA repair; however, the long-term outcomes in large samples are lacking. This study was designed to assesses the perioperative and long-term results of thoracoabdominal aortic repair using normothermic iliac perfusion. METHODS: We retrospectively analyzed 156 patients having Crawford extent II or III thoracoabdominal aortic aneurysm replacement with normothermic iliac perfusion from 2012 to 2022. Primary endpoints were composite adverse events and long-term survival, which encompassed 30-day mortality, persistent stroke, persistent paraplegia, and acute renal failure needing continuous dialysis. The cohort was divided into two subgroups based on the use of selective visceral and cold renal perfusion techniques. RESULTS: The combined adverse event rate was 14.1%. Specific rates were: 30-day mortality (4.5%), persistent stroke (1.9%), persistent paraplegia (4.5%), and renal failure requiring persistent dialysis (3.2%). The median follow-up time was 67 months. Overall survival rates at 1, 3, 5, 7, and 10 years were 91.6%, 90.0%, 85.4%, 77.6%, and 69.7%, respectively. Subgroup analysis showed the visceral and renal perfusion group had a significantly reduced adverse event incidence compared to the nonperfusion group (6.5% vs. 19.1%, P=0.026). Multivariable logistic regression analysis confirmed selective visceral and cold renal perfusion techniques as protective factors against postoperative adverse events (OR 0.30, 95%CI 0.09-0.94; P=0.038). Multivariable Cox regression analysis identified age ≥50 years (HR 2.63, 95%CI 1.10-6.27; P=0.029) and NYHA grade ≥III (HR: 3.20, 95% CI: 1.04-9.87; P=0.043) as independent risk factors predicting overall survival. CONCLUSIONS: Normothermic iliac perfusion is a feasible option for thoracoabdominal aortic repair with cost benefits and simpler management, and selective visceral and cold renal perfusion techniques may further improve its safety and effectiveness. However, enhanced vigilance and meticulous care are essential, particularly for elderly patients and those with cardiac insufficiency.

6.
Mar Pollut Bull ; 206: 116676, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38991610

ABSTRACT

Understanding mercury (Hg) concentrations in mesopelagic and mid-trophic fishes is important for assessing Hg accumulation in oceanic ecosystems and higher-order predators. This study measured total Hg (THg) concentrations in the whole body of 16 abundant mesopelagic fish species sampled in two distinct sites within the Tasman Sea. Across all species, total Hg concentrations ranged from 0.02 to 0.48 µg g-1 dry weight (0.01 to 0.15 µg g-1 wet weight). Total Hg concentrations varied with vertical migration patterns, with shallower migrators exhibiting higher THg. Females typically had statistically higher THg concentrations than males. Positive correlations between THg concentration and standard length were observed for some but not all species. At the community level, THg concentrations correlated positively with estimated trophic position and foraging habitat, as inferred by stable isotope values. These findings contribute to our understanding of Hg cycling in oceanic ecosystems and the potential for biomagnification in oceanic top-order predators.

7.
Digit Health ; 10: 20552076241259047, 2024.
Article in English | MEDLINE | ID: mdl-38840661

ABSTRACT

Background: Falls pose a serious health risk for the elderly, particular for those who are living alone. The utilization of WiFi-based fall detection, employing Channel State Information (CSI), emerges as a promising solution due to its non-intrusive nature and privacy preservation. Despite these advantages, the challenge lies in optimizing cross-individual performance for CSI-based methods. Objective: This study aimed to develop a resilient real-time fall detection system across individuals utilizing CSI, named TCS-Fall. This method was designed to offer continuous monitoring of activities over an extended timeframe, ensuring accurate and prompt detection of falls. Methods: Extensive CSI data on 1800 falls and 2400 daily activities was collected from 20 volunteers. The grouped coefficient of variation of CSI amplitudes were utilized as input features. These features capture signal fluctuations and are input to a convolutional neural network classifier. Cross-individual performance was extensively evaluated using various train/test participant splits. Additionally, a user-friendly CSI data collection and detection tool was developed using PyQT. To achieve real-time performance, data parsing and pre-processing computations were optimized using Numba's just-in-time compilation. Results: The proposed TCS-Fall method achieved excellent performance in cross-individual fall detection. On the test set, AUC reached 0.999, no error warning ratio score reached 0. 955 and correct warning ratio score reached of 0.975 when trained with data from only two volunteers. Performance can be further improved to 1.00 when 10 volunteers were included in training data. The optimized data parsing/pre-processing achieved over 20× speedup compared to previous method. The PyQT tool parsed and detected the fall within 100 ms. Conclusions: TCS-Fall method enables excellent real-time cross-individual fall detection utilizing WiFi CSI, promising swift alerts and timely assistance to elderly. Additionally, the optimized data processing led to a significant speedup. These results highlight the potential of our approach in enhancing real-time fall detection systems.

8.
Pediatr Dermatol ; 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38923547

ABSTRACT

An 8-year-old girl presented with white papules on the eyelid margins due to lipoid proteinosis. Microwave therapy resulted in significant reduction of the lesions. The case highlights a safe and effective treatment for eyelid lesions associated with lipoid proteinosis. In addition, we report two novel heterozygous variants in the extracellular matrix protein 1 (ECM1) gene.

9.
Parasitol Res ; 123(6): 231, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829429

ABSTRACT

Cryptosporidium spp. are protozoa commonly found in domestic and wild animals. Limited information is available on Cryptosporidium in deer worldwide. In this study, 201 fecal samples were collected from Alpine musk deer on three farms in Gansu Province, China. Detection and subtyping of Cryptosporidium were performed by PCR and sequence analysis of the SSU rRNA and gp60 genes. The prevalence of Cryptosporidium infection in Alpine musk deer was 3.9% (8/201), with infection rates of 1.0% (1/100), 2.8% (1/36), and 9.2% (6/65) in three different farms. All positive samples for Cryptosporidium were from adult deer. Two Cryptosporidium species were identified, including C. parvum (n = 2) and C. xiaoi (n = 6). The C. parvum isolates were subtyped as IIdA15G1, while the C. xiaoi isolates were subtyped as XXIIIa (n = 2) and XXIIIg (n = 4). The IIdA15G1 subtype of C. parvum was found for the first time in deer. These results provide important insights into the identity and human infectious potential of Cryptosporidium in farmed Alpine musk deer.


Subject(s)
Cryptosporidiosis , Cryptosporidium , Deer , Feces , Animals , Deer/parasitology , Cryptosporidiosis/parasitology , Cryptosporidiosis/epidemiology , Cryptosporidium/genetics , Cryptosporidium/isolation & purification , Cryptosporidium/classification , China/epidemiology , Feces/parasitology , Prevalence , DNA, Protozoan/genetics , Phylogeny , Polymerase Chain Reaction , Sequence Analysis, DNA , Genotype , DNA, Ribosomal/genetics , DNA, Ribosomal/chemistry
10.
BMC Genomics ; 25(1): 612, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890564

ABSTRACT

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.


Subject(s)
Blood Pressure , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Blood Pressure/genetics , Gene Expression Profiling , Hypertension/genetics , Transcriptome , Polymorphism, Single Nucleotide , Male , Risk Assessment , Female , Sodium Chloride, Dietary/adverse effects
11.
Adv Sci (Weinh) ; : e2308393, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38867657

ABSTRACT

The mechanism involved in major depressive disorder (MDD) is well-studied but the mechanistic origin of the heterogeneous antidepressant effect remains largely unknown. Single-cell RNA-sequencing (scRNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) on peripheral blood mononuclear cells from 8 healthy individuals and 8 MDD patients before or after 12 weeks of antidepressant treatment is performed. scRNA-seq analysis reveals a lower proportion of naive T cells, particularly CD4+ naive T cells, in MDD patients compared to controls, and in nonresponders versus responders at the baseline. Flow cytometry data analysis of an independent cohort of 35 patients and 40 healthy individuals confirms the findings. Enrichment analysis of differentially expressed genes indicated obvious immune activation in responders. A specific activated CD4+ naive T population in responders characterized by enhanced mitogen-activated protein kinases (MAPK) pathway is identified. E-twenty six (ETS) is proposed as an upstream regulator of the MAPK pathway and heterogeneous differentiation in activated CD4+ naive T population is associated with the response to antidepressant treatment in MDD patients. A distinct immune feature manifested by CD4+ naive T cells during antidepressant treatment in MDD is identified. Collectively, this proposes the molecular mechanism that underlies the heterogeneous antidepressant outcomes for MDD.

12.
ACS Nano ; 18(26): 17251-17266, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38907727

ABSTRACT

Designing adaptive and smart hydrogel wound dressings to meet specific needs across different stages of wound healing is crucial. Here, we present a composite hydrogel, GSC/PBE@Lut, that offers self-regulating release of cupric ions and luteolin and modulates mechanical properties to promote chronic wound healing. The double network hydrogel, GSC, is fabricated through photo-cross-linking of gelatin methacrylate, followed by Cu2+-alginate coordination cross-linking. On one hand, GSC allows for rapid Cu2+ release to eliminate bacteria in the acidic pH environment during inflammation and reduces the hydrogel's mechanical strength to minimize tissue trauma during early dressing changes. On the other hand, GSC enables slow Cu2+ release during the proliferation stage, promoting angiogenesis and biocompatibility. Furthermore, the inclusion of pH- and reactive oxygen species (ROS)-responsive luteolin nanoparticles (PBE@Lut) in the hydrogel matrix allows for controlled release of luteolin, offering antioxidant and anti-inflammatory effects and promoting anti-inflammatory macrophage polarization. In a murine model of Staphylococcus aureus infected wounds, GSC/PBE@Lut demonstrates exceptional therapeutic benefits in antibacterial, anti-inflammatory, angiogenic, and tissue regeneration. Overall, our results suggest that smart hydrogels with controlled bioactive agent release and mechanical modulation present a promising solution for treating chronic wounds.


Subject(s)
Anti-Bacterial Agents , Copper , Hydrogels , Luteolin , Staphylococcus aureus , Wound Healing , Wound Healing/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Copper/chemistry , Copper/pharmacology , Animals , Mice , Staphylococcus aureus/drug effects , Luteolin/pharmacology , Luteolin/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Alginates/chemistry , Reactive Oxygen Species/metabolism , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Hydrogen-Ion Concentration , Gelatin/chemistry , Humans , Drug Liberation , Methacrylates/chemistry , Nanoparticles/chemistry , Microbial Sensitivity Tests
13.
Stem Cell Res Ther ; 15(1): 133, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704588

ABSTRACT

BACKGROUND: Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic organoids is an unaddressed challenge because of the complexity of hematopoietic tissues. METHODS: To manufacture hematopoietic organoids, we obtained CD34+ hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34+ HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids. RESULTS: The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation. CONCLUSIONS: These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.


Subject(s)
Granulocyte Colony-Stimulating Factor , Hematopoietic Stem Cells , Organoids , Humans , Organoids/metabolism , Organoids/drug effects , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/drug effects , Hematopoietic Stem Cells/cytology , Granulocyte Colony-Stimulating Factor/pharmacology , Human Embryonic Stem Cells/cytology , Human Embryonic Stem Cells/metabolism , Reactive Oxygen Species/metabolism , Regeneration/drug effects , Cell Differentiation/drug effects , Antigens, CD34/metabolism
14.
Bioact Mater ; 38: 455-471, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38770426

ABSTRACT

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.

15.
Nano Lett ; 24(22): 6610-6616, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38780077

ABSTRACT

In pursuit of higher energy density in lithium-ion batteries, silicon (Si) has been recognized as a promising candidate to replace commercial graphite due to its high theoretical capacity. However, the pulverization issue of Si microparticles during lithiation/delithiation results in electrical contact loss and increased side reactions, significantly limiting its practical applications. Herein, we propose to utilize liquid metal (LM) particles as the bridging agent, which assemble conductive MXene (Ti3C2Tx) sheets via coordination chemistry, forming cage-like structures encapsulating mSi particles as self-healing high-energy anodes. Due to the integration of robust Ti3C2Tx sheets and deformable LM particles as conductive buffering cages, simultaneously high-rate capability and cyclability can be realized. Post-mortem analysis revealed the cage structural integrity and the maintained electrical percolating network after cycling. This work introduces an effective approach to accommodate structural change via a resilient encapsulating cage and offers useful interface design considerations for versatile battery electrodes.

16.
STAR Protoc ; 5(2): 103080, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38776227

ABSTRACT

Co-immunoprecipitation (coIP) is an experimental technique to study protein-protein interactions (PPIs). However, single-step coIP can only be used to identify the interaction between two proteins and does not solve the interaction testing of ternary complexes. Here, we present a protocol to test for the formation of ternary protein complexes in vivo or in vitro using a two-step coIP approach. We describe steps for cell culture and transfection, elution of target proteins, and two-step coIP including western blot analyses. For complete details on the use and execution of this protocol, please refer to Li et al.1.


Subject(s)
Immunoprecipitation , Immunoprecipitation/methods , Humans , Protein Interaction Mapping/methods , Proteins/metabolism , Blotting, Western/methods , Transfection , Animals , Protein Binding , Multiprotein Complexes/metabolism , Multiprotein Complexes/chemistry , HEK293 Cells
17.
Angew Chem Int Ed Engl ; 63(29): e202403531, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38709182

ABSTRACT

Quasi-one-dimensional (quasi-1D) van der Waals crystal fibrous red phosphorus (RP) exhibits pronounced in-plane optical anisotropy, positioning it as a potential candidate for polarization-related micro-nano devices. Unfortunately, a comprehensive investigation into the complex refractive index of fibrous RP and the structure-activity relationship connecting the distinctive quasi-1D structure with optical anisotropy is currently deficient. Herein, we have collectively determined the complex refractive index of the fibrous RP flakes within the ab-plane through Kramers-Kronig (KK) analysis and theoretical calculation. Notably, the maximum birefringence of fibrous RP reaches 0.642@475 nm with an absolute extinction coefficient of only 0.08, superior to the reported traditional optical crystals and the emerging low-dimensional materials as well. The remarkable birefringence can be attributed to the synergistic influence of the large electronic dipole polarizability, anisotropic electron density distribution and the distortion of stereochemically active lone pair (SCALP). This work demonstrates the potential of fibrous RP for polarization-sensitive devices, illuminating possibilities to exploit novel giant birefringent crystals based on the structure-activity relationship.

18.
Bioorg Med Chem Lett ; 108: 129813, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38788964

ABSTRACT

Succinate dehydrogenase inhibitors are essential fungicides used in agriculture. To explore new pyrazole-carboxamides with high fungicidal activity, a series of N-substitutedphenyl-3-di/trifluoromethyl-1-methyl-1H-pyrazole-4-carboxamides bearing a branched alkyl ether moiety were designed and synthesized. The in vitro bioassay indicated that some target compounds displayed appreciable fungicidal activity. For example, compounds 5d and 5e showed high efficacy against S. sclerotiorum with EC50 values of 3.26 and 1.52 µg/mL respectively, and also exhibited excellent efficacy against R. solani with EC50 values of 0.27 and 0.06 µg/mL respectively, which were comparable or superior to penflufen. The further in vivo bioassay on cucumber leaves demonstrated that 5e provided strong protective activity of 94.3 % against S. sclerotiorum at 100 µg/mL, comparable to penflufen (99.1 %). Cytotoxicity assessment against human renal cell lines (239A cell) revealed that 5e had low cytotoxicity within the median effective concentrations. Docking study of 5e with succinate dehydrogenase illustrated that R-5e formed one hydrogen bond and two π-π stacking interactions with amino acid residues of target enzyme, while S-5e formed only one π-π stacking interaction with amino acid residue. This study provides a valuable reference for the design of new succinate dehydrogenase inhibitor.


Subject(s)
Fungicides, Industrial , Molecular Docking Simulation , Pyrazoles , Succinate Dehydrogenase , Pyrazoles/chemistry , Pyrazoles/pharmacology , Pyrazoles/chemical synthesis , Humans , Structure-Activity Relationship , Fungicides, Industrial/pharmacology , Fungicides, Industrial/chemical synthesis , Fungicides, Industrial/chemistry , Succinate Dehydrogenase/antagonists & inhibitors , Succinate Dehydrogenase/metabolism , Microbial Sensitivity Tests , Molecular Structure , Ascomycota/drug effects , Amides/chemistry , Amides/pharmacology , Amides/chemical synthesis , Dose-Response Relationship, Drug , Ethers/chemistry , Ethers/pharmacology , Ethers/chemical synthesis , Rhizoctonia
19.
Front Plant Sci ; 15: 1332788, 2024.
Article in English | MEDLINE | ID: mdl-38699539

ABSTRACT

For a long time, human activities have been prohibited in ecologically protected areas in the Ebinur Lake Wetland National Nature Reserve (ELWNNR). The implementation of total closure is one of the main methods for ecological protection. For arid zones, there is a lack of in-depth research on whether this measure contributes to ecological restoration in the reserve. The Normalized Difference Vegetation Index (NDVI) is considered to be the best indicator for ecological monitoring and has a key role to play in assessing the ecological impacts of total closure. In this study, we used Sentinel-2, Landsat-8, and Moderate Resolution Imaging Spectroradiometer (MODIS) remote sensing data to select optimal data and utilized Sen slope estimation, Mann-Kendall statistical tests, and the geographical detector model to quantitatively analyze the normalized difference vegetation index (NDVI) dynamics and its driving factors. Results were as follows: (1) The vegetation distribution of the Ebinur Lake Wetland National Nature Reserve (ELWNNR) had obvious spatial heterogeneity, showing low distribution in the middle and high distribution in the surroundings. The correlation coefficients of Landsat-8 and MODIS, Sentinel-2 and MODIS, and Sentinel-2 and Landsat-8 were 0.952, 0.842, and 0.861, respectively. The NDVI calculated from MODIS remote sensing data was higher than the value calculated by Landsat-8 and Sentinel-2 remote sensing images, and Landsat-8 remote sensing data were the most suitable data. (2) NDVI indicated more degraded areas on the whole, but the ecological recovery was obvious in the localized areas where anthropogenic closure was implemented. The ecological environment change was the result of the joint action of man and nature. Man-made intervention will change the local ecological environment, but the overall ecological environment change was still dominated by natural environmental factors. (3) Factors affecting the distribution of NDVI in descending order were as follows: precipitation > evapotranspiration > land use type > elevation > vegetation type > soil type > soil erosion > slope > temperature > slope direction. Precipitation was the main driver of vegetation change in ELWNNR. The synergistic effect of the factors showed two-factor enhancement and nonlinear enhancement, and the combined effect of the driving factors would increase the influence on NDVI.

20.
Acta Pharmacol Sin ; 2024 May 17.
Article in English | MEDLINE | ID: mdl-38760544

ABSTRACT

Cardiac fibrosis is a detrimental pathological process, which constitutes the key factor for adverse cardiac structural remodeling leading to heart failure and other critical conditions. Circular RNAs (circRNAs) have emerged as important regulators of various cardiovascular diseases. It is known that several circRNAs regulate gene expression and pathological processes by binding miRNAs. In this study we investigated whether a novel circRNA, named circNSD1, and miR-429-3p formed an axis that controls cardiac fibrosis. We established a mouse model of myocardial infarction (MI) for in vivo studies and a cellular model of cardiac fibrogenesis in primary cultured mouse cardiac fibroblasts treated with TGF-ß1. We showed that miR-429-3p was markedly downregulated in the cardiac fibrosis models. Through gain- and loss-of-function studies we confirmed miR-429-3p as a negative regulator of cardiac fibrosis. In searching for the upstream regulator of miR-429-3p, we identified circNSD1 that we subsequently demonstrated as an endogenous sponge of miR-429-3p. In MI mice, knockdown of circNSD1 alleviated cardiac fibrosis. Moreover, silence of human circNSD1 suppressed the proliferation and collagen production in human cardiac fibroblasts in vitro. We revealed that circNSD1 directly bound miR-429-3p, thereby upregulating SULF1 expression and activating the Wnt/ß-catenin pathway. Collectively, circNSD1 may be a novel target for the treatment of cardiac fibrosis and associated cardiac disease.

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