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1.
J Am Chem Soc ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982611

ABSTRACT

The structural dynamics of artificial assemblies, in aspects such as molecular recognition and structural transformation, provide us with a blueprint to achieve bioinspired applications. Here, we describe the assembly of redox-switchable chiral metal-organic cages Λ8/Δ8-[Pd6(CoIIL3)8]28+ and Λ8/Δ8-[Pd6(CoIIIL3)8]36+. These isomeric cages demonstrate an on-off chirality logic gate controlled by their chemical and stereostructural dynamics tunable through redox transitions between the labile CoII-state and static CoIII-state with a distinct Cotton effect. The transition between different states is enabled by a reversible redox process and chiral recognition originating in the tris-chelate Co-centers. All cages in two states are thoroughly characterized by NMR, ESI-MS, CV, CD, and X-ray crystallographic analysis, which clarify their redox-switching behaviors upon chemical reduction/oxidation. The stereochemical lability of the CoII-center endows the Λ8/Δ8-CoII-cages with efficient chiral-induction by enantiomeric guests, leading to enantiomeric isomerization to switch between Λ8/Δ8-CoII-cages, which can be stabilized by oxidation to their chemically inert forms of Λ8/Δ8-CoIII-cages. Kinetic studies reveal that the isomerization rate of the Δ8-CoIII-cage is at least an order of magnitude slower than that of the Δ8-CoII-cage even at an elevated temperature, while its activation energy is 16 kcal mol-1 higher than that of the CoII-cage.

2.
Inorg Chem ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007651

ABSTRACT

Carbon dioxide (CO2) coupled with epoxide to generate cyclic carbonate stands out in carbon neutrality due to its 100% atom utilization. In this work, the mechanism of CO2 cycloaddition with propylene oxide (PO) cocatalyzed by windmill-shaped polyoxovanadate, [(C2N2H8)4(CH3O)4VIV4VV4O16]·4CH3OH (V8-1), and n-Bu4NX (X = Br, I) was thoroughly investigated using density functional theory (DFT) calculations. The ring-opening, CO2-insertion, and ring-closing steps of the process were extensively studied. Our work emphasizes the synergistic effect between V8-1 and n-Bu4NX (X = Br, I). Through the analysis of an independent gradient model based on Hirshfeld partition (IGMH), it was found that the attack of n-Bu4NX (X = Br, I) on Cß of PO triggers a distinct attractive interaction between the active fragment and the surrounding framework, serving as the primary driving force for the ring opening of PO. Furthermore, the effect of different cocatalysts was explored, with n-Bu4NI being more favorable than n-Bu4NBr. Moreover, the role of V8-1 in the CO2 cycloaddition reaction was clarified as not only acting as Lewis acid active sites but also serving as "electron sponges". This work is expected to advance the development of novel catalysts for organic carbonate formation.

3.
Brain Res Bull ; 215: 111027, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971477

ABSTRACT

BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.

4.
Front Pharmacol ; 15: 1393693, 2024.
Article in English | MEDLINE | ID: mdl-38855753

ABSTRACT

Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.

5.
Plant J ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829920

ABSTRACT

Cucumber plants are highly susceptible to the hemibiotroph oomycete Phytophthora melonis. However, the mechanism of resistance to cucumber blight remains poorly understood. Here, we demonstrated that cucumber plants with impairment in the biosynthesis of brassinosteroids (BRs) or gibberellins (GAs) were more susceptible to P. melonis. By contrast, increasing levels of endogenous BRs or exogenously application of 24-epibrassinolide enhanced the resistance of cucumber plants against P. melonis. Furthermore, we found that both knockout and overexpression of the BR biosynthesis gene CYP85A1 reduced the endogenous GA3 content compared with that of wild-type plants under the condition of inoculation with P. melonis, and the enhancement of disease resistance conferred by BR was inhibited in plants with silencing of the GA biosynthetic gene GA20ox1 or KAO. Together, these findings suggest that GA homeostasis is an essential factor mediating BRs-induced disease resistance. Moreover, BZR6, a key regulator of BR signaling, was found to physically interact with GA20ox1, thereby suppressing its transcription. Silencing of BZR6 promoted endogenous GA biosynthesis and compromised GA-mediated resistance. These findings reveal multifaceted crosstalk between BR and GA in response to pathogen infection, which can provide a new approach for genetically controlling P. melonis damage in cucumber production.

6.
Lab Chip ; 24(14): 3480-3489, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38899528

ABSTRACT

Optofluidic regulation of blood microflow in vivo represents a significant method for investigating illnesses linked to abnormal changes in blood circulation. Currently, non-invasive strategies are limited to regulation within capillaries of approximately 10 µm in diameter because the adaption to blood pressure levels in the order of several hundred pascals poses a significant challenge in larger microvessels. In this study, using laser-induced microbubble formation within microvessels of the mouse auricle, we regulate blood microflow in small vessels with diameters in the tens of micrometers. By controlling the laser power, we can control the growth and stability of microbubbles in vivo. This controlled approach enables the achievement of prolonged ischemia and subsequent reperfusion of blood flow, and it can also regulate the microbubbles to function as micro-pumps for reverse blood pumping. Furthermore, by controlling the microbubble, narrow microflow channels can be formed between the microbubbles and microvessels for assessing the apparent viscosity of leukocytes, which is 76.9 ± 11.8 Pa·s in the in vivo blood environment. The proposed design of in vivo microbubble valves opens new avenues for constructing real-time blood regulation and exploring cellular mechanics within living organisms.


Subject(s)
Lasers , Microbubbles , Microvessels , Animals , Mice , Microvessels/physiology
7.
Neuroimage ; 297: 120701, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38914210

ABSTRACT

Due to a high degree of symptom overlap in the early stages, with movement disorders predominating, Parkinson's disease (PD) and multiple system atrophy (MSA) may exhibit a similar decline in motor areas, yet they differ in their spread throughout the brain, ultimately resulting in two distinct diseases. Drawing upon neuroimaging analyses and altered motor cortex excitability, potential diffusion mechanisms were delved into, and comparisons of correlations across distinct disease groups were conducted in a bid to uncover significant pathological disparities. We recruited thirty-five PD, thirty-seven MSA, and twenty-eight matched controls to conduct clinical assessments, electromyographic recording, and magnetic resonance imaging scanning during the "on medication" state. Patients with neurodegeneration displayed a widespread decrease in electrophysiology in bilateral M1. Brain function in early PD was still in the self-compensatory phase and there was no significant change. MSA patients demonstrated an increase in intra-hemispheric function coupled with a decrease in diffusivity, indicating a reduction in the spread of neural signals. The level of resting motor threshold in healthy aged showed broad correlations with both clinical manifestations and brain circuits related to left M1, which was absent in disease states. Besides, ICF exhibited distinct correlations with functional connections between right M1 and left middle temporal gyrus in all groups. The present study identified subtle differences in the functioning of PD and MSA related to bilateral M1. By combining clinical information, cortical excitability, and neuroimaging intuitively, we attempt to bring light on the potential mechanisms that may underlie the development of neurodegenerative disease.

8.
Chem Commun (Camb) ; 60(58): 7475-7478, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38938189

ABSTRACT

Here, we explain why the Energy Gap Law and the energy inversion related to the charge-transfer state have opposite effects on the trend of nonradiative energy loss of organic solar cells. The root is the existing condition of energy inversion. There is indeed a certain probability of energy inversion, but it will eventually be implicit or explicit as determined by the hybridization, which depends on the electron-withdrawing unit of the donor, giving rise to different stacking sites. The triplet-state hybridization leads to an explicit characteristic, while singlet-state hybridization leads to an implicit characteristic.

9.
Int J Biol Macromol ; 273(Pt 2): 133063, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38880443

ABSTRACT

The oral delivery of doxorubicin (DOX), an anti-cancer drug, encounters multiple hurdles such as limited gastrointestinal permeability, P-glycoprotein-mediated efflux, brief intestinal residence, and rapid degradation. This study introduced a novel approach utilizing hyaluronic acid (HA)-grafted fatty acid monoglycerides (HGD) to encapsulate DOX, forming HGD-DOX nanoparticles, aimed at enhancing its oral bioavailability. Drug encapsulated by HGD provided several advantages, including extended drug retention in the gastrointestinal tract, controlled release kinetics, and promotion of lymphatic absorption in the intestine. Additionally, HGD-DOX nanoparticles could specifically target CD44 receptors, potentially increasing therapeutic efficacy. The uptake mechanism of HGD-DOX nanoparticles primarily involved clathrin-mediated, caveolin-mediated and macropinocytosis endocytosis. Pharmacokinetic analysis further revealed that HGD significantly prolonged the in vivo residence time of DOX. In vivo imaging and pharmacodynamic studies indicated that HGD possessed tumor-targeting capabilities and exhibited a significant inhibitory effect on tumor growth, while maintaining an acceptable safety profile. Collectively, these findings position HGD-DOX nanoparticles as a promising strategy to boost the oral bioavailability of DOX, offering a potential avenue for improved cancer treatment.


Subject(s)
Doxorubicin , Hyaluronan Receptors , Hyaluronic Acid , Nanoparticles , Doxorubicin/administration & dosage , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Hyaluronic Acid/chemistry , Animals , Nanoparticles/chemistry , Hyaluronan Receptors/metabolism , Humans , Administration, Oral , Mice , Drug Carriers/chemistry , Cell Line, Tumor , Drug Delivery Systems , Xenograft Model Antitumor Assays
10.
Exp Ther Med ; 28(2): 305, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38873045

ABSTRACT

Fas-activated serine/threonine kinase domain 1 (FASTKD1), a known modulator of mitochondrial-mediated cell death and survival processes, has garnered attention for its potential role in various biological contexts. However, its involvement in gastric cancer remains unclear. Thus, the present study aimed to investigate the relationship between FASTKD1 expression and key factors, including clinicopathological characteristics, immune infiltration and m6A modification in stomach adenocarcinoma (STAD). The expression of FASTKD1 was analyzed in STAD and normal adjacent tissues to assess its association with clinicopathological characteristics and survival prognosis. Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used in this study. Additionally, the findings were validated through immunohistochemical staining. Co-expression analysis of FASTKD1 was performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment analysis, Gene Set Enrichment Analysis (GSEA) and LinkedOmics database analysis. An in-depth analysis was conducted using databases, such as Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), GEO and TCGA to explore the potential correlation between FASTKD1 expression and immune infiltration and m6A modification in STAD. The results revealed that FASTKD1 was significantly upregulated across different tumor types, including STAD. Notably, FASTKD1 was able to distinguish between tumor and normal tissue samples with accuracy. Furthermore, the expression levels of FASTKD1 were significantly associated with clinical stage and survival. Through GO/KEGG enrichment analysis and GSEA, it was revealed that the genes co-expressed with FASTKD1 were active in a variety of biological processes. Within the TIMER, GEPIA and TCGA databases, a notable inverse correlation was observed between FASTKD1 expression and the abundance of immune cell subsets. Notably, significant correlations were established between FASTKD1 and m6A modification genes, YTHDF1 and LRPPRC, in both TCGA and GEO datasets. In conclusion, FASTKD1 may serve a significant role in m6A modification and immune infiltration processes, making it a potentially valuable diagnostic and prognostic biomarker in STAD.

11.
Int J Surg ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38896867

ABSTRACT

BACKGROUND: Micropapillary (MP) and solid(S) pattern adenocarcinoma are highly malignant subtypes of lung adenocarcinoma. In today's era of increasingly conservative surgery for small lung cancer, effective preoperative identification of these subtypes is greatly important for surgical planning and long term survival of patients. METHODS: For this retrospective study, the presence of MP and/or S was evaluated in 2167 consecutive patients who underwent surgical resection for clinical stage IA1-2 lung adenocarcinoma. MP and/or S pattern-positive patients and negative-pattern patients were matched at a ratio of 1:3. The Lasso regression model was used for data dimension reduction and imaging signature building. Multivariate logistic regression was used to establish the predictive model, presented as an imaging nomogram. The performance of the nomogram was assessed based on calibration, identification, and clinical usefulness, and internal and external validation of the model was conducted. RESULTS: The proportion of solid components (PSC), Sphericity, entropy, Shape, bronchial honeycomb, nodule shape, sex, and smoking were independent factors in the prediction model of MP and/or S lung adenocarcinoma. The model showed good discrimination with an area under the ROC curve of 0.85. DCA demonstrated that the model could achieve good benefits for patients. RCS analysis suggested a significant increase in the proportion of MP and/or S from 11% to 48% when the PSC value was 68%. CONCLUSION: Small MP and/or S adenocarcinoma can be effectively identified preoperatively by their typical 3D and 2D imaging features.

12.
Epilepsy Behav Rep ; 26: 100671, 2024.
Article in English | MEDLINE | ID: mdl-38708366

ABSTRACT

KCNH5 gene encodes for the voltage-gated potassium channel protein Kv10.2. Here, we investigated the clinical features of developmental and epileptic encephalopathy (DEE) in five Chinese pediatric patients with a missense mutation (p.R327H) in KCNH5 gene. These patients had undergone video EEG to evaluate background features and epileptiform activity, as well as 3.0 T MRI scans for structural analysis and intelligence assessments using the Gesell Developmental Observation or Wechsler Intelligence Scale for Children. Seizure onset occurs between 4 and 10 months of age, with focal and generalized tonic-clonic seizures being common. Initial EEG findings showed multiple multifocal sharp waves, sharp slow waves or spike slow waves, and spike waves. Brain MRI revealed widened extracerebral space in only one patient. Mechanistically, the KCNH5 mutation disrupts the two hydrogen bonds between Arg327 and Asp304 residues, potentially altering the protein's structural stability and function. Almost 80 % of patients receiving add-on valproic acid (VPA) therapy experienced a reduction in epileptic seizure frequency. Altogether, this study presents the first Chinese cohort of pediatric DEE patients with the KCNH5 p.R327H mutation, highlighting focal seizures as the predominant seizure type and incomplete mutation penetrance. Add-on VPA therapy was likely effective in the early stages of DEE pathogenesis.

14.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38619373

ABSTRACT

Two-dimensional materials possess a large number of interesting and important properties. Various methods have been developed to assemble two-dimensional aggregates. Assembly of colloidal particles can be achieved with laser-heating-induced thermal convective flow. In this paper, an opto-hydrodynamic binding method is proposed to assemble colloidal particles dispersed in a solution into multilayer structures. First, we use polystyrene (PS) microspheres to study the feasibility and characteristics of the assembly method. PS microspheres and monodispersed magnetic silica microspheres (SLEs) are dispersed in a solution to form a binary mixture system. Under the action of an external uniform magnetic field, SLEs in the solution form chains. An SLE chain is heated by a laser beam. Due to the photothermal effect, the SLE chain is heated to produce a thermal gradient, resulting in thermal convection. The thermal convection drives the PS beads to move toward the heated SLE chain and finally stably assemble into multilayer aggregates on both sides of the SLE chain. The laser power affects the speed and result of the assembly. When the laser power is constant, the degree of constraint of the PS microbeads in different layers is also different. At the same time, this method can also assemble the biological cells, and the spacing of different layers of cells can be changed by changing the electrolyte concentration of the solution. Our work provides an approach to assembling colloidal particles and cells, which has a potential application in the analysis of the collective dynamics of microparticles and microbes.

15.
Article in English | MEDLINE | ID: mdl-38646816

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) impairs cognitive functions and peripheral systems, including skeletal muscles. The PS19 mouse, expressing the human tau P301S mutation, shows cognitive and muscular pathologies, reflecting the central and peripheral atrophy seen in AD. METHODS: We analysed skeletal muscle morphology and neuromuscular junction (NMJ) through immunohistochemistry and advanced image quantification. A factorial Analysis of Variance assessed muscle weight, NCAM expression, NMJ, myofibre type distribution, cross-sectional areas, expression of single or multiple myosin heavy-chain isoforms, and myofibre grouping in PS19 and wild type (WT) mice over their lifespan (1-12 months). RESULTS: Significant weight differences in extensor digitorum longus (EDL) and soleus muscles between WT and PS19 mice were noted by 7-8 months. For EDL muscle in females, WT weighed 0.0113 ± 0.0005 compared with PS19's 0.0071 ± 0.0008 (P < 0.05), and in males, WT was 0.0137 ± 0.0001 versus PS19's 0.0069 ± 0.0006 (P < 0.005). Similarly, soleus muscle showed significant differences; females (WT: 0.0084 ± 0.0004; PS19: 0.0057 ± 0.0005, P < 0.005) and males (WT: 0.0088 ± 0.0003; PS19: 0.0047 ± 0.0004, P < 0.0001). Analysis of the NMJ in PS19 mice revealed a marked reduction in myofibre innervation at 5 months, with further decline by 10 months. NMJ pre-terminals in PS19 mice became shorter and simpler by 5 months, showing a steep decline by 10 months. Genotype and age strongly influenced muscle NCAM immunoreactivity, denoting denervation as early as 5-6 months in EDL muscle Type II fibres, with earlier effects in soleus muscle Type I and II fibres at 3-4 months. Muscle denervation and subsequent myofibre atrophy were linked to a reduction in Type IIB fibres in the EDL muscle and Type IIA fibres in the soleus muscle, accompanied by an increase in hybrid fibres. The EDL muscle showed Type IIB fibre atrophy with WT females at 1505 ± 110 µm2 versus PS19's 1208 ± 94 µm2, and WT males at 1731 ± 185 µm2 versus PS19's 1227 ± 116 µm2. Similarly, the soleus muscle demonstrated Type IIA fibre atrophy from 5 to 6 months, with WT females at 1194 ± 52 µm2 versus PS19's 858 ± 62 µm2, and WT males at 1257 ± 43 µm2 versus PS19's 1030 ± 55 µm2. Atrophy also affected Type IIX, I + IIA, and IIA + IIX fibres in both muscles. The timeline for both myofibre and overall muscle atrophy in PS19 mice was consistent, indicating a simultaneous decline. CONCLUSIONS: Progressive and accelerated neurogenic sarcopenia may precede and potentially predict cognitive deficits observed in AD.

16.
Acta Physiol (Oxf) ; 240(4): e14123, 2024 04.
Article in English | MEDLINE | ID: mdl-38459766

ABSTRACT

AIMS: This study aimed to characterize the properties of locus coeruleus (LC) noradrenergic neurons in male and female mice. We also sought to investigate sex-specific differences in membrane properties, action potential generation, and protein expression profiles to understand the mechanisms underlying neuronal excitability variations. METHODS: Utilizing a genetic mouse model by crossing Dbhcre knock-in mice with tdTomato Ai14 transgenic mice, LC neurons were identified using fluorescence microscopy. Neuronal functional properties were assessed using patch-clamp recordings. Proteomic analyses of individual LC neuron soma was conducted using mass spectrometry to discern protein expression profiles. Data are available via ProteomeXchange with identifier PXD045844. RESULTS: Female LC noradrenergic neurons displayed greater membrane capacitance than those in male mice. Male LC neurons demonstrated greater spontaneous and evoked action potential generation compared to females. Male LC neurons exhibited a lower rheobase and achieved higher peak frequencies with similar current injections. Proteomic analysis revealed differences in protein expression profiles between sexes, with male mice displaying a notably larger unique protein set compared to females. Notably, pathways pertinent to protein synthesis, degradation, and recycling, such as EIF2 and glucocorticoid receptor signaling, showed reduced expression in females. CONCLUSIONS: Male LC noradrenergic neurons exhibit higher intrinsic excitability compared to those from females. The discernible sex-based differences in excitability could be ascribed to varying protein expression profiles, especially within pathways that regulate protein synthesis and degradation. This study lays the groundwork for future studies focusing on the interplay between proteomics and neuronal function examined in individual cells.


Subject(s)
Adrenergic Neurons , Locus Coeruleus , Red Fluorescent Protein , Mice , Female , Male , Animals , Locus Coeruleus/metabolism , Sex Characteristics , Proteomics , Mice, Transgenic , Mass Spectrometry
17.
J Hazard Mater ; 470: 134134, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38554514

ABSTRACT

Microbial remediation of cadmium-contaminated soil offers advantages like environmental friendliness, cost-effectiveness, and simple operation. However, the efficacy of this remediation process relies on obtaining dominant strains and a comprehensive understanding of their Cd adsorption mechanisms. This study identified two Cd-resistant bacteria, Burkholderia sp. 1-22 and Bacillus sp. 6-6, with significant growth-promoting effects from rice rhizosphere soil. The strains showed remarkable Cd resistance up to ∼200 mg/L and alleviated Cd toxicity by regulating pH and facilitating bacterial adsorption of Cd. FTIR analysis showed crucial surface functional groups, like carboxyl and amino groups, on bacteria played significant roles in Cd adsorption. The strains could induce CdCO3 formation via a microbially induced calcium precipitation (MICP) mechanism, confirmed by SEM-EDS, X-ray analysis, and elemental mapping. Pot experiments showed these strains significantly increased organic matter and enzyme activity (e.g., urease, sucrase, peroxidase) in the rhizosphere soil versus the control group. These changes are crucial for restricting Cd mobility. Furthermore, strains 6-6 and 1-22 significantly enhance plant root detoxification of Cd, alleviating toxicity. Notably, increased pH likely plays a vital role in enhancing Cd precipitation and adsorption by strains, converting free Cd into non-bioavailable forms.


Subject(s)
Bacillus , Burkholderia , Cadmium , Oryza , Rhizosphere , Soil Microbiology , Soil Pollutants , Oryza/microbiology , Oryza/growth & development , Cadmium/toxicity , Cadmium/metabolism , Soil Pollutants/metabolism , Soil Pollutants/toxicity , Burkholderia/metabolism , Adsorption , Bacillus/metabolism , Biodegradation, Environmental , Hydrogen-Ion Concentration , Plant Roots/microbiology , Plant Roots/growth & development , Plant Roots/metabolism
18.
J Clin Invest ; 134(9)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38470479

ABSTRACT

CD4+ T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-Seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4+ T cells resembling lymph node central memory (TCM) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of TCM. Brain CCR7+ CD4+ T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside CNS border tissues. Sequestering TCM cells in lymph nodes using FTY720 led to reduced CCR7+ CD4+ T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL757 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4+ T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4+ T cells in CNS immune surveillance, and their decline during chronic SIV highlights their responsiveness to neuroinflammation.


Subject(s)
Brain , CD4-Positive T-Lymphocytes , Macaca mulatta , Receptors, CCR7 , Simian Acquired Immunodeficiency Syndrome , Simian Immunodeficiency Virus , Animals , Simian Acquired Immunodeficiency Syndrome/immunology , Simian Acquired Immunodeficiency Syndrome/drug therapy , Simian Immunodeficiency Virus/immunology , CD4-Positive T-Lymphocytes/immunology , Receptors, CCR7/genetics , Receptors, CCR7/metabolism , Receptors, CCR7/immunology , Brain/immunology , Brain/metabolism , Brain/virology , Brain/pathology , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/pathology , Immunologic Surveillance
19.
Langmuir ; 40(14): 7463-7470, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38551336

ABSTRACT

The light-fueled microparticle oscillator, exemplifying sustained driving in a static light source, potentially holds applications in fundamental physics, cellular manipulation, fluid dynamics, and various other soft-matter systems. The challenges of photodamage due to laser focusing on particles and the control of the oscillation direction have always been two major issues for microparticle oscillators. Here, we present an optical-thermal method for achieving a 3D microparticle oscillator with a fixed direction by employing laser heating of the gold film surface. First, the microparticle oscillation without direction limitation is studied. The photothermal conversion originates from the laser heating of a gold film. The oscillation mechanism is the coordination of the forces exerted on the particles, including the thermal convective force, thermophoresis force, and gravity. Subsequently, the additional Marangoni convection force, generated by the temperature gradient on the surface of a microbubble, is utilized to control the oscillation direction of the microparticle. Finally, a dual-channel oscillation mode is achieved by utilizing two microbubbles. During the oscillation process, the microparticle is influenced by flow field forces and temperature gradient force, completely avoiding optical damage to the oscillating microparticle.

20.
Dalton Trans ; 53(14): 6275-6281, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38506644

ABSTRACT

The detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) is not only of great significance in the areas of biomedicine and neurochemistry but also helpful in disease diagnosis and pathology research. Due to their diverse structures, designability, and large specific surface areas, metal-organic frameworks (MOFs) have recently caught considerable attention in the electrochemical field. Herein, a family of heterometallic MOFs with amino modification, MIL-125(Ti-Al)-xNH2 (x = 0%, 25%, 50%, 75%, and 100%), were synthesized and employed as electrochemical sensors for the detection of AA, DA, and UA. Among them, MIL-125(Ti-Al)-75%NH2 exhibited the most promising electrochemical behavior with 40% doping of carbon black in 0.1 M PBS (pH = 7.10), which displayed individual detection performance with wide linear detection ranges (1.0-6.5 mM for AA, 5-100 µM for DA and 5-120 µM for UA) and low limits of detection (0.215 mM for AA, 0.086 µM for DA, and 0.876 µM for UA, S/N = 3). Furthermore, the as-prepared MIL-125(Ti-Al)-75%NH2/GCE provided a promising platform for future application in real sample analysis, owing to its excellent anti-interference performance and good stability.


Subject(s)
Dopamine , Metal-Organic Frameworks , Dopamine/analysis , Uric Acid/analysis , Ascorbic Acid/chemistry , Electrodes , Titanium , Electrochemical Techniques
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