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1.
BMC Biol ; 22(1): 132, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38835016

ABSTRACT

BACKGROUND: ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is thought to play a significant role both in tumor suppression and tumor initiation, which is highly dependent upon context. Previous studies have suggested that ARID1A deficiency may contribute to cancer development. The specific mechanisms of whether ARID1A loss affects tumorigenesis by RNA editing remain unclear. RESULTS: Our findings indicate that the deficiency of ARID1A leads to an increase in RNA editing levels and alterations in RNA editing categories mediated by adenosine deaminases acting on RNA 1 (ADAR1). ADAR1 edits the CDK13 gene at two previously unidentified sites, namely Q113R and K117R. Given the crucial role of CDK13 as a cyclin-dependent kinase, we further observed that ADAR1 deficiency results in changes in the cell cycle. Importantly, the sensitivity of ARID1A-deficient tumor cells to SR-4835, a CDK12/CDK13 inhibitor, suggests a promising therapeutic approach for individuals with ARID1A-mutant tumors. Knockdown of ADAR1 restored the sensitivity of ARID1A deficient cells to SR-4835 treatment. CONCLUSIONS: ARID1A deficiency promotes RNA editing of CDK13 by regulating ADAR1.


Subject(s)
Adenosine Deaminase , Cyclin-Dependent Kinases , DNA-Binding Proteins , RNA Editing , RNA-Binding Proteins , Transcription Factors , Adenosine Deaminase/metabolism , Adenosine Deaminase/genetics , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Humans , Transcription Factors/metabolism , Transcription Factors/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Cyclin-Dependent Kinases/metabolism , Cyclin-Dependent Kinases/genetics , Cell Line, Tumor , CDC2 Protein Kinase
2.
Comput Biol Med ; 178: 108456, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38909449

ABSTRACT

Large-scale electron microscopy (EM) has enabled the reconstruction of brain connectomes at the synaptic level by serially scanning over massive areas of sample sections. The acquired big EM data sets raise the great challenge of image mosaicking at high accuracy. Currently, it simply follows the conventional algorithms designed for natural images, which are usually composed of only a few tiles, using a single type of keypoint feature that would sacrifice speed for stronger performance. Even so, in the process of stitching hundreds of thousands of tiles for large EM data, errors are still inevitable and diverse. Moreover, there has not yet been an appropriate metric to quantitatively evaluate the stitching of biomedical EM images. Here we propose a two-stage error detection method to improve the EM image mosaicking. It firstly uses point-based error detection in combination with a hybrid feature framework to expedite the stitching computation while maintaining high accuracy. Following is the second detection of unresolved errors with a newly designed metric of EM stitched image quality assessment (EMSIQA). The novel detection-based mosaicking pipeline is tested on large EM data sets and proven to be more effective and as accurate when compared with existing methods.

3.
Cell Res ; 34(7): 504-521, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38811766

ABSTRACT

Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.


Subject(s)
Adenine Nucleotide Translocator 2 , Mitochondria , Mitochondrial Membranes , RNA, Double-Stranded , Animals , Adenine Nucleotide Translocator 2/metabolism , Adenine Nucleotide Translocator 2/genetics , Humans , RNA, Double-Stranded/metabolism , Mitochondria/metabolism , Mitochondrial Membranes/metabolism , Mice , Immunity, Innate , RNA Transport , HEK293 Cells , Mice, Inbred C57BL
4.
Biochim Biophys Acta Mol Cell Res ; 1871(5): 119740, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38697303

ABSTRACT

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. The termination of GABA transmission is through the action of GABA transporters (GATs). mGAT4 (encoded by Slc6a11) is another GAT besides GAT1 (encoded by Slc6a1) that functions in GABA reuptake in CNS. Research on the function of mGAT4 is still in its infancy. We developed an mGat4 knockout mouse model (mGat4-/- mice) and performed a series of behavioral analyses for the first time to study the effect of mGat4 on biological processes in CNS. Our results indicated that homozygous mGat4-/- mice had less depression, anxiety-like behavior and more social activities than their wild-type littermate controls. However, they had weight loss and showed motor incoordination and imbalance. Meanwhile, mGat4-/- mice showed increased pain threshold and hypoalgesia behavior in nociceptive stimulus and learning and memory impairments. The expression of multiple components of the GABAergic system including GAD67, GABAA and KCC2 was altered. There is little or no compensatory change in mGat1. In a word, mGat4 may play a key role in normal motor coordination, sensation, emotion, learning and memory and could be the potential target of neurological disorders.


Subject(s)
GABA Plasma Membrane Transport Proteins , Mice, Knockout , Animals , Male , Mice , Anxiety/genetics , Anxiety/metabolism , Behavior, Animal , Depression/genetics , Depression/metabolism , GABA Plasma Membrane Transport Proteins/genetics , GABA Plasma Membrane Transport Proteins/metabolism , gamma-Aminobutyric Acid/metabolism , Glutamate Decarboxylase/metabolism , Glutamate Decarboxylase/genetics , K Cl- Cotransporters , Mice, Inbred C57BL , Symporters/genetics , Symporters/metabolism
5.
Article in English | MEDLINE | ID: mdl-38752269

ABSTRACT

The Gt(ROSA)26Sor ( ROSA26) and H11 loci are commonly used as safe harbors for the construction of targeted transgenic mice. However, it remains unclear whether these two loci have distinct effects on transgene expression. In this study, we insert three differently colored fluorescent protein expression cassettes (EGFP, tdTomato and mTagBFP2) driven by the CAG promoter into the ROSA26 and H11 loci. We generate five single-transgenic mouse models and a triple-transgenic mouse model expressing three distinct fluorescent proteins simultaneously. Our results reveal that the efficiency of transgene expression is greater at the ROSA26 locus with a reverse orientation relative to the transcription of the ROSA26 gene. In most tissues examined, the efficiency of transgene expression at the ROSA26 locus exceeds that at the H11 locus. Moreover, the expression profiles of identical transgenes display discrepancies across various tissues, and notably, substantial heterogeneity in transgene expression is discernible within cells of the same tissue. Our findings offer a valuable reference for the selection of safe harbors and strategies for the construction of transgenic mouse models.

6.
Protein Cell ; 2024 May 09.
Article in English | MEDLINE | ID: mdl-38721690

ABSTRACT

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

7.
Eur J Ophthalmol ; : 11206721241249503, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689460

ABSTRACT

PURPOSE: To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). METHODS: Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. RESULTS: At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). CONCLUSIONS: For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

9.
Environ Int ; 185: 108550, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38452466

ABSTRACT

Nanoscale zero-valent iron (Fe) is a promising nanomaterial for remediating heavy metal-contaminated soils. Melatonin (MT) is essential to alleviate environmental stress in plants. However, the conjunction effects of Fe and MT (FeMT) on rice Cd, As accumulation and the mechanism of soil chemical and microbial factors interaction are unclear. Here, a pot experiment was conducted to evaluated the effects of the FeMT for rice Cd, As accumulation and underlying mechanisms. The findings showed that FeMT significantly reduced grains Cd by 92%-87% and As by over 90%, whereas improving grains Fe by over 213%. Soil available-Cd and iron plaques-Cd (extracted by dithionite-citrate-bicarbonate solution, DCB-Cd) significantly regulated roots Cd, thus affected Cd transport to grains. Soil pH significantly affected soil As and DCB-As, which further influenced roots As uptake and the transport to shoots and grains. The interactions between the soil bacterial community and soil Fe, available Fe, and DCB-Fe together affected root Fe absorption and transportation in rice. FeMT significantly influenced rhizosphere soil bacterial α- and ß-diversity. Firmicutes as the dominant phylum exhibited a significant positive response to FeMT measure, and acted a key role in reducing soil Cd and As availability mainly by improving iron-manganese plaques. The increase of soil pH caused by FeMT was beneficial only for Actinobacteriota growth, which reduced Cd, As availability probably through complexation and adsorption. FeMT also showed greater potential in reducing human health and ecological risks by rice consumption and straw returning. These results showed the important role of both soil chemical and microbial factors in FeMT-mediated rice Cd, As reduction efficiency. This study opens a novel strategy for safe rice production and improvement of rice iron nutrition level in heavy-metals polluted soil, but also provides new insights into the intricate regulatory relationships among soil biochemistry, toxic elements, microorganism, and plants.


Subject(s)
Melatonin , Metals, Heavy , Oryza , Soil Pollutants , Humans , Iron/chemistry , Soil/chemistry , Cadmium/analysis , Melatonin/pharmacology , Oryza/chemistry , Metals, Heavy/analysis , Bacteria , Soil Pollutants/analysis
10.
Environ Sci Pollut Res Int ; 31(18): 27037-27051, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38502266

ABSTRACT

Graphene-based material is widely used to remove arsenic from water due to its layered structure with high surface area. Here, we have successfully synthesized Fe-La bimetallic modified graphite sheet materials to more efficiently remove As(III) from aqueous solution. The results showed that Fe-La-graphite sheets (FL-graphite sheets) have a larger specific surface area (194.28 m2·g-1) than graphite sheets (2.80 m2·g-1). The adsorption capacity of FL-graphite sheets for As(III) was 51.69 mg·g-1, which was higher than that of graphite sheets (21.91 mg·g-1), La-graphite sheets (26.06 mg·g-1), and Fe-graphite sheets (40.26 mg·g-1). The FL-graphite sheets conformed to the Freundlich and Dubinin-Radushkevich isotherm, and the maximum adsorption capacity was 53.62 mg·g-1. The removal process obeys intra-particle diffusion and pore diffusion for As(III). The results of batch adsorption experiments and characterization analyses demonstrated that oxidation, ligand exchange, and inner sphere complexation mechanisms involved in the adsorption of FL-graphite sheets to As(III) in comparison with graphite sheets. In addition, electrostatic attraction mechanism was found vital in the adsorption. Ecotoxicity assessment revealed that FL-graphite sheets have little influence on rice germination and growth, but reduced the toxicity of As(III) to rice. Therefore, the FL-graphite sheets have good practical application value in purifying As(III) polluted water with litter ecotoxicity.


Subject(s)
Arsenic , Graphite , Iron , Thermodynamics , Water Pollutants, Chemical , Graphite/chemistry , Graphite/toxicity , Water Pollutants, Chemical/toxicity , Water Pollutants, Chemical/chemistry , Kinetics , Arsenic/chemistry , Iron/chemistry , Adsorption , Water Purification/methods
11.
Micromachines (Basel) ; 15(3)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38542640

ABSTRACT

Deterministic polishing based on jet electrochemical machining (Jet-ECM) is a stress-free machining method for low-rigidity and ultra-precision workpieces. The nozzle is equivalent to a special tool in deterministic polishing, and the workpiece material is removed using the mechanism of electrochemical dissolution at the position where the nozzle passes. By precisely regulating the nozzle's movement speed and dwell time, the quantity of material removed from the workpiece at a designated position can be finely adjusted. With this mechanism, the improvement of the workpiece shape accuracy can be achieved by planning the nozzle trajectory and nozzle movement speed. However, due to the positioning errors of the polishing device, the actual position of the nozzle may deviate from the theoretical position, resulting in errors in material removal amount, which affects the accuracy and stability of the polishing process. This study established a mathematical model to analyze the influence of nozzle positioning errors in deterministic polishing based on Jet-ECM. This model has been used to design a specific deterministic polishing device based on Jet-ECM. With the proposed deterministic polishing device, the surface shape of the workpiece is converged. The surface peak-to-valley (PV) value of the φ 50 mm workpiece (valid dimensions = 90% of the central region) indicated that the shape error of the surface was reduced from 2.67 µm to 1.24 µm in 34 min. The power spectral density (PSD) method was used to evaluate the height distribution and height characteristics of the workpiece surface. The results show that the low frequency spatial error is reduced significantly after processing. This study improves the accuracy of the stress-free deterministic polishing methods and further expands the use of deterministic polishing in industry.

12.
Comput Biol Med ; 170: 108067, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38301513

ABSTRACT

BACKGROUND: Ocular Adnexal Lymphoma (OAL) is a non-Hodgkin's lymphoma that most often appears in the tissues near the eye, and radiotherapy is the currently preferred treatment. There has been a controversy regarding the prognostic factors for systemic failure of OAL radiotherapy, the thorough evaluation prior to receiving radiotherapy is highly recommended to better the patient's prognosis and minimize the likelihood of any adverse effects. PURPOSE: To investigate the risk factors that contribute to incomplete remission in OAL radiotherapy and to establish a hybrid model for predicting the radiotherapy outcomes in OAL patients. METHODS: A retrospective chart review was performed for 87 consecutive patients with OAL who received radiotherapy between Feb 2011 and August 2022 in our center. Seven image features, derived from MRI sequences, were integrated with 122 clinical features to form comprehensive patient feature sets. Chemometric algorithms were then employed to distill highly informative features from these sets. Based on these refined features, SVM and XGBoost classifiers were performed to classify the effect of radiotherapy. RESULTS: The clinical records of from 87 OAL patients (median age: 60 months, IQR: 52-68 months; 62.1% male) treated with radiotherapy were reviewed. Analysis of Lasso (AUC = 0.75, 95% CI: 0.72-0.77) and Random Forest (AUC = 0.67, 95% CI: 0.62-0.70) algorithms revealed four potential features, resulting in an intersection AUC of 0.80 (95% CI: 0.75-0.82). Logistic Regression (AUC = 0.75, 95% CI: 0.72-0.77) identified two features. Furthermore, the integration of chemometric methods such as CARS (AUC = 0.66, 95% CI: 0.62-0.72), UVE (AUC = 0.71, 95% CI: 0.66-0.75), and GA (AUC = 0.65, 95% CI: 0.60-0.69) highlighted six features in total, with an intersection AUC of 0.82 (95% CI: 0.78-0.83). These features included enophthalmos, diplopia, tenderness, elevated ALT count, HBsAg positivity, and CD43 positivity in immunohistochemical tests. CONCLUSION: The findings suggest the effectiveness of chemometric algorithms in pinpointing OAL risk factors, and the prediction model we proposed shows promise in helping clinicians identify OAL patients likely to achieve complete remission via radiotherapy. Notably, patients with a history of exophthalmos, diplopia, tenderness, elevated ALT levels, HBsAg positivity, and CD43 positivity are less likely to attain complete remission after radiotherapy. These insights offer more targeted management strategies for OAL patients. The developed model is accessible online at: https://lzz.testop.top/.


Subject(s)
Eye Neoplasms , Lymphoma, Non-Hodgkin , Humans , Male , Child, Preschool , Female , Retrospective Studies , Chemometrics , Diplopia , Hepatitis B Surface Antigens , Eye Neoplasms/diagnostic imaging , Eye Neoplasms/radiotherapy , Lymphoma, Non-Hodgkin/diagnostic imaging , Lymphoma, Non-Hodgkin/radiotherapy , Lymphoma, Non-Hodgkin/pathology , Algorithms
13.
Biomater Sci ; 12(2): 375-386, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-37997042

ABSTRACT

There is a high demand from aging people for facial fillers with desirable biocompatibility and lasting filling effects to overcome facial depression. Novel injectable regenerated silk fibroin (RSF) microparticles were facilely printed from a glycidyl methacrylate-modified silk fibroin hydrogel to address this issue. The ß-sheet content and mechanical properties of the RSF hydrogel can be simply modulated by the number of freeze-thawing cycles, and the swelling rate of the RSF hydrogel in saline was negligible. The printed RSF microparticles were uniform, and their diameter was about 300-500 µm, which could be adjusted by the pore sizes of the printed screens. After the injection with a 26-gauge needle, the size distribution of RSF microparticles had no noticeable variation, suggesting that the microparticles could bear the shear strain without breaking during the injection. The in vitro experiments demonstrated that RSF not only had desirable biocompatibility but also facilitated fibroblast migration. The subcutaneous injection experiments demonstrated that the RSF microparticles formed a lasting spot in the injected site. The tissue sections revealed that the RSF microparticles were still distinct on week 8, and blood vessels formed around the microparticles. These promising data demonstrate that the printed RSF microparticles have great potential for facial rejuvenation.


Subject(s)
Fibroins , Humans , Hydrogels , Protein Conformation, beta-Strand , Injections, Subcutaneous , Freezing , Silk
14.
Aquat Toxicol ; 267: 106808, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38159456

ABSTRACT

Copper is an essential biometal for cell development and function, however, unbalanced copper homeostasis in T cell development and the underlying mechanisms are largely unexplored. Here, we use a zebrafish model to investigate the effect of copper overload in T cell development. We show that copper stressed zebrafish larvae exhibit a significant reduction in T cells with increased cell apoptosis and impaired cell proliferation. T cell progenitors, hematopoietic stem and progenitor cells, also exhibit increased cell apoptosis. Copper overload induces production of ROS and the down-regulations of its resistance genes foxos, and ectopic expression of foxo3a, ROS scavenger GSH, could both effectively rescue the reduction of T cells in copper overload larvae. Moreover, foxm1-cytoskeleton axis, parallel to ROS-foxo axis, also mediates the copper overload induced T cell developmental defects. Meanwhile, ROS destroys expression of cytoskeleton rather than of foxm1 in the cells to induce cell apoptosis and the impaired proliferation. The functional integrity of copper transporters cox17 and atp7b are required for copper stress in inducing T cell apoptosis and proliferation impairment. Our findings demonstrate that the down-stream ROS-foxo/cytoskeleton and foxm1-cytoskeleton signaling pathways contribute jointly to copper overload induced T cell apoptosis and proliferation defects, which are depend on the integral function of Cox17 and Atp7b, and provide new insight into the copper homeostasis in T lymphocyte development.


Subject(s)
Copper , Water Pollutants, Chemical , Animals , Copper/toxicity , Copper/metabolism , Zebrafish/metabolism , Reactive Oxygen Species/metabolism , T-Lymphocytes/metabolism , Water Pollutants, Chemical/toxicity , Apoptosis , Cell Proliferation
15.
Front Neuroinform ; 17: 1337766, 2023.
Article in English | MEDLINE | ID: mdl-38088986

ABSTRACT

[This corrects the article DOI: 10.3389/fninf.2023.1118419.].

16.
ACS Appl Nano Mater ; 6(21): 19639-19650, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37969784

ABSTRACT

Electrochemical synthesis has emerged as a promising approach for the large-scale production of graphene-based two-dimensional (2D) materials. Electrochemical intercalation of ions and molecules between graphite layers plays a key role in the synthesis of graphene with controllable thickness. However, there is still a limited understanding regarding the impact of intercalant molecules. Herein, we investigated a series of anionic species (i.e., ClO4-, PF6-, BF4-, HSO4-, CH3SO3-, and TsO-) and examined their wedging process between the weakly bonded layered materials driven by electrochemistry. By combining cyclic voltammetry, X-ray diffraction (XRD), and Raman spectroscopy, along with density functional theory (DFT) calculations, we found that stage-2 graphite intercalation compounds (GICs) can be obtained through intercalation of ClO4-, PF6-, or BF4- anions into the adjacent graphene bilayers. The anodic exfoliation step based on ClO4--GIC in (NH4)2SO4 (aq.) resulted in the formation of bilayer-rich (>57%) electrochemically exfoliated graphene oxide (EGO), with a high yield (∼85 wt %). Further, the physicochemical properties of these EGO can be readily customized through electrochemical reduction and modification with different surfactants. This versatility allows for precise tailoring of EGO, making it feasible for energy and electronic applications such as electrodes in electrochemical capacitors and functional composites in wearable electronics.

17.
Nat Commun ; 14(1): 7406, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-37973914

ABSTRACT

Major depressive disorder (MDD) is one of the most common and disabling mental disorders, and current strategies remain inadequate. Although mesenchymal stromal cells (MSCs) have shown beneficial effects in experimental models of depression, underlying mechanisms remain elusive. Here, using murine depression models, we demonstrated that MSCs could alleviate depressive and anxiety-like behaviors not due to a reduction in proinflammatory cytokines, but rather activation of dorsal raphe nucleus (DRN) 5-hydroxytryptamine (5-HT) neurons. Mechanistically, peripheral delivery of MSCs activated pulmonary innervating vagal sensory neurons, which projected to the nucleus tractus solitarius, inducing the release of 5-HT in DRN. Furthermore, MSC-secreted brain-derived neurotrophic factor activated lung sensory neurons through tropomyosin receptor kinase B (TrkB), and inhalation of a TrkB agonist also achieved significant therapeutic effects in male mice. This study reveals a role of peripheral MSCs in regulating central nervous system function and demonstrates a potential "lung vagal-to-brain axis" strategy for MDD.


Subject(s)
Depressive Disorder, Major , Mesenchymal Stem Cells , Humans , Mice , Animals , Male , Serotonin , Dorsal Raphe Nucleus , Anxiety/therapy
18.
Antioxidants (Basel) ; 12(11)2023 Oct 26.
Article in English | MEDLINE | ID: mdl-38001770

ABSTRACT

Antimony (Sb) is a hazardous metal element that is potentially toxic and carcinogenic. Melatonin (MT) is an indole compound with antioxidant properties that plays an essential role in plant growth and alleviates heavy metal stresses. Nevertheless, little is known about the effects and mechanisms of exogenous MT action on rice under Sb stress. The aim of this experiment was to explore the mechanism of MT reducing Sb toxicity in rice via hydroponics. The results showed that Sb stress significantly inhibited the growth of rice, including biomass, root parameters, and root viability. Exogenous MT obviously alleviated the inhibition of Sb stress on seedling growth and increased biomass, root parameters, and root viability by 15-55%. MT significantly reduced the total Sb content in rice and the subcellular Sb contents in roots by nearly 20-40% and 12.3-54.2% under Sb stress, respectively. MT significantly decreased the contents of malondialdehyde (MDA, by nearly 50%), ROS (H2O2 and O2·-, by nearly 20-30%), and RNS (NO and ONOO-) in roots under Sb stress, thus reducing oxidative stress and cell membrane damage. Furthermore, MT reversed Sb-induced phytotoxicity by increasing the activities of antioxidant enzymes (SOD, POD, CAT, and APX) by nearly 15% to 50% and by regulating the AsA-GSH cycle. In conclusion, this study demonstrates the potential of MT to maintain redox homeostasis and reduce Sb toxicity in rice cells, decreasing the content of Sb in rice and thereby alleviating the inhibition of Sb on rice growth. The results provided a feasible strategy for mitigating Sb toxicity in rice.

19.
Adv Mater ; : e2306358, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37992728

ABSTRACT

The irregular expression or activity of enzymes in the human body leads to various pathological disorders and can therefore be used as an intrinsic trigger for more precise identification of disease foci and controlled release of diagnostics and therapeutics, leading to improved diagnostic accuracy, sensitivity, and therapeutic efficacy while reducing systemic toxicity. Advanced synthesis strategies enable the preparation of polymers with enzymatically activatable skeletons or side chains, while understanding enzymatically responsive mechanisms promotes rational incorporation of activatable units and predictions of the release profile of diagnostics and therapeutics, ultimately leading to promising applications in disease diagnosis and treatment with superior biocompatibility and efficiency. By overcoming the challenges, new opportunities will emerge to inspire researchers to develop more efficient, safer, and clinically reliable enzymatically activatable polymeric carriers as well as prodrugs.

20.
BMC Surg ; 23(1): 309, 2023 Oct 12.
Article in English | MEDLINE | ID: mdl-37828530

ABSTRACT

BACKGROUND: There is no consensus on the optimal reconstruction technique after proximal gastrectomy. The purpose of this study was to retrospectively compare the surgical outcomes among esophagogastrostomy (EG) anastomosis, gastric tube (GT) reconstruction and double-tract (DT) reconstruction in patients who underwent laparoscopic proximal gastrectomy (LPG) to clarify the superior reconstruction method. METHODS: This study enrolled 164 patients who underwent LPG at the Northern Jiangsu People's Hospital in Jiangsu between January 2017 to January 2022 (EG: 51 patients; GT: 77 patients; DT: 36 patients). We compared the clinical and pathological characteristics, surgical features, postoperative complications, nutritional status, and quality of life (QOL) among the above three groups. RESULTS: Mean operative time was longer with the DT group than the remaining two groups (p = 0.001). With regard to postoperative complications, considerable differences in the postoperative reflux symptoms (p = 0.042) and reflux esophagitis (p = 0.040) among the three groups were found. For the nutritional status, total protein, hemoglobin and albumin reduction rates in the GT group were significantly higher than the other two groups at 12 months postoperatively. In the PGSAS-45, three assessment items were better in the DT group significantly compared with the esophageal reflux subscale (p = 0.047, Cohen's d = 0.44), dissatisfaction at the meal (p = 0.009, Cohen's d = 0.58), and dissatisfaction for daily life subscale (p = 0.012, Cohen's d = 0.56). CONCLUSIONS: DT after LPG is a valuable reconstruction technique with satisfactory surgical outcomes, especially regarding reduced reflux symptoms, improving the postoperative nutritional status and QOL.


Subject(s)
Esophagitis, Peptic , Laparoscopy , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Quality of Life , Treatment Outcome , Retrospective Studies , Laparoscopy/methods , Gastrectomy/methods , Anastomosis, Surgical/methods , Postoperative Complications/epidemiology , Postoperative Complications/surgery
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