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1.
Surg Endosc ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844732

ABSTRACT

OBJECTIVE: To investigate the risk factors for delayed postoperative bleeding after endoscopic submucosal dissection (ESD) in patients with gastric precancerous lesions and to construct a risk prediction model. METHODS: This retrospective analysis included clinical data from patients with gastric precancerous lesions who underwent ESD at Wuhan University People's Hospital between November 2016 and June 2022. An XGBoost model was built to predict delayed bleeding after ESD using risk factors identified by univariable and multivariate logistic regression analysis. The model was evaluated using receiver operating characteristic curves (ROC), and SHapely Additive exPlanations (SHAP) analysis was used to interpret the model. RESULTS: Seven factors were statistically associated with delayed postoperative bleeding in gastric precancerous lesions after ESD: age, low-grade intraepithelial neoplasia, hypertension, lesion size ≥ 40 mm, operative time ≥ 120 min, female, and nonuse of hemoclips. A risk prediction model was established. In the training cohort, the model achieved an AUC of 0.97 (0.96-0.98), a sensitivity of 0.90, a specificity of 0.94, and an F1 score of 0.91. In the validation cohort, the AUC was 0.94(0.90-0.98), with a sensitivity of 0.85, a specificity of 0.89, and an F1 score of 0.85. In the test cohort, the AUC was 0.94 (0.89-0.99), the sensitivity was 0.80, the specificity was 0.92, and the F1 score was 0.84, indicating strong predictive capability. CONCLUSION: In this study, an XGBoost prediction model for assessing the risk of delayed postoperative bleeding after ESD in patients with gastric precancerous lesions was developed and validated. This model can be applied in clinical practice to effectively predict the risk of post-ESD bleeding for individual patients.

2.
Langmuir ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860838

ABSTRACT

Metal-organic frameworks (MOFs) based on tin (Sn) have shown great potential as materials for lithium storage, thanks to their ability to alleviate volume expansion due to the homogeneous distribution of Sn in a porous matrix framework. However, the weak mechanical strength of the porous Sn-MOF structure has been a major challenge, leading to pulverization during the discharging/charging process. To overcome this issue, we have developed a feasible strategy to strengthen the Sn-MOF mechanical properties by incorporating SiO2/GeO2 nanoparticles during the synthesis process. The resulting composites of Sn-Si and Sn-Ge exhibited high energy density and long-term cycle stability, thanks to their synergistic effect in alloying and conversion reactions. Our density functional theory (DFT) calculations have revealed that the rigid SiO2/GeO2 nanoparticles enhance the Sn-MOF mechanical properties, including Young's and shear moduli, which contribute to the long-term cycle stability of these composites.

3.
Small ; : e2312046, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38829034

ABSTRACT

Accurate construction of artificial nano-chaperones' structure is crucial for precise regulation of protein conformational transformation, facilitating effective treatment of proteopathy. However, how the ligand-anchors of nano-chaperones affect the spatial conformational changes in proteins remains unclear, limiting the development of efficient nano-chaperones. In this study, three types of gold nanoparticles (AuNPs) with different core/ligands interface anchor structures (Au─NH─R, Au─S─R, and Au─C≡C─R, R = benzoic acid) are synthesized as an ideal model to investigate the effect of interfacial anchors on Aß and amylin fibrillization. Computational results revealed that the distinct interfacial anchors imparted diverse distributions of electrostatic potential on the nanointerface and core/ligands bond strength of AuNPs, leading to differential interactions with amyloid peptides. Experimental results demonstrated that all three types of AuNPs exhibit site-specific inhibitory effects on Aß40 fibrillization due to preferential binding. For amylin, amino-anchored AuNPs demonstrate strong adsorption to multiple sites on amylin and effectively inhibit fibrillization. Conversely, thiol- and alkyne-anchored AuNPs adsorb at the head region of amylin, promoting folding and fibrillization. This study not only provided molecular insights into how core/ligands interfacial anchors of nanomaterials induce spatial conformational changes in amyloid peptides but also offered guidance for precisely engineering artificial-chaperones' nanointerfaces to regulate the conformational transformation of proteins.

4.
Nat Commun ; 15(1): 4827, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844451

ABSTRACT

Adipose progenitor cells (APCs) are heterogeneous stromal cells and help to maintain metabolic homeostasis. However, the influence of obesity on human APC heterogeneity and the role of APC subpopulations on regulating glucose homeostasis remain unknown. Here, we find that APCs in human visceral adipose tissue contain four subsets. The composition and functionality of APCs are altered in patients with type 2 diabetes (T2D). CD9+CD55low APCs are the subset which is significantly increased in T2D patients. Transplantation of these cells from T2D patients into adipose tissue causes glycemic disturbance. Mechanistically, CD9+CD55low APCs promote T2D development through producing bioactive proteins to form a detrimental niche, leading to upregulation of adipocyte lipolysis. Depletion of pathogenic APCs by inducing intracellular diphtheria toxin A expression or using a hunter-killer peptide improves obesity-related glycemic disturbance. Collectively, our data provide deeper insights in human APC functionality and highlights APCs as a potential therapeutic target to combat T2D. All mice utilized in this study are male.


Subject(s)
Diabetes Mellitus, Type 2 , Glucose , Homeostasis , Obesity , Single-Cell Analysis , Stem Cells , Humans , Animals , Single-Cell Analysis/methods , Diabetes Mellitus, Type 2/metabolism , Male , Mice , Stem Cells/metabolism , Glucose/metabolism , Obesity/metabolism , Obesity/pathology , Adipocytes/metabolism , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/cytology , Adipose Tissue/metabolism , Adipose Tissue/cytology , Mice, Inbred C57BL , Lipolysis , Female , Middle Aged
5.
Sci Bull (Beijing) ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38879416

ABSTRACT

Given that it was a once-in-a-century emergency event, the confinement measures related to the coronavirus disease 2019 (COVID-19) pandemic caused diverse disruptions and changes in life and work patterns. These changes significantly affected water consumption both during and after the pandemic, with direct and indirect consequences on biodiversity. However, there has been a lack of holistic evaluation of these responses. Here, we propose a novel framework to study the impacts of this unique global emergency event by embedding an environmentally extended supply-constrained global multi-regional input-output model (MRIO) into the drivers-pressure-state-impact-response (DPSIR) framework. This framework allowed us to develop scenarios related to COVID-19 confinement measures to quantify country-sector-specific changes in freshwater consumption and the associated changes in biodiversity for the period of 2020-2025. The results suggest progressively diminishing impacts due to the implementation of COVID-19 vaccines and the socio-economic system's self-adjustment to the new normal. In 2020, the confinement measures were estimated to decrease global water consumption by about 5.7% on average across all scenarios when compared with the baseline level with no confinement measures. Further, such a decrease is estimated to lead to a reduction of around 5% in the related pressure on biodiversity. Given the interdependencies and interactions across global supply chains, even those countries and sectors that were not directly affected by the COVID-19 shocks experienced significant impacts: Our results indicate that the supply chain propagations contributed to 79% of the total estimated decrease in water consumption and 84% of the reduction in biodiversity loss on average. Our study demonstrates that the MRIO-enhanced DSPIR framework can help quantify resource pressures and the resultant environmental impacts across supply chains when facing a global emergency event. Further, we recommend the development of more locally based water conservation measures-to mitigate the effects of trade disruptions-and the explicit inclusion of water resources in post-pandemic recovery schemes. In addition, innovations that help conserve natural resources are essential for maintaining environmental gains in the post-pandemic world.

6.
J Cancer ; 15(10): 2981-2993, 2024.
Article in English | MEDLINE | ID: mdl-38706911

ABSTRACT

Background and Objectives: PLD2 has been identified as playing a critical role in cancer cell motility and migration and other pathophysiological processes. We investigated the expression of PLD2 and its biological functions and clinical implications in human colorectal cancer. Materials and Methods: In this study, the expressions of PLD2 were analyzed in CRC cell lines and CRC samples by RT-PCR, western blot and immunohistochemistry. The PLD enzyme activity was studied using an PLD detection kit. We also performed matrigel invasion assay to evaluate the invasive capabilities in CRC cells. The expressions of EMT-related markers were quantified at mRNA and protein level using RT-PCR and western blot. We performed high-throughput RNA sequencing on PLD2 knockdown and overexpression CRC cell lines to explore the changes in gene expression associated with PLD2. Result: Herein, we showed that PLD2 expression was relatively low in CRC cell lines and CRC samples and PLD2 deficiency was significantly correlated with more advanced clinical phenotype regarding lymphatic and distant metastasis and poor patient survival. We also detected that PLD2 knockdown favored epithelial-mesenchymal transition (EMT) and thus promoted CRC invasion and metastasis. Further exploration uncovered that the expressions of several important genes closely related to metabolic pathways in CRC were noticeably altered due to PLD2 deficiency, including ID1, IFIT4, OASL, IFIT2 and CTAG2. Conclusion: Our results revealed that PLD2 deficiency promotes cell invasion and metastasis in CRC via EMT indicating PLD2 might have an important implication in carcinogenesis and progression and would be a new therapeutic target for cancer treatment.

7.
Heliyon ; 10(9): e30000, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38694083

ABSTRACT

Background: Trigeminal neuralgia (TN) secondary to a dural arteriovenous fistula (DAVF) is quite rare, and the goal of treatment is to resolve both the fistula and the pain. Case presentation: We herein report a case of TN secondary to a DAVF in a 64-year-old woman with a 1-year history of right-sided TN. Brain magnetic resonance imaging and digital subtraction angiography showed a right tentorial DAVF. Interventional embolization was performed, but the pain was not relieved after the operation. Six months later, we performed microvascular decompression of the trigeminal nerve. During the operation, we electrocoagulated the tortuous and dilated malformed vein, which was compressing the trigeminal nerve, to reduce its diameter and mitigate the compression on the cisternal segment of the trigeminal nerve. That patient's pain was relieved postoperatively. In addition, we reviewed the literature of TN caused by DAVF and found a total of 30 cases, 22 of which were treated by interventional embolization. Of these 22 cases, the interventional embolization healed the fistula with pain relief in 14 cases and healed the fistula without pain relief in 8 cases. We found that the venous drainage methods of the 8 cases were all classified into the posterior mesencephalic group. Conclusions: We believe that this drainage pattern contributes to the more common occurrence of unrelieved pain. For such patients, microvascular decompression can be performed with intraoperative coagulation to narrow the dilated veins until the cisternal segment of the trigeminal nerve is no longer compressed. Satisfactory curative effects can be obtained using this technique.

8.
Opt Lett ; 49(9): 2293-2296, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38691702

ABSTRACT

We experimentally realized a high-speed nested anti-resonant nodeless fiber (NANF) transmission with the assistance of the polarization division multiplexing (PDM) and probabilistic shaping (PS) technology. In this system, a low-complexity multiple-input multiple-output (MIMO) real-valued equalizer (RVE) is integrated with decision-directed carrier phase estimation (DDCPE), which is robust against the IQ cross talk and a tiny phase disturbance between PS symbols. By using the proposed MIMO-RVEDDCPE, the 60-Gbaud PDM-PS-256QAM signal has been delivered through 2-km NANF satisfying the soft-decision forward error correction (SD-FEC) threshold.

9.
BMC Surg ; 24(1): 154, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745320

ABSTRACT

BACKGROUND: Hemifacial spasm (HFS) is most effectively treated with microvascular decompression (MVD). However, there are certain challenges in performing MVD for HFS when the vertebral artery (VA) is involved in compressing the facial nerve (VA-involved). This study aimed to introduce a "bridge-layered" decompression technique for treating patients with VA-involved HFS and to evaluate its efficacy and safety to treat patients with HFS. METHODS: A single-center retrospective analysis was conducted on the clinical data of 62 patients with VA-involved HFS. The tortuous trunk of VA was lifted by a multi-point "bridge" decompression technique to avoid excessive traction of the cerebellum and reduce the risk of damage to the facial-acoustic nerve complex. To fully decompress all the responsible vessels, the branch vessels of VA were then isolated using the "layered" decompression technique. RESULTS: Among the 62 patients, 59 patients were cured immediately after the surgery, two patients were delayed cured after two months, and one had occasional facial muscle twitching after the surgery. Patients were followed up for an average of 19.5 months. The long-term follow-up results showed that all patients had no recurrence of HFS during the follow-up period, and no patients developed hearing loss, facial paralysis, or other permanent neurological damage complications. Only two patients developed tinnitus after the surgery. CONCLUSION: The "bridge-layered" decompression technique could effectively treat VA-involved HFS with satisfactory safety and a low risk of hearing loss. The technique could be used as a reference for decompression surgery for VA-involved HFS.


Subject(s)
Hemifacial Spasm , Microvascular Decompression Surgery , Vertebral Artery , Humans , Hemifacial Spasm/surgery , Female , Male , Middle Aged , Retrospective Studies , Vertebral Artery/surgery , Adult , Microvascular Decompression Surgery/methods , Treatment Outcome , Aged , Decompression, Surgical/methods , Follow-Up Studies
10.
Int J Biol Macromol ; 269(Pt 2): 132139, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719008

ABSTRACT

Accumulating salinity in soil critically affected growth, development, and yield in plant. However, the mechanisms of plant against salt stress largely remain unknown. Herein, we identified a gene named SmCYP78A7a, which encoded a cytochrome P450 monooxygenase and belonged to the CYP78A sub-family, and its transcript level was significantly up-regulated by salt stress and down-regulated by dehydration stress. SmCYP78A7a located in the endoplasmic reticulum. Silencing of SmCYP78A7a enhanced susceptibility of eggplant to salt stress, and significantly down-regulated the transcript levels of salt stress defense related genes SmGSTU10 and SmWRKY11 as well as increased hydrogen peroxide (H2O2) content and decreased catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) enzyme activities. In addition, SmCYP78A7a transient expression enhanced eggplant tolerance to salt stress. By chromatin immunoprecipitation PCR (ChIP-PCR), luciferase reporter assay, and electrophoretic mobility shift assay (EMSA), SmWRKY11 activated SmCYP78A7a expression by directly binding to the W-box 6-8 (W-box 6, W-box 7, and W-box 8) within SmCYP78A7a promoter to confer eggplant tolerance to salt stress. In summary, our finds reveal that SmCYP78A7a positively functions in eggplant response to salt stress via forming a positive feedback loop with SmWRKY11, and provide a new insight into regulatory mechanisms of eggplant to salt stress.


Subject(s)
Cytochrome P-450 Enzyme System , Gene Expression Regulation, Plant , Plant Proteins , Salt Stress , Solanum melongena , Solanum melongena/genetics , Solanum melongena/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Salt Stress/genetics , Gene Expression Regulation, Plant/drug effects , Plant Proteins/genetics , Plant Proteins/metabolism , Feedback, Physiological , Transcription Factors/metabolism , Transcription Factors/genetics , Hydrogen Peroxide/metabolism , Salt Tolerance/genetics
11.
Proc Natl Acad Sci U S A ; 121(22): e2314619121, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38776375

ABSTRACT

Humoral immunity depends on the germinal center (GC) reaction where B cells are tightly controlled for class-switch recombination and somatic hypermutation and finally generated into plasma and memory B cells. However, how protein SUMOylation regulates the process of the GC reaction remains largely unknown. Here, we show that the expression of SUMO-specific protease 1 (SENP1) is up-regulated in GC B cells. Selective ablation of SENP1 in GC B cells results in impaired GC dark and light zone organization and reduced IgG1-switched GC B cells, leading to diminished production of class-switched antibodies with high-affinity in response to a TD antigen challenge. Mechanistically, SENP1 directly binds to Paired box protein 5 (PAX5) to mediate PAX5 deSUMOylation, sustaining PAX5 protein stability to promote the transcription of activation-induced cytidine deaminase. In summary, our study uncovers SUMOylation as an important posttranslational mechanism regulating GC B cell response.


Subject(s)
B-Lymphocytes , Cysteine Endopeptidases , Germinal Center , PAX5 Transcription Factor , Sumoylation , Germinal Center/immunology , Germinal Center/metabolism , PAX5 Transcription Factor/metabolism , PAX5 Transcription Factor/genetics , Animals , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Cysteine Endopeptidases/metabolism , Cysteine Endopeptidases/genetics , Mice , Immunoglobulin Class Switching , Humans , Cytidine Deaminase/metabolism , Cytidine Deaminase/genetics , Immunity, Humoral , Mice, Inbred C57BL
12.
Am J Trop Med Hyg ; 110(6): 1152-1157, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38697072

ABSTRACT

Soil-transmitted helminthiasis remains a notable health problem in developing countries. In 1990 in Shanghai, a city in eastern China, 47% of the population was affected. Due to a series of comprehensive approaches, the prevalence decreased to 0.5% in 2009. We collected 10-year surveillance data to assess the epidemic situation of soil-transmitted helminth (STH) infections in Shanghai. Stool samples and questionnaires from participants were collected. The Kato-Katz technique was used to detect infections with Ascaris lumbricoides, hookworm (Ancylostoma duodenale and Necator americanus), and Trichuris trichiura. From 2014 to 2023, a total of 77,685 participants were screened for parasitic infections, and the overall prevalence of STH infections decreased from 0.1% to 0% in Shanghai. Of 77,685 participants, 25 (0.03%) were positive for intestinal helminths, with the most common parasite being A. lumbricoides (72.0%). Generally, elderly participants from rural areas with lower education levels were more likely to be infected with STHs. A total of 2,914 questionnaires were collected, and most respondents (72.6%) had good knowledge about the transmission routes of STHs. However, 12.3% of participants did not know the damage to health caused by STHs, and 19.3% had no idea of how to prevent infection. These data demonstrate the current state of STH infections in Shanghai. The results suggest that various comprehensive measures should be encouraged, continuously implemented, and strengthened accordingly so that STH elimination can be integrated into the Healthy China initiative by 2030.


Subject(s)
Ascaris lumbricoides , Helminthiasis , Soil , Humans , China/epidemiology , Helminthiasis/epidemiology , Helminthiasis/transmission , Adult , Soil/parasitology , Middle Aged , Male , Female , Adolescent , Child , Young Adult , Aged , Animals , Prevalence , Ascaris lumbricoides/isolation & purification , Child, Preschool , Feces/parasitology , Ascariasis/epidemiology , Ascariasis/transmission , Intestinal Diseases, Parasitic/epidemiology , Intestinal Diseases, Parasitic/transmission , Trichuriasis/epidemiology , Trichuriasis/transmission , Surveys and Questionnaires , Hookworm Infections/epidemiology , Hookworm Infections/transmission , Infant , Trichuris/isolation & purification
13.
Neural Netw ; 177: 106367, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38754215

ABSTRACT

While computer vision has proven valuable for medical image segmentation, its application faces challenges such as limited dataset sizes and the complexity of effectively leveraging unlabeled images. To address these challenges, we present a novel semi-supervised, consistency-based approach termed the data-efficient medical segmenter (DEMS). The DEMS features an encoder-decoder architecture and incorporates the developed online automatic augmenter (OAA) and residual robustness enhancement (RRE) blocks. The OAA augments input data with various image transformations, thereby diversifying the dataset to improve the generalization ability. The RRE enriches feature diversity and introduces perturbations to create varied inputs for different decoders, thereby providing enhanced variability. Moreover, we introduce a sensitive loss to further enhance consistency across different decoders and stabilize the training process. Extensive experimental results on both our own and three public datasets affirm the effectiveness of DEMS. Under extreme data shortage scenarios, our DEMS achieves 16.85% and 10.37% improvement in dice score compared with the U-Net and top-performed state-of-the-art method, respectively. Given its superior data efficiency, DEMS could present significant advancements in medical segmentation under small data regimes. The project homepage can be accessed at https://github.com/NUS-Tim/DEMS.


Subject(s)
Image Processing, Computer-Assisted , Humans , Image Processing, Computer-Assisted/methods , Neural Networks, Computer , Algorithms , Databases, Factual
14.
Immunity ; 57(6): 1289-1305.e9, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38772366

ABSTRACT

Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.


Subject(s)
Adipose Tissue , Homeostasis , Insulin Resistance , Lymphocytes , Mitochondria , Obesity , Programmed Cell Death 1 Receptor , Protein Serine-Threonine Kinases , Animals , Insulin Resistance/immunology , Programmed Cell Death 1 Receptor/metabolism , Mice , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Mitochondria/metabolism , Humans , Adipose Tissue/metabolism , Adipose Tissue/immunology , Obesity/immunology , Obesity/metabolism , Lymphocytes/immunology , Lymphocytes/metabolism , AMP-Activated Protein Kinases/metabolism , Mice, Inbred C57BL , Mice, Knockout , Immunity, Innate , Male , Mitophagy/immunology , AMP-Activated Protein Kinase Kinases
15.
Comput Biol Med ; 173: 108388, 2024 May.
Article in English | MEDLINE | ID: mdl-38569235

ABSTRACT

The COVID-19 pandemic has resulted in hundreds of million cases and numerous deaths worldwide. Here, we develop a novel classification network CECT by controllable ensemble convolutional neural network and transformer to provide a timely and accurate COVID-19 diagnosis. The CECT is composed of a parallel convolutional encoder block, an aggregate transposed-convolutional decoder block, and a windowed attention classification block. Each block captures features at different scales from 28 × 28 to 224 × 224 from the input, composing enriched and comprehensive information. Different from existing methods, our CECT can capture features at both multi-local and global scales without any sophisticated module design. Moreover, the contribution of local features at different scales can be controlled with the proposed ensemble coefficients. We evaluate CECT on two public COVID-19 datasets and it reaches the highest accuracy of 98.1% in the intra-dataset evaluation, outperforming existing state-of-the-art methods. Moreover, the developed CECT achieves an accuracy of 90.9% on the unseen dataset in the inter-dataset evaluation, showing extraordinary generalization ability. With remarkable feature capture ability and generalization ability, we believe CECT can be extended to other medical scenarios as a powerful diagnosis tool. Code is available at https://github.com/NUS-Tim/CECT.


Subject(s)
COVID-19 , Humans , COVID-19 Testing , Pandemics , Neural Networks, Computer , Image Processing, Computer-Assisted
16.
Cereb Cortex ; 34(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38652554

ABSTRACT

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.


Subject(s)
Brain Mapping , Indoles , Magnetic Resonance Imaging , Humans , Male , Female , Adult , Young Adult , Odorants , Brain/physiology , Brain/diagnostic imaging , Olfactory Perception/physiology , Emotions/physiology , Smell/physiology
17.
Genome Med ; 16(1): 60, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658971

ABSTRACT

BACKGROUND: Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood. METHODS: The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis. RESULTS: The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1+, C1Q+, and GPNMB+ showed enhanced contact with tumor cells expressing NR5A1 + , TBX19+, and POU1F1+, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1+ macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis. CONCLUSIONS: In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.


Subject(s)
Macrophages , Neuroendocrine Tumors , Pituitary Neoplasms , Single-Cell Analysis , Transcriptome , Tumor Microenvironment , Humans , Neuroendocrine Tumors/genetics , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/immunology , Neuroendocrine Tumors/metabolism , Pituitary Neoplasms/genetics , Pituitary Neoplasms/immunology , Pituitary Neoplasms/pathology , Pituitary Neoplasms/metabolism , Tumor Microenvironment/immunology , Tumor Microenvironment/genetics , Animals , Mice , Macrophages/metabolism , Macrophages/immunology , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology , Gene Expression Regulation, Neoplastic , Gene Expression Profiling , Phenotype , Apoptosis/genetics , Cell Lineage/genetics
18.
Nat Commun ; 15(1): 2809, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38561334

ABSTRACT

Protein arginine methyltransferase 9 (PRMT9) is a recently identified member of the PRMT family, yet its biological function remains largely unknown. Here, by characterizing an intellectual disability associated PRMT9 mutation (G189R) and establishing a Prmt9 conditional knockout (cKO) mouse model, we uncover an important function of PRMT9 in neuronal development. The G189R mutation abolishes PRMT9 methyltransferase activity and reduces its protein stability. Knockout of Prmt9 in hippocampal neurons causes alternative splicing of ~1900 genes, which likely accounts for the aberrant synapse development and impaired learning and memory in the Prmt9 cKO mice. Mechanistically, we discover a methylation-sensitive protein-RNA interaction between the arginine 508 (R508) of the splicing factor 3B subunit 2 (SF3B2), the site that is exclusively methylated by PRMT9, and the pre-mRNA anchoring site, a cis-regulatory element that is critical for RNA splicing. Additionally, using human and mouse cell lines, as well as an SF3B2 arginine methylation-deficient mouse model, we provide strong evidence that SF3B2 is the primary methylation substrate of PRMT9, thus highlighting the conserved function of the PRMT9/SF3B2 axis in regulating pre-mRNA splicing.


Subject(s)
Alternative Splicing , RNA , Animals , Humans , Mice , Arginine/metabolism , Mice, Knockout , Mutation , Protein-Arginine N-Methyltransferases/metabolism , RNA/metabolism , RNA Precursors/metabolism , RNA Splicing/genetics
19.
Phys Chem Chem Phys ; 26(17): 13087-13093, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38628113

ABSTRACT

The valley polarization, induced by the magnetic proximity effect, in monolayer transition metal dichalcogenides (TMDCs), has attracted significant attention due to the intriguing fundamental physics. However, the enhancement and modulation of valley polarization for real device applications is still a challenge. Here, using first-principles calculations we investigate the valley polarization properties of monolayer TMDCs CrS2 and CrSe2 and how to enhance the valley polarization by constructing Janus CrSSe (with an internal electric field) and modulate the polarization in CrSSe by applying external electric fields. Janus CrSSe exhibits inversion symmetry breaking, internal electric field, spin-orbit coupling, and compelling spin-valley coupling. A magnetic substrate of the MnO2 monolayer can induce a modest magnetic moment in CrSe2, CrSe2, and CrSSe. Notably, the Janus structure with an internal electric field has a much larger valley p compared with its non-Janus counterparts. Moreover, the strength of valley polarization can be further modulated by applying external electric fields. These findings suggest that Janus materials hold promise for designing and developing advanced valleytronic devices.

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