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1.
Plants (Basel) ; 13(17)2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39273980

ABSTRACT

Histone modification plays a crucial role in chromatin remodeling and regulating gene expression, and participates in various biological processes, including plant development and responses to stress. Several gene families related to histone modification have been reported in various plant species. However, the identification of members and their functions in the rice (Oryza sativa L.) histone modification gene family (OsHM) at the whole-genome level remains unclear. In this study, a total of 130 OsHMs were identified through a genome-wide analysis. The OsHM gene family can be classified into 11 subfamilies based on a phylogenetic analysis. An analysis of the genes structures and conserved motifs indicates that members of each subfamily share specific conserved protein structures, suggesting their potential conserved functions. Molecular evolutionary analysis reveals that a significant number of OsHMs proteins originated from gene duplication events, particularly segmental duplications. Additionally, transcriptome analysis demonstrates that OsHMs are widely expressed in various tissues of rice and are responsive to multiple abiotic stresses. Fourteen OsHMs exhibit high expression in rice anthers and peaked at different pollen developmental stages. RT-qPCR results further elucidate the expression patterns of these 14 OsHMs during different developmental stages of anthers, highlighting their high expression during the meiosis and tetrad stages, as well as in the late stage of pollen development. Remarkably, OsSDG713 and OsSDG727 were further identified to be nucleus-localized. This study provides a fundamental framework for further exploring the gene functions of HMs in plants, particularly for researching their functions and potential applications in rice anthers' development and male sterility.

2.
Cell Syst ; 15(9): 824-837.e6, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39236711

ABSTRACT

Most cancer types lack targeted therapeutic options, and when first-line targeted therapies are available, treatment resistance is a huge challenge. Recent technological advances enable the use of assay for transposase-accessible chromatin with sequencing (ATAC-seq) and RNA sequencing (RNA-seq) on patient tissue in a high-throughput manner. Here, we present a computational approach that leverages these datasets to identify drug targets based on tumor lineage. We constructed gene regulatory networks for 371 patients of 22 cancer types using machine learning approaches trained with three-dimensional genomic data for enhancer-to-promoter contacts. Next, we identified the key transcription factors (TFs) in these networks, which are used to find therapeutic vulnerabilities, by direct targeting of either TFs or the proteins that they interact with. We validated four candidates identified for neuroendocrine, liver, and renal cancers, which have a dismal prognosis with current therapeutic options.


Subject(s)
Chromatin , Neoplasms , Transcriptome , Humans , Chromatin/genetics , Chromatin/metabolism , Neoplasms/genetics , Neoplasms/therapy , Neoplasms/drug therapy , Transcriptome/genetics , Transcription Factors/genetics , Transcription Factors/metabolism , Gene Regulatory Networks/genetics , Gene Expression Regulation, Neoplastic/genetics , Machine Learning , Computational Biology/methods
3.
J Hazard Mater ; 480: 135808, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39288524

ABSTRACT

There is a correlation between long-term manganese (Mn) exposure and the Parkinson's-like disease (PD), with depression as an early symptom of PD. However, the direct relationship between Mn exposure and depression, and the mechanisms involved, remain unclear. We found that Mn exposure led to depressive-like behavior and mild cognitive impairment in mice, with Mn primarily accumulating in the cornu ammonis 3 (CA3) area of the hippocampus. Mice displayed a reduction in neuronal dendritic spines and damage to astrocytes specifically in the CA3 area. Spatial metabolomics revealed that Mn downregulated glutamic acid decarboxylase 1 (GAD1) expression in astrocytes, disrupting the Glutamine-Glutamate-γ-aminobutyric acid (GlnGluGABA) metabolic cycle in the hippocampus, leading to neurotoxicity. We established an in vitro astrocyte Gad1 overexpression (OEX) model and found that the cultured medium from Gad1 OEX astrocytes reversed neuronal synaptic damage and the expression of gamma-aminobutyric acid (GABA) related receptors. Using the astrocyte Gad1 OEX mouse model, results showed that OEX of Gad1 ameliorated depressive-like behavior and cognitive dysfunction in mice. These findings provide new insight into the important role of GAD1 mediated GlnGluGABA metabolism disorder in Mn exposure induced depressive-like behavior. This study offers a novel sight to understanding abnormal emotional states following central nervous system damage induced by Mn exposure.

4.
J Neurosci Res ; 102(9): e25381, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39283065

ABSTRACT

Assessing the glymphatic system activity using diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS) may be helpful to understand the pathophysiology of moyamoya disease (MMD). 63 adult patients with MMD and 20 healthy controls (HCs) were included for T1-weighted images, T2-FLAIR, pseudocontinuous arterial spin labeling, and DTI. 60 patients had digital subtraction angiography more than 6 months after combined revascularization. The Suzuki stage, postoperative Matsushima grade, periventricular anastomoses (PA), enlarged perivascular spaces (EPVS), deep and subcortical white matter hyperintensities (DSWMH), DTI-ALPS, cerebral blood flow (CBF), and cognitive scales of MMD patients were assessed. MMD patients were divided into early and advanced stage based on the Suzuki stage. We detected lower DTI-ALPS in patients with advanced stage relative to HCs (p = 0.046) and patients with early stage (p = 0.004), hemorrhagic MMD compared with ischemic MMD (p = 0.048), and PA Grade 2 compared with Grade 0 (p = 0.010). DTI-ALPS was correlated with the EPVS in basal ganglia (r = -0.686, p < 0.001), Suzuki stage (r = -0.465, p < 0.001), DSWMH (r = -0.423, p = 0.001), and global CBF (r = 0.300, p = 0.017) and cognitive scores (r = 0.343, p = 0.018). The DTI-ALPS of patients with good postoperative collateral formation was higher compared to those with poor postoperative collateral formation (p = 0.038). In conclusion, the glymphatic system was impaired in advanced MMD patients and may affected cognitive function and postoperative neoangiogenesis.


Subject(s)
Cerebrovascular Circulation , Diffusion Tensor Imaging , Glymphatic System , Moyamoya Disease , Humans , Moyamoya Disease/diagnostic imaging , Moyamoya Disease/surgery , Moyamoya Disease/pathology , Moyamoya Disease/physiopathology , Female , Male , Glymphatic System/diagnostic imaging , Glymphatic System/pathology , Adult , Middle Aged , Cerebrovascular Circulation/physiology , Young Adult , Angiography, Digital Subtraction , Brain/diagnostic imaging , Brain/pathology
5.
Transl Cancer Res ; 13(8): 4242-4256, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39262462

ABSTRACT

Background: Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer in adults. This study aimed to obtain data on immune cell infiltration based on public datasets and to examine the prognostic significance of SH2 domain containing 4A (SH2D4A) for GBM. Methods: SH2D4A expression in GBM was analyzed using a Tumor Immunity Estimation Resource (TIMER) 2.0 dataset, and a gene expression profile interaction analysis (GEPIA), and the results were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The Chinese Glioma Genome Atlas (CGGA) dataset was used to assess the effect of SH2D4A on GBM patient survival. The SH2D4A co-expression network of the LinkedOmics dataset and GeneMANIA dataset was also investigated. Least absolute shrinkage and selection operator (LASSO) regression models and a nomogram were constructed to assess the prognosis of GBM patients. A Gene Set Enrichment Analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset to find functional differences. The relationship between SH2D4A expression and tumor-infiltrating immune cells was analyzed using xCELL, the Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, and the TIMER dataset. Results: We discovered that SH2D4A expression was upregulated in GBM patients, and elevated SH2D4A expression was also substantially correlated with tumor grade. The survival curve analysis and multivariate Cox regression analysis showed that high SH2D4A expression was a significant independent predictor of poor overall survival (OS) in GBM patients. The immunoassay results suggested that altered SH2D4A expression may affect the immune infiltration of GBM tissues and thus the survival outcomes of GBM patients. Conclusions: In addition to being a possible prognostic marker and therapeutic target for GBM, SH2D4A may also accelerate the progression of GBM.

6.
Am J Cancer Res ; 14(8): 3800-3815, 2024.
Article in English | MEDLINE | ID: mdl-39267661

ABSTRACT

Aberrant RSPO1 expression is implicated in tumor progression across various cancers and correlates with anti-cancer immune cell characteristics. However, the specific role of R-spondin 1 (RSPO1) in lung adenocarcinoma (LUAD) remains unclear. In this study, we utilized data from The Cancer Genome Atlas (TCGA) to assess RSPO1 expression across 33 tumor types. Kaplan-Meier (K-M) analysis revealed the prognostic significance of RSPO1 in various cancers. Using statistical software R, we examined RSPO1's associations with immune cell infiltration, methylation, mutation, and competing endogenous RNA (ceRNA) networks. Exploration via the Tumor Immune Single Cell Hub (TISCH) database uncovered RSPO1's link to the tumor microenvironment (TME) and identified potential small molecule drug targets. We further investigated RSPO1's impact on LUAD cell proliferation, metastasis, and the Wnt pathway in vitro. Our findings highlight RSPO1's role in cancer progression and suggest its potential as both a prognostic marker and therapeutic target in LUAD, implicating the modulation of the Wnt pathway.

7.
ACS Nano ; 18(35): 24024-24034, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39167054

ABSTRACT

In recent years, there has been considerable push toward the biomedical applications with active particles, which have great potential to revolutionize disease diagnostics and therapy. The direct penetration of active particles through the cell membrane leads to more efficient intracellular delivery than previously considered endocytosis processes but may cause membrane disruption. Understanding fundamental behaviors of cell membranes in response to such extreme impacts by active particles is crucial to develop active particle-based biomedical technologies and manage health and safety issues in this emerging field. Unfortunately, the physical principles underlying the nonequilibrium behaviors from endocytosis to direct penetration remain elusive, and experiments are challenging. Here, we present a computed dynamic phase diagram for transmembrane transport of active particles and identify four characteristic dynamic phases in endocytosis and direct penetration according to the particle activity and membrane tension. The boundaries dividing these phases are analytically obtained with theoretical models, elucidating the nonequilibrium physics and criteria for the transition between different phases. Furthermore, we numerically and experimentally show three distinct dynamic regimes related to the interplay between necking and wrapping during the endocytosis process of active particles, which strikingly contrast the regimes for passive particles. Overall, these findings could be useful for sharpening the understanding of basic principles underlying biological issues related to the safe and efficient biomedical applications of such emerging matters.


Subject(s)
Cell Membrane , Endocytosis , Cell Membrane/metabolism , Cell Membrane/chemistry , Biological Transport , Humans , Models, Biological , Particle Size
8.
Nature ; 633(8028): 182-188, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39112712

ABSTRACT

Taurine is a conditionally essential micronutrient and one of the most abundant amino acids in humans1-3. In endogenous taurine metabolism, dedicated enzymes are involved in the biosynthesis of taurine from cysteine and in the downstream metabolism of secondary taurine metabolites4,5. One taurine metabolite is N-acetyltaurine6. Levels of N-acetyltaurine are dynamically regulated by stimuli that alter taurine or acetate flux, including endurance exercise7, dietary taurine supplementation8 and alcohol consumption6,9. So far, the identities of the enzymes involved in N-acetyltaurine metabolism, and the potential functions of N-acetyltaurine itself, have remained unknown. Here we show that the body mass index associated orphan enzyme phosphotriesterase-related (PTER)10 is a physiological N-acetyltaurine hydrolase. In vitro, PTER catalyses the hydrolysis of N-acetyltaurine to taurine and acetate. In mice, PTER is expressed in the kidney, liver and brainstem. Genetic ablation of Pter in mice results in complete loss of tissue N-acetyltaurine hydrolysis activity and a systemic increase in N-acetyltaurine levels. After stimuli that increase taurine levels, Pter knockout mice exhibit reduced food intake, resistance to diet-induced obesity and improved glucose homeostasis. Administration of N-acetyltaurine to obese wild-type mice also reduces food intake and body weight in a GFRAL-dependent manner. These data place PTER into a central enzymatic node of secondary taurine metabolism and uncover a role for PTER and N-acetyltaurine in body weight control and energy balance.


Subject(s)
Body Weight , Eating , Hydrolases , Obesity , Taurine , Animals , Female , Humans , Male , Mice , Eating/physiology , Glucose/metabolism , Homeostasis , Hydrolases/deficiency , Hydrolases/genetics , Hydrolases/metabolism , Hydrolysis , Kidney/metabolism , Liver/metabolism , Liver/enzymology , Mice, Inbred C57BL , Mice, Knockout , Obesity/metabolism , Obesity/enzymology , Taurine/metabolism , Taurine/analogs & derivatives , Carrier Proteins/genetics , Carrier Proteins/metabolism , Acetic Acid/metabolism , Exercise , Body Mass Index , Weight Loss , Secondary Metabolism , Energy Metabolism , Brain Stem/metabolism
9.
Artif Intell Med ; 156: 102950, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39163727

ABSTRACT

Artificial intelligence is constantly revolutionizing biomedical research and healthcare management. Disease comorbidity is a major threat to the quality of life for susceptible groups, especially middle-aged and elderly patients. The presence of multiple chronic diseases makes precision diagnosis challenging to realize and imposes a heavy burden on the healthcare system and economy. Given an enormous amount of accumulated health data, machine learning techniques show their capability in handling this puzzle. The present study conducts a review to uncover current research efforts in applying these methods to understanding comorbidity mechanisms and making clinical predictions considering these complex patterns. A descriptive metadata analysis of 791 unique publications aims to capture the overall research progression between January 2012 and June 2023. To delve into comorbidity-focused research, 61 of these scientific papers are systematically assessed. Four predictive analytics of tasks are detected: disease comorbidity data extraction, clustering, network, and risk prediction. It is observed that some machine learning-driven applications address inherent data deficiencies in healthcare datasets and provide a model interpretation that identifies significant risk factors of comorbidity development. Based on insights, both technical and practical, gained from relevant literature, this study intends to guide future interests in comorbidity research and draw conclusions about chronic disease prevention and diagnosis with managerial implications.


Subject(s)
Comorbidity , Machine Learning , Humans , Chronic Disease , Preventive Health Services/methods , Risk Assessment/methods , Risk Factors
10.
Sensors (Basel) ; 24(16)2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39204981

ABSTRACT

For the purpose of improving performance and reducing the fabrication difficulty of terahertz traveling wave tubes (TWTs), this paper proposes a novel single-section high-gain slow wave structure (SWS), which is named the symmetrical quasi-synchronous step-transition (SQSST) folded waveguide (FW). The SQSST-FW SWS has an artificially designed quasi-synchronous region (QSR) to suppress self-oscillations for sustaining a high gain in an untruncated circuit. Simultaneously, a symmetrical design can improve the efficiency performance to some extent. A prototype of the SQSST-FW SWS for 650 GHz TWTs is designed based on small-signal analysis and numerical simulation. The simulation results indicate that the maximum saturation gain of the designed 650 GHz SQSST-FW TWT is 39.1 dB in a 34.3 mm slow wave circuit, occurring at the 645 GHz point when a 25.4 kV 15 mA electron beam and a 0.43 mW sinusoidal input signal are applied. In addition, a maximum output power exceeding 4 W is observed at the 648 GHz point using the same beam with an increased input power of around 2.8 mW.

11.
Neurosci Bull ; 2024 Aug 04.
Article in English | MEDLINE | ID: mdl-39097850

ABSTRACT

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by progressive axonopathy, jointly leading to the dying back of the motor neuron, disrupting both nerve signaling and motor control. In this review, we highlight the roles of axonopathy in ALS progression, driven by the interplay of multiple factors including defective trafficking machinery, protein aggregation, and mitochondrial dysfunction. Dysfunctional intracellular transport, caused by disruptions in microtubules, molecular motors, and adaptors, has been identified as a key contributor to disease progression. Aberrant protein aggregation involving TDP-43, FUS, SOD1, and dipeptide repeat proteins further amplifies neuronal toxicity. Mitochondrial defects lead to ATP depletion, oxidative stress, and Ca2+ imbalance, which are regarded as key factors underlying the loss of neuromuscular junctions and axonopathy. Mitigating these defects through interventions including neurotrophic treatments offers therapeutic potential. Collaborative research efforts aim to unravel ALS complexities, opening avenues for holistic interventions that target diverse pathological mechanisms.

12.
Adv Sci (Weinh) ; 11(31): e2400623, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38898767

ABSTRACT

Solar-driven interfacial evaporation is an emerging desalination technology that can potentially relieve the freshwater scarcity issue. To obtain high and continuous evaporation rates for all-weather, chemically engineered structural materials have been widely explored for simultaneous photothermal and electrothermal conversion. However, many previously reported fabrication processes involve poor integration and considerable energy loss. Herein, a scalable photo-electro-thermal textile is proposed to enable high efficiency, long-term salt rejection, and solar-driven desalination. Specifically, the photo-electro-thermal yarns with a core (commercial electric wire)-shell (polypyrrole-decorated Tencel) structure realize the integration of electrothermal and photothermal conversion. The wrapping eccentricity of 1.53 mm and pitch of 3 T cm-1 for the electric wire are rationally regulated to achieve a high surface temperature of over 52 °C at a 3 V DC input. As a result, exceptional and stable evaporation rates of 5.57 kg m-2 h-1 (pure water) and 4.89 kg m-2 h-1 (3.5 wt.% brine) under 1 kW m-2·radiation with a 3 V input voltage are realized. Practical application shows that the textiles can achieve high water collection of over 46 kg m-2 d-1 over the whole day of operation. The constructed photo-electro-thermal textile-based evaporator provides an effective method for commercial and scalable photo-electro-thermal conversion to achieve high-performance and salt-resistant solar-driven desalination.

13.
World J Clin Cases ; 12(17): 3235-3242, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38898830

ABSTRACT

BACKGROUND: This reported procedure combines the orthopedic surgical robot with the unilateral biportal endoscopy-lumbar interbody fusion (UBE-LIF), utilizing the UBE's wide viewing field and operating space to perform minimally invasive decompressive fusion of the lesioned segment, and the orthopedic surgical robot's intelligence and precision to perform percutaneous pedicle screw placement. The advancement of this procedure lies in the superposition of advantages and offsetting disadvantages of the two new technologies, and the maximum effect of treatment is achieved with maximum minimization of invasiveness and precision under the monitoring of imaging instruments to maximize the benefit of patients, and this review reports a case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE for reference. CASE SUMMARY: A 44-year-old patient presented to our hospital. Combining various clinical data, we diagnosed the patient with lumbar disc herniation with radiculopathy, lumbar spondylolisthesis, and lumbar spinal stenosis. We developed a surgical plan of "UBE decompression + UBE-LIF + orthopedic surgery robot-assisted percutaneous pedicle screw implantation for internal fixation". The results were satisfactory. CONCLUSION: We present an extremely rare case of multiple-segment lumbar decompression and fusion surgery for lumbar disc herniation via robot-assisted UBE and achieved good results. Therefore, the technique is worthy of clinical promotion.

14.
Elife ; 122024 Jun 06.
Article in English | MEDLINE | ID: mdl-38842277

ABSTRACT

Flexible responses to sensory stimuli based on changing rules are critical for adapting to a dynamic environment. However, it remains unclear how the brain encodes and uses rule information to guide behavior. Here, we made single-unit recordings while head-fixed mice performed a cross-modal sensory selection task where they switched between two rules: licking in response to tactile stimuli while rejecting visual stimuli, or vice versa. Along a cortical sensorimotor processing stream including the primary (S1) and secondary (S2) somatosensory areas, and the medial (MM) and anterolateral (ALM) motor areas, single-neuron activity distinguished between the two rules both prior to and in response to the tactile stimulus. We hypothesized that neural populations in these areas would show rule-dependent preparatory states, which would shape the subsequent sensory processing and behavior. This hypothesis was supported for the motor cortical areas (MM and ALM) by findings that (1) the current task rule could be decoded from pre-stimulus population activity; (2) neural subspaces containing the population activity differed between the two rules; and (3) optogenetic disruption of pre-stimulus states impaired task performance. Our findings indicate that flexible action selection in response to sensory input can occur via configuration of preparatory states in the motor cortex.


Subject(s)
Motor Cortex , Animals , Mice , Motor Cortex/physiology , Male , Somatosensory Cortex/physiology , Neurons/physiology , Female , Optogenetics , Behavior, Animal/physiology
15.
Sensors (Basel) ; 24(12)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38931492

ABSTRACT

A staggered vane-shaped slot-line slow-wave structure (SV-SL SWS) for application in W-band traveling wave tubes (TWTs) is proposed in this article. In contrast to the conventional slot-line SWSs with dielectric substrates, the proposed SWS consists only of a thin metal sheet inscribed with periodic grooves and two half-metal enclosures, which means it can be easily manufactured and assembled and has the potential for mass production. This SWS not only solves the problem of the dielectric loading effect but also improves the heat dissipation capability of such structures. Meanwhile, the SWS design presented here covers a -15 dB S11 frequency range from 87.5 to 95 GHz. The 3-D simulation for a TWT based on the suggested SWS is also investigated. Under dual-electron injection conditions with a total voltage of 17.2 kV and a total current of 0.3 A, the maximum output power at 90 GHz is 200 W, with a 3 dB bandwidth up to 4 GHz. With a good potential for fabrication using microfabrication techniques, this structure can be a good candidate for millimeter-wave TWT applications.

16.
NPJ Precis Oncol ; 8(1): 133, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38879686

ABSTRACT

Neurofibromatosis type 2 (NF2) is a tumor suppressor gene implicated in various tumors, including mesothelioma, schwannomas, and meningioma. As a member of the ezrin, radixin, and moesin (ERM) family of proteins, merlin, which is encoded by NF2, regulates diverse cellular events and signalling pathways, such as the Hippo, mTOR, RAS, and cGAS-STING pathways. However, the biological role of NF2 in tumorigenesis has not been fully elucidated. Furthermore, cross-cancer mutations may exert distinct biological effects on tumorigenesis and treatment response. In addition to the functional inactivation of NF2, the codeficiency of other genes, such as cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B), BRCA1-associated protein-1 (BAP1), and large tumor suppressor 2 (LATS2), results in unique tumor characteristics that should be considered in clinical treatment decisions. Notably, several recent studies have explored the metabolic and immunological features associated with NF2, offering potential insights into tumor biology and the development of innovative therapeutic strategies. In this review, we consolidate the current knowledge on NF2 and examine the potential connection between cancer metabolism and tumor immunity in merlin-deficient malignancies. This review may provide a deeper understanding of the biological roles of NF2 and guide possible therapeutic avenues.

17.
JTO Clin Res Rep ; 5(5): 100672, 2024 May.
Article in English | MEDLINE | ID: mdl-38715965

ABSTRACT

Introduction: Malignant pleural mesothelioma (MPM) is a rare and universally lethal malignancy with limited treatment options. Immunotherapy with immune checkpoint inhibitors (ICIs) has recently been approved for unresectable MPM, but response to ICIs is heterogeneous, and reliable biomarkers for prospective selection of appropriate subpopulations likely to benefit from ICIs remain elusive. Methods: We performed multiscale integrative analyses of published primary tumor data set from The Cancer Genome Atlas (TCGA) and the French cohort E-MTAB-1719 to unravel the tumor immune microenvironment of MPM deficient in BAP1, one of the most frequently mutated tumor suppressor genes (TSGs) in the disease. The molecular profiling results were validated in independent cohorts of patients with MPM using immunohistochemistry and multiplex immunohistochemistry. Results: We revealed that BAP1 deficiency enriches immune-associated pathways in MPM, leading to increased mRNA signatures of interferon alfa/gamma response, activating dendritic cells, immune checkpoint receptors, and T-cell inflammation. This finding was confirmed in independent patient cohorts, where MPM tumors with low BAP1 levels are associated with an inflammatory tumor immune microenvironment characterized by increased exhausted precursor T-cells and macrophages but decreased myeloid-derived suppressor cells (MDSCs). In addition, BAP1low MPM cells are in close proximity to T cells and therefore can potentially be targeted with ICIs. Finally, we revealed that BAP1-proficient MPM is associated with a hyperactive mitogen-activated protein kinase (MAPK) pathway and may benefit from treatment with MEK inhibitors (MEKis). Conclusion: Our results suggest that BAP1 plays an immunomodulatory role in MPM and that BAP1-deficient MPM may benefit from immunotherapy, which merits further clinical investigation.

18.
Environ Pollut ; 351: 124059, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38703979

ABSTRACT

The hazards of man-made chiral compounds are of great public concern, with reports of worrying stereoselective compounds and an urgent need to assess their transport. This study evaluated the transport of 2-arylpropionic acid derivatives enantiomers (2-APA) in porous media under a variety of solution chemistry conditions via column packing assays. The results revealed the introduction of Malic acid (MA) enantiomers enhanced the mobility of 2-APA enantiomers, but the enhancement effect was different for different 2-APA enantiomers. Batch sorption experiments confirmed that the MA enantiomers occupied the sorption site of the quartz sand, thus reducing the deposition of the 2-APA enantiomer. Homo- or heterochirality between 2-APA and MA dominates the transport of 2-APA enantiomers, with homochirality between them triggering stronger retention and vice versa. Further evaluating the effect of solution chemistry conditions on the transport of 2-APA enantiomers, increased ionic strength attenuated the mobility of 2-APA enantiomers, whereas introduced coexisting cations enhanced the retention of 2-APA enantiomers in the column. The redundancy analyses corroborated these solution chemistry conditions were negatively correlated with the transport of 2-APA enantiomers. The coupling of pH and these conditions reveals electrostatic forces dominate the transport behavior and stereoselective interactions of 2-APA enantiomers. Distinguishing the transport of enantiomeric pair helps to understand the difference in stereoselectivity of enantiomers and promises to remove the more hazardous one.


Subject(s)
Propionates , Stereoisomerism , Propionates/chemistry , Porosity , Adsorption , Malates/chemistry , Hydrogen-Ion Concentration
19.
J Transl Med ; 22(1): 518, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816750

ABSTRACT

BACKGROUND: Dysbiosis of the gut microbiota is pivotal in Crohn's disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown. METHODS: CD patients were divided into an HBOT group (n = 10) and a control group (n = 10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16 S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed. RESULTS: HBOT significantly reduced the level of C-reactive protein (CRP) (80.79 ± 42.05 mg/L vs. 33.32 ± 18.31 mg/L, P = 0.004) and the Crohn's Disease Activity Index (CDAI) (274.87 ± 65.54 vs. 221.54 ± 41.89, P = 0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P = 0.089) and remission (20%vs.50%, P = 0.160) at week 4. CONCLUSIONS: HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605 .


Subject(s)
Crohn Disease , Dysbiosis , Gastrointestinal Microbiome , Hyperbaric Oxygenation , Inflammation , Crohn Disease/therapy , Crohn Disease/microbiology , Humans , Dysbiosis/therapy , Dysbiosis/microbiology , Animals , Female , Male , Inflammation/therapy , Adult , Intestines/microbiology , Middle Aged , Fecal Microbiota Transplantation , Mice , Mice, Inbred C57BL , Young Adult
20.
ACS Sens ; 9(5): 2575-2584, 2024 05 24.
Article in English | MEDLINE | ID: mdl-38695880

ABSTRACT

Although electronic textiles that can detect external stimuli show great promise for fire rescue, existing firefighting clothing is still scarce for simultaneously integrating reliable early fire warning and real-time motion sensing, hardly providing intelligent personal protection under complex high-temperature conditions. Herein, we introduce an "all-in-one" hierarchically sandwiched fabric (HSF) sensor with a simultaneous temperature and pressure stimulus response for developing intelligent personal protection. A cross-arranged structure design has been proposed to tackle the serious mutual interference challenge during multimode sensing using two separate sets of core-sheath composite yarns and arrayed graphene-coated aerogels. The functional design of the HSF sensor not only possesses wide-range temperature sensing from 25 to 400 °C without pressure disturbance but also enables highly sensitive pressure response with good thermal adaptability (up to 400 °C) and wide pressure detection range (up to 120 kPa). As a proof of concept, we integrate large-scalable HSF sensors onto conventional firefighting clothing for passive/active fire warning and also detecting spatial pressure and temperature distribution when a firefighter is exposed to high-temperature flames, which may provide a useful design strategy for the application of intelligent firefighting protective clothing.


Subject(s)
Pressure , Temperature , Textiles , Textiles/analysis , Humans , Fires , Firefighters , Protective Clothing , Graphite/chemistry , Wearable Electronic Devices
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