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1.
Nat Commun ; 15(1): 7746, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39232011

ABSTRACT

Beige fat activation involves a fuel switch to fatty acid oxidation following chronic cold adaptation. Mitochondrial acyl-CoA synthetase long-chain family member 1 (ACSL1) localizes in the mitochondria and plays a key role in fatty acid oxidation; however, the regulatory mechanism of the subcellular localization remains poorly understood. Here, we identify an endosomal trafficking component sortilin (encoded by Sort1) in adipose tissues that shows dynamic expression during beige fat activation and facilitates the translocation of ACSL1 from the mitochondria to the endolysosomal pathway for degradation. Depletion of sortilin in adipocytes results in an increase of mitochondrial ACSL1 and the activation of AMPK/PGC1α signaling, thereby activating beige fat and preventing high-fat diet (HFD)-induced obesity and insulin resistance. Collectively, our findings indicate that sortilin controls adipose tissue fatty acid oxidation by substrate fuel selection during beige fat activation and provides a potential targeted approach for the treatment of metabolic diseases.


Subject(s)
Adaptor Proteins, Vesicular Transport , Adipocytes , Coenzyme A Ligases , Diet, High-Fat , Energy Metabolism , Mitochondria , Animals , Male , Mice , 3T3-L1 Cells , Adaptor Proteins, Vesicular Transport/metabolism , Adaptor Proteins, Vesicular Transport/genetics , Adipocytes/metabolism , Adipose Tissue, Beige/metabolism , Coenzyme A Ligases/metabolism , Coenzyme A Ligases/genetics , Fatty Acids/metabolism , Insulin Resistance , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/metabolism , Obesity/metabolism , Obesity/genetics , Oxidation-Reduction , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Protein Transport , Signal Transduction , Thermogenesis
2.
PLoS One ; 19(9): e0304485, 2024.
Article in English | MEDLINE | ID: mdl-39226294

ABSTRACT

OBJECTIVE: This study aims to explore the impact of Nesfatin-1 on type 2 diabetic erectile dysfunction (T2DMED) and its underlying mechanism in regulating the phenotypic switching of corpus cavernosum smooth muscle cells (CCSMCs). METHODS: Twenty-four 4-week-old male C57 wild-type mice were randomly assigned to the control group, model group, and Nesfatin-1 treatment group. Monitoring included body weight, blood glucose levels, and penile cavernous pressure (ICP). Histochemistry and Western blot analyses were conducted to assess the expressions of α-SMA, OPN, and factors related to the PI3K/AKT/mTOR signaling pathway. CCSMCs were categorized into the control group, high glucose and high oleic acid group (GO group), Nesfatin-1 treatment group (GO+N group), sildenafil positive control group (GO+S group), and PI3K inhibitor group (GO+N+E group). Changes in phenotypic markers, cell morphology, and the PI3K/AKT/mTOR signaling pathway were observed in each group. RESULTS: (1) Nesfatin-1 significantly ameliorated the body size, body weight, blood glucose, glucose tolerance, and insulin resistance in T2DMED mice. (2) Following Nesfatin-1 treatment, the ICP/MSBP ratio and the peak of the ICP curve demonstrated a significant increase. (3) Nesfatin-1 significantly enhanced smooth muscle and reduced collagen fibers in the corpus cavernosum. (4) Nesfatin-1 notably increased α-SMA expression and decreased OPN expression in CCSMCs. (5) Nesfatin-1 elevated PI3K, p-AKT/AKT, and p-mTOR/mTOR levels in penile cavernous tissue. CONCLUSIONS: Nesfatin-1 not only effectively improves body weight and blood glucose levels in diabetic mice but also enhances erectile function and regulates the phenotypic switching of corpus cavernosum smooth muscle. The potential mechanism involves Nesfatin-1 activating the PI3K/AKT/mTOR signaling pathway to induce the conversion of CCSMCs to a contractile phenotype.


Subject(s)
Erectile Dysfunction , Myocytes, Smooth Muscle , Nucleobindins , Penis , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Animals , Male , Erectile Dysfunction/metabolism , Erectile Dysfunction/drug therapy , Erectile Dysfunction/etiology , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , TOR Serine-Threonine Kinases/metabolism , Mice , Myocytes, Smooth Muscle/metabolism , Nucleobindins/metabolism , Penis/metabolism , Phenotype , Mice, Inbred C57BL , Osteopontin/metabolism , Calcium-Binding Proteins/metabolism , Actins/metabolism , DNA-Binding Proteins/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/complications , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/complications
3.
Plants (Basel) ; 13(17)2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39273992

ABSTRACT

Far-red lights (FRs), with a wavelength range between 700 and 800 nm, have substantial impacts on plant growth, especially horticultural crops. Previous studies showed conflicting results on the effects of FRs on vegetable growth and quality. Therefore, we conducted a meta-analysis on the influence of FRs on vegetable growth, aiming to provide a comprehensive overview of their effects on the growth and nutritional indicators of vegetables. A total of 207 independent studies from 55 literature sources were analyzed. The results showed that FR treatment had significant effects on most growth indicators, including increasing the fresh weight (+25.27%), dry weight (+21.99%), plant height (+81.87%), stem diameter (+12.91%), leaf area (+18.57%), as well as reducing the content of chlorophyll (-11.88%) and soluble protein (-11.66%), while increasing soluble sugar content (+19.12%). Further subgroup analysis based on various factors revealed significant differences in the effects of FR on different physiological indicators, such as FR intensity, plant species, duration of FR exposure, and the ratio of red light to FR. In general, moderate FR treatment is beneficial for vegetable growth. This study provides important references and guidelines for optimizing the application of FR in the future.

4.
Article in English | MEDLINE | ID: mdl-39276333

ABSTRACT

Lithium difluoro(oxalate) borate (LiDFOB) contributes actively to cathode-electrolyte interface (CEI) formation, particularly safeguarding high-voltage cathode materials. However, LiNixCozMnyO2-based batteries benefit from the LiDFOB and its derived CEI only with appropriate electrolyte design while a comprehensive understanding of the underlying interfacial mechanisms remains limited, which makes the rational design challenging. By performing ab initio calculations, the CEI evolution on the LiNi0.8Co0.1Mn0.1O2 has been investigated. The findings demonstrate that LiDFOB readily adheres to the cathode via semidissociative configuration, which elevates the Li deintercalation voltage and remains stable in solvent. Electrochemical processes are responsible for the subsequent cleavage of B-F and B-O bonds, while the B-F bond cleavage leading to LiF formation is dominant in the presence of adequate Li+ with a substantial Li intercalation energy. Thus, impregnation is established as an effective method to regulate the conversion channel for efficient CEI formation, which not only safeguards the cathode's structure but also counters electrolyte decomposition. Consequently, in comparison to utilizing LiDFOB as an electrolyte additive, employing LiDFOB impregnation in the NCM811/Li cell yields significantly improved cycling stability for over 2000 h.

5.
iScience ; 27(9): 110785, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39286503

ABSTRACT

Supernumerary teeth are common developmental anomalies of dentition. However, the factors and mechanisms driving their formation remain largely unknown. Here, we report that conditional knockout of Fst, encoding an antagonist for the transforming growth factor ß (TGF-ß) signaling pathway, in both oral epithelium and mesenchyme of mice (Fst CKO ) led to supernumerary upper incisor teeth, arising from the lingual dental epithelium of the native teeth and preceded by an enlarged and split lingual cervical loop. Fst-deficiency greatly activated TGF-ß signaling in developing maxillary incisor teeth, associated with increased epithelium cell proliferation. Moreover, Fst CKO teeth exhibited increased expression of Tbx1, Sp6, and Sox2, which were identified as direct targets of TGF-ß/SMAD2 signaling. Finally, we show that upregulation of Tbx1 in response to Fst-deficiency was largely responsible for the formation of extra teeth in Fst CKO mice. Taken together, our investigation indicates a novel role for Fst in controlling murine tooth number by restricting TGF-ß signaling.

6.
Carbohydr Polym ; 346: 122570, 2024 Dec 15.
Article in English | MEDLINE | ID: mdl-39245477

ABSTRACT

This study investigated the influence of Konjac Glucomannan (KGM) with varying degrees of polymerization (DKGMx) on the gelatinization and retrogradation characteristics of wheat starch, providing new insights into starch-polysaccharide interactions. This research uniquely focuses on the effects of DKGMx, utilizing multidisciplinary approaches including Rapid Visco Analysis (RVA), Differential Scanning Calorimetry (DSC), rheological testing, Low-Field Nuclear Magnetic Resonance (LF-NMR), and molecular simulations to assess the effects of DKGMx on gelatinization temperature, viscosity, structural changes post-retrogradation, and molecular interactions. Our findings revealed that higher degrees of polymerization (DP) of DKGMx significantly enhanced starch's pasting viscosity and stability, whereas lower DP reduced viscosity and interfered with retrogradation. High DP DKGMx promoted retrogradation by modifying moisture distribution. Molecular simulations revealed the interplay between low DP DKGMx and starch molecules. These interactions, characterized by increased hydrogen bonds and tighter binding to more starch chains, inhibited starch molecular rearrangement. Specifically, low DP DKGMx established a dense hydrogen bond network with starch, significantly restricting molecular mobility and rearrangement. This study provides new insights into the role of the DP of DKGMx in modulating wheat starch's properties, offering valuable implications for the functional improvement of starch-based foods and advancing starch science.


Subject(s)
Mannans , Polymerization , Starch , Triticum , Triticum/chemistry , Starch/chemistry , Viscosity , Mannans/chemistry , Hydrogen Bonding , Rheology , Molecular Dynamics Simulation , Calorimetry, Differential Scanning
7.
J Trace Elem Med Biol ; 86: 127512, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39232337

ABSTRACT

BACKGROUND: Prolonged exposure to excessive arsenic (As) and its compounds can cause damage to multiple systems, including respiratory, cardiovascular, immune, nervous, and endocrine systems. Manifestations include changes in skin pigmentation, excessive keratosis on palms and soles, gastrointestinal symptoms, and anemia. The liver as an important detoxification organ of the body, is a significant target organ for arsenic toxicity, and liver diseases are common. So far, the molecular mechanism has not been fully elucidated. Evidence suggests that taurodeoxycholic acid (TUDCA) has a protective role in arsenic-induced liver injury. This study aims to reveal potential target genes at the transcriptional level following TUDCA intervention, providing insights for the intervention of arsenic-induced liver injury. METHODS: The TUDCA intervention model of arsenic liver injury in C57BL/6 N mice was established. The experiment was divided into two phases and lasted for 24 weeks. The phase I trial (12 weeks) was divided into control, low, middle and high groups according to the dose of As. The phaseⅡtrial (12 weeks) was administered in combination with 10 mg/L sodium arsenite (the first stage high arsenic group) and TUDCA, so subsequent groups was named with H indicating high arsenic. Divide into four groups: control group(C), TUDCA solvent control group(H-Vehicle), TUDCA combined with As group(H-TUDCA), arsenic group (As). As was ingested through free water and TUDCA was administered to mice by gavage at a dose of 0.1 mL/10 g.b.w (100 mg/kg) once a day for 12 weeks. The differential expression gene (DEG) profile was obtained from the second batch of mouse liver tissues by RNA sequencing technology. Comparative transcriptomic analysis methods were used to identify co-varying DEGs between arsenic induction and TUDCA intervention, along with their associated pathways. QRT-PCR was utilized for validation. RESULTS: Transcriptome results showed that 487 DEGs were identified after arsenic induction. TUDCA intervention identified 231 DEGs (p-values < 0.05 and | log2(fold change) | > 1). The comparison of "AS vs C" and "H_TUDCA vs AS" identified 65 covariant DEGs, and further screened the TUDCA pathways and related genes among these genes,six pathways and 11 genes (Ccl21a, Ccr7, Mdm2, Slc2a4, Akr1b7, Pnpla3, Dusp8, Hspa1a, Cyp7a1, Cybrd1, Trpm6) were obtained. Next, we screened for covariant DEGs among the top 50 potential hub genes in arsenic-induced DEGS, and obtained 7 (Hbb-bs, Hspa1a, Mdm2, Slc2a4, Ptk6, Egr1, and Dusp8). Finally, the intersection of Hub gene and pathway gene was selected as the target genes Dusp8, Hspa1a, Mdm2 and Slc2a4. The sequencing results showed that the mRNA expressions of Dusp8, Hspa1a and Mdm2 were significantly increased after arsenic induction, while the expression of Slc2a4 was significantly decreased (P<0.05). Conversely, TUDCA intervention reversed these DEGs changes, consistent with QRT-PCR validation results. CONCLUSION: This study contributes to understanding the potential health effects of arsenic-induced liver injury, identifying new potential targets, and providing references for TUDCA intervention.

8.
Front Immunol ; 15: 1440819, 2024.
Article in English | MEDLINE | ID: mdl-39257586

ABSTRACT

Background: Natural infection or vaccination have provided robust immune defense against SARS-CoV-2 invasion, nevertheless, Omicron variants still successfully cause breakthrough infection, and the underlying mechanisms are poorly understood. Methods: Sequential blood samples were continuously collected at different time points from 252 volunteers who were received the CanSino Ad5-nCoV (n= 183) vaccine or the Sinovac CoronaVac inactivated vaccine (n= 69). The anti-SARS-CoV-2 prototype and Omicron BA.5.2 as well as XBB.1.16 variant neutralizing antibodies (Nab) in sera were detected by ELISA. Sera were also used to measure pseudo and live virus neutralization assay. The associations between the anti-prototype Nab levels and different HLA-ABC alleles were analyzed using artificial intelligence (AI)-deep learning techniques. The frequency of B cells in PBMCs was investigated by flow cytometry assay (FACs). Results: Individuals carrying the HLA-B*15 allele manifested the highest concentrations of anti-SARS-CoV-2 prototype Nab after vax administration. Unfortunately, these volunteers are more susceptible to Omicron BA.5.2 breakthrough infection due to their sera have poorer anti-BA.5.2 Nab and lower levels of viral neutralization efficacy. FACs confirmed that a significant decrease in CD19+CD27+RBD+ memory B cells in these HLA-B*15 population compared to other cohorts. Importantly, generating lower concentrations of cross-reactive anti-XBB.1.16 Nab post-BA.5.2 infection caused HLA-B*15 individuals to be further infected by XBB.1.16 variant. Conclusions: Individuals carrying the HLA-B*15 allele respond better to COVID-19 vax including the CanSino Ad5-nCoV and the Sinovac CoronaVac inactivated vaccines, but are more susceptible to Omicron variant infection, thus, a novel vaccine against this population is necessary for COVID-19 pandemic control in the future.


Subject(s)
Alleles , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , Male , Adult , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , Middle Aged , HLA-B Antigens/genetics , HLA-B Antigens/immunology
9.
Nat Commun ; 15(1): 7676, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39227619

ABSTRACT

Vertical field effect transistor (VFET), in which the semiconductor is sandwiched between source/drain electrodes and the channel length is simply determined by the semiconductor thickness, has demonstrated promising potential for short channel devices. However, despite extensive efforts over the past decade, scalable methods to fabricate ultra-short channel VFETs remain challenging. Here, we demonstrate a layer-by-layer transfer process of large-scale indium gallium zinc oxide (IGZO) semiconductor arrays and metal electrodes, and realize large-scale VFETs with ultra-short channel length and high device performance. Within this process, the oxide semiconductor could be pre-deposited on a sacrificial wafer, and then physically released and sandwiched between metals, maintaining the intrinsic properties of ultra-scaled vertical channel. Based on this lamination process, we realize 2 inch-scale VFETs with channel length down to 4 nm, on-current over 800 A/cm2, and highest on-off ratio up to 2 × 105, which is over two orders of magnitude higher compared to control samples without laminating process. Our study not only represents the optimization of VFETs performance and scalability at the same time, but also offers a method of transfer large-scale oxide arrays, providing interesting implication for ultra-thin vertical devices.

10.
New Phytol ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39155709

ABSTRACT

Understanding limiting factors of phenotypic plasticity is essential given its critical role in shaping biological adaptation and evolution in changing environments. It has been proposed that the pattern of phenotypic correlation could constrain trait plasticity. However, the interplay between phenotypic plasticity and integration has remained contentious. We experimentally simulated climate warming in juveniles of three subalpine tree species by exposing them to three-year in situ open-top chambers (OTCs), and then measured functional plasticity of 72 eco-physiological traits to evaluate whether phenotypic integration constituted an intrinsic constraint to plasticity. We also tested the relationship between the differences in plasticity and maintenance in trait integration. Phenotypic plasticity was positively associated with integration in deciduous tree species under warming. The difference in the plasticity of two paired traits could predict their integration in different environments, where traits displaying more similar plasticity were more likely to be correlated. Our study showed no indication that phenotypic integration constrained plasticity. More importantly, we demonstrated that differential plasticity between traits might result in a notable reorganization of the trait associations, and that warming commonly induced a tighter phenotype. Our study provides new insights into the interplay between phenotypic plasticity and integration in subalpine trees under climate warming.

11.
Article in English | MEDLINE | ID: mdl-39152833

ABSTRACT

Background Unilateral naevoid telangiectasia (UNT) is a rare disease with only sporadic cases reported. The pathogenesis remains elusive and especially in paediatric patients, effective and safe treatment is still uncertain. Objectives The purpose of this study was to summarise the clinical characteristics of UNT, explore the possible pathogenesis and evaluate the efficacy and safety of pulsed dye laser (PDL) therapy. Materials and Methods The epidemiological data, clinical manifestations, laboratory tests and pathological features of paediatric patients with UNT were retrospectively reviewed. PDL treatment was done on some of the patients. Clinical documents and patient images before and after treatment were assessed to evaluate efficacy and adverse events. Results Most of the cases (9/11) presented with unilateral lesions. The laboratory results of all the 11 cases were normal. Histological examination in six cases revealed multiple, dilated veins in the reticular dermis. Vascular endothelial growth factor (VEGF) staining was positive, whereas oestrogen receptor staining was negative. Nine cases were treated with PDL which was shown to be effective and safe. Conclusion UNT has typical clinical manifestations. The pathogenesis of this disease could be linked to VEGF; however, more research and confirmation are needed. PDL is an effective and safe treatment for UNT.

12.
Chemosphere ; 364: 142979, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39098348

ABSTRACT

Wet distillers grains, as a waste biomass with a large annual output, pose a threat to the environment and food industry. Herein, artificial humic acid (AHA) was first produced from wet distillers grains in a dual-stage microwave-assisted hydrothermal process. The influence of temperature on AHA's characteristics was investigated and compared with natural humic acid (NHA) and standard humic acid (SHA). A high yield of AHA at 20.6% was obtained at 200 °C with a total reaction time of 1 h, which is 1.8-3.1 times that obtained in traditional single-stage hydrothermal process. Increasing the reaction temperature induced the formation of phenolic hydroxyl in AHA. AHA was rich in aromaticity and carboxylic acid structure, showing similar spectral characteristics to NHA. The distribution of molecular weight of AHA was mostly 5797 Da, which decreased by 15% compared to SHA. The optimal concentration of AHA to promote seedling growth was 0.2 g/L, and the root length was 2.0 times that of the control. The microwave hydrothermal process is a facile and efficient approach to preparing AHA from waste biomass with high moisture content.

13.
J Acoust Soc Am ; 156(2): 774-782, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39110637

ABSTRACT

Underwater noise pollution from pile driving is now attracting increasing attention. However, most of the current numerical and semi-analytical models for predicting the noise are still expensive and time-consuming, and the near-field noise and far-field noise have to be obtained from different models. This paper proposes an efficient semi-analytical solution for predicting underwater noise in both near field and far field with only one model, whose computational efficiency is orders of magnitude higher than that of the finite element model. It is the first time that the Baranov-Novak thin-layer model for soil-pile interaction has been extended to the subject of underwater noise prediction during pile installation, taking into account pile-fluid-soil interaction. The solutions are obtained using the Laplace transform and the variable separation method. By comparing the prediction results with the five reported research cases, it is shown that the error of the proposed model is within reasonable limits for both near-field and far-field noise predictions.

14.
Ann Hepatol ; : 101536, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39151890

ABSTRACT

INTRODUCTION AND OBJECTIVES: Radioresistance is a common problem in the treatment of many cancers, including hepatocellular carcinoma (HCC). Previous studies have shown that circROBO1 is highly expressed in HCC tissues and acts as a cancer promoter to accelerate the malignant progression of HCC. However, the role and mechanism of circROBO1 in HCC radioresistance remain unclear. MATERIALS AND METHODS: CircROBO1, microRNA (miR)-136-5p and RAD21 expression levels were analyzed by quantitative real-time PCR. Cell function and radioresistance were evaluated by colony formation assay, cell counting kit 8 assay, EdU assay and flow cytometry. Protein expression was determined using western blot analysis. RNA interaction was analyzed by dual-luciferase reporter assay and RNA pull-down assay. In vivo experiments were performed by constructing mice xenograft models. RESULTS: CircROBO1 was highly expressed in HCC, and its knockdown inhibited HCC cell proliferation and promoted apoptosis to enhance cell radiosensitivity. On the mechanism, circROBO1 could serve as miR-136-5p sponge to positively regulate RAD21. MiR-136-5p inhibitor or RAD21 overexpression reversed the regulation of circROBO1 knockdown on the radiosensitivity of HCC cells. Also, circROBO1 interference improved the radiosensitivity of HCC tumors in vivo. CONCLUSIONS: CircROBO1 might be a promising target for treating HCC radioresistance.

15.
Spectrochim Acta A Mol Biomol Spectrosc ; 323: 124898, 2024 Dec 15.
Article in English | MEDLINE | ID: mdl-39116597

ABSTRACT

Because ascorbic acid (AA) is one of the basic elements to maintain the normal physiological functions of human body, it is urgent to develop a material that can achieve efficient, rapid and in-situ detection for AA. A new fluorescence organic compound 4',4'''-(benzo[c][1,2,5]thiadiazole-4,7-diyl)bis([1,1'-biphenyl]-4-carboxylic acid) (H2BTBC) based on benzothiadiazole group has been synthesized, which can detect Fe3+ ions by fluorescence turn-off effect with a detection limit of 0.015 µM, as well as recognize linear amines by fluorescence turn-on effect. Moreover, a highly stable Tb(III) metal-organic framework has been solvothermally prepared with H2BTBC, namely {[(CH3)2NH2]2[Tb2(BTBC)4]∙solvents}n (JXUST-39), which can selectively detect AA among biological fluids by fluorescence enhancement effect with a detection limit of 0.077 µM. In addition, the mechanism for JXUST-39 detecting AA is possibly the cooperative effect of absorbance-caused enhancement and charge transfer between JXUST-39 and AA. Moreover, LED lamp beads, fluorescent films and fluorescent detection test paper based on JXUST-39 were prepared to achieve portable detection via fluorescence enhancement effect.

16.
J Psychiatry Neurosci ; 49(4): E252-E262, 2024.
Article in English | MEDLINE | ID: mdl-39122409

ABSTRACT

BACKGROUND: Psychosis involves a distortion of thought content, which is partly reflected in anomalous ways in which words are semantically connected into utterances in speech. We sought to explore how these linguistic anomalies are realized through putative circuit-level abnormalities in the brain's semantic network. METHODS: Using a computational large-language model, Bidirectional Encoder Representations from Transformers (BERT), we quantified the contextual expectedness of a given word sequence (perplexity) across 180 samples obtained from descriptions of 3 pictures by patients with first-episode schizophrenia (FES) and controls matched for age, parental social status, and sex, scanned with 7 T ultra-high field functional magnetic resonance imaging (fMRI). Subsequently, perplexity was used to parametrize a spectral dynamic causal model (DCM) of the effective connectivity within (intrinsic) and between (extrinsic) 4 key regions of the semantic network at rest, namely the anterior temporal lobe, the inferior frontal gyrus (IFG), the posterior middle temporal gyrus (MTG), and the angular gyrus. RESULTS: We included 60 participants, including 30 patients with FES and 30 controls. We observed higher perplexity in the FES group, indicating that speech was less predictable by the preceding context among patients. Results of Bayesian model comparisons showed that a DCM including the group by perplexity interaction best explained the underlying patterns of neural activity. We observed an increase of self-inhibitory effective connectivity within the IFG, as well as reduced self-inhibitory tone within the pMTG, in the FES group. An increase in self-inhibitory tone in the IFG correlated strongly and positively with inter-regional excitation between the IFG and posterior MTG, while self-inhibition of the posterior MTG was negatively correlated with this interregional excitation. LIMITATION: Our design did not address connectivity in the semantic network during tasks that selectively activated the semantic network, which could corroborate findings from this resting-state fMRI study. Furthermore, we do not present a replication study, which would ideally use speech in a different language. CONCLUSION: As an explanation for peculiar speech in psychosis, these results index a shift in the excitatory-inhibitory balance regulating information flow across the semantic network, confined to 2 regions that were previously linked specifically to the executive control of meaning. Based on our approach of combining a large language model with causal connectivity estimates, we propose loss in semantic control as a potential neurocognitive mechanism contributing to disorganization in psychosis.


Subject(s)
Magnetic Resonance Imaging , Psychotic Disorders , Schizophrenia , Semantics , Humans , Male , Female , Adult , Schizophrenia/diagnostic imaging , Schizophrenia/physiopathology , Young Adult , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/physiopathology , Temporal Lobe/diagnostic imaging , Temporal Lobe/physiopathology , Speech/physiology , Bayes Theorem , Brain/diagnostic imaging , Brain/physiopathology , Nerve Net/diagnostic imaging , Nerve Net/physiopathology
17.
Arch Toxicol ; 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39120795

ABSTRACT

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0 mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.

18.
Int J Biol Macromol ; 277(Pt 3): 134232, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39098667

ABSTRACT

In this study, double enzyme hydrolysis significantly enhanced the DPP-IV inhibition rate compared to single enzyme. The α + K enzymes exhibited the highest inhibition rate. Ultrasonic pretreatment for 30 min improved the hydrolysis efficiency and DPP-IV inhibition rate, potentially due to the structural changes in hydrolysates, such as the increased surface hydrophobicity, and reduced particle size, α-helix and ß-turn. Six peptides were screened and verified in vitro. QPY, WPEYL, and YPPQVM displayed competitive inhibition, while LPAAP and IPAPSFPRL displayed mixed competitive/non-competitive inhibition. The interactions between these six peptides and DPP-IV primarily occurred through hydrogen bonds, electrostatic and hydrophobic interactions. Network pharmacological analysis indicated that LPAAP might inhibit DPP-IV activity trough interactions with diabetes-related targets such as CASP3, HSP90AA1, MMP9, and MMP9. These results uncover the potential mechanism of regulating blood glucose by camel milk hydrolysates, establishing camel milk peptide as a source of DPP-IV inhibitory peptide.


Subject(s)
Camelus , Dipeptidyl Peptidase 4 , Dipeptidyl-Peptidase IV Inhibitors , Milk , Peptides , Animals , Dipeptidyl Peptidase 4/chemistry , Dipeptidyl Peptidase 4/metabolism , Milk/chemistry , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Peptides/chemistry , Peptides/pharmacology , Hydrolysis , Hydrophobic and Hydrophilic Interactions , Amino Acid Sequence , Humans
19.
Anal Methods ; 16(36): 6079-6097, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39212159

ABSTRACT

Nonenzymatic electrochemical biosensors, renowned for their high sensitivity, multi-target analysis capabilities, and miniaturized integration, align well with the requirements of non-invasive, multi-index integrated, continuous monitoring, and user-friendly wearable biosensors in sports science. In the past three years, novel strategies targeting specific responses to sports biomarkers have opened new avenues for applications in sports science. However, these advancements also pose challenges in achieving adequate sensitivity and specificity for online analysis of complex sweat bio-samples. Our article focuses on three key nonenzymatic electrochemical biosensing strategies: antigen-antibody reactions, nucleic acid aptamer recognition, and molecular imprinting capture. We delve into strategies to enhance specificity and sensitivity in the application of biosensors in sports science, including shortening signal transduction paths through built-in signal probes, increasing reaction sites through increased surface area and the introduction of nanostructures, multi-target analyses, and microfluidic techniques.


Subject(s)
Aptamers, Nucleotide , Biomarkers , Biosensing Techniques , Electrochemical Techniques , Molecularly Imprinted Polymers , Biosensing Techniques/methods , Biosensing Techniques/instrumentation , Humans , Biomarkers/analysis , Aptamers, Nucleotide/chemistry , Molecularly Imprinted Polymers/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Antibodies/immunology , Antibodies/chemistry , Sports , Molecular Imprinting/methods , Sweat/chemistry
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