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1.
ACS Appl Mater Interfaces ; 16(19): 24943-24950, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38693823

RESUMO

Designing high-performance polarization-sensitive photodetectors is essential for photonic device applications. Anisotropic one-dimensional (1D) van der Waals (vdW) materials have provided a promising platform to that end. Despite significant advances in 1D vdW photonic devices, their performance is still far from delivering practical potential. Herein, we propose the design of high-performance polarization-sensitive photodetectors using unique 1D vdW materials. By leveraging the chemical vapor transport technique, we successfully fabricate high-quality 1D vdW Nb2Pd1-xSe5 (x = 0.29) nanowires. The 1D vdW Nb2Pd1-xSe5 photodetector exhibits a high mobility of ∼56 cm2/(V s) and superior photoresponse performance, including a high responsivity of 1A/W and an ultrafast response time of ∼8 µs under 638 nm illumination. Moreover, the 1D vdW Nb2Pd1-xSe5 photodetector demonstrates excellent polarization-sensitive photoresponse with a degree of linear polarization (DOLP) up to 0.85 and can be modulated by adjusting the gate voltage, laser power density, and wavelength. Those exceptional performance are believed to be relevant to the symmetry-reduction induced by the partial occupation of Pd sites. This study offers feasible approaches to enhance the anisotropy of 1D vdW materials and the modulation of their polarization-sensitive photoresponse, which may provide deep insights into the physical origin of anisotropic properties of 1D vdW materials.

2.
Int J Med Sci ; 21(6): 1176-1186, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774752

RESUMO

Background: To uncover the potential significance of JAK-STAT-SOCS1 axis in penile cancer, our study was the pioneer in exploring the altered expression processes of JAK-STAT-SOCS1 axis in tumorigenesis, malignant progression and lymphatic metastasis of penile cancer. Methods: In current study, the comprehensive analysis of JAK-STAT-SOCS1 axis in penile cancer was analyzed via multiple analysis approaches based on GSE196978 data, single-cell data (6 cancer samples) and bulk RNA data (7 cancer samples and 7 metastasis lymph nodes). Results: Our study observed an altered molecular expression of JAK-STAT-SOCS1 axis during three different stages of penile cancer, from tumorigenesis to malignant progression to lymphatic metastasis. STAT4 was an important dominant molecule in penile cancer, which mediated the immunosuppressive tumor microenvironment by driving the apoptosis of cytotoxic T cell and was also a valuable biomarker of immune checkpoint inhibitor treatment response. Conclusions: Our findings revealed that the complexity of JAK-STAT-SOCS1 axis and the predominant role of STAT4 in penile cancer, which can mediate tumorigenesis, malignant progression, and lymphatic metastasis. This insight provided valuable information for developing precise treatment strategies for patients with penile cancer.


Assuntos
Progressão da Doença , Janus Quinases , Metástase Linfática , Neoplasias Penianas , Fator de Transcrição STAT4 , Proteína 1 Supressora da Sinalização de Citocina , Humanos , Masculino , Neoplasias Penianas/patologia , Neoplasias Penianas/genética , Neoplasias Penianas/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Metástase Linfática/patologia , Metástase Linfática/genética , Janus Quinases/metabolismo , Fator de Transcrição STAT4/metabolismo , Fator de Transcrição STAT4/genética , Regulação Neoplásica da Expressão Gênica , Carcinogênese/genética , Carcinogênese/patologia , Transdução de Sinais , Microambiente Tumoral/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia
3.
Microbiol Spectr ; : e0379623, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712963

RESUMO

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

4.
Toxicol Lett ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759937

RESUMO

Autophagy has been implicated in the developmental toxicity of multiple organs in offspring caused by adverse environmental conditions during pregnancy. We have previously found that prenatal caffeine exposure (PCE) can cause fetal overexposure to maternal glucocorticoids, leading to chondrodysplasia. However, whether autophagy is involved and what role it plays has not been reported. In this study, a PCE rat model was established by gavage of caffeine (120mg/kg.d) on gestational day 9-20. The results showed that reduced cartilage matrix synthesis in male fetal rats in the PCE group was accompanied by increased autophagy compared to the control group. Furthermore, the expression of mTOR, miR-421-3p, and glucocorticoid receptor (GR) in male fetal rat cartilage of PCE group was increased. At the cellular level, we confirmed that corticosterone inhibited matrix synthesis in fetal chondrocytes while increasing autophagic flux. However, administration of autophagy enhancer (rapamycin) or inhibitor (bafilomycin A1 or 3-methyladenine) partially increased or further decreased aggrecan expression respectively. At the same time, we found that corticosterone could increase the expression of miR-421-3p through GR and target to inhibit the expression of mTOR, thereby enhancing autophagy. In conclusion, PCE can cause chondrodysplasia and autophagy enhancement in male fetal rats. Intrauterine high corticosterone activates GR/miR-421-3p signaling and down-regulates mTOR signaling in fetal chondrocytes, resulting in enhanced autophagy, which can partially compensate for corticosterone-induced fetal chondrodysplasia. This study confirmed the compensatory protective effect of autophagy on the developmental toxicity of fetal cartilage induced by PCE and its epigenetic mechanism, providing novel insights for exploring the early intervention and therapeutic target of fetal-originated osteoarthritis.

5.
Chem Biol Interact ; : 111060, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38761876

RESUMO

Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.

6.
Nat Commun ; 15(1): 2818, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561369

RESUMO

Interplay between innate and adaptive immune cells is important for the antitumor immune response. However, the tumor microenvironment may turn immune suppressive, and tumor associated macrophages are playing a role in this transition. Here, we show that CD276, expressed on tumor-associated macrophages (TAM), play a role in diminishing the immune response against tumors. Using a model of tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in BLCA male mice we show that genetic ablation of CD276 in TAMs blocks efferocytosis and enhances the expression of the major histocompatibility complex class II (MHCII) of TAMs. This in turn increases CD4 + and cytotoxic CD8 + T cell infiltration of the tumor. Combined single cell RNA sequencing and functional experiments reveal that CD276 activates the lysosomal signaling pathway and the transcription factor JUN to regulate the expression of AXL and MerTK, resulting in enhanced efferocytosis in TAMs. Proving the principle, we show that simultaneous blockade of CD276 and PD-1 restrain tumor growth better than any of the components as a single intervention. Taken together, our study supports a role for CD276 in efferocytosis by TAMs, which is potentially targetable for combination immune therapy.


Assuntos
Macrófagos Associados a Tumor , Neoplasias da Bexiga Urinária , Animais , Masculino , Camundongos , Eferocitose , Evasão da Resposta Imune , Macrófagos/metabolismo , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Neoplasias da Bexiga Urinária/metabolismo
7.
Int J Cancer ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561936

RESUMO

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

8.
Prev Med Rep ; 41: 102719, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38623579

RESUMO

Obesity is a major risk factor of hypertension, therefore quantifying the contribution of obesity to hypertension is necessary. The current study aimed to investigate the changes in population-attributable fractions (PAFs) of hypertension associated with general obesity and abdominal obesity over the recent 2 decades among the US population, as well as important sub-populations. This report was performed based on national-level cross-sectional data for 46,535 adults aged 18 years and older and 20,745 children aged 8-17 from the US National Health and Nutrition Examination Survey 1999-2018. The PAFs of hypertension due to general obesity and abdominal obesity were calculated by sex, race/ethnicity, and survey year. The linear regression analysis was used to evaluate the secular trends of PAFs over the years. The prevalence of general obesity and abdominal obesity presented significantly increasing trends during the past 2 decades in the US. The PAFs of hypertension due to general obesity increased steadily from 11.9 % to 15.1 % in women with a slope of 0.38 % (95 % CI: 0.31 - 0.45 %) and from 8.4 % to 13.4 % in men with a slope of 0.46 % (95 % CI: 0.36 - 0.56 %). Similar increasing trends were also observed for the PAFs due to abdominal obesity in both women and men. Additionally, there were significantly different trends of PAFs in various races/ethnicities. Over the past 2 decades, the contributions of obesity to hypertension were gradually rising among US population, which emphasizes the importance of controlling weight to further reduce the burden of hypertension.

9.
Anal Chem ; 96(15): 5897-5905, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38557023

RESUMO

Current diagnostic methods for thyroid diseases, including blood tests, ultrasound, and biopsy, always have difficulty diagnosing thyroiditis accurately, occasionally mistaking it for thyroid cancer. To address this clinical challenge, we developed Ox-PGP1, a novel fluorescent probe realizing rapid, noninvasive, and real-time diagnostic techniques. This is the first imaging tool capable of noninvasively distinguishing between thyroiditis and thyroid cancer. Ox-PGP1 was introduced as a fluorescent probe custom-built for the specific detection and quantification of pyroglutamate aminopeptidase 1 (PGP-1), a known pivotal biomarker of inflammation. Ox-PGP1 overcame the disadvantages of traditional enzyme-responsive fluorescent probes that relied on the intramolecular charge transfer (ICT) mechanism, including the issue of high background fluorescence, while offering exceptional photostability under laser irradiation. The spectral properties of Ox-PGP1 were meticulously optimized to enhance its biocompatibility. Furthermore, the low limit of detection (LOD) of Ox-PGP1 was determined to be 0.09 µg/mL, which demonstrated its remarkable sensitivity and precision. Both cellular and in vivo experiments validated the capacity of Ox-PGP1 for accurate differentiation between normal, inflammatory, and cancerous thyroid cells. Furthermore, Ox-PGP1 showed the potential to rapidly and sensitively differentiate between autoimmune thyroiditis and anaplastic thyroid carcinoma in a mouse model, achieving results in just 5 min. The successful design and application of Ox-PGP1 represent a substantial advancement in technology over traditional diagnostic approaches, potentially enabling earlier interventions for thyroid diseases.


Assuntos
Neoplasias da Glândula Tireoide , Tireoidite , Animais , Camundongos , Piroglutamil-Peptidase I , Corantes Fluorescentes , Tireoidite/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Imagem Óptica
10.
Ecotoxicol Environ Saf ; 277: 116380, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677068

RESUMO

The interaction between microplastics (MPs) and cadmium (Cd) poses a threat to agricultural soil environments, and their effects on plant growth and rhizosphere microbial community functions are not yet clear. In this study, energy sorghum was used as a test plant to investigate the effects of two types of MPs, polystyrene (PS) and polyethylene (PE), at different particle sizes (13 µm, 550 µm) and concentrations (0.1%, 1% w/w), and Cd, as well as their interactions, on the growth of sorghum in a soil-cultivation pot experiment. The results showed that the combined effects of MP and Cd pollution on the dry weight and Cd accumulation rate in sorghum varied depending on the type, concentration, and particle size of the MPs, with an overall trend of increasing stress from combined pollution with increasing Cd content and accumulation. High-throughput sequencing analysis revealed that combined MP and Cd pollution increased bacterial diversity, and the most significant increase was observed in the abundance-based coverage estimator (ACE), Shannon, and Sobs indices in the 13 µm 1% PS+Cd treatment group. Metagenomic analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed that 19 groups of metabolic pathways, including microbial metabolism and methane metabolism, differed significantly under combined MP and Cd pollution. Hierarchical clustering results indicated that Cd treatment and combined MP and Cd treatment affected the abundances of sorghum rhizosphere soil nitrogen (N) and phosphorus (P) cycling genes and that the type of MP present was an important factor affecting N and P cycling genes. The results of this study provide a basis for exploring the toxic effects of combined MP and Cd pollution and for conducting soil environmental risk assessments.


Assuntos
Cádmio , Microplásticos , Rizosfera , Microbiologia do Solo , Poluentes do Solo , Sorghum , Sorghum/efeitos dos fármacos , Sorghum/microbiologia , Cádmio/toxicidade , Poluentes do Solo/toxicidade , Microplásticos/toxicidade , Solo/química , Tamanho da Partícula , Bactérias/efeitos dos fármacos
11.
China CDC Wkly ; 6(14): 277-281, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38634102

RESUMO

What is already known about this topic?: The mortality rate and disease burden associated with falls among the elderly in China are on the rise. Interventions can play a crucial role in preventing and managing falls. What is added by this report?: The application of the "5E" injury prevention strategy led to a decrease in both the occurrence of falls and the likelihood of subsequent falls. Regular physical activity and maintaining a positive outlook were identified as protective measures against falls, while sleep issues and hearing impairment were found to increase the risk of falling. What are the implications for public health practice?: The group-based comprehensive intervention strategy is crucial as it offers an innovative intervention model and empirical evidence for decreasing fall rates among elderly individuals living in rural areas.

12.
Eur J Pharmacol ; 974: 176609, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38677536

RESUMO

PURPOSE: Diabetic cardiomyopathy is a prevalent cardiovascular complication of diabetes mellitus. This study aimed to investigate the effects of ginsenoside Rb1 (GRb1) on the diabetic myocardium. METHODS: Leptin receptor-deficient db/db mice and palmitic acid (PA)-treated cardiomyocyte models were utilized. Cardiac systolic and diastolic function, mitochondrial morphology, and respiratory chain function were determined. The expression of mitochondrial dynamics proteins was measured. Mitofusin 2 (Mfn2) overexpression and inhibition were achieved by lentiviral infection and small interfering RNA (siRNA) transfection. RESULTS: In comparison to non-diabetic mice, db/db mice exhibited significant increases in body weight, blood glucose, blood lipids, and cardiac free fatty acid levels. This was accompanied by myocardial hypertrophy and left ventricular diastolic dysfunction, which were significantly ameliorated by GRb1 intervention. Stimulation with PA increased oxidative stress and apoptosis, and decreased viability in H9c2 cardiomyocytes. PA also reduced sarcomere contractility and relaxation in adult mice ventricular myocytes. PA-induced cellular and mitochondrial damage were reversed with GRb1 treatment. The cardiac tissue of db/db mice and PA-treated cardiomyocytes exhibited a decrease in Mfn2 expression, which was markedly improved by GRb1. Mfn2 overexpression reversed PA-induced mitochondrial fragmentation and functional damage in cardiomyocytes, while inhibition of Mfn2 expression by siRNA transfection blocked the protective effects of GRb1. CONCLUSION: GRb1 alleviated myocardial lipid accumulation and mitochondrial injury, and attenuated ventricular diastolic dysfunction in diabetic mice. The regulation of Mfn2 was involved in the protective effects of GRb1 against lipotoxic myocardial injury.

13.
Bioengineering (Basel) ; 11(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38534485

RESUMO

B0 field inhomogeneity is a long-lasting issue for Cardiac MRI (CMR) in high-field (3T and above) scanners. The inhomogeneous B0 fields can lead to corrupted image quality, prolonged scan time, and false diagnosis. B0 shimming is the most straightforward way to improve the B0 homogeneity. However, today's standard cardiac shimming protocol requires manual selection of a shim volume, which often falsely includes regions with large B0 deviation (e.g., liver, fat, and chest wall). The flawed shim field compromises the reliability of high-field CMR protocols, which significantly reduces the scan efficiency and hinders its wider clinical adoption. This study aims to develop a dual-channel deep learning model that can reliably contour the cardiac region for B0 shim without human interaction and under variable imaging protocols. By utilizing both the magnitude and phase information, the model achieved a high segmentation accuracy in the B0 field maps compared to the conventional single-channel methods (Dice score: 2D-mag = 0.866, 3D-mag = 0.907, and 3D-mag-phase = 0.938, all p < 0.05). Furthermore, it shows better generalizability against the common variations in MRI imaging parameters and enables significantly improved B0 shim compared to the standard method (SD(B0Shim): Proposed = 15 ± 11% vs. Standard = 6 ± 12%, p < 0.05). The proposed autonomous model can boost the reliability of cardiac shimming at 3T and serve as the foundation for more reliable and efficient high-field CMR imaging in clinical routines.

14.
Mediators Inflamm ; 2024: 7459054, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549714

RESUMO

Background: Cerebral ischemia-reperfusion injury is a common complication of ischemic stroke that affects the prognosis of patients with ischemic stroke. The lipid-soluble diterpene Tanshinone IIA, which was isolated from Salvia miltiorrhiza, has been indicated to reduce cerebral ischemic injury. In this study, we investigated the molecular mechanism of Tanshinone IIA in alleviating reperfusion-induced brain injury. Methods: Middle cerebral artery occlusion animal models were established, and neurological scores, tetrazolium chloride staining, brain volume quantification, wet and dry brain water content measurement, Nissl staining, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were performed. The viability of cells was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays, while cell damage was measured by lactate dehydrogenase release in the in vitro oxygen glucose deprivation model. In addition, enzyme-linked immunosorbent assay, flow cytometry, western blotting, and reverse transcription-quantitative polymerase chain reaction were used to evaluate the therapeutic effect of Tanshinone IIA on ischemia/reperfusion (I/R) induced brain injury, as well as its effects on the inflammatory response and neuronal apoptosis, in vivo and in vitro. Furthermore, this study validated the targeting relationship between miR-124-5p and FoxO1 using a dual luciferase assay. Finally, we examined the role of Tanshinone IIA in brain injury from a molecular perspective by inhibiting miR-124-5p or increasing FoxO1 levels. Results: After treatment with Tanshinone IIA in middle cerebral artery occlusion-reperfusion (MCAO/R) rats, the volume of cerebral infarction was reduced, the water content of the brain was decreased, the nerve function of the rats was significantly improved, and the cell damage was significantly reduced. In addition, Tanshinone IIA effectively inhibited the I/R-induced inflammatory response and neuronal apoptosis, that is, it inhibited the expression of inflammatory cytokines IL-1ß, IL-6, TNF-α, decreased the expression of apoptotic protein Bax and Cleaved-caspase-3, and promoted the expression of antiapoptotic protein Bcl-2. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) cell model, Tanshinone IIA also inhibited the expression of inflammatory factors in neuronal cells and inhibited the occurrence of neuronal apoptosis. In addition, Tanshinone IIA promoted the expression of miR-124-5p. Transfection of miR-124-5p mimic has the same therapeutic effect as Tanshinone IIA and positive therapeutic effect on OGD cells, while transfection of miR-124-5p inhibitor has the opposite effect. The targeting of miR-124-5p negatively regulates FoxO1 expression. Inhibition of miR-124-5p or overexpression of FoxO1 can weaken the inhibitory effect of Tanshinone IIA on brain injury induced by I/R, while inhibition of miR-124-5p and overexpression of FoxO1 can further weaken the effect of Tanshinone IIA. Conclusion: Tanshinone IIA alleviates ischemic-reperfusion brain injury by inhibiting neuroinflammation through the miR-124-5p/FoxO1 axis. This finding provides a theoretical basis for mechanistic research on cerebral ischemia-reperfusion injury.


Assuntos
Abietanos , Lesões Encefálicas Traumáticas , Isquemia Encefálica , AVC Isquêmico , MicroRNAs , Traumatismo por Reperfusão , Humanos , Ratos , Animais , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/complicações , Oxigênio/metabolismo , Reperfusão/efeitos adversos , Glucose/metabolismo , Água , Apoptose
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124162, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38522377

RESUMO

In recent years, hemi-cyanine dyes have been widely used as biological probes due to their red-light emission characteristics and high fluorescence quantum yield. In this study, we synthesized a novel hemi-cyanine dye containing a tetrahydropyridine ring. A lysosomal target was introduced into its structure to create a new pH-sensitive near-infrared fluorescent probe that successfully targeted lysosomes. The results showed that when the probe solution was excited at the absorption wavelength of 650 nm, its fluorescence emission wavelength was about 700 nm, and the peak intensity changed with different pH values in a wide range. Therefore, this probe enabled non-invasive detection of changes in the acidic environment of lysosomes in living organisms and showed good imaging capabilities. Moreover, the probe displays high sensitivity and good stability. The theoretical calculation of a probe structure has also been completed to discuss the relationship between structure and property.


Assuntos
Corantes Fluorescentes , Quinolinas , Humanos , Fluorescência , Corantes Fluorescentes/química , Concentração de Íons de Hidrogênio , Lisossomos/química , Quinolinas/análise , Células HeLa
16.
J Hazard Mater ; 469: 134085, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38522197

RESUMO

Composite pollution by microplastics and heavy metals poses a potential threat to the soilplant system and has received increasing attention. Plant growth-promoting bacteria (PGPB) have good application potential for the remediation of combined microplastic and heavy metal pollution, but few related studies exist. The present study employed a pot experiment to investigate the effects of inoculation with the PGPB Bacillus sp. SL-413 and Enterobacter sp. VY-1 on sorghum growth and Cd accumulation under conditions of combined cadmium (Cd) and polyethylene (PE) pollution. Cd+PE composite contamination led to a significant reduction in sorghum length and biomass due to increased toxicity. Inoculation with Bacillus sp. SL-413 and Enterobacter sp. VY-1 alleviated the stress caused by Cd+PE complex pollution, and the dry weight of sorghum increased by 25.7% to 46.1% aboveground and by 12.3% to 45.3% belowground. Bacillus sp. SL-413 and Enterobacter sp. VY-1 inoculation increased the Cd content and accumulation in sorghum and improved the phytoremediation efficiency of Cd. The inoculation treatment effectively alleviated the nutrient stress caused by the reduction in soil mineral nutrients due to Cd+PE composite pollution. The composition of the soil bacterial communities was also affected by the Cd, Cd+PE and bacterial inoculation treatments, which affected the diversity of the soil bacterial communities. Network analyses indicated that bacterial inoculation regulated the interaction of rhizospheric microorganisms and increased the stability of soil bacterial communities. The Mantel test showed that the changes in the soil bacterial community and function due to inoculation with Bacillus sp. SL-413 and Enterobacter sp. VY-1 were important factors influencing sorghum growth and Cd remediation efficiency. The results of this study will provide new evidence for the research on joint plantmicrobe remediation of heavy metal and microplastic composite pollution.


Assuntos
Bacillus , Metais Pesados , Poluentes do Solo , Sorghum , Cádmio/análise , Biodegradação Ambiental , Plásticos , Polietileno , Solo , Rizosfera , Microplásticos , Metais Pesados/toxicidade , Metais Pesados/análise , Enterobacter , Poluentes do Solo/análise
17.
Alcohol Clin Exp Res (Hoboken) ; 48(5): 781-794, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38503560

RESUMO

BACKGROUND: Previously, we demonstrated that Spp1-/- mice exhibit a greater susceptibility to alcohol-induced liver injury than wild-type (WT) mice. Notably, alcohol triggers the expression of osteopontin (encoded by SPP1) in hepatocytes. However, the specific role of hepatocyte-derived SPP1 in either mitigating or exacerbating alcohol-associated liver disease (AALD) has yet to be elucidated. We hypothesized that hepatocyte-derived SPP1 plays a role in AALD by modulating the regulation of steatosis. METHODS: We analyzed hepatic SPP1 expression using four publicly available datasets from patients with alcoholic hepatitis (AH). Additionally, we examined SPP1 expression in the livers of WT mice subjected to either a control or ethanol Lieber-DeCarli (LDC) diet for 6 weeks. We compared the relationship between SPP1 expression and significantly dysregulated genes in AH with controls using correlation and enrichment analyses. To investigate the specific impact of hepatocyte-derived SPP1, we generated hepatocyte-specific Spp1 knock-out (Spp1ΔHep) mice and subjected them to either a control or ethanol Lieber-DeCarli diet for 6 weeks. RESULTS: Alcohol induced hepatic SPP1 expression in both humans and mice. Our analysis, focusing on genes correlated with SPP1, revealed an enrichment of fatty acid oxidation (FAO) in three datasets, and peroxisome proliferator-activated receptor signaling in one dataset. Notably, FAO genes correlating with SPP1 were downregulated in patients with AH. Ethanol-fed WT mice exhibited higher serum-free fatty acids (FFAs), adipose tissue lipolysis, and hepatic fatty acid (FA) transporters. In contrast, ethanol-fed Spp1ΔHep mice displayed lower liver triglycerides, FFAs, and serum alanine transaminase and greater FAO gene expression than WT mice, indicating a protective effect against AALD. Primary hepatocytes from Spp1∆Hep mice exhibited heightened expression of genes encoding proteins involved in FAO. CONCLUSIONS: Alcohol induces the expression of SPP1 in hepatocytes, leading to impaired FAO and contributing to the development of AALD.

18.
Cancers (Basel) ; 16(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38539565

RESUMO

The spectral quality of magnetic resonance spectroscopic imaging (MRSI) can be affected by strong magnetic field inhomogeneities, posing a challenge for 3D-MRSI's widespread clinical use with standard scanner-equipped 2nd-order shim coils. To overcome this, we designed an empirical unified shim-RF head coil (32-ch RF receive and 51-ch shim) for 3D-MRSI improvement. We compared its shimming performance and 3D-MRSI brain coverages against the standard scanner shim (2nd-order spherical harmonic (SH) shim coils) and integrated parallel reception, excitation, and shimming (iPRES) 32-ch AC/DC head coil. We also simulated a theoretical 3rd-, 4th-, and 5th-order SH shim as a benchmark to assess the UNIfied shim-RF coil (UNIC) improvements. In this preliminary study, the whole-brain coverage was simulated by using B0 field maps of twenty-four healthy human subjects (n = 24). Our results demonstrated that UNIC substantially improves brain field homogeneity, reducing whole-brain frequency standard deviations by 27% compared to the standard 2nd-order scanner shim and 17% compared to the iPRES shim. Moreover, UNIC enhances whole-brain coverage of 3D-MRSI by up to 34% compared to the standard 2nd-order scanner shim and up to 13% compared to the iPRES shim. UNIC markedly increases coverage in the prefrontal cortex by 147% and 47% and in the medial temporal lobe and temporal pole by 29% and 13%, respectively, at voxel resolutions of 1.4 cc and 0.09 cc for 3D-MRSI. Furthermore, UNIC effectively reduces variations in shim quality and brain coverage among different subjects compared to scanner shim and iPRES shim. Anticipated advancements in higher-order shimming (beyond 6th order) are expected via optimized designs using dimensionality reduction methods.

19.
Heliyon ; 10(5): e27465, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463768

RESUMO

Background: Lactylation is a significant post-translational modification bridging the gap between cancer epigenetics and metabolic reprogramming. However, the association between lactylation and prognosis, tumor microenvironment (TME), and response to drug therapy in various cancers remains unclear. Methods: First, the expression, prognostic value, and genetic and epigenetic alterations of lactylation genes were systematically explored in a pan-cancer manner. Lactylation scores were derived for each tumor using the single-sample gene set enrichment analysis (ssGSEA) algorithm. The correlation of lactylation scores with clinical features, prognosis, and TME was assessed by integrating multiple computational methods. In addition, GSE135222 data was used to assess the efficacy of lactylation scores in predicting immunotherapy outcomes. The expression of lactylation genes in breast cancers and gliomas were verified by RNA-sequencing. Results: Lactylation genes were significantly upregulated in most cancer types. CREBBP and EP300 exhibited high mutation rates in pan-cancer analysis. The prognostic impact of the lactylation score varied by tumor type, and lactylation score was a protective factor for KIRC, ACC, READ, LGG, and UVM, and a risk factor for CHOL, DLBC, LAML, and OV. In addition, a high lactylation score was associated with cold TME. The infiltration levels of CD8+ T, γδT, natural killer T cell (NKT), and NK cells were lower in tumors with higher lactylation scores. Finally, immunotherapy efficacy was worse in patients with high lactylation scores than other types. Conclusion: Lactylation genes are involved in malignancy formation. Lactylation score serves as a promising biomarker for predicting patient prognosis and immunotherapy efficacy.

20.
Ying Yong Sheng Tai Xue Bao ; 35(1): 255-267, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38511463

RESUMO

The optimization of production-living-ecology (PLE) space is an important basis for promoting regional high-quality development. Taking the Dongting Lake Eco-economic Zone as an example, from the perspective of improving the comprehensive benefits of the development and protection of the PLE space, we coupled the GMOP-FLUS model, and proposed an optimization method combining the scenario configuration and the bottom line protection of the PLE space. We compared the three optimization scenarios (economic optimization scenario, ecological optimization scenario, and multi-objective optimization scenario), and coordinated the conflict areas of two lines to clarify the comprehensive optimization scheme of the PLE space in the Dongting Lake Eco-economic Zone. The results showed the characteristics of increasing production space and living space and decreasing ecological space from 2010 to 2020, resulting in the partial loss of land ecological and environmental benefits. Under the economic optimization scenario, the ecological optimization scenario promoted the rapid growth of regional economy but damaged regional ecological security. The ecological optimization scenario inhibited regional economic development. The multi-objective optimization scenario led to improvement of economic and ecological benefits of the PLE space, which increased by 2.0% and 1.3%, respectively. The multi-objective optimization scenario was the best optimization scenario among the three scenarios. By superimposing the best scenario and the two-line conflict regional coordination results, we obtained the comprehensive optimization scheme for 2030. The production space, living space, and ecological space areas of the scheme were 25777.18, 2062.94, and 32552.68 km2, respectively. Based on the natural and social conditions, combining the comprehensive optimization scheme, we put forward different control suggestions for each type of PLE space. Our results could provide reference for the rational formulation of territorial spatial planning and the formulation of policies for the coordinated development of ecological environment and social economy in the Dongting Lake Eco-economic Zone.


Assuntos
Conservação dos Recursos Naturais , Ecologia , Conservação dos Recursos Naturais/métodos , Lagos , Desenvolvimento Econômico , China , Ecossistema
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