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1.
J Adv Res ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876192

RESUMO

BACKGROUND: Nuclear pore complexes (NPCs) are the architectures entrenched in nuclear envelop of a cell that regulate the nucleo-cytoplasmic transportation of materials such as proteins and RNAs for proper functioning of a cell. The appropriate localization of proteins and RNAs within the cell is essential for its normal functionality. For such a complex transportation of materials across the NPC, around 60 proteins are involved comprising nucleoporins, karyopherins and RAN system proteins that play a vital role in NPC's structure formation, cargo translocation across NPC, and cargoes' rapid directed transportation respectively. In various cancers, the structure and function of NPC is often exaggerated, following altered expressions of its nucleoporins and karyopherins, affecting other proteins of associated signaling pathways. Some inhibitors of karyopherins at present have potential to regulate the altered level/expression of these karyopherin molecules. AIM OF REVIEW: This review summarizes the data from 1990 to 2023, mainly focusing on recent studies that illustrate the structure and function of NPC, the relationship and mechanisms of nucleoporins and karyopherins with colorectal cancer, as well as therapeutic values, in order to understand the pathology and underlying basis of colorectal cancer associated with NPC. This is the first review to our knowledge elucidating the detailed updated studies targeting colorectal cancer at NPC. The review also aims to target certain karyopherins, nups and their possible inhibitors and activators molecules as a therapeutic strategy. KEY SCIENTIFIC CONCEPTS OF REVIEW: NPC structure provides understanding, how nucleoporins and karyopherins as key molecules are responsible for appropriate nucleocytoplasmic transportation. Many studies provide evidences describing the role of disrupted nucleoporins and karyopherins not only in CRC but also in other non-hematological and hematological malignancies. At present, some inhibitors of karyopherins have therapeutic potential for CRC, however development of more potent inhibitors may provide more effective therapeutic strategies for CRC in near future.

2.
J Hazard Mater ; 474: 134865, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38861902

RESUMO

With the massive release of microplastics (MPs) into the environment, research related to MPs is advancing rapidly. Effective research methods are necessary to identify the chemical composition, shape, distribution, and environmental impacts of MPs. In recent years, artificial intelligence (AI)-driven machine learning methods have demonstrated excellent performance in analyzing MPs in soil and water. This review provides a comprehensive overview of machine learning methods for the prediction of MPs for various tasks, and discusses in detail the data source, data preprocessing, algorithm principle, and algorithm limitation of applied machine learning. In addition, this review discusses the limitation of current machine learning methods for various task analysis in MPs along with future prospect. Finally, this review finds research potential in future work in building large generalized MPs datasets, designing high-performance but low-computational-complexity algorithms, and evaluating model interpretability.

3.
Biochem Pharmacol ; 225: 116334, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38824967

RESUMO

Alcoholic liver injury (ALI) stands as a prevalent affliction within the spectrum of complex liver diseases. Prolonged and excessive alcohol consumption can pave the way for liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Recent findings have unveiled the protective role of proline serine-threonine phosphatase interacting protein 2 (PSTPIP2) in combating liver ailments. However, the role of PSTPIP2 in ALI remains mostly unknown. This study aimed to determine the expression profile of PSTPIP2 in ALI and to uncover the mechanism through which PSTPIP2 affects the survival and apoptosis of hepatocytes in ALI, using both ethyl alcohol (EtOH)-fed mice and an EtOH-induced AML-12 cell model. We observed a consistent decrease in PSTPIP2 expression both in vivo and in vitro. Functionally, we assessed the impact of PSTPIP2 overexpression on ALI by administering adeno-associated virus 9 (AAV9)-PSTPIP2 into mice. The results demonstrated that augmenting PSTPIP2 expression significantly shielded against liver parenchymal distortion and curbed caspase-dependent hepatocyte apoptosis in EtOH-induced ALI mice. Furthermore, enforcing PSTPIP2 expression reduced hepatocyte apoptosis in a stable PSTPIP2-overexpressing AML-12 cell line established through lentivirus-PSTPIP2 transfection in vitro. Mechanistically, this study also identified signal transducer and activator of transcription 3 (STAT3) as a direct signaling pathway regulated by PSTPIP2 in ALI. In conclusion, our findings provide compelling evidence that PSTPIP2 has a regulatory role in hepatocyte apoptosis via the STAT3 pathway in ALI, suggesting PSTPIP2 as a promising therapeutic target for ALI.


Assuntos
Apoptose , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3 , Animais , Apoptose/fisiologia , Apoptose/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Camundongos , Masculino , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/prevenção & controle , Etanol/toxicidade , Etanol/administração & dosagem , Hepatócitos/metabolismo , Hepatócitos/patologia , Linhagem Celular , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética
5.
Nat Commun ; 15(1): 4813, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844461

RESUMO

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ's role in augmenting the sensitivity of the IFN-ß pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ's effectiveness.


Assuntos
Antivirais , Ensaios de Triagem em Larga Escala , Nitrocompostos , Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Tiazóis , Animais , Vírus da Síndrome Respiratória e Reprodutiva Suína/efeitos dos fármacos , Nitrocompostos/farmacologia , Suínos , Antivirais/farmacologia , Ensaios de Triagem em Larga Escala/métodos , Síndrome Respiratória e Reprodutiva Suína/tratamento farmacológico , Síndrome Respiratória e Reprodutiva Suína/virologia , Tiazóis/farmacologia , Replicação Viral/efeitos dos fármacos , Linhagem Celular , Viremia/tratamento farmacológico , Viremia/virologia
6.
Sci Rep ; 14(1): 12940, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839834

RESUMO

An equivalent analytical model of sloshing in a two-dimensional (2-D) rigid rectangular container equipped with multiple vertical baffles is presented. Firstly, according to the subdomain partition approach, the total liquid domain is partitioned into subdomains with the pure interface and boundary conditions. The separation of variables is utilized to achieve the velocity potential for subdomains. Then, sloshing characteristics are solved according to continuity and free surface conditions. According to the mode orthogonality of sloshing, the governing motion equation for sloshing under horizontal excitation is given by introducing generalized time coordinates. Besides, by producing the same hydrodynamic shear and overturning moment as those from the original container-liquid-baffle system, a mass-spring analytical model of the continuous liquid sloshing is established. The equivalent masses and corresponding locations are presented in the model. The feasibility of the present approach is verified by conducting comparative investigations. Finally, by utilizing normalized equivalent model parameters, the sloshing behaviors of the baffled container are investigated regarding baffle positions and heights as well as the liquid height, respectively.

7.
Environ Sci Pollut Res Int ; 31(28): 41032-41045, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38842781

RESUMO

The problem of soil and water contamination caused by Cr(VI) discharged from the dyeing, electroplating, and metallurgical industries is becoming increasingly serious, posing a potentially great threat to the environment and public health. Therefore, it is crucial to develop a fast, efficient, and cost-effective adsorbent for remediating Cr-contaminated wastewater. In this work, MgAl-LDH/commercial-activated carbon nanocomposites (LDH-CACs) are prepared with hydrothermal. The effects of preparation and reaction conditions on the composite properties are first investigated, and then its adsorption behavior is thoroughly explored. Finally, a potential adsorption mechanism is proposed by several characterizations like SEM-EDS, XRD, FTIR, and XPS. The removal of Cr(VI) reaches 72.47% at optimal conditions, and the adsorption study demonstrates that LDH-CAC@1 has an extremely rapid adsorption rate and a maximum adsorption capacity of 116.7 mg/g. The primary removal mechanisms include adsorption-coupled reduction, ion exchange, surface precipitation, and electrostatic attraction. The reusability experiment illustrates that LDH-CAC@1 exhibits promising reusability. This study provides an effective adsorbent with a remarkably fast reaction, which has positive environmental significance for the treatment of Cr(VI) wastewater.


Assuntos
Carvão Vegetal , Cromo , Poluentes Químicos da Água , Adsorção , Cromo/química , Poluentes Químicos da Água/química , Carvão Vegetal/química , Nanocompostos/química , Purificação da Água/métodos , Águas Residuárias/química , Carbono/química
8.
Cell Rep Med ; 5(6): 101594, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38843843

RESUMO

When applied as the standard therapeutic modality, intensity-modulated radiotherapy (IMRT) improves local control and survival rates in patients with nasopharyngeal carcinoma (NPC). However, distant metastasis continues to be the leading cause of treatment failure. Here, we review the most recent optimization strategies for combining chemotherapy with IMRT in high-risk patients with locoregionally advanced NPC. We focus on major clinical trials on induction chemotherapy and metronomic adjuvant chemotherapy, emphasizing their efficacy in mitigating distant metastasis and prognosis. We also highlight innovations in reducing toxicity in low-risk patients, particularly through approaches of excluding chemotherapy, adopting equivalent low-toxicity drugs, or selectively exempting lymph nodes with low metastatic risk from irradiation. These approaches have provided positive treatment outcomes and significantly enhanced patients' quality of life. Finally, we provide an overview of the evolving immunotherapy landscape, with a focus on the ongoing trials and future potential of immune checkpoint inhibitors in advanced NPC treatment.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Imunoterapia/métodos , Radioterapia de Intensidade Modulada/métodos , Resultado do Tratamento , Inibidores de Checkpoint Imunológico/uso terapêutico , Ensaios Clínicos como Assunto , Qualidade de Vida
9.
Commun Biol ; 7(1): 728, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877285

RESUMO

Benzodiazepines, commonly used for anxiolytics, hinder conditioned fear extinction, and the underlying circuit mechanisms are unclear. Utilizing remimazolam, an ultra-short-acting benzodiazepine, here we reveal its impact on the thalamic nucleus reuniens (RE) and interconnected hippocamposeptal circuits during fear extinction. Systemic or RE-specific administration of remimazolam impedes fear extinction by reducing RE activation through A type GABA receptors. Remimazolam enhances long-range GABAergic inhibition from lateral septum (LS) to RE, underlying the compromised fear extinction. RE projects to ventral hippocampus (vHPC), which in turn sends projections characterized by feed-forward inhibition to the GABAergic neurons of the LS. This is coupled with long-range GABAergic projections from the LS to RE, collectively constituting an overall positive feedback circuit construct that promotes fear extinction. RE-specific remimazolam negates the facilitation of fear extinction by disrupting this circuit. Thus, remimazolam in RE disrupts fear extinction caused by hippocamposeptal intermediation, offering mechanistic insights for the dilemma of combining anxiolytics with extinction-based exposure therapy.


Assuntos
Benzodiazepinas , Extinção Psicológica , Medo , Hipocampo , Núcleos da Linha Média do Tálamo , Medo/efeitos dos fármacos , Animais , Benzodiazepinas/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Hipocampo/metabolismo , Extinção Psicológica/efeitos dos fármacos , Masculino , Núcleos da Linha Média do Tálamo/efeitos dos fármacos , Núcleos da Linha Média do Tálamo/fisiologia , Núcleos da Linha Média do Tálamo/metabolismo , Ratos , Ansiolíticos/farmacologia , Camundongos
10.
Biomed Pharmacother ; 176: 116850, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38834006

RESUMO

Depression is a prevalent psychiatric disorder with accumulating evidence implicating dysregulation of extracellular adenosine triphosphate (ATP) levels in the medial prefrontal cortex (mPFC). It remains unclear whether facilitating endogenous ATP production and subsequently increasing extracellular ATP level in the mPFC can exert a prophylactic effect against chronic social defeat stress (CSDS)-induced depressive-like behaviors and enhance stress resilience. Here, we found that nicotinamide mononucleotide (NMN) treatment effectively elevated nicotinamide adenine dinucleotide (NAD+) biosynthesis and extracellular ATP levels in the mPFC. Moreover, both the 2-week intraperitoneal (i.p.) injection and 3-week oral gavage of NMN prior to exposure to CSDS effectively prevented the development of depressive-like behavior in mice. These protective effects were accompanied with the preservation of both NAD+ biosynthesis and extracellular ATP level in the mPFC. Furthermore, catalyzing ATP hydrolysis by mPFC injection of the ATPase apyrase negated the prophylactic effects of NMN on CSDS-induced depressive-like behaviors. Prophylactic NMN treatment also prevented the reduction in GABAergic inhibition and the increase in excitability in mPFC neurons projecting to the lateral habenula (LHb). Collectively, these findings demonstrate that the prophylactic effects of NMN on depressive-like behaviors are mediated by preventing extracellular ATP loss in the mPFC, which highlights the potential of NMN supplementation as a novel approach for protecting and preventing stress-induced depression in susceptible individuals.


Assuntos
Trifosfato de Adenosina , Comportamento Animal , Depressão , Camundongos Endogâmicos C57BL , Mononucleotídeo de Nicotinamida , Córtex Pré-Frontal , Estresse Psicológico , Animais , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Masculino , Trifosfato de Adenosina/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Depressão/tratamento farmacológico , Depressão/prevenção & controle , Depressão/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Camundongos , Comportamento Animal/efeitos dos fármacos , Derrota Social , NAD/metabolismo , Modelos Animais de Doenças
11.
BMC Public Health ; 24(1): 1531, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844910

RESUMO

BACKGROUND: To investigate the changes in the unhealthy eye-related behaviors of junior middle school students during the COVID-19 pandemic and the double reduction policy and its relationship with myopia. METHODS: Data were obtained from the 2019-2022 Tianjin Children and Youth Myopia, Common Diseases and Health Influencing Factors Survey. Latent profile analysis (LPA) and a generalized linear model (GLM) were applied to analyze the effect of eye-related behavior classes on myopia. RESULTS: A total of 2508 junior middle school students were included. The types of eye-related behavior were categorized into the medium-healthy behavior group, heavy academic burden and near-eye behavior group, insufficient lighting group and high-healthy behavior group. Students with heavy academic burdens and near-eye behavior were more likely to develop myopia than were those in the high-healthy group (OR = 1.466, 95% CI = 1.203-1.787; P < 0.001). CONCLUSIONS: The dual reduction policy has a positive effect on improving unhealthy eye-related behaviors, and the prevention and control of myopia through the use of different combinations of eye-related behaviors are heterogeneous among junior middle school students. In the post-COVID-19 period, we should continue to implement a double reduction policy and formulate targeted eye-related behavior strategies to provide an important reference for the prevention and control of myopia among children and adolescents during public health emergencies in the future.


Assuntos
COVID-19 , Miopia , Estudantes , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , Miopia/epidemiologia , Miopia/psicologia , Miopia/prevenção & controle , Masculino , Feminino , Adolescente , Criança , Estudantes/psicologia , Estudantes/estatística & dados numéricos , China/epidemiologia , Comportamentos Relacionados com a Saúde , Pandemias , Instituições Acadêmicas , Inquéritos e Questionários
12.
Int Heart J ; 65(3): 498-505, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38825494

RESUMO

This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.


Assuntos
Interleucina-10 , Leucócitos Mononucleares , MicroRNAs , Infarto do Miocárdio , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , MicroRNAs/sangue , MicroRNAs/genética , Interleucina-10/sangue , Interleucina-10/metabolismo , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Inflamação/genética , Inflamação/sangue , Inflamação/metabolismo , Estudos de Casos e Controles
13.
Biomaterials ; 311: 122664, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38889597

RESUMO

In order to guide the formulation of post-stroke treatment strategy in time, it is necessary to have real-time feedback on collateral circulation and revascularization. Currently used near-infrared II (NIR-II) probes have inherent binding with endogenous albumin, resulting in significant background signals and uncontrollable pharmacokinetics. Therefore, the albumin-escaping properties of the new probe, IR-808AC, was designed, which achieved timely excretion and low background signal, enabling the short-term repeatable injection for visualization of cerebral vessels and perfusion. We further achieved continuous observation of changes in collateral vessels and perfusion during the 7-d period in middle cerebral artery occlusion mice using IR-808AC in vivo. Furthermore, using IR-808AC, we confirmed that remote ischemic conditioning could promote collateral vessels and perfusion. Finally, we evaluated the revascularization after thrombolysis on time in embolic stroke mice using IR-808AC. Overall, our study introduces a novel methodology for safe, non-invasive, and repeatable assessment of collateral circulation and revascularization in real-time that is crucial for the optimization of treatment strategies.

14.
Pestic Biochem Physiol ; 202: 105946, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879333

RESUMO

Eriochloa villosa (Thunb.) Kunth is a troublesome weed widely distributed in maize (Zea mays L.) fields in Northeast China. Many populations of E. villosa have evolved resistance to nicosulfuron herbicides, which inhibit acetolactate synthase (ALS). The objectives of this research were to confirm that E. villosa is resistant to nicosulfuron and to investigate the basis of nicosulfuron resistance. Whole-plant dose-response studies revealed that the R population had not developed a high level of cross-resistance and exhibited greater resistant (25.62-fold) to nicosulfuron than that of the S population and had not yet developed a high level of cross-resistance. An in vitro ALS activity assay demonstrated that the I50 of nicosulfuron was 6.87-fold greater in the R population than the S population. However, based on ALS gene sequencing, the target ALS gene in the R population did not contain mutations. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that ALS gene expression between the R and S populations was significantly different after nicosulfuron application, but no differences were observed in the gene copy number. After the cytochrome P450 inhibitor malathion or the GST inhibitor NBD-Cl was applied, the resistant E. villosa population exhibited increased sensitivity to nicosulfuron. Based on the activities of GSTs and P450s, the activities of the R population were greater than those of the S population after nicosulfuron application. This is the first report that the resistance of E. villosa to ALS inhibitors results from increased target gene expression and increased metabolism. These findings provide a theoretical foundation for the effective control of herbicide-resistant E. villosa.


Assuntos
Acetolactato Sintase , Resistência a Herbicidas , Herbicidas , Piridinas , Compostos de Sulfonilureia , Compostos de Sulfonilureia/farmacologia , Acetolactato Sintase/genética , Acetolactato Sintase/metabolismo , Acetolactato Sintase/antagonistas & inibidores , Resistência a Herbicidas/genética , Herbicidas/farmacologia , Piridinas/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Poaceae/genética , Poaceae/efeitos dos fármacos
15.
Huan Jing Ke Xue ; 45(6): 3153-3164, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897739

RESUMO

The accurate prediction of spatial variation trends in groundwater SO42- is of great significance for improving groundwater quality and regional groundwater management level. The multi-source spatio-temporal data such as land cover data, soil parameter data, digital elevation data, and groundwater pH value in the plain area of the Yarkant River Basin in 2011, 2014, 2017, and 2020 were used as characteristic variables to analyze their correlation with groundwater SO42- concentration. To enhance the prediction accuracy, the Bayesian optimization algorithm (BOA) was used to optimize the random forest regression (RFR). Based on the BOA-RFR model, the importance of the characteristic variables was analyzed, the prediction accuracy of the model was evaluated, and the groundwater SO42- prediction map was generated. The results showed that pH value, ground elevation (GE), and percentage of bare land (BAR) in the contribution area were important parameters influencing groundwater hydrochemical composition, which were significantly negatively correlated with groundwater SO42- concentration, and the importance of impact factors for predicting groundwater SO42- concentration exceeded 25 %. The geostatistical interpolation method was used as an auxiliary tool for the predictive modeling of spatial distribution. After adding auxiliary samples, the R2 of groundwater SO42- concentration prediction of the BOA-RFR model was greater than 0.96, and the maximum values of RMSE and MAE were reduced by 4.7 % and 23.8 %, respectively, compared with the minimum values of the model with fewer samples. The SO42- concentration prediction map showed that high SO42- groundwater was enriched in the northeast of the plain area of the Yarkand River Basin, an area that was expanding.

16.
Natl Sci Rev ; 11(7): nwad270, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38883291

RESUMO

Room-temperature superconductivity has been a long-held dream of mankind and a focus of considerable interest in the research field of superconductivity. Significant progress has recently been achieved in hydrogen-based superconductors found in superhydrides (hydrides with unexpectedly high hydrogen contents) that are stabilized under high-pressure conditions and are not capturable at ambient conditions. Of particular interest is the discovery of a class of best-ever-known superconductors in clathrate metal superhydrides that hold the record for high superconductivity (e.g. T c = 250-260 K for LaH10) among known superconductors and have great promise to be those that realize the long-sought room-temperature superconductivity. In these peculiar clathrate superhydrides, hydrogen forms unusual 'clathrate' cages containing encaged metal atoms, of which such a kind was first reported in a calcium hexa-superhydride (CaH6) showing a measured high T c of 215 K under a pressure of 170 GPa. In this review, we aim to offer an overview of the current status of research progress on the clathrate metal superhydride superconductors, discuss the superconducting mechanism and highlight the key features (e.g. structure motifs, bonding features, electronic structure, etc.) that govern the high-temperature superconductivity. Future research direction along this line to find room-temperature superconductors will be discussed.

17.
Int J Obes (Lond) ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806646

RESUMO

OBJECTIVE: To evaluate the causal relationship between sleep fragmentation (SF) parameters with general and abdominal obesity in free-living conditions. METHODS: SF parameters were assessed by ActiGraph accelerometers for 7 consecutive days. Obesity was measured at baseline and 1-year follow-up with InBody S10 body composition analyzer. RESULTS: At baseline, the mean age of the study population was 18.7 years old (SD = 0.9) and 139 (35.7%) were male. Each 1-unit increase of baseline sleep fragmentation index (SFI) was associated with 0.08 kg/m2-increase of body mass index (BMI) (95% CI: 0.03, 0.14), 0.20%-increase of percentage of body fat (PBF) (95% CI: 0.07, 0.32), 0.15 kg-increase of fat mass (FM) (95% CI: 0.03, 0.27), 0.15 cm-increase of waist circumference (WC) (95% CI: 0.03, 0.26) and 0.91 cm2-increase of visceral fat area (VFA) (95% CI: 0.36, 1.46) at the 1-year follow-up. In addition, each 1-unit increase of baseline SFI was associated with 15% increased risk of general obesity (OR = 1.15, 95% CI = 1.04-1.28; p = 0.006) and 7% increased risk of abdominal obesity (OR = 1.07, 95% CI = 1.01-1.13; p = 0.021) in the following year. CONCLUSIONS: Fragmented sleep is independently associated with an increased risk of both general and abdominal obesity. The result highlights SF as a modifiable risk factor for the prevention and treatment of obesity.

18.
Plants (Basel) ; 13(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38794468

RESUMO

AIM: Plants distributed between southern Taiwan and the north of the Philippines are spread among numerous small islands in an area crossed by the powerful Kuroshio current. Oceanic currents can be effective seed-dispersal agents for coastal plant species. Moreover, the Luzon Strait is an area prone to tropical cyclones. The aim of this study is to look at the dispersal capability of an endangered coastal plant species, the Mearns fig (Ficus pedunculosa var. mearnsii), using both experimental and population genetics methods. LOCATION: Southern Taiwan, the Philippines, and the islands between Luzon and Taiwan Island. METHODS: This study combined two types of analysis, i.e., buoyancy experiments on syconia and double digest restriction-associated DNA sequencing (ddRAD), to analyze the population genetics of the Mearns fig. RESULTS: We first discovered that mature Mearns fig syconia could float in seawater. They have a mean float duration of 10 days to a maximum of 21 days. Germination rates varied significantly between Mearns fig seeds that had undergone different durations of flotation treatment. Population genetic analysis shows a high degree of inbreeding among various Mearns fig populations. Moreover, no isolation by distance was found between the populations and individuals. MAIN CONCLUSIONS: From our analysis of the genetic structure of the Mearns fig populations, we can clearly highlight the effect of the Kuroshio oceanic current on the seed dispersal of this fig tree. Comprehensive analysis has shown that Mearns fig seeds are still viable before the mature syconium sinks into the seawater, and so they could use the Kuroshio Current to float to the current population locations in Taiwan.

19.
Biomaterials ; 309: 122609, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38754290

RESUMO

The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed. The specifically designed DDS exhibits a successive targeting property, enabling it to precisely target ICC cells and their mitochondria. By specifically targeting the mitochondria, DDS produces reactive oxygen species (ROS) through its sonodynamic therapy effect, achieving a more potent reduction in ATP levels compared to non-targeted approaches, through the impairment of mitochondrial function. Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production. This dual-action strategy on both mitochondria and lipids can hinder energy utilization to restore drug sensitivity to BGJ398 in ICC. Moreover, an orthotopic mice model of drug-resistant ICC was developed, which serves as an exacting platform for evaluating the multifunction of designed DDS. Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Metabolismo dos Lipídeos , Mitocôndrias , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/metabolismo , Animais , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/metabolismo , Antígenos CD36/metabolismo , Estruturas Metalorgânicas/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos BALB C , Lipase/metabolismo
20.
Nat Metab ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698281

RESUMO

Diabetic cardiomyopathy is characterized by myocardial lipid accumulation and cardiac dysfunction. Bile acid metabolism is known to play a crucial role in cardiovascular and metabolic diseases. Takeda G-protein-coupled receptor 5 (TGR5), a major bile acid receptor, has been implicated in metabolic regulation and myocardial protection. However, the precise involvement of the bile acid-TGR5 pathway in maintaining cardiometabolic homeostasis remains unclear. Here we show decreased plasma bile acid levels in both male and female participants with diabetic myocardial injury. Additionally, we observe increased myocardial lipid accumulation and cardiac dysfunction in cardiomyocyte-specific TGR5-deleted mice (both male and female) subjected to a high-fat diet and streptozotocin treatment or bred on the diabetic db/db genetic background. Further investigation reveals that TGR5 deletion enhances cardiac fatty acid uptake, resulting in lipid accumulation. Mechanistically, TGR5 deletion promotes localization of CD36 on the plasma membrane through the upregulation of CD36 palmitoylation mediated by the palmitoyl acyltransferase DHHC4. Our findings indicate that the TGR5-DHHC4 pathway regulates cardiac fatty acid uptake, which highlights the therapeutic potential of targeting TGR5 in the management of diabetic cardiomyopathy.

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