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1.
Pathol Res Pract ; 258: 155357, 2024 May 20.
Article En | MEDLINE | ID: mdl-38772116

Member of the V-type ATPase family have attracted vast attention in tumor progression. Nevertheless, the specific member of V-ATPase, ATP6V1C2, its regulatory function in colorectal cancer (CRC) progression was poorly understood. In this study, comprehensive analyses demonstrated the role of ATP6V1C2 in CRC progression and drug screening based on ATP6V1C2 was carried out. As a result, among the ATPV1s family, ATP6V1C2 was significantly highly expressed in CRC. Immuno-infiltration analysis suggests that, the interaction between CRC cells and immune cells resulting in reduced immune and estimate scores. GSEA analysis found that, ATP6V1C2 negatively correlates with immune cells,especially CD8T cells. Next, Ecotyper database queries indicated that ATP6V1C2 was negatively correlates with characteristic gene expression in CD8T cells. Then, COX regression analysis and survival curves made it clear that ATP6V1C2 is positively correlates with clinicopathological progression leading to poor CRC prognosis. CellMiner explore told us LOR-253 and Sonidegib may be effective in CRC cancer treatment. Molecular Docking between ATP6V1C2 and 9 first-line and 9 natural drugs showed that ATP6V1C2 was recognized by the best geometrical and energetic matching pattern of 2 First-line and 4 natural drugs. RT-PCR and immunoblotting confirmed that ATP6V1C2 was significantly overexpressed in CRC. Four natural drugs screened by molecular docking were effective in cell proliferation inhibition by CCK8 test. In summary, ATP6V1C2 may be a new therapeutic target for CRC. The illustration is shown in Figure 9.

2.
Phytochem Anal ; 2024 May 21.
Article En | MEDLINE | ID: mdl-38772567

BACKGROUND: Lysimachia christinae Hance (LCH) is a traditional medicine used to treat gallstone disease and cholecystitis. Despite its known anti-inflammatory and choleretic effects, its quality has not been extensively evaluated. OBJECTIVE: In this study, we aimed to establish a reliable quality evaluation method for LCH via fingerprint, spectrum-effect relationship, and quantitative analyses of multicomponents by a single marker (QAMS). METHODS: First, the fingerprints and anti-inflammatory and choleretic activities of 14 LCH batches were determined. Then, the gray relation analysis method was used to analyze the peak areas of the fingerprint profile and pharmacodynamic data. Subsequently, the characteristic peaks were tentatively identified using high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Finally, rutin was selected as the internal reference material, and QAMS was used to analyze the LCH components. RESULTS: Pharmacodynamic experiments confirmed that LCH exerted anti-inflammatory and choleretic effects. Moreover, 15 flavonoids related to the anti-inflammatory and choleretic effects of LCH were identified. Notably, relative error percentage between the QAMS and external standard method was less than 5%. CONCLUSION: This study successfully established a comprehensive evaluation method for the qualitative and quantitative analyses of LCH.

3.
Anal Chem ; 2024 May 22.
Article En | MEDLINE | ID: mdl-38774984

Zearalenone (ZEN) is an extremely hazardous chemical widely existing in cereals, and its high-sensitivity detection possesses significant significance to human health. Here, the cathodic aggregation-induced electrochemiluminescence (AIECL) performance of tetraphenylethylene nanoaggregates (TPE NAs) was modulated by solvent regulation, based on which an electrochemiluminescence (ECL) aptasensor was constructed for sensitive detection of ZEN. The aggregation state and AIECL of TPE NAs were directly and simply controlled by adjusting the type of organic solvent and the fraction of water, which solved the current shortcomings of low strength and weak stability of the cathode ECL signal for TPE. Impressively, in a tetrahydrofuran-water mixed solution (volume ratio, 6:4), the relative ECL efficiency of TPE NAs reached 16.03%, which was 9.2 times that in pure water conditions, and the maximum ECL spectral wavelength was obviously red-shifted to 617 nm. In addition, "H"-shape DNA structure-mediated dual-catalyzed hairpin self-assembly (H-D-CHA) with higher efficiency by the synergistic effect between the two CHA reactions was utilized to construct a sensitive ECL aptasensor for ZEN analysis with a low detection limit of 0.362 fg/mL. In conclusion, solvent regulation was a simple and efficient method for improving the performance of AIECL materials, and the proposed ECL aptasensor had great potential for ZEN monitoring in food safety.

4.
Materials (Basel) ; 17(9)2024 Apr 26.
Article En | MEDLINE | ID: mdl-38730830

This study is aimed at examining the mesoscopic mechanical response and crack development characteristics of asphalt mixtures using the three-dimensional discrete element approach via particle flow code (PFC). The material is considered an assembly of three phases of aggregate, mortar, and voids, for which three types of contact are identified and described using a modified Burgers model allowing for bond failure and crack formation at contact. The laboratory splitting test is conducted to determine the contact parameters and to provide the basis for selecting three different load levels used in the indirect tensile fatigue test and simulation. The reliability of the simulation is verified by comparing the fatigue lives and dissipated energies against those from the test. Under cyclic loading, the internal tensile and compressive force chains vary dynamically as a response to the cyclic loading; both are initially concentrated beneath the top loading strip and then extend downward along the loading line. The compressive chains are oriented roughly vertically and develop an elliptic shape as damage grows, while the tensile chains are mostly horizontal and become denser. An analysis based on the histories of the numbers of different contact types indicates that damage mainly originates from bond failures among the aggregate particles and at the aggregate-mortar interfaces. In terms of location, cracking is initiated below the loading point (consistent with observations from the force chains) and propagates downward and laterally, leading to the macrocrack along the vertical diameter. The findings provide a mesoscopic understanding of the fatigue damage initiation and propagation in asphalt mixture.

5.
ISA Trans ; 2024 May 04.
Article En | MEDLINE | ID: mdl-38729908

Unsupervised domain adaptation has been extensively researched in rotating-machinery cross-domain fault diagnosis. A multi-source domain adaptive network based on local kernelized higher-order moment matching is constructed in this research for rotating-machinery fault diagnosis. Firstly, a multi-branch network is designed to map each source-target pair to a domain-specific shared space and to extract domain-invariant features using domain adversarial thought. Then, a local kernelized higher-order moment matching algorithm is proposed to perform fine-grained matching in shared category subspace. Finally, a feature fusion strategy based on the local domain distribution deviation is applied to synthesize the output features of multiple classifiers to obtain diagnostic results. The experimental validation of two-branch and three-branch networks on two public datasets is carried out and average diagnostic accuracies both exceed 99%. The results demonstrate the effectiveness and superiority of the approach.

6.
Front Aging Neurosci ; 16: 1403142, 2024.
Article En | MEDLINE | ID: mdl-38774266

Type I interferons (IFN-I) represent a group of pleiotropic cytokines renowned for their antiviral activity and immune regulatory functions. A multitude of studies have unveiled a critical role of IFN-I in the brain, influencing various neurological processes and diseases. In this mini-review, I highlight recent findings on IFN-I's effects on brain aging, Alzheimer's disease (AD) progression, and central nervous system (CNS) homeostasis. The multifaceted influence of IFN-I on brain health and disease sheds light on the complex interplay between immune responses and neurological processes. Of particular interest is the cGAS-STING-IFN-I axis, which extensively participates in brain aging and various forms of neurodegeneration. Understanding the intricate role of IFN-I and its associated pathways in the CNS not only advances our comprehension of brain health and disease but also presents opportunities for developing interventions to modify the process of neurodegeneration and prevent age-related cognitive decline.

7.
Cancer Control ; 31: 10732748241255212, 2024.
Article En | MEDLINE | ID: mdl-38769789

OBJECTIVE: A high number of Non-Small Cell Lung Cancer (NSCLC) patients with brain metastasis who have not had surgery often have a negative outlook. Radiotherapy remains a most common and effective method. Nomograms were developed to forecast the cancer-specific survival (CSS) and overall survival (OS) in NSCLC individuals with nonoperative brain metastases who underwent radiotherapy. METHODS: Information was gathered from the Surveillance, Epidemiology, and End Results (SEER) database about patients diagnosed with NSCLC who had brain metastases not suitable for surgery. Nomograms were created and tested using multivariate Cox regression models to forecast CSS and OS at intervals of 1, 2, and 3 years. RESULTS: The research involved 3413 individuals diagnosed with NSCLC brain metastases who had undergone radiotherapy but had not experienced surgery. These participants were randomly divided into two categories. The analysis revealed that gender, age, ethnicity, marital status, tumor location, tumor laterality, tumor grade, histology, T stage, N stage, chemotherapy, tumor size, lung metastasis, bone metastasis, and liver metastasis were significant independent predictors for OS and CSS. The C-index for the training set for predicting OS was .709 (95% CI, .697-.721), and for the validation set, it was .705 (95% CI, .686-.723), respectively. The C-index for predicting CSS was .710 (95% CI, .697-.722) in the training set and .703 (95% CI, .684-.722) in the validation set, respectively. The nomograms model, as suggested by the impressive C-index, exhibits outstanding differentiation ability. Moreover, the ROC and calibration curves reveal its commendable precision and distinguishing potential. CONCLUSIONS: For the first time, highly accurate and reliable nomograms were developed to predict OS and CSS in NSCLC patients with non-surgical brain metastases, who have undergone radiotherapy treatment. The nomograms may assist in tailoring counseling strategies and choosing the most effective treatment method.


Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Nomograms , SEER Program , Humans , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Male , Female , Brain Neoplasms/secondary , Brain Neoplasms/radiotherapy , Brain Neoplasms/mortality , Lung Neoplasms/radiotherapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Middle Aged , Aged , Prognosis , Adult
8.
J Agric Food Chem ; 2024 May 23.
Article En | MEDLINE | ID: mdl-38779705

The monofloral honey from Schefflera octophylla (Lour.) Harms (MH-Sco) are of high economic value due to their rarity and potential medicinal benefits. However, the limited investigations on the relationship of phytogenic components between the plant S. octophylla (P-Sco) and MH-Sco have an impact on MH-Sco authentication. Herein, the tentative phytogenic markers of MH-Sco were screened by comparing the metabolites of MH-Sco obtained by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS)-based untargeted metabolomics with the identified phytogenic chemicals from P-Sco. Combined with the mass and NMR spectral information, 3α-hydroxylup-20(29)-ene-23,28-dioic acid (HLEDA) was finally identified as the phytogenic marker of MH-Sco. A targeted ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS)-based method was established and validated based on the purified monomer standard to measure HLEDA levels in honey samples. HLEDA determined in MH-Sco was with the content from 0.303 to 0.440 mg/kg, while HLEDA was absent in honey samples from other botanical origins, indicating the reliability of HLEDA as a chemical marker in MH-Sco authentication. This study provides the theoretical basis and industry guidance for honey quality control for commercial consumption.

9.
ACS Appl Mater Interfaces ; 16(20): 26121-26129, 2024 May 22.
Article En | MEDLINE | ID: mdl-38728577

The design of aqueous zinc-ion batteries (ZIBs) that have high specific capacity and long-term stability is essential for future large-scale energy storage systems. Cathode materials with extended π-conjugation and abundant active sites are desirable to enhance the charge storage performance and the cycling stability of the aqueous ZIB. Based on this concept, 6,9-dihydropyrazino[2,3-g]quinoxaline-2,3,7,8(1H,4H)-tetrone was chosen as the monomer to be electropolymerized onto carbon cloth (PDHPQ-Tetrone/CC). When used as the cathode material for aqueous ZIBs, an exceptional cycling life (>20,000 cycles) at a current density of 10 A g-1 was achieved, with the specific capacity maintained at 82.8% and with the Coulombic efficiency at around 100% throughout cycling. At the charge-discharge current density of 0.1 A g-1, the ZIB with PDHPQ-Tetrone/CC achieved a high specific capacity of 248 mAh g-1. Kinetic analyses showed that both surface-capacitive-controlled processes and semi-infinite diffusion-controlled processes contribute to the stored charge. The charge storage mechanism was investigated with ex situ characterizations and involves the redox processes of carbonyl/hydroxyl and amino/imino groups coupled with insertion and extraction of both Zn2+ and H+.

10.
Sci Total Environ ; 934: 173072, 2024 May 09.
Article En | MEDLINE | ID: mdl-38734093

The pollution of deep-sea microplastics has received increasing attention. As a special ecosystem in the deep sea, the cold seep area is of great significance for studying the distribution of microplastics in the deep sea. In this work, the distribution and characteristics of microplastics in seawater, sediments, and shellfish in the Haima cold seep area and the correlation between the characteristics of microplastics in different media and the type of media were studied. Microplastics were found in all three media. The abundance of microplastics in different samples from the Haima cold seep area ranged 1.8-3.8 items/L for the seawater, 11.47-96.8 items/kg (d.w.) for the surface sediments, and 0-5 items/individual (0-0.714 items/g) for the shellfish. The amount of microplastics ingested by shellfish varied among different species. The microplastics in these three media were mainly fibrous, dark-colored, small-sized rayon, polyethylene terephthalate (PET), and polyethylene (PE). In the correlation analysis of microplastic characteristics among the three media, it was found that the characteristics of microplastics in different media in the same area were closely related, and each pair of variables showed a significant positive correlation (P ≤ 0.05). The distinctive geographical conditions would accelerate the interchange of microplastics among various media. Principal component analysis showed that habitat contribute to microplastic feature differences in shellfish. Differences in correlation were observed between the characteristics of shellfish microplastics in different regions and the characteristics of microplastics in surrounding seawater and sediments.

11.
J Med Chem ; 67(10): 8296-8308, 2024 May 23.
Article En | MEDLINE | ID: mdl-38739678

Platinum-drug-based chemotherapy in clinics has achieved great success in clinical malignancy therapy. However, unpredictable off-target toxicity and the resulting severe side effects in the treatment are still unsolved problems. Although metabolic glycan labeling-mediated tumor-targeted therapy has been widely reported, less selective metabolic labeling in vivo limited its wide application. Herein, a novel probe of B-Ac3ManNAz that is regulated by reactive oxygen species in tumor cells is introduced to enhance the recognition and cytotoxicity of DBCO-modified oxaliplatin(IV) via bioorthogonal chemistry. B-Ac3ManNAz was synthesized from Ac4ManNAz by incorporation with 4-(hydroxymethyl) benzeneboronic acid pinacol ester (HBAPE) at the anomeric position, which is confirmed to be regulated by ROS and could robustly label glycans on the cell surface. Moreover, N3-treated tumor cells could enhance the tumor accumulation of DBCO-modified oxaliplatin(IV) via click chemistry meanwhile reduce the off-target distribution in normal tissue. Our strategy provides an effective metabolic precursor for tumor-specific labeling and targeted cancer therapies.


Antineoplastic Agents , Oxaliplatin , Polysaccharides , Prodrugs , Reactive Oxygen Species , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/chemical synthesis , Oxaliplatin/pharmacology , Oxaliplatin/chemistry , Humans , Reactive Oxygen Species/metabolism , Polysaccharides/chemistry , Polysaccharides/metabolism , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Mice , Cell Line, Tumor , Mice, Inbred BALB C , Mice, Nude
12.
Article En | MEDLINE | ID: mdl-38769195

BACKGROUND: High-resolution mapping offers superior accuracy in delineating conduction features; however, certain characteristics are still linked to elevated recurrence rates of atrial tachycardia (AT), suggesting the influence of additional mechanisms. This study systematically assessed the substrate of functional conduction block (FCB) regions in relation to the mechanisms of multiple ATs. METHODS: In this study, the Carto system facilitated the mapping of ATs in 13 patients undergoing ablation, each presenting with more than two AT variants. FCB regions were marked and further analyzed. RESULTS: A total of 33 sustained ATs were mapped across the patient cohort. FCB regions showed convertibility in 7 of 13 patients (54%). Three kinds of presentations can be summarized by the FCB region: Firstly, the FCB region could act as the main obstacle sustaining the localized reentrant pathway, for which rounding obviously has a direct correlation with the mechanism of the AT (27%). Secondly, the FCB regions could act as obstacle lines to reorganize the propagation of the reentry in localized AT and macroreentrant AT (55%). Lastly, the FCB region could act as a bystander and may not be related to the mechanism of the ATs (18%). The potentials in FCB regions mostly performed low voltages or fragmented potentials (FPs) in the ATs which they did not perform the conduction block (90%). CONCLUSION: In multiple ATs, FCB regions may not be uncommon. The participation of FCB regions in the mechanism of ATs showed three different kinds of performance. The dynamic nature of this substrate may provide insight into the reasons for the high recurrence of related ATs.

13.
Plant Dis ; 2024 May 02.
Article En | MEDLINE | ID: mdl-38698521

Fusarium pseudograminearum is an important plant pathogen that invades many crops (Zhang et al. 2018). Since it was first discovered in Australia in 1951, F. pseudograminearum has been reported in many countries and regions and caused huge economic losses (Burgess et al. 2001). In 2012, crown rot of wheat caused by F. pseudograminearum was discovered for the first time in Henan Province, China (Li et al. 2012). Wheat (Triticum aestivum L.) is one of the most important food crops in Xinjiang Uygur Autonomous Region (XUAR), with 1.07 million hectares cultivated in 2020. In June 2023, a survey of crown rot disease was carried out in winter wheat cv. Xindong 20 in Hotan area, XUAR, China (80.148907°E, 37.051474°N). About 5% of wheat plants showed symptoms of crown rot such as browning of the stem base and white head. The disease was observed in 85% of wheat fields. In order to identify the pathogens, 36 pieces of diseased stem basal tissue, 0.5 cm in length, were collected and sterilized with 75% alcohol for 30s and 5% NaOCl solution for 2 min, then rinsed three times with sterile water and placed on potato dextrose agar (PDA) medium at 25°C. A total of 27 isolates with consistent morphological characteristics were obtained using single-spore technique (Leslie and Summerell. 2006), and the isolation rate was 75%. The isolates grew rapidly on PDA, produced large numbers of fluffy white hyphae, and pink pigment accumulated in the medium. The isolates were grown on 2% mung bean flour medium and identified by morphological and molecular methods. Macroconidia were abundant, relatively slender, curved to almost straight, commonly two to seven septate, and averaged 22 to 72 × 1.8 to 4.9 µm. Microconidia were not observed. The morphological characters are consistent with Fusarium (Aoki and O'Donnell. 1999). Two isolates (LP-1 and LP-3) were selected for molecular identification. Primers EF1/EF2 (5'-ATGGGTAAGGARGACAAGAC-3'/5'-GGARGTACCAGTSATCATG-3') were used to amplify a portion of the EF-1α gene (O'Donnell et al. 1998). The two 696 bp PCR products were sequenced and submitted to GenBank. The EF-1α gene sequences (GenBank Accession No: PP062794 and PP062795) shared 99.9% identity (695/696) with published F.pseudograminearum sequences (e.g., OP105187, OP105184, OP105179, OP105173). The identification was further confirmed by F. pseudograminearum species-specific PCR primers Fp1-1/Fp1-2 (Aoki and O'Donnell. 1999). The expected PCR products of 518 bp were produced only in F. pseudograminearum. Pathogenicity tests of LP-1 and LP-3 isolates were performed on 7-day-old seedlings of winter wheat cv. Xindong 20 using the drip inoculation method with a 10-µl of a 106 macroconidia ml-1 suspension near the stem base (Xu et al. 2017). The experiment was repeated five times in a 20 to 25°C greenhouse. Control seedlings were treated with sterile water. After 4 weeks, wheat seedling death and crown browning occurred in the inoculated plants with over 90% incidence. No symptoms were observed in the control plants. The pathogen was reisolated from the inoculated plants by the method described above and identified by morphological and PCR amplification using F. pseudograminearum species-specific primers Fp1-1/Fp1-2. No F. pseudograminearum was isolated from the control plants, fulfilling Koch's postulates. To our knowledge, this is the first report of F. pseudograminearum causing crown rot of winter wheat in XUAR of China. Since F. pseudograminearum can cause great damage to wheat, one of the most important food crops in China, necessary measures should be taken to prevent the spread of F. pseudograminearum to other regions.

14.
Sci Rep ; 14(1): 11295, 2024 05 17.
Article En | MEDLINE | ID: mdl-38760401

Intercropping with Pleurotus ostreatus has been demonstrated to increase the tea yield and alleviate soil acidification in tea gardens. However, the underlying mechanisms remain elusive. Here, high-throughput sequencing and Biolog Eco analysis were performed to identify changes in the community structure and abundance of soil microorganisms in the P. ostreatus intercropped tea garden at different seasons (April and September). The results showed that the soil microbial diversity of rhizosphere decreased in April, while rhizosphere and non-rhizosphere soil microbial diversity increased in September in the P. ostreatus intercropped tea garden. The diversity of tea tree root microorganisms increased in both periods. In addition, the number of fungi associated with organic matter decomposition and nutrient cycling, such as Penicillium, Trichoderma, and Trechispora, was significantly higher in the intercropped group than in the control group. Intercropping with P. ostreatus increased the levels of total nitrogen (TN), total phosphorus (TP), and available phosphorus (AP) in the soil. It also improved the content of secondary metabolites, such as tea catechins, and polysaccharides in tea buds. Microbial network analysis showed that Unclassified_o__Helotiales, and Devosia were positively correlated with soil TN and pH, while Lactobacillus, Acidothermus, and Monascus were positively correlated with flavone, AE, and catechins in tea trees. In conclusion, intercropping with P. ostreatus can improve the physical and chemical properties of soil and the composition and structure of microbial communities in tea gardens, which has significant potential for application in monoculture tea gardens with acidic soils.


Microbiota , Plant Roots , Pleurotus , Rhizosphere , Soil Microbiology , Soil , Tea , Pleurotus/growth & development , Pleurotus/metabolism , Plant Roots/microbiology , Tea/microbiology , Soil/chemistry , Camellia sinensis/microbiology , Nitrogen/metabolism , Nitrogen/analysis , Phosphorus/analysis , Phosphorus/metabolism , Fungi/metabolism , Bacteria/classification , Bacteria/genetics , Bacteria/metabolism , Hydrogen-Ion Concentration
15.
Med ; 2024 May 17.
Article En | MEDLINE | ID: mdl-38761802

BACKGROUND: Achieving universal health coverage (UHC) involves all individuals attaining accessible health interventions at an affordable cost. We examined current patterns and temporal trends of cancer mortality and UHC across sociodemographic index (SDI) settings, and quantified these association. METHODS: We used data from the Global Burden of Disease Study 2019 and Our World in Data. The UHC effective coverage index was obtained to assess the potential population health gains delivered by health systems. The estimated annual percentage change (EAPC) with a 95% confidence interval (CI) was calculated to quantify the trend of cancer age-standardized mortality rate (ASMR). A generalized linear model was applied to estimate the association between ASMR and UHC. FINDINGS: The high (EAPC = -0.9% [95% CI, -1.0%, -0.9%]) and high-middle (-0.9% [-1.0%, -0.8%]) SDI regions had the fastest decline in ASMR (per 100,000) for total cancers from 1990 to 2019. The overall UHC effective coverage index increased by 27.9% in the high-SDI quintile to 62.2% in the low-SDI quintile. A negative association was observed between ASMR for all-cancer (adjusted odds ratio [OR] = 0.87 [0.76, 0.99]), stomach (0.73 [0.56, 0.95]), breast (0.64 [0.52, 0.79]), cervical (0.42 [0.30, 0.60]), lip and oral cavity (0.55 [0.40, 0.75]), and nasopharynx (0.42 [0.26, 0.68]) cancers and high UHC level (the lowest as the reference). CONCLUSIONS: Our findings strengthen the evidence base for achieving UHC to improve cancer outcomes. FUNDING: This work is funded by the China National Natural Science Foundation and Chinese Academy of Medical Sciences Innovation Fund for Medical Science.

16.
BMC Cancer ; 24(1): 504, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38644473

BACKGROUND: Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective treatment currently. Proteolysis-targeting chimeric molecules (PROTACs) may provide new therapeutic avenues for treatment of podophyllotoxin derivatives-resistant SCLC with LM, warranting further exploration. METHODS: The SCLC cell line H128 expressing luciferase were mutated by MNNG to generate H128-Mut cell line. After subcutaneous inoculation of H128-Mut into nude mice, H128-LM and H128-BPM (brain parenchymal metastasis) cell lines were primarily cultured from LM and BPM tissues individually, and employed to in vitro drug testing. The SCLC-LM mouse model was established by inoculating H128-LM into nude mice via carotid artery and subjected to in vivo drug testing. RNA-seq and immunoblotting were conducted to uncover the molecular targets for LM. RESULTS: The SCLC-LM mouse model was successfully established, confirmed by in vivo live imaging and histological examination. The upregulated genes included EZH2, SLC44A4, VEGFA, etc. in both BPM and LM cells, while SLC44A4 was particularly upregulated in LM cells. When combined with PROTAC EZH2 degrader-1, the drug sensitivity of cisplatin, etoposide (VP16), and teniposide (VM26) for H128-LM was significantly increased in vitro. The in vivo drug trials with SCLC-LM mouse model demonstrated that PROTAC EZH2 degrader-1 plus VM26 or cisplatin/ VP16 inhibited H128-LM tumour significantly compared to VM26 or cisplatin/ VP16 alone (P < 0.01). CONCLUSION: The SCLC-LM model effectively simulates the pathophysiological process of SCLC metastasis to the leptomeninges. PROTAC EZH2 degrader-1 overcomes chemoresistance in SCLC, suggesting its potential therapeutic value for SCLC LM.


Drug Resistance, Neoplasm , Enhancer of Zeste Homolog 2 Protein , Lung Neoplasms , Mice, Nude , Podophyllotoxin , Small Cell Lung Carcinoma , Animals , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Small Cell Lung Carcinoma/metabolism , Mice , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Lung Neoplasms/metabolism , Drug Resistance, Neoplasm/drug effects , Enhancer of Zeste Homolog 2 Protein/metabolism , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , Podophyllotoxin/pharmacology , Podophyllotoxin/analogs & derivatives , Podophyllotoxin/therapeutic use , Cell Line, Tumor , Meningeal Carcinomatosis/drug therapy , Meningeal Carcinomatosis/secondary , Xenograft Model Antitumor Assays , Proteolysis/drug effects
17.
Mater Adv ; 5(7): 2968-2973, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38572482

Metal carbonate hydroxides have emerged as novel and promising candidates for water splitting due to their good electrochemical properties and eco-friendly features. In this study, the hierarchical mesoporous structure of nickel carbonate hydroxide hydrate (Ni2(CO3)(OH)2·4H2O) was synthesized by a one-pot facile hydrothermal method. It demonstrated photocatalytic properties for the first time, exhibiting a hydrogen evolution reaction yield of 10 µmol g-1 h-1 under white light irradiation with a nominal power of 0.495 W. This facile synthesis strategy and the good photocatalytic properties indicate that nickel carbonate hydroxide is a promising material for application in photocatalytic hydrogen evolution.

18.
Wound Repair Regen ; 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38602090

An argon-based low-temperature plasma jet (LTPJ) was used to treat chronically infected wounds in Staphylococcus aureus-laden mice. Based on physicochemical property analysis and in vitro antibacterial experiments, the effects of plasma parameters on the reactive nitrogen and oxygen species (RNOS) content and antibacterial capacity were determined, and the optimal treatment parameters were determined to be 4 standard litre per minute and 35 W. Additionally, the plasma-treated activation solution had a bactericidal effect. Although RNOS are related to the antimicrobial effect of plasma, excess RNOS may be detrimental to wound remodelling. In vivo studies demonstrated that medium-dose LTPJ promoted MMP-9 expression and inhibited bacterial growth during the early stages of healing. Moreover, LTPJ increased collagen deposition, reduced inflammation, and restored blood vessel density and TGF-ß levels to normal in the later stages of wound healing. Therefore, when treating chronically infected wounds with LTPJ, selecting the medium dose of plasma is more advantageous for wound recovery. Overall, our study demonstrated that low-temperature plasma jets may be a potential tool for the treatment of chronically infected wounds.

19.
New J Chem ; 48(15): 6704-6713, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38628578

FeNbO4 sonocatalysts were successfully synthesized by a simple hydrothermal route at pH values of 3, 5, 7, 9 and 11. The catalysts were characterized by XRD, XPS, TEM, SEM, N2 adsorption and DRS to analyse the effect of pH parameters on the physicochemical properties of the materials during hydrothermal synthesis. The sonocatalytic activity of FeNbO4 microspheres was evaluated by using acid orange 7 (AO7) as the simulated contaminant. The experimental results showed that the best sonocatalytic degradation ratio (97.45%) of organic dyes could be obtained under the conditions of an initial AO7 concentration of 10 mg L-1, an ultrasonic power of 200 W, a catalyst dosage of 1.0 g L-1, and a pH of 3. Moreover, the sonocatalysts demonstrated consistent durability and stability across multiple test cycles. After active species capture experiments and calculation of the energy band, a possible mechanism was proposed based on the special Fenton-like mechanism and the dissociation of H2O2. This research shows that FeNbO4 microspheres can be used as sonocatalysts for the purification of organic wastewater, which has a promising application prospect.

20.
Nat Commun ; 15(1): 3392, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38649379

Brain-like energy-efficient computing has remained elusive for neuromorphic (NM) circuits and hardware platform implementations despite decades of research. In this work we reveal the opportunity to significantly improve the energy efficiency of digital neuromorphic hardware by introducing NM circuits employing two-dimensional (2D) transition metal dichalcogenide (TMD) layered channel material-based tunnel-field-effect transistors (TFETs). Our novel leaky-integrate-fire (LIF) based digital NM circuit along with its Hebbian learning circuitry operates at a wide range of supply voltages, frequencies, and activity factors, enabling two orders of magnitude higher energy-efficient computing that is difficult to achieve with conventional material and/or device platforms, specifically the silicon-based 7 nm low-standby-power FinFET technology. Our innovative 2D-TFET based NM circuit paves the way toward brain-like energy-efficient computing that can unleash major transformations in future AI and data analytics platforms.

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