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1.
Ecotoxicol Environ Saf ; 282: 116682, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39002380

ABSTRACT

The effectiveness, tolerance, and safety of pesticides must be established before their scientific or rational. This study evaluates the field control efficacy of broflanilide, tetraniliprole, and chlorantraniliprole in combating Spodoptera frugiperda in maize crops, as well as the resistance of S. frugiperda to these three diamide pesticides after exposure. By assessing field control efficiency, toxicity, effects on development and reproduction, and detoxification enzyme activity of these diamide pesticides on S. frugiperda, highlights broflanilide's significant insecticidal potential. A highly sensitive and efficient method using QuEChERS/HPLCMS/MS was developed to simultaneously detect residues of these three pesticides on maize. Initial concentrations of broflanilide, tetraniliprole, and chlorantraniliprole ranged from 2.13 to 4.02 mg/kg, with their respective half-lives varying between 1.23 and 1.51 days. Following foliar application, by the time of harvest, the terminal residue concentrations of these pesticides were all under 0.01 mg/kg. Chronic dietary intake risk assessments and cumulative chronic dietary exposure for three pesticides indicated that the general population's terminal residue concentration was within acceptable limits. Not only does this research provide valuable insights into field control efficiency, insecticidal effects, resistance, residues, and risk assessment results of broflanilide, tetraniliprole, and chlorantraniliprole on maize, but additionally, it also paves the way for setting suitable Maximum Residue Limits (MRLs) values based on pre-harvest interval values, rational dosage, and application frequency.

2.
EClinicalMedicine ; 73: 102702, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39007066

ABSTRACT

Background: MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively. Methods: This multicentre, single-arm, phase 1b/2 trial aimed to explore the efficacy, pharmacokinetics, and safety of MIL62 combined with lenalidomide in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Eligible patients included those who had histopathologically confirmed CD20 positive FL (grade 1-3a) or MZL and failed to be treated with rituximab. Patients received intravenously infused MIL62 1000 mg (cycle 1: day 1, 15; cycles 2-8: day 1, cycles 10 and 12: day 1) combined with oral lenalidomide (once a day, days 2-22, the initial dose was 10 mg, and the maximum dose was 20 mg) for 12 cycles, 28 days as a cycle. The primary endpoint was objective response rate (ORR) assessed by investigator per Lugano 2014 criteria every 3 cycles. This study was registered in ClinicalTrials.gov (NCT04110301). Findings: Between November 22, 2019 and December 22, 2020, 54 patients were enrolled from 11 hospitals in China and received study treatment. Fifty patients were included in the efficacy analysis set, and 43 patients (86%, 95% CI: 73, 94) achieved objective response, meeting the pre-specified primary endpoint. Disease control rate was 96% (48/50, 95% CI: 86, 100), proportion of patients with duration of response (DoR) > 6 months was 77% (33/43). The median follow-up for survival was 12.3 months (IQR 12.0-12.6). The 1-year progression-free survival rate was 72% (95% CI: 57, 83), 9-month DoR rate was 74% (95% CI: 58, 85), and 1-year overall survival rate was 98% (95% CI: 85, 100). Most common TRAEs were neutropenia (93%, 50/54), leukopenia (85% 46/54), thrombocytopenia (61% 33/54), lymphopenia (32% 17/54), and alanine aminotransferase increased (20% 11/54). Interpretation: MIL62 combined with lenalidomide showed promising efficacy in patients with R/R FL and MZL. A multicentre, randomized, open-label, phase Ⅲ trial of MIL62 combined with lenalidomide versus lenalidomide in anti-CD20 monoclonal antibody refractory FL patients is ongoing (NCT04834024). Funding: Beijing Mabworks Biotech Co. Ltd, Beijing China and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

4.
bioRxiv ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39005277

ABSTRACT

In recent years, wearable electrocardiograms have risen in popularity as a solution for personal monitoring of heart activity. However, this technology has limitations in diagnostic capability and structural function monitoring. Meanwhile, auscultation of the heart remains a fundamental tool for physicians in diagnosis and monitoring of heart disease largely unaddressed in a convenient wearable format. The present work outlines a promising system currently under investigation, allowing user-initiated 10-second chest-sound recordings to be transmitted over Bluetooth-Low-Energy, with an innovative package design providing inherent noise reduction and a high signal-to-noise ratio. The device has been tested on healthy individuals, and system response has been validated against calibrated electrocardiogram recording equipment to analyze signal capture fidelity.

5.
Langmuir ; 40(28): 14641-14651, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38962868

ABSTRACT

In the circulating water system of coastal power plants, various kinds of ions have a great influence on the formation and growth of CaCO3 scales. This paper focuses on investigating the influence of existing ions on the pulse electrodeposition behaviors of CaCO3 scales. Different concentrations of ions, such as Fe3+, Mg2+, PO43- and SiO32-, are introduced to simulate the actual seawater environment, and their influence on the CaCO3 scale deposition behaviors is assessed by linear sweep voltammetry, chronoamperometry, and electrochemical impedance spectroscopy tests. The surface coverage of the CaCO3 scale layer is evaluated through the residual current density and polarization resistance values, while the crystal structure and surface compactness of the layer are confirmed by the scanning electron microscope and X-ray diffractometer tests. Results indicate that high concentrations of Mg2+, Fe3+, and PO43- ions have the most significant inhibitory effect on the pulse electrodeposition of CaCO3 scales, among which the inhibition effect of Mg2+ ions is mainly reflected in the change of crystal morphology of CaCO3, that is, the crystallization growth process is inhibited. The inhibition effect of PO43- ions is mainly reflected in the gradually reduced coverage and density of CaCO3 crystals on the electrode surface, suggesting that the crystallization nucleation process is inhibited, while Fe3+ ions have a certain inhibition effect on both the crystallization nucleation and growth processes. Furthermore, lower concentrations of SiO32- ions also display a significant inhibition effect on the crystallization nucleation and growth process, and the inhibition effect weakens with increased concentration. This study provides a theoretical basis for exploring the removal of ions in the industrial water softening field.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 702-707, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926956

ABSTRACT

OBJECTIVE: To investigate the effect of progression of disease within 24 months (POD24) on overall survival (OS) in patients with mantle cell lymphoma (MCL), and compare the clinical characteristics between POD24 and non-POD24 patients. METHODS: A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020. According to the occurrence of POD24, the patients were grouped for prognostic evaluation and clinical characteristics comparison. RESULTS: Univariate Cox regression analysis showed that POD24, PLT, albumin, MIPI score, ECOG PS score, LDH were the factors influencing OS in newly diagnosed MCL patients (all P < 0.05). The results of multivariate Cox regression analysis showed that POD24ï¼»HR=16.797(95%CI : 3.671-76.861),P < 0.001ï¼½, albumin<40 g/Lï¼»HR=3.238(95%CI :1.095-9.572),P =0.034ï¼½ and ECOG PS score≥2ï¼»HR=4.005(95%CI :1.033-15.521),P =0.045ï¼½ were independent risk factors influencing OS in MCL patients. The incidence of PLT<100×109/L (33.3% vs 5.9%, P =0.033) and ECOG PS score ≥2 (45.5% vs 5.9%, P =0.040) were significantly higher in POD24 patients than those in non-POD24 patients. CONCLUSION: POD24 is an independent poor prognostic factor affecting the OS of MCL patients, and the patients with PLT<100×109/L and ECOG PS score≥2 at diagnosis have a higher probability of POD24.


Subject(s)
Disease Progression , Lymphoma, Mantle-Cell , Humans , Prognosis , Retrospective Studies , Male , Female , Survival Rate , Proportional Hazards Models , Middle Aged
7.
Sci Total Environ ; 944: 173799, 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-38852863

ABSTRACT

Micro-nanoplastics (MNPs) pollution as a global environmental issue has received increasing interest in recent years. MNPs can enter and accumulate in the organisms including human beings mainly via ingestion and inhalation, and large amounts of foodborne MNPs have been frequently detected in human intestinal tracts and fecal samples. MNPs regulate the structure composition and metabolic functions of gut microbiota, which may cause the imbalance of intestinal ecosystems of the hosts and further mediate the occurrence and development of various diseases. In addition, a growing number of MNPs-degrading strains have been isolated from organismal feces. MNPs-degraders colonize the plastic surfaces and form the biofilms, and the long-chain polymers of MNPs can be biologically depolymerized into short chains. In general, MNPs are gradually degraded into small molecule substances (e.g., N2, CH4, H2O, and CO2) via a series of enzymatic catalyses, mainly including biodeterioration, fragmentation, assimilation, and mineralization. In this review, we outline the current progress of MNPs effects on gut microbiota and MNPs degradation by gut microbiota, which provide a certain theoretical basis for fully understanding the knowledge gaps on MNPs-related biological effect and biodegradation.


Subject(s)
Biodegradation, Environmental , Gastrointestinal Microbiome , Gastrointestinal Microbiome/physiology , Humans , Microplastics , Nanoparticles , Environmental Pollutants/metabolism
8.
Article in English | MEDLINE | ID: mdl-38906671

ABSTRACT

BACKGROUND AND PURPOSE: Preoperative assessment of meningioma consistency is beneficial for optimizing surgical strategy and prognosis of patients. We aim to develop a non-invasive prediction model for meningioma consistency utilizing magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI). MATERIALS AND METHODS: Ninety-four patients (52yr ± 22, 69 females, 25 males) diagnosed with meningioma were recruited in the study. Each patient underwent preoperative T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), DTI, and MRE. Combined MRE-DTI model was developed based on multiple logistic regression. Intraoperative tumor descriptions served as clinical criteria for evaluating meningioma consistency. The diagnostic efficacy in determining meningioma consistency was evaluated using receiver operating characteristic (ROC) curve. Further validation was conducted in twenty-seven stereotactic biopsies using indentation tests and underlying mechanism was investigated by histologic analysis. RESULTS: Among all the imaging modalities, MRE demonstrated the highest efficacy with the shear modulus magnitude (|G*|) achieving an area under the curve (AUC) of 0.81 (95% CI: 0.70-0.93). When combined with DTI, the diagnostic accuracy further increased (AUC: 0.88, 95% CI: 0.78-0.97), surpassing any modality alone. Indentation measurement based on stereotactic biopsies further demonstrated that the MRE-DTI model was suitable for predicting intra-tumor consistency. Histological analysis suggested that meningioma consistency may be correlated with tumor cell density and fibrous content. CONCLUSIONS: The MRE-DTI combined model is effective in noninvasive prediction of meningioma consistency. ABBREVIATIONS: MRE = magnetic resonance elastography; FA = fractional anisotropy; ROC = receiver operating characteristic; AUC = area under curve.

9.
Fitoterapia ; 177: 106097, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38945490

ABSTRACT

Doxorubicin (Dox)-induced cardiotoxicity (DIC) has limited its clinical application. It is crucial to discover more effective substances to treat DIC. In this study, a zebrafish model is used to evaluate the inhibition of DIC in the lipids in American ginseng (AGL) compared with the lipids in soybeans (SOL) and in egg yolks (YOL). A lipidomics approach based on Q Exactive LC-MS/MS is employed to monitor, identify, and analyze the lipid composition of three lipid samples. The H9c2 cell was used to investigate the key lipid in AGL for its effect mechanism in alleviating DIC. The results showed that AGL alleviated DIC on zebrafish by increasing the stroke volume, heart rate, and fractional shortening compared to SOL and YOL. A total of 216 differential lipids were identified among the three types of lipids using lipidomics. Besides, a fatty acid with 18 carbons and four double bonds, FA (18:4) was the dominant proportion in AGL and possessed the highest variable importance of projection (VIP) value. FA (18:4) also showed significant bioactivity to alleviate DIC in zebrafish. Furthermore, FA (18:4) reduced the ferric ions and reactive oxygen species (ROS) accumulation, increased GPX4 expression, and relieved mitochondrial damage to inhibit Dox-induced ferroptosis in H9c2 cells. Therefore, the composition characteristic and anti-DIC effect of AGL were revealed; FA (18,4) was identified for the first time to be a novel active component of AGL against DIC by inhibiting ferroptosis. These results provide a new understanding of AG-derived bioactive lipids and their potential benefits for heart health.

10.
BMC Urol ; 24(1): 118, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858691

ABSTRACT

PURPOSE: To present the experience of ileal ureter with ileocystoplasty (IUC), and compare the outcomes of IUC in minimally invasive procedures to open procedures. PATIENTS AND METHODS: From December 2017 to April 2023, twenty patients underwent IUC in open or minimally invasive (including laparoscopic and robotic) procedures. The baseline characteristics, perioperative data and follow-up outcomes were collected. Success was defined as relief of clinical symptoms, stable postoperative serum creatine and absence of radiographic obstruction. The perioperative and follow-up outcomes of open procedures and minimally invasive procedures were compared. RESULTS: The etiology included pelvic irradiation (14/20), urinary tuberculosis (3/20) and surgical injury (3/20). Bilateral ureter strictures were repaired in 15 cases. The surgeries conducted consisted of open procedures in 9 patients and minimally invasive procedures in 11 patients. Compared to open procedures, minimally invasive surgeries had less median estimated blood loss (EBL) (100 ml vs. 300 min, p = 0.010) and shorter postoperative hospitalization (27 d vs. 13 d, p = 0.004). Two patients in the open group experienced grade 3 complications (sigmoid fistula and acute cholecystitis in one patient, and pulmonary embolism in another patient). Over a median follow-up period of 20.1 months, the median bladder functional capacity was 300 ml, with a 100% success rate of IUC. CONCLUSION: IUC is feasible in both open and minimally invasive procedures, with acceptable complications and a high success rate. Minimally invasive procedures can have less EBL and shorter postoperative hospitalization than open procedure. However, prospective studies with larger groups and longer follow-up are needed.


Subject(s)
Ileum , Minimally Invasive Surgical Procedures , Ureter , Urinary Bladder , Urologic Surgical Procedures , Humans , Male , Female , Ileum/surgery , Adult , Treatment Outcome , Middle Aged , Urinary Bladder/surgery , Urologic Surgical Procedures/methods , Ureter/surgery , Minimally Invasive Surgical Procedures/methods , Retrospective Studies , Time Factors , Laparoscopy/methods , Aged , Robotic Surgical Procedures
11.
Micromachines (Basel) ; 15(6)2024 May 22.
Article in English | MEDLINE | ID: mdl-38930645

ABSTRACT

In order to solve the problems of methods that use a single form of sensing, the ease of causing deformation damage to the targets with a low hardness during grasping, and the slow sliding inhibition of a prosthetic hand when the grasping target slides, which are problems that exist in most current intelligent prosthetic hands, this study introduces an adaptive control strategy for prosthetic hands based on multi-sensor sensing. Using a force-sensing resistor (FSR) to collect changes in signals generated after contact with a target, a prosthetic hand can classify the target's hardness level and adaptively provide the desired grasping force so as to reduce the deformation of and damage to the target in the process of grasping. A fiber-optic sensor collects the light reflected by the object to identify its surface roughness, so that the prosthetic hand adaptively adjusts the sliding inhibition method according to the surface roughness information to improve the grasping efficiency. By integrating information on the hardness and surface roughness of the target, an adaptive control strategy for a prosthetic hand is proposed. The experimental results showed that the adaptive control strategy was able to reduce the damage to the target by enabling the prosthetic hand to achieve stable grasping; after grasping the target with an initial force and generating sliding, the efficiency of slippage inhibition was improved, the target could be stably grasped in a shorter time, and the hardness, roughness and weight ranges of targets that could be grasped by the prosthetic hand were enlarged, thus improving the success rate of stable grasping under extreme conditions.

12.
IEEE Trans Image Process ; 33: 3964-3976, 2024.
Article in English | MEDLINE | ID: mdl-38913511

ABSTRACT

Monocular depth estimation (MDE) is a fundamental task in computer vision and has drawn increasing attention. Recently, some methods reformulate it as a classification-regression task to boost the model performance, where continuous depth is estimated via a linear combination of predicted probability distributions and discrete bins. In this paper, we present a novel framework called BinsFormer, tailored for the classification-regression-based depth estimation. It mainly focuses on two crucial components in the specific task: 1) proper generation of adaptive bins; and 2) sufficient interaction between probability distribution and bins predictions. To specify, we employ a Transformer decoder to generate bins, novelly viewing it as a direct set-to-set prediction problem. We further integrate a multi-scale decoder structure to achieve a comprehensive understanding of spatial geometry information and estimate depth maps in a coarse-to-fine manner. Moreover, an extra scene understanding query is proposed to improve the estimation accuracy, which turns out that models can implicitly learn useful information from the auxiliary environment classification task. Extensive experiments on the KITTI, NYU, and SUN RGB-D datasets demonstrate that BinsFormer surpasses state-of-the-art MDE methods with prominent margins. Code and pretrained models are made publicly available at https://github.com/zhyever/ Monocular-Depth-Estimation-Toolbox/tree/main/configs/ binsformer.

13.
J Med Chem ; 67(13): 10743-10773, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38919032

ABSTRACT

Beta-1,3-glucuronosyltransferase (B3GAT3), overexpressed in hepatocellular carcinoma (HCC) and negatively correlated to prognosis, is a promising target for cancer therapy. Currently, no studies have reported small molecule inhibitors of B3GAT3. In this study, we designed and synthesized a series of small-molecule inhibitors of B3GAT3 through virtual screening and structure optimization. The lead compound TMLB-C16 exhibited potent B3GAT3 inhibitory activity (KD = 3.962 µM) by effectively suppressing proliferation and migration, and inducing cell cycle arrest and apoptosis in MHCC-97H (IC50= 6.53 ± 0.18 µM) and HCCLM3 (IC50= 6.22 ± 0.23 µM) cells. Furthermore, compound TMLB-C16 demonstrated favorable pharmacokinetic properties with a relatively high bioavailability of 68.37%. It significantly inhibited tumor growth in both MHCC-97H and HCCLM3 xenograft tumor models without causing obvious toxicity. These results indicate that compound TMLB-C16 is an effective small molecule inhibitor of B3GAT3, providing a basis for the future development of B3GAT3-targeted drugs.


Subject(s)
Acetamides , Antineoplastic Agents , Carcinoma, Hepatocellular , Cell Proliferation , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemical synthesis , Cell Proliferation/drug effects , Cell Line, Tumor , Acetamides/chemistry , Acetamides/pharmacology , Acetamides/chemical synthesis , Acetamides/therapeutic use , Mice , Structure-Activity Relationship , Apoptosis/drug effects , Mice, Nude , Drug Discovery , Mice, Inbred BALB C , Xenograft Model Antitumor Assays , Molecular Docking Simulation , Male , Cell Movement/drug effects , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/therapeutic use , Enzyme Inhibitors/chemical synthesis
14.
ACS Nano ; 18(27): 17509-17520, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38918939

ABSTRACT

There is growing concern about the distribution of nanoplastics (NPs) in the central nervous system (CNS), whereas intrusion is poorly understood. In this study, fluorescent-labeled polystyrene NPs (PS-NPs) were microinjected into different areas of zebrafish embryo to mimic different routes of exposure. PS-NPs were observed in the brain, eyes, and spinal cord through gametal exposure. It indicated that maternally derived PS-NPs were specially distributed in the CNS of zebrafish during early development. Importantly, these NPs were stranded in the CNS but not transferred to other organs during development. Furthermore, using neuron GFP-labeled transgenic zebrafish, colocalization between NPs and the neuron cells revealed that NPs were mostly enriched in the CNS surrounded but not the neurons. Even so, the intrusion of NPs into the CNS induced the significant upregulation of some neurotransmitter receptors, leading to an inhibited effect on the movement of zebrafish larvae. This work provides insights into understanding the intrusion and distribution of NPs in the CNS and the subsequent potential adverse effects.


Subject(s)
Central Nervous System , Polystyrenes , Zebrafish , Animals , Zebrafish/embryology , Central Nervous System/metabolism , Central Nervous System/drug effects , Polystyrenes/chemistry , Nanoparticles/chemistry , Nanoparticles/metabolism , Animals, Genetically Modified , Microplastics/toxicity
15.
Nat Prod Res ; : 1-11, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38824676

ABSTRACT

Bupleurum chinense polysaccharide has a wide range of biological activities. In this study, Bupleurum chinense polysaccharides (BPs), BPs-1 (30 kDa) and BPs-2 (2000 kDa) with different molecular weights were isolated and prepared by ultrafiltration interception method. The structures of BPs, BPs-1 and BPs-2 were characterised by monosaccharide composition, GC-MS, Fourier transform infra-red spectroscopy and nuclear magnetic resonance. The results showed that the monosaccharide composition of BPs with different molecular weights was the same, but the proportion was different. BPs, BPs-1 and BPs-2 were mainly connected by Glup-(1→,→2,4)-Araf-(1→,→6)-Glup-(1→). The anti-inflammatory activity screening experiment in vitro showed that BPs-1 had stronger anti-inflammatory effect. Antioxidant experiments showed that BPs-2 had high free radical scavenging activity. This study laid a foundation for elucidating the fine structure and structure-activity relationship of Bupleurum chinense polysaccharides and will promote the product development of Bupleurum chinense polysaccharides.

16.
Opt Express ; 32(10): 17525-17534, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38858934

ABSTRACT

The anisotropic optical properties of aluminum scandium nitride (Al1-xScxN) thin films for both ordinary and extraordinary light are investigated. A quantitative analysis of the band structures of the wurtzite Al1-xScxN is carried out. In addition, Al1-xScxN photonic waveguides and bends are fabricated on 8-inch Si substrates. With x = 0.087 and 0.181, the light propagation losses are 5.98 ± 0.11 dB/cm and 8.23 ± 0.39 dB/cm, and the 90° bending losses are 0.05 dB/turn and 0.08 dB/turn at 1550 nm wavelength, respectively.

17.
Phys Chem Chem Phys ; 26(22): 15831-15843, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38787657

ABSTRACT

High performance computing (HPC) is renowned for its capacity to tackle complex problems. Meanwhile, quantum computing (QC) provides a potential way to accurately and efficiently solve quantum chemistry problems. The emerging field of quantum-centric high performance computing (QCHPC), which merges these two powerful technologies, is anticipated to enhance computational capabilities for solving challenging problems in quantum chemistry. The implementation of QCHPC for quantum chemistry requires interdisciplinary research and collaboration across multiple fields, including quantum chemistry, quantum physics, computer science and so on. This perspective provides an introduction to the quantum algorithms that are suitable for deployment in QCHPC, focusing on conceptual insights rather than technical details. Parallel strategies to implement these algorithms on quantum-centric supercomputers are discussed. We also summarize high performance quantum emulating simulators, which are considered a viable tool to explore QCHPC. We conclude with challenges and outlooks in this field.

18.
Biomater Sci ; 12(12): 3100-3111, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38712522

ABSTRACT

In this study, we developed a ROS-responsive thermosensitive poly(ethylene glycol)-polypeptide hydrogel loaded with a chemotherapeutic drug, doxorubicin (Dox), an antiviral imidazoquinoline, resiquimod (R848), and antibody targeting programmed cell death protein 1 (aPD-1) for local chemoimmunotherapy. The hydrogel demonstrated controllable degradation and sustained drug release behavior according to the concentration of ROS in vitro. Following intratumoral injection into mice bearing B16F10 melanoma, the Dox/R848/aPD-1 co-loaded hydrogel effectively inhibited tumor growth, prolonged animal survival time and promoted anti-tumor immune responses with low systemic toxicity. In the postoperative model, the Dox/R848/aPD-1 co-loaded hydrogel exhibited enhanced tumor recurrence prevention and long-term immune memory effects. Thus, the hydrogel-based local chemoimmunotherapy system demonstrates potential for effective anti-tumor treatment and suppression of tumor recurrence.


Subject(s)
Doxorubicin , Hydrogels , Immunotherapy , Peptides , Reactive Oxygen Species , Animals , Hydrogels/chemistry , Hydrogels/administration & dosage , Doxorubicin/chemistry , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Peptides/chemistry , Peptides/administration & dosage , Peptides/pharmacology , Mice , Reactive Oxygen Species/metabolism , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Melanoma, Experimental/therapy , Melanoma, Experimental/immunology , Mice, Inbred C57BL , Polyethylene Glycols/chemistry , Cell Line, Tumor , Temperature , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Drug Delivery Systems , Drug Liberation , Drug Carriers/chemistry
19.
Article in English | MEDLINE | ID: mdl-38814422

ABSTRACT

Pharmacological studies have shown that Cedrol (CE) exhibits extensive biological activities, including anti-inflammatory and analgesic. Moreover, it can inhibit the NF-κB pathway and the expression of various associated proteins. This study aimed to investigate the role of CE in postmenopausal osteoporosis. The results showed that intragastric administration of CE (10 and 20 mg/kg) significantly improved the bone microstructure damage and increased bone mineral density, trabecular bone volume, and bone trabecular thickness in ovariectomized (OVX) rats (p < 0.05). CE treatment additionally made a well-organized arrangement of bone trabeculae and improved its thickness and density. Compared with the OVX group, the levels of tartrate-resistant acid phosphatase from 5b and C-terminal telopeptide of type I collagen were significantly reduced by 42.75% and 49.27% in the OVX + CE rats (p < 0.05). TRAP staining visually showed that the number of osteoclasts in the femur tissue of CE-treated rats was less than that of the OVX group. The expressions of nuclear factor of activated T-cells, cytoplasmic 1, acid phosphatase 5, and cathepsin K in OVX + CE rats were significantly decreased by 51.61%, 46.07%, and 50.34% compared to the OVX group (p < 0.01). In addition, CE intervention effectively reduced the phosphorylation levels of P65 and IκBα and inhibited the NF-κB signaling pathway. Meanwhile, CE diminished the number of multinucleated osteoclasts induced by receptor activator for nuclear factor-κB ligand and hindered cell fusion as well as nuclear translocation of osteoclast precursor cells P65. In conclusion, CE inhibits osteoclastogenesis by suppressing the activation of the NF-κB signaling pathway, thereby alleviating postmenopausal osteoporosis.

20.
J Hazard Mater ; 472: 134509, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38704907

ABSTRACT

Aged nanoplastics (aged-NPs) have unique characteristics endowed by environmental actions, such as rough surface, high oxygen content. Although studies have highlighted the potential hazards of aged-NPs, limited research has provided strategies for aged-NPs pollution remediation. The dietary intervention of quercetin is a novel insight to address the health risks of aged-NPs. This study explored the impact of aged-NPs on intestinal barrier homeostasis at the environmentally relevant dose and investigated the alleviating effects of quercetin on aged-NPs toxicity through transcriptomics and molecular biology analysis. It indicated that aged-NPs induced intestinal barrier dysfunction, which was characterized by higher permeability, increased inflammation, and loss of epithelial integrity, while quercetin restored it. Aged-NPs disrupted redox homeostasis, upregulated inflammatory genes controlled by AP-1, and led to Bax-dependent mitochondrial apoptosis. Quercetin intervention effectively mitigated inflammation and apoptosis by activating the Nrf2. Thus, quercetin decreased intestinal free radical levels, inhibiting the phosphorylation of p38 and JNK. This study unveiled the harmful effects of aged-NPs on intestinal homeostasis and the practicability of dietary intervention against aged-NPs toxicity. These findings broaden the understanding of the NPs toxicity and provide an effective dietary strategy to relieve the health risks of NPs. ENVIRONMENTAL IMPLICATIONS: Growing levels of NPs pollution have represented severe health hazards to the population. This study focuses on the toxic mechanism of aged-NPs on the intestinal barrier and the alleviating effect of quercetin dietary intervention, which considers the environmental action and relevant dose. It revealed the harmful effects of aged-NPs on intestinal inflammation with the key point of free radical generation. Furthermore, a quercetin-rich diet holds significant promise for addressing and reversing intestinal damage caused by aged-NPs by maintaining intracellular redox homeostasis. These findings provide an effective dietary strategy to remediate human health risks caused by NPs.


Subject(s)
Homeostasis , Nanoparticles , Quercetin , Quercetin/pharmacology , Homeostasis/drug effects , Humans , Nanoparticles/toxicity , Nanoparticles/chemistry , Intestinal Mucosa/metabolism , Intestinal Mucosa/drug effects , Animals , NF-E2-Related Factor 2/metabolism , Apoptosis/drug effects , Intestines/drug effects , Caco-2 Cells , Antioxidants/pharmacology
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