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1.
Front Pharmacol ; 15: 1414635, 2024.
Article in English | MEDLINE | ID: mdl-39221146

ABSTRACT

The dried root and rhizome of Alpinia officinarum Hance (A. officinarum) have been widely used in traditional Chinese medicine for thousands of years to alleviate pain, promote digestion, warm the stomach, and disperse cold. This review aims to comprehensively and in-depth summarize the most recent research on the traditional uses, phytochemistry, pharmacokinetics, and pharmacology of A. officinarum. By searching various databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, and China National Knowledge Infrastructure (CNKI) for literature on "A. officinarum Hance," as well as relevant textbooks and digital documents, an overall and critical review of the subject was conducted. The traditional uses of A. officinarum were summarized, and 337 compounds from A. officinarum were summarized, including flavonoids, diarylheptanoids, volatile oils, and other compounds. Studies have found that the crude extract of A. officinarum and its compounds has a wide range of biological activities, such as improving gastrointestinal function, anti-inflammatory properties, anti-tumor activity, antibacterial properties, memory enhancement, and analgesic effects. Modern pharmacological studies have provided strong evidence and explanations for the traditional medicinal uses of A. officinarum, which brings a broad prospect for its medicinal use. However, more research is needed to explore the structure-activity relationship and potential mechanisms of action of its bioactive chemicals. Furthermore, it is essential to conduct more clinical trials in order to accelerate research and development of the drug.

2.
NPJ Precis Oncol ; 8(1): 189, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237596

ABSTRACT

Pathological complete response (pCR) serves as a critical measure of the success of neoadjuvant chemotherapy (NAC) in breast cancer, directly influencing subsequent therapeutic decisions. With the continuous advancement of artificial intelligence, methods for early and accurate prediction of pCR are being extensively explored. In this study, we propose a cross-modal multi-pathway automated prediction model that integrates temporal and spatial information. This model fuses digital pathology images from biopsy specimens and multi-temporal ultrasound (US) images to predict pCR status early in NAC. The model demonstrates exceptional predictive efficacy. Our findings lay the foundation for developing personalized treatment paradigms based on individual responses. This approach has the potential to become a critical auxiliary tool for the early prediction of NAC response in breast cancer patients.

3.
J Colloid Interface Sci ; 677(Pt A): 704-717, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39116568

ABSTRACT

The environmental contamination caused by organophosphorus pesticides (for example, triazophos) is an escalating concern. To mitigate this issue, this study introduces a novel Al6Si2O13/WO2.72 (ASO/WO) nanocomposite photocatalyst, which markedly enhances the photocatalytic degradation of triazophos. The optimized nanocomposite material with a 60.0 % ASO loading (60-ASO/WO) achieves a degradation rate of 86.3 % for triazophos within 140.0 min, marginally exceeding 60-ASO/WO3 (72.6 %) and significantly outperforming individual ASO (65.0 %), WO (59.5 %), and WO3 (56.2 %). This catalyst retains 88.9 % of its activity after five cycles, showcasing exceptional efficiency and stability. Additionally, its electrochemical surface area (ECSA, 310.0 cm2), total organic carbon (TOC, removal rate of 73.7 %), photocurrent, and electrochemical impedance are all optimal. X-ray photoelectron spectroscopy (XPS), electron paramagnetic resonance (EPR), and theoretical calculations elucidate the critical role of oxygen vacancies and the S-scheme heterojunction in augmenting charge separation and photocatalytic performance, corroborating the synergistic effect of oxygen defects and the S-scheme. While individual factors can enhance photocatalytic activity, their combination results in a more pronounced effect. Liquid chromatography-mass spectrometry (LCMS) identifies the principal degradation intermediates, including 1-phenyl-3-hydroxy-1, 2, 4-triazole, diethyl thiophosphate, and 3, 5, 6-trichloro-2-pyridinol, underscoring the material's potential in environmental remediation.

4.
Hortic Res ; 11(8): uhae180, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39108576

ABSTRACT

Somatic embryogenesis (SE) is not only the most effective method among various strategies for the asexual propagation of forest trees but also a basis for genetic improvement. However, some bottlenecks, such as the recalcitrance of initiation, the maintenance of embryogenic potential during proliferation and the low efficiency of maturation as well as high rate of abnormal embryo development remain unresolved. These bottlenecks refer to complex mechanisms, including transcriptional regulatory networks, epigenetic modifications and physiological conditions. In recent years, several small molecules utilized in animal stem cell research have exhibited positive effects on plant regeneration, including conifer species, which offers a potential novel approach to overcome the challenges associated with SE in conifers. In this review, we summarize the small molecules used in conifers, including redox substances, epigenetic regulatory inhibitors and other metabolism-related molecules, which overcome these difficulties without the use of genetic engineering. Moreover, this approach also has the advantages of dynamic reversibility, simple operation, and simultaneous regulation of multiple targets, which might be one of the best choices for optimizing plant regeneration systems including SE.

5.
Heliyon ; 10(12): e32612, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39183879

ABSTRACT

Seed dispersal is an important ecological process and has important implications for plant population expansion and regeneration. Seed dispersal not only reduces the probability of death due to seed density but also facilitates seedling establishment. Many studies have focused on the effect of one or two factors on seed dispersal. However, little is known about studies on the effect of multiple factors and their interactions on seed dispersal. Here, we conducted a field experiment to explore how seed size, soil burial, and seed peeling affect the dispersal and hoarding of seeds of Quercus liaotungensis in dispersal animals. We found that large seeds were preferentially selected by animals, and the predation after dispersal, hoarding after dispersal, predation distance after dispersal, and hoarding distance after dispersal of large seeds were significantly greater than small seeds, which is more beneficial to the plant expansion and regeneration. Soil burial increased the time of seed intact in situ, significantly increased predation in situ, and reduced predation after dispersal, predation distance after dispersal, and hoarding distance after dispersal, which is not beneficial to the plant population expansion and regeneration. Seed peeling reduced the time of seed intact in situ, and the predation after dispersal was significantly greater than that of unpeeled seeds, which is not beneficial to the plant population. We did not find the interactions between seed size, soil burial, and seed peeling on dispersal. The effects of a single factor may be more than their interactions between seed size, soil burial and seed peeling on dispersal. These results implied that seed size, soil burial and seed peeling may affect plant population expansion and regeneration by affecting the dispersal and hoarding of animals.

6.
Biomater Sci ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39189321

ABSTRACT

Diabetic foot ulcers (DFUs) are one of the most serious complications of diabetes, often leading to necrosis and amputation. DFU is caused by the intricate diabetic microenvironment, including ischemia, hypoxia, hyperinflammation, reduced angiogenesis, and persistent infection. Traditional wound dressings made of single or mixed materials often struggle to meet all the requirements for effective diabetic wound healing. In contrast, multilayer dressings comprising more than single layers have the potential to address these challenges by combining their diverse chemical and physical properties. In this study, we developed a bilayer hydrogel comprising a GelMA-ALG-nano-ZnO protective film and a COL1-PRP regenerative hydrogel for facilitating diabetic wound healing. We demonstrated the protective properties against bacterial infection of the protective film, while highlighting the regenerative potential of the COL1-PRP hydrogel in promoting fibroblast and MUVEC migration, extracellular matrix secretion and deposition, and angiogenesis. Importantly, the bilayer hydrogel exhibited superior efficacy in promoting full-thickness wound healing in a diabetic rat model compared to its single-layer hydrogel counterparts. This multi-layer approach offers a promising strategy for addressing the complexities of diabetic foot treatment and improving clinical outcomes.

7.
Food Chem ; 460(Pt 3): 140722, 2024 Dec 01.
Article in English | MEDLINE | ID: mdl-39106753

ABSTRACT

Tyrosinase (Polyphenol oxidase), a key enzyme in enzymatic browning, is an attractive target for developing new anti-browning agents in the food industry. In this work, twenty pyrazole-1,2,4-triazole derivatives (3a-3n, 4a-4f) were synthesized and tested in vitro, most of compounds showed potent anti-tyrosinase activity. Of these, 3c (IC50 = 1.02 ± 0.08 µM) was found to be 14 folds stronger than kojic acid (IC50 = 14.74 ± 1.23 µM) and behaved as a mixed type inhibitor. Besides, the disappeared peak of dopaquinone in the HPLC assay intuitively validated the inhibitory effect of 3c. Copper ions chelating, fluorescence quenching and molecular docking assays showed that coordination with copper is the key to play a role. Furthermore, 3c exhibited excellent anti-browning ability for the Rosa roxburghii Tratt, the non-enzymatic browning experiment showed that 3c could prevent browning in non-enzymatic ways. It is suggested that these derivatives could serve as the leading compounds to find more efficient anti-browning agents in the future.


Subject(s)
Enzyme Inhibitors , Molecular Docking Simulation , Monophenol Monooxygenase , Pyrazoles , Triazoles , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/chemistry , Triazoles/chemistry , Triazoles/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Pyrazoles/chemistry , Pyrazoles/pharmacology , Structure-Activity Relationship , Drug Design , Fungal Proteins/chemistry , Fungal Proteins/antagonists & inhibitors , Molecular Structure , Maillard Reaction
8.
Sci Total Environ ; 951: 175596, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39155000

ABSTRACT

The widespread occurrence of aerated plain soils underscores their significant role in the global soil methane (CH4) sink budget. However, plain soils are poorly characterized in terms of spatial variability of CH4 uptake and the relevant control. We investigated the intra- and inter-site spatial variability of CH4 uptake through flux measurements in intact soil cores from five non-wetland sites within the Yellow River Delta, each representing a distinct land use/cover type. Methane uptake rates were highest in undisturbed forest cores. The rates were very low, often falling below the detection limit, in cores from the other four sites. The significant correlation between CH4 uptake and bulk density across sites suggests the integrative role of bulk density for the effects of different disturbances (including salt stress and succession) on CH4 uptake. Methane uptake was heterogeneous at the within-site scale as indicated by large coefficients of variations (CVs). Soil texture variation manipulated the within-site pattern of CH4 uptake in the low-salinity sites. Salt affected the spatial variation of CH4 uptake only at high level of salinity. Neither Potter's nor Ridgwell's models effectively captured the within-site variation of CH4 uptake due to a texture-associated bias in the models. Establishing a quantitative relationship between CH4 uptake and clay content at the field scale in alluvial plain soils will facilitate the refinement of model parameters linked to texture and rectify biases in CH4 estimation. These results provide an insight for the biogeochemical control of CH4 uptake in alluvial plain soils and have important application for improving CH4 models.

9.
J Am Chem Soc ; 146(36): 24842-24854, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39186017

ABSTRACT

Atomically dispersed Fe-N-C catalysts emerged as promising alternatives to commercial Pt/C for the oxygen reduction reaction. However, the majority of Fe-N-C catalysts showed unsatisfactory activity and durability due to their inferior O-O bond-breaking capability and rapid Fe demetallization. Herein, we create a pseudo-phthalocyanine environment coordinated diatomic iron (Fe2-pPc) catalyst by grafting the core domain of iron phthalocyanine (Fe-Nα-Cα-Nß) onto defective carbon. In situ characterizations and theoretical calculation confirm that Fe2-pPc follows the fast-kinetic dissociative pathway, whereby Fe2-pPc triggers bridge-mode oxygen adsorption and catalyzes direct O-O radical cleavage. Compared to traditional Fe-N-C and FePc-based catalysts exhibiting superoxo-like oxygen adsorption and an *OOH-involved pathway, Fe2-pPc delivers a superior half-wave potential of 0.92 V. Furthermore, the ultrastrong Nα-Cα bonds in the pPc environment endow the diatomic iron active center with high tolerance for reaction-induced geometric stress, leading to significantly promoted resistance to demetallization. Upon an unprecedented harsh accelerated degradation test of 150,000 cycles, Fe2-pPc experiences negligible Fe loss and an extremely small activity decay of 17 mV, being the most robust candidate among previously reported Fe-N-C catalysts. Zinc-air batteries employing Fe2-pPc exhibit a power density of 255 mW cm-2 and excellent operation stability beyond 440 h. This work brings new insights into the design of atomically precise metallic catalysts.

10.
Int J Biol Macromol ; 276(Pt 1): 134005, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39053819

ABSTRACT

With the increasing consumption of organic solvents in chemical and pharmaceutical industries, the environment pollution of volatile organic compounds (VOCs) has become an urgent problem. Therefore, the rapid-visual detection method is of great significance in the analysis of VOCs. Based on the fluorescence quenching/enhancement mechanism of carbon quantum dots (CQDs), with the help of carboxymethyl cellulose membrane with porous and large specific surface area structure, a series of green CQDs@carboxymethyl cellulose composite film (CQDs@CMC composite film) was prepared in this study. In the typical-targeted pollutants (toluene) detection application, a fluorescence spectroscopy method was established which could achieve the high sensitivity and strong specificity detection. The mainly conclusions were as follows: The fluorescence spectrometric detection method for toluene: A kind of hydrophobic Lmi/Bet CQDs@CMC composite film was prepared and characterized with imidazole/betaine CQDs and porous carboxymethyl cellulose composite film as raw materials. The toluene detection performance was studied, and the recognition mechanism was explored. The results showed that toluene enhanced the fluorescence of Lmi/Bet CQDs@CMC composite film. The fluorescence intensity of composite films was proportional to toluene concentration when the toluene concentration ranged from 200 to 2200 mg/L. The detection limit of toluene was 1.169 mg/L, which provides a theoretical basis for the detection of toluene by fluorescence spectrometry.


Subject(s)
Carbon , Carboxymethylcellulose Sodium , Quantum Dots , Toluene , Quantum Dots/chemistry , Carboxymethylcellulose Sodium/chemistry , Toluene/chemistry , Toluene/analysis , Carbon/chemistry , Spectrometry, Fluorescence/methods , Gases/analysis , Gases/chemistry , Limit of Detection , Volatile Organic Compounds/analysis , Volatile Organic Compounds/chemistry
11.
Genet Test Mol Biomarkers ; 28(7): 281-288, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38949978

ABSTRACT

Objective: To investigate the association between ACTN4 gene mutation and primary nephrotic syndrome (PNS) in children in Guangxi Autonomous Region, China. Methods: The high-throughput sequencing technology was used to sequence ACTN4 gene in 155 children with PNS in Guangxi Autonomous Region in China, with 98 healthy children serving as controls. Twenty-three exon-specific capture probes targeting ACTN4 were designed and used to hybridize with the genomic DNA library. The targeted genomic region DNA fragments were enriched and sequenced. The protein levels of ACTN4 in both case and control groups were quantified using ELISA method. Results: Bioinformatics analysis revealed five unique ACTN4 mutations exclusively in patients with PNS, including c.1516G>A (p.G506S) on one exon in 2 patients, c.1442 + 10G>A at the splice site in 1 patient, c.1649A>G (p.D550G) on exon in 1 patient, c.2191-4G>A at the cleavage site in 2 patients, and c.2315C>T (p.A772V) on one exon in 1 patient. The c.1649A>G (p.D550G) and c.2315C>T (p.A772V) were identified from the same patient. Notably, c.1649A>G (p.D550G) represents a novel mutation in ACTN4. In addition, three other ACTN4 polymorphisms occurred in both case and control groups, including c.162 + 6C>T (1 patient in case group and 2 patients in control group), c.572 + 11G>A (1 patient in case group and 2 patients in control group), and c.2191-5C>T (4 patients in the case group and 3 patients in control group). The serum ACTN4 concentration in the case group was markedly higher, averaging 544.7 ng/mL (range: 264.6-952.6 ng/mL), compared with 241.20 ng/mL (range: 110.75-542.35 ng/mL) in the control group. Conclusion: Five ACTN4 polymorphisms were identified among children with PNS in Guangxi Autonomous Region, China, including the novel mutation c.1649A>G. The lower serum levels of α-actinin-4 in the case group suggest that this protein might play a protective role in PNS.


Subject(s)
Actinin , Nephrotic Syndrome , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Actinin/genetics , Case-Control Studies , China/epidemiology , Exons/genetics , Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing/methods , Mutation , Nephrotic Syndrome/genetics , East Asian People/genetics
12.
Phytopathology ; 114(7): 1502-1514, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39023506

ABSTRACT

Late blight, caused by the notorious pathogen Phytophthora infestans, poses a significant threat to potato (Solanum tuberosum) crops worldwide, impacting their quality as well as yield. Here, we aimed to investigate the potential use of cinnamaldehyde, carvacrol, and eugenol as control agents against P. infestans and to elucidate their underlying mechanisms of action. To determine the pathogen-inhibiting concentrations of these three plant essential oils (PEOs), a comprehensive evaluation of their effects using gradient dilution, mycelial growth rate, and spore germination methods was carried out. Cinnamaldehyde, carvacrol, and eugenol were capable of significantly inhibiting P. infestans by hindering its mycelial radial growth, zoospore release, and sporangium germination; the median effective inhibitory concentration of the three PEOs was 23.87, 8.66, and 89.65 µl/liter, respectively. Scanning electron microscopy revealed that PEOs caused the irreversible deformation of P. infestans, resulting in hyphal shrinkage, distortion, and breakage. Moreover, propidium iodide staining and extracellular conductivity measurements demonstrated that all three PEOs significantly impaired the integrity and permeability of the pathogen's cell membrane in a time- and dose-dependent manner. In vivo experiments confirmed the dose-dependent efficacy of PEOs in reducing the lesion diameter of potato late blight. Altogether, these findings provide valuable insight into the antifungal mechanisms of PEOs vis-à-vis late blight-causing P. infestans. By utilizing the inherent capabilities of these natural compounds, we could effectively limit the harmful impacts of late blight on potato crops, thereby enhancing agricultural practices and ensuring the resilience of global potato food production.


Subject(s)
Cymenes , Eugenol , Oils, Volatile , Phytophthora infestans , Plant Diseases , Solanum tuberosum , Phytophthora infestans/drug effects , Phytophthora infestans/physiology , Solanum tuberosum/microbiology , Oils, Volatile/pharmacology , Plant Diseases/microbiology , Plant Diseases/prevention & control , Eugenol/pharmacology , Cymenes/pharmacology , Monoterpenes/pharmacology , Mycelium/drug effects , Mycelium/growth & development , Plant Oils/pharmacology , Hyphae/drug effects , Hyphae/growth & development , Spores/drug effects , Spores/physiology , Acrolein/analogs & derivatives
13.
ACS Nano ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39042820

ABSTRACT

High-entropy materials (HEMs) have garnered extensive attention owing to their diverse and captivating physicochemical properties. Yet, fine-tuning morphological properties of HEMs remains a formidable challenge, constraining their potential applications. To address this, we present a rapid, low-energy consumption diethylenetriamine (DETA)-assisted microwave hydrothermal method for synthesizing a series of two-dimensional high-entropy selenides (HESes). Subsequently, the obtained HESes are harnessed for photocatalytic water splitting. Noteworthy is the optimized HESes, Cd0.9Zn1.2Mn0.4Cu1.8Cr1.2Se4.5, showcasing an output rate of hydrogen of 16.08 mmol h-1 g-1 and a quantum efficiency of ca. 30% under 420 nm monochromatic LED irradiation. It is revealed that the photocatalytic performance of these HESes stems not only from the enlarged specific surface area and enhanced photogenerated charge carrier utilization efficiency but also from the promoted formation of the Cd-Hads bond, influenced by multiple principal elements on the Cd. These findings provide a guide for the design of HEMs tailored for various applications.

14.
Micromachines (Basel) ; 15(7)2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39064436

ABSTRACT

This paper investigates the asymptotic tracking problem for a class of second-order electromagnetic micromirror model with output performance constraints and anomaly control, which is subject to model parameter uncertainties and external disturbances. Specifically, this paper formulates the trajectory tracking control problem of an electromagnetic micromirror as a closed-loop control trajectory tracking problem based on the general solution framework of output regulation. Moreover, the extended internal model is introduced to reformulate the closed-loop control problem into a state stabilization problem of the augmented system. Based on the augmented system, an internal model backstepping controller is proposed by integrating the barrier Lyapunov Functions (BLF) and the Nussbaum gain function with the backstepping structure.This controller not only satisfies the output performance constraints of the micromirror, but also maintains the control performance in anomalous control situations. The final performance simulation demonstrates the efficacy of the proposed controller.

15.
BMC Cardiovasc Disord ; 24(1): 333, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961333

ABSTRACT

BACKGROUND: Oxidative stress may contribute to cardiac ryanodine receptor (RyR2) dysfunction in diabetic cardiomyopathy. Ginsenoside Rb1 (Rb1) is a major pharmacologically active component of ginseng to treat cardiovascular diseases. Whether Rb1 treat diabetes injured heart remains unknown. This study was to investigate the effect of Rb1 on diabetes injured cardiac muscle tissue and to further investigate its possible molecular pharmacology mechanisms. METHODS: Male Sprague-Dawley rats were injected streptozotocin solution for 2 weeks, followed 6 weeks Rb1 or insulin treatment. The activity of SOD, CAT, Gpx, and the levels of MDA was measured; histological and ultrastructure analyses, RyR2 activity and phosphorylated RyR2(Ser2808) protein expression analyses; and Tunel assay were performed. RESULTS: There was decreased activity of SOD, CAT, Gpx and increased levels of MDA in the diabetic group from control. Rb1 treatment increased activity of SOD, CAT, Gpx and decreased the levels of MDA as compared with diabetic rats. Neutralizing the RyR2 activity significantly decreased in diabetes from control, and increased in Rb1 treatment group from diabetic group. The expression of phosphorylation of RyR2 Ser2808 was increased in diabetic rats from control, and were attenuated with insulin and Rb1 treatment. Diabetes increased the apoptosis rate, and Rb1 treatment decreased the apoptosis rate. Rb1 and insulin ameliorated myocardial injury in diabetic rats. CONCLUSIONS: These data indicate that Rb1 could be useful for mitigating oxidative damage, reduced phosphorylation of RyR2 Ser2808 and decreased the apoptosis rate of cardiomyocytes in diabetic cardiomyopathy.


Subject(s)
Antioxidants , Apoptosis , Diabetes Mellitus, Experimental , Diabetic Cardiomyopathies , Ginsenosides , Myocytes, Cardiac , Oxidative Stress , Rats, Sprague-Dawley , Ryanodine Receptor Calcium Release Channel , Streptozocin , Animals , Diabetes Mellitus, Experimental/drug therapy , Male , Oxidative Stress/drug effects , Ryanodine Receptor Calcium Release Channel/metabolism , Ryanodine Receptor Calcium Release Channel/drug effects , Ginsenosides/pharmacology , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/drug therapy , Diabetic Cardiomyopathies/pathology , Diabetic Cardiomyopathies/physiopathology , Diabetic Cardiomyopathies/etiology , Apoptosis/drug effects , Antioxidants/pharmacology , Phosphorylation , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Myocytes, Cardiac/metabolism , Myocardium/pathology , Myocardium/metabolism , Insulin , Malondialdehyde/metabolism
16.
Front Immunol ; 15: 1412693, 2024.
Article in English | MEDLINE | ID: mdl-39076970

ABSTRACT

Background: Esophageal cancer (ESCA) is one of the most common tumors in the world, and treatment using neoadjuvant therapy (NT) based on radiotherapy and/or chemotherapy has still unsatisfactory results. Neoadjuvant immunochemotherapy (NICT) has also become an effective treatment strategy nowadays. However, its impact on the tumor microenvironment (TME) and regulatory mechanisms on T cells and NK cells needs to be further elucidated. Methods: A total of 279 cases of ESCA who underwent surgery alone [non-neoadjuvant therapy (NONE)], neoadjuvant chemotherapy (NCT), and NICT were collected, and their therapeutic effect and survival period were compared. Further, RNA sequencing combined with biological information was used to analyze the expression of immune-related genes. Immunohistochemistry, immunofluorescence, and quantitative real-time PCR (qRT-PCR) were used to verify the activation and infiltration status of CD8+ T and CD16+ NK cells, as well as the function and regulatory pathway of killing tumor cells. Results: Patients with ESCA in the NICT group showed better clinical response, median survival, and 2-year survival rates (p < 0.05) compared with the NCT group. Our RNA sequencing data revealed that NICT could promote the expression of immune-related genes. The infiltration and activation of immune cells centered with CD8+ T cells were significantly enhanced. CD8+ T cells activated by PD-1 inhibitors secreted more IFN-γ and cytotoxic effector factor cells through the transcription factor of EOMES and TBX21. At the same time, activated CD8+ T cells mediated the CD16+ NK cell activation and secreted more IFN-γ to kill ESCA cells. In addition, the immunofluorescence co-staining results showed that more CD276+ tumor cells and CD16+ NK cells were existed in pre-NCT and pre-NICT group. However, CD276+ tumor cells were reduced significantly in the post-NICT group, while they still appeared in the post-NCT group, which means that CD16+ NK cells can recognize and kill CD276+ tumor cells after immune checkpoint blocker (ICB) treatment. Conclusion: NICT can improve the therapeutic effect and survival period of resectable ESCA patients. NICT could promote the expression of immune-related genes and activate CD8+ T and CD16+ NK cells to secrete more IFN-γ to kill ESCA cells. It provides a theoretical basis and clinical evidence for its potential as an NT strategy in ESCA.


Subject(s)
CD8-Positive T-Lymphocytes , Esophageal Neoplasms , Killer Cells, Natural , Neoadjuvant Therapy , Receptors, IgG , Tumor Microenvironment , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/immunology , Esophageal Neoplasms/mortality , Killer Cells, Natural/immunology , Killer Cells, Natural/metabolism , Neoadjuvant Therapy/methods , Male , Female , Receptors, IgG/metabolism , Receptors, IgG/genetics , CD8-Positive T-Lymphocytes/immunology , Middle Aged , Tumor Microenvironment/immunology , Aged , GPI-Linked Proteins/metabolism , Treatment Outcome , Immunotherapy/methods , Adult , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism
17.
Anticancer Drugs ; 35(8): 780-788, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38958648

ABSTRACT

The aim of this study was to observe the therapeutic effect of sintilimab combined with a modified docetaxel + cisplatin + fluorouracil (DCF) regimen on advanced gastric cancer and its effect on Th1/Th2 immune balance. Ninety-eight cases of advanced gastric cancer patients who visited our hospital from April 2020 to May 2022 were selected and divided into 48 cases each in the conventional group and the research group by random number table method; the DCF regimen was adopted in the conventional group, and sintilimab combined with modified DCF regimen was adopted in the research group, and the therapeutic effects of the patients in the two groups and the changes of Th1/Th2 immune indexes were compared. CEA, CA199, CA242, CD168 AQ3, and IL-4 in the study group were lower than those in the conventional group at the end of three cycles of treatment, and the difference was statistically significant ( P  < 0.001). The levels of IFN-γ and IL-4 in the study group at the end of three cycles of treatment were higher than those in the conventional group ( P  < 0.001). The incidence of adverse reactions during treatment in the study group was lower than that in the conventional group ( P  < 0.001), and the grading of adverse reactions in the study group was milder than that in the conventional group. Sintilimab combined with a modified DCF regimen in the treatment of advanced gastric cancer not only improves the therapeutic effect but also positively affects the Th1/Th2 immune balance, which provides better immune regulation for patients with advanced gastric cancer.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Cisplatin , Docetaxel , Fluorouracil , Stomach Neoplasms , Humans , Stomach Neoplasms/drug therapy , Stomach Neoplasms/immunology , Stomach Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Male , Female , Middle Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Fluorouracil/administration & dosage , Cisplatin/administration & dosage , Docetaxel/administration & dosage , Docetaxel/therapeutic use , Interleukin-4 , Th1-Th2 Balance/drug effects , Aged , Th1 Cells/immunology , Th1 Cells/drug effects , Interferon-gamma , Th2 Cells/immunology , Th2 Cells/drug effects , Adult
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 322: 124783, 2024 Dec 05.
Article in English | MEDLINE | ID: mdl-38972098

ABSTRACT

Due to the high-dimensionality, redundancy, and non-linearity of the near-infrared (NIR) spectra data, as well as the influence of attributes such as producing area and grade of the sample, which can all affect the similarity measure between samples. This paper proposed a t-distributed stochastic neighbor embedding algorithm based on Sinkhorn distance (St-SNE) combined with multi-attribute data information. Firstly, the Sinkhorn distance was introduced which can solve problems such as KL divergence asymmetry and sparse data distribution in high-dimensional space, thereby constructing probability distributions that make low-dimensional space similar to high-dimensional space. In addition, to address the impact of multi-attribute features of samples on similarity measure, a multi-attribute distance matrix was constructed using information entropy, and then combined with the numerical matrix of spectral data to obtain a mixed data matrix. In order to validate the effectiveness of the St-SNE algorithm, dimensionality reduction projection was performed on NIR spectral data and compared with PCA, LPP, and t-SNE algorithms. The results demonstrated that the St-SNE algorithm effectively distinguishes samples with different attribute information, and produced more distinct projection boundaries of sample category in low-dimensional space. Then we tested the classification performance of St-SNE for different attributes by using the tobacco and mango datasets, and compared it with LPP, t-SNE, UMAP, and Fisher t-SNE algorithms. The results showed that St-SNE algorithm had the highest classification accuracy for different attributes. Finally, we compared the results of searching the most similar sample with the target tobacco for cigarette formulas, and experiments showed that the St-SNE had the highest consistency with the recommendation of the experts than that of the other algorithms. It can provide strong support for the maintenance and design of the product formula.

19.
BMJ Open ; 14(6): e077903, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858156

ABSTRACT

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in China. The combination of immune checkpoint inhibitors (ICIs) and antiangiogenic drugs, such as bevacizumab and tyrosine kinase inhibitors, has been recommended as first-line treatment for advanced HCC. However, two-thirds of patients did not benefit from this form of immunotherapy. Currently, data on the subsequent regimen for patients previously treated with ICIs are lacking. Studies have shown that the combination of radiotherapy (RT) and ICIs is a potentially effective second-line therapy for HCC. This study aims to assess the efficacy and safety of combined therapy with stereotactic body RT (SBRT), sintilimab and IBI305 (a biosimilar of bevacizumab) in patients with HCC following the progression of first-line ICI therapy. METHODS AND ANALYSIS: This study is an open-label, single-arm, single-centre, phase 2 trial of 21 patients with advanced HCC in whom previous ICI therapy has failed. Participants will receive approximately 30-40 Gy/5-8F SBRT, followed by 200 mg sintilimab and 15 mg/kg IBI305 intravenously every 3 weeks. Treatment will continue until the development of unacceptable toxicity or disease progression. We will use Simon's two-stage design, with the objective response rate (ORR) as the primary endpoint. Secondary endpoints include ORR of lesions without RT, disease control rate, progression-free survival, overall survival and safety. ETHICS AND DISSEMINATION: The study was authorised by the Medical Ethics Committee. Dissemination of results will occur via a peer-reviewed publication and other relevant media. TRIAL REGISTRATION NUMBER: ChiCTR2200056068.


Subject(s)
Antibodies, Monoclonal, Humanized , Carcinoma, Hepatocellular , Liver Neoplasms , Radiosurgery , Adult , Aged , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Carcinoma, Hepatocellular/therapy , Clinical Trials, Phase II as Topic , Combined Modality Therapy , Immune Checkpoint Inhibitors/therapeutic use , Immunotherapy/methods , Liver Neoplasms/therapy , Radiosurgery/methods , Radiosurgery/adverse effects
20.
Small ; : e2401384, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940385

ABSTRACT

Understanding the reconstruction mechanism to rationally design cost-effective electrocatalysts for oxygen evolution reaction (OER) is still challenging. Herein, a defect-rich NiMoO4 precatalyst is used to explore its OER activity and reconstruction mechanism. In situ generated oxygen vacancies, distorted lattices, and edge dislocations expedite the deep reconstruction of NiMoO4 to form polycrystalline Ni (oxy)hydroxides for alkaline oxygen evolution. It only needs ≈230 and ≈285 mV to reach 10 and 100 mA cm-2, respectively. The reconstruction boosted by the redox of Ni is confirmed experimentally by sectionalized cyclic voltammetry activations at different specified potential ranges combined with ex situ characterization techniques. Subsequently, the reconstruction route is presented based on the acid-base electronic theory. Accordingly, the dominant contribution of the adsorbate evolution mechanism to reconstruction during oxygen evolution is revealed. This work develops a novel route to synthesize defect-rich materials and provides new tactics to investigate the reconstruction.

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