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1.
Nat Commun ; 15(1): 3838, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38714685

ABSTRACT

The powerful capability of reconfigurable intelligent surfaces (RISs) in tailoring electromagnetic waves and fields has put them under the spotlight in wireless communications. However, the current designs are criticized due to their poor frequency selectivity, which hinders their applications in real-world scenarios where the spectrum is becoming increasingly congested. Here we propose a filtering RIS to feature sharp frequency-selecting and 2-bit phase-shifting properties. It permits the signals in a narrow bandwidth to transmit but rejects the out-of-band ones; meanwhile, the phase of the transmitted signals can be digitally controlled, enabling flexible manipulations of signal propagations. A prototype is designed, fabricated, and measured, and its high quality factor and phase-shifting characteristics are validated by scattering parameters and beam-steering phenomena. Further, we conduct a wireless communication experiment to illustrate the intriguing functions of the RIS. The filtering behavior enables the RIS to perform wireless signal manipulations with anti-interference ability, thus showing big potential to advance the development of next-generation wireless communications.

2.
Front Pharmacol ; 15: 1308655, 2024.
Article in English | MEDLINE | ID: mdl-38449808

ABSTRACT

Objective: Psoralea corylifolia L. (FP) has received increasing attention due to its potential hepatotoxicity. Methods: In this study, zebrafish were treated with different concentrations of an aqueous extract of FP (AEFP; 40, 50, or 60 µg/mL), and the hepatotoxic effects of tonicity were determined by the mortality rate, liver morphology, fluorescence area and intensity of the liver, biochemical indices, and pathological tissue staining. The mRNA expression of target genes in the bile acid metabolic signaling pathway and lipid metabolic pathway was detected by qPCR, and the mechanism of toxicity was initially investigated. AEFP (50 µg/mL) was administered in combination with FXR or a peroxisome proliferator-activated receptor α (PPARα) agonist/inhibitor to further define the target of toxicity. Results: Experiments on toxic effects showed that, compared with no treatment, AEFP administration resulted in liver atrophy, a smaller fluorescence area in the liver, and a lower fluorescence intensity (p < 0.05); alanine transaminase (ALT), aspartate transaminase (AST), and γ-GT levels were significantly elevated in zebrafish (p < 0.01), and TBA, TBIL, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were elevated to different degrees (p < 0.05); and increased lipid droplets in the liver appeared as fatty deposits. Molecular biological validation revealed that AEFP inhibited the expression of the FXR gene, causing an increase in the expression of the downstream genes SHP, CYP7A1, CYP8B1, BSEP, MRP2, NTCP, peroxisome proliferator-activated receptor γ (PPARγ), ME-1, SCD-1, lipoprotein lipase (LPL), CPT-1, and CPT-2 and a decrease in the expression of PPARα (p < 0.05). Conclusion: This study demonstrated that tonic acid extracts are hepatotoxic to zebrafish through the inhibition of FXR and PPARα expression, thereby causing bile acid and lipid metabolism disorders.

3.
Zhongguo Zhong Yao Za Zhi ; 49(2): 354-360, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38403311

ABSTRACT

This study aimed to examine the morphological, physiological, and biochemical alterations occurring in Notopterygium incisum seeds throughout their developmental stages, with the objective of establishing a theoretical foundation for the cultivation of superior quality seeds. The experimental materials utilized in this study were the seeds of N. incisum at various stages of development following anthesis. Through the employment of morphological observation and plant physiology techniques, the external morphology, nutrients, enzyme activity, and endogenous hormones of the seeds were assessed. The results revealed a transition in seed coat color from light green to brown during the growth and development of N. incisum seeds. Additionally, as the seeds matured, a decrease in water content was observed. Conversely, starch content exhibited a progressive increase, while sucrose content displayed fluctuations. At 7 days after anthesis, the soluble sugar content attained its highest level of 4.52 mg·g~(-1), whereas the soluble protein content reached its maximum of 6.00 mg·g~(-1) at 14 days after anthesis and its minimum of 4.94 mg·g~(-1) at 42 days after anthesis. The activity of superoxide dismutase(SOD) exhibited an initial increase, followed by a decrease, and eventually reached a stable state. Conversely, the activities of catalase(CAT) and peroxidase(POD) demonstrated a decrease initially, followed by an increase, and then another decrease. The levels of the four endogenous hormones, namely gibberellin(GA_3), zeatin riboside(ZR), auxin(IAA), and abscisic acid(ABA), in the seeds displayed significant variations, with IAA and ABA exhibiting considerably higher levels compared to the other hormones. The levels of plant growth-promoting hormones, represented by IAA, generally displayed a pattern of initial increase followed by a subsequent decrease during seed development, while the plant growth-inhibiting hormone ABA showed the opposite trend. The findings indicate that the alterations in nutrient composition, antioxidant enzyme activity, and endogenous hormone levels vary throughout the maturation process of N. incisum seeds. These observations hold relevance for the cultivation of N. incisum seeds.


Subject(s)
Gibberellins , Plant Growth Regulators , Abscisic Acid , Seeds , Hormones/metabolism , Germination/physiology
4.
New Phytol ; 242(2): 351-371, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38416367

ABSTRACT

Tropical forest root characteristics and resource acquisition strategies are underrepresented in vegetation and global models, hampering the prediction of forest-climate feedbacks for these carbon-rich ecosystems. Lowland tropical forests often have globally unique combinations of high taxonomic and functional biodiversity, rainfall seasonality, and strongly weathered infertile soils, giving rise to distinct patterns in root traits and functions compared with higher latitude ecosystems. We provide a roadmap for integrating recent advances in our understanding of tropical forest belowground function into vegetation models, focusing on water and nutrient acquisition. We offer comparisons of recent advances in empirical and model understanding of root characteristics that represent important functional processes in tropical forests. We focus on: (1) fine-root strategies for soil resource exploration, (2) coupling and trade-offs in fine-root water vs nutrient acquisition, and (3) aboveground-belowground linkages in plant resource acquisition and use. We suggest avenues for representing these extremely diverse plant communities in computationally manageable and ecologically meaningful groups in models for linked aboveground-belowground hydro-nutrient functions. Tropical forests are undergoing warming, shifting rainfall regimes, and exacerbation of soil nutrient scarcity caused by elevated atmospheric CO2. The accurate model representation of tropical forest functions is crucial for understanding the interactions of this biome with the climate.


Las características de las raíces de los bosques tropicales y las estrategias de adquisición de recursos están subrepresentadas en modelos de vegetación, lo que dificulta la predicción del efecto de cambio de clima para estos ecosistemas ricos en carbono. Los bosques tropicales a menudo tienen combinaciones únicas a nivel mundial de alta biodiversidad taxonómica y funcional, estacionalidad de precipitación, y suelos infértiles, dando lugar a patrones distintos en los rasgos y funciones de las raíces en comparación con los ecosistemas de latitudes más altas. Integramos los avances recientes en nuestra comprensión de la función subterránea de los bosques tropicales en modelos de vegetación, centrándonos en la adquisición de agua y nutrientes. Ofrecemos comparaciones de avances recientes en la comprensión empírica y de modelos de las características de las raíces que representan procesos funcionales importantes en los bosques tropicales. Nos centramos en: (1) estrategias de raíces finas para adquisición de recursos del suelo, (2) acoplamiento y compensaciones entre adquisición del agua y de nutrientes, y (3) vínculos entre funciones sobre tierra y debajo del superficie en bosques tropicales. Sugerimos vías para representar estas comunidades de plantas extremadamente diversas en grupos computacionalmente manejables y ecológicamente significativos en modelos. Los bosques tropicales se están calentando, tienen cambios en los regímenes de lluvias, y tienen una exacerbación de la escasez de nutrientes del suelo causada por el elevado CO2 atmosférico. La representación precisa de las funciones de los bosques tropicales en modelos es crucial para comprender las interacciones de este bioma con el clima.


Subject(s)
Ecosystem , Plant Roots , Nitrogen , Forests , Soil , Plants , Water , Tropical Climate , Trees
5.
ACS Omega ; 9(5): 5705-5714, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38343962

ABSTRACT

The efficiency of reservoir imbibition in continental tight sandstone reservoirs is severely hindered due to their intricate wettability characteristics. To address this challenge, we propose a novel synergistic approach that combines low-frequency vibration and nanofluid treatment. This method integrates physical shear and chemical wettability alteration to effectively modify the wettability of neutral oil-wet tight sandstone, thereby enhancing the imbibition process. In this study, we formulated a TX-100 nanofluid system through physical modification. By utilizing the contact angle as a benchmark for evaluation, we investigated the impact of low-frequency fluctuations on the wettability of oil-wet sandstone. Subsequently, we identified the optimal combination of wave parameters. Through isothermal adsorption experiments and mechanical analyses of oil droplets subjected to fluctuations, we systematically elucidated the mechanism by which fluctuations collaborate with nanofluids to alter the wettability of oil-wet sandstone. Furthermore, we evaluated the oil displacement efficiency of cores subjected to the combined action of low-frequency fluctuations and nanofluid treatment. Our findings revealed that the TX-100 nanofluid reduced the static contact angle of oil-wet sandstone by 58%. When assisted by the optimal fluctuation parameters, the nanofluid treatment contributed to a 64% reduction in the contact angle of strongly oil-wet sandstone. This effect further amplified the reversal of wettability in oil-wet sandstone. Through the application of various wave-assisted treatment agents, the efficiency of oil removal was increased by a minimum of 16%. Moreover, the recovery degree of wave-assisted nanofluid imbibition experienced a remarkable enhancement of 30.39%. Nuclear magnetic resonance analysis demonstrated a significant improvement in pore sizes smaller than 1 µm as a result of the composite process.

6.
Environ Sci Pollut Res Int ; 31(15): 23091-23105, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38413526

ABSTRACT

As one of the most rapidly developing cities in China, Shenzhen grapples with an increasing challenge in managing water resources due to escalating conflicts with its soaring water demand. This study established a system dynamics (SD) model based on a causal loop diagram to explore the intricate interconnections within the urban water resources system. Through simulating water supply and demand in Shenzhen from 2021 to 2035, the model identified key sensitive factors and examined various utilization scenarios for multiple water resources. Results indicated that water scarcity posed a significant obstacle to Shenzhen's development. To tackle this challenge, several effective measures should be implemented, including enhancing water conservation capabilities, developing seawater resources, promoting water reuse, optimizing the economic structure, and managing population growth. Prioritizing water conservation efforts and maximizing the utilization of seawater resources were regarded as the most impactful strategies in alleviating the water crisis. Furthermore, the relationship between water conservation capabilities and seawater utilization scale was analyzed using the SD model, contributing to the development of a comprehensive water resources management strategy. The findings from this study would provide insights into robust methods for allocating water resources, thereby enhancing sustainable water management strategies applicable to regions facing similar challenges.


Subject(s)
Water Resources , Water Supply , Cities , China , Water , Conservation of Natural Resources/methods , Urbanization
7.
J Asian Nat Prod Res ; 26(6): 699-713, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38213072

ABSTRACT

Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype.


Subject(s)
Asthma , Autophagy , Inflammation , Saponins , T-Lymphocytes , Triterpenes , Animals , Saponins/pharmacology , Asthma/drug therapy , Triterpenes/pharmacology , Triterpenes/chemistry , Mice , Autophagy/drug effects , T-Lymphocytes/drug effects , Inflammation/drug therapy , Mice, Nude , Molecular Structure , Signal Transduction/drug effects , Mice, Inbred BALB C
8.
Medicine (Baltimore) ; 103(2): e36944, 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38215106

ABSTRACT

RATIONALE: Abnormal bleeding due to low fibrinogen (Fib) and coagulation factor XIII (FXIII) levels after lumbar vertebral surgery is exceedingly rare. Excessive bleeding is also associated with secondary hyperfibrinolysis. This report presents a case of abnormal incision bleeding caused by coagulation factor XIII deficiency (FXIIID) and secondary hyperfibrinolysis in a state of low fibrinogen after lumbar vertebral surgery. PATIENT CONCERNS: A middle-aged woman experienced prolonged incision and excessive bleeding after lumbar vertebral surgery. DIAGNOSIS: Combined with coagulation factors, coagulation function tests, and thromboelastography, the patient clinical presentation supported the diagnosis of FXIIID and secondary hyperfibrinolysis in a hypofibrinogenemic state. INTERVENTIONS: Cryoprecipitat, Fresh Frozen Plasma, Fibrinogen Concentrate, Leukocyte-depleted Red Blood Cells, Hemostatic (Carbazochrome Sodium Sulfonate; Hemocoagulase Bothrops Atrox for Injection; Tranexamic Acid). OUTCOMES: After approximately a month of replacement therapy and symptom treatment, the patient coagulation function significantly improved, and the incision healed without any hemorrhage during follow-up. LESSONS: Abnormal postoperative bleeding may indicate coagulation and fibrinolysis disorders that require a full set of coagulation tests, particularly coagulation factors. Given the current lack of a comprehensive approach to detect coagulation and fibrinolysis functions, a more comprehensive understanding of hematology is imperative. The current treatment for FXIIID involves replacement therapy, which requires supplementation with both Fib and FXIII to achieve effective hemostasis.


Subject(s)
Factor XIII Deficiency , Middle Aged , Female , Humans , Factor XIII Deficiency/complications , Factor XIII/therapeutic use , Lumbar Vertebrae/surgery , Blood Coagulation Factors , Fibrinogen , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/therapy
9.
Ecotoxicol Environ Saf ; 269: 115791, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38070417

ABSTRACT

Aluminum (Al), a non-essential metal for plant growth, exerts significant phytotoxic effects, particularly on root growth. Anthropogenic activities would intensify Al's toxic effects by releasing Al3+ into the soil solution, especially in acidic soils with a pH lower than 5.5 and rich mineral content. The severity of Al-induced phytotoxicity varies based on factors such as Al concentration, ionic form, plant species, and growth stages. Al toxicity leads to inhibited root and shoot growth, reduced plant biomass, disrupted water uptake causing nutritional imbalance, and adverse alterations in physiological, biochemical, and molecular processes. These effects collectively lead to diminished plant yield and quality, along with reduced soil fertility. Plants employ various mechanisms to counter Al toxicity under stress conditions, including sequestering Al in vacuoles, exuding organic acids (OAs) like citrate, oxalate, and malate from root tip cells to form Al-complexes, activating antioxidative enzymes, and overexpressing Al-stress regulatory genes. Recent advancements focus on enhancing the exudation of OAs to prevent Al from entering the plant, and developing Al-tolerant varieties. Gene transporter families, such as ATP-Binding Cassette (ABC), Aluminum-activated Malate Transporter (ALMT), Natural resistance-associated macrophage protein (Nramp), Multidrug and Toxic compounds Extrusion (MATE), and aquaporin, play a crucial role in regulating Al toxicity. This comprehensive review examined recent progress in understanding the cytotoxic impact of Al on plants at the cellular and molecular levels. Diverse strategies developed by both plants and scientists to mitigate Al-induced phytotoxicity were discussed. Furthermore, the review explored recent genomic developments, identifying candidate genes responsible for OAs exudation, and delved into genome-mediated breeding initiatives, isolating transgenic and advanced breeding lines to cultivate Al-tolerant plants.


Subject(s)
Alkaloids , Aluminum , Aluminum/toxicity , Aluminum/metabolism , Malates/metabolism , Plant Breeding , Plants/metabolism , Alkaloids/pharmacology , Organic Chemicals/metabolism , Soil/chemistry , Plant Roots/metabolism , Gene Expression Regulation, Plant
10.
Adv Sci (Weinh) ; 11(7): e2306181, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38064159

ABSTRACT

Due to its ability to adapt to a variety of electromagnetic (EM) environments, the sensing-enabled metasurface has garnered significant attention. However, large-scale EM-field sensing to obtain more information is still very challenging. Here, an adaptive information metasurface is proposed to enable intelligent sensing and wave manipulating simultaneously or more specifically, to realize intelligent target localization and beam tracking adaptively. The metasurface is composed of an array of meta-atoms, and each is loaded with two PIN diodes and a sensing-channel structure, for polarization-insensitive and programmable beamforming and sensing. By controlling the state of the PIN diode, the proposed meta-atom has 1-bit phase response in the designed frequency band, while the sensing loss keeps higher than -10 dB for both "ON" and "OFF" states. Hence there is nearly no interaction between the beamforming and sensing modes. Experiments are conducted to show multiple functions of the metasurface, including intelligent target sensing and self-adaptive beamforming, and the measured results are in good agreement with the numerical simulations and theoretical calculations.

11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1005118

ABSTRACT

ObjectiveTo develop traditional Chinese medicine (TCM) formulae for the treatment of nonsevere coronavirus disease 2019 (COVID-19) and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways, and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China, a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19, the calculation was carried out, and the artificial intelligent methods for compositing formulae, that are exhaustive method and parallel computing, were used to obtain candidate compound formulas. Finally, with reference to professional experience, an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b (Il1b), C-X-C motif chemokine ligand 2 (Cxcl2), C-X-C motif chemokine ligand 10 (Cxcl10), C-C motif chemokine ligand 2 (Ccl2), nitric oxide synthase 2 (Nos2), and prostaglandin-endoperoxide synthase 2 (Ptgs2) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in RAW264.7 cells treated with lipopolysaccharide (LPS). ResultsIn macrophages and lung epithelial cells, 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome, and the result showed that Yinqiao Powder and Pingwei Powder (银翘散合平胃散, YQPWP) ranked first, reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally, YQPWP had the function of scattering wind and clearing heat, resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula, and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin (翘蒡术皮饮, QBZPY) based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells, with the reversing rates of 100%. The chief medicinal of QBZPY, including Lianqiao (Fructus Forsythiae), Xixiancao (Herba Siegesbeckiae) and Niubangzi (Fructus Arctii), can down-regulate multiple signaling pathways related with virus infection, immune response, and epithelial damage. RT-qPCR results indicated that compared with the model group, the QBZPY group down-regulated the mRNA expression of Il1b, tumor necrosis factor (Tnf), Cxcl2, Cxcl10, Ccl2, Nos2 and Ptgs2 induced by LPS in RAW264.7 cells (P<0.05 or P<0.01). ConclusionBased on targeted transcriptome analysis, expert experience in TCM and artificial intelligence, QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.

12.
Sci Total Environ ; 912: 169578, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38154631

ABSTRACT

Coastal shallow waters are highly vulnerable to pollution, often leading to the development of intricate eutrophication zones. However, accurately determining these areas poses a significant challenge due to the complex interplay of estuarine hydrodynamics and nutrient transformation. To address such issue, a novel method was proposed to identify high-nutrient zones through calculating the continuous zonation of released tracers when their instantaneous concentrations declined to 1/e of their initial values. The method was well tested using idealized estuary models with varying shape parameters, water depths and river discharges. The results consistently revealed that the boundaries of high-nutrient zones fell within the mixed zone, characterized by salinity levels of 10- 20 psu. In Shenzhen Bay, a typical shallow bay, distinct differences were observed in the concentrations of dissolved inorganic nitrogen (DIN) and PO43-. Both the 20 psu isohaline and the proposed method effectively identified the partition boundary of high DIN and PO43- in 2001-2010, but only the newly proposed method demonstrated accuracy in delineating the actual high-nutrient zone during the continuous nutrient reduction period from 2010 to 2020. This study provides a practical and feasible approach that can serve as an auxiliary decision-making tool for managing estuarine water environments, and it has potential to facilitate the implementation of timely and effective measures for pollution control.

13.
Mol Ther ; 32(2): 490-502, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38098228

ABSTRACT

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated T cell activation effects. These innovative drugs are not only armed with the powerful T cell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity in vitro and in vivo. Surprisingly, they can also induce the activation of T cell chemotaxis signals, which may promote T cell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs.


Subject(s)
Neoplasms , T-Lymphocytes , Humans , Superantigens/therapeutic use , Antigens, Neoplasm , Cell Death
14.
Heliyon ; 9(12): e22605, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38107270

ABSTRACT

Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system with a low early diagnosis rate. Owing to the side effects, tolerance, and patient contraindications of existing therapies, effective drug treatments for HCC remain a major clinical challenge. However, using approved or investigational drugs not initially intended for cancer therapy is a promising strategy for resolving this problem because their safety have been tested in clinic. Therefore, this study evaluated differentially expressed genes between liver cancer and normal tissues in a cohort of patients with HCC from The Cancer Genome Atlas and applied them to query a connectivity map to identify candidate anti-HCC drugs. As a result, fluphenazine was identified as a candidate for anti-HCC therapy in vitro and in vivo. Fluphenazine suppressed HCC cell proliferation and migration and induced cell cycle arrest and apoptosis, possibly owing to disrupted lysosomal function, blocking autophagy flux. Additionally, in vivo studies demonstrated that fluphenazine suppresses HCC subcutaneous xenografts growth without causing severe side effects. Strikingly, fluphenazine could be used as an analgesic to alleviate oxaliplatin-induced pain as well as pain related anxiety-like behavior. Therefore, fluphenazine could be a novel liver cancer treatment candidate.

15.
World J Gastrointest Surg ; 15(11): 2553-2563, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38111756

ABSTRACT

BACKGROUND: Although the location of proximal cancer of the remnant stomach is the same as that of primary proximal cancer of the stomach, its clinical characteristics and prognosis are still controversial. AIM: To evaluate the clinicopathological features and prognosis factors of gastric stump cancer (GSC) and primary proximal gastric cancer (PGC). METHODS: From January, 2005 to December, 2016, 178 patients with GSC and 957 cases with PGC who received surgical treatment were enrolled. Patients in both groups underwent 1:1 propensity score matching analysis, and both clinical and pathological data were systematically collected for statistical purposes. Quality of life was evaluated by the C30 and STO22 scale between GSC-malignant (GSC following gastric cancer) and GSC-benign (GSC following benign lesions of the stomach). RESULTS: One hundred and fifty-two pairs were successfully matched after propensity score matching analysis. Of the 15 demographic and pathological variables collected, the analysis further revealed that the number of lymph nodes and positive lymph nodes were different prognostic and clinicopathological factors between PGC and GSC. Univariate and multivariate analyses showed that gender, differentiation degree and tumor-node-metastasis stage were independent risk factors for patients with GSC. Gender, vascular invasion, differentiation degree, depth of infiltration, positive lymph nodes, and tumor-node-metastasis stage were independent risk factors for patients with PGC. The 5-year overall survival and cancer-specific survival of patients with GSC were significantly lower than those in the PGC group, the scores for overall quality of life in the GSC-malignant group were lower than the GSC-benign, and the differences were statistically significant. CONCLUSION: The differences in clinicopathological characteristics between GSC and PGC were clarified, and PGC had a better prognosis than GSC.

16.
Environ Sci Pollut Res Int ; 30(59): 124407-124415, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37966645

ABSTRACT

Organotin compounds (OTs) accumulate in fish easily, however, research on their influencing factors is still limited. This study collected 25 species of fish with different diets, habitats, and age from the Three Gorges Reservoir (TGR), the largest deep-water river channel-type reservoir in China, and analyzed the accumulation characteristics of OTs in these fish. The results showed that tributyltin (TBT) and triphenyltin (TPhT) were the dominant OTs in fish from the TGR. The correlation between OTs concentration and age, body length, and body weight varied with fish species. The concentrations of TBT and TPhT in carnivorous fish (mean, 25.78 and 11.69 ng Sn/g dw, respectively) were higher than those in other diet fish (P<0.01), but there was no significant difference in fish at different habitat water layers (P>0.05). In addition, the degradation rates of TBT and TPhT in different fish species were all below 50%. In summary, the accumulation of TBT and TPhT in fish is mainly influenced by diet, and both TBT and TPhT were difficult to degrade in fish. These results reveal the pollution characteristics of OTs in fish from the TGR, and can improve our understanding of the factors influencing TBT and TPhT accumulation in freshwater fish.


Subject(s)
Organotin Compounds , Trialkyltin Compounds , Water Pollutants, Chemical , Animals , Trialkyltin Compounds/metabolism , Fishes/metabolism , China , Environmental Monitoring , Water , Water Pollutants, Chemical/analysis
17.
Eur J Pharmacol ; 960: 176128, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-37866747

ABSTRACT

Programmed cell death receptor/ligand 1 (PD-1/PD-L1) blockade therapy for various cancers induces itch. However, few studies have evaluated the mechanism underlying PD-1/PD-L1 inhibitor-induced itch. This study aimed to establish and evaluate a mouse model of acute itch induced by PD-1/PD-L1 inhibitors and to explore the role of the PD-1/PD-L1 pathway in chronic itch. The intradermal injection of the PD-1/PD-L1 small molecule inhibitors, or anti-PD-1/PD-L1 antibodies in the nape of the neck in the mice elicited intense spontaneous scratches. The model was evaluated using pharmacological methods. The number of scratches was reduced by naloxone but not by antihistamines or the transient receptor potential (TRP) channel inhibitor. Moreover, the PD-1 receptor was detected in the spinal cord of the mouse models of chronic itch that exhibited acetone, diethyl ether, and water (AEW)-induced dry skin, imiquimod-induced psoriasis, and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced allergic contact dermatitis. Intrathecal PD-L1 (1 µg, 4 times a week for 1 week) suppressed the activation of the microglia in the spinal dorsal horn to relieve the chronic itch that was elicited by imiquimod-induced psoriasis and DNFB-induced allergic contact dermatitis. Although the activation of the microglia in the spinal dorsal horn was not detected in the AEW-treated mice, intrathecal PD-L1 still reduced the number of scratches that were elicited by AEW. Our findings suggest that histamine receptor inhibitors or TRP channel inhibitors have limited effects on PD-1/PD-L1 inhibitor-induced itch and that spinal PD-1 is important for the spinal activation of the microglia, which may underlie chronic itch.


Subject(s)
Dermatitis, Allergic Contact , Psoriasis , Animals , Mice , Programmed Cell Death 1 Receptor , Dinitrofluorobenzene/adverse effects , B7-H1 Antigen , Imiquimod/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Pruritus/metabolism , Spinal Cord Dorsal Horn/metabolism , Dermatitis, Allergic Contact/drug therapy , Disease Models, Animal , Psoriasis/drug therapy , Mice, Inbred C57BL
18.
Nat Commun ; 14(1): 6796, 2023 10 25.
Article in English | MEDLINE | ID: mdl-37880211

ABSTRACT

Digital pathology allows computerized analysis of tumor ecosystem using whole slide images (WSIs). Here, we present single-cell morphological and topological profiling (sc-MTOP) to characterize tumor ecosystem by extracting the features of nuclear morphology and intercellular spatial relationship for individual cells. We construct a single-cell atlas comprising 410 million cells from 637 breast cancer WSIs and dissect the phenotypic diversity within tumor, inflammatory and stroma cells respectively. Spatially-resolved analysis identifies recurrent micro-ecological modules representing locoregional multicellular structures and reveals four breast cancer ecotypes correlating with distinct molecular features and patient prognosis. Further analysis with multiomics data uncovers clinically relevant ecosystem features. High abundance of locally-aggregated inflammatory cells indicates immune-activated tumor microenvironment and favorable immunotherapy response in triple-negative breast cancers. Morphological intratumor heterogeneity of tumor nuclei correlates with cell cycle pathway activation and CDK inhibitors responsiveness in hormone receptor-positive cases. sc-MTOP enables using WSIs to characterize tumor ecosystems at the single-cell level.


Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Ecosystem , Triple Negative Breast Neoplasms/genetics , Tumor Microenvironment
19.
Heliyon ; 9(9): e19233, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37674842

ABSTRACT

Liver hepatocellular carcinoma (LIHC) is a major malignant tumor of the digestive system with a high incidence rate and poor early diagnosis. Coiled-coil domain-containing protein 115 (CCDC115), an accessory component of vacuolar-ATPase with dramatically abnormal expression, is associated with survival outcomes of cancer patients. However, the role of CCDC115 in LIHC remains unclear. In this study, we aimed to determine the functional role of CCDC115 in LIHC by examining CCDC115 expression, and its influence on LIHC prognosis. Through extensive statistical analyses, using LIHC patient databases, we observed that CCDC115 expression significantly increased in tumor tissues of LIHC patients. In addition, CCDC115 expression correlated with the poor prognosis. Additionally, CCDC115 was found to be involved in several cancer-related pathways, specifically the PI3K-Akt pathway. The expression of CCDC115 was positively correlated with human leukocyte antigen molecules as well as with immune checkpoint molecules in LIHC patients. We performed in vitro experiments and confirmed that the expression of CCDC115 significantly affects the proliferation potential, metastasis and sorafenib resistance of liver cancer cells, as well as some key protein expression in PI3K-Akt pathway. These results indicate that CCDC115 could serve as a diagnostic and prognostic biomarker of LIHC, and targeting CCDC115 may provide a potential strategy to enhance the efficacy of liver cancer therapy.

20.
Sci Total Environ ; 904: 166677, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37659524

ABSTRACT

The environmental issue of lead (Pb), cadmium (Cd), and tetracycline (TC) contamination in cereal crops has become a growing concern worldwide. An in-depth understanding of this issue would be of importance to promote effective management strategies for heavy metals and antibiotics worldwide. The present study was conducted to assess the toxic effects of heavy metals (Cd, Pb) and antibiotics (TC) on Triticum aestivum (T. aestivum, common wheat) based on studies conducted in the past 22 years. Data pertaining to the growth and development of T. aestivum were extracted and analyzed from 89 publications spanning from 2000 to 2022. Our results showed that Pb, Cd and TC significantly reduced growth and development by 11 %, 9 %, and 5 %, respectively. Additionally, significant accumulation of Cd (42 %) and Pb (17 %) was observed in T. aestivum samples, although there was little change in TC accumulation, which showed limited absorption, accumulation, and translocation of TC in wheat plants. Pb had the greatest impact on the yield of T. aestivum, followed by Cd, while TC had no apparent effect. Furthermore, exposure to Cd, Pb and TC reduced the photosynthetic rate due to chlorophyll reduction, with Cd having the most pronounced effect (58 %), followed by Pb (37 %) and TC (8 %). Cd exposure also significantly enhanced gaseous exchange (37 %) compared to TC and Pb, which reduced gaseous exchange by 4 % and 10 %, respectively. However, the treatments with TC (>50-100 mgL-1), Pb (>1000-2000 mg L-1) and Cd (>500-1000 mg L-1) increased the defense system of T. aestivum samples by 38 %, 15 %, and 11 %, respectively. The obtained findings have significant implications for risk assessment, pollution prevention, and remediation strategies to address soil contamination from Pb, Cd and TC in farmland.


Subject(s)
Metals, Heavy , Soil Pollutants , Cadmium/analysis , Triticum , Lead/toxicity , Lead/analysis , Metals, Heavy/analysis , Soil , Anti-Bacterial Agents/pharmacology , Growth and Development , Tetracyclines/analysis , Soil Pollutants/analysis
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