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BACKGROUND: The marbling trait of cattle muscles, being a key indicator, played an important role in evaluating beef quality. Two breeds of cattle, namely a high-marbling (Angus) and a low-marbling (Nanyang) one, with their cattle muscles selected as our samples for transcriptome sequencing, were aimed to identify differentially expressed long non-coding RNAs (lncRNAs) and their targets associated with the marbling trait. RESULTS: Transcriptome sequencing identified 487 and 283 differentially expressed mRNAs and lncRNAs respectively between the high-marbling (Angus) and low-marbling (Nanyang) cattle muscles. Twenty-seven pairs of differentially expressed lncRNAs-mRNAs, including eighteen lncRNAs and eleven target genes, were found to be involved in fat deposition and lipid metabolism. We established a positive correlation between fourteen up-regulated (NONBTAT000849.2, MSTRG.9591.1, NONBTAT031089.1, MSTRG.3720.1, NONBTAT029718.1, NONBTAT004228.2, NONBTAT007494.2, NONBTAT011094.2, NONBTAT015080.2, NONBTAT030943.1, NONBTAT021005.2, NONBTAT021004.2, NONBTAT025985.2, and NONBTAT023845.2) and four down-regulated (NONBTAT000850.2, MSTRG.22188.3, MSTRG.22188.4, and MSTRG.22188.5) lncRNAs and eleven genes related to adiponectin family protein (ADIPOQ), cytochrome P450 family (CYP4V2), 3-hydroxyacyl-CoA dehydratase family (HACD4), kinesin family (KIF5C), lipin family (LPIN2), perilipin family (PLIN1), prostaglandin family (PTGIS), solute carrier family (SLC16A7, SLC2213, and SLCO4C1), and containing a transmembrane domain protein family (VSTM1). CONCLUSIONS: These candidate genes and lncRNAs can be regarded as being responsible for regulating the marbling trait of cattle. lncRNAs along with the variations in intramuscular fat marbling established a foundation for elucidating the genetic basis of high marbling in cattle.
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ARN Largo no Codificante , ARN Mensajero , Animales , Bovinos/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Perfilación de la Expresión Génica , Transcriptoma , Músculo Esquelético/metabolismoRESUMEN
Immunosuppression is a major hallmark of tumor progression in non-small cell lung cancer (NSCLC). Cluster of differentiation 147 (CD147), an important pro-tumorigenic factor, is closely linked to NSCLC immunosuppression. However, the role of CD147 di-methylation in the immunosuppressive tumor microenvironment (TME) remains unclear. Here, di-methylation of CD147 at Lys148 (CD147-K148me2) is identified as a common post-translational modification (PTM) in NSCLC that is significantly associated with unsatisfying survival outcomes among NSCLC sufferers, especially those in the advanced stages of the disease. The methyltransferase NSD2 catalyzes CD147 to generate CD147-K148me2. Further analysis demonstrates that CD147-K148me2 reestablishes the immunosuppressive TME and promotes NSCLC progression. Mechanistically, this modification promotes the interaction between cyclophilin A (CyPA) and CD147, and in turn, increases CCL5 gene transcription by activating p38-ZBTB32 signaling, leading to increased NSCLC cell-derived CCL5 secretion. Subsequently, CD147-K148me2-mediated CCL5 upregulation facilitates M2-like tumor-associated macrophage (TAM) infiltration in NSCLC tissues via CCL5/CCR5 axis-dependent intercellular crosstalk between tumor cells and macrophages, which is inhibited by blocking CD147-K148me2 with the targeted antibody 12C8. Overall, this study reveals the role of CD147-K148me2-driven intercellular crosstalk in the development of NSCLC immunosuppression, and provides a potential interventional strategy for PTM-targeted NSCLC therapy.
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Basigina , Carcinoma de Pulmón de Células no Pequeñas , Quimiocina CCL5 , Neoplasias Pulmonares , Receptores CCR5 , Microambiente Tumoral , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Basigina/metabolismo , Basigina/genética , Ratones , Animales , Receptores CCR5/metabolismo , Receptores CCR5/genética , Quimiocina CCL5/metabolismo , Quimiocina CCL5/genética , Microambiente Tumoral/inmunología , Macrófagos/metabolismo , Macrófagos/inmunología , Línea Celular Tumoral , Terapia de Inmunosupresión , Modelos Animales de Enfermedad , Transducción de SeñalRESUMEN
The hydrological regime is considered to be the major factor that affects the distribution of arbuscular mycorrhiza (AM) fungi in wetlands. We aimed to investigate the responses of AM fungal community to different hydrological gradients. Illumina Miseq sequencing technology was used to study the AM fungal community structure in roots and rhizosphere soils of Phragmites australis in different moisture areas (dry area, alternating wet and dry area, and flooded area) in Mengjin Yellow River wetland. The rhizosphere soils and roots hosted different AM fungal communities. In roots, the AM fungal colonization and Chao1 richness in dry area were significantly higher than that in alternating wet and dry area and flooded area, but the community composition did not vary clearly under different water conditions. In rhizosphere soils, the Chao1 richness of AM fungi in flooded area was significantly higher than that in alternating wet and dry area and dry area, and the AM fungal community structure obviously differed across different areas. The redundancy analyses indicated that changes in the AM fungal community in soils were associated with altered soil properties, and the abundance of the dominant genus Glomus was mostly positively correlated with alkali-hydrolyzable nitrogen in soils. This study helps us to understand the responses of AM fungal community to hydrological gradients in wetlands.
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BACKGROUND AND OBJECTIVE: Periodontitis is intimately associated with the development of various systemic diseases, among which type 2 diabetes mellitus (T2DM) has a bidirectional relationship with the pathogenesis of periodontitis. The objective of the present work was to investigate the role of berberine (BBR) in periodontitis with T2DM and related mechanisms. METHODS: The mRNA expression of macrophage polarization-related factors in the microenvironment of periodontal inflammation was detected using real-time quantitative PCR (RT-qPCR). The experimental periodontitis model was constructed in wild-type (WT) and T2DM (db/db) mice, which were administered BBR after 7 days of modeling. Alveolar bone loss (ABL) in each group of mice was measured utilizing micro-computed tomography images. RT-qPCR was performed to analyze the levels of macrophage polarization-related factors in mouse gingiva. Lastly, using western blotting and RT-qPCR, the signaling pathway of BBR affecting macrophage polarization in the microenvironment of periodontitis was explored. RESULTS: BBR inhibited M1 polarization and stimulated M2 polarization in the periodontitis microenvironment. BBR decreased ABL in the WT and T2DM periodontitis models. And BBR reduced the production of proinflammatory cytokines and increased anti-inflammatory cytokine expression in the gingiva of WT and T2DM model mice. Ultimately, BBR mediates its anti-inflammatory effects on periodontitis through inhibition of the NF-κB pathway. CONCLUSIONS: BBR had a therapeutic effect on T2DM-associated periodontitis via inhibiting the NF-κB pathway to affect macrophage polarization, which may have implications for the new pharmacological treatment of T2DM-associated periodontitis.
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Pérdida de Hueso Alveolar , Berberina , Diabetes Mellitus Tipo 2 , Macrófagos , FN-kappa B , Periodontitis , Transducción de Señal , Animales , Periodontitis/complicaciones , Periodontitis/tratamiento farmacológico , Ratones , FN-kappa B/metabolismo , Macrófagos/efectos de los fármacos , Berberina/farmacología , Berberina/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/prevención & control , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL , Microtomografía por Rayos X , Activación de Macrófagos/efectos de los fármacos , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicacionesRESUMEN
The purpose of this study is to evaluate the influences of Chinese yam polysaccharide (CYP) dietary supplementation on the composition of intramuscular fat (IMF) and fatty acids (FA) in thigh and breast muscles of broilers. Three hundred and sixty healthy one-day-old broilers (the breed of Crossbred chicken is named 817) with gender-balanced and similar body weight (39 ± 1 g) were randomly allocated into four groups (control, CYP1, CYP2, and CYP3 groups). Broilers in the control group were only fed a basal diet, and broilers in CYP1 group were fed the same diets further supplemented with 250 mg/kg CYP, the CYP2 group was fed the same diets further supplemented with 500 mg/kg CYP, and the CYP3 group was fed the same diets further supplemented with 1000 mg/kg CYP, respectively. Each group consisted of three replicates and each replicate consisted of 30 birds. The feeding days were 48 days. The results observed that the CYP2 group (500 mg/kg) can up-regulate the mRNA expression levels of ß-catenin in thigh muscle compared to the control group. At the same time, all CYP groups (CYP1, CYP2, and CYP3 groups) can up-regulate mRNA expression of Wnt1 and ß-catenin in breast muscle, while mRNA expression of PPARγ and C/EBPα in breast and thigh muscles could be down-regulated (p < 0.05). In summary, 500 mg/kg of CYP dietary supplementation can reduce IMF content and improve the FAs composition, enhancing the nutritional value of chicken meat.
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Chinese yam polysaccharide (CYP) has received attention in recent years owing to its positive nutritional and medicinal characteristics. Copper is an essential trace metal in animals, which plays an important role in iron absorption and hemoglobin synthesis. However, no published study has evaluated Chinese yam polysaccharide copper complex (CYP-Cu) as a dietary additive in broilers. This study was conducted to investigate the effects of dietary CYP-Cu on growth performance, immunity, and oxidative resistance in broilers. A total of 360 1-day-old 817 broiler chickens were randomly divided into 4 groups, with 3 replicates of 30 birds each and were fed a basal diet with the addition of 0 (control group), 0.02, 0.10, and 0.50 g/kg CYP-Cu. The feeding trial lasted 48 days. On day 28 and day 48, 6 broilers in each group were slaughtered, respectively. Then the parameters of growth and carcass, serum biochemistry, immunity, and antioxidation, and the expression level of hepatic antioxidative genes were investigated. The results showed that compared with the control group, the supplementation of dietary CYP-Cu could improve the indexes of the growth, carcass, serum biochemistry, immunity and oxidation resistance in broilers, such as average daily gain (ADG), the slaughter percentage (SP), semi-evisceration weight percentage (SEWP), eviscerated carcass weight percentage (EWP), breast muscle percentage (BMP), leg muscle percentage (LMP), serum albumin (ALB), high density lipoprotein (HDL), insulin-like growth factor I (IGF-I), triiodothyronine (T3), thyroxine (T4), growth hormone (GH), insulin (INS), immunoglobulin M (IgM), immunoglobulin G (IgG), immunoglobulin A (IgA), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), complement 3 (C3), complement 4 (C4), total superoxide dismutase (T-SOD), total antioxidative capacity (T-AOC), glutathione peroxidase (GSH-Px), and glutathione s-transferase (GSH-ST); these parameters in the 0.10 g/kg CYP-Cu treated group were significantly increased (P < 0.05) in the total trial period, with the exceptions that feed conversion ratio (FCR) and serum low density lipoprotein (LDL), malondialdehyde (MDA) were decreased in the total trial period. In addition, the antioxidative gene mRNA expression of Nuclear factor E2-related factor 2 (Nrf 2), Superoxide dismutase 1 (SOD 1), Superoxide dismutase 2 (SOD 2), and Catalase (CAT) were upregulated in the liver (P < 0.05). These results indicated that the supplementation of dietary CYP-Cu improved the growth, immunity, and oxidation resistance of broilers, and the addition of 0.10 g/kg CYP-Cu in broiler diets is recommended, which suggests that CYP-Cu may be a promising green feed additive in the poultry industry.
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The study aimed to evaluate the influences of the dietary supplementation of Chinese yam polysaccharide (CYP) on the carcass performance, antioxidant capacity, and meat quality of broilers. Three hundred and sixty healthy 1-day-old broilers with similar body weight (39 ± 1 g, gender balanced) were randomly divided into four groups (control, CYP1, CYP2, and CYP3 groups). In the control group, broilers were fed a basal diet with CYP, and the CYP1, CYP2, and CYP3 groups were fed diets supplemented with 250, 500, and 1000 mg/kg CYP, respectively. There were three replicates in each group, 30 birds in each replicate, and the feeding trial lasted for 48 days. Statistical analysis was performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA) by one-way analysis of variance. The results showed that compared with the control group, dietary supplementation with 500 mg/kg CYP can improve live weight, half-eviscerated carcass percentage, eviscerated carcass percentage, and thigh muscle percentage. Moreover, dietary supplementation with 500 mg/kg CYP can improve the contents of total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GPX), and glutathione s-transferase (GST) in serum (p < 0.05). Meanwhile, the mRNA expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1), superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), and catalase (CAT) in the liver; the mRNA expression levels of HO-1, NQO1, GPX1, and CAT in the breast muscle; and the mRNA expression levels of NQO1, SOD1, and CAT in the thigh muscle of broilers in the CYP2 group were significantly increased (p < 0.05). In addition, the yellowness and shear force of the thigh and breast muscles and the content of malondialdehyde (MDA) in the serum of broilers in the control group were higher than that in the CYP2 groups (p < 0.05). The results demonstrated that the CYP2 group had the best effect on improving meat quality. In conclusion, dietary supplementation with 500 mg/kg CYP can improve the meat quality of broilers by improving carcass quality, meat color, shear force, and antioxidant capacity.
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The purpose of this experiment was to investigate the effects of Chinese yam polysaccharides (CYP) in diets on the immune function of broilers. A total of 360 (1-day-old, sex balance) healthy growing broilers with similar body weight (39.54 ± 0.51 g) were randomly divided into control (0.00 g/kg), CYP I (0.25 g/kg), CYP II (0.50 g/kg), and CYP III (1.00 g/kg) groups. Each group contains 3 replicates with 30 broilers in each replicate, and the feeding trial lasted 48 d. The results showed that compared with the control group, the CYP II group had higher thymus index, serum IgA, complement C3, C4, IGF-I, T3, T4, INS, GH, IL-2, IL-4, IL-6, and TNF-α levels (P < 0.05) at 28, 48 d, respectively. In addition, the spleen index, serum IgM and IgG concentrations in CYP II group were higher than those in the control group at 28 d (P < 0.05). Results indicated that 0.50 g/kg CYP supplementation improved the immune function of broilers, and the CYP has a potential biological function as a green additive in broilers.
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In this study, a schwertmannite-like mineral was synthesized for the removal of lead (Pb) and chromium (Cr) from contaminated wastewater. A shaking flask test was performed (150 r/min, 1 h) with FeSO4·7H2O, H2O2, Na2SiO3, and CaCl2 added for the mineral synthesis reaction. Results show that optimal performance was achieved with the addition of 1.24 g/L FeSO4·7H2O, 0.75 g/L H2O2, 1.27 g/L Na2SiO3, and 0.44 g/L CaCl2 at a water temperature of 28 °C, with coexisting ion (Na+, K+, Mg2+) concentrations of 1.50 mmol/L and 0.50 mmol/L EDTA as a complexing agent. Under these optimal conditions, maximum Pb and Cr removal rates of 95.08% and 97.99%, respectively, were achieved within the first 1 min of the mineral synthesis reaction, with the synthesis reaction completed by 6 min. The simultaneous removal of Pb and Cr during the schwertmannite-like material synthesis process occurred via electrostatic adsorption and coprecipitation. When the concentration of the complexing agent was increased from 0.75 to 6.03 mmol/L, the Pb removal rate decreased from 71.88 to 35.45%, and the Cr removal rate decreased from 95.13 to 75.07%, showing that Pb and Cr removal exhibited significant levels of inhibition. In contrast, varying reaction temperatures induced no significant differences. The Pb and Cr dissolution rates from Pb/Cr-containing schwertmannite-like minerals were 8.18% and 2.86% after 40 days, respectively. Therefore, the risk of secondary dissolution of heavy metals is small.
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Cromo , Contaminantes Químicos del Agua , Cromo/análisis , Aguas Residuales , Plomo , Peróxido de Hidrógeno , Cloruro de Calcio , Contaminantes Químicos del Agua/análisis , Adsorción , Minerales , Concentración de Iones de HidrógenoRESUMEN
PURPOSE: This study investigated and tested a novel cone-beam computed tomography (CBCT) scanning technique capable of obtaining clear contours of soft tissues in the esthetic area. METHODS: Twenty-three periodontally healthy participants underwent this novel CBCT scanning technique. Soft tissue morphological parameters were measured on the CBCT images obtained. Intraoral clinical data were also collected at the same locations, and the accuracy of the CBCT method was tested. RESULTS: The median (interquartile range [IQR]) of the supracrestal gingival tissue thickness as 0.91 (0.73-1.13) mm, and the thickness of the central incisors was significantly greater than that of the canines (P < 0.05). The median (IQR) of keratinized tissue thickness was 0.73 (0.55-0.91) mm, which also showed a significantly greater thickness in the central incisors than in the canines (P < 0.05). Bland-Altman analysis suggested that CBCT could be accurate for measuring soft tissues in the esthetic area. CONCLUSION: The novel CBCT technique described yields clear contours of soft tissues in the esthetic area without the need for auxiliary tools. Moreover, measurements of soft tissue morphological parameters on CBCT appear to be accurate.
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Tomografía Computarizada de Haz Cónico , Diente , Tomografía Computarizada de Haz Cónico/métodos , Estética , Encía/diagnóstico por imagen , HumanosRESUMEN
PURPOSE: A consistent relationship between CMT and DDH has been established. However, whether the presence of CMT has effect on clinical outcomes of DDH remains unanswered. This study aimed to evaluate clinical features and management of DDH in patients with CMT. METHODS: We reviewed the medical records of 54 patients (91 hips) simultaneously diagnosed with DDH and CMT and included 54 patients (97 hips) with only DDH by random number method as the control group. Clinical and examination outcomes were recorded and compared, respectively. RESULTS: The mean follow-up was 18.1 ± 14.5 months (range, 2 to 72 mo). In the DDH and CMT group, the age of initial treatment was lower (100.8 ± 92.3 vs. 229.0 ± 157.4 d, P < 0.001), and the rate of male significantly increased (42.6% vs. 11.1%, P < 0.001). Before treatment, development degree of hip was better than that of the DDH group. Therefore, patients with CMT had approximately 14 times greater odds of conservative treatment success than children in the DDH group (OR, 13.84; 95% CI, 3.16 to 60.60). CONCLUSION: We concluded that CMT was not the risk factor for the failure of treatment. On the contrary, the identification of CMT may be beneficial to early discovery and treatment of DDH when we remain vigilant to perform physical exam and screen imaging of DDH for patients with CMT.
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Displasia del Desarrollo de la Cadera , Luxación Congénita de la Cadera , Tortícolis , Niño , Luxación Congénita de la Cadera/complicaciones , Luxación Congénita de la Cadera/diagnóstico , Luxación Congénita de la Cadera/terapia , Humanos , Lactante , Masculino , Estudios Retrospectivos , Tortícolis/congénito , Tortícolis/diagnóstico , Tortícolis/etiología , Tortícolis/terapiaRESUMEN
This experiment was conducted to evaluate the effects of dietary Chinese yam polysaccharides (CYP) on myogenic differentiation 1 (MYOD1), myogenin (MYOG), and myostatin (MSTN) mRNA expression of breast and thigh muscle tissues in broilers. A total of 360 (1-day-old, gender-balanced) crossbred broilers chicks with similar body weight (BW) were randomly distributed into four groups, with three replicates in each group and each replicate included 30 broilers. The feeding trial lasted for 48 days. Experimental broilers were fed 0.00 mg/kg basal diet (control group), 250 mg/kg, 500 mg/kg, and 1000 mg/kg CYP, respectively. The results showed that CYP250 and CYP500 groups had higher thigh muscle percentage (TMP) compared to the control group (p < 0.05). Meanwhile, the expression of MYOD1, MYOG mRNA in breast muscle tissues of CYP500 and CYP1000 groups was higher (p < 0.05), and the expression of MSTN mRNA in thigh muscle of CYP250, CYP500, and CYP1000 groups was lower than that of the control group (p < 0.05). In addition, there was no significant difference in the expression of MYOD1 mRNA in the thigh muscle tissue of each group (p > 0.05). Bivariate correlation analysis showed that the expression levels of MYOD1, MYOG, and MSTN mRNA in the thigh muscle tissue of broiler chickens in the CYP500 group were positively correlated with TMP. However, the expression of MYOG mRNA in thigh muscle tissue of the CYP1000 group was negatively correlated with TMP. In general, this study indicated that appropriate dietary CYP supplementation influenced the growth and development of thigh muscle tissue in broilers by altering TMP and muscle tissue development-related genes expression. Therefore, CYP could be used as a potential feed additive to promote the development of muscle tissues in broilers.
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Pollos , Dioscorea , Animales , Pollos/metabolismo , Suplementos Dietéticos/análisis , Dioscorea/genética , Muslo , Músculo Esquelético/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Peso CorporalRESUMEN
Non-small cell lung cancer (NSCLC) is a highly malignant tumor, with a significant mortality and morbidity. With the development of tumor immunotherapy, chimeric antigen receptor T cells (CART) gets increasingly attention and achieves prominent contributions in the treatment of hematologic malignancies. However, CART therapy for NSCLC proceeds slowly and further researches need to be investigated. In our study, we performed bioinformatics analysis to evaluate the significant role of CD147 in NSCLC. The expression level of CD147 was detected in human NSCLC cell lines and NSCLC tissues. Meanwhile, CD147-CART was constructed and identified. Cell cytotoxicity and cytokine secretion were performed to evaluate the efficacy of CD147-CART. We also constructed cell-derived xenograft (CDX) model and patient-derived xenograft (PDX) model, which was used to further investigate the safety and efficacy of CD147-CART in vivo. Our observations show that CD147 is a specific tumor antigen of NSCLC and plays an essential role in NSCLC progression, which can be used as a target for CART therapy in NSCLC. CD147-CART cells exhibit robust cytotoxicity and cytokine production in vitro, suggesting a strong anti-tumor activity against NSCLC tumor cells. Importantly, CD147-CART cells have strong anti-tumor activity against NSCLC cells in vivo in both CDX and PDX models and no adverse side effects. Our findings show that CD147-CART immunotherapy for NSCLC is safe and effective, which is an ideal and promising medical patch for treating NSCLC.
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Immuno-checkpoint inhibitors (ICIs) bring a promising prospect for patients with cancers, which restrains the growth of tumor cells by enhancing anti-tumor activity. Nevertheless, not all patients benefit from the administration of ICIs monotherapy. The partial response or resistance to ICIs is mainly due to the complex and heterogenous tumor microenvironment (TME). The combined therapy is necessary for improving the efficacy of tumor treatment. Chemotherapy is reported not only to kill tumor cells directly, but also to stimulate effective anti-tumor immune responses. Several combined therapies of ICIs and chemotherapeutic agents have been approved for the first-line treatment of cancers, including PD-1/PD-L1 inhibitors. This review summarizes the potential mechanisms of the combined therapy of ICIs and chemotherapeutic agents in inducing immunogenic cell death (ICD) and reprogramming TME, and elucidates the possible anti-tumor effects of combined therapy from the perspective of metabolic reprogramming and microbiome reprogramming.
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Antineoplásicos , Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inmunoterapia/métodos , Neoplasias/tratamiento farmacológico , Microambiente Tumoral , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Lung cancer is a common malignant tumor that threatens human life and is associated with high morbidity and mortality rates. Calreticulin (CALR) is a antigen characteristic of immunogenic cell death in non-small cell lung cancer (NSCLC), which is closely related to anti-tumor immunity, but its specific mechanism in anti-tumor immunity remains unclear. METHODS: Immunohistochemical staining was performed to detect the expression of CALR and dendritic cell-lysosome-associated membrane glycoprotein (DC-LAMP) in NSCLC tissues. The cell supernatant was used to induce migration and maturation of dendritic cells (DCs). Western blot and real-time PCR were used to investigate the corresponding molecule expression in the CALR-Toll-like receptor 4 (TLR4)-MyD88 signaling pathway. In vivo experiments were conducted to evaluate the role of mCALR in lung cancer progression. RESULTS: The expression of CALR on NSCLC cell membrane (mCALR) and DC infiltration in NSCLC were positively correlated and were closely related to the prognosis of NSCLC patients. Moreover, mCALR facilitated the migration and maturation of DCs by activating CALR-TLR4-MyD88 signaling and increasing the secretion of TNFα and CCL19, which was inhibited by the loss of TLR4. In vivo experiments demonstrated that mCALR inhibited lung cancer progression by facilitating DC infiltration in lung cancer tissues. CONCLUSION: Our study explores the function and mechanism of the CALR-TLR4 complex in DC migration and maturation and investigates the inhibitory effect of the CALR-TLR4 complex on lung cancer progression, providing a theoretical basis and ideas for immunotherapy of NSCLC.
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Antimony (Sb) traces in water pose a serious threat to human health due to their negative effects. In this work, nanoscale zero-valent iron (Fe0) supported on activated carbon (nZVI) was employed for eliminating Sb(V) from the drinking water. To better understand the overall process, the effects of several experimental variables, including pH, dissolved oxygen (DO), coexisting ions, and adsorption kinetics on the removal of Sb(V) from the SW were investigated by employing fixed-bed column runs or batch-adsorption methods. A pH of 4.5 and 72 h of equilibrium time were found to be the ideal conditions for drinking water. The presence of phosphate (PO43-), silicate (SiO42-), chromate (CrO42-) and arsenate (AsO43-) significantly decreased the rate of Sb(V) removal, while humic acid and other anions exhibited a negligible effect. The capacity for Sb(V) uptake decreased from 6.665 to 2.433 mg when the flow rate was increased from 5 to 10 mL·min-1. The dynamic adsorption penetration curves of Sb(V) were 116.4% and 144.1% with the weak magnetic field (WMF) in fixed-bed column runs. Considering the removal rate of Sb(V), reusability, operability, no release of Sb(V) after being incorporated into the iron (hydr)oxides structure, it can be concluded that WMF coupled with ZVI would be an effective Sb(V) immobilization technology for drinking water.
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SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.
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Enzima Convertidora de Angiotensina 2/metabolismo , Anticuerpos Monoclonales Humanizados/farmacología , Basigina/antagonistas & inhibidores , Basigina/metabolismo , Tratamiento Farmacológico de COVID-19 , COVID-19/metabolismo , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , SARS-CoV-2/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Animales , Basigina/genética , COVID-19/genética , Chlorocebus aethiops , Síndrome de Liberación de Citoquinas/genética , Síndrome de Liberación de Citoquinas/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Ratones , Ratones Transgénicos , SARS-CoV-2/genética , Células VeroRESUMEN
The effectiveness of nanoscale zero-valent iron(nZVI) immobilized on activated carbon (nZVI/AC) in removing antimonite (Sb(III)) from simulated contaminated water was investigated with and without a magnetic fix-bed column reactor. The experiments were all conducted in fixed-bed columns. A weak magnetic field (WMF) was proposed to increase the exclusion of paramagnetic Sb(III) ions by nZVI/AC. The Sb(III) adsorption to the nZVI and AC surfaces, as well as the transformation of Sb(III) to Sb(V) by them, were both increased by using a WMF in nZVI/AC. The increased sequestration of Sb(III) by nZVI/AC in the presence of WMF was followed by faster nZVI corrosion and dissolution. Experiments were conducted as a function of the pH of the feed solution (pH 5.0-9.0), liquid flow rate (5-15 mL·min-1), starting Sb(III) concentration (0.5-1.5 mg·L-1), bed height nZVI/AC (10-40 cm), and starting Sb(III) concentration (0.5-1.5 mg·L-1). By analyzing the breakthrough curves generated by different flow rates, different pH values, different inlet Sb(III) concentrations, and different bed heights, the adsorbed amounts, equilibrium nZVI uptakes, and total Sb(III) removal percentage were calculated in relation to effluent volumes. At pH 5.0, the longest nZVI breakthrough time and maximal Sb(III) adsorption were achieved. The findings revealed that the column performed effectively at the lowest flow rate. With increasing bed height, column bed capacity and exhaustion time increased as well. Increasing the Sb(III) initial concentration from 0.5 to 1.5 mg·L-1 resulted in the rise of adsorption bed capacity from 3.45 to 6.33 mg·g-1.
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OBJECTIVE: Fixation with an elastic stable intramedullary nail (ESIN) is a widely used technique for the treatment of humeral shaft fractures. Ultrasonography (US) is used as an auxiliary tool and alternative to radiography during surgery to reduce radiation damage, but whether it is effective in pediatric patients is not known. In this study we evaluated the utility of US in the treatment of pediatric humeral shaft fractures by closed reduction and fixation with an ESIN. METHODS: Children who were admitted to our hospital with humeral shaft fractures were retrospectively examined from January 2016 to March 2019. The patients were divided into 2 groups, US (treated by US-guided closed reduction and ESIN fixation) and non-US (treated with the same technique but with intraoperative radiography instead of US). The postoperative functional recovery of the 2 groups was compared. RESULTS: The study population comprised 28 boys and 17 girls (age range: 4-16 years) with humeral shaft fractures. US significantly reduced radiation exposure during the operation (P = 0.008), and intraoperative US facilitated the detection of nerve and vascular injury and aided surgical planning. There was no difference between the 2 groups in postoperative recovery based on the Constant-Murley shoulder score (CMS). CONCLUSIONS: These results demonstrate that US-guided closed reduction and ESIN fixation for humeral shaft fractures can limit radiation exposure and help doctors to determine the optimal surgical strategy to avoid radial nerve injury.
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The presence of arsenic (As) in drinking water is of serious concern due to its negative impact on human health. This work reports on the kinetics of nanoscale zero-valent iron (Fe0) supported by activated carbon (NZVI/AC) for the removal of As (V) species from aqueous solutions. To better understand the factors affecting this process, we investigated the effects of various experimental parameters including initial As (V) concentration, adsorbent dosage, pH, temperature, and coexisting ions on the adsorption kinetics using a batch-adsorption method. The optimum conditions for As (V) removal by NZVI/AC were found to be: 318 K, pH 3.5, an adsorbent dosage of 1.5 g/L, and an equilibrium time of 72 h. A greater mass of NZVI/AC, lower concentration of As (V) and lower pH positively promoted adsorption kinetics. The presence of phosphate (PO43-) and silicate (SiO42-) markedly inhibited As (V) removal kinetics. However, in the presence of 4.5 g/L NZVI/AC, ≥99.9% of As (V) was removed from raw groundwater.