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Induction of the transcriptional repressor Bcl-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T(FH) cells), which are essential for B cell-mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T(FH) differentiation by antagonizing Bcl-6. Here we found that the transcription factor TCF-1 was essential for both the initiation of T(FH) differentiation and the effector function of differentiated T(FH) cells during acute viral infection. Mechanistically, TCF-1 bound directly to the Bcl6 promoter and Prdm1 5' regulatory regions, which promoted Bcl-6 expression but repressed Blimp1 expression. TCF-1-null T(FH) cells upregulated genes associated with non-T(FH) cell lineages. Thus, TCF-1 functions as an important hub upstream of the Bcl-6-Blimp1 axis to initiate and secure the differentiation of T(FH) cells during acute viral infection.
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Diferenciación Celular/inmunología , Proteínas de Unión al ADN/inmunología , Factor Nuclear 1-alfa del Hepatocito/inmunología , Infecciones por Orthomyxoviridae/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Factores de Transcripción/inmunología , Animales , Diferenciación Celular/genética , Proteínas de Unión al ADN/genética , Centro Germinal/inmunología , Centro Germinal/metabolismo , Factor Nuclear 1-alfa del Hepatocito/genética , Virus de la Influenza A , Ratones , Ratones Noqueados , Factor 1 de Unión al Dominio 1 de Regulación Positiva , Proteínas Proto-Oncogénicas c-bcl-6 , Linfocitos T Colaboradores-Inductores/metabolismo , Factores de Transcripción/genéticaRESUMEN
Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation. Mechanistically, mTORC1-mediated phosphorylation of the transcription factor STAT3 induced the expression of the transcription factor TCF-1 by promoting STAT3 binding to the Tcf7 5'-regulatory region. Subsequently, TCF-1 bound to the Bcl6 promoter to induce Bcl6 expression, which launched the Tfr cell differentiation program. Thus, mTORC1 initiates Tfr cell differentiation by activating the TCF-1-Bcl-6 axis during immunization or infection.
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Inmunomodulación , Complejos Multiproteicos/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Biomarcadores , Diferenciación Celular/inmunología , Análisis por Conglomerados , Perfilación de la Expresión Génica , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Inmunización , Inmunofenotipificación , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Ratones Transgénicos , Complejos Multiproteicos/genética , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Linfocitos T Reguladores/citología , Serina-Treonina Quinasas TOR/genéticaRESUMEN
BACKGROUND: The Pseudorabies Virus (PRV) leading to pseudorabies and causes huge economic losses in pig industry. The development of novel PRV variations has diminished the efficacy of traditional vaccinations, and there is yet no medication that can stop the spread of PRV infection. Therefore, PRV eradication is challenging. Oregano essential oil, the plant-based ingredient for medication feed have been shown to has strong anti-herpesvirus activity, but no anti-PRV function has been reported. RESULTS: The current study assessed the anti-pseudorabies virus (PRV) activity of oregano essential oil and explored its mechanisms and most effective components against PRV. Our in vivo findings demonstrated that oregano essential oil could decrease the PRV load in tissues, mitigate tissue lesions, and enhance the survival rate of mice. The potential antiviral mechanism involves augmenting humoral and cellular immune responses in PRV-infected mice. To further investigate the most effective components of oregano essential oil against PRV, an in vitro study was conducted, revealing that oregano essential oil and its main constituents, carvacrol and thymol, all diminished PRV intracellular proliferation in vitro. Carvacrol exhibited the most potent anti-PRV effect, serving as the primary contributor to oregano essential oil's anti-PRV activity. The mechanisms underlying carvacrol's anti-PRV properties include the upregulation of cytokines TNF-α, IFN-ß, IFN-γ, IL-12, and the inhibition of PRV-induced apoptosis in BHK-21 cells. CONCLUSIONS: Our study provides an effective drug for the prevention and control of PRV infection.
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Quantum many-body scars are nonthermal excited eigenstates of nonintegrable Hamiltonians, which could support coherent revival dynamics from special initial states when scars form an equally spaced tower in the energy spectrum. For open quantum systems, engineering many-body scarred dynamics by a controlled coupling to the environment remains largely unexplored. Here, we provide a general framework to exactly embed quantum many-body scars into the decoherence-free subspaces of Lindblad master equations. The dissipative scarred dynamics manifest persistent periodic oscillations for generic initial states, and can be practically utilized to prepare scar states with potential quantum metrology applications. We construct the Liouvillian dissipators with the local projectors that annihilate the whole scar towers, and utilize the Hamiltonian part to rotate the undesired states out of the null space of dissipators. We demonstrate our protocol through several typical models hosting many-body scar towers and propose an experimental scheme to observe the dissipative scarred dynamics based on digital quantum simulations and resetting ancilla qubits.
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BACKGROUND: Cancer and sarcopenia are both closely related to lipid metabolism, but the relationship between lipid metabolism and patients with cancer and sarcopenia has not been thoroughly studied. The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a reliable measure of lipid metabolism. The purpose of this study was to determine the possible relationship between the NHHR and sarcopenia in individuals with cancer. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) database for individuals with cancer, with and without sarcopenia was analyzed using weighted multiple regression equations, weighted regression cubic spline (RCS) analysis, and weighted subgroup analysis. RESULTS: In total, 1,602 individuals with cancer were included, of whom 17.1% had sarcopenia. In Adjusted Model 2, the occurrence of sarcopenia was found to be significantly associated with a higher NHHR in cancer (95% confidence interval [CI]:1.01-1.39, P = 0.036). Individuals with high a NHHR had a 2.09-fold higher risk of developing sarcopenia in comparison to those with a low NHHR (95% CI:1.12-3.92, P = 0.022). RCS analysis further identified a U-shaped non-linear relationship between females with cancer and the muscle index. Subgroup analysis indicated that sex was a significant stratifying factor, whereas age, race, marital status, smoking and drinking habits, and history of cardiovascular disease, arthritis, hypertension, and diabetes had no significant impact. CONCLUSION: From the perspective of lipid metabolism, the NHHR may serve as an indicator for monitoring and preventing the occurrence of sarcopenia in individuals with cancer, particularly for females with cancer who appear to have greater sensitivity.
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HDL-Colesterol , Neoplasias , Sarcopenia , Humanos , Sarcopenia/sangre , Sarcopenia/epidemiología , Neoplasias/sangre , Neoplasias/complicaciones , Neoplasias/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , HDL-Colesterol/sangre , Anciano , Encuestas Nutricionales , Adulto , Factores de Riesgo , Colesterol/sangreRESUMEN
High-energy Li metal batteries (LMBs) consisting of Li metal anodes and high-voltage cathodes are promising candidates of the next generation energy-storage systems owing to their ultrahigh energy density. However, it is still challenging to develop high-voltage nonflammable electrolytes with superior anode and cathode compatibility for LMBs. Here, we propose an active diluent-anion synergy strategy to achieve outstanding compatibility with Li metal anodes and high-voltage cathodes by using 1,2-difluorobenzene (DFB) with high activity for yielding LiF as an active diluent to regulate nonflammable dimethylacetamide (DMAC)-based localized high concentration electrolyte (LHCE-DFB). DFB and bis(fluorosulfonyl)imide (FSI- ) anion cooperate to construct robust LiF-rich solid electrolyte interphase (SEI) and cathode electrolyte interphase (CEI), which effectively stabilize DMAC from intrinsic reactions with Li metal anode and enhance the interfacial stability of the Li metal anodes and LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) cathodes. LHCE-DFB enables ultrahigh Coulombic efficiency (98.7 %), dendrite-free, extremely stable and long-term cycling of Li metal anodes in Li || Cu cells and Li || Li cells. The fabricated NCM811 || Li cells with LHCE-DFB display remarkably enhanced long-term cycling stability and excellent rate capability. This work provides a promising active diluent-anion synergy strategy for designing high-voltage electrolytes for high-energy batteries.
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Spin-momentum coupling, which depends strongly on the relativistic effect of heavy elements in solids, is the basis of many phenomena in spintronics. In this Letter, we theoretically predict nonrelativistic spin-momentum coupling in two-dimensional materials. By proposing magnetic symmetry requirements for spin splitting in two-dimensional systems, we find that a simple twisting operation can realize nonrelativistic spin splitting in antiferromagnetic bilayers. Through first-principles calculations, we demonstrate that momentum-dependent spin splitting exists extensively in antiferromagnetic twisted bilayers with different crystal structures and twist angles. The size of the spin splitting caused by twisting is of the same order of magnitude as that arising from spin-orbit coupling. In particular, a transverse spin current with an extremely high charge-spin conversion ratio can be generated in twisted structures under an external electric field. The findings demonstrate the potential for achieving electrically controlled magnetism in materials without spin-orbit coupling.
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Thermal hydrolysis pretreatment (THP) of sludge can form the refractory brown melanoidins due to the occurrence of the Maillard reaction, which adversely involves the subsequent sludge anaerobic digestion (AD) process. However, details of the generation pattern of melanoidins and how they affect the sludge dewaterability remain largely unknown. This work aims to determine an approach to characterize and quantify the melanoidins created by THP of sludge. On this basis, the effect of melanoidins on sludge dewatering performance was revealed by adding synthetic melanoidins to the mixed sludge. Experimental results showed that three-dimensional fluorescence-region integration (3DEEM-FRI) could effectively distinguish melanoidins from other organic substances and achieve semi-quantitative characterization in sludge. The melanoidins significantly deteriorated the sludge dewaterability, and the lowest solids content of the filter cake (TS) was only 17.78% at the addition of 480 mg (g TS)-1, which was a drop of about 20% compared to the control group. The mechanism investigations indicated that the internal structure of sludge becoming particularly complicated and the opportunities for molecules to collide with each other enlarged because of the contribution of melanoidins, resulting in the increment of the sludge apparent viscosity and consistency coefficient (k), a decline of the flow behavior index (n) and a weakening of flowability. Melanoidins could capture massive water molecules and carry negative charges with the decrease of sludge particle size and zeta potential value, which enhanced the electrostatic repulsion between sludge particles and abated the flocculation ability, thus further aggravating the sludge dewatering performance.
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Bioensayo , Aguas del Alcantarillado , Hidrólisis , AlimentosRESUMEN
Eimeria magna is a common pathogen in rabbits, which results in lethargy, weight loss, diarrhea, and even death in severe cases after infection. The current method for preventing rabbit coccidiosis is to add anticoccidial drugs to the diet. However, there are many concerns about drug resistance and drug residues. In our study, the rEmMIC2 and rEmMIC3 proteins were cloned and expressed to evaluate potential as recombinant subunit vaccine candidate antigens. The protective effects of rEmMIC2 and rEmMIC3 were evaluated by the relative weight gain ratio, oocyst decrease rate, anticoccidial index, feed conversion ratio, pathological alterations, clinical symptoms, specific IgG antibody, and cytokine levels in rabbits. The molecular weights of rEmMIC2 and rEmMIC3 were 18.69 kDa and 17.47 kDa, respectively. After the coccidia challenge, the control groups showed anorexia and soft poop, whereas the experimental group showed few anorexia symptoms. Significantly different from the control group, the relative weight gain ratios of the immunized rEmMIC2 and rEmMIC3 groups were 78.37% and 75.29%, respectively, and the oocyst reduction was 77.95% and 76.09%, respectively, and the anticoccidial index was 171.12 and 169.29, respectively. IgG antibody, IFN-γ, IL-4, IL-10, and IL-17 levels were significantly increased in the experimental group. The results showed that rEmMIC2 and rEmMIC3 have potential as vaccine candidate antigens.
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Coccidiosis , Eimeria , Enfermedades de las Aves de Corral , Vacunas Antiprotozoos , Animales , Conejos , Anorexia , Coccidiosis/prevención & control , Coccidiosis/veterinaria , Citocinas , Inmunoglobulina G , Oocistos , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
Adenylate kinases (ADKs) are one of the important enzymes regulating adenosine triphosphate (ATP) metabolism in Echinococcus granulosus sensu lato. The objective of the present study was to explore the molecular characteristics and immunological properties of E. granulosus sensu stricto (G1) adenylate kinase 1 (EgADK1) and adenylate kinase 8 (EgADK8). EgADK1 and EgADK8 were cloned and expressed, and the molecular characteristics of EgADK1 and EgADK8 were analyzed through different bioinformatics tools. Western blotting was used to examine the reactogenicity of recombinant adenylate kinase 1 (rEgADK1) and recombinant adenylate kinase 8 (rEgADK8) and to evaluate their diagnostic value. The expression profiles of EgADK1 and EgADK8 in 18-day-old strobilated worms and protoscoleces were analyzed by quantitative real-time PCR, and their distribution in 18-day-old strobilated worms, the germinal layer, and protoscoleces was determined by immunofluorescence localization. EgADK1 and EgADK8 were successfully cloned and expressed. Bioinformatics analysis predicted that EgADK1 and EgADK8 have multiple phosphorylation sites and B-cell epitopes. Compared with EgADK8, EgADK1 and other parasite ADKs have higher sequence similarity. In addition, both cystic echinococcosis (CE)-positive sheep sera and Cysticercus tenuicollis-infected goat sera could recognize rEgADK1 and rEgADK8. EgADK1 and EgADK8 were localized in protoscoleces, the germinal layer, and 18-day-old strobilated worms. EgADK1 and EgADK8 showed no significant difference in their transcription level in 18-day-old strobilated worms and protoscoleces, suggesting that EgADK1 and EgADK8 may play an important role in the growth and development of E. granulosus sensu lato. Since EgADK1 and EgADK8 can be recognized by other parasite-positive sera, they are not suitable as candidate antigens for the diagnosis of CE.
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Equinococosis , Echinococcus granulosus , Animales , Ovinos , Echinococcus granulosus/genética , Adenilato Quinasa , Genotipo , Equinococosis/parasitología , Reacción en Cadena en Tiempo Real de la Polimerasa , Cabras/parasitologíaRESUMEN
Sarcoptes scabiei (S. scabiei) is an ectoparasite that can infest humans and 150 mammalian host species, primarily causing pruritus, crust, and alopecia. However, neither the pathological process of host skin under S. scabiei infection nor the mechanism of S. scabiei infection in regulating apoptosis and keratinization of host skin has been studied yet. In this study, a total of 56 rabbits were artificially infested with S. scabiei, and the skin samples were collected at seven different time points, including 6 h, 12 h, day 1, day 3, 1 week, 4 weeks, and 8 weeks, whereas a group of eight rabbits served as controls. We measured epidermal thickness by H&E staining, observed the skin ultrastructure by electron microscopy, and detected the degree of skin apoptosis by TUNEL staining. The level of transcription of genes related to apoptosis and keratinization was detected by quantitative real-time PCR (qRT-PCR), and the level of Bcl-2 protein expression was further detected using immunohistochemistry. Our results showed that, with increased infestation time, the epidermal layer of the rabbit skin exhibited significant thickening and keratinization, swollen mitochondria in the epidermal cells, and increased skin apoptosis. The level of caspase-1, 3, 8, 10, 14, and Bcl-2 mRNA expression was increased, whereas the level of keratin 1 and 5 was decreased after S. scabiei infestation. In conclusion, S. scabiei infestation causes thickening of the epidermis, which may be related to apoptosis-induced proliferation and skin keratinization.
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Ácaros y Garrapatas , Sarcoptidae , Escabiosis , Piel , Animales , Humanos , Conejos , Apoptosis , Mamíferos , Sarcoptes scabiei/genética , Escabiosis/patología , Queratinas/metabolismo , Piel/metabolismoRESUMEN
Metabolites play critical roles in macrophage polarization and in their function in response to infection and inflammation. α-aminobutyric acid (AABA), a non-proteinogenic amino acid which can be generated from methionine, threonine, serine, and glycine, has not been studied extensively in relation to macrophage polarization and function. In this study, we aimed to investigate the immunomodulatory function of AABA in regulating M1 macrophage polarization and function in vitro and in vivo. We stimulated bone-marrow-derived macrophages with lipopolysaccharide (LPS) to generate M1 macrophages. Subsequently, we induced sepsis and colitis in mice, followed by treatment with AABA. We then analyzed the samples using ELISA, real-time PCR, Western blotting, flow cytometry, and histopathological analysis to evaluate cytokine secretion, inflammatory gene expression, macrophage activation, disease progression, and inflammation severity. Additionally, metabolomic and chromatin immunoprecipitation-qPCR were conducted to investigate the function of AABA on metabolic reprogramming and epigenetic modifications of M1 macrophages. Our results revealed that AABA inhibited M1 macrophage polarization and function, which led to prolonged survival in septic mice and reduced disease severity in colitis mice. Mechanically, AABA promoted oxidative phosphorylation (OXPHOS) and glutamine and arginine metabolism while inhibiting glycolysis. Moreover, AABA could increase the occupancy of trimethylation of histone H3K27 at the promoter regions of M1 macrophage-associated inflammatory genes, which contributed to the inhibition of M1 macrophage polarization. These findings suggest that AABA may have therapeutic potential for inflammatory diseases by regulating macrophage polarization and function through metabolic and epigenetic pathways.
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Colitis , Macrófagos , Ratones , Animales , Macrófagos/metabolismo , Inflamación/metabolismo , Colitis/genética , Colitis/metabolismo , Epigénesis Genética , Lipopolisacáridos/farmacología , Activación de MacrófagosRESUMEN
Psoroptes ovis, a common surface-living mite of domestic and wild animals worldwide, results in huge economic losses and serious welfare issues in the animal industry. P. ovis infestation rapidly causes massive eosinophil infiltration in skin lesions, and increasing research revealed that eosinophils might play an important role in the pathogenesis of P. ovis infestation. Intradermal injection of P. ovis antigen invoked massive eosinophil infiltration, suggesting that this mite should contain some relative molecules involved in eosinophil accumulation in the skin. However, these active molecules have not yet been identified. Herein, we identified macrophage migration inhibitor factor (MIF) in P. ovis (PsoMIF) using bioinformatics and molecular biology methods. Sequence analyses revealed that PsoMIF appeared with high similarity to the topology of monomer and trimer formation with host MIF (RMSD = 0.28 angstroms and 2.826 angstroms, respectively) but with differences in tautomerase and thiol-protein oxidoreductase active sites. Reverse transcription PCR analysis (qRT-PCR) results showed that PsoMIF was expressed throughout all the developmental stages of P. ovis, particularly with the highest expression in female mites. Immunolocalization revealed that MIF protein located in the ovary and oviduct of female mites and also localized throughout the stratum spinosum, stratum granulosum, and even basal layers of the epidermis in skin lesions caused by P. ovis. rPsoMIF significantly upregulated eosinophil-related gene expression both in vitro (PBMC: CCL5, CCL11; HaCaT: IL-3, IL-4, IL-5, CCL5, CCL11) and in vivo (rabbit: IL-5, CCL5, CCL11, P-selectin, ICAM-1). Moreover, rPsoMIF could induce cutaneous eosinophil accumulation in a rabbit model and increased the vascular permeability in a mouse model. Our findings indicated that PsoMIF served as one of the key molecules contributing to skin eosinophil accumulation in P. ovis infection of rabbits.
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Eosinofilia , Factores Inhibidores de la Migración de Macrófagos , Infestaciones por Ácaros , Ácaros , Psoroptidae , Ratones , Animales , Conejos , Femenino , Ovinos , Psoroptidae/genética , Infestaciones por Ácaros/parasitología , Infestaciones por Ácaros/patología , Eosinófilos , Interacciones Huésped-Parásitos , Factores Inhibidores de la Migración de Macrófagos/genética , Interleucina-5 , Leucocitos Mononucleares/patologíaRESUMEN
Distiller's grains (DGs) are solid mixtures that remain after the production of alcoholic beverages. A large amount of DGs is produced each year during the brewing process. Currently, they are mostly used as a feedstock or substrate in the feed industry. However, the lack of a comprehensive understanding of the chemical composition of DGs is a major constraint on their further development and application for high-value-added usages. Some studies were published on the bioactive constituents of DGs in several different types of journals. Data were therefore collated to provide a comprehensive overview of these natural products. DGs are rich in phenols, phytosterols, and fatty acids, in addition to general lipid and protein constituents. These compounds and their related extracts possess diverse biological activities, including antioxidant, anti-inflammatory, and anti-hyperglycaemic effects. We hope that this review will provide research incentives for the further development and utilisation of DGs to develop high-value-added products.
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Bebidas Alcohólicas , Proteínas , Antioxidantes/farmacología , Grano Comestible , Estructuras de las Plantas , Alimentación AnimalRESUMEN
At present, there is no effective treatment for prostate cancer (PCa). Previous studies have reported that miR-34a is significantly downregulated in PCa cells; therefore, modulation of miR-34a expression might be a promising therapeutic approach for PCa treatment. To this end, we first verified the downregulation of miR-34a in prostate tumors from a transgenic adenocarcinoma mouse prostate (TRAMP) model. We found that miR-34a overexpression significantly inhibited the cell cycle, viability, and migration of PCa cells by targeting its downstream genes. Next, we tested the concept of intraprostatic injection of rAAV9·pri-miR-34a into 8-week-old TRAMP mice to inhibit PCa progression. We observed that the treatment lowered body weights significantly compared to the control treatment starting at 30 weeks after injection. rAAV9·pri-miR-34a treatment also obviously extended the lifespan of TRAMP mice. Moreover, we confirmed that the neoplasia in the treated prostates was significantly diminished compared to that in the control group. In addition, overexpressed miR-34a downregulated the expression of its target genes. Taken together, our results demonstrated, for the first time, the potential of rAAV-mediated efficient modulation of miR-34a expression in the prostate to inhibit PCa progression by regulating its downstream gene expression.
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MicroARNs , Neoplasias de la Próstata , Animales , Línea Celular Tumoral , Proliferación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , MicroARNs/uso terapéutico , Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/terapiaRESUMEN
Solid-state thermoelectric (TE) technology is a promising approach to harvest low-grade waste heat (<573 K) and converts it to useful electricity in industrial and civilian settings. After decades of efforts in improving the figure-of-merit (zT) of TE materials, the development of advanced modules has started springing up in recent years. Although high-performance modules have been largely reported based on the successful material improvement, it remains less investigated how and whether the module-level designs can further increase the conversion efficiency. Herein, following the recent demonstration of a tellurium (Te)-free TE generator, an increase is demonstrated in the efficiency by reducing both the electrical and thermal energy losses through simply optimizing geometric factors of filling factor and leg-pair numbers. These module-level optimizations enable a record conversion efficiency of 8.2% under a ∆T ≈ 260 K, thus fulfilling 90% of the theoretical efficiency of the materials and solidly exceeding the Bi2 Te3 modules. Furthermore, module robustness against > 10 160 thermal cycles while preserving a relative efficiency of 95% is demonstrated. These findings highlight the importance of the optimization strategy at the module level and demonstrate the feasibility of using Te-free thermoelectric compounds to harvest the omnipresent low-grade heat.
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Stimulated Raman transition is a fundamental method to coherently manipulate quantum states in different physical systems. Phase-coherent dichromatic radiation fields matching the energy level splitting are the key to realizing stimulated Raman transition. Here we demonstrate a flexible-tuning, spectrum-clean and fiber-compatible method to generate a highly phase-coherent and high-power multi-tone laser. This method features the utilization of a broadband fiber Mach-Zehnder modulator working at carrier suppression condition and second harmonic generation. We generate a multi-tone continuous-wave 532 nm laser with a power of 1.5 Watts and utilize it to manipulate the spin and motional states of a trapped 171Yb+ ion via stimulated Raman transition. For spin state manipulation, we acquire an effective Rabi frequency of 2π × 662.3 kHz. Due to the broad bandwidth of the fiber modulator and nonlinear crystal, the frequency gap between tones can be flexibly tuned. Benefiting from the features above, this method can manipulate 171Yb+ and 137Ba+ simultaneously in the multi-species ion trap and has potential to be widely applied in atomic, molecular and optical physics.
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BACKGROUND: Axillary vein/subclavian vein (AxV/SCV) and Internal jugular vein (IJV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer patients for chemotherapy. Previous research focused on comparison of complications while patient comfort was ignored. This study aims to compare patient comfort, surgery duration and complications of IVAP implantation between IJV and AxV/SCV approaches. METHODS: Two hundred forty-eight breast cancer patients were enrolled in this randomized controlled study from August 2020 to June 2021. Patients scheduled to undergo IVAP implantation were randomly and equally assigned to receive central venous catheters with either AxV /SCV or IJV approaches. All patients received comfort assessment using a comfort scale table at day 1, day 2 and day 7 after implantation. Patient comfort, procedure time of operation as well as early complications were compared. RESULTS: Patient comfort was significantly better in the AxV/SCV group than that of IJV group in day 1 (P < 0.001), day 2 (P < 0.001) and day 7(P = 0.023). Procedure duration in AxV/SCV group was slightly but significantly shorter than IJV group (27.14 ± 3.29 mins vs 28.92 ± 2.54 mins, P < 0.001). More early complications occurred in AxV/SCV group than IJV group (11/124 vs 2/124, P = 0.019). No difference of complications of artery puncture, pneumothorax or subcutaneous hematoma between these two groups but significantly more catheter misplacement in AxV/SCV group than IJV group (6/124 vs 0/124, P = 0.029). Absolutely total risk of complications was rather low in both groups (8.87% in AxV/SCV group and 1.61% in IJV group). CONCLUSIONS: Our study indicates that patients with AxV/SCV puncture have higher comfort levels than IJV puncture. AxV/SCV puncture has shorter procedure duration but higher risk of early complications, especially catheter misplacement. Both these two approaches have rather low risk of complications. Consequently, our study provides an alternative choice for breast cancer patients to reach better comfort.
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Neoplasias de la Mama/tratamiento farmacológico , Cateterismo Venoso Central/psicología , Catéteres Venosos Centrales/efectos adversos , Satisfacción del Paciente/estadística & datos numéricos , Punciones/psicología , Adulto , Axila/irrigación sanguínea , Vena Axilar , Neoplasias de la Mama/psicología , Cateterismo Venoso Central/métodos , Femenino , Humanos , Venas Yugulares , Persona de Mediana Edad , Punciones/efectos adversos , Punciones/métodos , Vena Subclavia , Factores de Tiempo , Ultrasonografía IntervencionalRESUMEN
Appropriate migration of cytotoxic T effector cells into the tumors is crucial for their antitumor function. Despite the controversial role of PI3K-Akt in CD8+ T cell mTORC1 activation, a link between Akt-mTORC1 signaling and CD8+ trafficking has been demonstrated. We have recently discovered that TCR-induced calcineurin activates DAPK1, which interacts with TSC2 via its death domain and phosphorylates TSC2 via its kinase domain to mediate mTORC1 activation in CD8+ T cells. However, whether DAPK1 regulates CD8+ trafficking into tumors remains unclear. Here, using pharmacological inhibitor and genetic approaches, we found that like rapamycin, inhibition of DAPK1 activity led to enhanced expression of the homing receptors CD62L and CCR7. Deletion of either kinase domain or death domain in the T cell compartment reduced the T cell activation and maintained the expression of CD62L and CCR7. DAPK1-DD-deficient mice were more susceptible to tumor growth and deficiency of DAPK1 activity significantly reduced the migratory ability of CD8+ into the tumors. These data revealed a crucial role of DAPK1-mTORC1 in mediating CD8+ trafficking and antitumor function.
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Linfocitos T CD8-positivos/inmunología , Movimiento Celular/inmunología , Proteínas Quinasas Asociadas a Muerte Celular/inmunología , Inmunidad Celular , Activación de Linfocitos , Neoplasias Experimentales/inmunología , Animales , Linfocitos T CD8-positivos/patología , Línea Celular Tumoral , Proteínas Quinasas Asociadas a Muerte Celular/genética , Ratones , Ratones Noqueados , Neoplasias Experimentales/genética , Neoplasias Experimentales/patologíaRESUMEN
During chronic viral infection, virus-specific CD8(+) T cells become exhausted, exhibit poor effector function and lose memory potential. However, exhausted CD8(+) T cells can still contain viral replication in chronic infections, although the mechanism of this containment is largely unknown. Here we show that a subset of exhausted CD8(+) T cells expressing the chemokine receptor CXCR5 has a critical role in the control of viral replication in mice that were chronically infected with lymphocytic choriomeningitis virus (LCMV). These CXCR5(+) CD8(+) T cells were able to migrate into B-cell follicles, expressed lower levels of inhibitory receptors and exhibited more potent cytotoxicity than the CXCR5(-) [corrected] subset. Furthermore, we identified the Id2-E2A signalling axis as an important regulator of the generation of this subset. In patients with HIV, we also identified a virus-specific CXCR5(+) CD8(+) T-cell subset, and its number was inversely correlated with viral load. The CXCR5(+) subset showed greater therapeutic potential than the CXCR5(-) [corrected] subset when adoptively transferred to chronically infected mice, and exhibited synergistic reduction of viral load when combined with anti-PD-L1 treatment. This study defines a unique subset of exhausted CD8(+) T cells that has a pivotal role in the control of viral replication during chronic viral infection.