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1.
Opt Lett ; 48(6): 1395-1398, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36946936

RESUMEN

A thermal lens insensitive regenerative amplifier (RA) with a dual Yb:CaYAlO4 (Yb:CYA) crystal configuration for extending gain spectra is demonstrated for the first time, to the best of our knowledge. By orthogonalizing the orientation of two a-cut Yb:CYA crystals in one RA, the Q switched spectrum with a full width at half maximum of 15.4 nm is generated, which is 1.5 and 1.6 times of the Q switched spectral bandwidth with π- and σ-polarization, respectively. With chirped pulses injection, this RA can deliver laser pulses with an average power exceeding 10 W at the repetition rate of 20-800 kHz and pulse energy of 1.5 mJ at 1 kHz. This is the highest average power from the Yb:CYA RA to the best of our knowledge. Finally, compressed pulses of 163 fs with 92% overall efficiency are realized. Thanks to the heat insensitive cavity design and excellent thermodynamic properties of the Yb:CYA crystal, the output laser beam is close to the diffraction limit with an M2 value of 1.07 × 1.07.

2.
Arch Microbiol ; 205(3): 97, 2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36823480

RESUMEN

For different breeds of dogs with acute diarrhea, the gut microbiota and metabolome profiles are unclear. This prospective observational study analyzed the gut microbiomes of poodles with acute diarrhea and Labrador retrievers with acute diarrhea based on 16S amplicon sequencing, with respective healthy dogs as controls. Fecal non-target metabolomics and metagenomics were performed on poodles with acute diarrhea. This study found that the diversity and structure of the microbial community differed significantly between the two breeds in cohorts of healthy dogs. Two breeds of dogs with acute diarrhea demonstrated different changes in microbial communities and metabolic functions. The metabolism of starch and sucrose was significantly decreased in dogs with acute diarrhea, which may be attributed to the reduced activity of dextran dextrinase. Non-targeted metabolomics identified 21 abnormal metabolic pathways exhibited by dogs with acute diarrhea, including starch, amino acid, bile acid metabolism, etc., and were closely related to specific intestinal flora. This study provided new insights into breed specificity and the development of dietary treatment strategy in canine gastrointestinal disease.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Perros , Animales , Metabolómica , Metaboloma , Almidón/análisis , Diarrea , Heces , ARN Ribosómico 16S
3.
Opt Express ; 30(15): 26297-26305, 2022 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-36236824

RESUMEN

We demonstrate the simultaneous temporal contrast enhancement and spectral broadening via nonlinear elliptical polarization rotation in a solid thin plate. The efficiency, temporal contrast enhancement, spectral broadening, pulse compression and power stability are experimentally investigated. With this simple and efficient scheme, the temporal cleaned pulses with energy of 325 µJ and total efficiency of 30% are obtained. The temporal contrast and spectral bandwidth of the filtered pulse are 1011 and 104 nm, respectively. The pulse compressed from 180 fs to 45.8 fs is realized by utilizing chirped mirrors, corresponding to a compression factor of 3.93. With stable output power, presented scheme could be implemented in the ultra-intense femtosecond laser facilities.

4.
Opt Express ; 30(14): 24276-24284, 2022 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-36236985

RESUMEN

We demonstrate the generation of high average power femtosecond laser radiation by combination of an Nd-doped picosecond amplifier and a multi-pass cell device. With this efficient and robust scheme, the pulse duration of a picosecond amplifier is compressed from 9.13 ps to 477 fs, corresponding to a compression factor of 19.1. The average power before and after pulse compression is 77 W and 56.5 W respectively, so the overall transmission reaches 73.4%. The presented scheme offers a viable route toward low-cost and simple configuration high power femtosecond lasers driven by Nd-doped picosecond amplifiers.

5.
Opt Lett ; 46(19): 5075-5078, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34598272

RESUMEN

A few-cycle mid-infrared (MIR) laser is demonstrated via nonlinear self-compression in solid thin plates. In this novel solution, the anomalous material dispersion in the MIR band and the chirp induced by self-phase modulation are mutually compensated, which can achieve self-compression. Finally, with the 4 µm laser injection with 4.8 mJ/155 fs and few-cycle pulses with 3.44 mJ, 29.4 fs are generated with a high efficiency of 71.7%, and the system maintains very good spectral stability in 10 days. Compared with other post-compression methods, this self-compression technique has the advantages of high efficiency and robust and large energy expansion scale, which can be further extended to MIR lasers with other wavelengths and higher peak power.

6.
Endocr Pract ; 27(8): 790-797, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33831552

RESUMEN

OBJECTIVE: Many patients with type 2 diabetes treated with premixed insulin gradually have inadequate glycemic control and switch to a basal-bolus regimen, which raises some concerns for weight gain and increased hypoglycemic risk. Switching to combination use of glp-1 agonist and basal insulin may be an alternative option. METHODS: After a 12-week premixed human insulin 70/30 dosage optimization period, 200 patients with HbA1c of 7.0% to 10.0% were randomized into 24-week treatment groups with exenatide twice a day plus glargine or with aspart 70/30 twice a day. RESULTS: After 24 weeks, the patients receiving exenatide plus glargine (n = 90) had improved HbA1c control compared with those receiving aspart 70/30 (n = 90) (least squares mean change: ‒0.59 vs ‒0.13%; difference [95% CI]: ‒0.45 [‒0.74 to ‒0.17]) in the full analysis set population. Weight decreased 3.5 kg with exenatide and decreased 0.4 kg with aspart 70/30 (P < .001). The insulin dose was reduced 10.7 units/day (95% CI, ‒12.2 to ‒9.2 units; P < .001) with exenatide, and increased 9.7 units/day (95% CI, 8.2 to 11.2 units; P < .001) with aspart 70/30. The most common adverse events were gastrointestinal adverse effects in the exenatide group (nausea [21%], vomiting [16%], diarrhea [13%]). The incidence of hypoglycemia was similar in 2 groups (27% for exenatide and 38% for aspart 70/30; P = .1). CONCLUSION: In premixed human insulin‒treated patients with type 2 diabetes with inadequate glycemic control, switching to exenatide twice a day plus glargine was superior to aspart 70/30 twice a day for glycemic and weight control.


Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Exenatida , Hemoglobina Glucada/análisis , Control Glucémico , Humanos , Hipoglucemiantes , Insulina , Insulina Aspart , Insulina Glargina
7.
Diabetes Obes Metab ; 19(11): 1513-1520, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28296055

RESUMEN

AIM: To investigate the efficacy, safety and tolerability of saxagliptin compared with acarbose in Chinese patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy. METHODS: SMART was a 24-week, multicentre, randomized, parallel-group, open-label Phase IV study conducted at 35 sites in China (September 24, 2014 to September 29, 2015). The primary outcome was absolute change from baseline in HbA1c at Week 24. Secondary outcomes assessed at Week 24 included the proportion of patients achieving HbA1c < 7.0%, the proportion of patients with gastrointestinal adverse events (GI AEs), and the proportion of patients achieving HbA1c < 7.0% without GI AEs. Safety and tolerability were also assessed in all patients who received ≥1 dose of study medication. RESULTS: Four-hundred and eighty-eight patients were randomized (1:1) to saxagliptin or acarbose via a central randomization system (interactive voice/web response system); 241 and 244 patients received saxagliptin and acarbose, respectively, and 238 and 243 of these had ≥1 pre- and ≥1 post-baseline efficacy values recorded. Saxagliptin was non-inferior to acarbose for glycaemic control [Week 24 HbA1c change: -0.82% and -0.78%, respectively; difference (95% confidence interval): -0.04 (-0.22, 0.13)%], with similar proportions of patients in both treatment groups achieving HbA1c < 7.0%. However, fewer GI AEs were reported with saxagliptin compared with acarbose, and a greater number of patients who received saxagliptin achieved HbA1c < 7.0% without GI AEs compared with those receiving acarbose. CONCLUSION: Both therapies had similar efficacy profiles. However, saxagliptin was associated with fewer GI AEs, suggesting it might be preferential for clinical practice. CLINICAL TRIAL REGISTRATION NUMBER: NCT02243176, clinicaltrials.gov.


Asunto(s)
Acarbosa/uso terapéutico , Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipéptidos/uso terapéutico , Resistencia a Medicamentos/efectos de los fármacos , Metformina/uso terapéutico , Adamantano/uso terapéutico , Adulto , Anciano , Pueblo Asiatico , Glucemia/efectos de los fármacos , Glucemia/metabolismo , China , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etnología , Quimioterapia Combinada , Femenino , Humanos , Hipoglucemia/inducido químicamente , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
8.
Phys Chem Chem Phys ; 19(5): 4125-4130, 2017 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-28111665

RESUMEN

The effect of the strain on the magnetic properties of metallic multilayers has been investigated by ab initio studies. Our results indicate that the magnetic anisotropy energy (MAE) of an Fe(001) surface can be drastically enhanced by capping with 5d elements. By choosing Ir-Fe multilayers as a model system, we demonstrate that the MAE which depends on the composition and the structure of the multilayers can be tuned in a large range by strain. Furthermore, our results show that not only the amplitude of the MAE but also the easy axis of Pt-Fe multilayers can be engineered by strain. Magnetization switching by strain is also investigated.

9.
Proc Natl Acad Sci U S A ; 110(37): 15103-8, 2013 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-23980178

RESUMEN

Activity-dependent gene transcription, including that of the brain-derived neurotrophic factor (Bdnf) gene, has been implicated in various cognitive functions. We previously demonstrated that mutant mice with selective disruption of activity-dependent BDNF expression (BDNF-KIV mice) exhibit deficits in GABA-mediated inhibition in the prefrontal cortex (PFC). Here, we show that disruption of activity-dependent BDNF expression impairs BDNF-dependent late-phase long-term potentiation (L-LTP) in CA1, a site of hippocampal output to the PFC. Interestingly, early-phase LTP and conventional L-LTP induced by strong tetanic stimulation were completely normal in BDNF-KIV mice. In parallel, attenuation of activity-dependent BDNF expression significantly impairs spatial memory reversal and contextual memory extinction, two executive functions that require intact hippocampal-PFC circuitry. In contrast, spatial and contextual memory per se were not affected. Thus, activity-dependent BDNF expression in the hippocampus and PFC may contribute to cognitive and behavioral flexibility. These results suggest distinct roles for different forms of L-LTP and provide a link between activity-dependent BDNF expression and behavioral perseverance, a hallmark of several psychiatric disorders.


Asunto(s)
Conducta Animal/fisiología , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/fisiología , Región CA1 Hipocampal/fisiología , Corteza Prefrontal/fisiología , Animales , Factor Neurotrófico Derivado del Encéfalo/deficiencia , Cognición/fisiología , Condicionamiento Psicológico/fisiología , Expresión Génica , Potenciación a Largo Plazo/genética , Potenciación a Largo Plazo/fisiología , Masculino , Aprendizaje por Laberinto/fisiología , Memoria a Corto Plazo/fisiología , Ratones , Ratones Noqueados , Ratones Mutantes
10.
Heliyon ; 10(12): e33145, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39022044

RESUMEN

CD19 is a surface antigen on B cells that regulates B cell activation and proliferation, participating in B cell signaling. It is expressed in all B cell lineage tumor diseases, making CD19 a significant marker for detecting B cell tumor diseases and an important target for related immunotherapies. In recent years, with the deepening research on canine and feline diseases and the establishment of animal models, the demand for cat CD19 monoclonal antibodies (mAbs) has been steadily increasing. We successfully prepared cat CD19-specific monoclonal antibodies using a KLH-conjugated cat CD19 peptide as an antigen and optimized the antibody production method. The obtained monoclonal antibodies' molecular and cellular affinities were identified using CD19 peptides, eukaryotic overexpressed proteins, and peripheral blood mononuclear cells (PBMCs). The results indicate that the CD19-3H9 and CD19-8A7 monoclonal antibodies prepared in this study specifically bind to the CD19 molecule, demonstrating their suitability for use in ELISA, Western blot, and cell assays. This study successfully produced cat CD19 monoclonal antibodies with specificity and optimized the antibody preparation method, laying the foundation for the diagnosis and targeted drug combination therapy of B cell tumor diseases in both humans and pets.

11.
Microbiol Spectr ; 11(4): e0059023, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37428087

RESUMEN

Changes in diet and environment can lead to acute diarrhea in companion animals, but the composition and interactions of the gut microbiome during acute diarrhea remain unclear. In this multicenter case-control study, we investigated the relationship between intestinal flora and acute diarrhea in two breeds of cats. Acutely diarrheic American Shorthair (MD, n = 12) and British Shorthair (BD, n = 12) and healthy American Shorthair (MH, n = 12) and British Shorthair (BH, n = 12) cats were recruited. Gut microbial 16S rRNA sequencing, metagenomic sequencing, and untargeted metabolomic analysis were performed. We observed significant differences in beta-diversity (Adonis, P < 0.05) across breeds and disease state cohorts. Profound differences in gut microbial structure and function were found between the two cat breeds. In comparison to healthy British Shorthair cats, Prevotella, Providencia, and Sutterella were enriched while Blautia, Peptoclostridium, and Tyzzerella were reduced in American Shorthair cats. In the case-control cohort, cats with acute diarrhea exhibited an increased abundance of Bacteroidota, Prevotella, and Prevotella copri and a decreased abundance of Bacilli, Erysipelotrichales, and Erysipelatoclostridiaceae (both MD and BD cats, P < 0.05). Metabolomic analysis identified significant changes in the BD intestine, affecting 45 metabolic pathways. Moreover, using a random forest classifier, we successfully predicted the occurrence of acute diarrhea with an area under the curve of 0.95. Our findings indicate a distinct gut microbiome profile that is associated with the presence of acute diarrhea in cats. However, further investigations using larger cohorts of cats with diverse conditions are required to validate and extend these findings. IMPORTANCE Acute diarrhea is common in cats, and our understanding of the gut microbiome variations across breeds and disease states remains unclear. We investigated the gut microbiome of two cat breeds (British Shorthair and American Shorthair) with acute diarrhea. Our study revealed significant effects of breeds and disease states on the structure and function of the gut microbiota in cats. These findings emphasize the need to consider breed-related factors in animal nutrition and research models. Additionally, we observed an altered gut metabolome in cats with acute diarrhea, closely linked to changes in bacterial genera. We identified a panel of microbial biomarkers with high diagnostic accuracy for feline acute diarrhea. These findings provide novel insights into the diagnosis, classification, and treatment of feline gastrointestinal diseases.


Asunto(s)
Microbioma Gastrointestinal , Gatos , Animales , ARN Ribosómico 16S/genética , Estudios de Casos y Controles , Heces/microbiología , Diarrea/veterinaria , Diarrea/microbiología , Firmicutes/genética
12.
Proc Natl Acad Sci U S A ; 106(14): 5942-7, 2009 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-19293383

RESUMEN

Transcription of Bdnf is controlled by multiple promoters, which drive expression of multiple transcripts encoding for the same protein. Promoter IV contributes significantly to activity-dependent brain-derived neurotrophic factor (BDNF) transcription. We have generated promoter IV mutant mice (BDNF-KIV) by inserting a GFP-STOP cassette within the Bdnf exon IV locus. This genetic manipulation results in disruption of promoter IV-mediated Bdnf expression. BDNF-KIV animals exhibited significant deficits in GABAergic interneurons in the prefrontal cortex (PFC), particularly those expressing parvalbumin, a subtype implicated in executive function and schizophrenia. Moreover, disruption of promoter IV-driven Bdnf transcription impaired inhibitory but not excitatory synaptic transmission recorded from layer V pyramidal neurons in the PFC. The attenuation of GABAergic inputs resulted in an aberrant appearance of spike-timing-dependent synaptic potentiation (STDP) in PFC slices derived from BDNF-KIV, but not wild-type littermates. These results demonstrate the importance of promoter IV-dependent Bdnf transcription in GABAergic function and reveal an unexpected regulation of STDP in the PFC by BDNF.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Corteza Prefrontal/fisiología , Regiones Promotoras Genéticas/fisiología , Transmisión Sináptica , Transcripción Genética , Animales , Potenciales Postsinápticos Excitadores , Potenciales Postsinápticos Inhibidores , Ratones , Ratones Mutantes , Potenciales Sinápticos
13.
Front Immunol ; 13: 918241, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35990633

RESUMEN

Activated effector T cells (Teff) and/or compromised regulatory T cells (Treg) underlie many chronic inflammatory diseases. We discovered a novel pathway to regulate survival and expansion of Teff without compromising Treg survival and a potential therapeutic to treat these diseases. We found dimethylguanidino valeric acid (DMGV) as a rheostat for Teff survival: while cell-intrinsic DMGV generated by Alanine-Glyoxylate Aminotransferase 2 (AGXT2) is essential for survival and expansion by inducing mitochondrial ROS and regulation of glycolysis, an excessive (or exogenous) DMGV level inhibits activated Teff survival, thereby the AGXT2-DMGV-ROS axis functioning as a switch to turn on and off Teff expansion. DMGV-induced ROS is essential for glycolysis in Teff, and paradoxically DMGV induces ROS only when glycolysis is active. Mechanistically, DMGV rapidly activates mitochondrial calcium uniporter (MCU), causing a surge in mitochondrial Ca2+ without provoking calcium influx to the cytosol. The mitochondrial Ca2+ surge in turn triggers the mitochondrial Na+/Ca2+ exchanger (NCLX) and the subsequent mitochondrial Na+ import induces ROS by uncoupling the Coenzyme Q cycle in Complex III of the electron transport chain. In preclinical studies, DMGV administration significantly diminished the number of inflammatory T cells, effectively suppressing chronic inflammation in mouse models of colitis and rheumatoid arthritis. DMGV also suppressed expansion of cancer cells in vitro and in a mouse T cell leukemic model by the same mechanism. Our data provide a new pathway regulating T cell survival and a novel mode to treat autoimmune diseases and cancers.


Asunto(s)
Guanidinas , Inflamación , Cetoácidos , Neoplasias , Linfocitos T , Transaminasas , Animales , Calcio/metabolismo , Supervivencia Celular/genética , Guanidinas/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/genética , Cetoácidos/uso terapéutico , Ratones , Mitocondrias/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Especies Reactivas de Oxígeno/metabolismo , Intercambiador de Sodio-Calcio/metabolismo , Linfocitos T/fisiología , Transaminasas/genética
14.
Front Immunol ; 13: 914381, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36045678

RESUMEN

Innate anti-inflammatory mechanisms are essential for immune homeostasis and can present opportunities to intervene inflammatory diseases. In this report, we found that YAP isoform 9 (YAP9) is an essential negative regulator of the potent inflammatory stimuli such as TNFα, IL-1ß, and LPS. YAP9 constitutively interacts with another anti-inflammatory regulator A20 (TNFAIP3) to suppress inflammatory responses, but A20 and YAP can function only in the presence of the other. YAP9 uses a short stretch of amino acids in the proline-rich domain (PRD) and transactivation domain (TAD) suppress the inflammatory signaling while A20 mainly uses the zinc finger domain 7 (ZF7). Cell-penetrating synthetic PRD, TAD, and ZF7 peptides act as YAP9 and A20 mimetics respectively to suppress the proinflammatory responses at the cellular level and in mice. Our data uncover a novel anti-inflammatory axis and anti-inflammatory agents that can be developed to treat acute or chronic conditions where TNFα, IL-1ß, or LPS plays a key role in initiating and/or perpetuating inflammation.


Asunto(s)
Inflamación/metabolismo , Lipopolisacáridos , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Señalizadoras YAP/metabolismo , Animales , Inflamación/tratamiento farmacológico , Lipopolisacáridos/metabolismo , Ratones , Isoformas de Proteínas/metabolismo , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo
15.
Front Immunol ; 12: 625667, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33777008

RESUMEN

During the last decade, immune checkpoint inhibition (ICI) has become a pillar of cancer therapy. Antibodies targeting CTLA-4 or PD-1/PD-L1 have been approved in several malignancies, with thousands of clinical trials currently underway. While the majority of cancer immunotherapies have traditionally focused on enhancing cytotoxic responses by CD8+ or NK cells, there are clear evidences that CD4+ T cell responses can modulate the immune response against tumors and influence the efficacy of ICI therapy. CD4+ T cells can differentiate into several subsets of helper T cells (Th) or regulatory T cells (Treg), with a wide range of effector and/or regulatory functions. Importantly, different Th subsets may have different and sometimes contrasting roles in the clinical response to ICI therapy, which in addition may vary depending on the organ and tumor niche. In this review, we discuss recent evidence that highlights how ICI therapy impacts Th1, Th9, and Th17 cells and vice versa. These data might be important designing better interventions that unleash the full potential of immune response against cancer.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos , Animales , Humanos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias/inmunología , Neoplasias/metabolismo , Neoplasias/patología , Fenotipo , Células TH1/inmunología , Células TH1/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Resultado del Tratamiento , Microambiente Tumoral
16.
Front Vet Sci ; 8: 640067, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33681335

RESUMEN

Mycoplasma synoviae is an important pathogen of poultry, causing significant economic losses in this industry. Analysis of the unique genes and shared genes among different M. synoviae strains and among related species is helpful for studying the molecular pathogenesis of M. synoviae and provides valuable molecular diagnostic targets to facilitate the identification of M. synoviae species. We selected a total of 46 strains, including six M. synoviae strains, from 25 major animal (including avian) Mycoplasma species/subspecies that had complete genome sequences and annotation information published in GenBank, and used them for comparative genomic analysis. After analysis, 16 common genes were found in the 46 strains. Thirteen single-copy core genes and the 16s rRNA genes were used for genetic evolutionary analysis. M. synoviae was found to have a distant evolutionary relationship not only with other arthritis-causing mycoplasmas, but also with another major avian pathogen, Mycoplasma gallisepticum, that shares the major virulence factor vlhA with M. synoviae. Subsequently, six unique coding genes were identified as shared among these M. synoviae strains that are absent in other species with published genome sequences. Two of the genes were found to be located in the genetically stable regions of the genomes of M. synoviae and were determined to be present in all M. synoviae isolated strains (n = 20) and M. synoviae-positive clinical samples (n = 48) preserved in our laboratory. These two genes were used as molecular diagnostic targets for which SYBR green quantitative PCR detection methods were designed. The two quantitative PCR methods exhibited good reproducibility and high specificity when tested on positive plasmid controls and genomic DNA extracted from different M. synoviae strains, other major avian pathogenic bacteria/mycoplasmas, and low pathogenic Mycoplasma species. The detection limit for the two genes was 10 copies or less per reaction. The clinical sensitivity and specificity of the quantitative PCR methods were both 100% based on testing chicken hock joint samples with positive or negative M. synoviae infection. This research provides a foundation for the study of species-specific differences and molecular diagnosis of M. synoviae.

17.
Front Immunol ; 12: 625783, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33717139

RESUMEN

Although cancers arise from genetic mutations enabling cells to proliferate uncontrollably, they cannot thrive without failure of the anticancer immunity due in a large part to the tumor environment's influence on effector and regulatory T cells. The field of immune checkpoint inhibitor (ICI) therapy for cancer was born out of the fact that tumor environments paralyze the immune cells that are supposed to clear them by activating the immune checkpoint molecules such as PD-1. While various subsets of effector T cells work collaboratively to eliminate cancers, Tregs enriched in the tumor environment can suppress not only the native anticancer immunity but also diminish the efficacy of ICI therapies. Because of their essential role in suppressing autoimmunity, various attempts to specifically deplete tumor-associated Tregs are currently underway to boost the efficacy of ICI therapies without causing systemic autoimmune responses. A better understanding the roles of Tregs in the anti-cancer immunity and ICI therapies should provide more specific targets to deplete intratumoral Tregs. Here, we review the current understanding on how Tregs inhibit the anti-cancer immunity and ICI therapies as well as the advances in the targeted depletion of intratumoral Tregs.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Neoplasias/inmunología , Neoplasias/terapia , Linfocitos T Reguladores/inmunología , Autoinmunidad , Humanos , Radioinmunoterapia , Microambiente Tumoral
18.
Biochem J ; 418(1): 61-71, 2009 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-18973473

RESUMEN

STAF [Sec (selenocysteine) tRNA gene transcription activating factor] is a transcription activating factor for a number of RNA Pol III- and RNA Pol II-dependent genes including the Trsp [Sec tRNA gene], which in turn controls the expression of all selenoproteins. Here, the role of STAF in regulating expression of Sec tRNA and selenoproteins was examined. We generated transgenic mice expressing the Trsp transgene lacking the STAF-binding site and made these mice dependent on the transgene for survival by removing the wild-type Trsp. The level of Sec tRNA was unaffected or slightly elevated in heart and testis, but reduced approximately 60% in liver and kidney, approximately 70% in lung and spleen and approximately 80% in brain and muscle compared with the corresponding organs in control mice. Moreover, the ratio of the two isoforms of Sec tRNA that differ by methylation at position 34 (Um34) was altered significantly, and the Um34-containing form was substantially reduced in all tissues examined. Selenoprotein expression in these animals was most affected in tissues in which the Sec tRNA levels were most severely reduced. Importantly, mice had a neurological phenotype strikingly similar to that of mice in which the selenoprotein P gene had been removed and their life span was substantially reduced. The results indicate that STAF influences selenoprotein expression by enhancing Trsp synthesis in an organ-specific manner and by controlling Sec tRNA modification in each tissue examined.


Asunto(s)
Envejecimiento/fisiología , ARN de Transferencia Aminoácido-Específico/genética , ARN de Transferencia Aminoácido-Específico/metabolismo , Selenoproteínas/metabolismo , Transactivadores/metabolismo , Animales , Encéfalo/metabolismo , Inmunohistoquímica , Ratones , Ratones Noqueados , Especificidad de Órganos , Fenotipo , Unión Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Selenoproteínas/genética , Tasa de Supervivencia , Transactivadores/genética
19.
J Diabetes Investig ; 11(4): 896-905, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32020731

RESUMEN

AIMS/INTRODUCTION: This secondary analysis of the 24-week SMART study examined the efficacy of add-on saxagliptin or acarbose to metformin across different patient subgroups with type 2 diabetes mellitus, based on baseline characteristics. MATERIALS AND METHODS: Randomized patients (n = 481) were classified into subgroups based on their baseline age (<65, ≥65 years), body mass index (BMI; <24, 24-<28, ≥28 kg/m2 ), glycated hemoglobin (HbA1c; <8%, 8-<9%, 9-<10%, ≥10%) and renal function (creatinine clearance 50-<80, ≥80 mL/min). Treatment effects on primary outcome (HbA1c) and key secondary outcomes of fasting plasma glucose (FPG), 2-h postprandial glucose and homeostatic model assessment of ß-cell function were assessed across patient subgroups. RESULTS: For saxagliptin, reductions in HbA1c from baseline to week 24 were consistent across different subgroups regardless of baseline age, body mass index, HbA1c and renal function (range -0.66 to -1.16%). Saxagliptin was associated with consistent reductions in FPG (-0.60 to -1.33 mmol/L) and 2-h postprandial glucose (-0.48 to -1.95 mmol/L) across the majority of subgroups studied. The efficacy of acarbose on FPG attenuated progressively with increasing baseline HbA1c (+0.86 to -1.43 mmol/L); an increase from baseline FPG was observed in patients with HbA1c >9%. The effect of acarbose on postprandial glucose was also variable (+0.23 to -3.38 mmol/L). CONCLUSIONS: As add-on to metformin, both saxagliptin and acarbose reduced HbA1c regardless of baseline HbA1c, age, body mass index and renal function; however, only saxagliptin was effective at a stable glycemic control (FPG and PPG). The efficacy of acarbose on FPG and PPG was significantly attenuated in patients with higher baseline HbA1c (≥8%).


Asunto(s)
Acarbosa/administración & dosificación , Adamantano/análogos & derivados , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipéptidos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Adamantano/administración & dosificación , Anciano , Glucemia/efectos de los fármacos , China , Diabetes Mellitus Tipo 2/sangre , Quimioterapia Combinada , Femenino , Hemoglobina Glucada/efectos de los fármacos , Control Glucémico/métodos , Humanos , Masculino , Persona de Mediana Edad , Periodo Posprandial , Resultado del Tratamiento
20.
BMJ Open ; 9(2): e022993, 2019 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-30782871

RESUMEN

OBJECTIVES: The aims of this study were to assess malnutrition risk in Chinese geriatric inpatients using Nutritional Risk Screening 2002 (NRS2002) and Mini-Nutritional Assessment (MNA), and to identify the most appropriate nutritional screening tool for these patients. DESIGN: Cross-sectional study. SETTING: Eight medical centres in Hubei Province, China. PARTICIPANTS: A total of 425 inpatients aged ≥70 years were consecutively recruited between December 2014 and May 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Nutritional risk was assessed using NRS2002, MNA, anthropometric measurements and biochemical parameters within 24 hours of admission. Comorbidities and length of hospitalisation were recorded. Nutritional parameters, body mass index (BMI) and length of hospital stay (LOS) were employed to compare MNA and NRS2002. Kappa analysis was used to evaluate the consistency of the two tools. RESULTS: The average age was 81.2±5.9 years (range, 70-98). The prevalence of undernutrition classified by NRS2002 and MNA was 40.9% and 58.6%, respectively. Patients undergoing malnutrition had lower BMI, haemoglobin, albumin and prealbumin (p<0.05), and longer LOS (p<0.05). The NRS2002 showed moderate agreement (κ=0.521, p<0.001) with MNA. Both tools presented significant correlation with age, BMI and laboratory parameters (p<0.001). In addition, a significant association between both tools and LOS was found (p<0.05). In addition, the NRS2002 was not different from MNA in predicting nutritional risk in terms of the area under the receiver operating characteristic curve (p>0.05). CONCLUSIONS: The results show a relatively high prevalence of malnutrition risk in our sample cohort. We found that NRS2002 and MNA were both suitable in screening malnutrition risk among Chinese geriatric inpatients.


Asunto(s)
Índice de Masa Corporal , Evaluación Geriátrica/métodos , Tiempo de Internación/estadística & datos numéricos , Desnutrición/diagnóstico , Tamizaje Masivo/métodos , Anciano , Anciano de 80 o más Años , China , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Pacientes Internos , Modelos Lineales , Masculino , Desnutrición/epidemiología , Evaluación Nutricional , Prevalencia , Curva ROC , Factores de Riesgo
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