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1.
Ann Oncol ; 35(1): 66-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37866811

RESUMO

BACKGROUND: Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance. PATIENTS AND METHODS: In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m2 every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety. RESULTS: A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel [median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144]. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively. CONCLUSIONS: Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports.


Assuntos
Anilidas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piridinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Docetaxel/uso terapêutico , Nivolumabe/uso terapêutico , Neoplasias Pulmonares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Microambiente Tumoral
2.
Phys Rev Lett ; 129(9): 097203, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36083669

RESUMO

In a joint effort of both experiments and first-principles calculations, we resolve a hotly debated controversy and provide a coherent picture on the pure spin transport between Ag/Bi and ferromagnets. We demonstrate a strong inverse Rashba-Edelstein effect (IREE) at the interface in between Ag/Bi with a ferromagnetic metal (FM) but not with a ferromagnetic insulator. This is in sharp contrast to the previously claimed IREE at Ag/Bi interface or inverse spin Hall effect dominated spin transport. A more than one order of magnitude modulation of IREE signal is realized for different Ag/Bi-FM interfaces, casting strong tunability and a new direction for searching efficient spintronics materials.

3.
Phys Rev Lett ; 129(15): 156401, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36269973

RESUMO

Chiral materials have attracted significant research interests as they exhibit intriguing physical properties, such as chiral optical response, spin-momentum locking, and chiral induced spin selectivity. Recently, layered transition metal dichalcogenide 1T-TaS_{2} has been found to host a chiral charge density wave (CDW) order. Nevertheless, the physical consequences of the chiral order, for example, in electronic structures and the optical properties, are yet to be explored. Here, we report the spectroscopic visualization of an emergent chiral electronic band structure in the CDW phase, characterized by windmill-shaped Fermi surfaces. We uncover a remarkable chirality-dependent circularly polarized Raman response due to the salient in-plane chiral symmetry of CDW, although the ordinary circular dichroism vanishes. Chiral Fermi surfaces and anomalous Raman responses coincide with the CDW transition, proving their lattice origin. Our Letter paves a path to manipulate the chiral electronic and optical properties in two-dimensional materials and explore applications in polarization optics and spintronics.

4.
Public Health ; 208: 80-88, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35728416

RESUMO

OBJECTIVES: This study aimed to investigate associations of resting heart rate (RHR) and blood pressure (BP) with all-cause and cardiovascular disease (CVD) mortality. STUDY DESIGN: A retrospective cohort study. METHODS: A total of 67,028 Chinese participants aged ≥60 years were included in the analysis. RHR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were evaluated according to quartiles ([41-69, 70-74, 75-79, 80-127 beats/min], [80-119, 120-129, 130-139, 140-238 mm Hg], and [40-70, 71-79, 80-84, 85-133 mm Hg]). Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and CVD mortality with RHR, SBP, and DBP. Restricted cubic splines were used to evaluate the dose-response association. RESULTS: During the 361,975 person-year follow-up, 9326 deaths were recorded, of which 5039 deaths were due to CVD. The risk of all-cause mortality was increased by 25% with the quartiles four vs quartile one of RHR (HR [95% CI]:1.25 [1.17-1.33]), and CVD mortality was increased by 32% (HR [95% CI]: 1.32 [1.22-1.44]). Similar results were observed when comparing the quartiles four vs quartile one of SBP with the risk of all-cause and CVD mortality (HRs [95% CIs]: 1.14 [1.07, 1.22] and 1.23 [1.12. 1.34]) and DBP with the risk of all-cause and CVD mortality (HRs [95% CIs]: 1.17 [1.11. 1.24] and 1.36 [1.26. 1.47]). We found linear associations of RHR, SBP, and DBP with all-cause and CVD mortality (Pnon-linearity >0.05), except for the approximately J-shaped association between DBP and all-cause mortality (Pnon-linearity = 0.008). There was a significant interaction of RHR and SBP with all-cause and CVD mortality (Pinteraction <0.05). CONCLUSIONS: RHR and BP increased the risk of all-cause and CVD mortality, especially fast RHR combined with high SBP.


Assuntos
Doenças Cardiovasculares , Hipertensão , Pressão Sanguínea/fisiologia , Frequência Cardíaca , Humanos , Estudos Retrospectivos , Fatores de Risco
5.
Phys Rev Lett ; 126(8): 086802, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33709762

RESUMO

Mesoscopic conductance fluctuations are a ubiquitous signature of phase-coherent transport in small conductors, exhibiting universal character independent of system details. In this Letter, however, we demonstrate a pronounced breakdown of this universality, due to the interplay of local and remote phenomena in transport. Our experiments are performed in a graphene-based interaction-detection geometry, in which an artificial magnetic texture is induced in the graphene layer by covering a portion of it with a micromagnet. When probing conduction at some distance from this region, the strong influence of remote factors is manifested through the appearance of giant conductance fluctuations, with amplitude much larger than e^{2}/h. This violation of one of the fundamental tenets of mesoscopic physics dramatically demonstrates how local considerations can be overwhelmed by remote signatures in phase-coherent conductors.

6.
Curr Microbiol ; 77(5): 865-874, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31938806

RESUMO

Schisandra chinensis (Turcz.) Baill (S. chinensis), an edible traditional medicine herb, has a strong constitution, which extract has good antibacterial activity. The study investigated its antibacterial properties on E. coli, to find a candidate for the development as new preservative. In vitro antibacterial assay showed that S. chinensis extract (SCE) effectively inhibited the growth of test bacteria with MBC of 18 mg/mL. In model cosmetic system of O/W emulsions, SCE possessed a great antibacterial capacity. The growth curves of E. coli treated with SCE exhibited an extended lag phase and restricted log phase. Scanning electron microscopy showed that the treated E. coli cells exhibited wrinkled and withered surfaces, and disappearing outmost layer, suggesting S. chinensis extract can damage S. aureus cell member and wall, in addition, the leakage of periplasm enzyme AKPase and the increased activities of Na+/K+-ATPase and Ca++-ATPase in cell membrane were also consistent with the microscopy results. Moreover, the S. chinensis extract can decrease the activities of dehydrogenase and total ATPase and the content of intracellular proteins, and bind with S. aureus DNA by electrostatic and groove binding. The results indicated that SCE might be a candidate cosmetic preservative for its good antibacterial activity and multiple targets on E. coli.


Assuntos
Antibacterianos/farmacologia , Cosméticos , Escherichia coli/efeitos dos fármacos , Extratos Vegetais/farmacologia , Schisandra/química , Membrana Externa Bacteriana/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos
7.
Mol Biol (Mosk) ; 54(3): 435-444, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32492006

RESUMO

Homology-directed (HD) genome modification offers an opportunity to precisely modify the genome. Despite reported successful cases, for many loci, precise genome editing remains challenging and inefficient in vivo. Here we report an effort to precisely knock-in a GFP reporter into gad locus mediated by CRISPR/Cas9 system in the zebrafish Danio rerio. PCR artifact was detected in testing for homologous recombination (HR), but was mitigated by optimizing PCR condition and decreasing the injected targeting plasmid concentration. Under this optimized condition, time course analysis revealed a decline of the HR-positive embryos at embryogenesis progressed. GFP signals also diminished at later developmental stages. The GFP signals were consistent with PCR detection, both of which suggested the loss of targeted insertion events at later stages. Such loss of insertion might be one underlying reason for the inability to obtain germ-line transgenic lines with GFP knocked into the gad locus. Our results suggest that the low HR efficiency associated with CRISPR-mediated knock-in is in part due to loss of insertion after targeted integration into the gad locus.


Assuntos
Sistemas CRISPR-Cas , Técnicas de Introdução de Genes , Recombinação Homóloga , Peixe-Zebra , Animais , Animais Geneticamente Modificados , Genes Reporter , Peixe-Zebra/genética
8.
Insect Mol Biol ; 28(4): 550-567, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30739379

RESUMO

The cotton mealybug Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae) is a polyphagous insect that attacks tens of plant and causes substantial economic loss. Insect chitinases are required to remove the old cuticle to allow for continued growth and development. Though insect chitinases have been well studied in tens of insects, their functions in mealybug are still not addressed. Here, we sequenced the transcriptomes of adult males and females, from which eight chitinase genes were identified. We then used the method of rapid amplification of cDNA ends to amplify their full length. Phylogenetic analysis indicated that these genes clustered into five subgroups. Among which, group II PsCht2 had the longest transcript and was highly expressed at second instar nymph. PsCht10, PsCht3-3 and PsIDGF were highly expressed in the adult females, whereas PsCht4 and PsCht4-1 were significantly expressed at the male pupa and adult male. Next, we knocked down all eight chitinase genes by feeding the double-stranded RNA. Knockdown of PsCht4 or PsCht4-1 led to the failure of moult and, silencing PsCht5 resulted in pupation defect, while silencing PsCht10 led to small body size, suggesting these genes have essential roles in development and can be used as a potential target for pest control.


Assuntos
Quitinases/genética , Hemípteros/genética , Proteínas de Insetos/genética , Muda/genética , Transcriptoma , Sequência de Aminoácidos , Animais , Quitinases/química , Quitinases/metabolismo , Feminino , Hemípteros/enzimologia , Hemípteros/crescimento & desenvolvimento , Hemípteros/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Masculino , Ninfa/enzimologia , Ninfa/genética , Ninfa/crescimento & desenvolvimento , Ninfa/metabolismo , Filogenia , Alinhamento de Sequência , Caracteres Sexuais , Fatores Sexuais
9.
Insect Mol Biol ; 28(6): 739-758, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31120160

RESUMO

In the wake of constant improvements in sequencing technologies, numerous insect genomes have been sequenced. Currently, 1219 insect genome-sequencing projects have been registered with the National Center for Biotechnology Information, including 401 that have genome assemblies and 155 with an official gene set of annotated protein-coding genes. Comparative genomics analysis showed that the expansion or contraction of gene families was associated with well-studied physiological traits such as immune system, metabolic detoxification, parasitism and polyphagy in insects. Here, we summarize the progress of insect genome sequencing, with an emphasis on how this impacts research on pest control. We begin with a brief introduction to the basic concepts of genome assembly, annotation and metrics for evaluating the quality of draft assemblies. We then provide an overview of genome information for numerous insect species, highlighting examples from prominent model organisms, agricultural pests and disease vectors. We also introduce the major insect genome databases. The increasing availability of insect genomic resources is beneficial for developing alternative pest control methods. However, many opportunities remain for developing data-mining tools that make maximal use of the available insect genome resources. Although rapid progress has been achieved, many challenges remain in the field of insect genomics.


Assuntos
Bases de Dados como Assunto , Genoma de Inseto , Controle de Insetos , Insetos/genética , Animais , Mapeamento Cromossômico , Bases de Dados Genéticas , Análise de Sequência de DNA
10.
Br J Nutr ; 122(4): 376-387, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31208474

RESUMO

Abnormal Ca homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating Ca levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase and Google Scholar) and related references with de novo results from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RR) and 95 % CI for the associations. The search yielded twenty eligible publications with eight cohort studies identified for the meta-analysis, which included a total of 89 165 participants. Comparing the highest with the lowest category of albumin-adjusted serum Ca, the pooled RR was 1·14 (95 % CI 1·05, 1·24) for T2DM (n 51 489). Similarly, serum total Ca was associated with incident T2DM (RR 1·25; 95 % CI 1·10, 1·42) (n 64 502). Additionally, the adjusted RR for 1 mg/dl increments in albumin-adjusted serum Ca or serum total Ca levels was 1·16 (95 % CI 1·07, 1·27) and 1·19 (95 % CI 1·11, 1·28), respectively. The observed associations remained with the inclusion of a cohort study with ionised Ca as the exposure. However, data pooled from neither case-control (n 4) nor cross-sectional (n 8) studies manifested a significant correlation between circulating Ca and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating Ca levels are associated with an augmented risk of T2DM.


Assuntos
Cálcio/sangue , Diabetes Mellitus Tipo 2/sangue , Homeostase , Humanos , Fatores de Risco
11.
Insect Mol Biol ; 27(6): 835-846, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30058753

RESUMO

Insect chitinases participate in numerous physiological processes such as nutrition, parasitism, morphogenesis and immunity. These properties make chitinases good targets for pest control. Rice striped stem borer (SSB), Chilo suppressalis Walker, is one of the most destructive pests of rice causing huge yield losses. In our previous work, we reported the identification of 12 SSB chitinase (CsCht) genes, and studied the functions of CsCht1 to 4. Here, we have extended our study to investigate the expression patterns and functions of CsCht5 to 12. All eight chitinase genes displayed distinct temporospatial expression profiles. We looked at the effect of knocking down each gene at the developmental stage where highest expression was observed. Knocking down CsCht5, CsCht6 and CsCht8 resulted in high mortality and delayed development. Although silencing CsCht7, CsCht9, CsCht10, CsCht11 and CsCht12 had no apparent effect on development, knocking down CsCht10 in SSB individuals that were simultaneously treated with Beauveria bassiana (Bb84) led to higher mortality rates and quicker death, suggesting CsCht10 has an essential role in protecting SSB from exogenous microorganisms. In summary, we elucidated the functions of eight SSB chitinase genes and found that CsCht10 could be a good candidate for pest control.


Assuntos
Quitinases/genética , Mariposas/enzimologia , Controle Biológico de Vetores , Animais , Beauveria/fisiologia , Quitinases/metabolismo , Mariposas/genética , Mariposas/crescimento & desenvolvimento , Mariposas/microbiologia , Interferência de RNA
12.
Zhonghua Zhong Liu Za Zhi ; 40(3): 201-205, 2018 Mar 23.
Artigo em Zh | MEDLINE | ID: mdl-29575839

RESUMO

Objective: To compare the clinicopathological characteristics of second primary lung cancer following breast cancer and lung metastases from breast cancer, and then to analyze the risk factors in breast cancer patients with second primary lung tumor. Methods: Clinical data of 55 breast cancer patients with second primary lung tumor and 205 breast cancer patients with solitary pulmonary metastasis in Shandong Cancer Hospital from January 2006 to January 2017 were retrospectively analyzed. The risk factors of primary lung cancer following breast cancer were analyzed using logistic regression model. Results: Second primary lung cancer in patients with first breast cancer accounted for approximately 21.2%(55/260) of pulmonary malignant solitary nodules, and 0.84%(55/6 580) of all breast cancer patients. The median intervals between the diagnosis of second primary lung cancer or lung metastasis and first breast cancer were 52 months and 42 months, respectively. These two groups showed significant difference between age, time interval between diagnoses, breast tumor size, axillary lymph node metastasis, estrogen receptor, molecular subtype (luminal B and triple-negative) and history of radiotherapy (P<0.05 for all). A multivariate logistic regression model confirmed that age (OR=1.088, P<0.001), breast tumor size(OR=0.480, P<0.001), and radiotherapy history (OR=3.460, P=0.004) were all independent factors for second primary lung cancer. Conclusions: For isolated pulmonary nodules in patients with breast cancer, especially for those with elder age, larger tumor size and radiotherapy history, we should distinguish the second primary lung cancer from pulmonary metastasis. The treatment regimen for lung metastasis and primary lung cancer in patients with breast cancer are entirely distinct. The timely histopathology examinations for pulmonary nodes in patients with breast cancer are recommended.


Assuntos
Neoplasias da Mama/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Segunda Neoplasia Primária/patologia , Nódulo Pulmonar Solitário/patologia , Fatores Etários , Axila , Neoplasias da Mama/química , Diagnóstico Diferencial , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Receptores de Estrogênio , Estudos Retrospectivos , Fatores de Tempo
13.
Med Oral Patol Oral Cir Bucal ; 22(2): e214-e218, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28160580

RESUMO

BACKGROUND: Relapse of granulomatous epulis is common after surgery because of local irritations, hormonal level in vivo, or incomplete resection. Currently, if recurrence occurs, then extraction of the teeth adjacent to the lesion is commonly performed, which may influence the aesthetics or masticatory function. Thus, a more effective and less aggressive treatment method is urgently demanded, particularly for the recurring lesion. This study investigated the effects of the intralesional pingyangmycin (PYM) injections for the recurrent granulomatous epulis and assessed the complications. MATERIAL AND METHODS: A total of 16 patients with recurrent granulomatous epulis underwent intralesional PYM injections, between July 2010 and June 2014. The effects and complications of the treatment were retrospectively reviewed. RESULTS: The total number of injections performed was 48 (for all patients). The median number of injections per patient was three (range, two to four). All cases completely recovered with no recurrence and resorption of the alveolar bone after a follow-up of more than 12 months. The complications included slight bleeding, local swelling and pain following injection. All these symptoms resolved 7 to 10 days after the injection. CONCLUSIONS: In summary, intralesional PYM injections may be a preferred option for recurring granulomatous epulis.


Assuntos
Bleomicina/análogos & derivados , Doenças da Gengiva/terapia , Granuloma/terapia , Escleroterapia , Adolescente , Adulto , Bleomicina/uso terapêutico , Criança , Feminino , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Adulto Jovem
14.
Artigo em Zh | MEDLINE | ID: mdl-28511298

RESUMO

Objective: To investigate the influence of aluminum chloride (AlCl(3)) solution on the embryon-ic development of zebrafish and neurobehavior of juvenile fish. Methods: The embryos of zebrafishat 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 55.0, 60.5, 66.6, 73.5, 80.5, or 100.0 mg/L, and embryonic hatching rates at 48 and 72 hours after fertilization were calculated. The embryos of zebrafishat 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 60.0, 72.0, 86.4, 103.7, or 124.4 mg/L, and the embryonic mortality rates at 12, 24, 48, 72, and 96 hours after fertilization were calculat-ed. The embryos of zebrafish at 6 hours after fertilization were exposed to AlCl(3) solution at a concentration of 0, 50, 100, 200, 400, or 800 µg/L, and the changes in the neurobehavior of juvenile fish were observed after hatching, including touch-escape reaction at 72 hours after fertilization and autonomic movement and panic es-cape reflex at 7 days after fertilization. Results: Compared with the 0 mg/L group, the≥66.6 mg/L group had a sig-nificant reduction in embryonic hatching rate at 48 and 72 hours after fertilization, and the ≥72.0 mg/L group had a significant increase in embryonic mortality rate at 96 hours after fertilization (P<0.05) . Compared with the 0 µg/L group, the≥100 µg/L group had a significant reduction in the number of times of touch-escape reaction (P<0.05) .Compared with the 0 and 50 µg/L groups, the 100-800 µg/L groups had significant reductions in total movement distance and average speed (P<0.05) . Compared with the dark period before illumination, all groups had a significant increase in movement speed during the light period of the panic escape reflex test (i.e., the third minute) (P<0.05) ; within 2 minutes after the light was turned off, there was no significant change in movement speed in the 0-200 µg/L groups (P>0.05) ; the 400 and 800 µg/L groups had a significant increase in movement speed (P<0.05) . Conclusion: AlCl(3) exposure may cause embryonic developmental disorder in zebrafish and ab-normal neurobehavior in juvenile fish.


Assuntos
Compostos de Alumínio/toxicidade , Cloretos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Peixe-Zebra/fisiologia , Cloreto de Alumínio , Animais , Embrião não Mamífero/embriologia , Embrião não Mamífero/metabolismo , Peixe-Zebra/embriologia
15.
Phys Rev Lett ; 117(11): 115001, 2016 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-27661697

RESUMO

Evidence of a nonlinear transition from mitigation to suppression of the edge localized mode (ELM) by using resonant magnetic perturbations (RMPs) in the EAST tokamak is presented. This is the first demonstration of ELM suppression with RMPs in slowly rotating plasmas with dominant radio-frequency wave heating. Changes of edge magnetic topology after the transition are indicated by a gradual phase shift in the plasma response field from a linear magneto hydro dynamics modeling result to a vacuum one and a sudden increase of three-dimensional particle flux to the divertor. The transition threshold depends on the spectrum of RMPs and plasma rotation as well as perturbation amplitude. This means that edge topological changes resulting from nonlinear plasma response plays a key role in the suppression of ELM with RMPs.

16.
Br J Dermatol ; 175(1): 102-12, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26873524

RESUMO

BACKGROUND: Lymphatic malformations (LMs), slow-flow vascular anomalies resulting from abnormal development of lymphatic channels, often progress rapidly after trauma or infection. OBJECTIVES: To explore the possible mechanism by which local infection promotes the progression of LMs. METHODS: Immunohistochemistry in serial sections and immunofluorescence were performed to label polarized macrophages. Tertiary lymphoid organs (TLOs) in LMs were identified using antibodies against CD3 (a T-cell marker), CD20 (a B-cell marker) and PNAd (a high endothelial venule marker). Pearson's correlation and cluster analysis were carried out to delineate the relationship between macrophage infiltration and TLO formation. Rat models of LM were established to examine the role of lipopolysaccharide in LM development. RESULTS: Compared with normal skin tissues, both M1- and M2-polarized macrophages were prevalent in LMs. Moreover, M2-polarized macrophages were significantly increased in infected LMs with an elevated density of TLOs. M2-polarized macrophages were observed in the centre of TLOs accompanied by intensive staining of macrophage colony-stimulating factor, a strong chemotactic factor for monocytes/macrophages, suggesting that macrophages might be recruited through TLOs. Cluster analysis and Pearson's correlation suggested a close relationship between macrophage infiltration and TLO formation. Furthermore, the expression of CD68 was also correlated with that of vascular endothelial growth factor (VEGF)-C and Ki67. Importantly, in an established LM rat model, lipopolysaccharide promoted the progression of the malformations with increased macrophage infiltration and TLO formation. CONCLUSIONS: M2-polarized macrophages that may be recruited through TLOs in infected LMs may contribute to the progression of the disease by secreting VEGF-C, and therefore accelerating the proliferation of lymphatic endothelial cells.


Assuntos
Infecções/imunologia , Vasos Linfáticos/anormalidades , Macrófagos/fisiologia , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Proliferação de Células/fisiologia , Modelos Animais de Doenças , Progressão da Doença , Células Endoteliais/imunologia , Células Endoteliais/fisiologia , Feminino , Lipopolissacarídeos/toxicidade , Macrófagos/imunologia , Macrófagos/metabolismo , Ratos Wistar , Fator C de Crescimento do Endotélio Vascular/metabolismo
17.
Heredity (Edinb) ; 116(1): 23-32, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26286667

RESUMO

The mountains of southwest China (MSC) harbor extremely high species diversity; however, the mechanism behind this diversity is unknown. We investigated to what degree the topography and climate change shaped the genetic diversity and diversification in these mountains, and we also sought to identify the locations of microrefugia areas in these mountains. For these purposes, we sampled extensively to estimate the intraspecific phylogenetic pattern of the Chinese mole shrew (Anourosorex squamipes) in southwest China throughout its range of distribution. Two mitochondrial genes, namely, cytochrome b (CYT B) and NADH dehydrogenase subunit 2 (ND2), from 383 archived specimens from 43 localities were determined for phylogeographic and demographic analyses. We used the continuous-diffusion phylogeographic model, extensive Bayesian skyline plot species distribution modeling (SDM) and approximate Bayesian computation (ABC) to explore the changes in population size and distribution through time of the species. Two phylogenetic clades were identified, and significantly higher genetic diversity was preserved in the southern subregion of the mountains. The results of the SDM, continuous-diffusion phylogeographic model, extensive Bayesian skyline plot and ABC analyses were congruent and supported that the Last Interglacial Maximum (LIG) was an unfavorable period for the mole shrews because of a high degree of seasonality; A. squamipes survived in isolated interglacial refugia mainly located in the southern subregion during the LIG and rapidly expanded during the last glacial period. These results furnished the first evidence for major Pleistocene interglacial refugia and a latitudinal effect in southwest China, and the results shedding light on the higher level of species richness in the southern subregion.


Assuntos
Variação Genética , Genética Populacional , Refúgio de Vida Selvagem , Musaranhos/genética , Animais , Teorema de Bayes , China , Mudança Climática , Citocromos b/genética , DNA Mitocondrial/genética , Funções Verossimilhança , Modelos Genéticos , Dados de Sequência Molecular , NADH Desidrogenase/genética , Filogenia , Filogeografia , Densidade Demográfica , Análise de Sequência de DNA
18.
Int J Immunogenet ; 43(1): 8-17, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26700854

RESUMO

Classical major histocompatibility complex (MHC) class I allelic polymorphism is essential for competent antigen presentation. To improve the genotyping efforts in the golden pheasant, it is necessary to differentiate more accurately between classical and nonclassical class I molecules. In our study, all MHC class I genes were isolated from one golden pheasant based on two overlapping PCR amplifications. In total, six full-length class I nucleotide sequences (A-F) were identified, and four were novel. Two (A and C) belonged to the IA1 gene, two (B and D) were alleles derived from the IA2 gene through transgene amplification, and two (E and F) comprised a third novel locus, IA3 that was excluded from the core region of the golden pheasant MHC-B. IA1 and IA2 exhibited the broad expression profiles characteristic of classical loci, while IA3 showed no expression in multiple tissues and was therefore defined as a nonclassical gene. Phylogenetic analysis indicated that the three IA genes in the golden pheasant share a much closer evolutionary relationship than the corresponding sequences in other galliform species. This observation was consistent with high sequence similarity among them, which likely arises from the homogenizing effect of recombination. Our careful distinction between the classical and nonclassical MHC class I genes in the golden pheasant lays the foundation for developing locus-specific genotyping and establishing a good molecular marker system of classical MHC I loci.


Assuntos
Evolução Molecular , Galliformes/imunologia , Genes MHC Classe I/imunologia , Seleção Genética , Alelos , Animais , Galliformes/genética , Variação Genética , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos
19.
Genet Mol Res ; 15(3)2016 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-27706721

RESUMO

The aim of this study was to conduct a systematic evaluation the correlation between polymorphisms in the estrogen receptor α gene (ESRα) and coronary heart disease susceptibility. Case-control studies until August 2015 analyzing the correlation between the ESRα PvuII T/C polymorphism and coronary heart disease were obtained from various electronic databases (CBM, CNKI, Wanfang Data, VIP, and MEDLINE, Cochrane Library, Embase, Springer, and Ovid. The data obtained from these studies were evaluated and valid data was extracted. A meta-analysis was performed using RevMan 5.0. Eleven cases, comprising 1742 patients with coronary heart disease and 2012 controls, that conformed to the inclusion criteria set in this study were extracted. The results of our meta-analysis indicated that the C and T alleles, the TC+CC and TT genotypes, and the CC and TT+TC genotypes did not differ significantly. The results of this meta-analysis confirmed that there was no correlation between polymorphisms in ESRα and coronary heart disease susceptibility in the Chinese population.


Assuntos
Doença das Coronárias/genética , Receptor alfa de Estrogênio/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Alelos , China , Doença das Coronárias/epidemiologia , Doença das Coronárias/patologia , Feminino , Genótipo , Humanos , Masculino , Fatores de Risco
20.
J Anim Physiol Anim Nutr (Berl) ; 100(3): 440-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26259765

RESUMO

This study assessed the effect of dietary vanadium (V) and vitamin C (VC) on production performance, egg quality and antioxidant status in laying hens. A total of 360 laying hens (31-week-old) were randomly allotted into a 3 × 3 factorial arrangement treatments (four replicates and 10 chicks per replicate) with three levels of dietary V (0, 5 and 10 mg/kg) and three levels of vitamin C (0, 50 and 100 mg/kg) for 12 weeks. The effect of V and VC did not alter egg production, egg weight, average daily feed intake and feed conversion ratio during 1-12 week. Albumen height and Haugh unit value were linearly decreased (p < 0.001) by addition of V, whereas the effect of 100 mg/kg VC was observed to counteract (p < 0.05) this effect in V-containing treatments during 1-12 week. Hens fed V-containing diet laid lighter (linear effect, p < 0.05) coloured eggs (higher lightness value, lower redness and yellowness value), and the VC exerted no influence on it during 1-12 week. The serum superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, ability to inhibit hydroxyl radical, were significantly decreased, and the malondialdehyde (MDA) and V contents were increased (p < 0.05) by effect of V during 4, 8 and 12 week. The effect of VC alone and the interactive effect between VC and V were shown to increase serum (p < 0.05) SOD activity in 4 week and decrease MAD levels in 12 week. The result indicate that V decreased the egg quality and caused the oxidative stress at level of 5 mg/kg and 10 mg/kg, and the addition of 100 mg/kg vitamin C can alleviate its egg quality reduction effect and can mitigate the oxidative stress to some extent.


Assuntos
Antioxidantes/metabolismo , Ácido Ascórbico/farmacologia , Galinhas/fisiologia , Ovos/normas , Vanádio/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Feminino
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