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1.
Ecol Evol ; 14(4): e11189, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38571808

RESUMO

The issue of poor sexual performance of some male giant pandas seriously impairs the growth and the genetic diversity of the captive population, yet there is still no clear understanding of the cause of the loss of this ability and its underlying mechanism. In this study, we analyzed the gut microbiota and its function in 72 fecal samples obtained from 20 captive male giant pandas, with an equal allocation between individuals capable and incapable of natural mating. Additionally, we investigated fecal hormone levels and behavioral differences between the two groups. A correlation analysis was then conducted among these factors to explore the influencing factors of their natural mating ability. The results showed significant differences in the composition of gut microbiota between the two groups of male pandas. The capable group had significantly higher abundance of Clostridium sensu stricto 1 (p adjusted = .0021, GLMM), which was positively correlated with fatty acid degradation and two-component system functions (Spearman, p adjusted < .05). Additionally, the capable group showed higher gene abundance in gut microbiota function including purine and pyrimidine metabolism and galactose metabolism, as well as pathways related to biological processes such as ribosome and homologous recombination (DEseq2, p adjusted < .05). We found no significant differences in fecal cortisol and testosterone levels between the two groups, and no difference was found in their behavior either. Our study provides a theoretical and practical basis for further studying the behavioral degradation mechanisms of giant pandas and other endangered mammal species.

2.
Nat Commun ; 15(1): 3464, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658536

RESUMO

TnpBs encoded by the IS200/IS605 family transposon are among the most abundant prokaryotic proteins from which type V CRISPR-Cas nucleases may have evolved. Since bacterial TnpBs can be programmed for RNA-guided dsDNA cleavage in the presence of a transposon-adjacent motif (TAM), these nucleases hold immense promise for genome editing. However, the activity and targeting specificity of TnpB in homology-directed gene editing remain unknown. Here we report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host. Interestingly, the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. By systematically characterizing TAM variants, we reveal that the TnpB recognizes a broad range of TAM sequences for gene editing including those that do not elicit apparent cell death. Importantly, TnpB shows a very high targeting specificity on targets flanked by a weak TAM. Taking advantage of this feature, we successfully leverage TnpB for efficient single-nucleotide editing with templated repair. The use of different weak TAM sequences not only facilitates more flexible gene editing with increased cell survival, but also greatly expands targeting scopes, and this strategy is probably applicable to diverse CRISPR-Cas systems.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Edição de Genes/métodos , Elementos de DNA Transponíveis/genética , Proteínas Arqueais/metabolismo , Proteínas Arqueais/genética , Transposases/metabolismo , Transposases/genética
3.
Proc Natl Acad Sci U S A ; 121(11): e2317430121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437540

RESUMO

Brown-and-white giant pandas (hereafter brown pandas) are distinct coat color mutants found exclusively in the Qinling Mountains, Shaanxi, China. However, its genetic mechanism has remained unclear since their discovery in 1985. Here, we identified the genetic basis for this coat color variation using a combination of field ecological data, population genomic data, and a CRISPR-Cas9 knockout mouse model. We de novo assembled a long-read-based giant panda genome and resequenced the genomes of 35 giant pandas, including two brown pandas and two family trios associated with a brown panda. We identified a homozygous 25-bp deletion in the first exon of Bace2, a gene encoding amyloid precursor protein cleaving enzyme, as the most likely genetic basis for brown-and-white coat color. This deletion was further validated using PCR and Sanger sequencing of another 192 black giant pandas and CRISPR-Cas9 edited knockout mice. Our investigation revealed that this mutation reduced the number and size of melanosomes of the hairs in knockout mice and possibly in the brown panda, further leading to the hypopigmentation. These findings provide unique insights into the genetic basis of coat color variation in wild animals.


Assuntos
Ursidae , Animais , Camundongos , Ursidae/genética , Peptídeo Hidrolases , Precursor de Proteína beta-Amiloide , Animais Selvagens , Camundongos Knockout
4.
PLoS One ; 19(2): e0296849, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306318

RESUMO

This meta-analysis aims to systematically compare the efficacy between phacoemulsification (PE) combined with goniosynechialysis (GSL) and PE alone for primary angle-closure disease (PACD) patients. All the data were searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was used to evaluate the quality of the included studies. Additionally, this meta-analysis was performed by using the Revman 5.4 software. Nine randomized controlled trials (RCTs) were included in this study. Compared with PE alone group, PE+GSL could result significant reduction in the IOP (MD, 1.81; p = 0.002). In the instrumental subgroup, also more reduction of IOP was shown in the PE+GSL group (MD, 2.11; p = 0.02). In the viscogonioplasty (VGP) subgroup, there was not no statistical difference between PE alone group and PE+GSL group (MD, 1.53; p = 0.11). Also, more reduction of peripheral anterior synechiae (PAS) was shown in the PE+GSL group (MD,59.15; p<0.00001). For the change in angle open distance (AOD)500, AOD 750, trabecular-iris space (TISA)500, number of glaucoma medications and best corrected visual acuity (BCVA), there was no difference between two groups (p = 0.25, 0.35, 0.17, 0.56, 0.08). For TISA 750, more improvement was shown in the PE+GSL group (p<0.00001). Instrumental separation had better effect on lowering IOP when it combined with PE. Both instrumental separation and VGP could reduce postoperative PAS. The operation of GSL has no obvious effect on postoperative vision.


Assuntos
Glaucoma de Ângulo Fechado , Doenças da Íris , Facoemulsificação , Humanos , Malha Trabecular/patologia , Pressão Intraocular , Glaucoma de Ângulo Fechado/complicações , Glaucoma de Ângulo Fechado/cirurgia , Glaucoma de Ângulo Fechado/patologia , Gonioscopia , Aderências Teciduais/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Semin Ophthalmol ; 39(1): 60-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37400160

RESUMO

PURPOSES: The purpose of this meta-analysis is to systematically compare the alignment accuracy and post uncorrected distance visual acuity (UDVA) between image-guided marking and manual marking for toric intraocular lens (IOL) in cataract surgery. METHODS: This work was done through the data searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software. RESULTS: A total of 6 randomized controlled trials (RCTs) were included. Compared with manual marking group, image-guided marking group had less toric IOL axis misalignment (MD, -1.98; 95%CI, -3.27 to -0.68; p = .003), less postoperative astigmatism (MD, -0.13; 95%CI, -0.21 to -0.05; p = .001), better postoperative UDVA (MD, -0.02; 95%CI, -0.04 to -0.01; p = .0003) and smaller difference vector (MD, -0.10; 95%CI, -0.14 to -0.06; p(0.00001). For the proportion of patients with residual refractive cylinder within 0.5 D, there was no difference between two groups (p = .07). CONCLUSION: Image-guided marking is prior to manual marking. As it can bring less toric IOL axis misalignment, less postoperative astigmatism, better postoperative UDVA and smaller difference vector for the patients with toric IOL implantation.


Assuntos
Astigmatismo , Catarata , Lentes Intraoculares , Facoemulsificação , Humanos , Implante de Lente Intraocular , Astigmatismo/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Refração Ocular , Catarata/complicações
6.
BMC Urol ; 23(1): 120, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37452418

RESUMO

BACKGROUND: This study aimed to explore the value of combined serum lipids with clinical symptoms to diagnose prostate cancer (PCa), and to develop and validate a Nomogram and prediction model to better select patients at risk of PCa for prostate biopsy. METHODS: Retrospective analysis of 548 patients who underwent prostate biopsies as a result of high serum prostate-specific antigen (PSA) levels or irregular digital rectal examinations (DRE) was conducted. The enrolled patients were randomly assigned to the training groups (n = 384, 70%) and validation groups (n = 164, 30%). To identify independent variables for PCa, serum lipids (TC, TG, HDL, LDL, apoA-1, and apoB) were taken into account in the multivariable logistic regression analyses of the training group, and established predictive models. After that, we evaluated prediction models with clinical markers using decision curves and the area under the curve (AUC). Based on training group data, a Nomogram was developed to predict PCa. RESULTS: 210 (54.70%) of the patients in the training group were diagnosed with PCa. Multivariate regression analysis showed that total PSA, f/tPSA, PSA density (PSAD), TG, LDL, DRE, and TRUS were independent risk predictors of PCa. A prediction model utilizing a Nomogram was constructed with a cut-off value of 0.502. The training and validation groups achieved area under the curve (AUC) values of 0.846 and 0.814 respectively. According to the decision curve analysis (DCA), the prediction model yielded optimal overall net benefits in both the training and validation groups, which is better than the optimal net benefit of PSA alone. After comparing our developed prediction model with two domestic models and PCPT-RC, we found that our prediction model exhibited significantly superior predictive performance. Furthermore, in comparison with clinical indicators, our Nomogram's ability to predict prostate cancer showed good estimation, suggesting its potential as a reliable tool for prognostication. CONCLUSIONS: The prediction model and Nomogram, which utilize both blood lipid levels and clinical signs, demonstrated improved accuracy in predicting the risk of prostate cancer, and consequently can guide the selection of appropriate diagnostic strategies for each patient in a more personalized manner.


Assuntos
Nomogramas , Neoplasias da Próstata , Masculino , Humanos , Antígeno Prostático Específico , Estudos Retrospectivos , Neoplasias da Próstata/patologia , Biópsia , Fatores de Risco
7.
Entropy (Basel) ; 25(5)2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37238493

RESUMO

Line detection is a fundamental technique in image processing. It can extract the required information, while the information that does not need attention can be ignored, thus reducing the amount of data. At the same time, line detection is also the basis of image segmentation and plays an important role in this process. In this paper, we implement a quantum algorithm based on a line detection mask for novel enhanced quantum representation (NEQR). We build a quantum algorithm for line detection in different directions and design a quantum circuit for line detection. The detailed module designed is also provided. On a classical computer, we simulate the quantum method, and the simulation results prove the feasibility of the quantum method. By analyzing the complexity of quantum line detection, we find that the computation complexity of the proposed method is improved compared to some similar edge detection algorithms.

8.
Foods ; 11(19)2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36230199

RESUMO

The fruit and leaves of mulberry (Morus alba L.) contain a variety of health-beneficial components. At present, although both alcoholic and non-alcoholic mulberry beverages are commercially available, studies on fermented alcoholic beverages mixed with both mulberry fruit and mulberry leaf are rare. In this study, different amounts (1, 2 and 3%, g/mL dry weight) of mulberry leaves were added during the alcoholic fermentation of mulberry juice. After 9 days of fermentation, the 1-deoxynojirimycin (DNJ) content increased from 61.12 ± 3.10 to 153.39 ± 3.98 µg/mL, and the quercetin content increased from 0.45 ± 0.01 to 20.14 ± 0.08 mg/L in the mulberry alcoholic beverages with the addition of mulberry leaves at 2%. Moreover, the ABTS+ scavenging capacity at the end of fermentation for the same sample was enhanced by 40.9%. In addition, the total sugar, total phenols, total anthocyanins, and γ-aminobutyric acid (GABA) contents of the fermented samples all decreased significantly at the end of fermentation. A total of 33 volatile compounds and 17 free amino acids were detected in the fermented alcoholic beverages with mulberry leaves added. The total free amino acid content increased with the increase in mulberry leaf addition. Principal component analysis showed that the addition of mulberry leaves during fermentation increased the contents of GABA, DNJ, total flavonols and protocatechuic acid in mulberry alcoholic beverages. All these studies revealed the dynamic changes in functional components in the alcoholic fermentation of mulberry juices with the addition of mulberry leaves. Overall, the addition of mulberry leaf powder at 2% was selected as the appropriate addition for producing mulberry alcoholic beverages with enhanced nutritional value.

9.
Foods ; 11(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36141001

RESUMO

Lactic acid fermentation is a promising method for developing sandwich seaweed scraps. The objectives of this study were to investigate the effect of fermentation with Lactiplantibacillus plantarum MMB-05, Lactiplantibacillus casei FJAT-7928, mixed bacteria (1:1, v/v) and control on the physicochemical indexes, in vitro antioxidant activity, and volatile compounds of Porphyra yezoensis sauce. Sensory evaluation was also performed. The results indicated that all lactic acid bacteria strains grew well in P. yezoensis sauce after 72 h of fermentation, with the viable cell counts of L. plantarum MMB-05 exceeding 10.0 log CFU/mL, the total phenolic content increasing by 16.54%, and the lactic acid content increasing from 0 to 44.38 ± 0.11 mg/mL. Moreover, the metabolism of these strains significantly increased the content of umami, sweet and sour free amino acids in P. yezoensis sauce. The total antioxidant capacity of L. plantarum MMB-05, L. casei FJAT-7928, mix and control groups increased by 594.59%, 386.49%, 410.27%, and 287.62%, respectively. Gas chromatography-ion mobility spectrometry (GC-IMS) analysis suggested that aldehydes and ketones accounted for the largest proportion, and the relative contents of acids and alcohols in P. yezoensis sauce increased significantly after lactic acid bacteria fermentation. In addition, the analysis of dynamic principal component analysis (PCA) and fingerprinting showed that the volatile components of the four treatment methods could be significantly distinguished. Overall, the L. plantarum MMB-05 could be recommended as an appropriate starter for fermentation of sandwich seaweed scraps, which provides a fundamental knowledge for the utilization of sandwiched seaweed scraps.

10.
Int J Mol Sci ; 23(15)2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35955649

RESUMO

Type III CRISPR-Cas systems show the target (tg)RNA-activated indiscriminate DNA cleavage and synthesis of oligoadenylates (cOA) and a secondary signal that activates downstream nuclease effectors to exert indiscriminate RNA/DNA cleavage, and both activities are regulated in a spatiotemporal fashion. In III-B Cmr systems, cognate tgRNAs activate the two Cmr2-based activities, which are then inactivated via tgRNA cleavage by Cmr4, but how Cmr4 nuclease regulates the Cmr immunization remains to be experimentally characterized. Here, we conducted mutagenesis of Cmr4 conserved amino acids in Saccharolobus islandicus, and this revealed that Cmr4α RNase-dead (dCmr4α) mutation yields cell dormancy/death. We also found that plasmid-borne expression of dCmr4α in the wild-type strain strongly reduced plasmid transformation efficiency, and deletion of CRISPR arrays in the host genome reversed the dCmr4α inhibition. Expression of dCmr4α also strongly inhibited plasmid transformation with Cmr2αHD and Cmr2αPalm mutants, but the inhibition was diminished in Cmr2αHD,Palm. Since dCmr4α-containing effectors lack spatiotemporal regulation, this allows an everlasting interaction between crRNA and cellular RNAs to occur. As a result, some cellular RNAs, which are not effective in mediating immunity due to the presence of spatiotemporal regulation, trigger autoimmunity of the Cmr-α system in the S. islandicus cells expressing dCmr4α. Together, these results pinpoint the crucial importance of tgRNA cleavage in autoimmunity avoidance and in the regulation of immunization of type III systems.


Assuntos
Proteínas Associadas a CRISPR , Sulfolobus , Autoimunidade/genética , Proteínas Associadas a CRISPR/genética , Sistemas CRISPR-Cas/genética , RNA/genética , Clivagem do RNA , Sulfolobus/genética
11.
Micromachines (Basel) ; 13(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36014111

RESUMO

This paper presents the design, simulation, fabrication, assembly, and testing of a miniature thermo-pneumatic optofluidic lens. The device comprises two separate zones for air heating and fluid pressing on a flexible membrane. A buried three-dimensional spiral microchannel connects the two zones without pumps or valves. The three-dimensional microfluidic structure is realized using a high-resolution three-dimensional printing technique. Multi-physics finite element simulations are introduced to assess the optimized air chamber design and the low-temperature gradient of the optical liquid. The tunable lens can be operated using a direct-current power supply. The temperature change with time is measured using an infrared thermal imager. The focal length ranges from 5 to 23 mm under a maximum voltage of 6 V. Because of the small size and robust actuation scheme, the device can potentially be integrated into miniature micro-optics devices for the fine-tuning of focal lengths.

12.
Mol Biol Rep ; 49(8): 7455-7464, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35624389

RESUMO

BACKGROUND: Stomata, which play important roles in both optimizing photosynthesis efficiency and adapting to stress, are closely related to IAA and ABA. In plants, the auxin influx carrier LAX3 has been found to play roles in development and stress tolerance. However, the function of LAX3 in stomata and in response to salt stress remains largely unknown. METHODS AND RESULTS: Here, we show that overexpression of wheat TaLAX3-1B in tobacco results in a decrease in stomatal aperture and a relatively closed state of the stomata. In addition, the stomatal movement of the OxTaLAX3-1B lines was less sensitive to ABA than that of the WT. Consistently, compared with the WT, the OxTaLAX3-1B lines showed significantly higher expression of stomate-, IAA- and ABA-related genes and endogenous IAA and ABA contents. Furthermore, compared with the WT, the OxTaLAX3-1B lines exhibited higher proline content, salt stress-related gene expression and ROS antioxidant enzyme activity but lower MDA content and ROS accumulation after salt treatment. CONCLUSIONS: The present results suggest that TaLAX3-1B plays a positive role in regulating stomatal closure and enhancing salt stress tolerance.


Assuntos
Regulação da Expressão Gênica de Plantas , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Secas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Salino/genética , Estresse Fisiológico/genética , /metabolismo
13.
Mol Biol Evol ; 39(6)2022 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-35599233

RESUMO

Incorrect species delimitation will lead to inappropriate conservation decisions, especially for threatened species. The takin (Budorcas taxicolor) is a large artiodactyl endemic to the Himalayan-Hengduan-Qinling Mountains and is well known for its threatened status and peculiar appearance. However, the speciation, intraspecies taxonomy, evolutionary history, and adaptive evolution of this species still remain unclear, which greatly hampers its scientific conservation. Here, we de novo assembled a high-quality chromosome-level genome of takin and resequenced the genomes of 75 wild takins. Phylogenomics revealed that takin was positioned at the root of Caprinae. Population genomics based on the autosome, X chromosome, and Y chromosome SNPs and mitochondrial genomes consistently revealed the existence of two phylogenetic species and recent speciation in takins: the Himalayan takin (B. taxicolor) and the Chinese takin (B. tibetana), with the support of morphological evidence. Two genetically divergent subspecies were identified in both takin species, rejecting three previously proposed taxonomical viewpoints. Furthermore, their distribution boundaries were determined, suggesting that large rivers play important roles in shaping the genetic partition. Compared with the other subspecies, the Qinling subspecies presented the lowest genomic diversity, higher linkage disequilibrium, inbreeding, and genetic load, thus is in urgent need of genetic management and protection. Moreover, coat color gene (PMEL) variation may be responsible for the adaptive coat color difference between the two species following Gloger's rule. Our findings provide novel insights into the recent speciation, local adaptation, scientific conservation of takins, and biogeography of the Himalaya-Hengduan biodiversity hotspot.


Assuntos
Genoma Mitocondrial , Ruminantes , Animais , Espécies em Perigo de Extinção , Especiação Genética , Genômica , Filogenia , Ruminantes/genética
14.
Mol Pain ; 18: 17448069221089596, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35266830

RESUMO

Calcium-dependent, neuronal adenylyl cyclase subtype 1 (AC1) is critical for cortical potentiation and chronic pain. NB001 is a first-in-class drug acting as a selective inhibitor against AC1. The present study delineated the pharmacokinetic (PK) properties of human-used NB001 (hNB001) formulated as immediate-release tablet. This first-in-human (FIH) study was designed as randomized, double-blind, placebo-controlled trial. hNB001 showed placebo-like safety and good tolerability in healthy volunteers. A linear dose-exposure relationship was demonstrated at doses between 20 mg and 400 mg. The relatively small systemic exposure of hNB001 in human showed low bioavailability of this compound through oral administration, which can be improved through future dosage research. Food intake had minimal impact on the absorption of hNB001 tablet. Animal experiments further confirmed that hNB001 had strong analgesic effect in animal models of neuropathic pain. In brain slice prepared from the anterior cingulate cortex (ACC), bath application of hNB001 blocked the induction of long-term potentiation (LTP). These results from both rodents and human strongly suggest that hNB001 can be safely used for the future treatment of different types of chronic pain in human patients.


Assuntos
Trifosfato de Adenosina , Inibidores de Adenilil Ciclases , Adenilil Ciclases , Dor Crônica , Neuralgia , Trifosfato de Adenosina/administração & dosagem , Trifosfato de Adenosina/efeitos adversos , Trifosfato de Adenosina/análogos & derivados , Inibidores de Adenilil Ciclases/administração & dosagem , Inibidores de Adenilil Ciclases/efeitos adversos , Adenilil Ciclases/metabolismo , Dor Crônica/tratamento farmacológico , Dor Crônica/enzimologia , Giro do Cíngulo/metabolismo , Humanos , Neuralgia/tratamento farmacológico , Neuralgia/enzimologia
15.
BMC Vet Res ; 18(1): 23, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996430

RESUMO

BACKGROUND: Semen cryopreservation has become an essential tool for conservation efforts of the giant panda (Ailuropoda melanoleuca); however, it is severely detrimental to sperm quality. Evidence has shown that antioxidants have the potential to reverse cryopreservation-induced damage in sperm. The purpose of this study was to screen effective antioxidants that could retain sperm quality during cryopreservation and to determine the optimal dose. Seven antioxidant groups, including resveratrol (RSV = 50 µM, RSV = 100 µM, RSV = 150 µM), lycium barbarum polysaccharide (LBP = 2 mg/mL, LBP = 4 mg/mL), laminaria japonica polysaccharides (LJP = 1 mg/mL) or combination (LBP = 2 mg/mL, LJP = 1 mg/mL and RSV = 100 µM) were assessed. RESULTS: RSV, LBP, LJP, or a combination of RSV, LBP, and LJP added to the freezing medium significantly improved sperm progressive motility, plasma membrane integrity, acrosome integrity, and mitochondrial activity during the cryopreservation process. Furthermore, the activities of glutathione peroxidase and superoxide dismutase were also improved. The levels of reactive oxygen species and malondialdehyde in semen were notably reduced. Hyaluronidase activity and acrosin activity were significantly increased in LBP-treated sperm. However, sperm total motility and DNA integrity were not significantly different between the groups. CONCLUSIONS: RSV (50 µM) or LBP (2 mg/mL) are the best candidate antioxidants for inclusion in the freezing medium to improve the quality of giant panda spermatozoa during semen cryopreservation.


Assuntos
Criopreservação , Medicamentos de Ervas Chinesas , Preservação do Sêmen , Espermatozoides , Ursidae , Animais , Antioxidantes , Criopreservação/veterinária , Masculino , Resveratrol/farmacologia , Análise do Sêmen/veterinária , Preservação do Sêmen/veterinária
16.
Medicine (Baltimore) ; 101(51): e32318, 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36595851

RESUMO

BACKGROUND: Bladder cancer (BC) is among the most frequent cancers globally. Although substantial efforts have been put to understand its pathogenesis, its underlying molecular mechanisms have not been fully elucidated. METHODS: The robust rank aggregation approach was adopted to integrate 4 eligible bladder urothelial carcinoma microarray datasets from the Gene Expression Omnibus. Differentially expressed gene sets were identified between tumor samples and equivalent healthy samples. We constructed gene co-expression networks using weighted gene co-expression network to explore the alleged relationship between BC clinical characteristics and gene sets, as well as to identify hub genes. We also incorporated the weighted gene co-expression network and robust rank aggregation to screen differentially expressed genes. RESULTS: CDH11, COL6A3, EDNRA, and SERPINF1 were selected from the key module and validated. Based on the results, significant downregulation of the hub genes occurred during the early stages of BC. Moreover, receiver operating characteristics curves and Kaplan-Meier plots showed that the genes exhibited favorable diagnostic and prognostic value for BC. Based on gene set enrichment analysis for single hub gene, all the genes were closely linked to BC cell proliferation. CONCLUSIONS: These results offer unique insight into the pathogenesis of BC and recognize CDH11, COL6A3, EDNRA, and SERPINF1 as potential biomarkers with diagnostic and prognostic roles in BC.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Redes Reguladoras de Genes
17.
Front Vet Sci ; 8: 759283, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869731

RESUMO

Cystic echinococcosis (CE) is a cosmopolitan zoonosis caused by the larval stage of Echinococcus granulosus, which affects humans and a wide range of mammalian intermediate hosts. Parasite tetraspanin proteins are crucial for host-parasite interactions, and therefore they may be useful for vaccine development or disease diagnosis. In the present study, the major antigen coding sequence of tetraspanin 11 (Eg-TSP11) from E. granulosus was determined. The results of immunolocalization showed that Eg-TSP11 was mainly located in the tegument of adult worms and protoscoleces. Western blotting analysis showed that the serum from dogs injected with recombinant Eg-TSP11 (rEg-TSP11) could recognize Eg-TSP11 among natural protoscolex proteins. Moreover, the serum from dogs with E. granulosus infection also recognized rEg-TSP11. Serum indirect enzyme-linked immunosorbent assays demonstrated that IgG levels gradually increased after the first immunization with rEg-TSP11 compared with those in the control group. Furthermore, the serum levels of interleukin 4, interleukin 5, and interferon gamma were significantly altered in the rEg-TSP11 group. Importantly, we found that vaccination with rEg-TSP11 significantly decreased worm burden and inhibited segment development in a dog model of E. granulosus infection. Based on these findings, we speculated that rEg-TSP11 might be a potential candidate vaccine antigen against E. granulosus infection in dogs.

18.
Medicine (Baltimore) ; 100(38): e27244, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559125

RESUMO

ABSTRACT: It has been reported that inflammation and immune system are related to prostate cancer. The neutrophil-to-lymphocyte ratio (NLR), as well as the platelet-to-lymphocyte ratio (PLR), have already been proposed as new indices to help diagnose prostate cancer (PCa). However, the monocyte-to-lymphocyte ratio (MLR) with regard to PCa has rarely been mentioned.To investigate the capability of the MLR to predict PCa.Patients who were pathologically diagnosed with PCa in our hospital and healthy control subjects who conformed to the inclusion criteria were enrolled. Patient data were recorded, including age, complete blood counts, blood biochemistry, and serum prostate-specific antigen (PSA) levels. The differences in these data between the groups were analyzed and the diagnostic value of the MLR was compared with PSA.Our study included a total of 100 patients with PCa and 103 healthy control subjects. Patients with PCa presented with a significantly higher NLR, MLR, and PLR compared to control subjects. However, the hemoglobin and lymphocyte levels were lower (P < .05) in PCa patients. The area under the curve (AUC) of PSA and ratio of free/total serum prostate-specific antigen were 0.899 (95% confidence interval [CI]: 0.857-0.942) and 0.872 (95% CI: 0.818-0.926), respectively, while the AUC of the MLR was 0.852 (95% CI: 0.798-0.906), which was higher than that of the NLR, PLR, and any other blood parameters. Additionally, the optimal cut-off value of the MLR for PCa was 0.264, with a specificity of 87.4% and a sensitivity of 72.0%. An evaluation of the diagnostic value of MLR + PSA gave an AUC of 0.936 (95% CI: 0.902-0.970). However, the AUC of MLR + PSA + f/tPSA was 0.996 (95% CI: 0.991-1.000). The diagnostic value of MLR + NLR + PSA gave an AUC of 0.945 (95% CI: 0.913-0.977), and the specificity is 0.971.PSA remains the most important diagnostic indicator. MLR combined with PSA and f/tPSA has the higher predictive value than PSA. It suggests that MLR may be another good predictive indicator of PCa. It can help reduce the clinical false positive rate.


Assuntos
Linfócitos , Monócitos , Valor Preditivo dos Testes , Neoplasias da Próstata/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Humanos , Contagem de Leucócitos/métodos , Contagem de Leucócitos/estatística & dados numéricos , Masculino , Prognóstico , Neoplasias da Próstata/sangue , Estudos Retrospectivos
19.
Parasit Vectors ; 14(1): 489, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556147

RESUMO

BACKGROUND: Cystic echinococcosis (CE) is a serious parasitic zoonosis caused by the larvae of the tapeworm Echinococcus granulosus. The development of an effective vaccine is one of the most promising strategies for controlling CE. METHODS: The E. granulosus 3-hydroxyacyl-CoA dehydrogenase (EgHCDH) gene was cloned and expressed in Escherichia coli. The distribution of EgHCDH in protoscoleces (PSCs) and adult worms was analyzed using immunofluorescence. The transcript levels of EgHCDH in PSCs and adult worms were analyzed using quantitative real-time reverse transcription PCR (RT-qPCR). The immune protective effects of the rEgHCDH were evaluated. RESULTS: The 924-bp open reading frame sequence of EgHCDH, which encodes a protein of approximately 34 kDa, was obtained. RT-qPCR analysis revealed that EgHCDH was expressed in both the PSCs and adult worms of E. granulosus. Immunofluorescence analysis showed that EgHCDH was mainly localized in the tegument of PSCs and adult worms. Western blot analysis showed that the recombinant protein was recognized by E. granulosus-infected dog sera. Animal challenge experiments demonstrated that dogs immunized with recombinant (r)EgHCDH had significantly higher serum IgG, interferon gamma and interleukin-4 concentrations than the phosphate-buffered saline (PBS) control group. The rEgHCDH vaccine was able to significantly reduce the number of E. granulosus and inhibit the segmental development of E. granulosus compared to the PBS control group. CONCLUSIONS: The results suggest that rEgHCDH can induce partial immune protection against infection with E. granulosus and could be an effective candidate for the development of new vaccines.


Assuntos
3-Hidroxiacil-CoA Desidrogenase/imunologia , Doenças do Cão/parasitologia , Equinococose/veterinária , Echinococcus granulosus/enzimologia , Proteínas de Helminto/imunologia , 3-Hidroxiacil-CoA Desidrogenase/genética , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Doenças do Cão/sangue , Doenças do Cão/imunologia , Cães , Equinococose/sangue , Equinococose/imunologia , Equinococose/parasitologia , Echinococcus granulosus/genética , Echinococcus granulosus/imunologia , Feminino , Imunofluorescência , Proteínas de Helminto/genética , Humanos , Imunização , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos Endogâmicos BALB C
20.
Appl Opt ; 60(18): 5302-5311, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34263767

RESUMO

Fluidic lenses based on electrowetting actuation are attractive for their wide focal tuning range, yet are limited by optical aberrations, either intrinsic to the lenses themselves or due to the optical imaging systems in which they are employed. However, the ability to control the meniscus shape that forms the lens refractive surface with a high degree of spatial accuracy will allow correction of and compensation for a wide range of these aberrations. We demonstrate here for what we believe, to the best of our knowledge, is the first time a tunable optofluidic lens controlled by 32 azimuthally placed electrodes for which most aberrations up to the fourth radial Zernike order may be corrected. Using both wavefront sensing and sensorless wavefront estimation techniques, it is shown that focal length tunability with a significant reduction in imaging aberrations and the ability to compensate for externally induced aberrations may be achieved using a single component.

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