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1.
Front Immunol ; 13: 911164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935962

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines provide essential tools for the control of the COVID-19 pandemic. A number of technologies have been employed to develop SARS-CoV-2 vaccines, including the inactivated SARS-CoV-2 particles, mRNA to express viral spike protein, recombinant spike proteins, and viral vectors. Here, we report the use of the vaccinia virus Tiantan strain as a vector to express the SARS-CoV-2 spike protein. When it was used to inoculate mice, robust SARS-CoV-2 spike protein-specific antibody response and T-cell response were detected. Sera from the vaccinated mice showed strong neutralizing activity against the ancestral Wuhan SARS-CoV-2, the variants of concern (VOCs) B.1.351, B.1.617.2, and the emerging B.1.1.529 (omicron). This finding supports the possibility of developing a new type of SARS-CoV-2 vaccine using the vaccinia virus vector.


Assuntos
COVID-19 , Vacinas Virais , Animais , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Camundongos , Pandemias , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus , Vírus Vaccinia/genética
2.
Comput Math Methods Med ; 2022: 4614665, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936357

RESUMO

The decline in sheep health and meat quality caused by seasonal nutritional deficiencies has always been an important problem in the production of naturally grazing sheep. Glucose metabolism is crucial in ruminants for adequate cell function and maintenance of the body tissues and systems. However, whether glucose metabolism, especially gluconeogenesis, is affected by seasonal grazing conditions has not been fully uncovered. Thus, twelve sheep from two seasons (dry and green grass periods) in natural grazing areas of Inner Mongolia, China, were selected for this study. Their serum glucose, insulin, PC, and PEPCK levels and volatile fatty acid (gluconeogenesis material) concentrations in rumen fluid were analyzed. The expression of key enzymes including PC, PEPCK, GLUT2, and G6P of gluconeogenesis and their regulators INSR, PI3K/AKT and p53-SIRT6-Fox01 in the liver was detected by real-time PCR and western blotting. The results revealed significant variances in gluconeogenesis and its indicators and showed p53-SIRT6-Fox01 as having potential regulation in different grazing periods. This study offers new insights into the mechanism of gluconeogenesis and adaptive regulation between dry grass period and green grass period and also provides a reference for maintaining the health of sheep and meat quality despite seasonal nutritional deficiencies.


Assuntos
Desnutrição , Sirtuínas , Animais , Gluconeogênese/fisiologia , Glucose , Fígado/metabolismo , Desnutrição/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ovinos , Sirtuínas/metabolismo , Proteína Supressora de Tumor p53/genética
3.
Front Endocrinol (Lausanne) ; 13: 869579, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937795

RESUMO

Objective: Metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are the leading chronic diseases worldwide. There are still many controversies about the association between serum bilirubin and MetS or NAFLD. This study aims to evaluate the association of serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) with MetS and NAFLD. Methods: Multiple databases were searched for relevant studies until November 2021. Randomized controlled trials, cross-sectional and cohort studies evaluating the association between serum bilirubin levels and MetS or NAFLD were included. Results: Twenty-four cross-sectional and cohort studies with 101, 517 participants were finally analyzed. Fifteen studies and 6 studies evaluated the association between bilirubin and MetS or NAFLD in health screening population, respectively, while 3 studies evaluated the association between bilirubin and non-alcoholic steatohepatitis (NASH) in NAFLD patients. Random effect model analysis showed the inverse association between TBIL and MetS in male (95%CI=0.71-0.96) and gender-neutral (95%CI=0.61-0.91) group. However, no significant association was found in females. Notably, the inverse association between DBIL and MetS was noticed in male (95%CI=0.36-0.75), female (95%CI=0.16-0.58) and gender-neutral population (95%CI=0.67-0.92). IBIL level was inversely associated with MetS in females (95%CI=0.52-0.96), whereas no statistical correlation presented in males. TBIL was not statistically correlated with NAFLD in gender-neutral or male subgroup. Similarly, there were no association between DBIL or IBIL and NAFLD in gender-neutral subgroup. However, the negative correlation between DBIL and NAFLD existed in males (95%CI=0.76-0.96). In NAFLD patients, IBIL analysis showed an inverse association with NASH (95%CI=0.01-0.12). Conclusion: Serum TBIL and DBIL levels, especially DBIL levels, assume an inverse correlation with MetS in healthy population. Serum IBIL is inversely associated with the onset and degree of NASH in NAFLD patients. Exogenous bilirubin supplement may be a potential strategy to assist in lowering the risk of developing MetS and NAFLD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021293349.


Assuntos
Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Bilirrubina , Estudos Transversais , Feminino , Humanos , Testes de Função Hepática , Masculino , Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia
4.
Virus Res ; : 198882, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35934258

RESUMO

To date, a total of seven human coronaviruses (HCoVs) have been identified, all of which are important respiratory pathogens. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has led to a global pandemic causing millions of infections and deaths. Here, we summarize the discovery and fundamental virology of HCoVs, discuss their zoonotic transmission and highlight the weak species barrier of SARS-CoV-2. We also discuss the possible origins of SARS-CoV-2 variants of concern identified to date and discuss the experimental challenges in characterizing mutations of interest and propose methods to circumvent them. As the COVID-19 treatment and prevention landscape rapidly evolves, we summarize current therapeutics and vaccines, and their implications on SARS-CoV-2 variants. Finally, we explore how interspecies transmission of SARS-CoV-2 may drive the emergence of novel strains, how disease severity may evolve and how COVID-19 will likely continue to burden healthcare systems globally.

5.
Comput Struct Biotechnol J ; 20: 3911-3923, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35950187

RESUMO

Increasing evidence has confirmed that cancer-associated fibroblasts (CAFs) recruit and induce regulatory T cells (Tregs) and macrophages but inhibit cytotoxic T lymphocyte infiltration to a certain extent, indicating that CAFs have a significant influence on the immunosuppressive microenvironment. However, the effect of CAFs on the immune microenvironment and immunotherapy response in pancreatic cancer remains unclear. Our research identified remarkable variation in CAF-associated molecules in multiple cancer types at the genetic and transcriptome levels. Two phenotypes were identified for 476 pancreatic cancer samples, and the different phenotypes exhibited significant variation in immune and inflammatory characteristics. Phenotype 1 exhibited higher levels of immune infiltration and lower expression of tumor-associated gene signatures than phenotype 2. We used a multipart approach to assess the prognostic value of CAF-associated molecules and constructed a CAF score model that could accurately predict patient prognosis. The CAF score accurately predicted infiltrating immune cell abundance, chemosensitivity, and the response to immunotherapy. Additionally, we found that the CAF-associated molecule FGFR4 may promote the proliferation and migration and inhibit the apoptosis of pancreatic cancer cells and is correlated with immune infiltration, suggesting its potential role as an oncogene. CAFs may promote the malignant biological behavior of pancreatic cancer through FGFR4. In summary, our research highlights potential relationships of the dysregulation of CAF-associated molecules with genome alterations and carcinogenesis in multiple malignancies. Our CAF-associated phenotypes and scoring system may enhance the understanding of pancreatic cancer chemotherapy sensitivity and immunotherapy response, providing new insights for personalized chemotherapy and immunotherapy.

6.
Foods ; 11(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35954051

RESUMO

Paper packaging materials are widely used in food packaging. However, it is difficult to extract trace chloropropanol from food packaging paper, so there is a lack of research on the leaching of chloropropanol from paper materials. Therefore, it is of positive significance to explore the leaching rule of chloropropanol in paper pulp for the safety of paper packaging materials, to reduce the risk of food packaging to food safety and to provide a theoretical basis for the formulation of safety standards for paper packaging materials. In order to study the content of chloropropanol in paper packaging paper more accurately, a response surface methodology was used to study the relationship between the amount of chloropropanol leaching and pulp concentration, leaching temperature and leaching time, as well as the interaction of each factor. The results showed that time, temperature and pulp concentration were the main factors affecting the leaching amount of chloropropanol from paper packaging materials. There were significant (p > 0.05) interactions between the time and pulp concentration, as well as temperature and pulp concentration. The leaching efficiency of chloropropanol was higher at a lower pulp concentration, and the leaching amount of chloropropanol was higher at a lower temperature. The temperature more significantly affected the leaching of chloropropanol in a low-concentration system than in a high-concentration system. Relevant studies have shown that the selection of solvent has an important effect on the extraction rate of target compounds. Therefore, in this experiment, different polar organic solvents (methanol, ethanol, formaldehyde solution) were added into the soaking solution to change the leaching amount of chloropropanol. The results showed that adding a certain amount of formaldehyde solution can obviously increase the leaching amount of chloropropanol in pulp.

7.
Int J Mol Sci ; 23(15)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35955757

RESUMO

Hemicellulose is a major component of the complex biomass recalcitrance structure of fiber cell walls. Even though biomass recalcitrance protects plants, it affects the effective utilization of lignocellulosic biomass resources. Therefore, the separation and extraction of hemicellulose is very important. In this study, an improved two-step alkali pretreatment method was proposed to separate hemicellulose efficiently. Firstly, 16.61% hemicellulose was extracted from bamboo by the weak alkali treatment. Then, the physical freezing and the alkali treatment were carried out by freezing at -20 °C for 12.0 h and thawing at room temperature, heating to 80 °C, and treating with 5.0% sodium hydroxide for 90 min; the extraction yield of hemicellulose reached 73.93%. The total extraction yield of the two steps was 90.54%, and the molecular weight and purity reached 44,865 g·mol-1 and 89.60%, respectively. It provides a new method for breaking the biomass recalcitrance of wood fiber resources and effectively extracting hemicellulose.

8.
Polymers (Basel) ; 14(15)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35956673

RESUMO

At present, the synthesis methods of crystalline porous materials often involve powder products, which not only affects the practical application but also has complex synthesis operations and limited scale. Based on the mechanochemical method, we choose COF-TpPa-1, preparing TpPa-1-DANC composites. Covalent organic frameworks (COFs) are a kind of crystalline material formed by covalent bonds of light elements. COFs possess well pore structure and high thermal stability. However, the state of synthesized powders limits their application. Cellulose nanocrystals (CNCs) are promising renewable micron materials with abundant hydroxyl groups on their surface. It is possible to prepare high-strength materials such as film, water, and aerogel. Firstly, the nanocellulose was oxidized by the sodium periodate method to obtain aldehyde cellulose nanocrystals (DANC). TpPa-1-DANC not only had the crystal characteristic peak of COFs at 2θ ≈ 5° but also had a BET surface area of 247 m2/g. The chemical bonds between COFs and DANC formed by Schiff base reaction appeared in FTIR and XPS. The pyrolysis behavior of the composite was characterized by TG-IR, which showed that the composite had good thermal stability. With the advantages of nanocellulose as a material in every dimension, we believe that this method can be conducive to the large-scale synthesis of COFs composites, and has the possibility of multi-form synthesis of COFs.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35960698

RESUMO

This study aims to systematically evaluate the efficacy of endoscopic resection (ER), laparoscopic resection (LR), laparoscopic endoscopic cooperative surgery (LECS), and open surgery (OpS) for gastrointestinal stromal tumors with small diameters (≤5 cm). Relevant studies were collected through Pubmed, Cochrane Library, and Embase databases. Operative time, hospital stays, time to liquid diet, intraoperative bleeding, and complications were used as outcome indicators for meta-analysis. Twenty-four retrospective cohort studies with 2406 participants were analyzed. LR and OpS groups had longer operating time than the ER group. ER, LECS, and LR groups had decreased lengths of hospital stay than the OpS group. Moreover, patients in LR and LECS groups had fewer complications than those in the OpS group. Endoscopic operation for small gastrointestinal stromal tumors contributes to shortened lengths of surgery and hospital stay. This reduces intraoperative blood loss and promotes gastroenteric functional recovery without increasing the risk of complications or tumor recurrence.

10.
Front Genet ; 13: 881948, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35938042

RESUMO

Background : Owing to complex molecular mechanisms in gastric cancer (GC) oncogenesis and progression, existing biomarkers and therapeutic targets could not significantly improve diagnosis and prognosis. This study aims to identify the key genes and signaling pathways related to GC oncogenesis and progression using bioinformatics and meta-analysis methods. Methods: Eligible microarray datasets were downloaded and integrated using the meta-analysis method. According to the tumor stage, GC gene chips were classified into three groups. Thereafter, the three groups' differentially expressed genes (DEGs) were identified by comparing the gene data of the tumor groups with those of matched normal specimens. Enrichment analyses were conducted based on common DEGs among the three groups. Then protein-protein interaction (PPI) networks were constructed to identify relevant hub genes and subnetworks. The effects of significant DEGs and hub genes were verified and explored in other datasets. In addition, the analysis of mutated genes was also conducted using gene data from The Cancer Genome Atlas database. Results: After integration of six microarray datasets, 1,229 common DEGs consisting of 1,065 upregulated and 164 downregulated genes were identified. Alpha-2 collagen type I (COL1A2), tissue inhibitor matrix metalloproteinase 1 (TIMP1), thymus cell antigen 1 (THY1), and biglycan (BGN) were selected as significant DEGs throughout GC development. The low expression of ghrelin (GHRL) is associated with a high lymph node ratio (LNR) and poor survival outcomes. Thereafter, we constructed a PPI network of all identified DEGs and gained 39 subnetworks and the top 20 hub genes. Enrichment analyses were performed for common DEGs, the most related subnetwork, and the top 20 hub genes. We also selected 61 metabolic DEGs to construct PPI networks and acquired the relevant hub genes. Centrosomal protein 55 (CEP55) and POLR1A were identified as hub genes associated with survival outcomes. Conclusion: The DEGs, hub genes, and enrichment analysis for GC with different stages were comprehensively investigated, which contribute to exploring the new biomarkers and therapeutic targets.

11.
Eye Contact Lens ; 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35916882

RESUMO

ABSTRACT: We present a case of ametropia corrected by small incision lenticule extraction (SMILE) in a corectopia eye after cataract surgery. The patient's optical zone, nomogram, and centration were carefully considered. The intended corrections were -6.60 - 1.25 × 175 OD and -6.85 - 0.50 × 10 OS. M-sized and S-sized cones were recorded in the right and left eye, respectively. The diameter of the right eye optical zone was 7.00 mm, whereas that of the left eye was 6.50 mm. The corneal vertex was determined using the film mark method as the scanning center. Three months after surgery, the uncorrected distance visual acuities were 20/20 OD and 20/13 OS. The effective optical zone was 6.5 and 5.5 mm in the right and left eyes, respectively. It is feasible to correct ametropia with SMILE in patients with corectopia after intraocular lens implantation. The large optical zone will compensate for the visual disturbance.

12.
Bioresour Technol ; 361: 127735, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35934248

RESUMO

The selectivity of alkali treatment (AT) for hemicellulose separation is reduced due to the alkali solubility of lignin. It was improved using freeze-thaw-assisted alkaline treatment (FT/AT). In this study, bamboo hemicellulose was separated via a one-step freeze-thaw-assisted alkali treatment (OFT/AT). The effects of freezing temperature, freezing time, alkali concentration, and treatment time on bamboo components were studied. The separation yield of hemicellulose was 73.26%, compared to 64.00% using conventional FT/AT. The separation of lignin and cellulose was inhibited as alkali concentration decreased from 7.0% to 5.0%. The extraction yield of hemicellulose increased from 46.35% to 56.12%. Structural analysis of extracted hemicellulose revealed the effective inhibition of the breakage of the xylose backbone and arabinose side chain of hemicellulose. This indicated that the molecular structure of extracted hemicellulose was relatively complete. It provides theoretical support for the efficient separation of hemicellulose by AT.

13.
Bioresour Technol ; 360: 127621, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35842067

RESUMO

In fact, effectively removing lignin from pulp fibers facilitates the conversion and utilization of cellulose. In this study, the residual lignin in eucalyptus pulp was separated using a high concentration of chlorine dioxide. The effects of chlorine dioxide dosage, temperature, and time on lignin removal were investigated. The optimal conditions are chlorine dioxide dosage 5.0%, reaction temperature 40 °C, and reaction time 30 min. The lignin removal yield is 88.21%. The removal yields of cellulose and hemicellulose are 2.28 and 17.00%, respectively. The treated eucalyptus pulp has higher fiber crystallinity and thermal stability. The carbon content on the fiber surface is significantly reduced. The results show that lignin is removed by efficient oxidation, and the degradation of carbohydrates is inhibited using high concentrations of chlorine dioxide at low temperatures and short reaction times. This provides theoretical support for high value conversion of cellulose.

14.
Int J Mol Sci ; 23(14)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35886851

RESUMO

The treatment of oily sludge (OS) can not only effectively solve environmental pollution but also contribute to the efficient use of energy. In this study, the separation effect of OS was analyzed through sodium lignosulfonate (SL)-assisted sodium persulfate (S/D) treatment. The effects of SL concentration, pH, temperature, solid-liquid ratio, revolving speed, and time on SL adsorption solubilization were analyzed. The effects of sodium persulfate dosage, demulsification temperature, and demulsification time on sodium persulfate oxidative demulsification were analyzed. The oil removal efficiency was as high as 91.28%. The results showed that the sediment was uniformly and finely distributed in the S/D-treated OS. The contact angle of the sediment surface was 40°, and the initial apparent viscosity of the OS was 56 Pa·s. First, the saturated hydrocarbons and aromatic hydrocarbons on the sediment surface were adsorbed by the monolayer adsorption on SL. Stubborn, cohesive oil agglomerates were dissociated. Sulfate radical anion (SO4-·) with a high oxidation potential, was formed from sodium persulfate. The oxidation reaction occurred between SO4-· and polycyclic aromatic hydrocarbons. A good three-phase separation effect was attained. The oil recovery reached 89.65%. This provides theoretical support for the efficient clean separation of oily sludge.


Assuntos
Petróleo , Adsorção , Hidrocarbonetos , Óleos , Esgotos
15.
Front Psychol ; 13: 901247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837627

RESUMO

Objective: The impact of the mindfulness-based stress reduction (MBSR) program on psychological outcomes and quality of life (QoL) in lung cancer patients remains unclear. This meta-analysis aimed to evaluate the effectiveness of the MBSR program on psychological states and QoL in lung cancer patients. Methods: Eligible studies published before November 2021 were systematically searched from PubMed, EMBASE, Cochrane Library, PsycINFO, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The risk of bias in eligible studies was assessed using the Cochrane tool. Psychological variables and QoL were evaluated as outcomes. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to grade the levels of evidence. Statistical analysis was conducted using RevMan 5.4 and STATA 14.0. Results: A total of 17 studies involving 1,680 patients were included for meta-analysis eventually. MBSR program significantly relieved cancer-related fatigue (standard mean difference [SMD], -1.26; 95% confidence interval [CI], -1.69 to -0.82; moderate evidence) and negative psychological states (SMD, -1.35; 95% CI, -1.69 to -1.02; low evidence), enhanced positive psychological states (SMD, 0.91; 95% CI, 0.56-1.27; moderate evidence), and improved quality of sleep (MD, -2.79; 95% CI, -3.03 to -2.56; high evidence). Evidence on MBSR programs' overall treatment effect for QoL revealed a trend toward statistical significance (p = 0.06, low evidence). Conclusion: Based on our findings, the MBSR program shows positive effects on psychological states in lung cancer patients. This approach should be recommended as a part of the rehabilitation program for lung cancer patients. Systematic Review Registration: https://archive.org/details/osf-registrations-mwvbq-v1, identifier: 10.17605/OSF.IO/MWVBQ.

16.
J Colloid Interface Sci ; 626: 995-1002, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35839680

RESUMO

Rational design of low-cost and efficient electrocatalyst for the anodic oxygen evolution reaction (OER) to replace noble-metal-based catalysts is greatly desired for the large-scale application of water electrocatalysis. And compared with the conventional powdery catalysts, the freestanding electrode architecture is more attractive owing to the enhanced kinetics and stability. In this work, we report an electrospinning-carbonization-post oxidation strategy to develop the freestanding N-doped carbon nanofibers anchored with Ni/NiO nanoparticles (denoted as Ni/NiO-NCNFs) as efficient OER electrocatalyst. In the synthesized Ni/NiO-NCNFs, the conductive ultrathin carbon layer could promote electron transfer and thus improve the electrocatalytic activity. Meanwhile, the ratio between Ni and NiO could be regulated by tuning the oxidation duration, so as to optimize the adsorption energy of intermediates and improve the OER activity. The Ni/NiO-NCNFs prepared with the oxidation time of 3 h exhibit a promising OER activity and long-term operation durability in 0.1 M KOH solution, requiring an overpotential as small as 153 mV to achieve a current density of 10 mA cm-2. Its overpotential is far lower than that of the reported OER catalysts. This work offers an efficient pathway to develop low-cost and highly active freestanding transitional metal-based OER electrocatalyst for potential renewable electrochemical energy conversion.

17.
Biomaterials ; 287: 121682, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35870264

RESUMO

Adenosine triphosphate (ATP) is an essential substance for maintaining tumor cell survival and proliferation. Inhibiting the ATP-producing pathways has emerged as a promising cancer treatment strategy. However, the antitumor efficiency of ATP inhibitors is compromised by the inter-compensation of multiple ATP-producing pathways in tumor cells and biological barriers in the complex tumor microenvironment (TME). Herein, we developed metformin (Met) and glucose oxidase (GOx) co-loaded manganese silicon nanoplatform MnSiO3@Met@GOx (MMG) for TME-responsive ATP dual inhibited starvation/chemodynamic synergistic therapy. Under the mildly acidic conditions in TME, MMG was decomposed, releasing Met and GOx for effective ATP suppression by inhibiting oxidative phosphorylation (OXPHOS) and aerobic glycolysis pathways, respectively. Meanwhile, GOx-catalyzed glucose oxidation increased tumor acidity and hydrogen peroxide (H2O2) concentration in tumors, which not only accelerated MMG decomposition and drug release but also promoted manganese ions-mediated Fenton-like reaction. In vitro and in vivo experiments further demonstrated the effectiveness and biosafety of MMG-based synergistic therapy. This study provides a novel strategy for tumor treatment based on tumor metabolism regulation.

18.
BMC Cancer ; 22(1): 804, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864471

RESUMO

BACKGROUND: RNA methylation refers to a form of methyl modification in RNA that modulates various epigenetic alterations. Mounting studies have focused on its potential mechanisms in cancer initiation and progression. However, the prognostic value and potential role of RNA methylation in the immune microenvironment of pancreatic cancer remain unclear. METHODS: Comprehensive bioinformatics analysis was performed to illuminate the expression profiles of RNA methylation modulators. In addition, the ConsensusClusterPlus algorithm was utilized to identify two remarkably different subtypes, and a feasible risk stratification method was established to accurately estimate prognosis. In addition, we validated our signature at the cytology and histology levels and conducted functional experiments to explore the biological functions of our key genes. RESULTS: Two subtypes with remarkable survival differences were identified by the consensus clustering algorithm. Cluster 2 tended to have higher expression levels of RNA methylation regulators and to be the high RNA methylation group. In addition, cluster 1 exhibited a significantly higher abundance of almost all immune cells and increased immune checkpoint expression compared to cluster 2. Chemotherapeutic sensitivity analysis indicated that there were significant differences in the sensitivity of four of the six drugs between different subgroups. Mutation investigation revealed a higher mutation burden and a higher number of mutations in cluster 2. An accurate and feasible risk stratification method was established based on the expression of key genes of each subtype. Patients with low risk scores exhibited longer survival times in one training (TCGA) and two validation cohorts (ICGC, GSE57495), with p values of 0.001, 0.0081, and 0.0042, respectively. In addition, our signature was further validated in a cohort from Fudan University Shanghai Cancer Center. The low-risk group exhibited higher immune cell abundance and immune checkpoint levels than the high-risk group. The characteristics of the low-risk group were consistent with those of cluster 1: higher stromal score, estimate score, and immune score and lower tumor purity. Additionally, cell function investigations suggested that knockdown of CDKN3 remarkably inhibited the proliferation and migration of pancreatic cancer cells. CONCLUSIONS: RNA methylation has a close correlation with prognosis, immune infiltration and therapy in pancreatic cancer. Our subtypes and risk stratification method can accurately predict prognosis and the efficacy of immune therapy and chemotherapy.


Assuntos
Biomarcadores Tumorais , Neoplasias Pancreáticas , Biomarcadores Tumorais/genética , China , Humanos , Metilação , Prognóstico , RNA , Microambiente Tumoral/genética
19.
Int Ophthalmol ; 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35840783

RESUMO

PURPOSE: To investigate the potential genetic defects in a five-generation Chinese family with autosomal dominant congenital cataract (ADCC). METHODS: Whole exome sequencing was performed to search the variants in the candidate genes associated with congenital cataract. Sanger sequencing was used to validate the variants and examine their co-segregation in the patients and their relatives. The potential effect of the variants was analyzed using several bioinformatic methods and further examined through Western blotting and co-immunoprecipitation. RESULTS: A missense variant c. 71 G > T (p. Gly24Val) in the CRYBA4 gene, a known ADCC candidate gene, was identified to be heterozygously present in the patients and co-segregate with cataract in the family. The mutation was absent in all of the searched databases, including our in-house exome sequences of 10,000 Chinese. The alignments of the amino acid sequences of CRYBA4 in a variety of species revealed that the amino acid residue Gly24 was evolutionarily highly conserved, and the in silico analysis predicted that the missense mutation of Gly24Val was damaging for the protein structure and function of CRYBA4. Then, the in vitro expression analysis further revealed that the Gly24Val mutation in CRYBA4 inhibited its binding with CRYBB1. The impaired interaction of ß-crystallin proteins may affect their water-solubility and contribute to the formation of precipitates in lens fiber cells. CONCLUSION: We identified a novel missense variant in the CRYBA4 gene as a pathogenic mutation of ADCC in a Chinese family. Our finding expanded the CRYBA4 variation spectrum associated with congenital cataracts.

20.
Risk Anal ; 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35822654

RESUMO

Social media analysis provides an alternate approach to monitoring and understanding risk perceptions regarding COVID-19 over time. Our current understandings of risk perceptions regarding COVID-19 do not disentangle the three dimensions of risk perceptions (perceived susceptibility, perceived severity, and negative emotion) as the pandemic has evolved. Data are also limited regarding the impact of social determinants of health (SDOH) on COVID-19-related risk perceptions over time. To address these knowledge gaps, we extracted tweets regarding COVID-19-related risk perceptions and developed indicators for the three dimensions of risk perceptions based on over 502 million geotagged tweets posted by over 4.9 million Twitter users from January 2020 to December 2021 in the United States. We examined correlations between risk perception indicator scores and county-level SDOH. The three dimensions of risk perceptions demonstrate different trajectories. Perceived severity maintained a high level throughout the study period. Perceived susceptibility and negative emotion peaked on March 11, 2020 (COVID-19 declared global pandemic by WHO) and then declined and remained stable at lower levels until increasing once again with the Omicron period. Relative frequency of tweet posts on risk perceptions did not closely follow epidemic trends of COVID-19 (cases, deaths). Users from socioeconomically vulnerable counties showed lower attention to perceived severity and susceptibility of COVID-19 than those from wealthier counties. Examining trends in tweets regarding the multiple dimensions of risk perceptions throughout the COVID-19 pandemic can help policymakers frame in-time, tailored, and appropriate responses to prevent viral spread and encourage preventive behavior uptake in the United States.

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