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1.
Artigo em Inglês | MEDLINE | ID: mdl-33794513

RESUMO

We have faced the challenges from atmosphere environment due to the exposing toxic gases or liquids. Moreover, we also need to test some gases such as acetone, ethanol, and petroleum for our health or safety. Therefore, it is important to develop various gas sensors for testing them. Sensing materials play important roles in determining the performance of gas sensors. Thus, a great deal of work has been focused on the material studies. In this content, we need to discuss different materials as gas sensing materials systematically, and further give comments on the status at present and future challenges. This inspire us to assemble this 2020 Gas Sensing Materials Roadmap for discussing 29 gas sensing materials and their applications in different gas sensors by different experts.

2.
Front Endocrinol (Lausanne) ; 12: 636272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33815293

RESUMO

Objective: The intestinal flora of gut microbiota in obese Chinese children and adolescents with and without insulin resistance (IR) was analyzed, as well as associations between the gut microbiota and two serum cytokines related to glucose metabolism, adropin and angiopoietin-like 4 (ANGPTL4). Methods: Clinical data, fecal bacterial composition, glucose-related hormones, and serum adipokines (adropin and ANGPTL4) were analyzed in 65 Chinese children with exogenous obesity. The composition of the gut microbiota was determined by 16S rRNA-based metagenomics and IR was calculated using the homeostasis model assessment (HOMA). Results: The 65 obese subjects were divided into two groups: insulin sensitive (IS) (n=40, 57.5% males) or IR (n=25, 60% males). Principal coordinates analysis revealed that the gut microbiota samples from the IS group clustered together and separated partly from the IR group (p=0.008). By Mann-Whitney U-test, at a phylum level, a reduction of Firmicutes and an increase of Bacteroidetes in the IR subjects was observed. LEfSe analysis revealed that IS subject, when compared to their IR counterparts, harbored members of the order Coriobacteriales, Turicibacterales, Pasteurellales and family Turicibacteraceae, that were significantly more abundant. In contrast, the IR subjects had members of family Peptococcaceae that were significantly more prevalent than the IS subjects (all p<0.05). Spearman's correlation analysis revealed that serum ANGPTL4 was positively associated with genus Bacteroides, Butyricimonas, and Alistipes, and adropin was positively associated with genus Anaerostipes and Alistipes, and negatively associated with genus Blautia (all p<0.05). Conclusion: In obese children, the gut microbiome in IR subjects was significantly discordant from the IS subjects, and the abundance of some metabolism-related bacteria correlated with the serum concentrations of adropin and ANGPTL4. These observations infer that the gut microbiota may be involved in the regulation of glucose metabolism in obesity.

3.
Cancer Epidemiol Biomarkers Prev ; 30(4): 676-681, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33811164

RESUMO

BACKGROUND: Skin cancer screening is routinely performed for members of melanoma-prone families, but longitudinal studies evaluating the efficacy of surveillance in this high-risk population are lacking. METHODS: We evaluated thickness for first primary melanomas diagnosed in melanoma-prone families (≥2 individuals with melanoma) enrolled in NCT00040352 (NCI familial melanoma study) from 1976 through 2014; enrolled patients received routine skin cancer screening and education about skin self-exams. We used linear and ordinal logistic regression models adjusted for gender and age with a generalized estimating equations approach to report changes in thickness and tumor (T) stage over time, comparing outcomes for NCI cases diagnosed before (pre-study) versus after study participation (prospective) and for NCI cases versus nonfamilial cases [Surveillance, Epidemiology, and End Results (SEER) 9 registries]. RESULTS: Tumor thickness was evaluated for 293 NCI (pre-study = 246; prospective = 47) patients. Compared with NCI pre-study cases, NCI prospective melanomas were thinner (0.6 vs. 1.1 mm; P < 0.001) and more likely to be T1 stage [39/47 (83%) vs. 98/246 (40%); P < 0.001]. Similar findings (P < 0.05) were observed for familial cases with and without germline CDKN2A and CDK4 mutations. Peters-Belson modeling suggested that calendar period effects of decreasing thickness in the general population (SEER 9) did not fully explain thickness trends in NCI families. CONCLUSIONS: Participation in a longitudinal surveillance program providing skin cancer screening and education about skin self-exams was associated with thinner melanomas for members of melanoma-prone families. IMPACT: The study findings support the clinical benefit of screening (physician and self) for this high-risk population.

4.
BMC Cardiovasc Disord ; 21(1): 164, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823799

RESUMO

BACKGROUND: The primary aim was to observe the predictive value of P-wave ECG index and left atrial appendage volume (LLAV) for atrial fibrillation recurrence after first radiofrequency catheter ablation. METHODS: A total of 196 patients with paroxysmal atrial fibrillation were enrolled. The preoperative LLAV was measured by cardiac enhanced CT. The P-wave ECG index including minimum P-wave duration (P-min), maximum P-wave duration (P-max), mean P-wave duration (mPWD), P-wave dispersion (PWD), P-wave terminal force in lead V1 (PtfV1), PR interval prolongation, and interatrial block (IAB) were analyzed and recorded in 12-lead ECG of sinus rhythm. RESULTS: According to the follow-up results, the patients were divided into two groups: the non-recurrence group and the recurrence group. P-min, PWD, P-max, PtfV1 ≥ 0.04 mV·s, PR interval prolongation, and the ratio of first and third-degree IAB in the recurrence group were higher than those in the non-recurrence group, with significant statistical differences (P < 0.05). Kaplan-Meier curve analysis was performed on time to atrial fibrillation recurrence after catheter ablation when PtfV1 ≥ 0.04 mv s by comparison between groups (Log Rank test: 2 = 4.739, P < 0.001). Kaplan-Meier curve analysis showed that the survival rate without recurrence of atrial fibrillation after catheter ablation was lower when the LLAV exceeded 8.0 mL (log-rank test P < 0.001). CONCLUSION: PWD, P-max, PtfV1, PR interval prolongation, first and third-degree IAB, and LLAV can effectively predict atrial fibrillation recurrence after radiofrequency catheter ablation. The combination might be a valid and alternative independent predictor of recurrence.

5.
J Atheroscler Thromb ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33746138

RESUMO

AIMS: To develop and validate a nomogram using retinal vasculature features and clinical variables to predict coronary artery disease (CAD) in patients with suspected angina. METHODS: The prediction model consisting of 795 participants was developed in a training set of 508 participants with suspected angina due to CAD, and data were collected from January 2018 to June 2019. The held-out validation was conducted with 287 consecutive patients from July 2019 to November 2019. All patients with suspected CAD received optical coherence tomography angiography (OCTA) examination before undergoing coronary CT angiography. LASSO regression model was used for data reduction and feature selection. Multivariable logistic regression analysis was used to develop the retinal vasculature model for predicting the probability of the presence of CAD. RESULTS: Three potential OCTA parameters including vessel density of the nasal and temporal perifovea in the superficial capillary plexus and vessel density of the inferior parafovea in the deep capillary plexus were further selected as independent retinal vasculature predictors. Model clinical electrocardiogram (ECG) OCTA (clinical variables+ECG+OCTA) was presented as the individual prediction nomogram, with good discrimination (AUC of 0.942 [95% CI, 0.923-0.961] and 0.897 [95% CI, 0.861-0.933] in the training and held-out validation sets, respectively) and good calibration. Decision curve analysis indicated the clinical applicability of this retinal vasculature nomogram. CONCLUSIONS: The presented retinal vasculature nomogram based on individual probability can accurately identify the presence of CAD, which could improve patient selection and diagnostic yield of aggressive testing before determining a diagnosis.

6.
ACS Sens ; 6(3): 1375-1383, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33660984

RESUMO

To address the growing demand for simultaneous imaging of multiple biomarkers in highly scattering media such as organotypic cell cultures, we introduce a new type of photoluminescent nanomaterial termed "tau-ruby" composed of ruby nanocrystals (Al2O3:Cr3+) with tunable emission lifetime. The lifetime tuning range from 2.4 to 3.2 ms was achieved by varying the Cr3+ dopant concentration from 0.8% to 0.2%, affording facile implementation of background-free detection. We developed inexpensive scalable production of tau-ruby characterized by bright emission, narrow spectrum (693 ± 2 nm), and virtually unlimited photostability upon excitation with affordable excitation/detection sources, noncytotoxic and insensitive to microenvironmental fluctuations. By functionalizing the surface of tau-rubies with targeting antibodies, we obtained different biomarkers suitable for multiplexed lifetime imaging. As a proof of principle, three tau-ruby bioprobes, characterized by three mean lifetimes, were deployed to label three µ-opioid receptor species expressed on transfected cancer cells, each fused to a unique epitope, so that three types of cells were lifetime-encoded. Robust decoding of photoluminescent signals that report on each cell type was achieved by using a home-built lifetime imaging system and resulted in high-contrast multiplexed lifetime imaging of the cells.

7.
Biomed Res Int ; 2021: 6644274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728335

RESUMO

Neurodevelopmental disorder caused by malformations of cortical development is a rare neurological disease. Heterozygous missense variants in the TUBG1 gene lead to malformations of human cortical development, which further result in intellectual disability, developmental retardation, and epilepsy. To the best of our knowledge, only thirteen patients and a total of nine pathogenic TUBG1 variants have been described in the published literature. This study reports the case details and genetic data analysis of a girl (aged 8 years, 9 months) with developmental delay, psychomotor regression, epilepsy, and left external ear deformity. A novel TUBG1 mutation was identified by whole-exome sequencing and Sanger sequencing, confirming that this mutation may be the cause of the neurodevelopmental disorders. This case report characterizes the phenotypic spectrum, molecular genetic findings, and functional consequences of novel pathogenic TUBG1 variants in neurodevelopmental disorders caused by cortical development malformations.

8.
Colorectal Dis ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33751772

RESUMO

Based on the high prevalence of endometriosis (EM) and the good chance of its deep infiltration, EM is frequently involving the colorectum and found during colonoscopy by accident. However, there are not always classical signs present on the surface of bowel mucosa due to its serosal origin. EM is hardly diagnosed and missed at colonoscopy.

9.
Exp Appl Acarol ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33709252

RESUMO

Ticks are obligate blood-sucking parasitic arthropods. When sucking the blood of hosts, they can also transmit a variety of pathogens to hosts that severely endanger the health of humans and animals. The spermatheca is an organ for the storage and protection of sperm and an important component of the reproductive system of female ticks. The spermatheca content changes dramatically over time after copulation. In particular, some proteins and polypeptide substances can influence the physiological functions of female ticks and promote blood feeding and egg laying by female ticks. To investigate the molecular mechanisms underlying the productive process of Haemaphysalis longicornis, data-independent acquisition (DIA) quantitative proteomics technology was used to perform in-depth research of the dynamic changes in all proteins in the spermatheca of ticks within a short time after copulation to look for key proteins in the spermatheca contents after copulation that affect the reproduction of female ticks in order to provide meaningful information for the comprehensive prevention and control of ticks.

10.
J Phycol ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33650119

RESUMO

The physiological response of symbiotic Symbiodiniaceae to high temperature is believed to result in coral bleaching. However, the potential effect of nitrogen availability on heat acclimatization of symbiotic Symbiodiniaceae is still unclear. In this study, physiological responses of Symbiodiniaceae Cladocopium goreaui to temperature and nitrogen-nutrient stress conditions were investigated. Nitrogen deficiency caused significant declines in cell concentration and chlorophyll content per cell, but significant increases in nitric oxide synthase activity, caspase3 activation level, and carbon content of C. goreaui at normal temperature. Algal cells under high temperature and nitrogen deficiency showed significant rises in Fv/Fm, catalase activity, and caspase3 activation level, but no significant changes in cell yield, cell size, chlorophyll content, superoxide dismutase, nitric oxide synthase activity, and cellular contents of nitrogen and carbon, in comparison with those under normal temperature and nitrogen deficiency. Growth, chlorophyll and nitrogen contents of algal cells under the high temperature and nitrogen-replete conditions were significantly higher than those under high temperature or nitrogen deficiency alone, whereas nitric oxide synthase activity, superoxide dismutase activity, catalase activity, carbon content, and caspase3 activation level exhibited opposite trends of variation. Transcriptomic and network analyses revealed ion transport and metabolic processes mainly involved in regulating these physiological activities under different temperature and nitrogen-nutrient. The totality of results shows that high temperature activates stress responses, induces antioxidant capacity of apoptosis, and limits the growth rate of C. goreaui. Adequate nitrogen-nutrient can improve the resilience of this Symbiodiniaceae against heat stress through repressed apoptosis, promoted ion transport, and optimized metabolism.

11.
Eur J Med Chem ; 214: 113225, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33550182

RESUMO

Pyruvate dehydrogenase kinases (PDKs) are promising therapeutic targets that have received increasing attentions in cancer metabolism. In this paper, we report the synthesis and biological evaluation of a series of novel dichloroacetophenones as potent PDKs inhibitors. Structure-activity relationship analysis enabled us to identify a potent compound 6u, which inhibited PDKs with an EC50 value of 0.09 µM, and reduced various cancer cells proliferation with IC50 values ranging from 1.1 to 3.8 µM, while show weak effect against non-cancerous L02 cell (IC50 > 10 µM). In the A375 xenograft model, 6u displayed an obvious antitumor activity at a dose of 5 mg/kg, but with no negative effect to the mice weight. Molecular docking suggested that 6u formed direct hydrogen bond interactions with Ser75 and Gln61 in PDK1, and meanwhile the aniline skeleton in 6u was sandwiched by the conserved hydrophobic residues Phe78 and Phe65, which contribute to the biochemical activity improvement. Moreover, 6u induced A375 cell apoptosis and cell arrest in G1 phase, and inhibited cancer cell migration. In addition, 6u altered glucose metabolic pathway in A375 cell by decreasing lactate formation and increasing ROS production and OCR consumption, which could serve as a potential modulator to reprogram the glycolysis pathway in cancer cell.

12.
Microb Cell Fact ; 20(1): 53, 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33639944

RESUMO

BACKGROUND: The term "metabolically healthy obese (MHO)" denotes a hale and salutary status, yet this connotation has not been validated in children, and may, in fact, be a misnomer. As pertains to obesity, the gut microbiota has garnered attention as conceivably a nosogenic or, on the other hand, protective participator. OBJECTIVE: This study explored the characteristics of the fecal microbiota of obese Chinese children and adolescents of disparate metabolic statuses, and the associations between their gut microbiota and circulating proinflammatory factors, such as IL-6, TNF-α, lipopolysaccharide-binding protein (LBP), and a cytokine up-regulator and mediator, leptin. RESULTS: Based on weight and metabolic status, the 86 Chinese children (ages 5-15 years) were divided into three groups: metabolically healthy obese (MHO, n = 42), metabolic unhealthy obese (MUO, n = 23), and healthy normal weight controls (Con, n = 21). In the MUO subjects, the phylum Tenericutes, as well as the alpha and beta diversity, were significantly reduced compared with the controls. Furthermore, Phylum Synergistetes and genus Bacteroides were more prevalent in the MHO population compared with controls. For the MHO group, Spearman's correlation analysis revealed that serum IL-6 positively correlated with genus Paraprevotella, LBP was positively correlated with genus Roseburia and Faecalibacterium, and negatively correlated with genus Lactobacillus, and leptin correlated positively with genus Phascolarctobacterium and negatively with genus Dialister (all p < 0.05). CONCLUSION: Although there are distinct differences in the characteristic gut microbiota of the MUO population versus MHO, dysbiosis of gut microsystem is already extant in the MHO cohort. The abundance of some metabolism-related bacteria associates with the degree of circulating inflammatory compounds, suggesting that dysbiosis of gut microbiota, present in the MHO children, conceivably serves as a compensatory or remedial response to a surfeit of nutrients.

13.
BMC Neurol ; 21(1): 49, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530932

RESUMO

BACKGROUND: Virus encephalitis is found to be a risk factor for acute retinal necrosis (ARN). CASE PRESENTATION: We herein presented a case of a 20-year-old teenage boy who suffered from encephalitis of unknown etiology with early negative pathologic results, and was primarily treated with systemic administration of high-dose steroids without antiviral therapy. He later had sudden vision loss in his right eye. Intravitreal and intravenous antiviral treatments were immediately started due to suspected ARN. Herpes simplex virus (HSV)-1 was identified later in the vitreous humor of the patient. After the surgery of retinal detachment (RD), obvious improvements in vision were observed. However, the patient had recurrent RD and vision declination 5 weeks later. CONCLUSIONS: The case with suspected viral encephalitis should be treated with antiviral therapy regardless of early virologic results in order to avoid complications of a missed viral encephalitis diagnosis, especially if systemic steroid treatment is being considered.

14.
Nat Commun ; 12(1): 757, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536423

RESUMO

Chordoma is a rare bone tumor with an unknown etiology and high recurrence rate. Here we conduct whole genome sequencing of 80 skull-base chordomas and identify PBRM1, a SWI/SNF (SWItch/Sucrose Non-Fermentable) complex subunit gene, as a significantly mutated driver gene. Genomic alterations in PBRM1 (12.5%) and homozygous deletions of the CDKN2A/2B locus are the most prevalent events. The combination of PBRM1 alterations and the chromosome 22q deletion, which involves another SWI/SNF gene (SMARCB1), shows strong associations with poor chordoma-specific survival (Hazard ratio [HR] = 10.55, 95% confidence interval [CI] = 2.81-39.64, p = 0.001) and recurrence-free survival (HR = 4.30, 95% CI = 2.34-7.91, p = 2.77 × 10-6). Despite the low mutation rate, extensive somatic copy number alterations frequently occur, most of which are clonal and showed highly concordant profiles between paired primary and recurrence/metastasis samples, indicating their importance in chordoma initiation. In this work, our findings provide important biological and clinical insights into skull-base chordoma.


Assuntos
Cordoma/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Proteína SMARCB1/genética , Neoplasias da Base do Crânio/genética , Fatores de Transcrição/genética , Sequenciamento Completo do Genoma/métodos , Adulto , Cordoma/patologia , Variações do Número de Cópias de DNA , Feminino , Genômica/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Neoplasias da Base do Crânio/patologia , Adulto Jovem
15.
Acta Ophthalmol ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629471

RESUMO

PURPOSE: To investigate the association between retinal microvasculature and the presence and severity of coronary artery disease (CAD) using optical coherence tomography angiography (OCTA). METHODS: The cross-sectional study was conducted in Guangdong Provincial People's Hospital, China. Retinal microvasculature parameters were measured by OCTA of the optic disc, including the vessel density (VD) and retinal nerve fibre thickness of the radial peripapillary capillary. In terms of the entire macula, VD of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and foveal density (FD-300) were included. The Gensini score was used to evaluate the severity of coronary artery obstructive lesions in CAD patients. RESULTS: A total of 410 participants (270 CAD patients and 140 controls) were included. Overall, participants showed significantly greater odds of having CAD in the lower versus higher VD for mean SCP, OR = 2.33 (95% CI 1.49-3.65); in the parafoveal SCP, OR = 2.68 (95% CI 1.70-4.23); and in the perifoveal SCP, OR = 2.36 (95% CI 1.49-3.72). Additionally, participants showed significantly greater odds of having CAD in the lower versus higher VD for mean DCP, OR = 4.04 (95% CI 2.53-6.45); in the parafoveal DCP, OR = 4.08 (95% CI 2.54-6.55); and in the perifoveal DCP, OR = 3.88 (95% CI 2.43-6.19). Among CAD patients, lower VD of DCP was associated with significantly greater adjusted Gensini scores (p = 0.004 for mean DCP; p = 0.035 for parafoveal DCP; p = 0.006 for perifoveal DCP). CONCLUSIONS: SCP and DCP were found to be associated with the presence of CAD among the whole population, while DCP was found to be associated with Gensini scores in CAD patients. Retinal microvasculature was associated with the presence and severity of coronary artery stenosis in CAD patients.

16.
Protein J ; 40(1): 119-130, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387247

RESUMO

Babesia microti is a protozoan that mainly parasitizes rodent and human erythrocytes. B. microti infection can result in changes in the expression levels of various proteins in the host serum. To explore the mechanism underlying the regulation of serum proteins by the host during B. microti infection, this study used a data-independent acquisition (DIA) quantitative proteomic approach to perform comprehensive quantitative proteomic analysis on the serum of B. microti-infected mice. We identified and analysed 333 serum proteins during the infectious stage and recovery stage within 30 days of infection by B. microti in mice. Through quantitative analysis, we found 57 proteins differentially expressed in the infection stage and 69 proteins differentially expressed in the recovery stage. Bioinformatics analysis revealed that these differentially expressed proteins were mainly concentrated in organelles, cell parts, and extracellular regions that are mainly involved in immune system, metabolic, and cellular processes. Additionally, the differentially expressed proteins mainly had catalytic activity. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis showed that many of the differentially expressed proteins participate in the complement and coagulation cascade reaction, including complement C3, complement FP, and coagulation factor XII. The results of this study can provide more information for the selection of biomarkers for the early clinical monitoring of babesiosis and help in the treatment of babesiosis.

17.
Endocr J ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33408314

RESUMO

Long noncoding RNAs (lncRNAs) have been reported to play critical role in the development of diabetic nephropathy (DN). However, the effects and mechanism of plasmacytoma variant translocation 1 (PVT1) remain poorly understood. The expression of PVT1, miR-23b-3p, early growth response factor 1 (EGR1), Fibronectin (FN), Collagen IV (Col IV), alpha smooth muscle actin (α-SMA), E-cadherin, and vimentin, transforming growth factor (TGF)-ß1 was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed by Cell Counting-8 (CCK-8) assay. Western blot assay was conducted to measure the protein levels of FN, Col IV, E-cadherin, α-SMA, vimentin, TGF-ß1, and EGR1. The interaction between miR-23b-3p and PVT1 or EGR1 was predicted by starBase or TargetScan and confirmed by the dual luciferase reporter assay. The oxidative stress factors were analyzed by corresponding kits. We found that the expression of PVT1 and EGR1 was increased and miR-23b-3p was decreased in serum samples of DN patients and HG-induced HRMCs. Knockdown of PVT1 significantly inhibited HG-induced proliferation, extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT), and oxidative stress in HRMCs, while these effects were abated by inhibiting miR-23b-3p. In addition, EGR1 was confirmed as downstream target of miR-23b-3p and miR-23b-3p could specially bind to PVT1. Besides, downregulation of PVT1 inhibited the progression of DN partially via upregulating miR-23b-3p and downregulating EGR1. In conclusion, our results suggested that PVT1 knockdown suppressed DN progression though functioning as ceRNA of miR-23b-3p to regulate EGR1 expression in vitro, providing potential value for the treatment of DN.

18.
Parasit Vectors ; 14(1): 61, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468223

RESUMO

BACKGROUND: Babesia is a protozoan parasite that infects red blood cells in some vertebrates. Some species of Babesia can induce zoonoses and cause considerable harm. As the largest immune organ in mammals, the spleen plays an important role in defending against Babesia infection. When infected with Babesia, the spleen is seriously injured but still actively initiates immunomodulatory responses. METHODS: To explore the molecular mechanisms underlying the immune regulation and self-repair of the spleen in response to infection, this study used data-independent acquisition (DIA) quantitative proteomics to analyse changes in expression levels of global proteins and in phosphorylation modification in spleen tissue after Babesia microti infection in mice. RESULTS: After mice were infected with B. microti, their spleens were seriously damaged. Using bioinformatics methods to analyse dynamic changes in a large number of proteins, we found that the spleen still initiated immune responses to combat the infection, with immune-related proteins playing an important role, including cathepsin D (CTSD), interferon-induced protein 44 (IFI44), interleukin-2 enhancer-binding factor 2 (ILF2), interleukin enhancer-binding factor 3 (ILF3) and signal transducer and activator of transcription 5A (STAT5A). In addition, some proteins related to iron metabolism were also involved in the repair of the spleen after B. microti infection, including serotransferrin, lactoferrin, transferrin receptor protein 1 (TfR1) and glutamate-cysteine ligase (GCL). At the same time, the expression and phosphorylation of proteins related to the growth and development of the spleen also changed, including protein kinase C-δ (PKC-δ), mitogen-activated protein kinase (MAPK) 3/1, growth factor receptor-bound protein 2 (Grb2) and P21-activated kinase 2 (PAK2). CONCLUSIONS: Immune-related proteins, iron metabolism-related proteins and growth and development-related proteins play an important role in the regulation of spleen injury and maintenance of homeostasis. This study provides an important basis for the diagnosis and treatment of babesiosis.

19.
Chemistry ; 27(20): 6283-6294, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33475219

RESUMO

Enzyme stereoselectivity control is still a major challenge. To gain insight into the molecular basis of enzyme stereo-recognition and expand the source of antiPrelog carbonyl reductase toward ß-ketoesters, rational enzyme design aiming at stereoselectivity inversion was performed. The designed variant Q139G switched the enzyme stereoselectivity toward ß-ketoesters from Prelog to antiPrelog, providing corresponding alcohols in high enantiomeric purity (89.1-99.1 % ee). More importantly, the well-known trade-off between stereoselectivity and activity was not found. Q139G exhibited higher catalytic activity than the wildtype enzyme, the enhancement of the catalytic efficiency (kcat /Km ) varied from 1.1- to 27.1-fold. Interestingly, the mutant Q139G did not lead to reversed stereoselectivity toward aromatic ketones. Analysis of enzyme-substrate complexes showed that the structural flexibility of ß-ketoesters and a newly formed cave together facilitated the formation of the antiPrelog-preferred conformation. In contrast, the relatively large and rigid structure of the aromatic ketones prevents them from forming the antiPrelog-preferred conformation.

20.
Ann Palliat Med ; 9(6): 4054-4065, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33302665

RESUMO

BACKGROUND: The prevalence of smoking among Chinese medical students in medical colleges is a matter of significant concern. This study aimed to explore the prevalence of smoking and the associated factors among these students. METHODS: A total of 7,728 students from 16 colleges in 12 provinces were surveyed to measure their smoking behaviors, attitudes toward tobacco control, and knowledge about smoking risk. An evaluation of campus environment and policy was conducted at the same time. Frequencies were calculated using weighted estimators for complex sampling. A two-level logistic regression model was used to assess factors associated with current smoking. RESULTS: The prevalence of smoking among male medical students in the 16 medical colleges was 12.8%. Students' participation in smoking, smoking initiation after school enrollment, and intention-to-quit-smoking rates may be influenced by their anti-tobacco attitude, the belief that smoking can help to relieve stress, their parents' smoking behaviors, their best friend's attitude towards smoking and second-hand smoke exposure (SHSE), and their awareness of tobacco hazards. CONCLUSIONS: This study provides sufficient evidence to support the implementation of systematic intervention strategies to decrease the smoking rate among male medical students. These strategies may include tobacco control education, smoking cessation technologies, communication, and the enforcement of smoke-free policies to create a tobacco-controlled campus environment.

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