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1.
JMIR Med Educ ; 7(4): e24027, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596575

RESUMO

BACKGROUND: Medical postgraduates' demand for data capabilities is growing, as biomedical research becomes more data driven, integrative, and computational. In the context of the application of big data in health and medicine, the integration of data mining skills into postgraduate medical education becomes important. OBJECTIVE: This study aimed to demonstrate the design and implementation of a medical data mining course for medical postgraduates with diverse backgrounds in a medical school. METHODS: We developed a medical data mining course called "Practical Techniques of Medical Data Mining" for postgraduate medical education and taught the course online at Peking Union Medical College (PUMC). To identify the background knowledge, programming skills, and expectations of targeted learners, we conducted a web-based questionnaire survey. After determining the instructional methods to be used in the course, three technical platforms-Rain Classroom, Tencent Meeting, and WeChat-were chosen for online teaching. A medical data mining platform called Medical Data Mining - R Programming Hub (MedHub) was developed for self-learning, which could support the development and comprehensive testing of data mining algorithms. Finally, we carried out a postcourse survey and a case study to demonstrate that our online course could accommodate a diverse group of medical students with a wide range of academic backgrounds and programming experience. RESULTS: In total, 200 postgraduates from 30 disciplines participated in the precourse survey. Based on the analysis of students' characteristics and expectations, we designed an optimized course structured into nine logical teaching units (one 4-hour unit per week for 9 weeks). The course covered basic knowledge of R programming, machine learning models, clinical data mining, and omics data mining, among other topics, as well as diversified health care analysis scenarios. Finally, this 9-week course was successfully implemented in an online format from May to July in the spring semester of 2020 at PUMC. A total of 6 faculty members and 317 students participated in the course. Postcourse survey data showed that our course was considered to be very practical (83/83, 100% indicated "very positive" or "positive"), and MedHub received the best feedback, both in function (80/83, 96% chose "satisfied") and teaching effect (80/83, 96% chose "satisfied"). The case study showed that our course was able to fill the gap between student expectations and learning outcomes. CONCLUSIONS: We developed content for a data mining course, with online instructional methods to accommodate the diversified characteristics of students. Our optimized course could improve the data mining skills of medical students with a wide range of academic backgrounds and programming experience.

2.
Zhongguo Zhen Jiu ; 41(10): 1089-94, 2021 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-34628740

RESUMO

OBJECTIVE: To compare the clinical therapeutic effect between deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle and conventional acupuncture in patients with trigeminal neuralgia (TN) of wind and heat, and explore its mechanism. METHODS: A total of 60 patients with TN of wind and heat were randomized into an observation group (30 cases) and a control group (30 cases). In the observation group, deep needling with round sharp needle was applied at Xiaguan (ST 7), and tapping with plum-blossom needle was applied at Yangbai (GB 14), Quanliao (SI 18), Dicang (ST 4), Sibai (ST 2), etc. of affected side. In the control group, conventional acupuncture was applied at the same acupoints selected in the observation group. The treatment was given once a day, 5 times a week for 4 weeks in the both groups. Before and after treatment, the scores of short-form McGill pain questionnaire (SF-MPQ), TCM syndrome, patient global impression of change (PGIC) and comprehensive symptom were observed, the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vasoactive intestinal peptide (VIP) and ß-endorphin (ß-EP) were detected, and the adverse reaction was observed in the both groups. RESULTS: After treatment, the scores of PRI, PPI, VAS, TCM syndrome, PGIC and comprehensive symptom and the serum levels of IL-6, TNF-α and VIP were decreased compared before treatment in the both groups (P<0.05), and the variations of above indexes in the observation group were larger than those in the control group (P<0.05). After treatment, the serum levels of ß-EP were increased compared before treatment in the both groups (P<0.05), and the variation of that in the observation group was larger than the control group (P<0.05). No severe adverse reaction was observed in the both groups. CONCLUSION: Deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle can effectively treat the trigeminal neuralgia of wind and heat and relieve pain, its therapeutic effect is superior to conventional acupuncture. The mechanism may be related to the regulation of serum IL-6, TNF-α, VIP and ß-EP.


Assuntos
Prunus domestica , Neuralgia do Trigêmeo , Flores , Temperatura Alta , Humanos , Neuralgia do Trigêmeo/terapia , Vento
3.
Clin Rheumatol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642881

RESUMO

INTRODUCTION: Biomarkers of bone and cartilage metabolism were proposed as early diagnosis indicators for knee osteoarthritis (OA), however, which were influenced by disease stage, age, and menopause state. Accurate diagnosis indicators are eagerly awaited. The current study aims to investigate associations of joint metabolism biomarkers and bone mineral density (BMD) with early knee OA in males and premenopausal females before age 50 years. METHOD: A total of 189 patients aged before 50 years with early knee OA and 152 healthy participants were enrolled. Levels of bone biomarkers (PINP, OC, and CTX-I) and cartilage biomarkers (PIIANP, COMP, CTX-II, and MMP-3) were assessed. BMD was measured at the lumbar, femoral neck, and hip. Multivariate regression analyses were performed to evaluate the relationship between biomarkers, BMD, and early knee OA. RESULTS: Serum COMP, urine CTX-II and BMD at femoral neck and hip were increased in premenopausal patients as compared to control; with serum PINP and OC reduced. Meanwhile, serum COMP, urine CTX-II, and BMD at femoral neck and hip showed positive associations with premenopausal early knee OA, while serum PINP had negative association. However, in male patients, only serum COMP was higher than control, and no association of biomarkers or BMD was found with early knee OA. CONCLUSIONS: The joint metabolism biomarkers and BMD showed multiple associations with early knee OA in premenopausal females, but not in males aged before 50 years. It was suggested that sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA. Key Points • The joint metabolism biomarkers and BMD are associated with early knee OA in premenopausal females, but not in males aged before 50 years. • Sex differences should be taken into account when evaluating cartilage and bone metabolism in early knee OA.

4.
Ecotoxicol Environ Saf ; 226: 112860, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34624534

RESUMO

The Yangtze River exhibits a high biodiversity and plays an important role in global biodiversity conservation. As the world's busiest inland river in regard to shipping, little attention has been paid to underwater noise pollution. In 2017, the underwater noise level in 25 riverside locations along the middle and lower reaches of the Yangtze River mainly at night time were investigated by using passive acoustic monitoring method. Approximately 88% and 40% of the sampled sites exhibit noise levels exceeding the underwater acoustic thresholds of causing responsiveness and temporary threshold shift, respectively, in cetacean. Noise pollution may impose a high impact on fish with physostomous swim bladders and Weberian ossicles, such as silver carp, bighead carp, goldfish and common carp, whereas it may affect fish with physoclistous swim bladders and without Weberian ossicles, such as lake sturgeon and paddlefish, to a lesser extent. Noise levels reductions of approximately 10 and 20 dB were observed in the middle and lower reaches, respectively, of the Yangtze River over the 2012 level. The green development mode of the ongoing construction of green shipping in the Yangtze River Economic Belt, including the development of green shipping lanes, ports, ships and transportation organizations, may account for the alleviated underwater noise pollution. Follow-up noise mitigation endeavors, such as the extension of ship speed restrictions and the study and implementation of the optimal navigation speed in ecologically important areas, are required to further reduce the noise level in the Yangtze River to protect local porpoises and fish.

5.
BMC Cancer ; 21(1): 1074, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34598688

RESUMO

BACKGROUND: The human miR-17-92 polycistron is the first reported and most well-studied onco-miRNA with a cluster of seven miRNAs. miR-17-5p, a member of the miR-17-92 family, plays an important role in tumor cell proliferation, apoptosis, migration and invasion. However, few studies have shown the role of miR-17-5p in the cell cycle of head and neck squamous cell carcinoma (HNSCC). METHODS: RT-qPCR was used to detect miR-17-5p expression levels in 64 HNSCC tissues and 5 cell lines. The relationship between the expression of miR-17-5p in the tissues and the clinical characteristics of the patients was analyzed. HNSCC cells were transfected with an miR-17-5p mimic or inhibitor to evaluate cell cycle distribution by flow cytometry. Cell cycle distribution of cells transfected with target gene was evaluated using flow cytometry. Dual-luciferase reporter assay was used to detect the regulatory effect of miR-17-5p on target gene expression. RESULTS: In the present study, we found that miR-17-5p expression in HNSCC tissues and cell lines was remarkably increased, and miR-17-5p is related to recurrence in HNSCC patients. Silencing miR-17-5p blocked HNSCC cells in G2/M phase, whereas its overexpression propelled cell cycle progression. More importantly, we verified that miR-17-5p negatively regulated CCNG2 mRNA and protein expression by directly targeting its 3'UTR. CONCLUSION: These findings suggest that miR-17-5p might act as a tumor promoter and prognostic factor for recurrence in HNSCC patients.

6.
J Leukoc Biol ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622967

RESUMO

ETO2 is a nuclear co-repressor, which plays a critical role in the regulation of the cell cycle, self-renewal capacity, and differentiation of hematopoietic progenitor cells. We identified novel fusion transcripts involving ETO2 and CTCF by RNA-seq in a multiple relapsed AML case. The CTCF-ETO2 and ETO2-CTCF chimeric genes were validated by RT-PCR and Sanger sequencing. In addition, both transcripts apparently promoted cell proliferation via JAK/STAT3 pathway that is sensitive to STAT3 inhibitors. The novel fusions may have prognostic value and pathogenic mechanisms in acute myeloid leukemia.

7.
J Hazard Mater ; 424(Pt A): 127323, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34601411

RESUMO

Foliar application of selenium nanoparticles (SeNPs) has been used to enhance Se concentration in winter wheat, but soil application of SeNPs on Se uptake in the crop and their transformation in soil are still limited. This study investigated the effects of varying sizes (50, 100, 200 nm) and concentrations (0, 2, 5, 25, 100 mg kg-1) of chemical synthesized SeNPs in soil on uptake and accumulation of Se in the crop at maturity and related mechanisms. SeNPs not only posed very low toxic to plant growth, except for leaf, but also significantly enhanced grain Se concentration. Regardless of concentration of SeNPs added to soil, the transformation rate of the larger sized SeNPs (200 nm) in soil was significantly (p < 0.05) higher than that of the smaller one, which is mainly due to the latter was more easily adsorbed onto soil organic matter and reluctant to be oxidized. Significantly higher grain Se concentration under the larger sized SeNPs contributed to significantly higher transformation rate of SeNPs and concentration of available Se in soil. The present study showed that the larger sized SeNPs in soil had significant advantages including higher grain Se concentration and Se utilization efficiency for wheat Se biofortification.

8.
J Am Chem Soc ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34609874

RESUMO

The boundary between molecular and metallic gold nanoclusters is of special interest. The difficulty in obtaining atomically precise nanoclusters larger than 2 nm limits the determination of such a boundary. The synthesis and total structural determination of the largest all-alkynyl-protected gold nanocluster (Ph4P)6[Au156(C≡CR)60] (R = 4-CF3C6H4-) (Au156) are reported. It presents an ideal platform for studying the relationship between the structure and the metallic nature. Au156 has a rod shape with the length and width of the kernel being 2.38 and 2.04 nm, respectively. The cluster contains a concentric Au126 core structure (Au46@Au50@Au30) protected by 30 linear RC≡C-Au-C≡CR staple motifs. It is interesting that Au156 displays multiple excitonic peaks in the steady-state absorption spectrum (molecular) and pump-power-dependent excited-state dynamics as revealed in the transient absorption spectrum (metallic), which indicates that Au156 is a critical crossover cluster for the transition from molecular to metallic state. Au156 is the smallest-sized gold nanocluster showing metal-like electron dynamics, and it is recognized that the cluster shape is one of the important factors determining the molecular or metallic nature of a gold nanocluster.

9.
Org Biomol Chem ; 19(34): 7333-7347, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34612358

RESUMO

The direct use structurally simple ketones as α-ketone radical sources for α-C(sp3)-H functionalization is a sustainable and powerful approach for constructing complex and multifunctional chemical scaffolds with diverse applications. The reactions of α-ketone radicals with alkenes, alkynes, enynes, imides, and imidazo[1,2-a]pyridines have broadened the structural diversity and complexity of ketones. Through chosen illustrative examples, we outline the recent progress in the development of methods that enable the radical α-C(sp3)-H functionalization of ketones, with an emphasis on radical initiation systems and possible mechanisms of the transformations. The application of these strategies is illustrated by the synthesis of several biologically active molecules and drug molecules. Further subdivision is based on substrate type and reaction type.

11.
J Agric Food Chem ; 69(37): 10819-10829, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34516131

RESUMO

A series of novel chromone derivatives containing dithioacetals were prepared, and their antiviral activity against tomato spotted wilt virus (TSWV) was studied. The results showed that compounds A1-A31 had good inhibitory activity against TSWV. The 3D-QSAR model was built to analyze the structure-activity relationship of the compounds. We further found that compounds A32 and A33 had excellent anti-TSWV activities based on the results of 3D-QSAR, which were better than the control agents ningnanmycin and ribavirin. To study the mode of action of these compounds on TSWV, the nucleocapsid protein of TSWV (TSWV N) was cloned, expressed, and purified in the study. The results of the microscale thermophoresis (MST) experiments indicate that compound A33 can better bind with TSWV N. The molecular docking experiment further indicated that the mode of action of the compound A33 is to inhibit the virus by blocking the combination of TSWV N and viral RNA. Therefore, this study has found that chromone compound A33 is a potential anti-TSWV agent that targets TSWV N.


Assuntos
Tospovirus , Cromonas/farmacologia , Simulação de Acoplamento Molecular , RNA Viral , Tospovirus/genética
12.
Brain ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581804

RESUMO

Genome-wide association studies showed that genetic variants at 2q33.1 were strongly associated with schizophrenia. However, potential causal variants in this locus and their roles in schizophrenia remain unknown. Here we identified two functional variants (rs796364 and rs281759) that disrupt CTCF, RAD21 and FOXP2 binding at 2q33.1. We systematically investigated the regulatory mechanisms of these two variants with serial experiments, including reporter gene assays and electrophoretic mobility shift assay (EMSA). Intriguingly, these two SNPs physically interacted with TYW5 and showed the most significant associations with TYW5 expression in human brain. Consistently, CRISPR-Cas9-mediated genome editing also confirmed the regulatory effect of these two SNPs on TYW5 expression. Additionally, expression analysis indicated that TYW5 was significantly up-regulated in brains of schizophrenia cases compared with controls, suggesting that rs796364 and rs281759 might confer schizophrenia risk by modulating TYW5 expression. We over-expressed TYW5 in mouse neural stem cells (NSCs) and rat primary neurons to mimic its up-regulation in schizophrenia cases, and found significant alterations in proliferation and differentiation of NSCs, as well as dendritic spine density following TYW5 overexpression, indicating its important roles in neurodevelopment and spine morphogenesis. Furthermore, we independently confirmed the association between rs796364 and schizophrenia in a Chinese cohort of 8,202 subjects. Finally, transcriptome analysis revealed that TYW5 affected schizophrenia-associated pathways. These lines of evidence consistently revealed that rs796364 and rs281759 might contribute to schizophrenia risk through regulating expression of TYW5, a gene whose expression dysregulation affects two important schizophrenia pathophysiologic processes (i.e. neurodevelopment and dendritic spine formation).

13.
BMC Infect Dis ; 21(1): 920, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488656

RESUMO

BACKGROUND: Most infants infected with Toxoplasma gondii are completely asymptomatic at birth, yet they may develop ocular and neurological sequelae in the first few months of life. Cases of congenital toxoplasmosis with severe jaundice early after birth combined with pancytopenia and splenomegaly are extremely rare. Here, we report on a rare case of congenital toxoplasmosis presenting with severe jaundice and hemolysis early after birth combined with pancytopenia and splenomegaly. CASE PRESENTATION: A male preterm infant with severe jaundice and splenomegaly was admitted to our department. Laboratory examinations revealed severe hyperbilirubinemia, increased reticulocytes, and pancytopenia. After comprehensive analysis and examination, the final diagnosis was congenital toxoplasmosis, and the infant was treated with azithromycin and subsequently trimethoprim-sulfamethoxazole. Regular follow-up revealed congenital toxoplasmosis in both eyes, which was surgically treated, while neurofunctional assessment results were unremarkable. In this case of congenital toxoplasmosis combined with severe jaundice, we treated the infant with two courses of azithromycin, followed by trimethoprim-sulfamethoxazole after the jaundice resolved. Clinical follow-up indicated that this treatment was effective with few side effects; thus, this report may serve as a valuable clinical reference. CONCLUSIONS: Timely diagnosis and adequate treatment are closely associated with congenital toxoplasmosis-related prognosis. Infants with congenital toxoplasmosis require long-term follow-up, focusing on nervous system development and ophthalmology.


Assuntos
Toxoplasma , Toxoplasmose Congênita , Azitromicina/uso terapêutico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Toxoplasmose Congênita/diagnóstico , Toxoplasmose Congênita/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
14.
Seizure ; 92: 158-165, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34525431

RESUMO

BACKGROUND: In recent years, studies have examined the relationship between febrile seizures in children and S100B protein with contradictory results. We systematically evaluated the relationship between children's febrile seizures and S100B protein levels. METHODS: We used Stata 11.0 software to conduct a meta-analysis of the included studies published in The China National Knowledge Infrastructure, VIP, Wanfang, Chinese Biology Medicine Disc, PubMed, Web of Science, Cochrane Library, and EMBASE databases as well as clinical trial registries in China, Europe, and the United States. RESULTS: Six case-control studies were finally included in the meta-analysis. The results of the meta-analysis showed that the serum S100B protein level of children with febrile seizures was 0.72 higher than the serum S100B protein level of healthy children (Z=6.85, 95% CI 0.52∼0.93, P<0.05). There was no difference in the serum S100B protein level between the children with febrile seizures and children with fever but without seizures (Z=0.70, 95% CI -0.20∼0.41, P>0.05). CONCLUSION: The level of serum S100B protein in children with febrile seizures was higher than that of healthy children and was statistically significant, whereas the increase in children with higher fever without seizures was not statistically significant. Because there was only a difference in serum S100B protein levels between children with febrile seizures and healthy children but not in febrile children without seizures as the strongest confounding factors for the results, febrile seizures do not elevate the level of S100B protein levels any more than fever.

15.
Fish Physiol Biochem ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581919

RESUMO

Memory drove a critical process of feeding habit transformation in Chinese perch when they re-trained to eat dead prey fish. To investigate the regulatory mechanism of cAMP-response element-binding protein (CREB) signaling pathway on the memory of Chinese perch during feeding habit transformation, the phosphorylation levels of upstream signal proteins of CREB between the control group (trained once) and the experimental group (trained twice) were measured. The results illustrated that the re-training was correlated to phosphorylation of extracellular regulated protein kinase (ERK1/2) and calcium/calmodulin-dependent protein kinase II (CaMKII), and dephosphorylation of protein kinase A (PKA) of Chinese perch. Inhibition of ERK1/2-CREB pathway decreased the mRNA levels of memory-related genes ((fos-related antigen 2 (fra2), CCAAT enhancer-binding protein delta (c/ebpb), immediate-early gene zif268 (zif268), proto-oncogenes c-fos (c-fox) and synaptotagmin-IV (sytIV)) and mRNA levels of appetite-related genes (agouti-related peptide (agrp) and ghrelin), and activation of PP1-CREB pathway increased the phosphorylated levels of CREB, the mRNA levels of memory-related genes (fra2, c/ebpb, zif268, and c-fox), and the mRNA levels of appetite-related genes (pro-opiomelanocortin (pomc) and leptin) in primary brain cells of Chinese perch. The memory in Chinese perch feeding habit transformation was associated with the ERK1/2-CREB and PP1-CREB pathways, which could regulate the transcription of memory-related genes and appetite-related genes.

16.
Arch Oral Biol ; 131: 105252, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34500260

RESUMO

OBJECTIVE: To sequentially track mandibular defect repair by using radiographic and histological techniques, so as to compare repair patterns of sensory denervated versus innervated mandibles. DESIGN: Forty Sprague-Dawley rats were subjected to unilateral inferior alveolar nerve (IAN) axotomy and bilateral 3 mm full-thickness circular osteotomy of their mandibles. Micro-CT and histological staining were applied to track the repair process of the mandibular defects at 1, 2, 4, and 8 weeks after surgery. RESULTS: The bone volume of both sides increased by 2 weeks post-operation, and then gradually decreased. The new bone volumes of the axotomy side were significantly less than that of the sham side at 1, 2, and 4 weeks post-surgery, whereas no significant differences were detected at 8 weeks post-surgery. Meanwhile, there were no significant differences in bone mineral density between the two sides during repair. Noteworthy, the repaired bone remained more vertically than horizontally aligned throughout the repair process. CONCLUSION: IAN axotomy decreases the quantity of bone calluses during the early stage of mandibular defect repair, but with no effect on the degree of mineralization. The shape of the defect area appeared to be aligned with the direction of local mechanical force produced by masticatory muscles.


Assuntos
Mandíbula , Nervo Mandibular , Animais , Axotomia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Nervo Mandibular/diagnóstico por imagem , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-X
17.
Radiother Oncol ; 164: 146-154, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34592360

RESUMO

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential to noninvasively detect expression of hypoxia inducible factor-1-alpha (HIF-1α), epidermal growth factor receptor (EGFR), and Ki-67 in nasopharyngeal carcinoma (NPC) by quantitatively measuring tumor blood flow, vascularity, and permeability. PURPOSE: We aim to explore the utility of DCE-MRI in detecting HIF-1α, EGFR, and Ki-67 expression levels using traditional Kety's/Tofts' modeling and quantitative transport mapping (QTM). MATERIALS AND METHODS: Eighty-nine NPC patients underwent DCE-MRI before treatment were enrolled. DCE-MRI was processed to generate the following kinetic parameters: |u| and D from the QTM model, tumor blood flow (TBF) from Kety's model, and Ktrans, Ve, and Kep from Tofts' model. Pretreatment levels of HIF-1α, EGFR, and Ki-67 were assessed by immunohistochemistry and classified into low and high expression groups. RESULTS: |u| (p < 0.001) and TBF (p = 0.015) values were significantly higher in the HIF-1α high-expression group compared to low-expression group. Only Ktrans (p = 0.016) was significantly higher in the EGFR high-expression group. Only |u| (p < 0.001) values were significantly higher in the Ki-67 high-expression group compared to low-expression group. Multiple linear regression analyses showed that |u| independently correlated with HIF-1α and Ki-67 expression, and Ktrans independently correlated with EGFR. The areas under the ROC curves of |u| for HIF-1α and Ki-67, and Ktrans for EGFR were 0.83, 0.74, and 0.70, respectively. CONCLUSION: |u| and Ktrans derived from DCE-MRI may be considered as noninvasive imaging markers for detecting hypoxia and proliferation in NPC patients.

18.
Anal Chem ; 93(34): 11800-11808, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34415158

RESUMO

Phage-borne peptides and antibody fragments isolated from phage display libraries have proven to be versatile and valuable reagents for immunoassay development. Due to the lack of convenient and mild-condition methods for the labeling of the phage particles, isolated peptide/protein affinity ligands are commonly removed from the viral particles and conjugated to protein tracers or nanoparticles for analytical use. This abolishes the advantage of isolating ready-to-use affinity binders and creates the risk of affecting the polypeptide activity. To circumvent this problem, we optimized the phage display system to produce phage particles that express the affinity binder on pIII and a polyglycine short peptide fused to pVIII that allows the covalent attachment of tracer molecules employing sortase A. Using a llama heavy chain only variable domain (VHH) against the herbicide 2,4-D on pIII as the model, we showed that the phage can be extensively decorated with a rhodamine-LPETGG peptide conjugate or the protein nanoluciferase (Nluc) equipped with a C-terminal LPETGG peptide. The maximum labeling amounts of rhodamine-LPETGG and Nluc-LPETGG were 1238 ± 63 and 102 ± 16 per phage, respectively. The Nluc-labeled dual display phage was employed to develop a phage bioluminescent immunoassay (P-BLEIA) for the detection of 2,4-D. The limit of detection and 50% inhibition concentration of P-BLEIA were 0.491 and 2.15 ng mL-1, respectively, which represent 16-fold and 8-fold improvement compared to the phage enzyme-linked immunosorbent assay. In addition, the P-BLEIA showed good accuracy for the detection of 2,4-D in spiked samples.


Assuntos
Bacteriófagos , Ensaio de Imunoadsorção Enzimática , Imunoensaio , Fragmentos de Imunoglobulinas , Biblioteca de Peptídeos
19.
Phytopathology ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34445896

RESUMO

Circular RNAs (circRNAs) are a group of covalently closed RNAs, and their biological function is largely unknown. In this study, we focused on circRNAs that are generated from exon back-splicing (exonic circRNAs). The linear RNA counterparts encode functional proteins, that we can compare and investigate the relationship between circular and linear RNAs. We compared circRNA expression profiles between untreated and Pseudomonas syringae-infected Arabidopsis, and identified and experimentally validated differentially expressed exonic circRNAs by multiple approaches. We found that exonic circRNAs are preferentially enriched in biological processes that associate with biotic and abiotic stress responses. We discovered that circR194 and circR4022 are involved in plant response against P. syringae infection, while circR11208 is involved in response against Botrytis cinerea infection. Intriguingly, our results indicate that these exonic circRNAs function synergistically with their corresponding linear RNAs. Furthermore, circR4022 and circR11208 also play substantial roles in Arabidopsis tolerance to salt stress. This study extends our understanding of the molecular functions of plant circRNAs.

20.
Proc Natl Acad Sci U S A ; 118(34)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34417297

RESUMO

Two independent structures of the proton-pumping, respiratory cytochrome bo 3 ubiquinol oxidase (cyt bo 3 ) have been determined by cryogenic electron microscopy (cryo-EM) in styrene-maleic acid (SMA) copolymer nanodiscs and in membrane scaffold protein (MSP) nanodiscs to 2.55- and 2.19-Å resolution, respectively. The structures include the metal redox centers (heme b, heme o 3 , and CuB), the redox-active cross-linked histidine-tyrosine cofactor, and the internal water molecules in the proton-conducting D channel. Each structure also contains one equivalent of ubiquinone-8 (UQ8) in the substrate binding site as well as several phospholipid molecules. The isoprene side chain of UQ8 is clamped within a hydrophobic groove in subunit I by transmembrane helix TM0, which is only present in quinol oxidases and not in the closely related cytochrome c oxidases. Both structures show carbonyl O1 of the UQ8 headgroup hydrogen bonded to D75I and R71I In both structures, residue H98I occupies two conformations. In conformation 1, H98I forms a hydrogen bond with carbonyl O4 of the UQ8 headgroup, but in conformation 2, the imidazole side chain of H98I has flipped to form a hydrogen bond with E14I at the N-terminal end of TM0. We propose that H98I dynamics facilitate proton transfer from ubiquinol to the periplasmic aqueous phase during oxidation of the substrate. Computational studies show that TM0 creates a channel, allowing access of water to the ubiquinol headgroup and to H98I.

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