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1.
Food Chem ; 398: 133913, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35964560

RESUMO

This experiment investigated the underlying mechanism of ultrasonic-assisted stewing to enhance the aroma intensity of chicken broth by measuring fat content, oil droplet sizes, zeta potential, viscosity, surface protein loading, lipid oxidation, and aroma compound concentrations. As the thermo-ultrasound time increased, the fat content increased from 0.3 % to 1.2 %, resulting in a milky white appearance. After 1 h of thermo-ultrasound, the broth had the smallest particle size and the highest surface protein load, viscosity, and emulsion stability, as well as the highest total amount of aroma-active compounds of 314.70 ng/mg. With the further extension of thermo-ultrasound time, lipid oxidation increased, but the stability of chicken broth decreased, lowering the content of aroma-active compounds. These outcomes suggested that thermo-ultrasound could enhance the aroma intensity of chicken broth by increasing the fat content and the emulsion stability of the broth.


Assuntos
Galinhas , Odorantes , Animais , Emulsões/química , Lipídeos , Proteínas de Membrana , Odorantes/análise , Ultrassom
2.
Neural Regen Res ; 18(5): 983-990, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36254978

RESUMO

Cerebral ischemia is a serious disease that triggers sequential pathological mechanisms, leading to significant morbidity and mortality. Although most studies to date have typically focused on the lysosome, a single organelle, current evidence supports that the function of lysosomes cannot be separated from that of the endolysosomal system as a whole. The associated membrane fusion functions of this system play a crucial role in the biodegradation of cerebral ischemia-related products. Here, we review the regulation of and the changes that occur in the endolysosomal system after cerebral ischemia, focusing on the latest research progress on membrane fusion function. Numerous proteins, including N-ethylmaleimide-sensitive factor and lysosomal potassium channel transmembrane protein 175, regulate the function of this system. However, these proteins are abnormally expressed after cerebral ischemic injury, which disrupts the normal fusion function of membranes within the endolysosomal system and that between autophagosomes and lysosomes. This results in impaired "maturation" of the endolysosomal system and the collapse of energy metabolism balance and protein homeostasis maintained by the autophagy-lysosomal pathway. Autophagy is the final step in the endolysosomal pathway and contributes to maintaining the dynamic balance of the system. The process of autophagosome-lysosome fusion is a necessary part of autophagy and plays a crucial role in maintaining energy homeostasis and clearing aging proteins. We believe that, in cerebral ischemic injury, the endolysosomal system should be considered as a whole rather than focusing on the lysosome. Understanding how this dynamic system is regulated will provide new ideas for the treatment of cerebral ischemia.

3.
Neural Regen Res ; 18(5): 1124-1131, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36255002

RESUMO

The onset of retinal degenerative disease is often associated with neuronal loss. Therefore, how to regenerate new neurons to restore vision is an important issue. NeuroD1 is a neural transcription factor with the ability to reprogram brain astrocytes into neurons in vivo. Here, we demonstrate that in adult mice, NeuroD1 can reprogram Müller cells, the principal glial cell type in the retina, to become retinal neurons. Most strikingly, ectopic expression of NeuroD1 using two different viral vectors converted Müller cells into different cell types. Specifically, AAV7m8 GFAP681::GFP-ND1 converted Müller cells into inner retinal neurons, including amacrine cells and ganglion cells. In contrast, AAV9 GFAP104::ND1-GFP converted Müller cells into outer retinal neurons such as photoreceptors and horizontal cells, with higher conversion efficiency. Furthermore, we demonstrate that Müller cell conversion induced by AAV9 GFAP104::ND1-GFP displayed clear dose- and time-dependence. These results indicate that Müller cells in adult mice are highly plastic and can be reprogrammed into various subtypes of retinal neurons.

4.
J Colloid Interface Sci ; 631(Pt B): 89-100, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36395630

RESUMO

Construction of multi-component heterostructures as a flame retardant reinforcer within a polymer is a favorable option to realize the synergistic effects between different types of reinforcers. However, it is difficult to improve polymer flame retardance as the poor compatibility of retardants with polymer matrix can lead to low dispersion. Herein, 3-D flower-like templated layered double hydroxides (LDH) and graphene (rGO) were prepared on the surface of a caprolactam-modified casein micelle template for integration with casein latex based on a blending-casting method. Temp@LDH-rGO hardly affected the stability of the casein-based latex, as its casein-based composite latex was used as a leather surface coating. The limiting oxygen index of finished leather increased up to 27.4% when casein-based 4% Temp@LDH-rGO composite latex was applied for leather finishing. In contrast, its heat release rate and smoke production rate were lowered to 55.686 kW/m2 and 2.239 m-2 s-1, respectively. According to the combustion analysis, the leather samples finished by casein-based Temp@LDH-rGO latex exhibited significant improvement in flame retardant and smoke suppression performance. The casein-based Temp@LDH-rGO composite latex has thus been demonstrated as a highly effective option for functional coatings in diverse fields (e.g., automobile interior decoration, furniture manufacturing, and firefighting equipment).


Assuntos
Retardadores de Chama , Látex , Caseínas , Hidróxidos , Fumaça
5.
Food Chem ; 402: 134303, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36152552

RESUMO

A novel extraction method of volatile aroma compounds (VACs) from walnut oil (WO) using monolithic material adsorption extraction (MMSE) was developed herein, and its efficiency was compared with the conventional extraction method based on solid-phase microextraction (SPME) combined with gas chromatography-olfactory-mass spectrometry (GC-O-MS). After protocol optimization of MMSE-RSC18, 77 volatile compounds (38 ones can be sniffed) were extracted from WO, thus having a better performance compared to SPME (56 volatile compounds, 35 ones can be sniffed). Subsequently, based on flavor dilution factors (FDs), odor activity values (OAVs), and recombination and omission experiments, key aroma-active compounds in WO were 1-octen-3-ol (OAV = 82.58), (E)-2-decenal (OAV = 4.10), linalool (OAV = 2.37), γ-dodecalactone (OAV = 2.30), 2-pentylfuran (OAV = 1.62), (E)-2-nonenal (OAV = 1.14) and pentanal (OAV = 1.04). Collectively, compared to HS-SPME, MMSE-RSC18 provided higher capture efficiency of VACs, enabling efficient extraction and analysis of sample aromas.


Assuntos
Juglans , Compostos Orgânicos Voláteis , Odorantes/análise , Adsorção , Cromatografia Gasosa-Espectrometria de Massas/métodos , Olfato , Compostos Orgânicos Voláteis/análise , Olfatometria/métodos
7.
Cell Oncol (Dordr) ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434360

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) cell-derived exosomal LncRNA SNHG16 is highly expressed and associated with poor overall survival of patients. Telocytes (TCs), as novel interstitial cells, have been reported to promote HCC metastasis. Therefore, in our study, we investigated whether a molecular interaction occurred between exosomal LncSNHG16 and TCs in the tumor microenvironment. METHODS: LncSNHG16 expression in HCC tissues and cell lines was measured, and bioinformatics analysis was performed. Exosomes were isolated and purified from HCC cells with LncSNHG16 overexpression/knockdown vectors and cocultured with TCs. Then, markers of the LncSNHG16/miR-942-3p/MMP9 axis were tested in TCs. Transwell assays and cell wound healing assays were designed to examine the invasion and migration of HCC cells after coincubation with TCs. RNA immunoprecipitation (RIP) assays and dual-luciferase gene reporter assays were performed to verify the binding effect of LncSNHG16, miR-942-3p, and MMP9 mRNA. In vivo, experimental animal models were established to confirm the effect of exosomal LncSNHG16-induced MMP9 expression on HCC metastasis. RESULTS: Exosomal LncSNHG16 was phagocytized by TCs and downregulated miR-942-3p, which induced targeted MMP9 upregulation, and it had specific binding sites with miR-942-3p in TCs to facilitate the migration of HCC cells in vitro and in vivo. Exosomal LncSNHG16 was found to act as a competing endogenous RNA of the miR-942-3p/MMP9 axis in TCs. CONCLUSION: Tumour-derived exosomal LncSNHG16 modulates MMP9 via competitively binding to miR-942-3p in TCs, thus promoting the metastasis of HCC.

8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(9): 1275-1280, 2022.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36411712

RESUMO

Chlamydia trachomatis (CT) genital tract infection is insidious, and patients often have no conscious symptoms.Delayed treatment after infection can lead to serious complications. Chlamydia muridarum (CM) genital tract infection in female mice can simulate CT genital tract infection in women, which is an ideal model to investigate the pathogenesis of CT. CM plasmid protein pGP3, chromosomal protein TC0237/TC0668, CM-specific CD8+ T cells, TNF-α, and IL-13 can induce genital tract inflammation, CD4+ T cells are responsible for CM clearance. However, tubal inflammation persists after genital tract CM is removed. Genital tract CM can spread spontaneously in vivo and colonize the gastrointestinal (GI) tract, but the GI tract CM cannot reverse spread to the genital tract. The survival time and number of CM transmitted from genital tract to GI tract are positively correlated with the long-term lesion of oviduct, while the CM inoculated directly into the GI tract has no pathogenicity in both the genital and GI tract. The double attack pattern of Chlamydia-induced genital tract inflammatory lesions is as follows: CM infection of oviduct epithelial cells initiates the process of oviduct repair as the first attack. After genital CM spreads to the GI tract, activated chlamydia-specific CD8+ T cells are recruited to the genital tract and secreted pro-fibrotic cytokines such as TNF-α and IL-13. This process is called the second attack which transform tubal repair initiated by the first attack into long-term tubal fibrosis/hydrosalpinx. Elucidating the pathogenic mechanism of Chlamydia infection can provide new ideas for the development of Chlamydia vaccine, which is expected to solve the problems of infertility caused by repeated CT infection in women.


Assuntos
Infecções por Chlamydia , Chlamydia muridarum , Infecções do Sistema Genital , Feminino , Camundongos , Animais , Interleucina-13 , Linfócitos T CD8-Positivos/patologia , Fator de Necrose Tumoral alfa , Infecções por Chlamydia/patologia , Genitália/patologia , Trato Gastrointestinal/patologia , Inflamação
9.
Biosensors (Basel) ; 12(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36354459

RESUMO

Since the 2019-nCoV outbreak was first reported, hundreds of millions of people all over the world have been infected. There is no doubt that improving the cure rate of 2019-nCoV is one of the most effective means to deal with the current serious epidemic. At present, Remdesivir (RDV) has been clinically proven to be effective in the treatment of SARS-CoV-2. However, the uncertain side effects make it important to reduce the use of drugs while ensuring the self-healing effect. We report an approach here with targeted therapy for the treatment of SARS-CoV-2 and other coronaviruses illness. In this study, mesoporous silica was used as the carrier of RDV, the nucleocapsid protein (N protein) aptamer was hybridized with the complementary chain, and the double-stranded DNA was combined with gold nanoparticles as the gates of mesoporous silica pores. When the RDV-loaded mesoporous silica is incubated with the N protein, aptamer with gold nanoparticles dissociate from the complementary DNA oligonucleotide on the mesoporous silica surface and bind to the N protein. The releasing of RDV was determined by detecting the UV-vis absorption peak of RDV in the solution. These results show that the RDV delivery system designed in this work has potential clinical application for the treatment of 2019-nCoV.


Assuntos
Aptâmeros de Nucleotídeos , COVID-19 , Nanopartículas Metálicas , Nanopartículas , Humanos , Dióxido de Silício , SARS-CoV-2 , Ouro , COVID-19/tratamento farmacológico
10.
J Sci Food Agric ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347590

RESUMO

BACKGROUND: The authors previously prepared a microencapsulated complex of thymol, carvacrol, and cinnamaldehyde (MEEO). This study aimed to evaluate the effect of MEEO on the intestinal mucosal barrier and homeostasis in weaning piglets. A comparison of the effect of MEEO versus chlortetracycline (CTC) was performed in this study. RESULTS: Piglets were divided into three groups - control (Con), MEEO, and CTC groups - and raised for 28 days. The results showed that MEEO significantly elevated the ratio of the villus height and the crypt depth in the jejunum and decreased the crypt depth in the ileum compared with the other groups (P < 0.05); it also upregulated the messenger ribonucleic acid (mRNA) expression of tight junction protein in the small intestine. Compared with the Con group, MEEO increased the concentration of secretory immunoglobulin A (sIgA), cathelicidin antimicrobial peptides (CAMP), and interleukin 10 (IL-10), while decreasing the interleukin 1 beta (IL-1ß) concentration in both jejunal and ileal mucosa (P < 0.05). The mRNA expression of jejunal mucosal MUC1 and ileal mucosal MUC2 was increased in the MEEO group compared with the other groups (P < 0.05). Intestinal microbial analysis showed that dietary treatment had little impact on the ileal microbial structure. A significant rise in the genus Lactobacillus was, however, found in the MEEO group. There is a positive correlation between the Lactobacillus and sIgA, and between the Lactobacillus and CAMP, indicating that an improvement in the mucosal barrier function by the addition of MEEO may be associated with the proliferation of Lactobacillus. CONCLUSION: Dietary supplementation with MEEO improves intestinal barrier function in weaning piglets, the effect of which was superior to CTC. © 2022 Society of Chemical Industry.

11.
Sci Rep ; 12(1): 19959, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402912

RESUMO

Cinnamon aqueous extract's active substance base remains unclear and its mechanisms, mainly the therapeutic target of anti-Alzheimer's disease (AD)-related GABAergic synaptic dysfunction, remain unclear. Here, 30 chemical components were identified in the aqueous extract of cinnamon using LC/MS; secondly, we explored the brain-targeting components of the aqueous extract of cinnamon, and 17 components had a good absorption due to the blood-brain barrier (BBB) limitation; thirdly, further clustering analysis of active ingredient targets by network pharmacology showed that the GABA pathway with GABRG2 as the core target was significantly enriched; then, we used prominent protein-protein interactions (PPI), relying on a protein-metabolite network, and identified the GABRA1, GABRB2 and GABRA5 as the closest targets to GABRG2; finally, the affinity between the target and its cognate active compound was predicted by molecular docking. In general, we screened five components, methyl cinnamate, propyl cinnamate, ( +)-procyanidin B2, procyanidin B1, and myristicin as the brain synapse-targeting active substances of cinnamon using a systematic strategy, and identified GABRA1, GABRB2, GABRA5 and GABRG2 as core therapeutic targets of cinnamon against Alzheimer's disease-related GABAergic synaptic dysfunction. Exploring the mechanism of cinnamon' activities through multi-components and multiple targets strategies promise to reduce the threat of single- target and symptom-based drug discovery failure.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Cinnamomum zeylanicum , Simulação de Acoplamento Molecular , Farmacologia em Rede , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Medicamentos de Ervas Chinesas/farmacologia
12.
Front Microbiol ; 13: 945463, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406461

RESUMO

Objective: To systematically evaluate the significance of Fusobacterium nucleatum (Fn) levels the clinicopathological impacts of cancer. Methods: Literature from Pubmed, Embase, and Web of Science was retrieved to collect all English literatures on the correlation between Fn and cancer, and the quality of literatures collected was assessed based on the Newcastle-Ottawa Quality Assessment Scale. The heterogeneity and sensitivity were detected by Stata 14.0 software, and the correlation between Fn and cancer clinicopathological as the effect variables was assessed according to the odds ratio (OR) and 95% confidence interval (CI). The forest plot was drawn. Results: A total of 19 articles meeting the inclusion criteria were selected. The incidence of Fn prevalence varied considerably (range: 6.1 to 83.3%) and was greater than 10% in 13 of 19 studies. Compared with those with no/low Fn levels, the high levels of Fn was positively associated with vascular invasion, nerve invasion, depth of invasion, and distant metastasis [vascular invasion: OR = 1.66, 95%CI(1.07, 2.57), I 2 = 21.9%, fixed effect model; nerve invasion: OR = 1.36, 95%CI(1.00, 1.84), I 2 = 43.1%, fixed effect model; infiltration depth: OR = 1.94, 95%CI(1.20, 3.15), I 2 = 67.2%, random effect model; distant metastasis: OR = 1.80, 95%CI(1.23, 2.64), I 2 = 3.4%, fixed effect model]. Patients with MLH1 methylation always present a higher Fn levels than those without methylation [OR = 2.53, 95%CI(1.42, 4.53), P = 0.01, I 2 = 57.5%, random effect model]. Further, Fn was associatedwith the molecular characteristics of cancers [MSI-H Vs. MSS/MSI-low: OR = 2.92, 95%CI(1.61, 5.32), P = 0.01, I 2 = 63.2%, random effect model; High Vs. Low/Negative CIMP: OR = 2.23, 95%CI(1.64, 3.03), P = 0.01, I 2 = 64.2%, random effect model; KRAS mutation Vs. wild-type: OR = 1.24, 95%CI(1.04, 1.48), P = 0.02, I 2 = 27.0%, fixed effect model; Present Vs. Abscent BRAF mutations: OR = 1.88, 95%CI(1.44, 2.45), P = 0.01, I 2 = 24.2%, fixed effect model]. The cancer patients with high levels of Fn often have worse RFS than those with no/low Fn levels[OR = 1.14, 95%CI(0.61, 1.68), P = 0.01, I 2 = 80.7%, random effect model]. Conclusion: This review and meta-analysis showed that Fn could be used to predict unfavorable prognosis and function as potential prognostic biomarkers in colorectal cancer (CRC). Our data may have implications for targeting Fn to develop strategies for cancer prevention and treatment.

13.
Cancer Commun (Lond) ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357174

RESUMO

Antibody-drug conjugates (ADCs) are a rapidly developing therapeutic approach in cancer treatment that has shown remarkable activity in breast cancer. Currently, there are two ADCs approved for the treatment of human epidermal growth factor receptor 2-positive breast cancer, one for triple-negative breast cancer, and multiple investigational ADCs in clinical trials. However, drug resistance has been noticed in clinical use, especially in trastuzumab emtansine. Here, the mechanisms of ADC resistance are summarized into four categories: antibody-mediated resistance, impaired drug trafficking, disrupted lysosomal function, and payload-related resistance. To overcome or prevent resistance to ADCs, innovative development strategies and combination therapy options are being investigated. Analyzing predictive biomarkers for optimal therapy selection may also help to prevent drug resistance.

14.
Microbiol Spectr ; : e0255722, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36374015

RESUMO

Antimicrobial resistance in bacteria is the most urgent global threat to public health, with extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) being one of the most documented examples. Nonetheless, the ESBL-E. coli transmission relationship among clinical sites and chicken farms remains unclear. Here, 408 ESBL-E. coli strains were isolated from hospitals and chicken farms in Sichuan Province and Yunnan Province in 2021. We detected blaCTX-M genes in 337 (82.62%) ESBL-E. coli strains. Although the isolation rate, prevalent sequence type (ST) subtypes, and blaCTX-M gene subtypes of ESBL-E. coli varied based on regions and sources, a few strains of CTX-ESBL-E. coli derived from clinical sites and chicken farms in Sichuan Province displayed high genetic similarity. This indicates a risk of ESBL-E. coli transmission from chickens to humans. Moreover, we found that the high-risk clonal strains ST131 and ST1193 primarily carried blaCTX-M-27. This indicates that drug-resistant E. coli from animal and human sources should be monitored. As well, the overuse of ß-lactam antibiotics should be avoided in poultry farms to ensure public health and build an effective regulatory mechanism of "farm to fork" under a One Health perspective. IMPORTANCE Bacterial drug resistance has become one of the most significant threats to human health worldwide, especially for extended-spectrum ß-lactamase-producing E. coli (ESBL-E. coli). Timely and accurate epidemiological surveys can provide scientific guidance for the adoption of treatments in different regions and also reduce the formation of drug-resistant bacteria. Our study showed that the subtypes of ESBL-E. coli strains prevalent in different provinces are somewhat different, so it is necessary to individualize treatment regimens in different regions, and it is especially important to limit and reduce antibiotic use in poultry farming since chicken-derived ESBL-E. coli serves as an important reservoir of drug resistance genes and has the potential to spread to humans, thus posing a threat to human health. The use of antibiotics in poultry farming should be particularly limited and reduced.

15.
Neuron ; 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36370710

RESUMO

The coordination mechanism of neural innate immune responses for axon regeneration is not well understood. Here, we showed that neuronal deletion of protein tyrosine phosphatase non-receptor type 2 sustains the IFNγ-STAT1 activity in retinal ganglion cells (RGCs) to promote axon regeneration after injury, independent of mTOR or STAT3. DNA-damage-induced cGAMP synthase (cGAS)-stimulator of interferon genes (STINGs) activation is the functional downstream signaling. Directly activating neuronal STING by cGAMP promotes axon regeneration. In contrast to the central axons, IFNγ is locally translated in the injured peripheral axons and upregulates cGAS expression in Schwann cells and infiltrating blood cells to produce cGAMP, which promotes spontaneous axon regeneration as an immunotransmitter. Our study demonstrates that injured peripheral nervous system (PNS) axons can direct the environmental innate immune response for self-repair and that the neural antiviral mechanism can be harnessed to promote axon regeneration in the central nervous system (CNS).

16.
Environ Microbiol ; 2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36335557

RESUMO

It remains unclear whether periphytic biofilms are beneficial to N cycling in paddy fields. Here, based on a national-scale field investigation covering 220 rice fields in China, the N accumulation potential of periphytic biofilms was found to decrease from 8.8 ± 2.4 to 4.5 ± 0.7 g/kg and 3.1 ± 0.6 g/kg with increasing habitat latitude and longitude, respectively. The difference in abundant and rare subcommunities likely accounts for their geo-difference in N accumulation potential. The N cycling pathways involved in periphytic biofilms inferred that soil N and N2 were two potential sources for N accumulation in periphytic biofilms. Meanwhile, some of the accumulated N may be lost via N2 , N2 O, NO, or NH3 outputs. Superficially, periphytic biofilms are double-edged swords to N cycling by increasing soil N through biological N fixation but accelerating greenhouse gas emissions. Essentially, augmented periphytic biofilms increased change of TN (ΔTN) content in paddy soil from -231.9 to 31.9 mg/kg, indicating that periphytic biofilms overall benefit N content enhancement in paddy fields. This study highlights the contribution of periphytic biofilms to N cycling in rice fields, thus, drawing attention to their effect on rice production and environmental security.

17.
J Am Heart Assoc ; 11(22): e027578, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36346048

RESUMO

Background Dilated cardiomyopathy (DCM), characterized by progressive left ventricular enlargement and systolic dysfunction, is the most common type of cardiomyopathy and a leading cause of heart failure and cardiac death. Accumulating evidence underscores the critical role of genetic defects in the pathogenesis of DCM, and >250 genes have been implicated in DCM to date. However, DCM is of substantial genetic heterogeneity, and the genetic basis underpinning DCM remains elusive in most cases. Methods and Results By genome-wide scan with microsatellite markers and genetic linkage analysis in a 4-generation family inflicted with autosomal-dominant DCM, a new locus for DCM was mapped on chromosome 15q13.1-q13.3, a 4.77-cM (≈3.43 Mbp) interval between markers D15S1019 and D15S1010, with the largest 2-point logarithm of odds score of 5.1175 for the marker D15S165 at recombination fraction (θ)=0.00. Whole-exome sequencing analyses revealed that within the mapping chromosomal region, only the mutation in the KLF13 gene, c.430G>T (p.E144X), cosegregated with DCM in the family. In addition, sequencing analyses of KLF13 in another cohort of 266 unrelated patients with DCM and their available family members unveiled 2 new mutations, c.580G>T (p.E194X) and c.595T>C (p.C199R), which cosegregated with DCM in 2 families, respectively. The 3 mutations were absent from 418 healthy subjects. Functional assays demonstrated that the 3 mutants had no transactivation on the target genes ACTC1 and MYH7 (2 genes causally linked to DCM), alone or together with GATA4 (another gene contributing to DCM), and a diminished ability to bind the promoters of ACTC1 and MYH7. Add, the E144X-mutant KLF13 showed a defect in intracellular distribution. Conclusions This investigation indicates KLF13 as a new gene predisposing to DCM, which adds novel insight to the molecular pathogenesis underlying DCM, implying potential implications for prenatal prevention and precision treatment of DCM in a subset of patients.


Assuntos
Cardiomiopatia Dilatada , Humanos , Cardiomiopatia Dilatada/metabolismo , Mutação , Linhagem , Proteínas Repressoras/genética , Proteínas de Ciclo Celular/genética , Fatores de Transcrição Kruppel-Like/genética
18.
BMC Bioinformatics ; 23(1): 470, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348299

RESUMO

BACKGROUND: The expression changes of some proteins are associated with cancer progression, and can be used as biomarkers in cancer diagnosis. Automated systems have been frequently applied in the large-scale detection of protein biomarkers and have provided a valuable complement for wet-laboratory experiments. For example, our previous work used an immunohistochemical image-based machine learning classifier of protein subcellular locations to screen biomarker proteins that change locations in colon cancer tissues. The tool could recognize the location of biomarkers but did not consider the effect of protein expression level changes on the screening process. RESULTS: In this study, we built an automated classification model that recognizes protein expression levels in immunohistochemical images, and used the protein expression levels in combination with subcellular locations to screen cancer biomarkers. To minimize the effect of non-informative sections on the immunohistochemical images, we employed the representative image patches as input and applied a Wasserstein distance method to determine the number of patches. For the patches and the whole images, we compared the ability of color features, characteristic curve features, and deep convolutional neural network features to distinguish different levels of protein expression and employed deep learning and conventional classification models. Experimental results showed that the best classifier can achieve an accuracy of 73.72% and an F1-score of 0.6343. In the screening of protein biomarkers, the detection accuracy improved from 63.64 to 95.45% upon the incorporation of the protein expression changes. CONCLUSIONS: Machine learning can distinguish different protein expression levels and speed up their annotation in the future. Combining information on the expression patterns and subcellular locations of protein can improve the accuracy of automatic cancer biomarker screening. This work could be useful in discovering new cancer biomarkers for clinical diagnosis and research.


Assuntos
Biomarcadores Tumorais , Neoplasias , Imuno-Histoquímica , Redes Neurais de Computação , Aprendizado de Máquina , Proteínas , Neoplasias/diagnóstico
19.
BMC Infect Dis ; 22(1): 831, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352356

RESUMO

BACKGROUND: At present, the role of inactivated vaccines in viral RNA shedding among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) breakthrough infections is still unknown. METHODS: We collected data of 147 coronavirus disease 2019 (COVID-19) patients with mild-to-moderate illness who were hospitalized in the Third People's Hospital of Yangzhou from 7 to 20 August 2021 and analyzed the differences in symptoms and laboratory tests among fully vaccinated (FV), partially vaccinated (PV) and unvaccinated (UV) patients. RESULTS: The median duration of viral RNA shedding was shorter in the FV (12 [IQR, 9.5-14] days) and PV (13 [IQR, 9-16.75] days) groups than in the UV group (15 [IQR, 11.75-17.25] days) (adjusted P < 0.001 and adjusted P = 0.23, respectively). The median titers of SARS-CoV-2-specific IgG and IgM were significantly higher in the FV (12.29 S/co [IQR, 2.08-63.59] and 0.3 S/co [IQR, 0.05-2.29], respectively) and PV (0.68 S/co [IQR, 0.14-28.69] and 0.12 S/co [0.03-5.23], respectively) groups than in the UV group (0.06 S/co [IQR, 0.03-0.47] and 0.04 S/co [IQR, 0.02-0.07]) (adjusted P < 0.001 and adjusted P = 0.008, respectively). CONCLUSIONS: Inactivated vaccines may shorten viral RNA shedding in breakthrough infected patients who have mild-to-moderate illness and may improve the ability of the host to generate specific antibodies to infection.


Assuntos
COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , RNA Viral , Estudos Retrospectivos , Vacinas de Produtos Inativados , Anticorpos Antivirais , Imunoglobulina G , Imunoglobulina M
20.
Materials (Basel) ; 15(21)2022 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-36363038

RESUMO

Surface-enhanced Raman spectroscopy (SERS) can be regarded as a powerful tool for probing chemical molecules by effectively enhancing Raman signals. However, the enhancement factors depend on the SERS template, the probed molecular structures, and the excitation laser wavelength. Herein, we proposed a simple and easily fabricated nanostructured template for SERS and analyzed the wavelength-dependent factors. Three types of golden nanopillar arrays on silicon wafers were designed and manufactured. The SERS signals of the Rhodamine 6G (R6G) molecules were extracted. Three laser sources, a blue 17 mW 458 nm diode laser, a green 20 mW 532 nm laser, and a red 6 mW 633 nm laser, were employed as the excitation laser sources. The 458 nm laser was located far from the resonate spectrum of R6G. The optical intensity distributions for the different SERS templates excited by three laser beams were also simulated. The enhancement factors (EFs) of R6G on the three nanostructured templates were measured and compared. The photoluminescence spectrum of the nanostructured templates and SERS signals of R6G were also measured. In addition, the experimental results concerned optical simulations. The analysis tool that was used was a convolution profile of multiple Lorentzian line shapes with a Gaussian profile. It is helpful to understand the SERS signals when the excitation laser wavelength is located out of the resonance region of molecules. It can also provide a new design approach to fabricate an SERS Template with a nanopillar array for different excitation wavelengths.

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