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1.
Cell Rep ; : 109109, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33932326

RESUMO

It is unclear whether individuals with enormous diversity in B cell receptor repertoires are consistently able to mount effective antibody responses against SARS-CoV-2. We analyzed antibody responses in a cohort of 55 convalescent patients and isolated 54 potent neutralizing monoclonal antibodies (mAbs). While most of the mAbs target the angiotensin-converting enzyme 2 (ACE2) binding surface on the receptor binding domain (RBD) of SARS-CoV-2 spike protein, mAb 47D1 binds only to one side of the receptor binding surface on the RBD. Neutralization by 47D1 is achieved independent of interfering RBD-ACE2 binding. A crystal structure of the mAb-RBD complex shows that the IF motif at the tip of 47D1 CDR H2 interacts with a hydrophobic pocket in the RBD. Diverse immunoglobulin gene usage and convergent epitope targeting characterize neutralizing antibody responses to SARS-CoV-2, suggesting that vaccines that effectively present the receptor binding site on the RBD will likely elicit neutralizing antibody responses in a large fraction of the population.

2.
Cancer Med ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33939316

RESUMO

BACKGROUND: Body mass index (BMI) has been reported to be inversely associated with incident risk of non-small cell lung cancer (NSCLC). However, the underlying mechanism is still unclear. This study aimed to investigate the role of DNA methylation in the relationship between BMI and NSCLC. METHODS: We carried out a genome-wide DNA methylation study of BMI in peripheral blood among 2266 Chinese participants by using Illumina Methylation arrays. For the BMI-related DNA methylation changes, their associations with NSCLC risk were further analyzed and their mediation effects on BMI-NSCLC association were also evaluated. RESULTS: The methylation levels of four CpGs (cg12593793, cg17061862, cg11024682, and cg06500161, annotated to LMNA, ZNF143, SREBF1, and ABCG1, respectively) were found to be significantly associated with BMI. Methylation levels of cg12593793, cg11024682, and cg06500161 were observed to be inversely associated with NSCLC risk [OR (95%CI) =0.22 (0.16, 0.31), 0.39 (0.30, 0.50), and 0.66 (0.53, 0.82), respectively]. Additionally, cg11024682 in SREBF1 and cg06500161 in ABCG1 mediated 45.3% and 19.5% of the association between BMI and decreased NSCLC risk, respectively. CONCLUSIONS: In this study, we identified four DNA methylation sites associated with BMI in the Chinese populations at the genome-wide significant level. We also found that the BMI-related methylations of SREBF1 and ABCG1 could mediate about a quintile-to-half of the effect of BMI on reduced NSCLC risk, which adds a potential mechanism underlying this association.

3.
J Hazard Mater ; 416: 125839, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33887567

RESUMO

Benzo[a]pyrene (B[a]P) is a typical carcinogen associated with increased lung cancer risk, but the underlying mechanisms remain unclear. This study aimed to investigate epigenome-wide DNA methylation associated with B[a]P exposure and their mediation effects on B[a]P-lung cancer association in two lung cancer case-control studies of 462 subjects. Their plasma levels of benzo[a]pyrene diol epoxide-albumin (BPDE-Alb) adducts and genome-wide DNA methylations were separately detected in peripheral blood by using enzyme-linked immunosorbent assay (ELISA) and genome-wide methylation arrays. The epigenome-wide meta-analysis was performed to analyze the associations between BPDE-Alb adducts and DNA methylations. Mediation analysis was applied to assess effect of DNA methylation on the B[a]P-lung cancer association. We identified 15 CpGs associated with BPDE-Alb adducts (P-meta < 1.0 × 10-5), among which the methylation levels at five loci (cg06245338, cg24256211, cg15107887, cg02211741, and cg04354393 annotated to UBE2O, SAMD4A, ACBD6, DGKZ, and SLFN13, respectively) mediated a separate 38.5%, 29.2%, 41.5%, 47.7%, 56.5%, and a joint 58.2% of the association between BPDE-Alb adducts and lung cancer risk. Compared to the traditional factors [area under the curve (AUC) = 0.788], addition of these CpGs exerted improved discriminations for lung cancer, with AUC ranging 0.828-0.861. Our results highlight DNA methylation alterations as potential mediators in lung tumorigenesis induced by B[a]P exposure.

4.
Int J Biol Macromol ; 182: 207-216, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831453

RESUMO

Arca subcrenata Lischke is a seafood with high nutritional value. In this study, we purified and characterized a novel water-soluble polysaccharide (ASPG-2) from Arca subcrenata with significant immunoregulatory effects and no apparent cell toxicity. ASPG-2 is a class of mixed-linkage α,ß-d-glucan backbones with α-linked side chains with a molecular weight of 4.39 × 105 Da. Its structure was characterized as a repeating unit consisting of (1 → 3)-ß-d-Glcp, (1 → 4)-α-d-Glcp, (1 → 4,6)-α-d-Glcp and (1 → 6)-α-d-Glcp. Using mouse RAW264.7 macrophages, we demonstrated that ASPG-2 exerted marked immunoregulatory effects by promoting the secretion of NO and increasing the phagocytosis of RAW264.7 cells in vitro. Moreover, flow cytometry analysis of the expression of the cell surface molecule CD86 revealed that ASPG-2 could polarize RAW264.7 cells into the M1 type. The immunomodulatory mechanism of ASPG-2 in macrophages was associated with the activation of the TLR4-MAPK/Akt-NF-κB signalling pathways. These results indicated that ASPG-2 might be researched and developed as a potential immunomodulatory agent or health product from marine organisms.

5.
Int J Biol Macromol ; 183: 145-157, 2021 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-33878360

RESUMO

Two novel glucans named MIPB50-W and MIPB50-S-1 were obtained from edible Morchella importuna with molecular weights (Mw) of 939.2 kDa and 444.5 kDa, respectively. MIPB50-W has a backbone of α-(1 → 4)-d-glucan, which was substituted at O-6 position by α-d-Glcp-(1→. Moreover, MIPB50-S-1 has a backbone of α-(1 → 4)-d-glucan, which was substituted at O-6 position by α-d-Glcp-(1 → 6)-α-d-Glcp-(1→. This is the first report about glucan found in Morchella mushrooms. Furthermore, MIPB50-W and MIPB50-S-1 strengthened the phagocytosis function and the promoted secretion of interleukins (IL)-6/tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO), which induced the activation of Toll-like receptor 2 (TLR2), TLR4 as well as mitogen activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Interestingly, MIPB50-S-1 performed the better immunomodulatory activity than that of MIPB50-W in almost all tests. Therefore, MIPB50-W and MIPB50-S-1 are potential immune-enhancing components of functional foods.

6.
Mol Med Rep ; 23(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33880579

RESUMO

Germacrone (GM) displays a wide range of antitumor, antioxidant and anti­inflammatory effects; however, to the best of our knowledge, the effects of GM on lung cancer cell apoptosis and cell cycle arrest have not been previously reported. The aim of the present study was to investigate discussed the effects of GM on the apoptosis and cycle arrest of lung cancer cells. Cell viability, proliferation and apoptosis were assessed by performing Cell Counting Kit­8, colony formation and TUNEL assays, respectively. Western blotting was performed to detect the expression levels of apoptosis­, cell cycle­ and Akt/MDM2 proto­oncogene (MDM2)/p53 signaling pathway­related proteins. Compared with the control group, 50, 100 and 200 µM GM significantly inhibited lung cancer cell proliferation, but significantly induced cell apoptosis and G1/S cell cycle arrest. GM also significantly altered the expression levels of Akt/MDM2/p53 signaling pathway­related proteins compared with the control group. Administration of Akt activator SC79 significantly reversed GM­mediated antiproliferative, proapoptotic and pro­cell cycle arrest effects in lung cancer cells. Therefore, the results of the present study demonstrated that GM induced lung cancer cell apoptosis and cell cycle arrest via the Akt/MDM2/p53 signaling pathway.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33905340

RESUMO

The Internet of Health Things (IoHT) is a concept that describes uniquely identifiable devices connected to the Internet and able to communicate with each other in the medical area. As one of the most important components of smart health monitoring and improvement systems, there are numerous challenges in the IoHT, among which cybersecurity is a major challenge that must be addressed with priority. As a well-received security solution to achieve fine-grained access control, ciphertext-policy weighted attribute-based encryption (CP-WABE) has the potential to ensure data security in the IoHT. However, many issues, such as inflexibility, poor computational capability, and insufficient storage efficiency in attributes comparison, remain. To address these issues, we propose a novel access policy expression method using 0-1 coding technology. Based on this method, a flexible and efficient CP-WABE is constructed for the IoHT. Our scheme supports not only weighted attributes but also any form of comparison of weighted attributes. Furthermore, we use offline/online encryption and outsourced decryption technology to ensure that the scheme can run on an inefficient IoT terminal. Both theoretical and experimental analyses show that our scheme is more efficient and feasible than other schemes. Moreover, security analysis indicates that our scheme achieves security against chosen-plaintext attack.

8.
Anal Methods ; 13(16): 1930-1938, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33913941

RESUMO

Extracellular vesicles (EVs) are nanoscale vesicles with a phospholipid bilayer. In the past few decades, EVs have gained more and more attention, which is attributed to their important roles in cell-to-cell communication. They are regarded as promising sources for disease biomarkers and have been explored for applications in early-stage diagnostics, monitoring of disease status, therapeutics and drug delivery. Nevertheless, EVs are a heterogeneous group of vesicles, and include two predominant classes: exosomes and microvesicles. The origins of these vesicles are diverse, which determines their differences in features and functions. To study the diversity of these EV subpopulations, it is essential to elucidate their compositions including proteins, metabolites, etc. Here, we presented a tandem extraction method to obtain metabolites and proteins from the same batch of EVs simultaneously, enabling a multi-omics differential analysis of exosomes and microvesicles in human plasma. As a result, we found 112 different proteins and 50 different metabolites between exosomes and microvesicles, demonstrating the diversity of these EV subpopulations. Furthermore, compared with human plasma, these two major classes of EVs showed distinct metabolome features, which indicated the necessity of analysing the metabolites derived from EVs to obtain a more comprehensive profile of the plasma metabolome, and the potential of EVs as important sources for biomarker screening.

9.
Sensors (Basel) ; 21(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803086

RESUMO

Angle-of-arrival (AoA) estimation in localized hybrid arrays suffers from phase ambiguity owing to its localized structure and vulnerability to noise. In this letter, we propose a novel phase shift design, allowing each subarray to exploit difference beam steering in two potential AoA directions. This enables the calibration of cross-correlations and an enhanced phase offset estimation between adjacent subarrays. We propose two unambiguous AoA estimation schemes based on the even and odd ratios of the number of antennas per subarray N to the number of different phase shifts per symbol K (i.e., N/K), respectively. The simulation results show that the proposed approach greatly improves the estimation accuracy as compared to the state of the art when the ratio N/K is even.

10.
BMC Surg ; 21(1): 201, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879122

RESUMO

BACKGROUND: Anastomosis-related complications are common after the radical resection of colon cancer. Among such complications, severe stenosis or completely occluded anastomosis (COA) are uncommon in clinical practice, and the separation of the anastomosis is even rarer. For such difficult problems as COA or anastomotic separation, clinicians tend to adopt surgical interventions, and few clinicians try to solve them through endoscopic operations. CASE PRESENTATION: In this article, we present a case of endoscopic treatment of anastomotic closure and separation after radical resection for sigmoid carcinoma. After imaging examination and endoscopic evaluation, we found that the patient had a COA accompanied by a 3-4 cm anastomotic separation. With the aid of fluoroscopy, we attempted to use the titanium clip marker as a guide to perform an endoscopic incision and successfully achieved recanalization. We used a self-expanding covered metal stent to bridge the intestinal canal to resolve the anastomotic separation. Finally, the patient underwent ileostomy takedown, and the postoperative recovery was smooth. The follow-up evaluation results showed that the anastomotic stoma was unobstructed. CONCLUSIONS: We reported the successful application of endoscopic technique in a rare case of COA and separation after colon cancer surgery, which is worth exploring and verifying through more clinical studies in the future.


Assuntos
Anastomose Cirúrgica/efeitos adversos , Colectomia/efeitos adversos , Colonoscopia/métodos , Constrição Patológica/cirurgia , Neoplasias do Colo Sigmoide/cirurgia , Deiscência da Ferida Operatória/cirurgia , Colo/diagnóstico por imagem , Colo/patologia , Colo/cirurgia , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Fluoroscopia , Humanos , Ileostomia , Laparoscopia , Masculino , Pessoa de Meia-Idade , Implantação de Prótese , Stents Metálicos Autoexpansíveis , Neoplasias do Colo Sigmoide/tratamento farmacológico , Deiscência da Ferida Operatória/diagnóstico por imagem , Deiscência da Ferida Operatória/etiologia
11.
J Phys Chem Lett ; : 3767-3772, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844918

RESUMO

Supramolecular co-assembly provides a brand-new powerful strategy for regulating simple organic molecules into various hierarchical nano- and microstructures as smart functional materials. In particular, chiral supramolecular assemblies with strong fluorescent emission have received extensive attention for their application as circularly polarized luminescence (CPL) emitters. Herein, we synthesized three achiral pyrene derivatives, but only the chiral co-assembly (R/S-NMe2-Py-2) can exhibit the regular and orderly helical nanofiber via π-π stacking interaction between chiral N,N'-dimethyl-binaphthyldiamine enantiomers (R/S-NMe2) and the achiral pyrene derivative (Py-2). Interestingly, this kind of 2:1 molar ratio (R/S-NMe2)2-Py-2 co-assembly with a helical nanofiber structure can emit a strong deep blue CPL signal from the achiral pyrene-based emitter, and the dissymmetry factor gem value can reach 0.027 (λem = 423 nm) in the film from spin-coating.

12.
Fertil Steril ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33845988

RESUMO

OBJECTIVE: To compare the effects of hyaluronic acid (HA)-enriched transfer medium versus standard medium on live birth rate after frozen embryo transfer (FET). DESIGN: Randomized, double-blind, controlled trial. SETTING: Two tertiary fertility centers. PATIENT(S): Infertile women aged <43 years at the time of in vitro fertilization undergoing FET. INTERVENTION(S): The women were randomly assigned to 2 groups in a 1:1 ratio. The HA group used EmbryoGlue (Vitrolife, Gothenburg, Sweden) with an HA concentration of 0.5 mg/mL, while the control group used supplemented G-2 (Vitrolife) medium with an HA concentration of 0.125 mg/mL. MAIN OUTCOME MEASURE(S): Live birth rate. RESULT(S): Five hundred fifty women were recruited from April 2016 to April 2018 and included in the intention-to-treat analysis. Eight women in the HA group and 5 women in the control group did not undergo FET because the embryos did not survive on thawing. One woman in the HA group cancelled FET because of fever. One woman in the HA group withdrew and received conventional medium. The 2 groups were similar in demographic characteristics. The live birth rates in the HA group and the control group were comparable (25.5% vs. 25.8%; relative risk 0.99; 95% confidence interval 0.74-1.31). The other clinical outcomes were also similar between the 2 groups. Logistic regression showed that the type of transfer medium was not associated with live birth. CONCLUSION(S): The use of HA-enriched transfer medium does not improve the live birth rate of FET compared with standard medium. TRIAL REGISTRATION NUMBER: NCT02725827 (ClinicalTrials.gov).

14.
Anal Methods ; 13(13): 1591-1600, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33729255

RESUMO

Exosomes are small membrane-bound vesicles secreted by most cell types and play an important role in cell-to-cell communication. Increasing evidence shows that exosomal proteins in urine may be used as novel biomarkers for certain diseases. Purified urinary exosomes are necessary for downstream studies and application development. However, conventional methods for exosome isolation and enrichment are technically challenging and time-consuming. Poor specificity, low recovery and instrumental dependence also limit the use of these methods. It is particularly urgent to develop a rapid and efficient extraction method for basic research and clinical application. Particularly, urine is a dilute solution system with relatively low abundance of exosomes, due to which the isolation of urinary exosome requires more efficient technology. Here, we propose a new strategy for facile exosome isolation from human urine by utilizing the ultrafiltration technique and the specific interaction of TiO2 with the phosphate groups on the lipid bilayer of exosomes. Downstream characterization and proteomic analysis indicate that high-quality exosomes can be obtained from human urine by this ultrafiltration-TiO2 series method in 20 minutes, and 91.5% exosomes with an intact structure are captured from urine by this method. Moreover, 1874 protein groups have been identified through LC-MS. The results show that the protein identification of our method is 23% higher at least than those obtained by conventional strategies. We also identified 30 differential proteins by comparing the urinary exosomes from healthy male and female volunteers. These proteins are related to biological processes, such as lipid metabolism, fatty acid metabolism and nucleotide metabolism. Our analysis reveals that combining conventional ultrafiltration and TiO2-based isolation is ideal to overcome the inherent limitations of identification of exosome proteins derived from urine, and yield highly pure exosome components for downstream proteomic analysis.

15.
mBio ; 12(2)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33785616

RESUMO

Cryptococcus neoformans causes deadly mycosis in immunocompromised individuals. Macrophages are key cells fighting against microbes. Extracellular vesicles (EVs) are cell-to-cell communication mediators. The roles of EVs from infected host cells in the interaction with Cryptococcus remain uninvestigated. Here, EVs from viable C. neoformans-infected macrophages reduced fungal burdens but led to shorter survival of infected mice. In vitro, EVs induced naive macrophages to an inflammatory phenotype. Transcriptome analysis showed that EVs from viable C. neoformans-infected macrophages activated immune-related pathways, including p53 in naive human and murine macrophages. Conserved analysis demonstrated that basic cell biological processes, including cell cycle and division, were activated by infection-derived EVs from both murine and human infected macrophages. Combined proteomics, lipidomics, and metabolomics of EVs from infected macrophages showed regulation of pathways such as extracellular matrix (ECM) receptors and phosphatidylcholine. This form of intermacrophage communication could serve to prepare cells at more distant sites of infection to resist C. neoformans infection.IMPORTANCE Cryptococcus neoformans causes cryptococcal meningitis, which is frequent in patients with HIV/AIDS, especially in less-developed countries. The incidence of cryptococcal meningitis is close to 1 million each year globally. Macrophages are key cells that protect the body against microbes, including C. neoformans Extracellular vesicles are a group of membrane structures that are released from cells such as macrophages that modulate cell activities via the transfer of materials such as proteins, lipids, and RNAs. In this study, we found that Cryptococcus neoformans-infected macrophages produce extracellular vesicles that enhance the inflammatory response in Cryptococcus-infected mice. These Cryptococcus neoformans-infected macrophage vesicles also showed higher fungicidal biological effects on inactivated macrophages. Using omics technology, unique protein and lipid signatures were identified in these extracellular vesicles. Transcriptome analysis showed that these vesicles activated immune-related pathways like p53 in naive macrophages. The understanding of this intermacrophage communication could provide potential targets for the design of therapeutic agents to fight this deadly mycosis.

16.
Parasit Vectors ; 14(1): 158, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726783

RESUMO

BACKGROUND: Neospora caninum is one of the main causes of abortion in pregnant animals. However, N. caninum-induced reproductive injury in male mice is still unclear. METHODS: Male BALB/c mice were infected with a bovine isolate of N. caninum, and the organ coefficients of the testis and epididymis were measured. Lesions in the testis and epididymis were observed by light microscopy and transmission electron microscopy. Expression of the spermatogenic cell apoptosis-related proteins p53 and caspase-3 was detected by western blot. The expression of spermatogenesis-related genes in the testis was detected by reverse transcription-PCR. Sperm morphology and motility were observed. The levels of nitric oxide (NO) and antisperm antibody (AsAb) in the testicular homogenates and hormones in the serum were detected by enzyme-linked immunosorbent assay. The reproductive capacity of the male mice was detected using a reproduction test. RESULTS: The organ coefficients of the testis and epididymis of the experimental group were significantly downregulated. Light microscopy examination revealed that the spermatogenic cells of the testis were arranged in a disordered manner, and the number was reduced. The number of sperm in the epididymal lumen was significantly reduced, and the cytoplasm exhibited vacuolation and degeneration. Ultrastructural studies revealed that the cells of the testis and epididymis tissues showed varying degrees of disease. The level of p53 and caspase-3 expression in the testis was significantly upregulated. The expression of the testicular spermatogenesis-related genes Herc4, Ipo11 and Mrto4 were strongly downregulated. Observation of sperm by microscopic examination revealed significantly reduced sperm density and sperm motility, and the number of sperm deformities was significantly increased. The level of NO and AsAb was significantly increased. The levels of luteinizing hormone, follicle-stimulating hormone and gonadotropin-releasing hormone were significantly upregulated, whereas the levels of testosterone, thyrotropin-releasing hormone, thyroxine and thyroid-stimulating hormone were significantly downregulated. After challenge, the infected male mice and healthy female mice were caged together: the subsequent fetal death rate was increased, and the conception rate, litter size, number of live births and the birth weight were significantly reduced. CONCLUSIONS: Infection of male BALB/c mice with the bovine isolate of N. caninum induced varying degrees of injury to the testis, epididymis and sperm of the mice, destroyed spermatogenesis and affected the reproductive capacity.

17.
Oxid Med Cell Longev ; 2021: 6621644, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33728021

RESUMO

Fatty liver disease (FLD), including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), is a serious chronic metabolic disease that affects a wide range of people. Lipid accumulation accompanied by oxidative stress and inflammation in the liver is the most important pathogenesis of FLD. The plant-based, high-fiber, and low-fat diet has been recommended to manage FLD for a long time. This review discusses the current state of the art into the effects, mechanisms, and clinical application of plant-based foods in NAFLD and AFLD, with highlighting related molecular mechanisms. Epidemiological evidence revealed that the consumption of several plant-based foods was beneficial to alleviating FLD. Further experimental studies found out that fruits, spices, teas, coffee, and other plants, as well as their bioactive compounds, such as resveratrol, anthocyanin, curcumin, and tea polyphenols, could alleviate FLD by ameliorating hepatic steatosis, oxidative stress, inflammation, gut dysbiosis, and apoptosis, as well as regulating autophagy and ethanol metabolism. More importantly, clinical trials confirmed the beneficial effects of plant-based foods on patients with fatty liver. However, several issues need to be further studied especially the safety and effective doses of plant-based foods and their bioactive compounds. Overall, certain plant-based foods are promising natural sources of bioactive compounds to prevent and alleviate fatty liver disease.

18.
Med Sci Monit ; 27: e929684, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690263

RESUMO

The treatment measures of medication-related osteonecrosis of the jaw (MRONJ) is a worldwide challenge in oral and maxillofacial surgery because of its unclear pathogenesis. Previous studies suggested that mesenchymal stem cells played important roles in promoting MRONJ lesion healing, but the detailed mechanisms were unknown. Increasing numbers of studies have demonstrated that exosomes derived from mesenchymal stem cells, especially adipose-derived stem cells, have key roles in stem cell-based therapies by accelerating bone remodeling, facilitating angiogenesis, and promoting wound healing. We hypothesized that exosomes derived from adipose-derived stem cells can prevent MRONJ by accelerating gingival healing and enhancing bone remodeling processes. Our results may provide a promising therapeutic option for MRONJ clinical therapy.

19.
Clin Chem ; 67(4): 672-683, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33788940

RESUMO

BACKGROUND: Infectious disease outbreaks such as the COVID-19 (coronavirus disease 2019) pandemic call for rapid response and complete screening of the suspected community population to identify potential carriers of pathogens. Central laboratories rely on time-consuming sample collection methods that are rarely available in resource-limited settings. METHODS: We present a highly automated and fully integrated mobile laboratory for fast deployment in response to infectious disease outbreaks. The mobile laboratory was equipped with a 6-axis robot arm for automated oropharyngeal swab specimen collection; virus in the collected specimen was inactivated rapidly using an infrared heating module. Nucleic acid extraction and nested isothermal amplification were performed by a "sample in, answer out" laboratory-on-a-chip system, and the result was automatically reported by the onboard information platform. Each module was evaluated using pseudovirus or clinical samples. RESULTS: The mobile laboratory was stand-alone and self-sustaining and capable of on-site specimen collection, inactivation, analysis, and reporting. The automated sampling robot arm achieved sampling efficiency comparable to manual collection. The collected samples were inactivated in as short as 12 min with efficiency comparable to a water bath without damage to nucleic acid integrity. The limit of detection of the integrated microfluidic nucleic acid analyzer reached 150 copies/mL within 45 min. Clinical evaluation of the onboard microfluidic nucleic acid analyzer demonstrated good consistency with reverse transcription quantitative PCR with a κ coefficient of 0.979. CONCLUSIONS: The mobile laboratory provides a promising solution for fast deployment of medical diagnostic resources at critical junctions of infectious disease outbreaks and facilitates local containment of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) transmission.


Assuntos
/métodos , Laboratórios , Unidades Móveis de Saúde , Patologia Molecular/métodos , RNA Viral/análise , Adulto , Automóveis , /instrumentação , Feminino , Humanos , Dispositivos Lab-On-A-Chip , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Coronavírus da Síndrome Respiratória do Oriente Médio/química , Técnicas de Diagnóstico Molecular/instrumentação , Técnicas de Diagnóstico Molecular/métodos , Pandemias , Patologia Molecular/instrumentação , Robótica , /química
20.
JAMA Netw Open ; 4(3): e213486, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33783517

RESUMO

Importance: Exhaled breath is an attractive option for cancer detection. A sensitive and reliable breath test has the potential to greatly facilitate diagnoses and therapeutic monitoring of lung cancer. Objective: To investigate whether the breath test is able to detect lung cancer using the highly sensitive high-pressure photon ionization time-of-flight mass spectrometry (HPPI-TOFMS). Design, Setting, and Participants: This diagnostic study was conducted with a prospective-specimen collection, retrospective-blinded evaluation design. Exhaled breath samples were collected before surgery and detected by HPPI-TOFMS. The detection model was constructed by support vector machine (SVM) algorithm. Patients with pathologically confirmed lung cancer were recruited from Peking University People's Hospital, and healthy adults without pulmonary noncalcified nodules were recruited from Aerospace 731 Hospital. Data analysis was performed from August to October 2020. Exposures: Breath testing and SVM algorithm. Main Outcomes and Measures: The detection performance of the breath test was measured by sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve (AUC). Results: Exhaled breath samples were from 139 patients with lung cancer and 289 healthy adults, and all breath samples were collected and tested. Of all participants, 228 (53.27%) were women and the mean (SD) age was 57.0 (11.4) years. After clinical outcomes were ascertained, all participants were randomly assigned into the discovery data set (381 participants) and the blinded validation data set (47 participants). The discovery data set was further broken into a training set (286 participants) and a test set (95 participants) to construct and test the detection model. The detection model reached a mean (SD) of 92.97% (4.64%) for sensitivity, 96.68% (2.21%) for specificity, and 95.51% (1.93%) for accuracy in the test set after 500 iterations. In the blinded validation data set (47 participants), the model revealed a sensitivity of 100%, a specificity of 92.86%, an accuracy of 95.74%, and an AUC of 0.9586. Conclusions and Relevance: This diagnostic study's results suggest that a breath test with HPPI-TOFMS is feasible and accurate for lung cancer detection, which may be useful for future lung cancer screenings.

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