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1.
Bioelectrochemistry ; 160: 108750, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38852385

ABSTRACT

Overuse of enrofloxacin (ENR) has posed a potential threat to ecosystems and public health, so it is critical to sensitive and accurate determination of ENR residues. In this work, a novel ultra-sensitive and specific electrochemical aptasensor was fabricated based on the cobalt diselenide loaded gold and platinum nanoflowers (Au@Pt NFs/ CoSe2) and Exonuclease III (Exo III)-assisted cycle amplification strategy for the detection of ENR. Au@Pt NFs/ CoSe2 nanosheets as the substrate material, with large surface area, accelerate electron transfer and attach more DNA probes on the electrode substrate, have effectively enhanced the electrochemical performance of the electrode. With the existence of Enrofloxacin (ENR), the aptamer recognizes and binds to ENR, thus the signal probe cDNA was released and immobilized onto the electrode surface to hybridized with methylene blue (MB) labelled DNA (MB-DNA), thereby triggering the Exo III-assisted cycle for further signal amplification. As expected, the prepared aptasensor demonstrated excellent sensitivity and selectivity, with a wide linear range from 5.0 × 10-6 ng/mL to 1.0 × 10-2 ng/mL for ENR, a low detection limit of 1.59 × 10-6 ng/mL. Consequently, this strategy provided a promising avenue for ultrasensitive and accurate detection of ENR in milk samples.

2.
Polymers (Basel) ; 16(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38891400

ABSTRACT

Shrinkage cracks are some of the most common defects in timber structures obtained from woods with an uneven distribution of moisture content and are subject to external dynamic environmental changes. To accurately predict the changes in the moisture content of wood components at any time and position, this study first applied the principles of food drying and established a moisture field model for laminated wood based on the analogy between heat and humidity transfer. A model for predicting the moisture content of wood that considers time and spatial distribution was then proposed. Second, by collecting relevant experimental data and establishing a finite element analysis model, three moisture absorption conditions (0-9.95%, 0-13.65%, and 0-17.91%) and four desorption conditions (34-5.5%, 28-8.3%, 31-11.8%, and 25.5-15.9%) were analyzed. In the moisture absorption comparison, the time needed to reach 95% equilibrium moisture content was 2.43 days, 4.07 days, and 6.32 days. The rate at which the internal components reached equilibrium moisture content exceeded 10 days. The temporal and spatial distribution of wood moisture content revealed the correctness of the proposed wood moisture field model. Finally, the moisture content prediction model was applied in the order of characteristic equation solutions, moisture content gradient difference, and laminated wood size. The results revealed that the established humidity field model can predict the wood moisture content and how it changes over time and in space. Notably, 1-2 orders for the solution of the characteristic equation are recommended when applying the prediction model. The greater the difference in moisture content, the faster the equilibrium moisture content is reached. The moisture content varies greatly based on the component size and position. Notably, the influence of moisture gradient and wood size on the average wood moisture content cannot be ignored.

3.
Appl Microbiol Biotechnol ; 108(1): 78, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38194141

ABSTRACT

African swine fever virus (ASFV) is a complex DNA virus and the only member of the Asfarviridae family. It causes high mortality and severe economic losses in pigs. The ASFV pB602L protein plays a key role in virus assembly and functions as a molecular chaperone of the major capsid protein p72. In addition, pB602L is an important target for the development of diagnostic tools for African swine fever (ASF) because it is a highly immunogenic antigen against ASFV. In this study, we expressed and purified ASFV pB602L and validated its immunogenicity in serum from naturally infected pigs with ASFV. Furthermore, we successfully generated an IgG2a κ subclass monoclonal antibody (mAb 7E7) against pB602L using hybridoma technology. Using western blot and immunofluorescence assays, mAb 7E7 specifically recognized the ASFV Pig/HLJ/2018/strain and eukaryotic recombinant ASFV pB602L protein in vitro. The 474SKENLTPDE482 epitope in the ASFV pB602L C-terminus was identified as the minimal linear epitope for mAb 7E7 binding, with dozens of truncated pB602l fragments characterized by western blot assay. We also showed that this antigenic epitope sequence has a high conservation and antigenic index. Our study contributes to improved vaccine and antiviral development and provides new insights into the serologic diagnosis of ASF. KEY POINTS: • We developed a monoclonal antibody against ASFV pB602L, which can specifically recognize the ASFV Pig/HLJ/2018/ strain. • This study found one novel conserved B-cell epitope 474SKENLTPDE482. • In the 3D structure, 474SKENLTPDE482 is exposed on the surface of ASFV pB602L, forming a curved linear structure.


Subject(s)
African Swine Fever Virus , African Swine Fever , Animals , Swine , African Swine Fever Virus/genetics , Epitopes, B-Lymphocyte/genetics , Antibodies, Monoclonal , Blotting, Western
4.
Virus Res ; 341: 199328, 2024 03.
Article in English | MEDLINE | ID: mdl-38262569

ABSTRACT

The outbreak of African Swine Fever (ASF) has caused huge economic losses to the pig industry. There are no safe and effective vaccines or diagnostics available. The p30 protein serves as a key target for the detection of ASFV antibodies and is an essential antigenic protein for early serological diagnosis. Here, the p30 protein was purified after being expressed in E. coli and its immunogenicity was verified in sera from pigs naturally infected with ASFV. Furthermore, a monoclonal antibody (McAb) designated as McAb 1B4G2-4 (subtype IgG1/kappa-type) was produced and it was verified to specifically recognize the ASFV Pig/HLJ/2018/strain and eukaryotic recombinant ASFV p30 protein. The epitope identified by McAb 1B4G2-4, defining the unique B-cell epitope 164HNFIQTI170, was located using peptide scanning. Comparing amino acid (aa) sequence revealed that this epitope is conserved in all reference ASFV strains from different regions of China, including the highly pathogenic strain Georgia 2007/1 (NC_044959.2) that is widely distributed. It is also exposed to the surface of the p30 protein, suggesting that it could be an important B-cell epitope. Our study may serve as a basis for the development of serological diagnostic methods and subunit vaccines.


Subject(s)
African Swine Fever Virus , African Swine Fever , Swine , Animals , African Swine Fever Virus/genetics , Epitopes, B-Lymphocyte/genetics , Viral Proteins/metabolism , Antibodies, Monoclonal , Escherichia coli/metabolism , Recombinant Proteins , Antibodies, Viral
6.
J Nanobiotechnology ; 21(1): 424, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37964304

ABSTRACT

The African swine fever (ASF) pandemics pose a significant threat to the global swine industry, and the development of safe and effective vaccines is a daunting but necessary challenge. The level and persistence of immunity are very important for the effectiveness of the vaccine. Targeting antigens to antigen presenting cells (APCs) can greatly enhance immunogenicity. In this study, we developed a self-assembled nano-ASFV vaccine candidate (NanoFVax) targeting DCs, by covalently coupling the self-assembled 24-mer ferritin with the dominant B and T cell epitopes of the highly immunogenic ASFV antigen (p72, CD2v, pB602L and p30) and fused with the chemokine receptor XCL1 (a DC targeting molecule) through the SpyTag/SpyCatcher protein ligase system. Compared to monomeric protein, the nanoparticle vaccines can induce a more robust T-cell response, and the high-level antibody response against ASFV can last for more than 231 days. Therefore, the NanoFVax is a novel and promising vaccine candidate for ASFV.


Subject(s)
African Swine Fever Virus , African Swine Fever , Animals , Swine , African Swine Fever/prevention & control , Nanovaccines , Epitopes, T-Lymphocyte , Immunity
7.
Heliyon ; 9(10): e20690, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37860534

ABSTRACT

Background: Advanced non-small cell lung cancer (NSCLC) is often complicated by leptomeningeal metastases (LMs), especially in patients carrying EGFR mutations. EGFR tyrosine kinase inhibitors (TKIs) are the first-line drug for patients with specific gene mutations, such as EGFR exon 19 deletion or exon 21 L858R mutation. However, after long-term TKI use, patients eventually develop drug resistance and acquire new mutations. Acquiring the EGFR T790 M mutation during TKI treatment is a marker for first/second generation TKI resistance. Osimertinib (a third-generation TKI) could overcome this resistance, especially for patients who have already developed NSCLC-LM. Treating NSCLC patients with osimertinib resistance is challenging. Our aim was to investigate whether afatinib is effective in NSCLC-LM patient who showed resistance to osimertinib. Herein, we report two patients with resistance to first- and third-generation TKIs who benefited from second-generation TKI. Case summary: Case one: A 43-year-old man was diagnosed with stage 3A NSCLC with EGFR exon 19 deletion. He underwent surgery and received 4 rounds of chemotherapy (oxaliplatin combined with liposomal paclitaxel), after which the disease was controlled by icotinib (a first-generation TKI) for 4 years. Then, he showed poor drug response and bone metastasis. A liquid biopsy was carried out, and the EGFR L858R/T790 M compound mutation was found. The patient was given osimertinib (a third-generation TKI). The patient was in a stable condition for 2 years and then he developed bilateral peripheral facial palsy. Brain MRI showed enhancement in the left temporal lobe and meninges, and cerebrospinal fluid (CSF) cytology detected tumour cells in the CSF. NSCLC-LM was diagnosed. His performance status (PS) score was 3-4. Liquid biopsy and next-generation sequencing were performed again. Different gene mutations and copy number alterations were found this time, including EGFR L858R, but without the EGFR T790 M mutation. His disease was controlled with intrathecal methotrexate and oral afatinib (a second generation TKI). The patient has shown clinical remission (PS score: 1-2) until now, which is longer than 10 months. Case two: A 50-year-old man was diagnosed with NSCLC in May 2020. He underwent one round of chemotherapy before thoracoscopic partial lobectomy of the right upper lung. Histological study of the lung tissue showed lung adenocarcinoma with the EGFR L858R mutation. Then, the disease was controlled with icotinib. One year later, he was diagnosed with NSCLC-LM. Liquid biopsy and sequencing showed an EGFR L858R/S768I compound mutation. The patient was treated with osimertinib. His condition was stable for 5 months before his central nervous system (CNS) symptoms were exacerbated. Liquid biopsy and sequencing were carried out again, and his gene mutation profile had not changed much. Then, the patient was given afatinib, and his condition has remained stable for 11 months. Conclusion: Afatinib might be suitable for NSCLC-LM patients with EGFR compound mutations who show resistance to icotinib and osimertinib, since it might help overcome first- and third-generation TKI resistance.

8.
Cell Rep ; 42(10): 113211, 2023 10 31.
Article in English | MEDLINE | ID: mdl-37792534

ABSTRACT

Hyperlipidemia impairs anti-tumor immune responses and is closely associated with increased human cancer incidence and mortality. However, the underlying mechanisms are not well understood. In the present study, we show that natural killer (NK) cells isolated from high-fat-diet mice or treated with oleic acid (OA) in vitro exhibit sustainable functional defects even after removal from hyperlipidemic milieu. This is accompanied by reduced chromatin accessibility in the promoter region of NK cell effector molecules. Mechanistically, OA exposure blunts P300-mediated c-Myc acetylation and shortens its protein half-life in NK cells, which in turn reduces P300 accumulation and H3K27 acetylation and leads to persistent NK cell dysfunction. NK cells engineered with hyperacetylated c-Myc mutants surmount the suppressive effect of hyperlipidemia and display superior anti-tumor activity. Our findings reveal the persistent dysfunction of NK cells in dyslipidemia milieu and extend engineered NK cells as a promising strategy for tumor immunotherapy.


Subject(s)
Hyperlipidemias , Neoplasms , Humans , Mice , Animals , Histones/metabolism , Killer Cells, Natural , Neoplasms/pathology , Hyperlipidemias/metabolism , Lipids
9.
Viruses ; 15(9)2023 08 30.
Article in English | MEDLINE | ID: mdl-37766252

ABSTRACT

African swine fever (ASF) is an acute, virulent, and highly fatal infectious disease caused by the African swine fever virus (ASFV). There is no effective vaccine or diagnostic method to prevent and control this disease currently, which highlights the significance of ASF early detection. In this study, we chose an early antigen and a late-expressed antigen to co-detect the target antibody, which not only helps in early detection but also improves accuracy and sensitivity. CP204L and B602L were successfully expressed as soluble proteins in an Escherichia coli vector system. By optimizing various conditions, a dual-antigen indirect ELISA for ASFV antibodies was established. The assay was non-cross-reactive with antibodies against the porcine reproductive and respiratory syndrome virus, classical swine fever virus, porcine circovirus type 2, and pseudorabies virus. The maximum serum dilution for detection of ASFV-positive sera was 1:1600. The intra-batch reproducibility coefficient of variation was <5% and the inter-batch reproducibility coefficient of variation was <10%. Compared with commercial kits, the dual-antigen indirect ELISA had good detection performance. In conclusion, we established a detection method with low cost, streamlined production process, and fewer instruments. It provides a new method for the serological diagnosis of ASF.


Subject(s)
African Swine Fever Virus , African Swine Fever , Animals , Swine , African Swine Fever/diagnosis , Reproducibility of Results , Antibodies , Enzyme-Linked Immunosorbent Assay , Escherichia coli
10.
Microbiol Spectr ; 11(3): e0179223, 2023 06 15.
Article in English | MEDLINE | ID: mdl-37222634

ABSTRACT

Amino acids play a crucial role in the growth and development of insects. Aphids cannot ingest enough amino acids in plant phloem to meet their requirements, and therefore, they are mainly dependent on the obligate symbiont Buchnera aphidicola to synthesize essential amino acids. Besides Buchnera, aphids may harbor another facultative symbiont, Arsenophonus, which alters the requirement of the cotton-melon aphid Aphis gossypii for amino acid. However, it is unclear how Arsenophonus regulates the requirement. Here, we found that Arsenophonus ameliorated growth performance of A. gossypii on an amino acid-deficient diet. A deficiency in lysine (Lys) or methionine (Met) led to changes in the abundance of Arsenophonus. Arsenophonus suppressed the abundance of Buchnera when aphids were fed a normal amino acid diet, but this suppression was eliminated or reversed when aphids were on a Lys- or Met-deficient diet. The relative abundance of Arsenophonus was positively correlated with that of Buchnera, but neither of them was correlated with the body weight of aphids. The relative expression levels of Lys and Met synthase genes of Buchnera were affected by the interaction between Arsenophonus infections and Buchnera abundance, especially in aphids reared on a Lys- or Met-deficient diet. Arsenophonus coexisted with Buchnera in bacteriocytes, which strengthens the interaction. IMPORTANCE The obligate symbiont Buchnera can synthesize amino acids for aphids. In this study, we found that a facultative symbiont, Arsenophonus, can help improve aphids' growth performance under amino acid deficiency stress by changing the relative abundance of Buchnera and the expression levels of amino acid synthase genes. This study highlights the interaction between Arsenophonus and Buchnera to ameliorate aphid growth under amino acid stress.


Subject(s)
Aphids , Buchnera , Gammaproteobacteria , Animals , Buchnera/genetics , Aphids/physiology , Amino Acids , Symbiosis , Methionine , Lysine
11.
J Mech Behav Biomed Mater ; 142: 105825, 2023 06.
Article in English | MEDLINE | ID: mdl-37031562

ABSTRACT

Ti6Al4V alloys have potential applications as bone implants. However, their poor biotribological performances affected the service life. In this work, carboxylic multi-walled carbon nanotubes (CMWNT) coatings were grafted on the surface of Ti6Al4V alloys by electrochemical deposition for enhancing the biotribological properties. The CMWNT coatings showed lower coefficient of friction and wear rates, with the reduction of wear rates of 6% in dry condition and 90% under simulated body fluid (SBF) lubrication. This result might be ascribed to the transfer of friction behavior from sliding friction to rolling friction. In addition, the tribological regularity of CMWNT coating with the frequency and load were discussed. Under dry friction, with the increase of frequency and the decrease of normal load, the COF of the CMWNT coating decreased. In SBF lubrication, the COF decreased and the wear rate increased with the increase of frequency. Moreover, the excellent anti-wear properties were observed at the below of 10 N. These findings indicate that the CMWNT coating has an excellent protective effect on titanium alloy, and has a certain application potential in the biomedical field.


Subject(s)
Nanotubes, Carbon , Titanium , Titanium/chemistry , Friction , Alloys/chemistry , Surface Properties
12.
Nat Commun ; 14(1): 1710, 2023 03 27.
Article in English | MEDLINE | ID: mdl-36973277

ABSTRACT

Liver-resident natural killer cells, a unique lymphocyte subset in liver, develop locally and play multifaceted immunological roles. However, the mechanisms for the maintenance of liver-resident natural killer cell homeostasis remain unclear. Here we show that early-life antibiotic treatment blunt functional maturation of liver-resident natural killer cells even at adulthood, which is dependent on the durative microbiota dysbiosis. Mechanistically, early-life antibiotic treatment significantly decreases butyrate level in liver, and subsequently led to defective liver-resident natural killer cell maturation in a cell-extrinsic manner. Specifically, loss of butyrate impairs IL-18 production in Kupffer cells and hepatocytes through acting on the receptor GPR109A. Disrupted IL-18/IL-18R signaling in turn suppresses the mitochondrial activity and the functional maturation of liver-resident natural killer cells. Strikingly, dietary supplementation of experimentally or clinically used Clostridium butyricum restores the impaired liver-resident natural killer cell maturation and function induced by early-life antibiotic treatment. Our findings collectively unmask a regulatory network of gut-liver axis, highlighting the importance of the early-life microbiota in the development of tissue-resident immune cells.


Subject(s)
Butyrates , Gastrointestinal Microbiome , Butyrates/pharmacology , Interleukin-18 , Liver , Killer Cells, Natural
13.
Materials (Basel) ; 16(6)2023 Mar 19.
Article in English | MEDLINE | ID: mdl-36984332

ABSTRACT

In order to accurately calculate the long-term prestress losses of prestressed tendons, a time-varying model of long-term prestress loss considering the interaction between concrete shrinkage, creep, and the stress relaxation of prestressed tendons was constructed. Then, a method for calculating the long-term prestress losses of concrete structures was developed. A long-term prestress loss test of a prestressed concrete T-beam in a long-term field test environment was carried out. The measured values of long-term prestress losses are compared with the calculated results of JTG 3362-2018, AASHTO LRFD-2007, and the time-varying law model. The results show that the long-term effective tension of the T-beam decreases gradually with the increase in the load holding time. At the beginning of loading, the tensile force changes rapidly and then gradually slows down. The later the tensile age or the higher the initial loading stress level, the smaller the long-term prestress losses of the prestressed tendons. The long-term prestress loss values calculated by JTG 3362-2018, AASHTO LRFD-2007, and the time-varying law model increase with the increase in the load holding time. In the early stage of loading, the rate of change slows down and tends to be stable. The calculated results of JTG 3362-2018 and AASHTO LRFD-2007 are significantly different from the measured values. However, the calculated results of the time-varying law model are in good agreement with the measured values. The average coefficients of variation of the long-term prestress loss calculated by JTG 3362-2018, AASHTO LRFD-2007, and the time-varying law model are 17%, 10%, and 5%, respectively. The time-varying law model of the long-term prestress losses of prestressed tendons is accurate, and the long-term prestress loss of prestressed reinforcement can be predicted effectively.

14.
Clin Neurol Neurosurg ; 225: 107572, 2023 02.
Article in English | MEDLINE | ID: mdl-36610238

ABSTRACT

BACKGROUND: Non-small cell lung cancer with leptomeningeal metastasis (NSCLC-LM) is emerging as a new management challenge for oncologists and is associated with poor prognosis. This study aimed to investigate the molecular characteristics and prognostic factors of NSCLC-LM. METHODS: This retrospective study included 97 patients with NSCLC-LM between January 2015 and October 2021. Progression-free survival (PFS) and overall survival (OS) were evaluated. Gene mutations were detected by next-generation sequencing (NGS). RESULTS: The median PFS and OS were 8.4 (95 % confidence interval [CI]: 4.839-11.901) and 14.0 (95 % CI: 9.254-18.746) months, respectively. Sixty-seven patients harboured epidermal growth factor receptor-mutated (EGFRm): L858R (34), 19del (29), T790M (13), and G719C with L861Q (1). Other mutations included ALK (5), ROS1 (3), KRAS (1), TP53 (14), MET amplification (6). The detection rate and types of circulating tumour DNA (ctDNA) in the cerebrospinal fluid (CSF) samples were higher than the paired plasma samples. Patients with EGFR mutations had a longer median OS than those without mutations (19.0 vs. 13.0 months, P = 0.015). Patients with gene mutations had shorter median OS than those without mutations, such as ALK (11.8 vs. 19.9 months, P = 0.014), ROS1 (12.7 vs. 19.8 months, P = 0.014), KRAS (4.0 vs. 19.0 months, P = 0.005), TP53 (15.0 vs. 19.0 months, P = 0.014), and MET amplification (6.0 vs. 19.0 months, P = 0.003). Multivariate analysis indicated that MET amplification was an independent predictor of poor survival. Along with Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥ 3, LM accompanied with brain parenchymal metastasis (BPM), extracranial disease, and seizures were independent predictors of poor survival, whereas intrathecal chemotherapy, and third-generation EGFR-TKIs were independent predictors of favorable survival. CONCLUSIONS: CSF ctDNA detected using NGS had a high sensitivity for NSCLC-LM, showing high potential in detecting driver and drug-resistant gene mutations. Genomic profiles, combined with clinically relevant prognostic factors, will guide individualised treatments and improve the outcomes of NSCLC-LM patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Meningeal Carcinomatosis , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Prognosis , ErbB Receptors/genetics , Retrospective Studies , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/therapeutic use , Proto-Oncogene Proteins p21(ras)/genetics , Mutation/genetics , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/therapeutic use , Meningeal Carcinomatosis/genetics
15.
Hepatology ; 78(2): 468-485, 2023 08 01.
Article in English | MEDLINE | ID: mdl-35815363

ABSTRACT

BACKGROUND AND AIMS: Natural killer (NK) cells are key players in tumor immunosurveillance, and metabolic adaptation manipulates their fate and functional state. The nicotinamide adenine dinucleotide (NAD + ) has emerged as a vital factor to link cellular metabolism and signaling transduction. Here, we identified NAD + metabolism as a central hub to determine the homeostasis and function of NK cells. APPROACH AND RESULTS: NAD + level was elevated in activated NK cells. NAD + supplementation not only enhanced cytokine production and cytotoxicity but also improved the proliferation and viability of NK cells. Intriguingly, the salvage pathway was involved in maintaining NAD + homeostasis in activated NK cells. Genetic ablation or pharmacological blockade of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD + salvage pathway, markedly destroyed the viability and function of NK cells. Mechanistically, NAD + salvage dictated the mitochondrial homeostasis and oxidative phosphorylation activity to support the optimal function of NK cells. However, in human HCC tissues, NAMPT expression and NAD + level were significantly down-regulated in tumor-infiltrating NK cells, which negatively correlated with patient survival. And lactate accumulation in the tumor microenvironment was at least partially responsible for the transcriptional repression of NAMPT in NK cells. Further, deficiency of Nampt in NK cells accelerated the growth of HCC and melanoma. Supplementation of the NAD + precursor nicotinamide mononucleotide (NMN) significantly improved NK antitumor response in both mouse and human cell-derived xenografts. CONCLUSIONS: These findings reveal NAD + salvage as an essential factor for NK-cell homeostasis and function, suggesting a potential strategy for invigorating NK cell-based immunotherapy.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Mice , Animals , NAD/metabolism , Nicotinamide Mononucleotide/metabolism , Cytokines/metabolism , Killer Cells, Natural/metabolism , Tumor Microenvironment
16.
Front Oncol ; 13: 1322635, 2023.
Article in English | MEDLINE | ID: mdl-38269023

ABSTRACT

Background: Brain metastases (BM), including brain parenchyma metastases (BPM) and leptomeningeal metastases (LM), are devastating metastatic complications in advanced cancer patients. Next-generation sequencing (NGS) is emerging as a new promising tool for profiling cancer mutation, which could facilitate the diagnosis of cancer. This retrospective study aimed to investigate the molecular genetic characteristics of non-small cell lung cancer (NSCLC) patients with BPM and LM using NGS. Methods: Cerebrospinal fluid (CSF) samples and paired plasma samples were collected from 37 patients of NSCLC-BM. We profiled genetic mutation characteristics using NGS from NSCLC-BM by comparing CSF circulating tumour DNA (ctDNA) with plasma ctDNA and primary tumour tissues. Results: Among the 37 patients with NSCLC-BM, 28 patients had LM with or without BPM, while 9 patients only had BPM. Driver and drug-resistant mutations in primary tumours with LM included: EGFR L858R (10, 35.7%), EGFR 19del (6, 21.4%), EGFR L858R+MET (1, 3.6%), EGFR L858R+S768I (1, 3.6%), ALK (2, 7.1%), ROS1 (1, 3.6%), negative (5, 17.9%), and unknown (2, 7.1%). In patients with NSCLC-LM, the detection rate and abundance of ctDNA in the CSF were significantly higher than those in paired plasma. The main driver mutations of NSCLC-LM remained highly consistent with those of the primary tumours, along with other unique mutations. Circulating tumour DNA was negative in the CSF samples of BPM patients. Patients with BMP had a higher ratio of EGFR 19del than L858R mutation (55.6% vs 11.1.%), whereas NSCLC patients with LM had a higher ratio of EGFR L858R than 19del mutation (50.0% vs 25.0%). Most patients with positive plasma ctDNA results were male (p = 0.058) and in an unstable state (p = 0.003). Conclusion: Our study indicated that the CSF ctDNA detected by NGS may reflect the molecular characteristics and heterogeneity of NSCLC-LM. Timely screening of patients with NSCLC for CSF ctDNA, especially for patients with positive plasma ctDNA, may facilitate the early detection of LM. Furthermore, patients with the EGFR 19del may have a higher risk of developing BPM.

17.
ACS Omega ; 7(35): 31081-31097, 2022 Sep 06.
Article in English | MEDLINE | ID: mdl-36092603

ABSTRACT

The poor biotribological properties and bioinertness of Ti6Al4V have restricted its application in biomedical materials. In this study, microgrooves of different widths were prepared on the surface of a Ti6Al4V alloy by laser treatment. The tribological properties under dry lubrication and simulated body fluid (SBF) lubrication conditions, the electrochemical corrosion properties in SBF solution, and the bone marrow mesenchymal stem cell (BMSC) behavior on the surfaces were systematically tested. The corresponding mechanisms were discussed. The results showed that Ti6Al4V with a microgroove width of 45 µm (Ti64-45) exhibited excellent wear resistance with decreasing wear rates of 89.79 and 85.43% under dry friction and SBF lubrication compared to the Ti64 sample, which might be due to the increase of surface microhardness. Moreover, the excellent anticorrosion performance of Ti64-45 was attributed to the grain refinement on the titanium alloy surface with a lower volume fraction ratio of ß phase to α phase. In addition, the microgrooves with a width of 45 µm are more conducive to BMSC proliferation and adhesion, related to promoting cell signal transduction due to cell extrusion. These studies imply that the microgroove structures are potential for application in the medical field.

18.
Environ Microbiol ; 24(8): 3764-3776, 2022 08.
Article in English | MEDLINE | ID: mdl-35129273

ABSTRACT

Transmission rate and role in hosts contribute to the prevalence of an endosymbiont. However, factors affecting transmission and role of facultative endosymbionts are still not well understood. Here, we illustrated that host plants and environmental temperatures affected the transmission, relative abundance and role of Arsenophonus in the cotton aphid Aphis gossypii. The transmission rate of this endosymbiont from mother aphids to offspring was relatively lower. High temperatures impeded the transmission, and infection rates declined as aphids were exposed to 30°C. Contents of amino acids and secondary metabolites were remarkably different among host plants. Aphids feeding on zucchini leaves containing a higher titre of amino acids and lower secondary metabolites harboured a relatively lower abundance of Arsenophonus. Concentrations of an amino acid and a plant secondary metabolite, cucurbitacin B, in aphid diet were not associated with Arsenophonus abundance. However, gossypol, another plant secondary metabolite, was strongly related with the abundance. Arsenophonus imparted a fitness benefit to aphids, and the benefit was dependent on host plants and gossypol concentration. In sum, plant secondary metabolite and environmental temperature affect transmission, relative abundance and role of Arsenophonus, which determine the endosymbiont prevalence in aphid populations.


Subject(s)
Aphids , Gammaproteobacteria , Gossypol , Amino Acids , Animals , Plants , Prevalence , Symbiosis , Temperature
19.
Photodermatol Photoimmunol Photomed ; 38(5): 489-494, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35075714

ABSTRACT

BACKGROUND: A light emitting diode (LED), with a wavelength of 308 nm, has been utilized in the dermatologic treatment of vitiligo. OBJECTIVES: We investigated the efficacy and safety of 308-nm LED for use in the treatment of vitiligo. METHODS: We conducted a retrospective study of 70 stable-stage vitiligo patients (with a total of 99 lesions) who received 308-nm LED treatment at the Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College from June 2018 to June 2020. Treatment efficacy was evaluated after 8 treatment sessions, 16 treatment sessions, and the final treatment session, to estimate the percentage of re-pigmentation in the treated area. The Kruskal-Wallis test was used for data analysis. RESULTS: Based on the final treatment session analysis of all 99 lesions, 0 lesions showed no response, 21 lesions showed poor response, 29 lesions showed moderate response, 23 lesions showed good response, and 26 lesions showed excellent response. The efficacy rate was 49.49%, and there was a significant correlation between the six distinct anatomical regions treated and re-pigmentation grade (χ2  = 13.419, p = .009). Among these regions, facial lesions showed the best response to treatment, while the hands and feet lesions showed the poorest response. CONCLUSIONS: The clinical efficacy of 308-nm LED treatment is limited based on the treatment area. It demonstrated significant practical application in the treatment of vitiligo.


Subject(s)
Pigmentation Disorders , Ultraviolet Therapy , Vitiligo , China , Follow-Up Studies , Humans , Retrospective Studies , Treatment Outcome , Vitiligo/radiotherapy
20.
Trials ; 22(1): 798, 2021 Nov 13.
Article in English | MEDLINE | ID: mdl-34774099

ABSTRACT

INTRODUCTION: Unstable angina pectoris (UAP) is the common type of coronary heart disease with the risk of developing into acute myocardial infarction (AMI). Currently, there are still numerous patients suffering from recurrent angina after revascularization or conventional medication due to the microvascular lesions, endothelial dysfunction, chronic inflammation, in-stent restenosis, and other factors. As an important part of China's medical and health care system, traditional Chinese medicine (TCM) has rich clinical experience in the treatment of UAP. According to the theory of TCM, Yang deficiency and blood stasis syndrome is a common type of UAP. Wen Xin decoction, as a type of Chinese herbal medicine, has been used in the clinic for years and shown great efficacy in the treatment of UAP with Yang deficiency and blood stasis syndrome. This study aims to evaluate the efficacy and safety of Wen Xin granular in patients with UAP. METHODS AND ANALYSIS: This is a double-blinded, randomized, placebo-controlled clinical trial. A total of 502 participants will be randomly allocated to the intervention group and the placebo group. Based on conventional medication, the intervention group will be treated with Wen Xin granular and the placebo group will be treated with Wen Xin granular placebo. The primary outcomes are major adverse cardiovascular events (MACE). Assessments will be performed 1 year after the treatment. The secondary outcomes include TCM symptom scale score, Seattle angina questionnaire, and thromboelastography. Assessments will be performed at baseline (before randomization) and 4 and 8 weeks after randomization. DISCUSSION: This trial will provide high-quality data on the benefits and risks of Wen Xin granular in patients with UAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT04661709 . Registered on 30 November 2020.


Subject(s)
Drugs, Chinese Herbal , Myocardial Infarction , Angina, Unstable/diagnosis , Angina, Unstable/drug therapy , Double-Blind Method , Drugs, Chinese Herbal/adverse effects , Humans , Medicine, Chinese Traditional , Randomized Controlled Trials as Topic , Treatment Outcome , Yang Deficiency
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