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1.
Oral Dis ; 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34129722

RESUMO

BACKGROUND AND OBJECTIVE: Host immunity is crucial during periodontal inflammations. B cells are considered to have a function of immunoregulation, and TLRs are considered to be crucial in this process. The present study illustrates the potential roles and rules of CD25+ B cells during periodontitis, especially its effect on regulating host IL-35 level and Th1, Th17, and Tregs differentiation. MATERIAL AND METHODS: The proportion of local and systemic CD25+ B cells subpopulations from periodontitis models were identified by flow cytometry. To illustrate further mechanism, B cells were cultured with a different type of TLRs activators. Expression of IL-10, IL-35, and TGF-ß was detected by ELISA and real time PCR. We also set adoptive transfer models by using CD25+ B cells. Alveolar bone erosion, Th1, Th17, and Tregs proportion and levels of IFN-γ, TNF-α, IL-1ß, and IL-17 were identified. RESULT: Periodontitis induces more CD25+ B cell subpopulations and promotes their IL-10, IL-35, and TGF-ßproduction. TLRs' activators enhanced Bregs proliferation and function. LPS+CpG obviously induced more CD25+ B cells differentiation and IL-10, IL-35, and TGF-ßproduction. Adoptive transfer of CD25+ B cells reduces alveolar bone destruction and local Tregs, proportion, especially the local level of IFN-γ and IL-17. In addition, adoptive transfer of CD25+ B cells remedies the pathological change of IL-1ß and Th1/Th17 proportion in local lesions. We did not find any significant difference in peripheral blood, regardless of group and detected items. CONCLUSION: Results of the present study clarify that CD25+ B cells enlarged and produced more IL10, IL-35 and TGF-ß during periodontitis, activation of TLR4 and TLR9 played crucial roles in this process. Also, CD25+ B cells alleviated periodontal inflammation and alveolar bone resorption. Our findings further expanded the potential of B cells during periodontitis.

2.
PLoS One ; 16(6): e0252138, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34081711

RESUMO

Facing the pressure of environment, sustainable development is the demand of the current construction industry development. Prefabricated construction technologies has been actively promoted in China. Cost has always been one of the important factors in the development of prefabricated buildings. The hidden cost of prefabricated buildings has a great impact on the total cost of the project, and it exists in the whole process of building construction. In this paper innovatively studies the cost of prefabricated buildings from the perspective of hidden cost. In order to analysis the hidden cost of prefabricated buildings, the influencing factor index system in terms of design, management, technology, policy and environment has been established, which includes 13 factors in total. And the hidden cost analysis model has been proposed based on FISM-BN, this model combines fuzzy interpretive structure model(FISM) with Bayesian network(BN). This model can comprehensively analyze the hidden cost through the combination of qualitative and quantitative methods. And the analysis process is dynamic, not fixed at a certain point in time to analyze the cost. We can get the internal logical relationship among the influencing factors of the hidden cost, and present it in the form of intuitive chart by FISM-BN. Furthermore the model could not only predict the probability of the hidden cost of prefabricated buildings and realize in-time control through causal reasoning, but also predict the posterior probability of other influencing factors through diagnostic reasoning when the hidden cost occurs and find out the key factors that lead to the hidden cost. Then the final influencing factors are determined after one by one check. Finally, the model is demonstrated on the hidden cost analysis of prefabricated buildings the probability of recessive cost is 26%. In the analysis and control of the hidden cost of prefabricated buildings, scientific and effective decision-making and reference opinions are provided for managers.

3.
Chemosphere ; 279: 130882, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34134437

RESUMO

A novel direct dual Z-scheme 3DOM (three-dimensional ordered macropores) SnS2-ZnS/ZrO2 composite was prepared by the template method combined with the in situ sulfur replacement technology. The composition, structure, morphology, and surface physicochemical properties of the composites were well characterized. The results indicate that it possesses a uniform and periodical macroporous structure, a large surface area (121.1 m2 g-1), broad visible light absorption, and high separation ability of photoinduced electron/hole pairs. 3DOM SnS2-ZnS/ZrO2 composite removed 96.8% of methyl orange within 210 min of simulated sunlight irradiation. Moreover, photocatalytic hydrogen production achieved the rate of 928.1 µmol g-1, which was 66.3 times as high as that of the commercial P25 after 8 h simulated sunlight irradiation. The enhanced photocatalytic performance mainly attributed to the direct dual Z-scheme system, which improves the charge separation efficiency and optimizes the charge transfer pathway. The charge transfer mechanism over the 3DOM SnS2-ZnS/ZrO2 is discussed in detail based on the results of radical trapping experiments. Our work paves a new way to design 3DOM materials with direct dual Z-scheme structure.


Assuntos
Sulfetos , Compostos de Zinco , Catálise , Hidrogênio
4.
J Biomed Nanotechnol ; 17(5): 921-931, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082877

RESUMO

Phenylketonuria (PKU) is a common disease associated with amino acid metabolism, and usually occurs in newborns. It can cause serious neurological diseases and even death. However, owing to inadequate-effective treatment, it can only be slowed by a low-phenylalanine (Phe) diet. In addition, PKU screening is essential for newborns in many countries. Therefore, rapid screening is crucial for preventing damage and meeting the large sample diagnosis demand. For confirmed patients, a convenient method to monitor their regular Phe levels is required. However, current clinical methods do not meet the rapid screening and convenient monitoring requirements. Herein, a rapid and facile electrochemical device based on platinum-doped reduced graphene oxide nanocomposites was developed to detect PKU biomarker-Phe. The results demonstrated that the developed electrode has great sensitivity, selectivity, and stability. The detection range was 0.0001 mM to 6 mM with a limit of detection of 0.01 µM. Therefore, this work offers a simple and rapid method for point-of-care PKU screening and daily monitoring.


Assuntos
Grafite , Nanocompostos , Fenilcetonúrias , Humanos , Recém-Nascido , Oxirredutases , Fenilcetonúrias/diagnóstico
5.
J Agric Food Chem ; 69(20): 5618-5627, 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-33979145

RESUMO

Natural products with minor side effects have been reported to be an effective adjuvant therapy for glucose and lipid metabolism disorders. Chrysin, a flavone, has a wide range of physiological effects, such as antioxidant, anti-inflammatory, anti-diabetes, anti-hyperlipidemia, and hepatoprotective. This study was designed to explore the effects and mechanism of chrysin on metabolic syndrome using insulin-resistant HepG2 cells and HFD/STZ-induced C57BL/6J mice. The results indicated that chrysin significantly decreased insulin resistance, oxidative stress, inflammation, and liver injury. In addition, chrysin improved glycogen synthesis and fatty acid oxidation and inhibited gluconeogenesis and fatty acid synthesis by regulating GSK3ß, G6Paes, PEPCK, SREBP1, FAS, and ACC1. Furthermore, the results of western blot and real-time PCR experiments demonstrated that chrysin modulated glucose and lipid metabolism through the AMPK/PI3K/AKT signaling pathway. Treatment with the AMPK inhibitor verified that AMPK activation is positively correlated with chrysin activity on glycolipid metabolism. This study confirms that chrysin is a potential treatment for glucose and lipid metabolism disorders.


Assuntos
Resistência à Insulina , Transtornos do Metabolismo dos Lipídeos , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Flavonoides , Glucose , Células Hep G2 , Humanos , Insulina/metabolismo , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
6.
ACS Chem Biol ; 16(6): 1050-1058, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34019369

RESUMO

Many bacterivorous and parasitic nematodes secrete signaling molecules called ascarosides that play a central role regulating their behavior and development. Combining stable-isotope labeling and mass spectrometry-based comparative metabolomics, here we show that ascarosides are taken up from the environment and metabolized by a wide range of phyla, including plants, fungi, bacteria, and mammals, as well as nematodes. In most tested eukaryotes and some bacteria, ascarosides are metabolized into derivatives with shortened fatty acid side chains, analogous to ascaroside biosynthesis in nematodes. In plants and C. elegans, labeled ascarosides were additionally integrated into larger, modular metabolites, and use of different ascaroside stereoisomers revealed the stereospecificity of their biosynthesis. The finding that nematodes extensively metabolize ascarosides taken up from the environment suggests that pheromone editing may play a role in conspecific and interspecific interactions. Moreover, our results indicate that plants, animals, and microorganisms may interact with associated nematodes via manipulation of ascaroside signaling.

7.
Comput Biol Med ; 134: 104436, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33984750

RESUMO

Clinical gait analysis incorporated with neuromusculoskeletal modelling could provide valuable information about joint movements and muscle functions during ambulation for children with cerebral palsy (CP). This study investigated how imposing pre-calculated joint angles during musculoskeletal model scaling influence the ankle joint angle and muscle force computation. Ten children with CP and equinus gait underwent clinical gait analysis. For each participant, a "default" (scaled without pre-calculated joint angles) and a "PJA" (scaled with pre-calculated ankle joint angles) model were generated to simulate their gait. Ankle joint angles were calculated with an inverse kinematic (IK) and direct kinematic (DK) approach. Triceps surae and tibialis anterior muscle forces were predicted by static optimisation and EMG-assisted modelling. We found that PJA-derived ankle angles showed a better agreement with what derived from the DK approach. The tibialis anterior muscle prediction was more likely to be affected by the scaling methods for the static optimisation approach and the gastrocnemius muscle force prediction was more likely to be influenced for the EMG-assisted modelling. This study recommends using the PJA model since the good consistency between IK and DK-derived joint angles facilitates communication among different research disciplines.

8.
J Biomech ; 123: 110513, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34038861

RESUMO

While previous studies have greatly improved our knowledge on the motion capability of the cervical spine, few reported on the kinematics of the entire head-neck complex (C0-T1) during dynamic activities of the head in the upright posture. This study investigated in vivo kinematics of the entire head-neck complex (C0-T1) of eight female asymptomatic subjects during dynamic left-right head axial rotation using a dual fluoroscopic imaging system and 3D-to-2D registration techniques. During one-sided head rotation (i.e., left or right head rotation), the primary rotation of the overall head-neck complex (C0-T1) reached 55.5 ± 10.8°, the upper cervical spine region (C0-2) had a primary axial rotation of 39.7 ± 9.6° (71.3 ± 8.5% of the overall C0-T1 axial rotation), and the lower cervical spine region (C2-T1) had a primary rotation of 10.0 ± 3.7° (18.6 ± 7.2% of the overall C0-T1 axial rotation). Coupled bending rotations occurred in the upper and lower cervical spine regions in similar magnitude but opposite directions (upper: contralateral bending of 18.2 ± 5.9° versus lower: ipsilateral bending of 21.4 ± 5.1°), resulting in a compensatory cervical lateral curvature that balances the head to rotate horizontally. Furthermore, upper cervical segments (C0-1 or C1-2) provided main mobility in different rotational degrees of freedom needed for head axial rotations. Additionally, we quantitatively described both coupled segmental motions (flexion-extension and lateral bending) by correlation with the overall primary axial rotation of the head-neck complex. This investigation offers comprehensive baseline data regarding primary and coupled motions of craniocervical segments during head axial rotation.

9.
J Nutr Sci Vitaminol (Tokyo) ; 67(2): 84-90, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33952739

RESUMO

Few studies have been performed to investigate the effect of vitamin D supplementation and T2DM in type 2 diabetic animal models. The present study aimed to explore the relationship between early 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the incidence of T2DM and determine whether early 1,25(OH)2D3 supplementation was associated with inflammation in KK-Ay mice. The KK-Ay mice were divided into 4 vitamin D treatment groups, the low-dose vitamin D supplementation group (VDS-L, 1.5 µg/kg 1,25(OH)2D3), moderate-dose vitamin D supplementation group (VDS-M, 3.0 µg/kg 1,25(OH)2D3), high-dose vitamin D supplementation group (VDS-H, 6.0 µg/kg 1,25(OH)2D3) and the model control group (MC). C57BL/6J mice were used as the controls. The treatment period lasted for 9 wk. During this treatment period, fasting blood glucose (FBG) level of the mice was measured on a weekly basis. The levels of lipid profile, insulin and inflammation biomarkers were determined after 9 wk of 1,25(OH)2D3 intragastric gavage. After 9 wk of 1,25(OH)2D3 intragastric gavage, FBG level was significantly decreased in the vitamin D treatment groups compared with the MC group. The number of T2DM incidence in the VDS-L group (n=7), VDS-M group (n=5) and VDS-H group (n=3) was lower than those in the MC group (n=10) on week 9. Moreover, serum C-reactive protein (CRP) and interleukin-6 (IL-6) in the vitamin D treatment groups were significantly suppressed by 1,25(OH)2D3 administration compared with the MC group. Early 1,25(OH)2D3 supplementation could effectively lower the incidence of T2DM via ameliorating inflammation in KK-Ay mice.

10.
Biol Pharm Bull ; 44(5): 714-723, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33952827

RESUMO

Ischemia-reperfusion injury (IRI) is the major cause of acute kidney injury (AKI). The previous studies demonstrated that Oridonin can protect kidney against IRI-induced AKI, but the underlying molecular mechanism is unclear. In this study, it showed that Oridonin significantly improved kidney damage, and inhibited the expression of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and MCP-1, as well as macrophage marker F4/80 in kidney and the secretion of inflammatory cytokins in serum of AKI mice in vivo. In addition, Oridonin also effectively reduced the expression and secretion of lipopolysaccharide (LPS)-induced inflammatory factors in macrophage cell line RAW264.7 in vitro. Notably, Oridonin strongly downregulated Mincle and AKT/nuclear factor-kappaB (NF-κB) signaling both in vivo and in vitro, and the results of cellular recovery experiments of overexpression of Mincle in macrophage suggested that Oridonin suppressed inflammatory response of macrophage through inhibiting Mincle, which may be the underlying mechanism of Oridonin improving injury in kidney of AKI mice. In summary, the above results indicated that Oridonin can protect kidney from IRI-induced inflammation and injury by inhibiting the expression of Mincle in macrophage.

11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(2): 283-287, 2021 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-33966711

RESUMO

Median arcuate ligament syndrome(MALS)is compression of the celiac trunk by the median arcuate ligament.Median arcuate ligament release is the corner stone for the surgical treatment of MALS.Open surgery,laparoscopic surgery,and robot-assisted surgery have been developed,among which laparoscopic surgery has been proposed as the preferred approach in view of its minimal trauma and short hospital stay.Auxiliary celiac plexus neurolysis could further alleviate the patient's discomfort.Moreover,vascular reconstitution is of vital importance in the case of persistent stenosis in the celiac artery despite of median arcuate ligament decompression.Vascular reconstruction has satisfactory long-term patency rate,while endovascular treatment is less invasive.This article aims to summarize the consensuses and advances and shed light on the surgical treatment of MALS.


Assuntos
Laparoscopia , Síndrome do Ligamento Arqueado Mediano , Artéria Celíaca/cirurgia , Constrição Patológica/cirurgia , Descompressão Cirúrgica , Humanos , Ligamentos/cirurgia , Síndrome do Ligamento Arqueado Mediano/cirurgia
12.
Autoimmunity ; : 1-9, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33974462

RESUMO

Sema4D, a member of the immune semaphorin family, plays crucial roles in the immune regulation, bone resorption and nervous system. It is also involved in angiogenesis and tumour progression. However, systemic studies on the correlation between Sema4D expression and the immune infiltration or clinical outcomes in tumours are still limited. Here, we analysed the landscape of Sema4D expression and its prognostic value in the cancer genome atlas pan-cancer as well as the correlation between Sema4D and immune cell infiltration by Tumour Immune Estimation Resource and Gene Expression Profiling interactive analysis online tools. Results showed that a higher Sema4D expression was significantly correlated with a favourable overall survival in diverse solid tumours including bladder cancer (Hazards Ratio (HR)=0.68, p = .0095), kidney renal clear cell carcinoma (HR = 0.61, p = .0016), melanoma (HR = 0.58, p = 6.6e-05) and thymoma (HR = 0.1, p = .011). Interestingly, Sema4D expression has positive correlation with various tumour infiltrating immune cells and immune cell biomarkers in these tumours. These results suggest that Sema4D could be a prospective biomarker for calculating hazard ratio of tumour patients and their tumour immune infiltration levels.

13.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946466

RESUMO

The species Pseudogymnoascus is known as a psychrophilic pathogenic fungus which is ubiquitously distributed in Antarctica. While the studies of its secondary metabolites are infrequent. Systematic research of the metabolites of the Antarctic fungus Pseudogymnoascus sp. HSX2#-11 led to the isolation of one new pyridine derivative, 4-(2-methoxycarbonyl-ethyl)-pyridine-2-carboxylic acid methyl ester (1), together with one pyrimidine, thymine (2), and eight diketopiperazines, cyclo-(dehydroAla-l-Val) (3), cyclo-(dehydroAla-l-Ile) (4), cyclo-(dehydroAla-l-Leu) (5), cyclo-(dehydroAla-l-Phe) (6), cyclo-(l-Val-l-Phe) (7), cyclo-(l-Leu-l-Phe) (8), cyclo-(l-Trp-l-Ile) (9) and cyclo-(l-Trp-l-Phe) (10). The structures of these compounds were established by extensive spectroscopic investigation, as well as by detailed comparison with literature data. This is the first report to discover pyridine, pyrimidine and diketopiperazines from the genus of Pseudogymnoascus.


Assuntos
Ascomicetos/química , Compostos de Nitrogênio/análise , Regiões Antárticas , Ascomicetos/metabolismo , Produtos Biológicos/química , Estrutura Molecular , Compostos de Nitrogênio/química , Metabolismo Secundário
14.
Cell Death Dis ; 12(5): 436, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33934111

RESUMO

Atherosclerotic plaque vulnerability and rupture increase the risk of acute coronary syndromes. Advanced lesion macrophage apoptosis plays important role in the rupture of atherosclerotic plaque, and endoplasmic reticulum stress (ERS) has been proved to be a key mechanism of macrophage apoptosis. Intermedin (IMD) is a regulator of ERS. Here, we investigated whether IMD enhances atherosclerotic plaque stability by inhibiting ERS-CHOP-mediated apoptosis and subsequent inflammasome in macrophages. We studied the effects of IMD on features of plaque vulnerability in hyperlipemia apolipoprotein E-deficient (ApoE-/-) mice. Six-week IMD1-53 infusion significantly reduced atherosclerotic lesion size. Of note, IMD1-53 lowered lesion macrophage content and necrotic core size and increased fibrous cap thickness and vascular smooth muscle cells (VSMCs) content thus reducing overall plaque vulnerability. Immunohistochemical analysis indicated that IMD1-53 administration prevented ERS activation in aortic lesions of ApoE-/- mice, which was further confirmed in oxidized low-density lipoproteins (ox-LDL) induced macrophages. Similar to IMD, taurine (Tau), a non-selective ERS inhibitor significantly reduced atherosclerotic lesion size and plaque vulnerability. Moreover, C/EBP-homologous protein (CHOP), a pro-apoptosis transcription factor involved in ERS, was significantly increased in advanced lesion macrophages, and deficiency of CHOP stabilized atherosclerotic plaques in AopE-/- mice. IMD1-53 decreased CHOP level and apoptosis in vivo and in macrophages treated with ox-LDL. In addition, IMD1-53 infusion ameliorated NLRP3 inflammasome and subsequent proinflammatory cytokines in vivo and in vitro. IMD may attenuate the progression of atherosclerotic lesions and plaque vulnerability by inhibiting ERS-CHOP-mediated macrophage apoptosis, and subsequent NLRP3 triggered inflammation. The inhibitory effect of IMD on ERS-induced macrophages apoptosis was probably mediated by blocking CHOP activation.

15.
Autophagy ; : 1-18, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33977871

RESUMO

Macroautophagy/autophagy plays an important role during the development of human cancer. BECN1 (beclin 1), a core player in autophagy regulation, is downregulated in many kinds of malignancy. The underlying mechanism, however, has not been fully illuminated. Here, we found that CUL3 (cullin 3), an E3 ubiquitin ligase, could interact with BECN1 and promote the K48-linked ubiquitination and degradation of this protein; In addition, CUL3 led to a decrease in autophagic activity through downregulating BECN1. We also found that KLHL38 was a substrate adaptor of the CUL3 E3 ligase complex-mediated ubiquitination and degradation of BECN1. In breast and ovarian cancer, CUL3 could promote the proliferation of tumor cells, and the expression of CUL3 was related to poor prognosis in patients. Our study reveals the underlying mechanism of BECN1 ubiquitination and degradation that affects autophagic activity and subsequently leads to tumor progression, providing a novel therapeutic strategy that regulates autophagy to combat cancer.Abbreviations: ATG: autophagy-related BECN1: beclin 1 CHX: cycloheximide CoIP: co-immunoprecipitation CUL3: cullin 3 IP: immunoprecipitation MS: mass spectrometry PtdIns3K: phosphatidylinositol 3-kinase UPS: ubiquitin-proteasome system.

16.
Aging Clin Exp Res ; 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33978925

RESUMO

BACKGROUND: Diet plays an important role in the development of age-related chronic diseases. However, the association between diet quality assessed by Healthy Eating Index (HEI)-2015, the latest version of HEI, and physical frailty among the general United States (US) elderly adults remains unclear. AIMS: The present study aims to explore the association between HEI-2015 and physical frailty in elderly adults using data from National Health and Nutrition Examination Survey (NHANES) 2011-2014. METHODS: HEI-2015 scores were calculated from 2 days 24-h recall interviews. Physical frailty status was assessed by four criteria developed by Fried et al.: exhaustion, weakness, low body mass, and low physical activity, and then categorized into robust (0 criteria), pre-frail (1-2 criteria), or frail (3-4 criteria). The binary and multinomial logistic regressions were used to examine the odds of frailty status. RESULTS: A total of 2345 participants aged 60 years or older were included. According to the 4-items frailty criteria, 51.1% participants were robust, 42.1% were pre-frail, and 6.8% were frail. Compared to the lowest HEI-2015 quartile, the elderly adults in the higher quartile had a lower odds of physical frailty (P < 0.05). Regarding the frailty criterion separately, higher HEI-2015 was associated with lower odds of exhaustion, weakness, low physical activity and unintentional weight loss, respectively (P < 0.05). Among 13 HEI-2015 components, adherence to the recommended intake of whole fruits and total vegetables components were less likely to be physically frail (P < 0.05). CONCLUSION: Higher HEI-2015 was inversely associated with lower odds of physical frailty in the US elderly adults.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33984631

RESUMO

The demand for analysis of carotenoids (CAR) and fat-soluble vitamins (FSV) is continuously expanding, but currently used sample preparation methods either require complicated extraction procedure or large sample volume, let alone the reliability of the results. This study aimed to develop a fast, high-efficient, and high-throughput method based on supported liquid extraction (SLE) for the simultaneous extraction of FSV and CAR from human serum before using high-performance liquid chromatography-diode array detector (HPLC-DAD) analysis. The optimization of SLE parameters was achieved through response surface methodology (RSM) based on the Box-Behnken design (BBD) and included serum-water-extraction solvent ratio and eluent volume. Under optimal conditions, the proposed method gives acceptable limits of detection (LOD) (0.005-0.3 µg/mL), good recovery (89.6-110.9%) as well as relative standard deviation (RSD) of less than 10.1% by consuming lower serum sample (100 µL) and less sample preparation time (2 min per sample). Compared with liquid-phase extraction (LLE), the SLE delivers rapid extraction with higher recovery, better reproducibility, and lower matrix effect for CAR and FSV analysis. The method has been successfully applied to quantify CAR and FSV levels in serum of healthy individuals and age-related macular degeneration (AMD) patients, demonstrating the feasibility of the proposed method for epidemiology and routine applications.

18.
J Thorac Oncol ; 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34033975

RESUMO

HYPOTHESIS: Tislelizumab, an anti-PD-1 antibody, was specifically engineered to minimize FcÉ£R macrophages binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous non-small cell lung cancer (nsq-NSCLC). METHODS: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB/IV nsq-NSCLC were randomized (2:1) to receive either Arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3W) or Arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary endpoint was progression-free response (PFS) assessed by an independent review committee; clinical response and safety/tolerability were secondary endpoints. RESULTS: Overall, 332 patients (n=222 [A]; n=110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 months; HR=0.645 [95% CI: 0.462, 0.902]; P=0.0044). Additionally, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the majority of reported AEs were grade 1-2 in severity. The most common grade ≥3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B]). CONCLUSIONS: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage.

19.
ACS Nano ; 2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037375

RESUMO

Carbonaceous materials have been considered as promising anodes for potassium-ion batteries (PIBs) because of their high electronic conductivity, eco-friendliness, and structural stability. However, the small interlayer spacing and serious volume expansion caused by the repeated insertion/extraction of large K-ions restrict their potassium-ion storage performance. Herein, F and N codoped carbon nanosheets (FNCS) with rich-edge defects are designed to resolve these problems. The F doping is in favor of the formation of more edge defects in the carbon layer, offering strong K+ adsorption capability and promoting the K+ storage. The ultrathin carbon nanosheets can provide a large contact area for the electrochemical reactions and shorten the transportation pathways for both K-ions and electrons. Consequently, the FNCS anode shows a high reversible capacity (610 mAh g-1 at 0.1 A g-1) and ultrastable cyclability over 4000 cycles at 5 A g-1. Moreover, K-ion full cells (FNCS|K2FeFe(CN)6) display excellent cycling stability (128 mAh g-1 at 1 A g-1 after 500 cycles) and rate capability (93 mAh g-1 at 20 A g-1). This design strategy can be extended to design other electrode materials for high-performance energy storage, such as magnesium-ion batteries, supercapacitors, and electrocatalysis.

20.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946798

RESUMO

G-protein-coupled receptors (GPCRs), especially chemokine receptors, are ideal targets for monoclonal antibody drugs. Considering the special multi-pass transmembrane structure of GPCR, it is often a laborious job to obtain antibody information about off-targets and epitopes on antigens. To accelerate the process, a rapid and simple method needs to be developed. The split-ubiquitin-based yeast two hybrid system (YTH) was used as a blue script for a new method. By fusing with transmembrane peptides, scFv antibodies were designed to be anchored on the cytomembrane, where the GPCR was co-displayed as well. The coupled split-ubiquitin system transformed the scFv-GPCR interaction signal into the expression of reporter genes. By optimizing the topological structure of scFv fusion protein and key elements, including signal peptides, transmembrane peptides, and flexible linkers, a system named Antigen-Antibody Co-Display (AACD) was established, which rapidly detected the interactions between antibodies and their target GPCRs, CXCR4 and CXCR5, while also determining the off-target antibodies and antibody-associated epitopes. The AACD system can rapidly determine the association between GPCRs and their candidate antibodies and shorten the research period for off-target detection and epitope identification. This system should improve the process of GPCR antibody development and provide a new strategy for GPCRs antibody screening.


Assuntos
Reações Antígeno-Anticorpo , Proteínas Imobilizadas/imunologia , Receptores Acoplados a Proteínas G/imunologia , Anticorpos de Cadeia Única/imunologia , Técnicas do Sistema de Duplo-Híbrido , Anticorpos Imobilizados/imunologia , Colorimetria , Proteínas de Ligação a DNA , Epitopos/imunologia , Genes Reporter , Humanos , Proteínas de Membrana , Domínios e Motivos de Interação entre Proteínas , Receptores CXCR4/imunologia , Receptores CXCR5/imunologia , Proteínas Recombinantes de Fusão/imunologia , Proteínas de Saccharomyces cerevisiae , Fatores de Transcrição , Ubiquitina/genética
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