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1.
BMC Public Health ; 22(1): 885, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35509051

RESUMO

BACKGROUND: We hypothesize higher air pollution and fewer greenness exposures jointly contribute to metabolic syndrome (MetS), as mechanisms on cardiometabolic mortality. METHODS: We studied the samples in the Chinese Longitudinal Healthy Longevity Survey. We included 1755 participants in 2012, among which 1073 were followed up in 2014 and 561 in 2017. We used cross-sectional analysis for baseline data and the generalized estimating equations (GEE) model in a longitudinal analysis. We examined the independent and interactive effects of fine particulate matter (PM2.5) and Normalized Difference Vegetation Index (NDVI) on MetS. Adjustment covariates included biomarker measurement year, baseline age, sex, ethnicity, education, marriage, residence, exercise, smoking, alcohol drinking, and GDP per capita. RESULTS: At baseline, the average age of participants was 85.6 (SD: 12.2; range: 65-112). Greenness was slightly higher in rural areas than urban areas (NDVI mean: 0.496 vs. 0.444; range: 0.151-0.698 vs. 0.133-0.644). Ambient air pollution was similar between rural and urban areas (PM2.5 mean: 49.0 vs. 49.1; range: 16.2-65.3 vs. 18.3-64.2). Both the cross-sectional and longitudinal analysis showed positive associations of PM2.5 with prevalent abdominal obesity (AO) and MetS, and a negative association of NDVI with prevalent AO. In the longitudinal data, the odds ratio (OR, 95% confidence interval-CI) of PM2.5 (per 10 µg/m3 increase) were 1.19 (1.12, 1.27), 1.16 (1.08, 1.24), and 1.14 (1.07, 1.21) for AO, MetS and reduced high-density lipoprotein cholesterol (HDL-C), respectively. NDVI (per 0.1 unit increase) was associated with lower AO prevalence [OR (95% CI): 0.79 (0.71, 0.88)], but not significantly associated with MetS [OR (95% CI): 0.93 (0.84, 1.04)]. PM2.5 and NDVI had a statistically significant interaction on AO prevalence (pinteraction: 0.025). The association between PM2.5 and MetS, AO, elevated fasting glucose and reduced HDL-C were only significant in rural areas, not in urban areas. The association between NDVI and AO was only significant in areas with low PM2.5, not under high PM2.5. CONCLUSIONS: We found air pollution and greenness had independent and interactive effect on MetS components, which may ultimately manifest in pre-mature mortality. These study findings call for green space planning in urban areas and air pollution mitigation in rural areas.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Síndrome Metabólica , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Biomarcadores/análise , China/epidemiologia , Estudos Transversais , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Humanos , Síndrome Metabólica/epidemiologia , Material Particulado/efeitos adversos , Material Particulado/análise
2.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(5): 567-572, 2022 May 15.
Artigo em Chinês | MEDLINE | ID: mdl-35570630

RESUMO

Objective: To investigate the surgical planning and the mid-term effectiveness of four major lower extremity arthroplasties (4JA) in patients with rheumatoid arthritis (RA). Methods: A clinical data of 25 patients with RA, who received 4JA and were followed up more than 3 years between June 2012 and September 2018, was retrospectively analyzed. There were 3 males and 22 females, with an average age of 48.6 years (range, 27-80 years). The body mass index ranged from 16.0 to 28.4 kg/m 2, with an average of 20.48 kg/m 2. The duration of RA ranged from 2 to 35 years (median, 21 years). There were 8 cases (12 sides) of knee valgus, 6 cases (12 side) of acetabular retraction, and 5 cases (10 sides) of hip stiffness. Among them, 20 patients underwent hip surgery first, and 5 patients underwent knee surgery first. Hip joint function was evaluated by Harris score, Hip Disability and Osteoarthritis Outcome Score (HOOS), hip range of motion, and Trendelenburg sign; knee joint function was evaluated by American Hospital for Special Surgery (HSS) score, knee range of motion and muscle strength, and a timed up and go (TUG) test was performed at last follow-up. X-ray films were used to observe whether the prosthesis was loose or displaced. Results: All 25 patients completed 4JA. Only 1 patient (1 side) had incision infection after operation, 3 patients (3 sides) had proximal femur fractures during operation. All patients were followed up 3.0-8.8 years, with an average of 5.8 years. At last follow-up, the Harris score, HOOS score, and range of motion of flexion, extension, and abduction of the hip joint significantly improved when compared with those before operation, and the patients with positive Trendelenburg sign decreased. The HSS score and range of motion of flexion and extension of the knee joint also significantly improved when compared with those before operation. There were significant differences in all indexes between pre- and post-operation ( P<0.05). The muscle strength was grade V. The TUG test ranged from 7.8 to 15.34 seconds (mean,10.79 seconds). X-ray films showed the prosthesis was not loose or displaced. Conclusion: When RA patients receive 4JA, adequate preoperative evaluation, rational selection of the timing and sequence of surgery, and maximal restoration of lower limb alignment can achieve good mid-term effectiveness.

3.
Front Public Health ; 10: 855310, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35570963

RESUMO

Background: The aging population conundrum and the gradual weakening of older adults' health and ability to obtain resources as they age have drawn attention to this population's health. Older adults' health relates not only to their own quality of life, but also to the development of families/society. Methods: We analyzed micro data from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study Follow-up Questionnaire, using the probit model, ordinary least squares model, and other methods. Results and Conclusions: Both formal and informal social support significantly impacted the physical and mental health of Chinese older adults, and the community environment moderated this relationship. To build a reasonable and effective social support system for older adults and improve their health, we suggest that stakeholders should continue to strengthen the formal and informal social support provided to older adults; they should also build a community-based care system, which will allow for the moderating role of community environment on the relationship between social support and older adults' health. Family and social support factors are important for older adults' health. We should enable the moderating role of community environment on the relationship between social support and health to be fully exerted, as well as build a community-based pension system.

4.
ACS Omega ; 7(17): 15145-15157, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35572750

RESUMO

Low-melting-point silicon-boron system alloys are promising for low-temperature reactive melt infiltration to reduce high-temperature damage to silicon carbide fibers during the densification of SiC/SiC composites. Meanwhile, the oxidation resistance of the alloys will have a large impact on the intrinsic oxidation resistance of the composite. Herein, three alloys, Si-14.88B-7Mo, Si-14.88B-7Ti, and Si-14.88B-7Cr, were fabricated to investigate the oxidation behavior in air at 1000-1400 °C. The results showed that the oxidation weight gains of the Si-B-Mo alloy after oxidation at 1400 °C for 100 h were 0.9 mg/cm-2, which were only 50 and 1.5% of those of Si-B-Ti and Si-B-Cr alloys, respectively. The excellent oxidation resistance of Si-B-Mo alloys at 1000-1400 °C was attributed to the formation of glassy-surface layers and the dense internal oxide layer. The dense oxide layer and the low solubility of Mo ions in SiO2 inhibit the volatilization of MoO3 and the oxidation reaction, reducing the oxidation rate of the Si-B-Mo alloy. The difference in the coefficients of thermal expansion for SiO2 and TiO2 led to penetrating cracks in the oxide layer of the Si-B-Ti alloy during cooling, thereby reducing the oxidation resistance. In addition, the rate of volatilization of Cr2O3 as CrO3 in an oxidation atmosphere above 1200 °C increased significantly in the Si-B-Cr alloy. The simultaneous volatilization of B2O3 and CrO3 resulted in the formation of loose oxide layers in the CrB2 region of the Si-B-Cr alloy, leading to severe oxidation.

5.
Front Oncol ; 12: 878639, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574414

RESUMO

Objective: To evaluate the clinical correlation of epithelial-mesenchymal transition (EMT) with PRL-3 and MMP9 expression in the circulating tumor cells (CTCs) of patients with colorectal cancer (CRC). Materials and Methods: Between January 2016 and December 2018, the EMT phenotype-based subsets of CTCs and the expression levels of PRL-3 and MMP9 in CTCs were identified, and their clinical values in 172 patients were evaluated. The CTCs were isolated, classified, and counted using the CanPatrol™ CTC filtration system. The CTC subsets (epithelial cells, mesenchymal cells and biphenotypic cells), as well as PRL-3 and MMP9 expression, were detected by RNA in situ hybridization. Results: CTCs were detected in 93.0% (160/172) of the included patients with CRC. Positive PRL-3 and MMP9 expression in CTC and M-CTC was found in 75.0% (102/136) and 80.8% (97/120) of the patients, respectively. The proportion of patients with positive PRL-3 and MMP9 expression in M-CTC was significantly associated with distant metastasis (p<0.05). The patients with ≥6 CTCs tended to show poorer progression-free survival (PFS) and overall survival (OS) rates (p=0.016, 0.02, respectively), and the patients with ≥3 M-CTC also showed poor PFS (p=0.0013). Additionally, the patients with positive PRL-3 and MMP9 expression in CTCs had significantly poorer PFS (p=0.0024) and OS (p=0.095) than the patients with negative PRL-3 and MMP9 expression. Multivariate Cox analysis uncovered that positive PRL-3 and MMP9 expression in CTCs may be an independent prognostic factor for worse PFS. Conclusion: EMT phenotypes and CTC numbers can be used as prognostic indicators for metastasis and survival in patients with CRC, and the combination of PRL-3 and MMP9 expression in CTCs is a promising clinical marker for patients with CRC.

6.
J Arthroplasty ; 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35490981

RESUMO

BACKGROUND: Different bearings have been used in total hip arthroplasty (THA), but the long-term performance is still controversial. The purpose of this study was to investigate whether there are differences when comparing THAs with five different bearings at a long-term follow-up of over 10 years. METHODS: From January 2010 to May 2012, 101 THA patients (134 hips) were divided into metal-on-metal group (MoM, 31 hips), metal-on-polyethylene group (MoP, 23 hips), ceramic-on-metal group (CoM, 21 hips), ceramic-on-ceramic group (CoC, 33 hips), and ceramic-on-polyethylene group (CoP, 26 hips). The mean follow-up period was 10.3 years. The Harris hip score (HSS), Western Ontario and McMaster Universities Osteoarthritis Index scores (WOMAC), range of motion (ROM), blood cell count, and liver-kidney function were measured. Serum and urine metal ion levels were measured using high-resolution inductively coupled plasma-mass spectrometry (ICP-MS) and blood lymphocytes analysis was counted by flow cytometry. RESULTS: No difference was observed in the HSS, WOMAC, ROM, blood cell count, or liver-kidney function among any of the five groups. Metal ion levels were significantly elevated in metal-containing bearings. Flow cytometry showed that no significant differences were found. Revision was performed due to pseudotumor in 3 patients. The implant survival rate was 96.7% and 93.3% for the MoM and CoC groups, which was significantly lower compared with other groups. CONCLUSIONS: Metal ion levels were elevated significantly in metal-containing bearings, especially in MoM THA patients. The implant survival rate was significantly lower in CoC and MoM THAs, which was mainly due to pseudotumor formation.

8.
Tuberculosis (Edinb) ; 134: 102210, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35526509

RESUMO

BACKGROUND: The expression of regulatory T cells (Tregs) is elevated in patients with active tuberculosis (TB) or multidrug-resistant TB. However, it remains uncertain whether Tregs mediate immune suppression in pleural tuberculoma (PTM). METHODS: Peripheral venous blood and clinical data were collected from 56 PTM patients and 50 healthy volunteers. The expression of CD38 and HLA-DR expression in T cell subsets and Tregs was determined by flow cytometry. RESULTS: PTM patients had significantly more Tregs than the matched healthy controls. The expression of CD4+T cells normalized after treatment. Although the median proportions of CD3+T, CD4+T, and CD8+T lymphocytes did not differ significantly between PTM patients and healthy controls, the CD4/CD8 ratio was higher in PTM patients. Moreover, the proportion of CD4+T lymphocytes expressing activation markers, including HLA-DR and CD38, was higher in PTM patients than healthy controls. Treg expression was positively associated with the level of CD4+T lymphocyte activation. CONCLUSIONS: The increased expression of Tregs seen in PTM patients, and subsequent decrease after treatment, indicate that Tregs play an important role in the immune reactivity of PTM.

9.
Sci China Life Sci ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35524910

RESUMO

Autologous fat-derived stromal vascular fraction (SVF) is a mixed cell population that has been used for many years in regenerative plastic surgery. In terms of animal and clinical research, this concise review was performed to evaluate the efficacy of SVF in knee degenerative joint disease (KDJD), which could cause pain, disability and severely affect patients' lives. Thirteen studies retrieved and screened from the databases were included, including six animal studies and seven clinical trials. The meta-analysis of clinical research shows that intra-articular injection of SVF, in combination with adjuvant surgery, could alleviate pain and improve early functional recovery for patients with KDJD at Kellgren-Lawrence (KL) grades II-III.

10.
J Virol ; 96(9): e0033622, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35404082

RESUMO

Epstein-Barr virus (EBV), the first identified human tumor virus, is etiologically associated with various kinds of malignant and benign diseases, accounting for 265,000 cancer incident cases and 164,000 cancer deaths in 2017. EBV prophylactic vaccine development has been gp350 centered for several decades. However, clinical studies show that gp350-centered vaccines fail to prevent EBV infection. Advances in the EBV infection mechanisms shed light on gB and gHgL, the two key components of the infection apparatus. In this study, for the first time, we utilized recombinant vesicular stomatitis virus (VSV) to display EBV gB (VSV-ΔG-gB/gB-G) or gHgL (VSV-ΔG-gHgL). In vitro studies confirmed successful virion production and glycoprotein presentation on the virion surface. In mouse models, VSV-ΔG-gB/gB-G or VSV-ΔG-gHgL elicited potent humoral responses. Neutralizing antibodies elicited by VSV-ΔG-gB/gB-G were prone to prevent B cell infection, while those elicited by VSV-ΔG-gHgL were prone to prevent epithelial cell infection. Combinatorial vaccination yields an additive effect. The ratio of endpoint neutralizing antibody titers to the endpoint total IgG titers immunized with VSV-ΔG-gHgL was approximately 1. The ratio of IgG1/IgG2a after VSV-ΔG-gB/gB-G immunization was approximately 1 in a dose-dependent, adjuvant-independent manner. Taken together, VSV-based EBV vaccines can elicit a high ratio of epithelial and B lymphocyte neutralizing antibodies, implying their unique potential as EBV prophylactic vaccine candidates. IMPORTANCE Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. In this study, for the first time, we reported the VSV-based EBV vaccines presenting two key components of the EBV infection apparatus, gB and gHgL. We confirmed potent antigen-specific antibody generation; these antibodies prevented EBV from infecting epithelial cells and B cells, and the IgG1/IgG2a ratio indicated balanced humoral-cellular responses. Taken together, we suggest VSV-based EBV vaccines are potent prophylactic candidates for clinical studies and help eradicate numerous EBV-associated malignant and benign diseases.

11.
Chem Asian J ; : e202200343, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35478382

RESUMO

For semiconductor photocatalysts with excellent performance in solar H2 production, broadening the utilization of solar irradiation is highly necessary to further improve the solar conversion efficiency. Herein, we combined a Cd0.5 Zn0.5 S photocatalyst with DPA/PdTPTBP microcrystals capable of red-to-blue photon upconversion, realizing substantial performance enhancement and an apparent quantum yield of 0.16% for H2 production driven by sub-bandgap photons (600∼650 nm). Meanwhile, this system could smoothly work with H2 production rate of 1.40 mmol g-1 h-1 for as long as 40 hours under 200 mW/cm2 irradiation with only 3% attenuation of photocatalytic activity. Moreover, the O2 -barrier property of DPA/PdTPTBP microcrystals assures that photocatalytic H2 production remains effective in the presence of 10% O2 by volume, which offers an opportunity for the photocatalytic application in O2 -enriched environments. The combination of O2 -resistant upconversion microcrystals and semiconductor catalysts is the most successful solution for the construction of TTA-UC-based photocatalytic H2 production system so far. The present study provides a clear guideline for designing new TTA-UC-based photocatalytic systems.

12.
Yi Chuan ; 44(4): 346-357, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35437242

RESUMO

Circadian rhythms have a cycle length of about 24 hours, i.e. a 24-hour internal clock. In order to adapt to the periodic changes of the circadian environment, almost all organisms on the earth, including algae, bacteria, plants, animals, etc., have evolved a special system-the circadian clock. It helps organisms to adapt to the daily changes in the environment and maintains the physiological process and the behavior in synchronization with the environment changes. Circadian rhythms are composed of an intracellular feedback loop that drives the expression of molecular components and their constitutive protein products to oscillate over a period of about 24 hours. Almost every aspect of the body's functions, including behavior and physiology, is regulated by the circadian clock, and shows obvious daily rhythms, such as sleep and wakefulness, alertness, body temperature fluctuations, urinary system, hormone secretion, immune regulation, and cytokine release. Circadian factors are also increasingly recognized for potentially affecting the occurrence, progression, treatment, and prognosis of a variety of diseases. This paper discusses several methods for measuring circadian behavior disorders in mice for different purposes, and shares experimental operations and analysis ideas, including the use of metabolism cage, wheel running activity, jet lag, lengthened light, bones photoperiod, as well as the T7-cycle. In addition, this paper also studies the possible reasons for variations caused by genetic backgrounds and light conditions. Given these methods, researchers can choose appropriate experiments to evaluate the influence of genetic factors, environmental factors or diseases on circadian behavior.


Assuntos
Relógios Circadianos , Ritmo Circadiano , Animais , Ritmo Circadiano/genética , Síndrome do Jet Lag , Camundongos , Atividade Motora/fisiologia , Fotoperíodo
13.
Front Public Health ; 10: 872030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433602

RESUMO

Background: The burden of cataracts was substantial in the current aging world. However, few epidemiological studies have examined the associations between climate and weather conditions and cataract in older populations. We aimed to investigate the associations of air relative humidity and temperature with cataracts in older adults in China. Methods: We used the cohort data from 2002, 2005, 2008, 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 62,595 Chinese older adults aged between 65 and 105 years were included in the analyses. City-level annual average air humidity and temperature during 2001 and 2017 (before the survey year) was used to measure population exposure. A cataract was self-reports based on the medical record or the doctor's diagnosis and 8,071 older adults had cataract. Covariates included socio-demographic, health status, lifestyles, and chronic conditions. We adopted the Generalized estimation equation (GEE) model to analyze the associations of relative humidity and temperature with cataracts. Results: We found that the average relative humidity (OR: 0.99; 95% CI: 0.98-0.99) in the past year was inversely associated with cataract likelihoods in older adults and a positive association between temperature (OR: 1.04; 95%CI: 1.03,1.05) in the past year and cataract likelihoods in older adults. The associations were robust in stratified analyses by sex, urban/rural residence, and education level. Furthermore, we found a nonlinear J-shaped relationship between temperature and cataract prevalence. Conclusion: Our findings provide the evidence that higher temperature and low relative humidity may be associated with cataracts in older adults.


Assuntos
Catarata , População Rural , Idoso , Idoso de 80 Anos ou mais , Catarata/epidemiologia , China/epidemiologia , Humanos , Umidade , Temperatura
14.
Nutrients ; 14(8)2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35458236

RESUMO

BACKGROUND: Iron overload is drawing attention in the development of knee osteoarthritis (OA). To identify the modifiable risk factors for iron-related pathological conditions, we examined the association between iron intake and the risk of knee OA progression. METHODS: A total of 1912 participants in the Osteoarthritis Initiative (OAI), aged 45-79 years and with at least one knee radiographic OA at baseline, were identified and were followed up to 6 years. The iron and other nutrient intake was measured by the validated Block Brief 2000 Food Frequency Questionnaire. The outcome measures were by radiographic progression on the basis of the Kellgren-Lawrence (KL) grade and the joint-space-narrowing (JSN) score. The association between the iron intake and the knee OA progression was examined by Cox proportional hazards models and restricted cubic spline (RCS) regression. RESULTS: Among the study participants, 409 participants experienced KL-grade progression, and 684 participants experienced JSN-score progression within 6 years. Overall, the association between iron intake and the risk of KL-grade progression followed a U shape (p for nonlinearity < 0.001). The risk of KL-grade progression was significantly lower in participants with iron intakes of <16.5 mg/day (per mg/day: adjusted hazard ratio (HR), 0.75; 95% CI (confidence interval), 0.64-0.89), and it was higher in those with iron intakes ≥16.5 mg/day (per mg/day: HR, 1.20; 95% CI, 1.04-1.38). Consistently, when the iron intake was assessed as deciles, compared to those in Deciles 3-5 (10.9-23.3 mg/day), the risk of KL-grade progression was higher for Deciles 1-2 (≤10.9 mg/day: HR, 1.57; 95% CI, 1.17-2.10) and for Deciles 6-10 (>23.3 mg/day: adjusted HR, 1.60; 95% CI, 1.19-2.16). Similar U-shaped relations were found for iron intake with the risk of JSN-score progression (p for nonlinearity = 0.035). CONCLUSIONS: There was a U-shaped association between the iron intake and the progression of knee OA, with an inflection point at about 16.5 mg/day, and minimal risk from 10.9 to 23.3 mg/day of iron intake. An appropriate iron intake was advisable for knee OA, whereas excessive or deficient iron intake increased the risk of knee OA progression.


Assuntos
Osteoartrite do Joelho , Progressão da Doença , Humanos , Ferro , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Fatores de Risco
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 381-385, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35395967

RESUMO

OBJECTIVE: To establish an animal model of acute B lymphoblastic leukemia (B-ALL) with minimal residual disease. METHODS: The transplanted tumor was formed by subcutaneous injection of 2×107 Nalm-6 cells, and the body weight, activity status and tumor formation status of nude mice were observed. Peripheral blood, bone marrow, liver and spleen and other tissues of nude mice were taken for pathological examination to understand whether the success of subcutaneous modeling was accompanied by systemic metastasis. RESULTS: There were 2×107 Nalm-6 cells injected subcutaneously in nude mice, (11.0±2.5) days later, the tumors of (3-4) × (3-4) mm were observed, the body weight of the nude mice was reduced and activity showed no limited. Infiltration of tumor cells in liver, spleen and bone marrow were observed in pathological sections. CONCLUSION: The animal model of subcutaneous tumor of B-ALL was successfully established in nude mice.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Animais , Peso Corporal , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasia Residual
17.
Oncogene ; 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468939

RESUMO

Kelch superfamily involves a variety of proteins containing multiple kelch motif and is well characterized as substrate adaptors for CUL3 E3 ligases, which play critical roles in carcinogenesis. However, the role of kelch proteins in lung cancer remains largely unknown. In this study, the non-small cell lung cancer (NSCLC) patients with higher expression of a kelch protein, kelch domain containing 3 (KLHDC3), showed worse overall survival. KLHDC3 deficiency affected NSCLC cell lines proliferation in vitro and in vivo. Further study indicated that KLHDC3 mediated CUL2 E3 ligase and tumor suppressor p14ARF interaction, facilitating the N-terminal ubiquitylation and subsequent degradation of p14ARF. Interestingly, Gefitinib-resistant NSCLC cell lines displayed higher KLHDC3 protein levels. Gefitinib and Osimertinib medications were capable of upregulating KLHDC3 expression to promote p14ARF degradation in the NSCLC cell lines. KLHDC3 shortage significantly increased the sensitivity of lung cancer cells to epidermal growth factor receptor (EGFR)-targeted drugs, providing an alternative explanation for the development of Gefitinib and Osimertinib resistance in NSCLC therapy. Our works suggest that CRL2KLHDC3 could be a valuable target to regulate the abundance of p14ARF and postpone the occurrence of EGFR-targeted drugs resistance.

18.
Nat Protoc ; 17(5): 1359-1384, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35396545

RESUMO

Insulin production is required for glucose homeostasis. Pancreatic islet ß cells are the only cells that produce insulin in humans; however, generation of functional ß cells in vitro from embryonic or adult tissues has been challenging. Here, we describe isolation of pancreatic islet progenitors from adult mice, which enables the efficient generation and long-term expansion of functional islet organoids in vitro. This protocol starts with purification of protein C receptor (Procr)-expressing islet progenitors. Coculture with endothelial cells generates islet organoids in vitro that can be expanded by passage. Functional maturation is achieved as a consequence of a prolonged culture period and cyclic glucose stimulation. Primary islet organoids form in 7-10 days. Subsequently, each passage takes 1 week, with the final maturation step requiring 3 weeks of additional culture. The resulting organoids are predominantly composed of ß cells but also contain small proportions of α, δ and pancreatic polypeptide cells. The organoids sense glucose and secrete insulin. This approach thus provides a strategy for ß cell generation in vitro and an organoid system to study islet regeneration and diseases.


Assuntos
Ilhotas Pancreáticas , Organoides , Animais , Células Endoteliais/metabolismo , Receptor de Proteína C Endotelial/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Camundongos
19.
Opt Express ; 30(9): 14103-14111, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35473161

RESUMO

We propose a graphene metamaterial consisting of several layers of longitudinally separated graphene nanoribbon array embedded into gain-assisted medium, demonstrating electromagnetically induced transparency-like spectra. Combined with finite-difference time-domain simulations, the transfer matrix method and temporal coupled-mode theory are adopted to quantitatively describe its transmission characteristics. These transmission characteristics can be tuned by altering the gain level in medium layer and the Fermi energy level in graphene. Additionally, it is the incorporation between gain medium and graphene nanoribbons with optimized geometrical parameters and Fermi energy level that the destructive interference between high order graphene plasmonic modes can be obtained, suggesting drastic phase transition with giant group delay and ultra-high group index up to 180 ps and 104, respectively. Our results can achieve efficient slow light effects for better optical buffers and other nonlinear applications.

20.
Pediatr Blood Cancer ; : e29715, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35482538

RESUMO

BACKGROUND: Blinatumomab, a CD3/CD19 BiTE® (bispecific T cell engager) molecule, was superior to high-risk third course consolidation chemotherapy (HC3) in prolonging event-free survival (EFS) in children with high-risk first relapse B-cell precursor acute lymphoblastic leukemia (B-ALL). Here, we report results from a post hoc measurable residual disease (MRD) analysis of this phase 3 study (NCT02393859). PROCEDURE: Children >28 days and <18 years with high-risk first-relapse B-ALL in cytomorphological complete remission (M1 marrow, <5% blasts) or with M2 marrow (≥5% and <25% blasts) after induction and two cycles of high-risk consolidation chemotherapy (baseline) were enrolled in this trial. Patients received one cycle of blinatumomab (15 µg/m2 /day, 4 weeks, continuous intravenous infusion) or HC3. The primary endpoint was EFS. In this post hoc analysis, patients with MRD <10-4 by PCR were grouped as having positive but not quantifiable (pbnq) or undetectable disease. RESULTS: A higher proportion of patients with MRD <10-4 had undetectable versus pbnq disease after blinatumomab (day 29) than after HC3 (p = 0.0367). Of the 22 patients with MRD ≥10-4 at baseline who achieved MRD remission after blinatumomab, 20 (91%) achieved MRD <10-4 remission by day 15. Patients treated with blinatumomab had improved EFS and overall survival compared with those treated with HC3 independent of end-of-induction or baseline (end-of-second consolidation) MRD levels. CONCLUSIONS: Blinatumomab was more efficacious than HC3 regardless of MRD status before treatment. These data support the role of blinatumomab in inducing deep MRD remission, negating the poor prognostic value of MRD.

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