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1.
Nano Lett ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533211

RESUMO

Picturing the atomic migration pathways of catalysts in a reactive atmosphere is of central significance for uncovering the underlying catalytic mechanisms and directing the design of high-performance catalysts. Here, we describe a reduction-controlled atomic migration pathway that converts nanoparticles to single atom alloys (SAAs), which has remained synthetically challenging in prior attempts due to the elusive mechanism. We achieved this by thermally treating the noble-metal nanoparticles M (M = Ru, Rh, Pd, Ag, Ir, Pt, and Au) on metal oxide (CuO) supports with H2/Ar. Atomic-level characterization revealed such conversion as the synergistic consequence of noble metal-promoted H2 dissociation and concomitant CuO reduction. The observed atomic migration pathway offers an understanding of the dynamic mechanisms study of nanomaterials formation and catalyst design.

2.
Adv Drug Deliv Rev ; : 114321, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35533789

RESUMO

Bacterial membrane vesicles (BMVs) have emerged as novel and promising platforms for the development of vaccines and immunotherapeutic strategies against infectious and noninfectious diseases. The rich microbe-associated molecular patterns (MAMPs) and nanoscale membrane vesicle structure of BMVs make them highly immunogenic. In addition, BMVs can be endowed with more functions via genetic and chemical modifications. This article reviews the immunological characteristics and effects of BMVs, techniques for BMV production and modification, and the applications of BMVs as vaccines or vaccine carriers. In summary, given their versatile characteristics and immunomodulatory properties, BMVs can be used for clinical vaccine or immunotherapy applications.

3.
Neurochem Res ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513760

RESUMO

The antiknock additive methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese(Mn) compound. Mn neurotoxicity caused by occupational Mn exposure (mostly inorganic MnCl2) is associated with motor and cognitive disturbances, referred to as Manganism. However, the impact of environmentally relevant Mn exposure on MMT-induced Manganism is poorly understood. In this investigation, we studied the effects of MMT on motor function and brain structure, and compared its effects with those of inorganic MnCl2. After adaptive feeding for 7 days, male and female Sprague-Dawley (SD) rats in the MMT-treated groups and positive control group were treated for 8 weeks with MMT (1, 2 and 4 mg/kg/i.g.) or MnCl2·4H2O (200 mg/kg/i.g.). Mn content in blood, liver, spleen and distinct brain regions was determined by inductively coupled plasma-mass spectrometer (ICP-MS). We found that MMT and MnCl2 exposure led to slower body-weight-gain in female rats, impaired motor and balance function and spatial learning and memory both in male and female rats. HE staining showed that MMT and MnCl2 led to altered structure of the substantia nigra pars compacta (SNpc), and Nissl staining corroborated MMT's propensity to damage the SNpc both in male and female rat. In addition, Immunostaining of the SNpc showed decreased TH-positive neurons in MMT- and MnCl2-treated rats, concomitant with Iba1 activation in microglia. Moreover, no statistically significant difference was noted between the rats in the H-MMT and MnCl2 groups. In summary, these findings suggest that MMT and MnCl2 exposure cause ultrastructural changes in the SNpc neurons culminating in altered motor behavior and cognition, suggesting that altered SNpc structure and function may underline the motor and cognitive deficits inherent to Manganism, and accounting for MMT and MnCl2's manifestations of atypical parkinsonism.

4.
Acta Pharmacol Sin ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459869

RESUMO

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a multifunctional protein under physiological and pathological conditions. In this study we investigated the roles of AGR2 in regulating cholesterol biogenesis, lipid-lowering efficiency of lovastatin as well as in protection against hypercholesterolemia/statin-induced liver injury. We showed that AGR2 knockout significantly decreased hepatic and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in mice with whole-body or hepatocyte-specific Agr2-null mutant, compared with the levels in their wild-type littermates fed a normal chow diet (NCD) or high-fat diet (HFD). In contrast, mice with AGR2 overexpression (Agr2/Tg) exhibited an increased cholesterol level. Mechanistic studies revealed that AGR2 affected cholesterol biogenesis via activation of AKT/sterol regulatory element-binding protein-2 (SREBP2), to some extent, in a PDI motif-dependent manner. Moreover, elevated AGR2 led to a significant decrease in the lipid-lowering efficacy of lovastatin (10 mg· kg-1· d-1, ip, for 2 weeks) in mice with hypercholesterolemia (hyperCho), which was validated by results obtained from clinical samples in statin-treated patients. We showed that lovastatin had limited effect on AGR2 expression, but AGR2 was inducible in Agr2/Tg mice fed a HFD. Further investigations demonstrated that drug-induced liver toxicity and inflammatory reactions were alleviated in hypercholesterolemic Agr2/Tg mice, suggesting the dual functions of AGR2 in lipid management and hyperCho/statin-induced liver injury. Importantly, the AGR2-reduced lipid-lowering efficacy of lovastatin was attenuated, at least partially, by co-administration of a sulfhydryl-reactive compound allicin (20 mg· kg-1· d-1, ip, for 2 weeks). These results demonstrate a novel role of AGR2 in cholesterol metabolism, drug resistance and liver protection, suggesting AGR2 as a potential predictor for selection of lipid-lowering drugs in clinic.

5.
Health Qual Life Outcomes ; 20(1): 64, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35443689

RESUMO

OBJECTIVES: Lifestyles, accounting for 53% in determining death, play a vital role in improving the health of older adults. Thus, this study aimed to explore the influencing factors of the health-promoting-lifestyles and interaction mechanisms among older adults. METHODS: A total of 8526 elders were selected by a three-stage stratified random cluster sampling method. Socioeconomic status, family relationships, social support, health-related quality of life (QOL), and health-promoting-lifestyles (HPLP) of older adults were assessed with the Social Support Rating Scale, the short form 36 health survey (SF-36) and Health-Promoting Lifestyle Profile. A structural equation model (SEM) was conducted to test the direct and indirect association between influencing factors with HPLP. RESULTS: In this study, there were 4901 older adults who were empty nesters, and 3625 were non-empty nesters. Of all respondents, the average QOL score of older adults was 62.28 ± 16.51, average social support score was 78.06 ± 7.50. The HPLP score of older adults was 105.9 ± 19.6, and the average score of subscales was 2.5 ± 0.5, which was at the medium level. Social support had a positive and direct effect on HPLP of older adults (total effect, 0.34). Meanwhile, social support mediated the relationship between socioeconomic (total effect, 0.17), QOL (total effect, 0.33) and HPLP. Family relationships had a small indirect effect on HPLP via social support (0.01). CONCLUSIONS: Social support is the strongest influencing factor in the health-promoting-lifestyles among older adults, followed by socioeconomic, health-related quality of life and family support. Thus, maintaining higher social support was important to improve the HPLP of older adults.


Assuntos
Relações Familiares , Qualidade de Vida , Idoso , China/epidemiologia , Estudos Transversais , Humanos , Estilo de Vida , Classe Social , Apoio Social , Inquéritos e Questionários
6.
J Virol ; 96(9): e0003822, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35420442

RESUMO

Due to the limitation of human studies with respect to individual difference or the accessibility of fresh tissue samples, how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in pathological complications in lung, the main site of infection, is still incompletely understood. Therefore, physiologically relevant animal models under realistic SARS-CoV-2 infection conditions would be helpful to our understanding of dysregulated inflammation response in lung in the context of targeted therapeutics. Here, we characterized the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicates human symptoms, including severe lung pathology and lymphopenia. We showed a reduction of lymphocyte populations and an increase of neutrophils in lung and then demonstrated the key role of neutrophil-mediated lung immunopathology in both mice and humans. Under severe conditions, neutrophils recruited by a chemokine-driven positive feedback produced elevated "fatal signature" proinflammatory genes and pathways related to neutrophil activation or releasing of granular content. In addition, we identified a new Cd177high cluster that is undergoing respiratory burst and Stfahigh cluster cells that may dampen antigen presentation upon infection. We also revealed the devastating effect of overactivated neutrophil by showing the highly enriched neutrophil extracellular traps in lung and a dampened B-cell function in either lung or spleen that may be attributed to arginine consumption by neutrophil. The current study helped our understanding of SARS-CoV-2-induced pneumonia and warranted the concept of neutrophil-targeting therapeutics in COVID-19 treatment. IMPORTANCE We demonstrated the single-cell landscape in lung and spleen upon SARS-CoV-2 infection in an acute severe disease mouse model that replicated human symptoms, including severe lung pathology and lymphopenia. Our comprehensive study revealed the key role of neutrophil-mediated lung immunopathology in SARS-CoV-2-induced severe pneumonia, which not only helped our understanding of COVID-19 but also warranted the concept of neutrophil targeting therapeutics in COVID-19 treatment.

7.
Orthop Surg ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35451209

RESUMO

OBJECTIVE: To explore the effect of diabetes mellitus (DM) on implant osseointegration of titanium screws. METHODS: Sixty rats were randomly divided into a DM group and a control group (each group, n = 30). DM group rats were injected with 1% Streptozotocin solution at 65 mg/kg to establish a DM model. Titanium screws were implanted into the rats' distal femurs in both groups. The rats were sacrificed for micro-CT scanning, micro-indentation, biomechanical detection, confocal Raman microspectroscopy, and histological and histomorphometric analysis at 4, 8, and 12 weeks post-implantation, respectively. Messenger RNA (mRNA) expression and protein expression of the related growth factors around the implant were analyzed using real-time polymerase chain reaction and Western blots. RESULTS: At 4, 8 and 12 weeks, micro-CT scanning, hematoxylin-eosin (HE) staining, Gieson's acid-magenta staining, and fluorescent labeled staining showed disorder in the bone tissue arrangement, a lack of new bone tissue, poor maturity and continuity, and poor trabecular bone parameters around the implant in the DM group. At 4, 8, and 12 weeks, the interfacial bone binding rate in the DM group was significantly lower (16.2% ± 4.8%, 25.7% ± 5.7%, 42.5% ± 5.8%, respectively) than that in the control group (23.6% ± 5.2%, 40.8% ± 6.3%, 64.2% ± 7.3%, respectively; P < 0.05). At 8 and 12 weeks, the elastic modulus (17.0 ± 1.8 and 15.1 ± 1.5 GPa, respectively) and trabecular bone hardness (571 ± 39 and 401 ± 37 MPa, respectively) in the DM group were significantly lower than the elastic modulus (23.4 ± 2.3 and 23.8 ± 1.8 GPa, respectively) and trabecular bone hardness (711 ± 45 and 719 ± 46 MPa, respectively) in the control group (P < 0.05). The maximum load required for the prosthesis pull-out experiment in the DM group at 4, 8, and 12 weeks (55.14 ± 6.74 N, 73.34 ± 8.43 N, and 83.45 ± 8.32 N, respectively) was significantly lower than that in the control group (77.45 ± 7.48 N, 93.28 ± 8.29 N, and 123.62 ± 9.43 N, respectively, P < 0.05). At 8 and 12 weeks, the mineral-to-collagen ratio in the DM group (6.56 % ± 1.35% and 4.45%± 1.25%, respectively) was significantly higher than that in the control group (5.31% ± 1.42% and 3.62% ± 1.33%, respectively, P < 0.05). At 12 weeks, mRNA and protein expression levels of bone morphogenetic protein 2, transforming growth factor-ß1, vascular endothelial growth factor, osteopontin, osteocalcin, and runt-related transcription factor 2 in the DM group were significantly lower than that in the control group. CONCLUSIONS: DM can negatively affect bone osseointegration, manifesting as disorder in bone tissue arrangement around the implant, a lack of new bone tissue, poor maturity and continuity, poor trabecular bone parameters and lower expression of the related growth factors.

8.
J Sep Sci ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442556

RESUMO

This paper aims to establish a simple and easy high-performance liquid chromatography system coupled with an ultraviolet detector suitable for simultaneous determination of 24 antiepileptic drugs in human plasma. Optimized chromatographic separation was performed on a ZORBAX Eclipse Plus-C18 (4.6 × 150 mm2 , 3.5 µm) column with acetonitrile and 5 mM potassium dihydrogen phosphate water solution as mobile phase. Note that, 24 antiepileptic drugs were divided into three groups and eluted with different gradient procedures, respectively. The column temperature was maintained at 35°C and the detection wavelength was set at 210 nm. Plasma was processed with ethyl acetate or acetonitrile. The calibration curves of 24 antiepileptic drugs demonstrated good linearity within the test range (r > 0.996). The intra- and inter-batch precision and accuracy were all less than 15%, while extraction recoveries were in the range of 74.57%-90.89% with the relative standard deviation values less than 15%. The validated methods have been successfully applied to determination of some antiepileptic drugs in rat or patient plasma. Those results indicated that the developed methods were simple and easy, and could be suitable for the determination of 24 antiepileptic drugs in plasma just by changing the gradient elution procedures of mobile phase.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35468947

RESUMO

Although haploidentical stem cell transplantation (haplo-HSCT) offers almost all acute lymphoblastic leukaemia (ALL) patients an opportunity for immediate transplantation, it exhibits a higher incidence of graft failure and graft versus host disease (GVHD). Mesenchymal stem cells (MSCs) are characterised by their haematopoiesis-promoting and immunomodulatory capacity. Thus, we designed a combination of haplo-HSCT and MSCs for ALL patients. ALL patients (n = 110) were given haploidentical HSCs combined with allogenic MSCs, and ALL patients without MSC infusion (n = 56) were included as controls. The 100-day cumulative incidences of grade ≥2 acute GVHD (aGVHD) and grade ≥3 aGVHD were 40.00% and 9.09% compared to 42.32% (P = 0.79) and 22.79% (P = 0.03) in patients without MSC infusion, respectively. The 3-year cumulative incidences of chronic GVHD (cGVHD) and extensive cGVHD were 22.27% and 10.27% compared to 32.14% (P = 0.19) and 22.21% (P = 0.04) in patients without MSC infusion, respectively. No significant differences in the 3-year relapse incidence, nonrelapse mortality, leukaemia-free survival or overall survival in groups with and without MSC cotransplantation were observed. Multivariate analysis showed that MSC infusion contributed to a lower risk of developing extensive cGVHD. Our data suggested that haplo-HSCT combined with MSCs may provide an effective and safe treatment for ALL patients.

10.
Biomaterials ; 284: 121516, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35436740

RESUMO

Tumor hyaluronan (HA) accumulation is closely associated with the formation of a hypoxic microenvironment that is highly immunosuppressive and severely hinders the efficacy of antitumor therapeutics. To address this problem, we develop an effective HA attenuation strategy that uses an integrated nanosystem based on mesoporous polydopamine (mPDA) with excellent photothermal conversion efficiency to boost hyaluronidase (HAase) activity remotely. Upon light irradiation, the thermal effect generated by mPDA not only directly kills tumor cells that produces an in situ vaccine effect, but also significantly boosts HAase activity (∼5 folds), leading to marked HA break down. Photoheat and HA degradation synergistically reduce tumor HIF-1α expression and reverse immunosuppressive responses. Using the synergistic treatment in a breast cancer model, we find decreased infiltration of immunosuppressive cells, including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells, increased immune-activated cells, such as mature dendritic cells and CD8+ T cells, and reduced immune checkpoint PD-L1 expression. The resulting relief from tumor microenvironment immunosuppression significantly contributes to an enhanced antitumor effect. This study provides an effective strategy to improve the hypoxic tumor microenvironment and simultaneously promote immune-mediated tumor regression.


Assuntos
Neoplasias , Microambiente Tumoral , Linfócitos T CD8-Positivos , Linhagem Celular Tumoral , Humanos , Hialuronoglucosaminidase , Imunoterapia/métodos
11.
Pathol Res Pract ; 234: 153911, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35489125

RESUMO

BACKGROUND: Pancreatic cancer (PC) is one of the most malignant solid tumors and its 5-year survival rate remains poor. Although immunotherapy has achieved certain therapeutic efficacy in some clinical trials, such treatment still shows low responses and overall remission rate. Therefore, it is urgently necessary to dissect the tumor microenvironment and optimize the immunotherapeutic strategies against this malignancy. METHODS: Using the multi-color immunohistochemistry assay, we investigated the expressions of B7-H3, B7-H4, HHLA2, CD8, and CD68 in 63 cases of PC tissues in a tissue microarray. Moreover, we analyzed immunolocalization features, clinical associations and prognostic values of these molecules. RESULTS: The expressions of B7-H3, B7-H4, and HHLA2 could be detected in cytokeratin staining positive (CK+) cancer epithelial cells, CD68+tumor-associated macrophages (TAMs), and even other cells defined as CK-CD8-CD68-. Higher expression of B7-H3 in tumor cells could predict a better survival of the PC patients. A positive correlation was found between the expressions of B7-H3 and HHLA2 in tumor cells, while there was a negative correlation between the expressions of B7-H4 and HHLA2 in tumor cells. A positive correlation was found between the expressions of B7-H3 and B7-H4 or HHLA2 in CD68+TAMs, but not B7-H4 and HHLA2. Tumor-infiltrating CD8+T cells in combination with CD68+TAMs could serve as an important predictor for the postoperative prognosis of PC patients. Higher expression of B7-H3, or HHLA2 in CD68+TAMs could serve as an important predictor for poorer prognosis of PC patients. Patients with B7-H3lowB7-H4low, B7-H3lowHHLA2low, or B7-H4lowHHLA2low on CD68+TAMs could have a better postoperative prognosis compared with the other sub-populations in the combinational analysis. CONCLUSIONS: Taken together, our study indicated variable expressions and prognostic values of B7-H3, B7-H4, and HHLA2, in human PC tissues, and demonstrated that these co-stimulator molecules expressed by CD68+TAMs could be used as important bio-markers for the prognostic prediction of PC patients. Moreover, these results supported that the evaluation of these markers could be used as essential candidate targets for immunotherapy against PC.

12.
Phytomedicine ; 101: 154087, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429924

RESUMO

BACKGROUND: Although triple-negative breast cancer (TNBC) accounts for only 15% of breast cancer cases, it is associated with a high relapse rate and poor outcome after standard treatment. Currently, the effective drugs and treatment strategies for TNBC remain limited, and thus, developing effective treatments for TNBC is pressing. Several studies have demonstrated that both chalcone and syringaldehyde have anticancer effect, but their potential anti-TNBC bioactivity are still unknown. PURPOSE: The present study aimed to synthesize a chalcone-syringaldehyde hybrid (CSH1) and explore its potential anti-TNBC effects and the underlying molecular mechanism. METHODS: Cell cytotoxicity was determined by 3-(4,5-dimethythiazol)-2,5-diphenyltetrazolium bromide (MTT). The activity of cell proliferation was measured by colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Cell cycle distribution and cell apoptosis were determined by fluorescence-activated cell sorter (FACS). The situation of DNA damage was observed using fluorescence microscopy. The ability of cell-matrix adhesion, migration and invasion was detected using cell adhesion assay and transwell assay. Transcriptome sequencing was performed to find out the changed genes. Levels of various signaling proteins were assessed by western blotting. RESULTS: CSH1 treatment triggered DNA damage and inhibited DNA replication, cell cycle arrest, and cell apoptosis via suppressing signal transducer and activator of transcription 3 (STAT3) phosphorylation. Whole genome RNA-seq analysis suggested that 4% of changed genes were correlated to DNA damage and repair, and nearly 18% of changed genes were functionally related to cell adhesion and migration. Experimental evidence indicated that CSH1 treatment significantly affected the distribution of focal adhesion kinase (FAK) and its phosphorylation, resulting in cell-matrix-adhesion reduction and migration inhibition of TNBC cells. Further mechanistic studies indicated that CSH1 inhibited TNBC cell proliferation, adhesion, and migration by inhibiting cytoskeleton-associated protein 2 (CKAP2)-mediated FAK and STAT3 phosphorylation signaling. CONCLUSION: These results suggest that CKAP2-mediated FAK and STAT3 phosphorylation signaling is a valuable target for TNBC treatment, and these findings also reveal the potential of CSH1 as a prospective TNBC drug.

13.
Med Ultrason ; 2022 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-35437527

RESUMO

AIMS: Acute pulmonary embolism (aPE) leads to a significant decrease in antegrade pulmonary blood volume (PBV), which can be measured by contrast echocardiography at the bedside. The aim of this work was to evaluate the feasibility and performance of PBV differentiating between patients with and without aPE. MATERIAL AND METHODS: A total of 89 patients underwent computed tomography pulmonary angiography (CTPA) for suspected aPE were enrolled in the study. Their clinical and conventional echocardiographic characteristics were collected. Contrast echocardiography with measurements of PBV were performed. RESULTS: There were 57 patients with aPE, with a mean Mastora pulmonary artery obstruction index (PAOI) of 56.14%. Pulmonary transit time (PTT), normalized PTT (nPTT) and PBV in patients with aPE was less than one half of those in patients without PE (p<0.05). There was significant negative correlation between PBV and Mastora PAOI (r=-0.897, p<0.01). None of the conventional echocardiographic parameters had an area under the receiver operating characteristic curve of >0.5, while it was 0.997(0.984~1.010) for PBV in differentiating between patients with aPE or not. The optimal cutoff valueof PBV was 370ml, with a sensitivity of 100%, a specificity of 95.45% and an accuracy of 96.55%. CONCLUSIONS: PBV had a powerful performance in differentiating between patients with aPE or not, and a PBV of <370ml indicated aPE. Contrast echocardiography is enormously useful in the recognition and differentiation of PE and can assess the severity of the PE and the patient's response to therapy.

14.
J Phys Condens Matter ; 34(25)2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35378517

RESUMO

We numerically calculate the local density of states (LDOS) in asymmetric Anderson model in mixed valence regime using hierarchical equations of motion approach. Based on the idea that the asymmetric line shape of LDOS around Fermi level stems from the interference between the single particle resonance and the Kondo resonance, we perform a fitting. From the fitting results, we obtain the Kondo temperatures and the Fano factors with changing the single particle energy. The tendency of Kondo temperature agrees with the previous analytic expressions and the Fano factors are in an expected variation of Fano resonance. Our study shows that the Fano-Kondo resonance can reasonably explain the asymmetric line shape of the LDOS around the Fermi level.

15.
Front Psychol ; 13: 813775, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432140

RESUMO

Background: Studies have found that poor sleep quality is negatively associated with subjective wellbeing in older adults, but the mechanisms underlying are unclear. In this study, we aimed to examine the mediating role of negative emotions and the moderating role of perceived social support in the relationship between sleep quality and subjective wellbeing in older adults with multimorbidity. Methods: A multi-stage random sampling method was used to select a sample of 3,266 older adults aged 60 years and older. The Memorial University of Newfoundland Scale of Happiness (MUNSH), Pittsburgh Sleep Quality Index (PSQI), Depression Anxiety Stress Scales-21 (DASS-21), and Perceived Social Support Scale (PSSS) were used to assess subjective wellbeing, sleep quality, negative emotional states, and perceived social support, respectively. The moderated mediation models were examined using SPSS PROCESS Version 3.3 software. Results: Sleep quality had a significant direct effect on subjective wellbeing in older adults (ß = -0.997, t = -11.783, p < 0.001). Negative emotions partially mediated the effect of sleep quality on subjective wellbeing (ab = -0.608, 95%CI: -0.728, -0.497). The indirect effect was moderated by perceived social support (ß = -0.038, 95%CI: -0.062, -0.014, p < 0.001; ß = -0.002, 95%CI: -0.004, -0.01, p = 0.008). Conclusion: Negative emotions increased the negative association between sleep quality and the subjective wellbeing of older adults with multimorbidity, and perceived social support played a moderating role. Psychological and behavioral interventions should be implemented as early as possible to promote mental health and enhance social support level of older adults with multimorbidity, and ultimately improve the subjective wellbeing of older adults.

16.
Biopreserv Biobank ; 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35377214

RESUMO

Background: RNA integrity of tumor tissues from 12 common organs was measured, and tumor tissues from liver were found to have the best RNA integrity in our previous study. The effects of preanalytical variables in the phase of pre- and postacquisition on RNA integrity were further assessed in hepatocellular carcinoma (HCC) tissues in this study. Methods: RNA integrity number (RIN) was measured in tissues from 146 HCC patients. First, 42 fresh HCC tumor tissues were newly collected to assess the effect of various preanalytical variables in the phase of preacquisition on RNA integrity. Second, eight paired HCC tumor and normal tissues were newly collected and used in the gradient course study of ex vivo ischemia time and freeze-thaw cycles on RNA integrity. Finally, 96 stock-frozen tumor tissues with various years of frozen storage were used to assess the effect of cryopreservation time. Results: RNA integrity was found to be independent of patient age, sex, clinical stage, tumor location, HBV infection status, tumor diameter, and surgical approach, but affected by tumor grade. Tumor tissues with a greater tumor grade had lower RIN. With the prolongation of ex vivo ischemia time, freeze-thaw cycles, and cryopreservation time, the RIN of HCC tissues showed decreasing trends. Significant decreases in RIN of the tumor and normal tissues were observed at 6 and 2 hours of ex vivo ischemia time, respectively, and significantly decreased RIN of tumor tissues was observed after six freeze-thaw cycles and 6 years of cryopreservation. Conclusions: Preanalytical variables in the phase of preacquisition such as tumor grade, and in the postacquisition phase such as ex vivo ischemia time, freeze-thaw times, and freeze-storage time both have effects on RNA integrity of HCC tissues. Tissue-based translational research should pay attention to preanalytical variables when collecting and utilizing tumor tissues.

17.
Sci Rep ; 12(1): 5712, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383254

RESUMO

Pulmonary cryptococcosis (PC) is a common fungal infectious disease, and infection can occur in patients with any immune function. To better understand PC, we compared the CT findings and histopathological results in immunocompetent and immunocompromised patients. The clinical data of 68 patients with PC were collected retrospectively and divided into the immunocompetent group and immunocompromised group. The clinical characteristics, CT manifestations and histopathological characteristics of the two groups of patients were compared. Forty-two patients (61.8%) were immunocompetent, and 26 patients (38.2%) were immunocompromised. Compared with immunocompromised patients, 57.14% (24/42) of immunocompetent patients were asymptomatic (p = 0.002). Compared with immunocompetent patients, cough (14/26, 53.9%) and fever (13/26, 50.0%) were the main symptoms in immunocompromised patients (p = 0.044, p = 0.007). Nodular lesions (97.6%, 41/42) were the most common CT type in immunocompetent patients, and the CT characteristic was a single lesion (25/42, 59.5%); the main histopathological type was nodular fibrogranuloma (30/42, 71.4%), and the main histopathological characteristic was inflammatory granuloma (31/42, 73.81%) formed by macrophage phagocytosis of Cryptococcus. Consolidation (15/26, 57.7%) was more common in the CT type of immunocompromised patients. Multiple lesions (24/26, 92.31%), air bronchial signs (19/26, 73.081%) and cavities (9/26, 34.62%) were the main CT characteristics. The mucinous colloid type (19/26, 73.1%) was its main histopathological type, which was mainly characterized by a small amount of surrounding inflammatory cell infiltration (17/26, 65.4%). There were significant differences in the classification and characteristics of CT and pathology between the two groups (p < 0.05). Through the CT manifestations and histopathological characteristics of PC under different immune function states, it was found that immune function has a significant impact on the CT manifestations and histopathological characteristics of patients with PC.


Assuntos
Criptococose , Pneumopatias Fúngicas , Humanos , Hospedeiro Imunocomprometido , Pneumopatias Fúngicas/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
18.
Chem Asian J ; : e202200131, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35415949

RESUMO

A highly efficient asymmetric Michael addition of bulky glycine imine to α,ß-unsaturated isoxazoles has been achieved by using 5 mol% of chiral cyclopropenimine as a chiral organo-superbase catalyst under mild conditions. Michael adducts were obtained in excellent yields (up to 97%) and stereoselectivities (up to>99 : 1 dr and 98% ee). A significant solvent effect was found in these chiral organosuperbase catalyzed asymmetric Michael reactions. Gram-scale preparation of Michael adducts and their transformations are realized to provide corresponding products without loss of stereoselectivities. The configurations of Michael adduct was determined by single-crystal X-ray diffraction analysis.

19.
RSC Adv ; 12(16): 10051-10061, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35424933

RESUMO

A dual-template magnetic molecularly imprinted polymer (Dt-MMIP) with a specific recognition capability for carbamazepine (CBZ) and lamotrigine (LTG) was synthesized using methacrylic acid as a functional monomer, and ethylene glycol dimethylmethacrylate as a cross-linking agent. A magnetic non-molecularly imprinted polymer without templates (MNIP) was also prepared using the same procedure. The prepared polymers were characterized using scanning electron microscopy, Fourier-transform infrared spectroscopy and adsorption experiments. Results indicated that both Dt-MMIPs and MNIPs were microspherical nanoparticles, and the surface of the Dt-MMIP was rougher than that of the MNIP. In addition, the prepared Dt-MMIPs possessed a higher adsorption capacity and better selectivity for CBZ and LTG than the MNIPs. The maximum static adsorption capacities of Dt-MMIP for CBZ and LTG were 249.5 and 647.9 µg g-1, respectively, whereas those of MNIP were 75.8 and 379.8 µg g-1, respectively. The obtained Dt-MMIPs were applied as a magnetic solid-phase extraction sorbent for the rapid and selective extraction of CBZ and LTG in rat serum samples, and determination was performed by high-performance liquid chromatography with UV detection (HPLC-UV). The developed method of dispersive SPE based on Dt-MMIPs coupled to HPLC-UV has good rapidity and selectivity, and application prospects in serum.

20.
Front Immunol ; 13: 832230, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320940

RESUMO

Background: Combination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in the treatment of many types of cancers and has become the mainstream in the comprehensive treatment of cancers. Ablation in combination with immunotherapy has achieved tremendous efficacy in some preclinical and clinical studies. To date, our team proved that ablation in combination with ICIs was a promising antitumor therapeutic strategy for the liver metastasis of colorectal cancer (CRC). Moreover, we found that the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was up-regulated after microwave ablation (MWA), indicating that TIGIT was involved in immunosuppression, and the combination of MWA and TIGIT blockade represented a potential clinical treatment strategy. Methods: In the present study, we examined the expression of TIGIT using a preclinical mouse model treated with MWA. Moreover, we evaluated the antitumor functions of MWA alone or in combination with TIGIT blockade by monitoring tumor growth and survival of the mice. Besides, we also detected the numbers of tumor-infiltrating lymphocytes (TILs), and effector molecules of CD8+ T cells using flow cytometry. Finally, we analyzed the single-cell RNA sequencing (scRNA-seq) data from the MWA and MWA plus anti-TIGIT groups. Results: The expression of TIGIT in various immune cells was up-regulated after MWA, and the addition of TIGIT blockade to MWA prolonged survival and delayed tumor growth in the MC38 tumor model. Taken together, our findings showed that TIGIT blockade in combination with MWA significantly promoted the expansion and functions of CD8+ TILs and reshaped myeloid cells in the tumor microenvironment (TME) using flow cytometry and scRNA-seq analysis. Conclusions: TIGIT blockade in combination with MWA was a novel treatment strategy for the liver metastasis of CRC, and this combination therapy could reprogram the TME toward an antitumor environment.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias Hepáticas , Animais , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Camundongos , Micro-Ondas , Receptores Imunológicos/metabolismo , Microambiente Tumoral
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