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1.
J Vis Exp ; (175)2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34633364

RESUMO

An efficient and stable transformation system is fundamental for gene function study and molecular breeding of plants. Here, we describe the use of an Agrobacterium rhizogenes mediated transformation system on pigeon pea. The stem is infected with A. rhizogenes carrying a binary vector, which induced callus after 7 days and adventitious roots 14 days later. The generated transgenic hairy root was identified by morphological analysis and a GFP reporter gene.To further illustrate the application range of this system, CcCIPK14 (Calcineurin B-like protein-interacting protein kinases) was transformed into pigeon pea using this transformation method. The transgenic plants were treated with jasmonic acid (JA) and abscisic acid (ABA), respectively, for the purpose of testing whether CcCIPK14 responds to those hormones. The results demonstrated that (1) exogenous hormones could significantly upregulate the expression levelof CcCIPK14, especially in CcCIPK14 over-expression (OE) plants; (2) the content of Genistein in CcCIPK14-OE lines was significantly higher than the control; (3) the expression level of two downstream key flavonoid synthase genes, CcHIDH1 and CcHIDH2, were up-regulated in the CcCIPK14-OE lines; and (4) the hairy root transgenic system can be used to study metabolically functional genes in non-model plants.

2.
BMC Pregnancy Childbirth ; 21(1): 682, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620123

RESUMO

BACKGROUND: To evaluate the impact of oral carbohydrate-rich (Ch-R) supplement taken 2 hours before an elective caesarean delivery (CD) on maternal and neonatal perioperative outcomes. METHODS: Ninety pregnant women undergoing elective CD were randomized into the Ch-R group, placebo group and fasting group equally. Participants' blood was drawn at three time points, before intervention, immediately after and 1 day after the surgery to measure maternal and neonatal biochemical indices. Meanwhile women's perioperative symptoms and signs were recorded. RESULTS: Eighty-eight pregnant women were finally included in the study. Women who had drunk Ch-R supplement had lower postoperative insulin level (ß = - 3.50, 95% CI - 5.45 to - 1.56), as well as postoperative HOMA-IR index (ß = - 0.74, 95% CI - 1.15 to - 0.34), compared with women who had fasted. Additionally, neonates of mothers who were allocated in the Ch-R group also had a higher glucose level, compared with neonates of mothers in the fasting group (ß = 0.40, CI 0.17 to 0.62). CONCLUSION: Oral Ch-R solution administered 2 hours before an elective CD may not only alleviate maternal postoperative insulin resistance, but also comfort women's preoperative thirst and hunger, compared to fasting. Additionally, it may increase neonatal glucose level as well. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000033163 . Data of Registration: 2020-5-22.

3.
J Hematol Oncol ; 14(1): 160, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620200

RESUMO

In this era of precision medicine, with the help of biomarkers, immunotherapy has significantly improved prognosis of many patients with malignant tumor. Deficient mismatch repair (dMMR)/microsatellite instability (MSI) status is used as a biomarker in clinical practice to predict favorable response to immunotherapy and prognosis. MSI is an important characteristic which facilitates mutation and improves the likelihood of a favorable response to immunotherapy. However, many patients with dMMR/MSI still respond poorly to immunotherapies, which partly results from intratumor heterogeneity propelled by dMMR/MSI. In this review, we discuss how dMMR/MSI facilitates mutations in tumor cells and generates intratumor heterogeneity, especially through type II interferon (IFN-γ) signaling and tumor-infiltrating lymphocytes (TILs). We discuss the mechanism of immunotherapy from the perspective of dMMR/MSI, molecular pathways and TILs, and we discuss how intratumor heterogeneity hinders the therapeutic effect of immunotherapy. Finally, we summarize present techniques and strategies to look at the tumor as a whole to design personalized regimes and achieve favorable prognosis.

4.
Curr Alzheimer Res ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34598665

RESUMO

BACKGROUND: Education could offer a protective effect on cognition in individuals with Subjective Cognitive Decline (SCD), which is considered to be the early stage of Alzheimer's Dis- ease (AD). However, the effect of education on cognition in SCD individuals with SCD-plus fea- tures is not clear. OBJECTIVE: The aim of the study was to explore the effect of education on cognition in SCD individ- uals with SCD-plus features. METHODS: A total of 234 individuals with SCD were included from the Sino Longitudinal Study on Cognitive Decline (SILCODE). Cognition was assessed across 4 domains (memory, executive, lan- guage, and general cognitive functions). Multiple linear regression models were constructed to ex- amine the effect of education on cognitive scores in individuals without worry (n=91) and with wor- ry (n=143). Furthermore, we assessed differences in effects between APOE ε4 noncarriers and APOE ε4 carriers in both groups. RESULTS: Multiple linear regression analysis showed a positive effect of education on memory, ex- ecutive, and language cognition in individuals without worry and all cognitive domains in individu- als with worry. Furthermore, we found a positive effect of education on executive cognition in APOE ε4 noncarriers without worry and language and general cognition in APOE ε4 carriers with- out worry. Meanwhile, education had a positive effect on all cognitive domains in APOE ε4 noncar- riers with worry and executive, language, and general cognition in APOE ε4 carriers with worry. CONCLUSION: This study indicates that education has the potential to delay or reduce cognitive dec- line in SCD individuals with SCD-plus features.

5.
Cytotherapy ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34593327

RESUMO

BACKGROUND AIMS: Despite the impressive efficacy of chimeric antigen receptor (CAR) T-cell therapy, adverse effects, including cytokine release syndrome and neurotoxicity, impede its therapeutic application, thus making the modulation of CAR T-cell activity a priority. The destabilizing domain mutated from Escherichia coli dihydrofolate reductase (DHFR) is inherently unstable and degraded by proteasomes unless it is stabilized by its chemical ligand trimethoprim (TMP), a Food and Drug Administration-approved drug. Here the authors reveal a strategy to modulate CAR T-cell activity at the protein level by employing DHFR and TMP as a chemical switch system. METHODS: First, the system was demonstrated to work in human primary T cells. To introduce the system to CAR T cells, DHFR was genetically fused to the carboxyl terminal of a third-generation CAR molecule targeting CD19 (CD19-CAR), constructing the CD19-CAR-DHFR fusion. RESULTS: The CD19-CAR-DHFR molecule level was shown to be modulated by TMP. Importantly, the incorporation of DHFR had no impact on the recognition specificity and normal function of the CAR molecule. Little adverse effect on cell proliferation and apoptosis was detected. It was proved that TMP could regulate cytokine secretion and the in vitro cytotoxicity of CD19-CAR-DHFR T cells. Furthermore, the in vivo anti-tumor efficacy was demonstrated to be controllable through the manipulation of TMP administration. The approach to control CD19-CAR also succeeded in 19-BBZ(71), another CD19-targeting CAR with a different structure. CONCLUSIONS: The proposed approach based on DHFR and TMP provides a facile strategy to bring CAR T-cell therapy under conditional user control, and the strategy may have the potential to be transplantable.

8.
J Am Chem Soc ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652134

RESUMO

Sodium reduction of [{SiNDipp}Mg] [{SiNDipp} = {CH2SiMe2N(Dipp)}2; Dipp = 2,6-i-Pr2C6H3] provides the Mg(I) species, [{SiNDipp}MgNa]2, in which the long Mg-Mg bond (>3.2 Å) is augmented by persistent Na-aryl interactions. Computational assessment indicates that this molecule is best considered to comprise a contiguous tetrametallic core, a viewpoint borne out by its reaction with CO, which results in ethynediolate formation mediated by the dissimilar metal centers.

9.
J Alzheimers Dis ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34657889

RESUMO

BACKGROUND: Evidence suggests that subjective cognitive decline (SCD) individuals with worry have a higher risk of cognitive decline. However, how SCD-related worry influences the functional brain network is still unknown. OBJECTIVE: In this study, we aimed to explore the differences in functional brain networks between SCD subjects with and without worry. METHODS: A total of 228 participants were enrolled from the Sino Longitudinal Study on Cognitive Decline (SILCODE), including 39 normal control (NC) subjects, 117 SCD subjects with worry, and 72 SCD subjects without worry. All subjects completed neuropsychological assessments, APOE genotyping, and resting-state functional magnetic resonance imaging (rs-fMRI). Graph theory was applied for functional brain network analysis based on both the whole brain and default mode network (DMN). Parameters including the clustering coefficient, shortest path length, local efficiency, and global efficiency were calculated. Two-sample T-tests and chi-square tests were used to analyze differences between two groups. In addition, a false discovery rate-corrected post hoc test was applied. RESULTS: Our analysis showed that compared to the SCD without worry group, SCD with worry group had significantly increased functional connectivity and shortest path length (p = 0.002) and a decreased clustering coefficient (p = 0.013), global efficiency (p = 0.001), and local efficiency (p <  0.001). The above results appeared in both the whole brain and DMN. CONCLUSION: There were significant differences in functional brain networks between SCD individuals with and without worry. We speculated that worry might result in alterations of the functional brain network for SCD individuals and then result in a higher risk of cognitive decline.

10.
Bioengineered ; 12(1): 7985-7994, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34666625

RESUMO

High altitude hypoxia (HAH) involves the pathogenesis of ulcerative colitis (UC) and gastrointestinal erosions. However, the mechanism of effects of HAH in colitis remains controversial. This study reports the immunomodulation mediated by HAH to enhancing the severity of UC in the mice model. BALB/c mice were used to establish the UC model by dextran sulfate sodium (DSS) compared to wild type mice. Mice groups were exposed to hypoxic conditions in a hypobaric chamber with an altitude of 5000 m for 7 days. Then, Spleen, mesenteric lymph nodes and colon tissues were collected. The activity of UC, the infiltration of the immune cells, and the released cytokines were investigated. Results showed that the severity of DSS-induced UC significantly increased in mice exposed to HAH. The analysis of pathological changes showed increased weight loss and decreased colon length accompanied by diarrhea and bloody feces in the hypobaric hypoxia group. Interestingly, the levels of inflammatory cytokines IL-17, TNF-α, and IFN-γ in the spleen and mesenteric lymph node showed a significant increase within the colon of the hypobaric hypoxia group. The population of Th 1 and Th 17 cells in the spleen was significantly increased in mice exposed to hypobaric hypoxia compared NC group. Suggesting that high altitude hypoxia enhances colitis in mice through activating the increase of inflammatory Th1 and Th17 lymphocytes. In conclusion, this study revealed that hypobaric hypoxia directly increases the severity of UC in the mice model via increasing the activity of inflammatory CD4+ Th1 and Th 17 lymphocytes.

11.
J Exp Clin Cancer Res ; 40(1): 327, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34656142

RESUMO

The efficacy of cancer immunotherapy largely depends on the tumor microenvironment, especially the tumor immune microenvironment. Emerging studies have claimed that microbes reside within tumor cells and immune cells, suggesting that these microbes can impact the state of the tumor immune microenvironment. For the first time, this review delineates the landscape of intra-tumoral microbes and their products, herein defined as the tumor microbe microenvironment. The role of the tumor microbe microenvironment in the tumor immune microenvironment is multifaceted: either as an immune activator, inhibitor, or bystander. The underlying mechanisms include: (I) the presentation of microbial antigens by cancer cells and immune cells, (II) microbial antigens mimicry shared with tumor antigens, (III) microbe-induced immunogenic cell death, (IV) microbial adjuvanticity mediated by pattern recognition receptors, (V) microbe-derived metabolites, and (VI) microbial stimulation of inhibitory checkpoints. The review further suggests the use of potential modulation strategies of the tumor microbe microenvironment to enhance the efficacy and reduce the adverse effects of checkpoint inhibitors. Lastly, the review highlights some critical questions awaiting to be answered in this field and provides possible solutions. Overall, the tumor microbe microenvironment modulates the tumor immune microenvironment, making it a potential target for improving immunotherapy. It is a novel field facing major challenges and deserves further exploration.

12.
13.
Beilstein J Org Chem ; 17: 2425-2432, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621404

RESUMO

The p-TsOH-catalyzed Diels-Alder reaction of 3-(indol-3-yl)maleimides with chalcone in toluene at 60 °C afforded two diastereoisomers of tetrahydropyrrolo[3,4-c]carbazoles, which can be dehydrogenated by DDQ oxidation in acetonitrile at room temperature to give the aromatized pyrrolo[3,4-c]carbazoles in high yields. On the other hand, the one-pot reaction of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones with chalcones or benzylideneacetone in acetonitrile in the presence of p-TsOH and DDQ resulted in polyfunctionalized carbazoles in satisfactory yields. The reaction mechanism included the DDQ oxidative dehydrogenation of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones to the corresponding 3-vinylindoles, their acid-catalyzed Diels-Alder reaction and sequential aromatization process.

14.
Adv Mater ; : e2104195, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622487

RESUMO

A "cooling-contraction" method to separate large-area (up to 4.2 cm in lateral size) graphene oxide (GO)-assembled films (of nanoscale thickness) from substrates is reported. Heat treatment at 3000 °C of such free-standing macroscale films yields highly crystalline "macroassembled graphene nanofilms" (nMAGs) with 16-48 nm thickness. These nMAGs present tensile strength of 5.5-11.3 GPa (with ≈3 µm gauge length), electrical conductivity of 1.8-2.1 MS m-1 , thermal conductivity of 2027-2820 W m-1 K-1 , and carrier relaxation time up to ≈23 ps. As a demonstration application, an nMAG-based sound-generator shows a 30 µs response and sound pressure level of 89 dB at 1 W cm-2 . A THz metasurface fabricated from nMAG has a light response of 8.2% for 0.159 W mm-2 and can detect down to 0.01 ppm of glucose. The approach provides a straightforward way to form highly crystallized graphene nanofilms from low-cost GO sheets.

15.
Transl Psychiatry ; 11(1): 499, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593760

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has caused large-scale economic and social losses and worldwide deaths. Although most COVID-19 patients have initially complained of respiratory insufficiency, the presence of neuropsychiatric manifestations is also reported frequently, ranging from headache, hyposmia/anosmia, and neuromuscular dysfunction to stroke, seizure, encephalopathy, altered mental status, and psychiatric disorders, both in the acute phase and in the long term. These neuropsychiatric complications have emerged as a potential indicator of worsened clinical outcomes and poor prognosis, thus contributing to mortality in COVID-19 patients. Their etiology remains largely unclear and probably involves multiple neuroinvasive pathways. Here, we summarize recent animal and human studies for neurotrophic properties of severe acute respiratory syndrome coronavirus (SARS-CoV-2) and elucidate potential neuropathogenic mechanisms involved in the viral invasion of the central nervous system as a cause for brain damage and neurological impairments. We then discuss the potential therapeutic strategy for intervening and preventing neuropsychiatric complications associated with SARS-CoV-2 infection. Time-series monitoring of clinical-neurochemical-radiological progress of neuropsychiatric and neuroimmune complications need implementation in individuals exposed to SARS-CoV-2. The development of a screening, intervention, and therapeutic framework to prevent and reduce neuropsychiatric sequela is urgently needed and crucial for the short- and long-term recovery of COVID-19 patients.


Assuntos
COVID-19 , Animais , Cefaleia , Humanos , Pandemias , SARS-CoV-2 , Convulsões
16.
Am J Ophthalmol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653355

RESUMO

PURPOSE: To compare outcomes of in-the-bag versus ciliary sulcus secondary intraocular lens (IOL) implantation for pediatric aphakia. DESIGN: Prospective interventional case series. METHODS: SETTING: institutional. PATIENT: Two hundred and two children (355 aphakic eyes) diagnosed as congenital cataracts and undergoing cataract extraction before 24 months of age. INTERVENTION: Pediatric aphakic eyes underwent either in-the-bag or ciliary sulcus secondary IOL implantation according to the amount of residual lens capsule and were followed for three years postoperatively. MAIN OUTCOME MEASURES: Adverse events (AEs), IOL tilt and decentration, best corrected visual acuity (BCVA) in operative eye. RESULTS: One hundred forty-four eyes (40.6%, 89 children) received in-the-bag IOL implantation (capsular group) and 211 (59.4%, 132 children) underwent ciliary sulcus IOL implantation (sulcus group). Kaplan-Meier curves showed that the time-dependent incidence of glaucoma-related adverse events (GRAEs) (P=0.005) and any AEs (P=0.002) were higher in the sulcus group. In-the-bag IOL implantation was a strong protective factor against GRAE (HR, 0.08, 95CI:0.01∼0.53; P=0.009) and any AEs (HR, 0.21 95CI: 0.08∼0.57; P=0.002). Clinically significant IOL decentration (>0.4mm) was more common in the sulcus group compared to the capsular group (vertical decentration: 29.8% vs. 15.7%, P=0.005; horizontal decentration: 30.3% vs. 9.35%, P<0.001). BCVA in the capsular group was better than that in the sulcus group (logarithm of the minimum angle of resolution [LogMAR] 0.56 vs. 0.67, P=0.014). CONCLUSIONS: Compared to ciliary sulcus secondary IOL implantation, in-the-bag IOL implantation reduced AEs, and yielded better IOL centration and BCVA for pediatric aphakia.

17.
Am J Ophthalmol ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34695398

RESUMO

PURPOSE: To identify risk factors for surgical failure after gonioscopy-assisted transluminal trabeculotomy (GATT) in juvenile open angle glaucoma (JOAG). DESIGN: Prospective, interventional case series. METHODS: Seventy eyes of 70 patients with JOAG underwent GATT as the initial surgery. Surgical success was defined as a post-operative intraocular pressure (IOP) of ≤21 mmHg with at least a 20% reduction from pre-operative IOP with or without the use of anti-glaucoma medication (qualified and complete success, respectively) at each post-operative visit. IOP spike was defined as IOP >30 mmHg and an increase of at least 10 mmHg from IOP prior to the spike, and then reduced to ≤21 mmHg. RESULTS: The median age at the time of surgery was 19.3 (range: 4.9-37.5) years with a visual field mean deviation (MD) -17.4±10.6 dB. Mean IOP decreased from 31.3±9.5 mmHg pre-operatively to 15.8±2.7 at 12 months post-operatively. The complete and qualified success rates were 74.3% and 91.4%, respectively. Fifty-two (74%) eyes had an IOP spike with a median spike duration of 3.5 days (range 1-21). Longer duration of IOP spike (P=0.009) and older age at the time of surgery (P=0.025) were both associated with worse surgical outcomes. Advanced disease was associated with prolonged IOP spike (P=0.007). CONCLUSIONS: GATT provided excellent outcomes in patients with severe JOAG. Older age and longer duration of post-operative IOP spike are risk factors for failure. Severe cases are more likely to have longer durations of IOP spike. Frequent IOP monitoring during the early post-operative period is needed to detect IOP spikes in these patients.

18.
Nanoscale ; 13(30): 13057-13064, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477789

RESUMO

We developed a water-soluble, stable and selective "turn-on" fluorescence sensing platform based on carbon quantum dots (CQDs) for rapid determination of phosphate (Pi) in aqueous solutions and for visualization of latent fingerprints on paper. The hydroxyl groups on the surface of the synthesized CQDs can be deprotonated by Pi to trigger the intramolecular charge transfer (ICT) process and the inhibition of excited-state proton transfer (ESPT), achieving a turn-on emission response. CQDs demonstrated the capability to selectively detect Pi over other common ions and biomolecules with the linear fluorescence intensity change in the range from 0 to 100 µM. Moreover, the paper sprayed with the CQD solution showed a remarkable blue emission speckle and a fingerprint upon addition of Pi solution and finger touching, respectively. Notably, the fingerprint images including level 3 details (crossover, bifurcation, termination, and island and sweat pores) are also clearly identified and distinguished, indicating their potential application in document security. We believe that the as-synthesized CQDs will provide a new tool for Pi detection in aqueous media and paper document security.


Assuntos
Pontos Quânticos , Carbono , Fluorescência , Íons , Fosfatos
19.
Aging Ment Health ; : 1-8, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34583593

RESUMO

Objective: Subjective cognitive decline (SCD) complaints as the early manifestation of mild cognitive impairment (MCI) may be harbingers of objective cognitive decline. SCD-questinnaire9 (SCD-Q9) is developed to investigate the early sign for MCI. However, few studies have reported its power for discriminating MCI from healthy controls (HCs). Therefore, this study aims to investigate the discrimination power of SCD-Q9 as a brief screening tool for early detection of SCD in MCI.Methods: 84 HCs and 205 people with MCI were recruited. Their demographic information and scores of SCD-Q9 were compared. A binary logistic regression model was used to analyze the potential affecting factors of MCI, and the Receiver Operating Characteristic analysis was applied to test the discrimination powers of those factors, including SCD-Q9.Results: (1) Single and total scores of SCD-Q9 were all lower in the MCI group than those in the HC group. (2) Ageing, lower education and higher total scores of SCD-Q9 were associated with MCI. (3) Area Under the Curves (AUC) of SCD-Q9 for discriminating MCI from HC group was 0.815 and when integrating age and education, the AUC improved slightly and reached 0.839. Additionally, the sensitivity and specificity were 68.8% and 85.7%, respectively when a cut-off value of 3 was applied.Conclusions: SCD-Q9 may be able to detect the subjective cognitive decline in MCI early, but it may be used together with other screening questionnaires to improve its sensitivity and further verification of its power is needed.

20.
Front Aging Neurosci ; 13: 686598, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483878

RESUMO

Alzheimer's disease (AD) has a long preclinical stage that can last for decades prior to progressing toward amnestic mild cognitive impairment (aMCI) and/or dementia. Subjective cognitive decline (SCD) is characterized by self-experienced memory decline without any evidence of objective cognitive decline and is regarded as the later stage of preclinical AD. It has been reported that the changes in structural covariance patterns are affected by AD pathology in the patients with AD and aMCI within the specific large-scale brain networks. However, the changes in structural covariance patterns including normal control (NC), SCD, aMCI, and AD are still poorly understood. In this study, we recruited 42 NCs, 35 individuals with SCD, 43 patients with aMCI, and 41 patients with AD. Gray matter (GM) volumes were extracted from 10 readily identifiable regions of interest involved in high-order cognitive function and AD-related dysfunctional structures. The volume values were used to predict the regional densities in the whole brain by using voxel-based statistical and multiple linear regression models. Decreased structural covariance and weakened connectivity strength were observed in individuals with SCD compared with NCs. Structural covariance networks (SCNs) seeding from the default mode network (DMN), salience network, subfields of the hippocampus, and cholinergic basal forebrain showed increased structural covariance at the early stage of AD (referring to aMCI) and decreased structural covariance at the dementia stage (referring to AD). Moreover, the SCN seeding from the executive control network (ECN) showed a linearly increased extent of the structural covariance during the early and dementia stages. The results suggest that changes in structural covariance patterns as the order of NC-SCD-aMCI-AD are divergent and dynamic, and support the structural disconnection hypothesis in individuals with SCD.

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