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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120282, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454131

RESUMO

The conversion of p-aminothiophenol (PATP) or p-nitrothiophenol (PNTP) to p,p'-dimercaptoazobenzene (DMAB) has been used as model reactions to study plasmon-catalyzed reaction on nanoparticles. Herein, we report the conversion of PNTP to DMAB which is triggered by SO32- ions on gold nanoparticles (AuNPs) for the first time. With the addition of SO32-, the Raman peaks at 1139, 1392, 1437 cm-1 appears, which indicates the formation of DMAB. The experiment results suggested that the synergistic effect of AuNPs and SO32- promoted the conversion of PNTP to DMAB. Besides, the proposed catalysis system is high selectivity to SO32- ions, which provides a new detection route to SO32- ions in the future. More importantly, the possible reaction mechanism has been put forward which is helpful to understand the surface plasmon-assisted catalytic reduction of PNTP on the surface of SERS substrate.


Assuntos
Ouro , Nanopartículas Metálicas , Catálise , Análise Espectral Raman , Compostos de Sulfidrila , Sulfitos
2.
Biomed Chromatogr ; : e5273, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725843

RESUMO

A simple and fast liquid chromatography-tandem mass spectrometry method was established and validated for the simultaneous determination of tenofovir alafenamide (TAF) and tenofovir (TNF) in human plasma. A simple protein precipitation procedure was employed to extract analytes from plasma. Chromatographic separation was performed on an Eclipse Plus C18 column utilizing a fast gradient elution starting with 2% of 2 mM ammonium acetate-formic acid (100/0.1, v/v) followed by increasing the percentages of acetonitrile. Detection was performed on a tandem mass spectrometer equipped with an electrospray ionization source operated in the positive ionization mode, using the transitions of m/z 477.2 → m/z 346.1 for TAF, and m/z 288.1 → m/z 176.1 for TNF. TAF-d5 and TNF-d7 were used as the internal standard of TAF and TNF, respectively. The method was validated in concentration ranges of 1.25-500 ng/mL for TAF and 0.300-15.0 ng/mL for TNF with acceptable accuracy and precision.

3.
Zhonghua Liu Xing Bing Xue Za Zhi ; 42(3): 538-543, 2021 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-34814426

RESUMO

Objective: To explore the status of HIV infection, time trends and related factors of MSM in Harbin from 2009 to 2018 and provide evidences for comprehensive prevention and control strategies of MSM HIV/AIDS. Methods: From April to July during 2009-2018, continuous cross-sectional studies were conducted on MSM recruited through snowball sampling. The unified questionnaire was used to collect demographic, behavioral, and serological information. The SPSS 23.0 software was used for statistical analysis, and the Joinpoint 4.8.0.1 software was applied to the annual percent change (APC) for time trends analysis using the Joinpoint regression model. Results: A total of 4 813 MSM were surveyed in Harbin from 2009 to 2018. The overall HIV antibody positive rate was 11.3 % ( 543/4 813). Joinpoint regression analysis showed that there was an increase in the HIV antibody positive rate from 2009 to 2015, while the segmentation point was in 2015 (Z=4.2, P<0.05) but, there was a decrease from 2015 to 2018(Z=-1.3, P=0.3). The positive rate of syphilis antibody was 12.9% (621/4 813). There was a decrease in the positive rate of syphilis antibodies from 2009 to 2013 (Z=-2.8,P<0.05). There was a decrease in the positive rate of syphilis antibodies from 2013 to 2018 (Z=-0.7,P=0.5). Results from multiple logistic aggression analysis showed that the risk factors associated with the prevalence of HIV infection including network recruitment (aOR=1.307, 95%CI: 1.057-1.617), age 30 and above (aOR=1.905, 95%CI: 1.235-2.939) and syphilis antibody positive (aOR=4.728, 95%CI: 3.751-5.961). Protective factors appeared: knowledge of HIV/AIDS (aOR=0.598, 95%CI: 0.433-0.825) and consistent use of condom during anal sex in the past six months (aOR=0.683, 95%CI: 0.550-0.850). Conclusions: The HIV antibody positive rate peaked in 2015 among MSM in Harbin from 2009 to 2018, first increased and then decreased. The positive rate of syphilis antibody showed a decreasing trend. Intervention models based on social media software, age 30 and above and syphilis antibody-positive need to be explored. It also promotes condom use and referral for syphilis among MSM.

5.
Exp Ther Med ; 22(6): 1435, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34707716

RESUMO

Flavonoids which are extracted from citrus peel and pulp have been reported to have multiple beneficial effects on human health. Isosinensetin (ISO) is a type of flavonoid compound, which has several protective effects including anticancer, antioxidant, antiviral, anti-inflammatory and bacteriostatic. However, the molecular mechanism of its antioxidant and anti-inflammatory effects remain unclear. The present study aimed to investigate the intervention effect and possible mechanism of ISO on human bronchial epithelial cells injured by fine particular matter ≤2.5 µm in diameter (PM2.5). In the present study, the cell viability was detected by Cell Counting Kit-8 method. The levels of pro-inflammatory cytokines were analyzed by ELISA. The level of reactive oxygen species (ROS) was detected by fluorescence probe. The expression levels of proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor ÐºΒ (NF-кB) proteins were detected by western blotting. The results revealed that ISO evidently increased the viability of 16-HBE cells and sharply decreased the levels of pro-inflammatory factors in cell culture supernatant. ISO significantly inhibited ROS release caused by PM2.5. Moreover, the expression levels of PCNA, Nrf2 and NF-кB proteins were downregulated after ISO incubation. These results indicated that ISO alleviated 16-HBE-cell injury by PM2.5 through the ROS-Nrf2/NF-кB signaling pathway.

6.
Huan Jing Ke Xue ; 42(11): 5460-5471, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708985

RESUMO

Although the adsorption capacity of titanium xerogel(TAX) for arsenite(As(Ⅲ)) is high(254 mg·g-1), the adsorption rate is slow. Therefore, TAX was loaded onto activated carbon, sponge, and resin to fabricate a supported adsorbent, and the arsenite removal performance was evaluated. Except sponge, activated carbon and resin could successfully load TAX. The results showed that resin and activated carbon loaded TAX improved the As(Ⅲ) removal performance, and more significantly by the resin-based materials. Through wet digestion and adsorption kinetics experiments, the amount of titanium loaded was approximately 1.4% and 5% in the activated carbon-based(TAX@AC) and resin-based(TAX@resin) materials, respectively. For the initial concentration of 1.0 mg·L-1 As(Ⅲ) solution, the adsorption rate constant of TAX@D201 was 0.85 mg·(g·min) -1, which was 21 times higher than that of unloaded TAX[0.04 mg·(g·min) -1]. Columns packed with TAX@resin could effectively lower arsenite concentration for up to 560 bed volumes, which is 2.8 times greater than that of the iron-based composites with the same metal mass. Therefore, loading TAX on macroporous resin is an effective strategy and provides an effective approach for the application of TAX in arsenite-containing groundwater.


Assuntos
Arsenitos , Poluentes Químicos da Água , Purificação da Água , Adsorção , Cinética , Titânio , Poluentes Químicos da Água/análise
7.
Mol Ecol Resour ; 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34689424

RESUMO

Fagaceae species are increasingly used as models to elucidate the process and mechanism of adaptation and speciation by integrating ecology, evolution and genomics. The genus Castanopsis belongs to the family Fagaceae and is mainly distributed across subtropical and tropical Asia. In the present study, we reported the first chromosome-scale genome assembly of Castanopsis tibetana, a common species of evergreen broadleaved forests in subtropical China. The combination of Nanopore sequencing and Hi-C technologies enabled a high-quality genome assembly. The final assembled genome size of C. tibetana was 878.6 Mb (97.6% of the estimated genome size), consisting of 477 contigs with an N50 length of 3.3 Mb. The benchmarking universal single-copy orthologue (BUSCO) assessment indicated a completeness of 93.0%. Hi-C scaffolding generated 12 pseudochromosomes, representing 98.7% of the assembled genome. Subsequently, 40,937 protein-coding genes were predicted and 90.04% of them were functionally annotated. More than 476.9 Mb of repetitive sequences (54.3% of the genome) were identified, and the percentage of the genome covered by TE elements was 39.98%. Comparative genomics analysis revealed that C. tibetana was most closely related to Castanea mollissima and diverged at 18.48 Ma, and that C. tibetana has undergone considerable gene family expansion and contraction. Evidence of positive selection was detected in 53 genes, which showed different arrangement pattern compared to Quercus robur. The chromosome-scale genome assembly of C. tibetana will expand Fagaceae genome resources across the family and provide a powerful comparative framework to study the adaptation and evolution of Fagaceae trees.

8.
Sci Rep ; 11(1): 19903, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615975

RESUMO

Blood leakage from the vessels in the eye is the hallmark of many vascular eye diseases. One of the preclinical mouse models of retinal blood leakage, the very-low-density-lipoprotein receptor deficient mouse (Vldlr-/-), is used for drug screening and mechanistic studies. Vessel leakage is usually examined using Fundus fluorescein angiography (FFA). However, interpreting FFA images of the Vldlr-/- model is challenging as no automated and objective techniques exist for this model. A pipeline has been developed for quantifying leakage intensity and area including three tasks: (i) blood leakage identification, (ii) blood vessel segmentation, and (iii) image registration. Morphological operations followed by log-Gabor quadrature filters were used to identify leakage regions. In addition, a novel optic disk detection algorithm based on graph analysis was developed for registering the images at different timepoints. Blood leakage intensity and area measured by the methodology were compared to ground truth quantifications produced by two annotators. The relative difference between the quantifications from the method and those obtained from ground truth images was around 10% ± 6% for leakage intensity and 17% ± 8% for leakage region. The Pearson correlation coefficient between the method results and the ground truth was around 0.98 for leakage intensity and 0.94 for leakage region. Therefore, we presented a computational method for quantifying retinal vascular leakage and vessels using FFA in a preclinical angiogenesis model, the Vldlr-/- model.

9.
EBioMedicine ; 73: 103632, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34688035

RESUMO

BACKGROUND: Pathological neovascularization in neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. Increasing evidence shows that cells of myeloid lineage play important roles in controlling pathological endothelium formation. Suppressor of cytokine signaling 3 (SOCS3) pathway has been linked to neovascularization. METHODS: We utilised a laser-induced choroidal neovascularization (CNV) mouse model to investigate the neovascular aspect of human AMD. In several cell lineage reporter mice, bone marrow chimeric mice and Socs3 loss-of-function (knockout) and gain-of-function (overexpression) mice, immunohistochemistry, confocal, and choroidal explant co-culture with bone marrow-derived macrophage medium were used to study the mechanisms underlying pathological CNV formation via myeloid SOCS3. FINDINGS: SOCS3 was significantly induced in myeloid lineage cells, which were recruited into the CNV lesion area. Myeloid Socs3 overexpression inhibited laser-induced CNV, reduced myeloid lineage-derived macrophage/microglia recruitment onsite, and attenuated pro-inflammatory factor expression. Moreover, SOCS3 in myeloid regulated vascular sprouting ex vivo in choroid explants and SOCS3 agonist reduced in vivo CNV. INTERPRETATION: These findings suggest that myeloid lineage cells contributed to pathological CNV formation regulated by SOCS3. FUNDING: This project was funded by NIH/NEI (R01EY030140, R01EY029238), BrightFocus Foundation, American Health Assistance Foundation (AHAF), and Boston Children's Hospital Ophthalmology Foundation for YS and the National Institutes of Health/National Heart, Lung and Blood Institute (U01HL098166) for PZ.

10.
Neurobiol Stress ; 15: 100396, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34568523

RESUMO

Adenosine deaminase acting on RNA1 (ADAR1) is a newly discovered epigenetic molecule marker that is sensitive to environmental stressors. A recent study has demonstrated that ADAR1 affects BDNF expression via miR-432 and is involved in antidepressant action. However, the detailed molecular mechanism is still unclear. We have uncovered a new molecular mechanism showing the involvement of miR-432 and circ_0000418 in mediating the antidepressant action of ADAR1. We demonstrate that the ADAR1 inducer (IFN-γ) alleviates the depressive-like behaviors of BALB/c mice treated with chronic unpredictable stress (CUS) exposure. Moreover, both in vivo and in vitro studies show that ADAR1 differently impacts miR-432 and circ_0000418 expressions. Furthermore, the in vitro results demonstrate that circ_0000418 oppositely affects BDNF expression. Together, our results indicate that ADAR1 affects CUS-induced depressive-like behavior and BDNF expression by acting on miR-432 and circ_0000418. Elucidation of this new molecular mechanism will not only provide insights into further understanding the important role of ADAR1 in stress-induced depressive-like behavior but also suggest a potential therapeutic strategy for developing novel anti-depressive drugs.

11.
Brain Res ; 1772: 147663, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555415

RESUMO

Neuropathic pain is a common complication of diabetes mellitus with poorly relieved by conventional analgesics. Metformin, a first-line drug for type 2 diabetes, reduces blood glucose by activating adenosine monophosphate protein kinase (AMPK) signalling system. However, the effect of Metformin on diabetic neuropathic pain is still unknown. In the present study, we showed that Metformin was capable of attenuating diabetes induced mechanical allodynia, and the analgesia effect could be blocked by Compound C (an AMPK inhibitor). Importantly, Metformin enhanced the phosphorylation level of AMPK in L4-6 DRGs of diabetic rats but not affect the expression of total AMPK. Intrathecal injection of AICAR (an AMPK agonist) could activate AMPK and alleviate the mechanical allodynia of diabetic rats. Additionally, phosphorylated AMPK and NF-κB was co-localized in small and medium neurons of L4-6 DRGs. Interestingly, the regulation of NF-κB in diabetic rats was obviously reduced when AMPK was activated by AICAR. Notably, Metformin could decrease NF-κB expression in L4-6 DRGs of diabetic rats, but the decrease was blocked by Compound C. In conclusion, Metformin alleviates diabetic mechanical allodynia via activation of AMPK signaling pathway in L4-6 DRGs of diabetic rats, which might be mediated by the downregulation of NF-κB, and this providing certain basis for Metformin to become a potential drug in the clinical treatment of diabetic neuropathic pain.

12.
Medicine (Baltimore) ; 100(35): e26777, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477117

RESUMO

ABSTRACT: Aim of the study was to determine the characteristics and prognosis, and to identify the risk factors for mortality in patients with primary Sjögren syndrome (pSS) with interstitial lung disease (pSS-ILD).A total of 1422 patients with SS were screened and 178 patients with pSS-ILD were recruited. The medical records and outcomes were retrospectively reviewed. Overall survival and case control study were performed to explore the predictors of death.Among 178 pSS-ILD patients, 87.1% were women. Mean age was 61.59 ±â€Š11.69-year-old. Median disease duration was 72.0 (24.0, 156.0) months. Nonspecific interstitial pneumonia was the predominant high-resolution computed tomography pattern (44.9%). Impairment in diffusion capacity was the most common abnormality of pulmonary function test (75.8%) and the most severe consequence. Type 1 respiratory failure and hypoxia were observed in 15.0% and 30.0% patients, respectively. Mean survival time after confirmation of pSS-ILD diagnosis was 9.0 (6.8, 13.0) years. The 10-year survival rate for all patients with pSS-ILD was 81.7%. Forty-four (24.7%) of 178 patients died during the follow-up period. The most predominant cause of death was respiratory failure (n = 27). Twenty-seven patients died of ILD and formed study group. The 78 patients who survived formed control group. Age and smoking were risk factors for mortality in patients with pSS-ILD. In addition, severity of ILD, as reflected by high-resolution computed tomography, pulmonary function test, and arterial blood gas, was an independent risk factor. However, inflammation status (erythrocyte sedimentation rate, C-reactive protein) and anti-Sjögren syndrome-related antigen A and anti-Sjögren syndrome-related antigen B were not.ILD is a severe complication of pSS. Age, smoking, and severity of lung involvement are more critical for prognosis rather than inflammation status and autoantibodies.


Assuntos
Doenças Pulmonares Intersticiais/classificação , Síndrome de Sjogren/mortalidade , Idoso , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Doenças Pulmonares Intersticiais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Sjogren/classificação , Síndrome de Sjogren/epidemiologia , Estatísticas não Paramétricas
13.
Regen Biomater ; 8(6): rbab016, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34484805

RESUMO

Magnesium (Mg) is an important element for its enhanced osteogenic and angiogenic properties in vitro and in vivo, however, the inherent alkalinity is the adverse factor that needs further attention. In order to study the role of alkalinity in regulating osteogenesis and angiogenesis in vitro, magnesium-silicocarnotite [Mg-Ca5(PO4)2SiO4, Mg-CPS] was designed and fabricated. In this study, Mg-CPS showed better osteogenic and angiogenic properties than CPS within 10 wt.% magnesium oxide (MgO), since the adversity of alkaline condition was covered by the benefits of improved Mg ion concentrations through activating Smad2/3-Runx2 signaling pathway in MC3T3-E1 cells and PI3K-AKT signaling pathway in human umbilical vein endothelial cells in vitro. Besides, provided that MgO was incorporated with 15 wt.% in CPS, the bioactivities had declined due to the environment consisting of higher-concentrated Mg ions, stronger alkalinity and lower Ca/P/Si ions caused. According to the results, it indicated that bioactivities of Mg-CPS in vitro were regulated by the double-edged effects, which were the consequence of Mg ions and alkaline environment combined. Therefore, if MgO is properly incorporated in CPS, the improved bioactivities could cover alkaline adversity, making Mg-CPS bioceramics promising in orthopedic clinical application for its enhancement of osteogenesis and angiogenesis in vitro.

14.
Sci Rep ; 11(1): 18587, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545132

RESUMO

Immune checkpoint blockade, an immunotherapy, has been applied in multiple systemic malignancies and has improved overall survival to a relatively great extent; whether it can be applied in breast cancer remains unknown. We endeavored to explore possible factors that may influence immunotherapy outcomes in breast cancer using several public databases. The possible treatment target TNF superfamily member 4 (TNFSF4) was selected from many candidates based on its abnormal expression profile, survival-associated status, and ability to predict immune system reactions. For the first time, we identified the oncogenic features of TNFSF4 in breast carcinoma. TNFSF4 was revealed to be closely related to treatment that induced antitumor immunity and to interact with multiple immune effector molecules and T cell signatures, which was independent of endocrine status and has not been reported previously. Moreover, the potential immunotherapeutic approach of TNFSF4 blockade showed underlying effects on stem cell expansion, which more strongly and specifically demonstrated the potential effects of applying TNFSF4 blockade-based immunotherapies in breast carcinomas. We identified potential targets that may contribute to breast cancer therapies through clinical analysis and real-world review and provided one potential but crucial tool for treating breast carcinoma that showed effects across subtypes and long-term effectiveness.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Imunoterapia/métodos , Ligante OX40/metabolismo , Neoplasias da Mama/metabolismo , Bases de Dados Factuais , Humanos
15.
Angew Chem Int Ed Engl ; 60(43): 23123-23127, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34448330

RESUMO

Transition-metal carbides have sparked unprecedented enthusiasm as high-performance catalysts in recent years. Still, the catalytic properties of copper carbide remain unexplored. By introducing subsurface carbon to Cu(111), a displacement reaction of a proton in a carboxyl acid group with a single Cu atom is demonstrated at the atomic scale and room temperature. Its occurrence is attributed to the C-doping-induced local charge of surface Cu atoms (up to +0.30 e/atom), which accelerates the rate of on-surface deprotonation via reduction of the corresponding energy barrier, thus enabling the instant displacement of a proton with a Cu atom when the molecules adsorb on the surface. This well-defined and robust Cuδ+ surface based on subsurface-carbon doping offers a novel catalytic platform for on-surface synthesis.

16.
Breast Cancer Res Treat ; 189(3): 725-736, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34392453

RESUMO

PURPOSE: To evaluate GT0918, a 2nd-generation AR antagonist, for its AR down-regulation activity among breast cancer patients. METHODS: The effect of GT0918 on AR protein expression was evaluated in AR expression breast cancer cells and in breast cancer xenograft model. A 3 + 3 phase I dose-escalation study was launched in Peking University Cancer Hospital. The endpoints included dose finding, safety, pharmacokinetics, and antitumor activity. RESULTS: GT0918 was demonstrated to effectively suppress the expression of AR protein and the growth of AR-positive breast cancer tumors in mouse xenograft tumor models. All patients treated with GT0918 were at a QD dose-escalation of five dose levels from 100 to 500 mg. The most common treatment-related AEs of any grade were asthenia, anemia, decreased appetite, increased blood cholesterol, increased blood triglycerides, decreased white blood cell count, and increased low-density lipoprotein. Grade 3 AEs were fatigue (2 of 18, 11.1%), aspartate aminotransferase increase (1 of 18, 5.6%), alanine aminotransferase increase (1 of 18, 5.6%), and neutrophil count decrease (1 of 18, 5.6%). Clinical benefit rate (CBR) in 16 weeks was 23.1% (3/13). Among 7 AR-positive patients, 6 can evaluate efficacy, and 2 completed 23.5- and 25-cycle treatment, respectively (as of 2020/1/20). PK parameters showed a fast absorption profile of GT0918 in the single-dose study. GT0918 and its major metabolite reached steady-state serum concentration levels at day 21 after multiple dosing. CONCLUSION: GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.


Assuntos
Antagonistas de Receptores de Andrógenos , Neoplasias da Mama , Animais , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Camundongos , Oxazóis , Receptores Androgênicos , Tioidantoínas
17.
J Psychosoc Oncol ; : 1-8, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34463191

RESUMO

PURPOSE: To determine how social media platform and cancer content is associated with the presence of social support in responses to young adult cancer caregivers' (YACC) posts. DESIGN: We retrospectively collected YACC's Facebook and/or Instagram posts and all responses from the first six months of caregiving. SAMPLE: Eligible YACC were 18-39, caring for a cancer patient diagnosed 6 months-5 years prior, spoke English, and used social media weekly. METHODS: Social media posts and responses were manually coded for five social support types, then transformed to depict the proportion of responses per post representing each type of support. Using mixed-effects models, we compared the distributions of responses with social support types by platform (Facebook vs. Instagram) and cancer content (no vs. yes). FINDINGS: More responses contained emotional support on Instagram than Facebook (B = 0.25, Standard Error (SE)=0.09, p = 0.007). More responses with cancer content contained -validation support (B = 0.20, SE = 0.07, p = 0.002), but fewer contained emotional (B=-0.17, SE = 0.07, p = 0.02) and instrumental support (B=-0.06, SE = 0.02, p = 0.001) than posts without cancer content. CONCLUSIONS: Studying the responsiveness of social media followers by platform and cancer content provides a foundation for intervention development. IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS: Emphasizing the suitability of different social media platforms for particular support seeking behaviors is essential.

18.
PLoS Biol ; 19(8): e3001304, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34437534

RESUMO

Tumor necrosis factor receptor-1 (TNFR1) signaling, apart from its pleiotropic functions in inflammation, plays a role in embryogenesis as deficiency of varieties of its downstream molecules leads to embryonic lethality in mice. Caspase-8 noncleavable receptor interacting serine/threonine kinase 1 (RIPK1) mutations occur naturally in humans, and the corresponding D325A mutation in murine RIPK1 leads to death at early midgestation. It is known that both the demise of Ripk1D325A/D325A embryos and the death of Casp8-/- mice are initiated by TNFR1, but they are mediated by apoptosis and necroptosis, respectively. Here, we show that the defects in Ripk1D325A/D325A embryos occur at embryonic day 10.5 (E10.5), earlier than that caused by Casp8 knockout. By analyzing a series of genetically mutated mice, we elucidated a mechanism that leads to the lethality of Ripk1D325A/D325A embryos and compared it with that underlies Casp8 deletion-mediated lethality. We revealed that the apoptosis in Ripk1D325A/D325A embryos requires a scaffold function of RIPK3 and enzymatically active caspase-8. Unexpectedly, caspase-1 and caspase-11 are downstream of activated caspase-8, and concurrent depletion of Casp1 and Casp11 postpones the E10.5 lethality to embryonic day 13.5 (E13.5). Moreover, caspase-3 is an executioner of apoptosis at E10.5 in Ripk1D325A/D325A mice as its deletion extends life of Ripk1D325A/D325A mice to embryonic day 11.5 (E11.5). Hence, an unexpected death pathway of TNFR1 controls RIPK1 D325A mutation-induced lethality at E10.5.


Assuntos
Caspase 8/fisiologia , Desenvolvimento Embrionário , Proteína Serina-Treonina Quinases de Interação com Receptores/fisiologia , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Animais , Caspases/metabolismo , Morte Celular , Camundongos , Cultura Primária de Células , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
19.
ACS Appl Mater Interfaces ; 13(34): 40451-40459, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34416812

RESUMO

Thanks to the low cost, free dendritic hazards, and high volumetric capacity, magnesium (Mg)-ion batteries have attracted increasing attention as alternative energy storage devices to lithium-ion batteries. Despite the successful development of electrode materials, the real-life application potential of Mg-ion full battery systems (MIFBSs) is largely hindered by the lack of suitable electrode couples and hence low diffusion kinetics, which induce low specific capacity, poor rate performance, and low working voltage. Herein, we report an aqueous rechargeable MIFBS by employing copper hexacyanoferrate (CuHCF) as the cathode and 3,4,9,10-perylene-tetracarboxylic acid diimide (PTCDI) as the anode in 1 moL L-1 MgCl2 electrolyte. The combination of PTCDI//CuHCF allows efficient redox and convenient intercalation/deintercalation of Mg2+ at the electrodes while facilitating a fast transfer of Mg2+ between the two electrodes. As a result, the system delivers a high capacity of ∼120.3 mAh g-1 at a current density of 0.5 A g-1 after 200 operation cycles with a broadened voltage range (0-1.95 V) and maintains a capacity of ∼97.8 mAh g-1 at 2.0 A g-1 after 1000 cycles. Even at a high current density of 5.0 A g-1, the battery provides a steady capacity of ∼81.4 mAh g-1 over 5000 cycles. Moreover, after being applied at 11.0 A g-1, the system can deliver a capacity of ∼126.5 mAh g-1 at 0.5 A g-1. This work emphasizes the great promise of developing suitable electrode couples for aqueous MIFBSs to achieve high capacity and high rate.

20.
J Neurosci ; 41(33): 7003-7014, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34266899

RESUMO

The structural plasticity of dendritic spines is considered to be an important basis of synaptic plasticity, learning, and memory. Here, we induced input-specific structural LTP (sLTP) in single dendritic spines in organotypic hippocampal slices from mice of either sex and performed ultrastructural analyses of the spines using efficient correlative light and electron microscopy. We observed reorganization of the PSD nanostructure, such as perforation and segmentation, at 2-3, 20, and 120 min after sLTP induction. In addition, PSD and nonsynaptic axon-spine interface (nsASI) membrane expanded unevenly during sLTP. Specifically, the PSD area showed a transient increase at 2-3 min after sLTP induction. The PSD growth was to a degree less than spine volume growth at 2-3 min and 20 min after sLTP induction but became similar at 120 min. On the other hand, the nsASI area showed a profound and lasting expansion, to a degree similar to spine volume growth throughout the process. These rapid ultrastructural changes in PSD and surrounding membrane may contribute to rapid electrophysiological plasticity during sLTP.SIGNIFICANCE STATEMENT To understand the ultrastructural changes during synaptic plasticity, it is desired to efficiently image single dendritic spines that underwent structural plasticity in electron microscopy. We induced structural long-term potentiation (sLTP) in single dendritic spines by two-photon glutamate uncaging. We then identified the same spines at different phases of sLTP and performed ultrastructural analysis by using an efficient correlative light and electron microscopy method. We found that postsynaptic density undergoes dramatic modification in its structural complexity immediately after sLTP induction. Meanwhile, the nonsynaptic axon-spine interface area shows a rapid and sustained increase throughout sLTP. Our results indicate that the uneven modification of synaptic and nonsynaptic postsynaptic membrane might contribute to rapid electrophysiological plasticity during sLTP.

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