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1.
Org Lett ; 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949871

RESUMO

An unprecedented approach for assembling a broad range of 1,2-diarylethane derivatives with fluorine-containing fully substituted carbon centers was developed. The protocol features straightforward operation, proceeds under metal-free condition, and accommodates a large variety of synthetically useful functionalities. The critical aspect to the success of this novel transformation lies in using aryldiazonium salts as both aryl radical progenitor and also as single electron acceptor which elegantly enables a radical-polar crossover manifold.

2.
J Biol Chem ; : 100655, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33901491

RESUMO

Highly conserved amino acids are generally anticipated to have similar functions across a protein superfamily, including that of the P2X ion channels, which are gated by extracellular ATP. However, whether and how these functions are conserved becomes less clear when neighboring amino acids are not conserved. Here, we investigate one such case, focused on the highly conserved residue from P2X4, E118 (rat P2X4 numbering, rP2X4), a P2X subtype associated with human neuropathic pain. When we compared the crystal structures of P2X4 with those of other P2X subtypes, including P2X3, P2X7 and AmP2X, we observed a slightly altered side-chain orientation of E118. We used protein chimeras, double mutant cycle analysis and molecular modeling to reveal that E118 forms specific contacts with amino acids in the "beak" region, which facilitates ATP binding to rP2X4. These contacts are not present in other subtypes due to sequence variance in the beak region, resulting in decoupling of this conserved residue from ATP recognition and/or channel gating of P2X receptors. Our study provides an example of a conserved residue with a specific role in functional proteins enabled by adjacent non-conserved residues. The unique role established by the E118-beak region contact provides a blueprint for the development of subtype-specific inhibitors of P2X4.

3.
Adv Mater ; : e2008709, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33860581

RESUMO

Ferroelectrics have been demonstrated as excellent building blocks for high-performance nonvolatile memories, including memristors, which play critical roles in the hardware implementation of artificial synapses and in-memory computing. Here, it is reported that the emerging van der Waals ferroelectric α-In2 Se3 can be used to successfully implement heterosynaptic plasticity (a fundamental but rarely emulated synaptic form) and achieve a resistance-switching ratio of heterosynaptic memristors above 103 , which is two orders of magnitude larger than that in other similar devices. The polarization change of ferroelectric α-In2 Se3 channel is responsible for the resistance switching at various paired terminals. The third terminal of α-In2 Se3 memristors exhibits nonvolatile control over channel current at a picoampere level, endowing the devices with picojoule read-energy consumption to emulate the associative heterosynaptic learning. The simulation proves that both supervised and unsupervised learning manners can be implemented in α-In2 Se3 neutral networks with high image recognition accuracy. Moreover, these heterosynaptic devices can naturally realize Boolean logic without an additional circuit component. The results suggest that van der Waals ferroelectrics hold great potential for applications in complex, energy-efficient, brain-inspired computing systems and logic-in-memory computers.

4.
Chemosphere ; 278: 130341, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33823353

RESUMO

Attractive membranes are critical for improving efficiencies of forward osmosis (FO) desalination process. In this study, a novel FO-PES-MoS2 thin film composite (TFC) membrane was assembled using the phase transfer method through merging MoS2 nanosheets into substrate casting solution. A sequence of characterization techniques was applied to test microstructures and physicochemical properties of the membranes and modification mechanisms based on MoS2 concentrations. Desalination efficiencies of the fabricated membranes were assessed by three NaCl draw solutions. Compared to the blank membrane, the MoS2-contained membranes had a thinner active layer, more upright and open pore structure, higher porosity, and lower surface roughness. 1 wt% MoS2 content was the optimal modification condition, and water flux increased by 35.01% under this condition. Simultaneously, reverse salt flux of the FO-PES-1-MoS2 membrane declined by 29.15% under 1 M NaCl draw solution, indicating increased salt ion rejection performance of the modified membranes. Moreover, Js/Jv ratio indicated that MoS2 nanosheets helped stabilize the desalination performance of the membranes. This study demonstrated that the novel FO-PES-MoS2 TFC membranes possessed improved performances and showed promising properties for saline water desalination.

5.
Vet Microbiol ; 257: 109080, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33915344

RESUMO

Pseudorabies virus (PRV) is related to alphaherpesvirus and varicellovirus. pUL16 is a conserved protein in all herpesviruses, and studies have shown that UL16 can interact with the viral proteins pUL11, pUL49, pUL21, gD, and gE. In this study, we found that pUL16 interacted with the viral capsid protein VP26, which could not translocate into the nucleus itself but did appear in the nucleus. We further determined whether pUL16 assists the translocation of VP26 into the nucleus. We found that pUL16 interacted with VP26 with or without viral proteins, and since VP26 itself did not contain a nuclear location signal, we concluded that pUL16 assisted the translocation of VP26 into the nucleus. Deletion of UL16 and UL35 significantly reduced the 50 % tissue culture infective dose, virulence, attachment, and internalization of PRV in cells. These results show that the interaction between pUL16 and VP26 influences the growth and virulence of pseudorabies virus. Our research is the first study to show that pUL16 interacts with VP26, which may explain the targeting site of UL16 and viral capsids. It is also the first to show that UL16 assists the transport of other viral proteins to organelles. Previous researches on pUL16 usually emphasized its interaction with pUL11, pUL21, and gE, and sometimes commented on pUL49 and gD. Our research focuses on the novel interaction between pUL16 and VP26, thereby enriching the studies on herpesviruses and possibly providing different directions for researchers.

6.
Huan Jing Ke Xue ; 42(5): 2502-2511, 2021 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-33884821

RESUMO

The use of heavy metal passivators to prevent vegetables from absorbing heavy metals is an important measure to control heavy metal-polluted vegetable fields and to ensure the safe production of vegetables. A pot experiment of planting three times in succession was conducted to study the effects of Bacillus megaterium N3 (N3), rice husk biochar (BC), sheep manure organic fertilizer (SM), strain N3 combined with biochar (BC+N3), and strain N3 combined with sheep manure (SM+N3) on Cd uptake and the functional stability of lettuce using a heavy metal passivator only at the first planting. The comprehensive applicability of the passivation materials was evaluated by the dynamic weighted comprehensive function. The results showed that when lettuce was planted for the first time, compared with the control, all the heavy metal passivators could significantly reduce (61.2%-81%) the Cd content in the edible part of the lettuce. However, in the third cultivation of lettuce, only SM+N3 could significantly reduce the Cd uptake by lettuce, which indicated that SM+N3 had the best functional stability. The dynamic weighted comprehensive function was used to evaluate the Cd content in the edible part of fresh lettuce, available Cd content in the soil, yield, and remediation cost. The results showed that the comprehensive applicability of SM+N3 was the best, followed by that of SM, BC+N3, and BC, and the comprehensive evaluation effect of strain N3 was the worst. The results of this study provide a theoretical basis and technical support for remediation of heavy metal-contaminated vegetable fields.


Assuntos
Metais Pesados , Poluentes do Solo , Animais , Cádmio/análise , Carvão Vegetal , Alface , Metais Pesados/análise , Ovinos , Solo , Poluentes do Solo/análise
7.
Neurochem Res ; 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881662

RESUMO

Steroid receptor coactivator 1 (SRC-1) is one of the coactivators recruited by the nuclear receptors (NRs) when NRs are activated by steroid hormones, such as glucocorticoid. SRC-1 is abundant in hippocampus and hypothalamus and is also related to some major risk factors for depression, implicated by its reduced expression after stress and its effect on hypothalamus-pituitary-adrenal gland axis function. However, whether SRC-1 is involved in the formation of depression remains unclear. In this study, we firstly established chronic unpredictable stress (CUS) to induce depressive-like behaviors in mice and found that SRC-1 expression was reduced by CUS. A large number of studies have shown that neuroinflammation is associated with stress-induced depression and lipopolysaccharide (LPS) injection can lead to neuroinflammation and depressive-like behaviors in mice. Our result indicated that LPS treatment also decreased SRC-1 expression in mouse brain, implying the involvement of SRC-1 in the process of inflammation and depression. Next, we showed that the chronic unpredictable mild stress (CUMS) failed to elicit the depressive-like behaviors and dramatically promoted the expression of SRC-1 in brain of wild type mice. What's more, the SRC-1 knockout mice were more susceptible to CUMS to develop depressive-like behaviors and presented the changed expression of glucocorticoid receptor. However, SRC-1 deficiency did not affect the microglia activation induced by CUMS. Altogether, these results indicate a correlation between SRC-1 level and depressive-like behaviors, suggesting that SRC-1 might be involved in the development of depression induced by stress.

8.
BMC Plant Biol ; 21(1): 177, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849439

RESUMO

BACKGROUND: Cottonseed is one of the major sources of vegetable oil. Analysis of the dynamic changes of fatty acid components and the genes regulating the composition of fatty acids of cottonseed oil is of great significance for understanding the biological processes underlying biosynthesis of fatty acids and for genetic improving the oil nutritional qualities. RESULTS: In this study, we investigated the dynamic relationship of 13 fatty acid components at 12 developmental time points of cottonseed (Gossypium hirsutum L.) and generated cottonseed transcriptome of the 12 time points. At 5-15 day post anthesis (DPA), the contents of polyunsaturated linolenic acid (C18:3n-3) and saturated stearic acid (C18:0) were higher, while linoleic acid (C18:2n-6) was mainly synthesized after 15 DPA. Using 5 DPA as a reference, 15,647 non-redundant differentially expressed genes were identified in 10-60 DPA cottonseed. Co-expression gene network analysis identified six modules containing 3275 genes significantly associated with middle-late seed developmental stages and enriched with genes related to the linoleic acid metabolic pathway and α-linolenic acid metabolism. Genes (Gh_D03G0588 and Gh_A02G1788) encoding stearoyl-ACP desaturase were identified as hub genes and significantly up-regulated at 25 DPA. They seemed to play a decisive role in determining the ratio of saturated fatty acids to unsaturated fatty acids. FAD2 genes (Gh_A13G1850 and Gh_D13G2238) were highly expressed at 25-50 DPA, eventually leading to the high content of C18:2n-6 in cottonseed. The content of C18:3n-3 was significantly decreased from 5 DPA (7.44%) to 25 DPA (0.11%) and correlated with the expression characteristics of Gh_A09G0848 and Gh_D09G0870. CONCLUSIONS: These results contribute to our understanding on the relationship between the accumulation pattern of fatty acid components and the expression characteristics of key genes involved in fatty acid biosynthesis during the entire period of cottonseed development.

9.
BMC Oral Health ; 21(1): 157, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765988

RESUMO

BACKGROUND: The aim of this study is to investigate three-dimensional quantitative analysis of buccal augmented tissue alterations after surgery using a modified coronally advanced tunnel (MCAT) technique combined with a de-epithelialized gingival graft (DGG) within 1 year post-op, based on intraoral scanning. METHODS: 25 Cairo class I gingival recession defects were treated using an MCAT technique with DGG. Digital impressions were taken using an intraoral scanner at baseline, 2 weeks, 6 weeks, 3 months, and 1 year after the surgery. Three-dimensional quantitative measurements within 1 year were analyzed for buccal augmented tissue after surgery, including postoperative gingival height gain (GHG), area gain (GAG), volume gain (GVG) and mean thickness (GMT) of region of interest, as well as the tissue thickness change at 1, 2, and 3 mm (TTC1, TTC2, and TTC3) apical to the cemento-enamel junction. RESULTS: Postoperative GHG, GAG, GVG, and GMT were distinctly encountered at 2 weeks post-op, then gradually decreased. At 1 year, GHG, GAG, GVG, and GMT were 2.211 ± 0.717 mm, 7.614 ± 2.511 mm2, 7.690 ± 4.335 mm3 and 0.965 ± 0.372 mm, respectively. Significant decreases were recorded between 6 weeks and 1 year in terms of GHG, GAG, and GVG. The GMT was sustained after 6 weeks with an increase of nearly 1 mm at 1 year. TTC1 and TTC2 yielded thicker tissue change than TTC3. CONCLUSIONS: Three-dimensional quantitative measurements taken via intraoral scanning showed that buccal augmented tissue acquired via MCAT with DGG tends to be stable after 3 months post-op. Digital measurement can be applied in periodontal plastic surgery as a clinically feasible and non-invasive evaluation method for achieving volumetric outcomes. TRIAL REGISTRATION: This study was retrospectively registered in the Chinese Clinical Trial Registry: ChiCTR1900026768. Date of registration: 21/10/2019.


Assuntos
Tecido Conjuntivo , Retração Gengival , Gengiva , Retração Gengival/cirurgia , Humanos , Estudos Prospectivos , Retalhos Cirúrgicos , Raiz Dentária , Resultado do Tratamento
10.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669144

RESUMO

A broadband visible light-absorbing [70]fullerene-BODIPY-triphenylamine triad (C70-B-T) has been synthesized and applied as a heavy atom-free organic triplet photosensitizer for photooxidation. By attaching two triphenylmethyl amine units (TPAs) to the π-core of BODIPY via ethynyl linkers, the absorption range of the antenna is extended to 700 nm with a peak at 600 nm. Thus, the absorption spectrum of C70-B-T almost covers the entire UV-visible region (270-700 nm). The photophysical processes are investigated by means of steady-state and transient spectroscopies. Upon photoexcitation at 339 nm, an efficient energy transfer (ET) from TPA to BODIPY occurs both in C70-B-T and B-T, resulting in the appearance of the BODIPY emission at 664 nm. Direct or indirect (via ET) excitation of the BODIPY-part of C70-B-T is followed by photoinduced ET from the antenna to C70, thus the singlet excited state of C70 (1C70*) is populated. Subsequently, the triplet excited state of C70 (3C70*) is produced via the intrinsic intersystem crossing of C70. The photooxidation ability of C70-B-T was studied using 1,5-dihydroxy naphthalene (DHN) as a chemical sensor. The photooxidation efficiency of C70-B-T is higher than that of the individual components of C70-1 and B-T, and even higher than that of methylene blue (MB). The photooxidation rate constant of C70-B-T is 1.47 and 1.51 times as that of C70-1 and MB, respectively. The results indicate that the C70-antenna systems can be used as another structure motif for a heavy atom-free organic triplet photosensitizer.


Assuntos
Compostos de Anilina/química , Compostos de Boro/química , Fulerenos/química , Luz , Fármacos Fotossensibilizantes/química , Estrutura Molecular , Oxirredução , Processos Fotoquímicos , Fármacos Fotossensibilizantes/síntese química
11.
Headache ; 61(4): 653-661, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33764538

RESUMO

OBJECTIVE: To assess long-term (up to 2 years) efficacy, tolerability, and safety of erenumab for the prevention of episodic migraine (EM) in Japanese patients. BACKGROUND: Previously published results from the double-blind treatment phase (DBTP) of a phase 2 clinical study have demonstrated the efficacy and safety of erenumab in Japanese patients with EM. METHODS: Patients completing the 24-week placebo-controlled DBTP could continue into the 76-week open-label treatment phase (OLTP), receiving erenumab 70 mg or 140 mg subcutaneously once monthly. The initial dose in the OLTP was erenumab 70 mg monthly, which was later changed to 140 mg. After study completion, the following were assessed: change from baseline in monthly migraine days (MMD), change from baseline in monthly acute migraine-specific medication days (MSMD), percentage of patients achieving ≥50% and ≥75% reduction in MMD, change from baseline in the 6-item Headache Impact Test (HIT-6™) score, and safety (exposure-adjusted patient-incidence of adverse events [AEs], calculated as number of patients per 100 patient-years). RESULTS: Of 475 patients enrolled in the DBTP, 459 (96.6%) continued in the OLTP. The mean (SD) MMD was 7.9 (2.3) at baseline with the overall change from baseline at week 100 of -2.9 (4.1) days. The monthly acute MSMD was 5.7 (2.8) at baseline with change from baseline at week 100 of -1.7 (3.7) days. The proportion of patients who achieved ≥50% and ≥75% reduction in MMD from baseline at week 100 was 177/398 (44.5%) and 94/398 (23.6%), respectively. The HIT-6™ score was 58.4 (5.4) at baseline with a change of -6.4 (8.2) at week 100. The exposure-adjusted patient-incidence of AEs during the OLTP was 207.1/100 patient-years for the combined erenumab group, similar to that observed for either erenumab (271.0/100 patient-years) or placebo (257.3/100 patient-years) during the DBTP, and no new safety signals were detected during the OLTP. CONCLUSION: Long-term erenumab treatment in Japanese patients with EM demonstrated sustained efficacy for up to 2 years, with a safety profile similar to previous studies, supporting erenumab as a potential new therapy for EM prevention in Japan.

12.
Plant Sci ; 305: 110827, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33691961

RESUMO

Anthocyanins are flavonoid pigments providing plants a range of colors from red, pink, orange to blue. Anthocyanins are synthesized in the cytosol but accumulate predominantly in the vacuoles through vacuolar sequestration involving glutathione S-transferases (GSTs) and multidrug and toxic compound extrusion (MATE) and the ATP binding cassette (ABC) transporters. However, little is known about anthocyanin-related GSTs in Upland cotton (Gossypium hirsutum L.). In this study, we performed genome-wide identification of GST genes in Upland cotton and identified GST genes functioning in accumulation of anthocyanins. We demonstrated that GhGSTF12 was able to complement the defective leaf color phenotypes of the Arabidopsis tt19 mutant caused by mutation in a GSTF gene. Virus-induced silencing of GhGSTF12 in the red leaf cultivar turned its red color to green and transient overexpression of GhGSTF12 accelerated anthocyanin accumulation in the red leaf cultivar but not in the green leaf cultivar. Collectively, GhGSTF12 may be involved in transport of anthocyanins from cytosol to vacuoles in cotton. These results also demonstrated a conserved function of plant GSTF genes in anthocyanin accumulation and provide a candidate gene for manipulating pigmentation in cotton tissues.

13.
Sci Prog ; 104(1): 36850421998137, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33719731

RESUMO

In view of the control effects of fluidic thrust vector technology for low-speed aircraft at high altitude/low density and low altitude/high density are studied. The S-A model of FLUENT software is used to simulate the flow field inside and outside the nozzle with variable control surface parameters, and the relationship between the area of control surface and the deflection effect of main flow at different altitudes is obtained. It is found that the fluidic thrust vectoring nozzle can effectively control the internal flow in the ground state and the high altitude/low density state. and the mainstream deflection angle can be continuously adjusted. The maximum deflection angle of the flow in the ground state is 21.86°, and the maximum deviation angle of the 20 km high altitude/low density state is 18.80°. The deflecting of the inner flow of the nozzle is beneficial to provide more lateral force and lateral torque for the aircraft. The high altitude/low density state is taken as an example. When the internal flow deflects 18.80°, the lateral force is 0.32 times the main thrust. For aircraft with high altitude and low density, sufficient lateral and lateral torque can make the flying aircraft more flexible, which can make up the shortcomings of the conventional rudder failure and even replace the conventional rudder surface.

14.
Huan Jing Ke Xue ; 42(3): 1093-1104, 2021 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742905

RESUMO

Identifying the quantitative source and hazardous areas of heavy metals in soils plays a pivotal role in soil pollution research, and can provide a basis for regional soil risk monitoring and environmental management. For this purpose, a total of 175 samples were collected in topsoils from Linzi, a typical petrochemical industrial city in Shandong Province. Positive matrix factorization (PMF) and factor analysis with non-negative constraints (FA-NNC) receptor models were applied to analyze the sources of the heavy metals. Based on the multivariate statistical simulation methods of min/max autocorrelation factors (MAF) and sequential Gaussian simulation (SGS), the distribution of heavy metal and potential pollution areas were determined. As, Co, Cr, and Mn were mainly affected by natural sources, their concentrations were dominated by the parent materials, and the high-value areas were distributed in the south of the study area. Hg was the most serious pollution element among the 10 heavy metals analyzed in Linzi and originated from atmosphere deposition from industrial emissions and coal combustion, and the highest values were distributed in the northeast of the study area. Cd, Cu, Ni, Pb, and Zn were dominated by natural sources and human activities. The hot-spot areas were mainly concentrated in the middle of the study area. The potentially contaminated areas of Cd and Hg were 580.80 km2 and 666.60 km2, about 85.04% and 97.59% of the total area, and should require more attention. The potential pollution area of most elements was small and scattered across the study area, accounting for less than 1%.

15.
Artigo em Inglês | MEDLINE | ID: mdl-33728997

RESUMO

BACKGROUND/AIMS: Liver injury and the Unfolded Protein Response (UPR) are tightly linked, but their relationship differs with cell-type and injurious stimuli. UPR initiation promotes hepatic stellate cell (HSC) activation and fibrogenesis, but the underlying mechanisms are unclear. Despite the complexity and overlap downstream of UPR transducers IRE1α, ATF6α, and PERK, previous research in HSCs primarily focused on IRE1α. Here, we interrogated the fibrogenic role of ATF6α or PERK in vitro and HSC-specific UPR signaling in vivo. METHODS/RESULTS: Overexpression of ATF6α, but not the PERK effector ATF4, promoted HSC activation and fibrogenic gene transcription in immortalized HSCs. Furthermore, ATF6α inhibition through Ceapin-A7, or Atf6a deletion, disrupted TGFß-mediated activation of primary hHSCs or mHSCs respectively. We interrogated the fibrogenic role of ATF6α in vivo through conditional HSC-specific Atf6a deletion. Atf6aHSCΔ/Δ mice displayed reduced fibrosis and HSC activation following bile-duct ligation (BDL) or CCl4-induced injury. The Atf6aHSCΔ/Δ phenotype differed from HSC-specific Ire1a deletion, as Ire1aHSCΔ/Δ mice showed reduced fibrogenic gene transcription no changes in fibrosis compared to Ire1afl/fl mice following BDL. Interestingly, ATF6α signaling increased in Ire1aΔ/Δ HSCs, while IRE1α signaling was upregulated in Atf6aΔ/Δ HSCs. Finally, we asked whether co-deletion of Arf6a and Ire1a additively limits fibrosis. Unexpectedly, fibrosis worsened in Atf6aHSCΔ/ΔIre1aHSCΔ/Δ mice following BDL, and Atf6aΔ/ΔIre1aΔ/Δ mHSCs showed increased fibrogenic gene transcription. CONCLUSIONS: ATF6α and IRE1α individually promote fibrogenic transcription in HSCs and ATF6α drives fibrogenesis in vivo. Unexpectedly, disruption of both pathways sensitizes the liver to fibrogenesis, suggesting that fine-tuned UPR signaling is critical for regulating HSC activation and fibrogenesis.

16.
J Affect Disord ; 282: 894-905, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33601733

RESUMO

BACKGROUND: A range of factors have been identified that contribute to greater incidence, severity, and prolonged course of post-traumatic stress disorder (PTSD), including: comorbid and/or prior psychopathology; social adversity such as low socioeconomic position, perceived discrimination, and isolation; and biological factors such as genomic variation at glucocorticoid receptor regulatory network (GRRN) genes. This complex etiology and clinical course make identification of people at higher risk of PTSD challenging. Here we leverage machine learning (ML) approaches to identify a core set of factors that may together predispose persons to PTSD. METHODS: We used multiple ML approaches to assess the relationship among DNA methylation (DNAm) at GRRN genes, prior psychopathology, social adversity, and prospective risk for PTS severity (PTSS). RESULTS: ML models predicted prospective risk of PTSS with high accuracy. The Gradient Boost approach was the top-performing model with mean absolute error of 0.135, mean square error of 0.047, root mean square error of 0.217, and R2 of 95.29%. Prior PTSS ranked highest in predicting the prospective risk of PTSS, accounting for >88% of the prediction. The top ranked GRRN CpG site was cg05616442, in AKT1, and the top ranked social adversity feature was loneliness. CONCLUSION: Multiple factors including prior PTSS, social adversity, and DNAm play a role in predicting prospective risk of PTSS. ML models identified factors accounting for increased PTSS risk with high accuracy, which may help to target risk factors that reduce the likelihood or course of PTSD, potentially pointing to approaches that can lead to early intervention. LIMITATION: One of the limitations of this study is small sample size.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Metilação de DNA/genética , Humanos , Aprendizado de Máquina , Estudos Prospectivos , Psicopatologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/genética
17.
Pathol Res Pract ; 220: 153270, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33640712

RESUMO

BACKGROUND: Insufficient high-intensity focused ultrasound (HIFU) can promote the rapid progression of the residual tumor through the hypoxia inducible factor-2α +(HIF-2α)/vascular endothelial growth factor A (VEGFA)/ephrin type-A receptor 2 (EphA2) pathway. Although sorafenib has been shown to significantly improve the survival of patients with advanced liver cancer, the use of sorafenib in residual tumor tissues following HIFU has rarely been elucidated. Thus, this study aimed to investigate the potential adjuvant therapeutic effects of sorafenib following HIFU in order to reduce the relapse rate following insufficient HIFU. METHODS: Xenograft tumors were established using nude mice injected with liver cancer cells. At approximately 4 weeks after the inoculation of the tumor cells (tumors reached 1.3-1.5 cm), all mice were randomly divided into 3 groups as follows: i) The control group (no treatment); ii) the HIFU-alone group, and iii) the combination group (HIFU + sorafenib), with 6 mice per group. The residual tumor volume was determined among the different treatment groups. The protein expression levels of HIF-2α, VEGFA and EphA2 were determined by immunohistochemistry and western blotting, and the mRNA levels were detected by RT-qPCR. The microvessel density (MVD) was calculated by CD31 immunohistochemistry staining. RESULTS: The results revealed that by comparing the control group, insufficient HIFU promoted HIF-2α, VEGFA and EphA2 expression (P < 0.05). Compared with the HIFU-alone group, the protein and mRNA levels of HIF-2α, VEGFA and EphA2 were markedly decreased in the group that received combined treatment with HIFU and sorafenib (P < 0.05). Similar results were obtained for MVD expression. Synergistic tumor growth inhibitory effects were also observed between the control group and HIFU group (P < 0.05). CONCLUSIONS: The findings of this study demonstrate that the expression of HIF-2α, VEGFA and EphA2 can be inhibited by sorafenib, and that sorafenib is likely to provide an effective adjunct treatment for patients with HCC following HIFU ablation.

18.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 116-120, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33627203

RESUMO

OBJECTIVE: To study the clinical effect of continuous subcutaneous insulin infusion (CSⅡ) versus multiple daily injection (MDI) on blood glucose control in children with type 1 diabetes mellitus (T1DM). METHODS: A retrospective analysis was performed on the medical data of 91 children with T1DM who were treated with CSⅡ for more than 1 year and 75 children with T1DM who were treated with MDI. The two groups were compared in terms of glycosylated hemoglobin (HbA1C) and the recurrence of diabetic ketoacidosis (DKA) to evaluate the difference in the efficacy during the 3-year follow-up. A survey was conducted for the children in the CSⅡ group and their family members to investigate the degree of satisfaction with insulin pump. RESULTS: There was no significant difference in age, sex, and course of diabetes between the CSⅡ and MDI groups at disease onset and in the first year, the second year, and the third year of follow-up (P > 0.05). There was no significant difference in the HbA1C level between the two groups at disease onset (P > 0.05), but in the first year of follow-up, the CSⅡ group had a significantly lower HbA1C level than the MDI group (P=0.04). There was no significant difference in the HbA1C level between the two groups in the second year and the third year of follow-up (P > 0.05). The CSⅡ group had a higher proportion of children with HbA1C < 7.5% than the MDI group in the first year, the second year, and the third year of follow-up (P > 0.05). Within the 3 years of follow-up, 2 children in the CSⅡ group and 8 in the MDI group experienced the recurrence of DKA. In the third year of follow-up, there was no significant difference in blood pressure and blood lipids between the CSⅡ and MDI groups (P > 0.05). Most children and their family members (87%) were satisfied with CSⅡ treatment. CONCLUSIONS: Children with T1DM treated with CSⅡ have a better control of blood glucose than those treated with MDI, and children and their family members are satisfied with CSⅡ treatment. Therefore, it holds promise for clinical application.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Insulinas , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Seguimentos , Humanos , Estudos Retrospectivos
19.
Nat Commun ; 12(1): 1306, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637763

RESUMO

Ferroelectric topological objects provide a fertile ground for exploring emerging physical properties that could potentially be utilized in future nanoelectronic devices. Here, we demonstrate quasi-one-dimensional metallic high conduction channels associated with the topological cores of quadrant vortex domain and center domain (monopole-like) states confined in high quality BiFeO3 nanoislands, abbreviated as the vortex core and the center core. We unveil via the phase-field simulation that the superfine metallic conduction channels along the center cores arise from the screening charge carriers confined at the core region, whereas the high conductance of vortex cores results from a field-induced twisted state. These conducting channels can be reversibly created and deleted by manipulating the two topological states via electric field, leading to an apparent electroresistance effect with an on/off ratio higher than 103. These results open up the possibility of utilizing these functional one-dimensional topological objects in high-density nanoelectronic devices, e.g. nonvolatile memory.

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