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1.
J Hazard Mater ; 441: 129819, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36084455

RESUMO

Data on the occurrences of legacy and alternative per- and polyfluoroalkyl substances (PFASs) in glioma are scarce. It remains unclear if PFASs exposure is related to the prevalence of glioma. A total of 137 glioma and 40 non-glioma brain tissue samples from patients recruited from the Nanfang Hospital, South China were analyzed for 17 PFAS compounds. Perfluorohexanoic acid, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (FOSA), and 6:2 chlorinated polyfluorinated ether sulfonate were frequently detected (> 60 %) in glioma. The total concentrations (range; median) of 17 PFASs in glioma (0.20-140; 3.1 ng g-1) were slightly higher than those in non-glioma (0.35-32; 2.2 ng g-1), but without statistical significance. The PFAS concentrations in males were statistically higher (p < 0.05) than those in females. Elevated glioma grades were associated with higher concentrations of PFOA, PFOS, and FOSA. Positive correlations were observed between PFAS concentrations (especially for PFOA) and Ki-67 or P53 expression, pathological molecular markers of glioma. Our findings suggested that exposure to PFASs might increase the probability to develop glioma. This is the first case study demonstrating associations between PFASs exposure and brain cancer. More evidences and potential pathogenic mechanisms warranted further investigations.

2.
Am J Cancer Res ; 12(8): 3729-3744, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119843

RESUMO

Due to the rapid proliferation, cancer cells have increased anabolic biosynthesis, which requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the catalysis of pyruvate carboxylase (PC) and glutaminase (GLS) respectively. In GLS-suppressed cancer cells, the PC-mediated pathway for anaplerosis is crucial to maintain cell growth and proliferation. Here, we investigated the regulatory role and molecular mechanism of N-myc downstream-regulated gene 2 (NDRG2) in PC and PC-mediated anaplerosis. NDRG2 interacted with PC and induced the degradation of PC in glutamine-deprived cells. NDRG2 also inhibited the activity of PC and PC-mediated anaplerosis. As a result, NDRG2 significantly inhibited the malignant growth and proliferation of glioma cells in combination with a glutamine antagonist. In addition, NDRG2 more significantly inhibited the protein level of PC in isocitrate dehydrogenase 1 (R132H)-mutant glioma cells than in wild-type glioma cells. These findings indicate that the molecular mechanism of NDRG2 inhibits PC-mediated anaplerosis and collaborates with glutamine antagonist to inhibit the malignant proliferation of glioma cells, thus providing a theoretical and experimental basis for targeting anaplerosis in glioma therapy.

4.
J Chem Phys ; 157(11): 114111, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36137799

RESUMO

Quantum time correlation functions (TCFs) involving two states are important for describing nonadiabatic dynamical processes such as charge transfer (CT). Based on a previous single-state method, we propose an imaginary-time open-chain path-integral (OCPI) approach for evaluating the two-state symmetrized TCFs. Expressing the forward and backward propagation on different electronic potential energy surfaces as a complex-time path integral, we then transform the path variables to average and difference variables such that the integration over the difference variables up to the second order can be performed analytically. The resulting expression for the symmetrized TCF is equivalent to sampling the open-chain configurations in an effective potential that corresponds to the average surface. Using importance sampling over the extended OCPI space via open path-integral molecular dynamics, we tested the resulting path-integral approximation by calculating the Fermi's golden rule CT rate constant within a widely used spin-boson model. Comparing with the real-time linearized semiclassical method and analytical result, we show that the imaginary-time OCPI provides an accurate two-state symmetrized TCF and rate constant in the typical turnover region. It is shown that the first bead of the open chain corresponds to physical zero-time and that the endpoint bead corresponds to final time t; oscillations of the end-to-end distance perfectly match the nuclear mode frequency. The two-state OCPI scheme is seen to capture the tested model's electronic quantum coherence and nuclear quantum effects accurately.

5.
J Chem Theory Comput ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36073792

RESUMO

Direct all-atom simulation of nonadiabatic dynamics in disordered condensed phases like liquid solutions and amorphous solids has been challenging. The first all-atom simulation of the photoinduced charge-transfer dynamics of a prototypical organic photovoltaic carotenoid-porphyrin-C60 molecular triad in explicit tetrahydrofuran is presented. Based on the Meyer-Miller mapping Hamiltonian, various semiclassical and mixed quantum-classical dynamics are employed, including the linearized semiclassical, symmetrical quasiclassical, mean-field Ehrenfest, classical mapping model, and spin-mapping model approaches. The all-atom nonadiabatic dynamics were compared to multi-state harmonic models with a globally shared bath, and the models built using the ensemble averages on the initial electronic state could reproduce the all-atom results. The solvent effect was found to be critical for the photoinduced charge transfer, and the time-dependent solute-solvent radial distribution functions revealed that only the nonadiabatic dynamics started with the effective forces on the initial electronic state could capture the correct nuclear dynamics. The proposed strategy for modeling condensed-phase nonadiabatic dynamics with atomistic details is readily applied to complex condensed-phase systems.

6.
Kidney Int ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36089186

RESUMO

Acute kidney injury (AKI) is a worldwide public health problem characterized by excessive inflammation with no specific therapy in clinic. Inflammation is not only a feature of AKI but also an essential promoter for kidney deterioration. Phosphoglycerate mutase 5 (PGAM5) was up-regulated and positively correlated with kidney dysfunction in human biopsy samples and mouse kidneys with AKI. PGAM5 knockout in mice significantly alleviated ischemia/reperfusion-induced kidney injury, mitochondrial abnormality and production of inflammatory cytokines. Elevated PGAM5 was found to be mainly located in kidney tubular epithelial cells and was also related to inflammatory response. Knockdown of PGAM5 inhibited the hypoxia/reoxygenation-induced cytosolic release of mitochondrial DNA (mtDNA) and binding of mtDNA with the cellular DNA receptor cGAS in cultured cells. cGAS deficiency also attenuated the inflammation and kidney injury in AKI. Mechanistically, as a protein phosphatase, PGAM5 was able to dephosphorylate the pro-apoptotic protein Bax and facilitate its translocation to mitochondrial membranes, and then initiate increased mitochondrial membrane permeability and release of mtDNA. Leaked mtDNA recognized by cGAS then initiated its downstream-coupled STING pathway, a component of the innate immune system that functions to detect the presence of cytosolic DNA. Thus, our results demonstrated mtDNA release induced by PGAM5-mediated Bax dephosphorylation and the activation of cGAS-STING pathway as critical determinants of inflammation and kidney injury. Hence, targeting this axis may be useful for treating AKI.

7.
Biomaterials ; 288: 121744, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35999081

RESUMO

While the miniaturization and motility of artificial nanomotors made them popular tools for exploring novel and innovative biomedical cancer treatment strategies, the integration of multiple functions on the small motor bodies is key to achieve further progress but remains unresolved. Here, we propose a dual-source powered Janus nanomotor whose composition integrates multiple photo-theranostic functions such as surface-enhanced Raman scattering (SERS) sensing, fluorescence imaging/photoacoustic imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). This nanomotor can be fabricated by sputtering a thin gold layer onto one side of mesoporous silica (mSiO2) combined with surface modification by photo-sensitizer, Raman reporter, and catalase. Upon illumination with 808 nm near-infrared light, the half-coated gold nanoshell serves as PAI/PTT agent, and by upconverting NIR to visible light, the pre-loaded photosensitizer can be excited by the upconverted light of UCNPs to convert the dissolved oxygen (O2) into reactive oxygen species for efficient PDT. Furthermore, ratiometric SERS signal can be captured to quantitatively detect the tumor marker, H2O2, in cellular microenvironments. The immobilized catalase as a nano-engine can catalyze endogenous H2O2 to O2. This function not only improves the hypoxic tumor microenvironment and therefore enhances PDT efficiency, but also provides a thrust force for deep penetration. As a proof of concept for the in vivo trial we performed cancer photo-theranostics where our nanomotors successfully treated a mouse breast tumor in a subcutaneous tumor model. The results are promising and encourage the use of an integrated nanomotor platform that could be further developed into a photo-theranostic agent for superficial cancer treatment.


Assuntos
Neoplasias , Fotoquimioterapia , Animais , Catalase/uso terapêutico , Linhagem Celular Tumoral , Ouro/uso terapêutico , Peróxido de Hidrogênio/uso terapêutico , Camundongos , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Medicina de Precisão , Nanomedicina Teranóstica/métodos , Microambiente Tumoral
9.
Science ; 377(6608): eabl6433, 2022 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-35981017

RESUMO

Weiss et al. (Reports, 2 July 2021, p. 107) incorrectly conclude that the residence time for floating microplastic stock at the ocean surface is ~2.4 years. We contend that this conclusion is fundamentally flawed, because the residence time is obtained through dividing a published oceanic stock of plastic debris by a doubtable river microplastic flux estimated by the authors.


Assuntos
Microplásticos , Oceanos e Mares , Rios , Monitoramento Ambiental , Fatores de Tempo , Resíduos/análise
10.
Acta Pharmacol Sin ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045219

RESUMO

Transforming growth factor-ß1 (TGF-ß1) is regarded as a key factor in promoting renal fibrosis during chronic kidney disease (CKD). Signaling transduction of TGF-ß1 starts with binding to TGF-ß type II receptor (Tgfbr2), a constitutively activated kinase that phosphorylates TGF-ß type I receptor (Tgfbr1), and then activates downstream Smad2/3 or noncanonical pathways. Previous studies show that cellular senescence is associated with the progression of CKD, and accelerated tubular cell senescence is implicated in promoting renal fibrosis. In the present study we investigated the renal parenchymal cell senescence in fibrosis from the sight of posttranslational regulation and focused on Tgfbr2, the important gatekeeper for TGF-ß1 downstream signaling. In mice with unilateral ureteral obstruction (UUO) and folic acid (FA)-induced fibrotic kidneys, we found that Tgfbr2 was markedly elevated without obvious change in its mRNA levels. As an important member of deubiquitinating enzymes, ubiquitin-specific protease 11 (Usp11) was also significantly increased in fibrotic kidneys, and co-distributed with Tgfbr2 in tubular epithelial cells. Pretreatment with Usp11 inhibitor mitoxantrone (MTX, 30 mg · kg-1 · d-1, i.p.) twice a week, for 2 weeks significantly attenuated the elevation of Tgfbr2, activation in downstream senescence-related signaling pathway, as well as renal senescence and fibrosis. In cultured mouse tubular epithelial cells (MTECs), treatment with angiotensin II (Ang-II, 10-7, 10-6 M) dose-dependently elevated both Tgfbr2 and Usp11 levels. Inhibition or knockdown on Usp11 attenuated Ang-II-induced elevation in Tgfbr2 level, and attenuated the activation of downstream senescent-related signaling pathway and as well as cell senescence. We conducted Co-IP experiments, which revealed that Usp11 was able to interact with Tgfbr2, and inhibition of Usp11 increased the ubiquitination of Tgfbr2. Taken together, these results demonstrate that the elevation of Usp11 under pathological condition is implicated in promoting renal fibrosis. Usp11 promotes the development of renal fibrosis by deubiquitinating Tgfbr2, reducing Tgfbr2 ubiquitination degradation, and then facilitating the activation of downstream senescent signaling pathway.

11.
ACS Nano ; 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36018321

RESUMO

Miniaturization of synthetic micro/nanomotors (MNMs) brings great application prospects but limits their functionalization ability. Here, we report self-fueled metal organic framework (MOF) micromotors that are endowed with capabilities of self-propulsion and antibacterial therapy by their material's intrinsic properties. The spontaneous degradation of the MOF micromotors in water would release their own constituting components of ions which act as fuels to propel themselves by ionic diffusionphoresis with a high energy conversion efficiency. Meanwhile, the metal cations released from the MOF micromotors can also serve as antibacterial reagents to kill Escherichia coli (E. coli) with motion enhanced efficacy, which could significantly accelerate the wound closure in a bacterially infected wound model in vivo. Our work provides a general guidance for constructing functional MNMs by taking advantage of the motors' own materials to achieve self-propulsion and on-demand task assignments, which would promote future development of highly integrated micro/nanorobotic systems at micro/nanoscale.

12.
Hum Vaccin Immunother ; : 2114255, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35993917

RESUMO

The purpose of this study was to investigate the outbreak trend of chickenpox and the epidemiological characteristics of outbreak related cases from 2017 to 2021, and compare the impact of voluntary self-funded single dose vaccination versus mandatory two-dose vaccine vaccination on varicella outbreaks. The data of varicella outbreaks in Jiangsu Province from 2017 to 2021 come from the national public health emergency management information system. We randomly chose 70 outbreaks from 2019 to 2020 for study in order to better understand the features and regularity of breakthrough varicella(BV). In pilot cities with two doses of free VarV, the number of outbreaks decreased from 306 in 2017 to 123 in 2021, while the total number of cases related to the outbreak decreased by 64.6% (P < .01), the median size of the outbreak decreased from 24 cases (range:6-146) to 21 cases (range:10-93) (P < .01), and the incidence rate also decreased from 2.01/100 to 1.33/100. The proportion of cases with high fever, severe rash and complications in the BV group was lower than that in the primary varicella (PV), and the differences were statistically significant. The incidence rate of varicella among students who had post-exposure prophylaxis (PEP) activities was 1.42% (488/ 33,878), and 1.63% (2468/ 148,943) among those who did not (p = .005). The single-dose varicella vaccination was less effective in controlling the outbreaks, and the success of the full implementation of the routine two-dose varicella vaccination plan in the pilot cities provided a basis for implementation in the whole province, and long-term follow-up studies are needed to evaluate the effect of the new strategy in the future.

13.
Gastroenterology ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35963369

RESUMO

BACKGROUND & AIMS: Current therapies for ulcerative colitis (UC) fail to achieve satisfactory disease control. Selective inhibition of Janus kinase (JAK) type 1 may improve clinical outcomes in patients with UC while avoiding side effects associated with pan-JAK inhibition. The safety and efficacy of the selective JAK1 inhibitor ivarmacitinib (formerly SHR0302) were evaluated in patients with moderate-to-severe, active UC. METHODS: AMBER2 was a double-blind, placebo-controlled, phase II trial conducted at 63 clinical centers in China, the United States, and Europe. Patients (N = 164) were randomized 1:1:1:1 to receive oral ivarmacitinib 8 mg once daily (QD), 4 mg twice daily (BID), or 4 mg QD, or placebo for 8 weeks, followed by an 8-week extension period. The primary endpoint was clinical response rate at week 8. Hochberg's procedure was used to control the study-wise type 1 error at alpha=0.1. RESULTS: A total of 146 (89.0%) patients completed 8 weeks of treatment. Week 8 clinical response rates were significantly higher in the 8 mg QD (46.3%; P = .066), 4 mg BID (46.3%; P = .059), and 4 mg QD (43.9%; P = .095) groups vs placebo (26.8%). Week 8 rates of clinical remission were 22.0% (P = .020), 24.4% (P = .013), and 24.4% (P = .011) in 3 ivarmacitinib treatment groups, respectively, vs 4.9% for placebo. During the initial 8-week period, treatment-emergent adverse events occurred in 43.9% to 48.8% of ivarmacitinib-treated patients and in 39.0% of the placebo group, and were predominantly mild. There were no deaths, or major adverse cardiovascular or thromboembolic events. CONCLUSION: Ivarmacitinib demonstrated clinical efficacy and was well tolerated in patients with moderate-to-severe, active, UC. Ivarmacitinib represents a promising new treatment for moderate-to-severe UC. CLINICALTRIALS: gov number, NCT03675477.

14.
J Theor Biol ; 551-552: 111242, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-35952756

RESUMO

BACKGROUND: Measles has re-emerged globally due to the accumulation of susceptible individuals and immunity gap, which causes challenges in eliminating measles. Routine vaccination and supplementary immunization activities (SIAs) have greatly improved measles control, but the impact of SIAs on the measles transmission dynamics remains unclear as the vaccine-induced immunity wanes. METHODS: We developed a comprehensive measles transmission dynamics model by taking into account population demographics, age-specific contact patterns, seasonality, routine vaccination, SIAs, and the waning vaccine-induced immunity. The model was calibrated by the monthly age-specific cases data from 2005 to 2018 in Jiangsu Province, China, and validated by the dynamic sero-prevalence data. We aimed to investigate the short-term and long-term impact of three-time SIAs during 2009-2012 (9.68 million and 4.25 million children aged 8 months-14 years in March 2009 and September 2010, respectively, and 140,000 children aged 8 months-6 years in March 2012) on the measles disease burden and explored whether additional SIAs could accelerate the measles elimination. RESULTS: We estimated that the cumulative numbers of measles cases from March 2009 to December 2012 (in the short run) and to December 2018 (in the long run) after three-time SIAs (base case) were 6,699 (95% confidence interval [CI]: 2,928-10,469), and 22,411 (15,146-29,675), which averted 45.0% (42.9%-47.0%) and 34.3% (30.7%-37.9%) of 12,226 (4,916-19,537) and 34,274 (21,350-47,199) cases without SIAs, respectively. The fraction of susceptibles for children aged 8-23 months and 2-14 years decreased from 8.3% and 10.8% in March 2009 to 5.8% and 5.8% in April 2012, respectively. However, the fraction of susceptibles aged 15-49 years and above 50 years increased gradually to about 15% in 2018 irrespective of SIAs due to the waning immunity. The measles elimination goal would be reached in 2028, and administrating additional one-off SIAs in September 2022 to children aged 8-23 months, or young adolescents aged 15-19 years could accelerate the elimination one year earlier. CONCLUSIONS: SIAs have greatly reduced the measles incidence and the fraction of susceptibles, but the benefit may wane over time. Under the current interventions, Jiangsu province would reach the measles elimination goal in 2028. Additional SIAs may accelerate the measles elimination one year earlier.


Assuntos
Vacina contra Sarampo , Sarampo , Adolescente , Criança , Suscetibilidade a Doenças , Humanos , Imunização , Programas de Imunização , Lactente , Sarampo/epidemiologia , Sarampo/prevenção & controle , Vacinação
15.
Europace ; 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35942655

RESUMO

AIMS: Activation mapping of premature atrial complexes (PACs) proves challenging due to interference by mechanical bumping and non-targeted ectopies. This study aims to compare the mapping efficacy, instant success, and long-term recurrence of catheter ablation for PACs with non-pulmonary vein (PV) and non-superior vena cava (SVC) origins between the novel dual-reference approach (DRA) and the routine single-reference approach (SRA) of mapping. METHODS AND RESULTS: Patients with symptomatic, drug-refractory PACs, or frequent residual PACs after atrial tachyarrhythmia ablation were enrolled. During activation mapping, the coronary sinus (CS) catheter was used as the only timing reference in the SRA group. In the DRA group, another catheter, which was spatially separated from the CS catheter, was used as the second reference. The timing difference between the two references was used to discriminate the targeted PACs from the uninterested rhythms. Procedural parameters and long-term recurrence were compared. A total of 188 patients (109 in SRA and 79 in DRA) were enrolled. The baseline characteristics were similar. Compared with the SRA group, the DRA group had less repeated mapping (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.004), shorter mapping (15 ± 6 vs. 23 ± 7 min, P < 0.001) and procedural time (119 ± 28 vs. 132 ± 22 min, P = 0.001), similar procedural complication rates (3.6 vs. 3.8%, P > 0.999), higher instant success (96.2 vs. 87.2%, P = 0.039), and lower recurrence rate (15.2 vs. 29.3%, hazard ratio 1.943, P = 0.033) during a 24-month follow-up. CONCLUSION: As a novel strategy, the DRA shortens the procedural time and improves both instant and long-term success of PAC ablation, serving as a promising approach in mapping PACs with non-PV and non-SVC origins.

16.
Front Immunol ; 13: 905634, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958596

RESUMO

Key point: Considering that vaccination with the sIPV and DTaP overlap at the ages of 3 and 4 months in China, to reduce the burden of treatment on parents and increase vaccination coverage rates, we designed a postmarket clinical study of co-administration. Background: The Sabin-strain-based inactivated poliovirus vaccine (sIPV) and the diphtheria-tetanus-acellular pertussis vaccine (DTaP) have been licensed in China for many years. To conduct a clinical study on the safety and immunogenicity of the sIPV when administered concomitantly with the DTaP. Methods: The study population was divided into three groups: group 1 was the sIPV+ DTaP concomitant administration group, group 2 was the sIPV inoculation group, and group 3 was the DTaP inoculation group. Blood samples were collected prevaccination and 30 days postvaccination, and serum antibody levels were detected. Results: This study showed that the seropositive and seroconversion rates of type 1, 2 and 3 poliovirus in group 1 were higher than those in group 2, with no statistically significant difference after vaccination (P>0.05). Groups 1 and 3 also showed similar responses for all vaccine antigens except anti-FHA (97.65 (94.09-99.36) vs. 100 (97.89-100)). The geometric mean titers (GMTs) for the DTaP and sIPV among the groups were comparable, and the non-inferiority t test result was P<0.001. The number of local adverse events (AEs) reported in group 1 (29.91%) were larger than those in group 2 (12.39%) and group 3 (21.93%), among which the most common was redness. Similarly, the most common systemic AE was fever. All 5 severe AE (SAE) cases were determined by experts to be unrelated to the vaccines during the study. Conclusions: The evidence of similar seroconversion and safety with co-administered DTaP and sIPV supports the co-administration supports the introduction of a strategy of simultaneous administration of both vaccines into routine infant immunization, and it could increase vaccination coverage and protect more infants from morbidity and mortality from these related diseases. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04054882?term=NCT04054882&cntry=CN&draw=2&rank=1, identifier NCT04054882.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Difteria , Poliomielite , Vacina Antipólio de Vírus Inativado , Tétano , Coqueluche , Anticorpos Antibacterianos , Criança , Difteria/prevenção & controle , Vacinas contra Difteria, Tétano e Coqueluche Acelular/efeitos adversos , Humanos , Lactente , Poliomielite/prevenção & controle , Poliovirus , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio Oral , Tétano/prevenção & controle , Vacinas Combinadas , Coqueluche/prevenção & controle
17.
Contrast Media Mol Imaging ; 2022: 9383982, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35833058

RESUMO

This research aimed to study the application of magnetic resonance imaging (MRI) under three-dimensional mark point positioning algorithm in stereotactic surgery for Parkinson's disease (PD) and improve clinical treatment effect. Eighty patients with PD in Tianjin Medical University General Hospital were selected as the research objects and randomly divided into two groups. The three-dimensional mark point positioning algorithm was applied to perform feature positioning on the MRI images of PD patients, and the international unified Parkinson's disease rating scale (UPDRS) was assessed before and after single-target surgery of the two groups. There was a significant difference in the postoperative treatment effect between the two groups compared with the preoperative one (P < 0.05). Among the patients in the observation group, 37 cases were marked as markedly effective, accounting for 92.5% of the total group; 1 case was ineffective and 2 cases were improved, accounting for 2.5% and 5%, respectively. In the control group, 35, 2, and 3 cases were assessed as markedly effective, ineffective, and improved, accounting for 87.5%, 5%, and 7.5%, respectively. The overall curative effect of the observation group was better than that of the control group, and the difference was significant (P < 0.05). The MRI manifestations of PD patients were diversified. MRI under the three-dimensional mark point positioning algorithm had a high value for the stereotactic treatment of PD patients, which was beneficial to the clinical surgery.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Algoritmos , Estimulação Encefálica Profunda/métodos , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/cirurgia , Resultado do Tratamento
18.
Chemosphere ; 306: 135512, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35779685

RESUMO

Wastewater problems caused by antibiotics and bacteria contamination have become the primary environmental concern due to their harm to terrestrial organisms and health risk. To obtain the efficient removal approach of antibiotics and bacteria, visible driven advanced oxidation process by photocatalyst for the efficient removal and reducing waterborne disease was demonstrated in this study. 2D/2D GO-Ag/P/BWO heterostructure photocatalyst (GO: graphene oxide, Ag: Ag, Ag2O; P: BiPO4; BWO: Bi2WO6) were synthesized for effectively purification of antibiotics and bacteria contaminated wastewater. GO added in synthesis of BWO (1st-hydrothermal) and induced of Ag dopants (2nd-hydrothermal) of GO-Ag/P/BWO were fabricated separately and marked as GO(I)-Ag/P/BWO and GO(II)-Ag/P/BWO, characterized by different tests (FT-IR, XRD, Raman, XPS, SEM, TEM, TG, UV-VIS, PL, photocurrent density, and EIS). To testify the visible light driven photocatalytic activity of the fabricated photocatalysts, Rhodamine B (Rh B) and amoxicillin (AMX) was chosen as model emerging organic contaminants and antibiotics, respectively. While gram-negative strain Escherichia coli (E. coli) was selected as model waterborne bacteria. The results showed that GO(II)-Ag/P/BWO photocatalyst was synthesized successfully, and possessed high crystallinity, low generated electron-hole recombination rate, and high photocurrent density. The system can produce energetic active species (h+, O2- and OH), exhibiting a superior performance towards removal of Rh B, AMX and E. coli under visible light irradiation. Comparing to other reported GO modified Bi based photocatalyst, GO(II)-Ag/P/BWO had stronger photocatalytic performance in degradation of Rh B, AMX and E. coli, which indicated its high prospects for practical application in environmental wastewater treatment.


Assuntos
Poluentes Ambientais , Águas Residuárias , Antibacterianos/química , Catálise , Poluentes Ambientais/farmacologia , Escherichia coli , Grafite , Luz , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Cell Death Discov ; 8(1): 312, 2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35810157

RESUMO

Non-small cell lung cancer (NSCLC) is highly malignant and heterogeneous form of lung cancer and involves various oncogene alterations. Glycolysis, an important step in tumor metabolism, is closely related to cancer progression. In this study, we investigated the biological function and mechanism of action of Gankyrin in glycolysis and its association with NSCLC. Analyzed of data from The Cancer Genome Atlas as well as NSCLC specimens and adjacent tissues demonstrated that Gankyrin expression was upregulated in NSCLC tissues compared to adjacent normal tissues. Gankyrin was found to significantly aggravate cancer-related phenotypes, including cell viability, migration, invasion, and epithelial mesenchymal transition (EMT), whereas Gankyrin silencing alleviated the malignant phenotype of NSCLC cells. Our results reveal that Gankyrin exerted its function by regulating YAP1 expression and increasing its nuclear translocation. Importantly, YAP1 actuates glycolysis, which involves glucose uptake, lactic acid production, and ATP generation and thus might contribute to the tumorigenic effect of Gankyrin. Furthermore, the Gankyrin-accelerated glycolysis in NSCLC cells was reversed by YAP1 deficiency. Gankyrin knockdown reduced A549 cell tumorigenesis and EMT and decreased YAP1 expression in a subcutaneous xenograft nude mouse model. In conclusion, both Gankyrin and YAP1 play important roles in tumor metabolism, and Gankyrin-targeted inhibition may be a potential anti-cancer therapeutic strategy for NSCLC.

20.
Org Biomol Chem ; 20(28): 5510-5514, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35788245

RESUMO

An efficient enantioselective Michael addition reaction of 2,3-dioxopyrrolidine with indole in aqueous media was developed by virtue of a chiral copper complex. This reaction features air tolerance, a broad substrate scope and mild reaction conditions. Furthermore, a gram-scale synthesis was conducted to afford the corresponding products with a high yield and excellent enantioselectivity. Moreover, the proposed mechanism was supported by control experiments, XPS investigation and DFT calculations.


Assuntos
Indóis , Lactamas , Catálise , Cobre , Estereoisomerismo , Água
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