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1.
J Am Chem Soc ; 146(27): 18699-18705, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38943601

RESUMO

Carbonyl nitrenes are versatile intermediates that have been extensively characterized; however, their phosphorus analogues remain largely unknown. Herein, we report the observation of a rare example of carbonyl phosphinidene NH2C(O)P, which was generated through the photolytic (193 nm) dehydrogenation of phosphinecarboxamide (NH2C(O)PH2) in a solid N2-matrix at 12 K. The characterization of NH2C(O)P in the triplet ground state with matrix-isolation IR and ultraviolet-visible (UV-vis) spectroscopy is supported by comprehensive isotope labeling experiments (D and 15N) and quantum chemical calculations. Upon visible-light irradiation at 680 nm, NH2C(O)P inserts into dihydrogen by the reformation of NH2C(O)PH2 with concomitant isomerization to the more stable aminophosphaketene (NH2PCO). Additionally, the photoisomerization of NH2C(O)PH2 to NH2C(OH) = PH along with decomposition by yielding hydrogen-bonded complexes HNCO···PH3 and HPCO···NH3 has been observed in the matrix.

2.
Eur Neurol ; 86(4): 229-241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37068471

RESUMO

INTRODUCTION: Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of ticagrelor on cerebrovascular outcomes in patients with vascular risk factors. METHODS: The PubMed, Cochrane Library, and Embase databases were systematically searched using the keywords stroke, ticagrelor, clopidogrel, and aspirin to identify randomized controlled trials (RCTs). Primary outcomes included reported stroke, ischemic stroke, and complex events; the secondary outcome was hemorrhagic stroke. The safety outcomes included major bleeding events, major or minor bleeding, and intracranial bleeding. The pooled odds ratio (OR), hazard ratios (HRs), and 95% confidence interval (CI) were calculated. We used I2 statistics to assess statistical heterogeneity. RESULTS: This meta-analysis included 15 RCTs involving 63,865 patients. Compared to the control group, ticagrelor reduced the risk of stroke (OR: 0.90; 95% CI: 0.81-0.99, p = 0.03; I2 = 3%), ischemic stroke (OR: 0.81; 95% CI: 0.74-0.90, p < 0.0001; I2 = 0%). Ticagrelor was not associated with an increased risk of all-cause mortality (OR: 0.94; 95% CI: 0.84-1.06, p = 0.31; I2 = 62%), major bleeding (OR: 1.06; 95% CI: 0.97-1.15, p = 0.20; I2 = 17%), hemorrhagic strokes (OR: 1.22, 95% CI: 0.76-1.96, p = 0.41; I2 = 0%), and intracranial hemorrhage (OR: 1.06; 95% CI: 0.78-1.43, p = 0.71; I2 = 12%). There was an increased risk of major or minor bleeding with ticagrelor compared to the control group (OR: 1.40; 95% CI: 1.19-1.66, p < 0.0001; I2 = 56%). Additional analyses demonstrated that ticagrelor reduced the risk of incident recurrent stroke (HR: 0.83; 95% CI: 0.75-0.93, p = 0.0009; I2 = 0%), recurrent ischemic stroke (HR: 0.79; 95% CI: 0.71-0.89, p < 0.0001; I2 = 0%) among patients with a history of acute ischemic stroke (AIS) or transient ischemic attack (TIA). There were no significant differences in safety outcomes. CONCLUSION: Ticagrelor is slightly better than clopidogrel and aspirin in preventing stroke, especially ischemic stroke, with significant safety risks. For patients with a history of AIS/TIA, the use of ticagrelor was superior to the use of clopidogrel or aspirin in reducing the risk of subsequent stroke. We believe that ticagrelor is a potential alternative to aspirin or clopidogrel in some cases, especially for patients with CYP2C19 deficiency.


Assuntos
Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Aspirina/efeitos adversos , Clopidogrel/uso terapêutico , Ticagrelor/uso terapêutico , Ataque Isquêmico Transitório/complicações , Inibidores da Agregação Plaquetária/efeitos adversos , Quimioterapia Combinada , Acidente Vascular Cerebral/complicações , Hemorragia/induzido quimicamente , Hemorragia/complicações , Hemorragia/tratamento farmacológico , Hemorragias Intracranianas/complicações , Resultado do Tratamento
3.
Mov Disord ; 37(3): 545-552, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34820915

RESUMO

BACKGROUND: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations. OBJECTIVE: We aimed to explore the potential causative gene for PKD. METHODS: A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing. RESULTS: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups. CONCLUSIONS: We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.


Assuntos
Coreia , Distonia , Proteínas de Membrana , Adolescente , Criança , Feminino , Humanos , Masculino , Coreia/genética , Distonia/genética , Proteínas de Membrana/metabolismo , Mutação/genética , Fenótipo
4.
Proc Natl Acad Sci U S A ; 116(28): 14019-14028, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31235588

RESUMO

It is well recognized that metastasis can occur early in the course of lung adenocarcinoma (LAD) development, and yet the molecular mechanisms driving this capability of rapid metastasis remain incompletely understood. Here we reported that a long noncoding RNA, LINC00673, was up-regulated in LAD cells. Of note, we first found that LINC00673-v4 was the most abundant transcript of LINC00673 in LAD cells and its expression was associated with adverse clinical outcome of LAD. In vitro and in vivo experiments demonstrated that LINC00673-v4 enhanced invasiveness, migration, and metastasis of LAD cells. Mechanistically, LINC00673-v4 augmented the interaction between DDX3 and CK1ε and thus the phosphorylation of dishevelled, which subsequently activated WNT/ß-catenin signaling and consequently caused aggressiveness of LAD. Antagonizing LINC00673-v4 suppressed LAD metastasis in vivo. Together, our data suggest that LINC00673-v4 is a driver molecule for metastasis via constitutively activating WNT/ß-catenin signaling in LAD and may represent a potential therapeutic target against the metastasis of LAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Caseína Quinase 1 épsilon/genética , RNA Helicases DEAD-box/genética , RNA Longo não Codificante/genética , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Ativação Transcricional , Via de Sinalização Wnt/genética
5.
Inorg Chem ; 60(8): 5771-5778, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33780618

RESUMO

The discovery of pyramidal inversion has continued to impact modern organic and organometallic chemistry. Sequential alkylation reactions of an N-heterocyclic carbene (NHC) ligated dicarbondiphosphide 1 with RI (R = Me, Et, or iBu) and ZnMe2 give rise to the highly stereoselective synthesis of cis-1,3-diphosphetanes 3. cis-3 is conformationally favorable at room temperature, whereas inversion to trans-3 is observed at 110 °C. One-electron oxidation of cis-3 with Fc+(BArF) (Fc = [Fe(C5H5)2]; BArF = [B(3,5-(CF3)2C6H3)4)]-) leads to the stereoselective formation of trans-1,3-diphosphetane radical cation salts 3•+(BArF), which can be reversibly transformed to cis-3 upon one-electron reduction. Salts 3•+(BArF) represent the first examples of 1,3-diphosphetane radical cations. These results provide a potential application of planar four-membered heterocycle-based building blocks for electrically fueled molecular switches.

6.
BMC Infect Dis ; 21(1): 1156, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34775956

RESUMO

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.


Assuntos
Antibacterianos , Infecções Pneumocócicas , Antibacterianos/uso terapêutico , Criança , China/epidemiologia , Humanos , Lactente , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/epidemiologia , Prescrições , Estudos Retrospectivos
7.
Clin Infect Dis ; 71(8): 1943-1946, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32301964

RESUMO

BACKGROUND: Since December 2019, SARS-CoV-2 has extended to most parts of China with >80 000 cases and to at least 100 countries with >60 000 international cases as of 15 March 2020. Here we used a household cohort study to determine the features of household transmission of COVID-19. METHODS: A total of 105 index patients and 392 household contacts were enrolled. Both index patients and household members were tested by SARS-CoV-2 RT-PCR. Information on all recruited individuals was extracted from medical records and confirmed or supplemented by telephone interviews. The baseline characteristics of index cases and contact patients were described. Secondary attack rates of SARS-CoV-2 to contact members were computed and the risk factors for transmission within the household were estimated. RESULTS: Secondary transmission of SARS-CoV-2 developed in 64 of 392 household contacts (16.3%). The secondary attack rate to children was 4% compared with 17.1% for adults. The secondary attack rate to the contacts within the households with index patients quarantined by themselves since onset of symptoms was 0% compared with 16.9% for contacts without quarantined index patients. The secondary attack rate to contacts who were spouses of index cases was 27.8% compared with 17.3% for other adult members in the households. CONCLUSIONS: The secondary attack rate of SARS-CoV-2 in household is 16.3%. Age of household contacts and spousal relationship to the index case are risk factors for transmission of SARS-CoV-2 within a household. Quarantine of index patients at home since onset of symptoms is useful to prevent the transmission of SARS-Co-2 within a household.


Assuntos
Infecções por Coronavirus/transmissão , Características da Família , Pneumonia Viral/transmissão , Adolescente , Adulto , Betacoronavirus , COVID-19 , Criança , Pré-Escolar , Estudos de Coortes , Infecções Comunitárias Adquiridas/transmissão , Busca de Comunicante/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Fatores de Tempo , Adulto Jovem
8.
Angew Chem Int Ed Engl ; 59(52): 23830-23835, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-32914528

RESUMO

Distonic radical cations (DRCs) with spatially separated charge and radical sites have, so far, largely been observed by gas-phase mass spectrometry and/or matrix isolation spectroscopy work. Herein, we disclose the isolation of a crystalline dicarbondiphosphide-based ß-distonic radical cation salt 3.+ (BARF) (BARF=[B(3,5-(CF3 )2 C6 H3 )4 )]- ) stable at room temperature and formed by a one-electron-oxidation-induced intramolecular skeletal rearrangement reaction. Such a species has been validated by electron paramagnetic resonance (EPR) spectroscopy, single-crystal X-ray diffraction, UV/Vis spectroscopy and density functional theory (DFT) calculations. Compound 3.+ (BARF) exhibits a large majority of spin density at a two-coordinate phosphorus atom (0.74 a.u.) and a cationic charge located predominantly at the four-coordinate phosphorus atom (1.53 a.u.), which are separated by one carbon atom. This species represents an isolable entity of a phosphorus radical cation that is the closest to a genuine phosphorus DRC to date.

9.
J Cell Mol Med ; 23(3): 1852-1864, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30515972

RESUMO

Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumours, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of their specific association with NSCLC have not been fully elucidated. Here, we report that a cytoplasmic lncRNA, DUXAP9-206 is overexpressed in NSCLC cells and closely related to NSCLC clinical features and poor patient survival. We reveal that DUXAP9-206 induced NSCLC cell proliferation and metastasis by directly interacting with Cbl-b, an E3 ubiquitin ligase, and reducing the degradation of epidermal growth factor receptor (EGFR) and thereby augmenting EGFR signaling in NSCLC. Notably, correlations between DUXAP9-206 and activated EGFR signaling were also validated in NSCLC patient specimens. Collectively, our findings reveal the novel molecular mechanisms of DUXAP9-206 in mediating the progression of NSCLC and DUXAP9-206 may serve as a potential target for NSCLC therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/secundário , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-cbl/metabolismo , RNA Longo não Codificante/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Proteínas Proto-Oncogênicas c-cbl/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Mov Disord ; 34(1): 138-141, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30485547

RESUMO

OBJECTIVE: Lymphocyte activation gene-3 (LAG-3) could mediate pathological α-synuclein transmission in neurodegeneration and may be involved in the pathogenesis of Parkinson's disease (PD). The aim of the present study was to explore soluble LAG-3 (sLAG-3) as a potential diagnostic biomarker for PD. METHODS: Serum sLAG-3 concentrations were measured by a quantitative ELISA for patients with PD, essential tremor (ET) and age- and sex-matched controls. The relationships between sLAG-3 and clinical phenotype were assessed via correlation analysis and logistic regression. RESULTS: Serum sLAG-3 levels in patients with PD were significantly higher than those in ET patients and age- and sex-matched controls. The area under the curve of serum sLAG-3 in differentiating PD from age- and sex-matched controls was 0.82. Serum sLAG-3 was associated with non-motor symptoms and excessive daytime sleep. CONCLUSION: sLAG-3 is a candidate novel biomarker for PD. © 2018 International Parkinson and Movement Disorder Society.


Assuntos
Antígenos CD/sangue , Tremor Essencial/sangue , Ativação Linfocitária/fisiologia , Doença de Parkinson/sangue , Biomarcadores/sangue , Tremor Essencial/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Fenótipo , Proteína do Gene 3 de Ativação de Linfócitos
11.
Chemistry ; 24(45): 11627-11636, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-29992671

RESUMO

A new phosphor of the type Gd8(1-x) Eu8 x V2 O17 (x=0-1.0) was synthesized through the solid-state reaction ceramics method. A pure phase formation was verified by using X-ray powder diffraction measurements. The luminescence of Gd8 V2 O17 :Eu3+ was investigated through optical and laser excitation spectroscopy. The luminescence curves were investigated in the temperature region 10 to 300 K. Gd8 V2 O17 shows a self-activated luminescence under excitation with UV- and near-UV light. The spectra, the decay lifetimes, and the thermal stability of Gd8(1-x) Eu8 x V2 O17 (x=0.005-1.0) strongly depend on both the Eu3+ concentration and the temperature. The tunable luminescence is realized by controlling the Eu3+ -doping level to adjust the host energy-transfer efficiency from the VO43- groups to the Eu3+ activators. At low Eu3+ concentrations (<30 mol %), the intensity and lifetime show an unusual change with an increase of the temperature from 10-300 K, that is, the luminescence experiences a straightforward enhancement. The energy transfer from the VO43- group to the Eu3+ ions could be accelerated with an increase of the temperature resulting in an unusual enhancement of the Eu3+ luminescence and lifetime. However, the emission of the Eu3+ ions decreased for highly Eu-doped samples (>30 mol %) with an increase of the temperature. The luminescence mechanism was discussed on the basis of the charge-transfer band of the Eu3+ ions, the doping concentration, and the proposed microstructures in the lattices.

12.
Nat Rev Drug Discov ; 23(8): 583-606, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38982305

RESUMO

Reactive oxygen species (ROS) in biological systems are transient but essential molecules that are generated and eliminated by a complex set of delicately balanced molecular machineries. Disruption of redox homeostasis has been associated with various human diseases, especially cancer, in which increased ROS levels are thought to have a major role in tumour development and progression. As such, modulation of cellular redox status by targeting ROS and their regulatory machineries is considered a promising therapeutic strategy for cancer treatment. Recently, there has been major progress in this field, including the discovery of novel redox signalling pathways that affect the metabolism of tumour cells as well as immune cells in the tumour microenvironment, and the intriguing ROS regulation of biomolecular phase separation. Progress has also been made in exploring redox regulation in cancer stem cells, the role of ROS in determining cell fate and new anticancer agents that target ROS. This Review discusses these research developments and their implications for cancer therapy and drug discovery, as well as emerging concepts, paradoxes and future perspectives.


Assuntos
Antineoplásicos , Neoplasias , Espécies Reativas de Oxigênio , Humanos , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Animais , Microambiente Tumoral/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Descoberta de Drogas , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo
13.
Dalton Trans ; 53(12): 5608-5615, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38439621

RESUMO

Profound insight into the electronic structures of occasionally observed µ2-P bridging phosphinines remains limited. In this work, we present the isolation and X-ray crystallographic characterization of a dimeric Rh(I) phosphinine complex exhibiting both η1-P and µ2-P phosphinine coordination modes. Variable temperature NMR analyses and DOSY spectrum measurement confirmed the presence of two types of fluxional phenomena in solution: η1-P phosphinine bonding and dissociation, and η1-P and µ2-P equilibrium. DFT calculations in conjunction with single crystal X-ray diffraction studies suggest that the µ2-P phosphinines donate four electrons via a σ-lone pair and a high-lying π-type electron pair, instead of two σ-lone pairs, forming σ- and π-three-center-two-electron bonds. The stronger π-type interactions lead to longer P-C bonds and larger negative coordination chemical shifts for µ2-P phosphinines. However, the binding interactions of µ2-P are thermodynamically weaker than those of η1-P. Reactivity studies further confirm the labile nature of the µ2-P phosphinine bonds, which could be easily converted to an η1-P phosphinine.

14.
Chem Sci ; 15(14): 5376-5384, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38577367

RESUMO

Distonic radical cations (DRCs) with spatially separated charge and radical sites are expected to show both radical and cationic reactivity at different sites within one molecule. However, such "dual" reactivity has rarely been observed in the condensed phase. Herein we report the isolation of crystalline 1λ2,3λ2-1-phosphonia-3-phosphinyl-cyclohex-4-enes 2a,b˙+, which can be considered delocalized DRCs and were completely characterized by crystallographic, spectroscopic, and computational methods. These DRCs contain a radical and cationic site with seven and six valence electrons, respectively, which are both stabilized via conjugation, yet remain spatially separated. They exhibit reactivity that differs from that of conventional radical cations (CRCs); specifically they show sequential radical and cationic reactivity at separated sites within one molecule in solution.

15.
Polymers (Basel) ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38675069

RESUMO

Polyether ether ketone (PEEK) is esteemed as a high-performance engineering polymer renowned for its exceptional mechanical properties and thermal stability. Nonetheless, the majority of polymer-based lubricating materials fail to meet the contemporary industrial demands for motion components regarding high speed, heavy loading, temperature resistance, and precise control. Utilizing 3D printing technology to design and fabricate intricately structured components, developing high-performance polymer self-lubricating materials becomes imperative to fulfill the stringent operational requirements of motion mechanisms. This study introduces a novel approach employing 3D printing technology to produce PEEK with varying filling densities and conducting in situ synthesis of zeolitic imidazolate framework (ZIF-8) nanomaterials on its surface to enhance PEEK's frictional performance. The research discusses the synthetic methodology, characterization techniques, and tribological performance evaluation of in situ synthesized ZIF-8 nanomaterials on PEEK surfaces. The findings demonstrate a significant enhancement in frictional performance of the composite material under low-load conditions, achieving a minimum wear rate of 4.68 × 10-6 mm3/N·m compared to the non-grafted PEEK material's wear rate of 1.091 × 10-5 mm3/N·m, an approximately 1.3 times improvement. Detailed characterization and analysis of the worn surface of the steel ring unveil the lubrication mechanism of the ZIF-8 nanoparticles, thereby presenting new prospects for the diversified applications of PEEK.

16.
Orphanet J Rare Dis ; 19(1): 236, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877584

RESUMO

OBJECTIVE: This study aimed to enhance the understanding of the role of estrogen in lymphangioleiomyomatosis(LAM) and to conclude the impact of estrogen-altering events on the condition and recent advances in estrogen-based treatments for LAM. RESULTS: LAM development is strongly linked to mutations in the tuberous sclerosis gene (TSC1/2) and the presence of estrogen. Estrogen plays a significant role in the spread of TSC2-deficient uterine leiomyoma cells to the lungs and the production of pulmonary LAM. Menstruation, pregnancy, estrogen medication, and other events that cause an increase in estrogen levels can trigger the disorder, leading to a sudden worsening of symptoms. Current findings do not support using estrogen-blocking therapy regimens. However, Faslodex, which is an estrogen receptor antagonist, presents new possibilities for future therapeutic approaches in LAM. CONCLUSION: Estrogen is crucial in the development and spread of LAM. The use of estrogen inhibitors or estrogen receptor antagonists alone does not provide good control of the disease or even poses a greater risk, and the use of a combination of mTOR receptor inhibitors, complete estrogen receptor antagonists, estrogen inhibitors, and autophagy inhibitors targeting important signaling pathways in LAM pathogenesis may be of greater benefit to the patient.


Assuntos
Estrogênios , Linfangioleiomiomatose , Linfangioleiomiomatose/metabolismo , Linfangioleiomiomatose/tratamento farmacológico , Linfangioleiomiomatose/patologia , Linfangioleiomiomatose/genética , Humanos , Estrogênios/metabolismo , Feminino
17.
Emerg Microbes Infect ; 13(1): 2332670, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38646911

RESUMO

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.


Assuntos
Antibacterianos , Tipagem de Sequências Multilocus , Infecções Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Antibacterianos/farmacologia , China/epidemiologia , População do Leste Asiático , Hospitais/estatística & dados numéricos , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/mortalidade , Estudos Prospectivos , Fatores de Risco , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/isolamento & purificação
18.
Orthop Surg ; 15(7): 1719-1729, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37154088

RESUMO

BACKGROUND: Hemiarthroplasty is the standard treatment for patients with femoral neck fractures (FNFs). Controversy exists over the use of bone cement in hip fractures treated with hemiarthroplasty. OBJECTIVE: We performed an updated systematic review and meta-analysis to compare cemented and uncemented hemiarthroplasty in patients with femoral neck fractures. METHODS: A literature review was conducted using Cochrane Library, ScienceDirect, PubMed, Embase, Medline, Web of Science, CNKI, VIP, Wang Fang, and Sino Med databases. Studies comparing cemented with uncemented hemiarthroplasty for FNFs in elderly patients up to June 2022 were included. Data were extracted, meta-analyzed, and pooled as risk ratios (RRs) and weighted mean differences (WMDs) with a 95% confidence interval (95% CI). RESULTS: Twenty-four RCTs involving 3471 patients (1749 cement; 1722 uncemented) were analyzed. Patients with cemented intervention had better outcomes regarding hip function, pain, and complications. Significant differences were found in terms of HHS at 6 weeks (WMD 12.5; 95% CI 6.0-17.0; P < 0.001), 3 months (WMD 3.3; 95% CI 1.6-5.0; P < 0.001), 4 months (WMD 7.3; 95% CI 3.4-11.2; P < 0.001), and 6 months (WMD 4.6; 95% CI 3.3-5.8; P < 0.001) postoperatively. Patients with cemented hemiarthroplasty had lower rates of pain (RR 0.59; 95% CI 0.39-0.9; P = 0.013), prosthetic fracture (RR 0.24; 95% CI 0.16-0.38; P < 0.001), subsidence/loosening (RR 0.29; 95% CI 0.11-0.78; P = 0.014), revisions (RR 0.59; 95% CI 0.40-0.89; P = 0.012), and pressure ulcers (RR 0.43; 95% CI 0.23-0.82; P = 0.01) at the expense of longer surgery time (WMD 7.87; 95% CI 5.71-10.02; P < 0.001). CONCLUSION: This meta-analysis demonstrated that patients with cemented hemiarthroplasty had better results in hip function and pain relief and lower complication rates at the expense of prolonged surgery time. Cemented hemiarthroplasty is recommended based on our findings.


Assuntos
Artroplastia de Quadril , Fraturas do Colo Femoral , Hemiartroplastia , Fraturas do Quadril , Humanos , Idoso , Hemiartroplastia/métodos , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fraturas do Colo Femoral/cirurgia , Fraturas do Colo Femoral/etiologia , Fraturas do Quadril/cirurgia , Cimentos Ósseos/efeitos adversos , Resultado do Tratamento , Artroplastia de Quadril/métodos
19.
Chem Sci ; 14(39): 10944-10952, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37829033

RESUMO

E,Z-isomers display distinct physical properties and chemical reactivities. However, investigations on heavy main group elements remain limited. In this work, we present the isolation and X-ray crystallographic characterization of N-heterocyclic vinyl (NHV) substituted diphosphenes as both E- and Z-isomers (L[double bond, length as m-dash]CH-P[double bond, length as m-dash]P-CH[double bond, length as m-dash]L, E,Z-2b; L = N-heterocyclic carbene). E-2b is thermodynamically more stable and undergoes reversible photo-stimulated isomerization to Z-2b. The less stable Z-isomer Z-2b can be thermally reverted to E-2b. Theoretical studies support the view that this E ↔ Z isomerization proceeds via P[double bond, length as m-dash]P bond rotation, reminiscent of the isomerization observed in alkenes. Furthermore, both E,Z-2b coordinate to an AuCl fragment affording the complex [AuCl(η2-Z-2b)] with the diphosphene ligand in Z-conformation, exclusively. In contrast, E,Z-2b undergo [2 + 4] and [2 + 1] cycloadditions with dienes or diazo compounds, respectively, yielding identical cycloaddition products in which the phosphorus bound NHV groups are in trans-position to each other. DFT calculations provide insight into the E/Z-isomerisation and stereoselective formation of Au(i) complexes and cycloaddition products.

20.
Front Med (Lausanne) ; 10: 1106412, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36999075

RESUMO

Background: Tuberculosis (TB) is a threat to public health that mostly affects people in developing countries. TB presenting as a soft tissue mass is rare and is usually seen in patients with muscular tuberculosis (MT). Case presentation: In this study, we present the clinical, radiographic, and pathological features of two cases and retrospective evaluations of an additional 28 patients who were diagnosed with MT. More patients were men (60.9%) than women (39.1%), with a male-to-female ratio of 1.6:1. The average age among male and female patients was 38.9 and 30.1 years, respectively. MT usually presents with painful or painless muscular nodules on the lower limbs. Imaging findings, including ultrasound, CT, and MRI, can be used to identify lesions and sites for biopsy. The most typical histopathological feature of MT is granulomatous inflammation with caseous necrosis and epithelioid granulomata. Acid-fast bacilli stain and polymerase chain reaction (PCR) assays are helpful in identifying tubercle bacillus. Conclusion: We describe two MT cases with lower-extremity muscular masses as the initial presentation. The results suggest that muscle biopsy and pathological analysis remain necessary for diagnosis. Most of the patients could be cured with standard antituberculosis therapy.

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