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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(9): 775-780, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34533123

RESUMO

Objective To investigate the effect of necrostatin-1 on locomotor recovery after spinal cord injury (SCI) in mice, and to explore the role of apoptosis and M1 type-microglia/macrophage-mediated pro-inflammation in the protective effect. Methods Male C57BL/6 mice were randomly divided into four groups: control group, necrostatin-1 group, SCI model group, necrostatin-1-treated group after SCI, with 20 mice in each. For SCI model group, mice were anesthetized with 10 g/L pentobarbital sodium with a dose of 8 mL/kg. After skin disinfection, T8 laminectomy was performed under operating microscope, and the T8 spinal cord was clearly revealed. The injury model was established with a device designed by our own with the parameter at 0.2 mm-width for 20 seconds. Manual urination was performed once a day. For necrostatin-1-treated group after SCI, 7.8 mg/kg of necrostatin-1 was intravenously administrated at the 1, 2, and 3 days after SCI. For necrostatin-1 group, necrostatin-1 was intravenously injected for three days. Basso Mouse Scale(BMS) score and standardized rump-height index were used to evaluate locomotor function at 1-, 3-, 5-, 7-, 10- and 14-day after injury. To observe cell apoptosis in injured cord, TUNEL staining was performed at 1-, 3-, 7-, and 14-day after injury. Western blot and immunohistochemical staining were performed to detect the expression of inducible nitric oxide synthase (iNOS), a classical marker of M1 type microglia/macrophage. Real time quantitative PCR was used to detect mRNA levels of TNF-α, interleukin-1ß (IL-1ß), IL-18, IL-4, IL-5, and IL-10. Results Necrostatin-1 significantly promoted the locomotor recovery in mice after SCI, reduced cell apoptosis around the SCI area; decreased the protein expression of M1 type microglia/macrophage marker iNOS and the number of iNOS-positive microglia/macrophage, and down-regulated the transcription levels of pro-inflammatory cytokines TNF-α, IL-18, and IL-1ß, while promoting the transcription of anti-inflammatory cytokines IL-4, IL-5, and IL-10. Conclusion Necrostatin-1 significantly promotes locomotor function recovery after SCI in mice by reducing the number of apoptotic cells and inhibiting M1 microglia/macrophages-mediated pro-inflammatory factors.


Assuntos
Microglia , Traumatismos da Medula Espinal , Animais , Apoptose , Imidazóis , Indóis , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Recuperação de Função Fisiológica , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico
2.
Neoplasia ; 23(11): 1078-1088, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34583246

RESUMO

OBJECTIVES: Current standard of care imaging, cytology, or cystic fluid analysis cannot reliably differentiate malignant from benign pancreatic cystic neoplasms. This study sought to determine if the metabolic profile of cystic fluid could distinguish benign and malignant lesions, as well as mucinous and non-mucinous lesions. METHODS: Metabolic profiling by untargeted mass spectrometry and quantitative nuclear magnetic resonance was performed in 24 pancreatic cyst fluid from surgically resected samples with pathological diagnoses and clinicopathological correlation. RESULTS: (Iso)-butyrylcarnitine distinguished malignant from benign pancreatic cysts, with a diagnostic accuracy of 89%. (Iso)-butyrylcarnitine was 28-fold more abundant in malignant cyst fluid compared with benign cyst fluid (P=.048). Furthermore, 5-oxoproline (P=.01) differentiated mucinous from non-mucinous cysts with a diagnostic accuracy of 90%, better than glucose (82% accuracy), a previously described metabolite that distinguishes mucinous from non-mucinous cysts. Combined analysis of glucose and 5-oxoproline did not improve the diagnostic accuracy. In comparison, standard of care cyst fluid carcinoembryonic antigen (CEA) and cytology had a diagnostic accuracy of 40% and 60% respectively for mucinous cysts. (Iso)-butyrylcarnitine and 5-oxoproline correlated with cyst fluid CEA levels (P<.0001 and P<.05 respectively). For diagnosing malignant pancreatic cysts, the diagnostic accuracies of cyst size > 3 cm, ≥ 1 high-risk features, cyst fluid CEA, and cytology are 38%, 75%, 80%, and 75%, respectively. CONCLUSIONS: (Iso)-butyrylcarnitine has potential clinical application for accurately distinguishing malignant from benign pancreatic cysts, and 5-oxoproline for distinguishing mucinous from non-mucinous cysts.

3.
J Med Chem ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34590489

RESUMO

Hepatocellular carcinoma (HCC) is rising steadily in incidence, and more effective methods are needed for early detection and image-guided surgery. Glypican-3 (GPC3) is a cell surface biomarker that is overexpressed in early-stage cancer but not in cirrhosis. An IRDye800-labeled 12-mer amino acid sequence was identified, and specific binding to GPC3 was validated in vitro and in orthotopically implanted HCC tumors in vivo. Over 4-fold greater binding affinity and 2-fold faster kinetics were measured by comparison with previous GPC3 peptides. Photoacoustic images showed peak tumor uptake at 1.5 h post-injection and clearance within ∼24 h. Laparoscopic and whole-body fluorescence images showed strong intensity from tumor versus adjacent liver with about a 2-fold increase. Immunofluorescence staining of human liver specimens demonstrated specific binding to HCC versus cirrhosis with 79% sensitivity and 79% specificity, and normal liver with 81% sensitivity and 84% specificity. The near-infrared peptide is promising for early HCC detection in clinical trials.

4.
Front Cell Infect Microbiol ; 11: 687827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557424

RESUMO

Background: Gut microbiota dysbiosis can contribute to the progression of atherosclerosis. We investigated the association of the gut microbiota and the severity of coronary artery lesions and prognosis of patients with ACS. Methods: In this case-control study, 402 ACS patients and 100 controls were enrolled from June 2017 to December 2018. The number of bacterial species was determined by real-time PCR. A SYNTAX score was calculated for all ACS patients based on their coronary angiography results. Results: Compared with the healthy controls, the gut microbial levels in Escherichia coli, Streptococcus, and Enterobacteriaceae were significantly increased in ACS patients, while the Lactobacillus level was significantly decreased. Lactobacillus level was as an independent predictor of disease severity on the coronary angiography [high vs. low SYNTAX score: adjusted odds ratio (aOR) = 0.024, 95% confidence interval (CI): 0.004-0.155] and myocardial necrosis [high vs. low cardiac troponin T (cTNT): aOR = 0.317, 95% CI: 0.099-0.914]. Subsequently, a higher Lactobacillus level was associated with a lower risk of an all-cause death [adjusted hazard ratio (aHR) = 0.239; 95% CI: 0.093-0.617] and major adverse cardiac events (MACE) in ACS patients (aHR = 0.208; 95% CI: 0.081-0.531). After stratifying by the type of ACS, a higher Lactobacillus level was significantly associated with the decreased risks of high SYNTAX score, all-cause death, and MACE in the STEMI subgroup but not in the NSTEMI and UAP subgroups. Conclusions: Lower Lactobacillus levels may indicate a higher risk of a more severe coronary atherosclerotic lesions and myocardial necrosis and worse prognosis for patients with ACS, particularly in the STEMI subgroup.

5.
Anal Chem ; 93(34): 11686-11691, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34461728

RESUMO

Single-nanoparticle-level sensing allows us to measure individual molecular interactions and probe environmental stimuli at nanometer-scale resolution. Despite these premises, limited success has been met hitherto due to the demanding challenge to distinguish a dimmed signal from a noisy background. Here, we describe an approach for high-sensitivity single-nanoparticle-level sensing of divalent copper (Cu2+) ions through near-infrared-to-visible upconversion luminescence against a near-null background. This nanosensor utilizes ytterbium- (Yb3+) and erbium (Er3+)-doped sodium yttrium fluoride (NaYF4) upconversion nanoparticles (UCNPs) (maximal emission at 540 nm when excited at 980 nm) as an energy donor, of which the surface attaches Cu2+-dependent DNAzymes labeled with BHQ1 dye (Black Hole Quencher 1, maximal absorption at 548 nm) as energy acceptors. Adding a hint amount of Cu2+ ions resulted in the cleavage of a BHQ1-containing moiety in DNAzymes, thus turning on upconversion luminescence for sensitive detection. Indeed, this approach allows us to perform single-nanoparticle-level detection of Cu2+ ions with extraordinary signal-to-noise ratios (SNRs, >277) for all measured concentrations that cover 3 orders of magnitude (from sub-nM to µM). Importantly, a limit of detection of 220 pM was achieved, about sevenfold lower than the one at the ensemble level. Moreover, a stochastic particle-to-particle sensing behavior was also identified, featuring single-nanoparticle-level detection. This work untaps the usage of UCNPs for high-sensitivity single-nanoparticle-level biosensing.


Assuntos
Cobre , Nanopartículas , Érbio , Fluoretos , Itérbio , Ítrio
6.
J Clin Lab Anal ; : e23972, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465008

RESUMO

The aim of the current study was to establish a simple method for effectively inducing memory T lymphocytes by the intraperitoneal injection of spleen lymphocytes into mice. In total, 75 mice were divided into the following groups: an injection group administered three doses of spleen lymphocytes (1 × 106 , 5 × 106 , and 1 × 107 cells), a transplantation group in which a 0.25-cm2 skin section from C57BL/6 mice was transplanted onto the back of the recipient, and a control group in which an equal volume of phosphate-buffered saline was injected. At 1, 2, or 3 months following transplantation, the following parameters were evaluated: quantity of T lymphocytes, percentage of cluster of differentiation 8+ (CD8+ ) memory T cells, and proliferation index of purified CD8+ memory T cells. No significant differences among groups were detected at 1 month (p > .05). However, the injection group administered 1 × 106 cells exhibited the highest proportion of CD8+ memory T cells among all groups at 2 months, and the proportions of CD8+ T cells were higher in the three injection groups than in the skin transplantation and control groups at 3 months. The proportions of memory T cells were higher in the injection groups administered 5 × 106 or 1 × 107 cells than in the skin transplantation and control groups at 3 months. The newly established method effectively induces memory T lymphocytes via the intraperitoneal injection of spleen lymphocytes in vivo and has potential applications in the field of immunotherapy.

7.
J Healthc Eng ; 2021: 1234003, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457215

RESUMO

To investigate the application and evaluation of effective quality management by objectives in patient care for persistent vacuum sealing drainage (VSD), a total of 164 patients with fractures of the hands and feet combined with soft tissue damage admitted to the department of hand and foot surgery in a provincial tertiary hospital from January 2018 to January 2020 were selected as study subjects. The patients were randomly divided into observation and control groups based on the types of fractures, with 82 patients in each group, and both groups underwent VSD surgery for treatment. Both of the groups were cared for VSD using the original nursing model and were compared in terms of treatment compliance, wound recovery, the occurrence of complications, and patient satisfaction with nursing work. The treatment compliance of patients in the observation group was higher than that of the control group (P < 0.05). Moreover, the wound healing condition in the observation group and the postoperative wound recovery data were better. The hospitalization time and the number of replacement suckers were less (P < 0.05), which met the requirements of statistical research. This confirmed that the application of quality management by objectives in patient care can improve patient compliance with treatment, promote wound healing, reduce the occurrence of corresponding postoperative complications in patients, and improve patient satisfaction with health nursing, which can be promoted for use in the workplace.

8.
Anal Biochem ; 630: 114341, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34411551

RESUMO

Simple, rapid, and accurate detection of the Mycobacterium tuberculosis complex (MTBC) and drug resistance is critical for improving patient care and decreasing the spread of tuberculosis. To this end, we have developed a new simple and rapid molecular method, which combines multienzyme isothermal rapid amplification and a lateral flow strip, to detect MTBC and simultaneously detect rifampin (RIF) resistance. Our findings showed that it has sufficient sensitivity and specificity for discriminating 118 MTBC strains from 51 non-tuberculosis mycobacteria strains and 11 of the most common respiratory tract bacteria. Further, compared to drug susceptibility testing, the assay has a sensitivity, specificity, and accuracy of 54.1%, 100.0%, and 75.2%, respectively, for detection of RIF resistance. Some of the advantages of this assay are that no special instrumentation is required, a constant low temperature of 39 °C is sufficient for the reaction, the turnaround time is less than 20 min from the start of the reaction to read out and the result can be seen with the naked eye and does not require specialized training. These characteristics of the new assay make it particularly useful for detecting MTBC and RIF resistance in resource-limited settings.

9.
J Fungi (Basel) ; 7(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34356957

RESUMO

Despite desert ecosystem being crucial to our understanding of natural geography, species evolution and global climate change, there is limited information on the dynamics of their composition and the diversity of endophytic fungi communities driven by plant identity and organ differentiation. Here, an extensive investigation of endophytic fungal microbiome in root, stem, and leaf organs associated with five xerophyte shrubs in an extremely arid desert, Northwest China, were examined. The fungal community dominated by Dothideomycetes and Pleosporales. Shrub species strongly drive the niche-based processes of endophytic fungi across the root, stem and leaf compartments. The diversity and composition of endophytic fungi in stem showed higher variability among plant species than leaf and root. The fungal communities in root libraries were more diverse and exhibited a remarkable differentiation of community composition. We further demonstrated the significant host preferences and tissue specificity of desert endophytic fungi, and unique specific taxa were also observed. The co-occurrence network revealed the coexistence of fungal endophytes in arid desert, and the root fungal network harbored the highest interspecies connectivity. Members of Pleosporales were the most common keystone species in the root fungal network. This is the first report of mycobiota in both plant species and organ differentiation in an extremely arid desert ecosystem.

10.
J Am Chem Soc ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449204

RESUMO

The cationic complex BeOCO+ is produced in a solid neon matrix. Infrared absorption spectroscopic study shows that it has a very high antisymmetric OCO stretching vibration of 2418.9 cm-1, which is about 71 cm-1 blue-shifted from that of free CO2. The quantum chemical calculations are in very good agreement with the experimental observation. Depending on the theoretical method, a linear or quasi-linear structure is predicted for the cation. The analysis of the electronic structure shows that the bonding of Be+ to one oxygen atom induces very little charge migration between the two moieties, but it causes a significant change in the σ-charge distribution that strengthens the terminal C-O bond, leading to the observed blue shift. The bonding analysis reveals that the Be+ ← OCO donation results in strong binding due to the interference of the wave function and a charge polarization within the CO2 fragment and hybridization to Be+ but only negligible charge donation.

11.
Neuroreport ; 32(14): 1223-1228, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34406991

RESUMO

OBJECTIVES: To assess the cognitive impairment in patients with type 2 diabetes mellitus (T2DM) using mismatch negativity (MMN) and to explore the relationship between cognitive impairment and diabetic peripheral neuropathy (DPN). METHODS: Sixty-six T2DM patients and 40 healthy controls were included. For each participant, mini-mental state examination (MMSE) was applied to assess the general cognitive function and MMN was elicited. T2DM patients were divided into two subgroups: subgroup DPN-, patients without DPN; subgroup DPN+, patients with DPN. The MMSE scores, MMN amplitudes and latencies were compared between the T2DM group and the control group using univariate analysis of variance procedures, and also among the controls, subgroup DPN- and subgroup DPN+. Pearson's correlation coefficients (r) were used to analyze potential confounding clinical factors associated with MMN. RESULTS: T2DM patients had significantly lower MMSE scores compared with controls (23.25 ± 2.86 vs. 27.15 ± 1.83; P < 0.01), whereas those of the two subgroups were not significantly different. Both subgroup DPN+ and DPN- had longer latencies and lower amplitudes of MMN than the controls. The latencies of MMN were significantly longer in subgroup DPN+ compared with subgroup DPN-. The latency of MMN was positively correlated with the duration of the disease. CONCLUSION: Cognitive decline exists in patients with T2DM irrespective of the presence of DPN. Patients with DPN may have more severe cognitive dysfunction than those without DPN. MMN may be a promising tool for evaluating cognitive function.

12.
J Proteomics ; 247: 104333, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34298185

RESUMO

Di-n-butyl phthalate (DBP), a common compound of phthalates, can pose a risk to humans as a contaminant in the food industry. At present, the molecular mechanism of gene and protein toxicity caused by DBP in human cells is unclear. This in vitro study investigated the potential of inactivated Lactobacillus acidophilus NCFM in alleviating the damage caused by DBP in Caco-2 cells. According to the results from transcriptome and proteome analyses, the Caco-2 cells treated by DBP was resulted finally endoplasmic reticulum stress and mitochondrial oxidative damage. The most important differentially expressed genes and proteins involved in Caco-2 cells treated with NCFM to relieve DBP's cytotoxicity were TNF, NF-κB, CREB, P21, GADD45, FOS and CASP3. The molecular mechanism of DBP toxicity alleviated by strain NCFM was involved the MAPK pathway, via DBP bind to strain NCFM and avoid the activation of TNF receptor by DBP, so down-regulated the NF-κB, CREB, P21, GADD45, and CASP3, relieving the apoptosis of Caco-2 cells. Overall, our data provide new insights into detoxification of phthalate by using Lactobacillus. SIGNIFICANCE: Here we sequenced and assembled the transcriptome from Caco-2 cells which were treated with 4 groups: Control, DBP, strain NCFM, and strain NCFM+DBP groups, and combined it with proteome to characterize DBP detoxification genes/proteins through multiomics analysis. The cell viability in DBP treated groups were significantly increased by NCFM strain, indicating NCFM strain has the ability to alleviate the cytotoxicity of DBP via their binding ability with toxins. Furthermore, the results of transcriptome and proteome analysis showed that the signaling pathway of strain NCFM can alleviate DBP toxicity through MAPK pathway, and the potential biomarkers were identified too. This research may provided new information for developing new detoxification strategies for DBP.

13.
Eur J Endocrinol ; 185(4): K1-K6, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34324429

RESUMO

Background: Many hormones display distinct circadian rhythms, driven by central regulators, hormonal bioavailability, and half-life. A set of 11-oxygenated C19 steroids (11-oxyandrogens) and pregnenolone sulfate (PregS) are elevated in congenital adrenal hyperplasia and other disorders, but their circadian patterns have not been characterized. Participants and methods: Peripheral blood was collected every 2 h over 24 h from healthy volunteer men (10 young, 18-30 years, and 10 older, 60-80 years). We used mass spectrometry to quantify 15 steroids, including androstenedione (A4), testosterone (T), 11ß-hydroxy- and 11-ketotestosterone (11OHT, 11KT),11ß-hydroxy- and 11-ketoandrostenedione (11OHA4, 11KA4), and 4 ∆5-steroid sulfates. Diurnal models including mesor (rhythm adjusted median), peak, and nadir concentrations, acrophase, and amplitude were computed. Results: 11OHA4 followed a rhythm similar to cortisol: acrophase 8:00 h, nadir 21:00 h and were similar in young and old men. 11KT had similar diurnal patterns, but the peak was lower in older than in young men, as was the case for A4. All four steroid sulfates were higher in young vs older men. PregS and 17-hydroxypregnenolone sulfate (17OHPregS) showed sustained elevations between 8:00 and 18:00 h, and nadirs around midnight, while DHEAS and AdiolS displayed minimal diurnal variations. All 4 11-oxyandrogens correlated tightly with cortisol (r from 0.54 for 11OHT to 0.81 for 11OHA4, P < 0.0001 for all), but very weakly with T, supporting their adrenal origin and ACTH governance. Conclusions: 11-Oxyandrogens, PregS, and 17OHPregS display distinct circadian and age variations, which should be accounted for when used as clinical biomarkers.


Assuntos
Androgênios/sangue , Ritmo Circadiano/fisiologia , Sulfatos/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Androgênios/química , Análise Química do Sangue/métodos , Voluntários Saudáveis , Humanos , Hidroxiesteroides/sangue , Cetosteroides/sangue , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Adulto Jovem
14.
J Immunother Cancer ; 9(7)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34321277

RESUMO

Immunotherapy for cancer is now a standard pillar in the armamentarium of treatments for many cancers. Immune checkpoint inhibitors, in particular, have resulted in significant therapeutic benefit and prolongation of survival in solid organ cancers, such as melanoma and lung cancer. However, the extent of benefit is not uniform. There are several groups studying predictors of benefit from these therapies. Recently, there has been a burgeoning interest in studying predictive biomarkers from the blood. These markers include circulating tumor DNA, circulating tumor cells, lymphocyte subpopulations, exosomes and metabolites to name a few. The logistics involved in such biomarker work are complex and rigorous with potential to impact a given study. Such pre-analytic components include development of a rigorous protocol, standard operating procedures for collection and storage of various blood components, ethics of patient consent, personnel involved as well as budget considerations. In this primer, we lay out representative aspects of each of the aforementioned components as a guide to blood-based biomarker research for immunotherapy studies in cancer.

15.
Clin Interv Aging ; 16: 1265-1274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262266

RESUMO

Purpose: Elderly people represent a growing stroke population with different pathophysiological states than younger. Whether intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is beneficial for elderly patients remains unclear. This study compared the efficacy and safety between elderly patients treated with MT alone and those treated with both IVT and MT. Patients and Methods: Patients aged ≥65 years who were eligible for IVT within 4.5 h from symptom onset were selected from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) registry, a prospective registry program for patients with endovascular treatment from 111 Chinese stroke centers. The primary efficacy outcome was the 90-day modified Rankin Scale score. We compared efficacy and safety outcomes using ordinal or binary logistic regression or a generalized linear model. Results: In total, 482 elderly patients were included: 187 (38.8%) received IVT and MT (bridging MT) and 295 (61.2%) received MT alone (direct MT). There was no significant difference in the 90-day modified Rankin Scale score between the two groups (median: 4 vs 4 points, respectively; adjusted ß=-0.048, P=0.822). The direct MT group had a shorter onset-to-puncture time (225 vs 255 min, respectively; adjusted ß=-55.074, P=0.002) and a lower rate of parenchymal hemorrhage type 2 within 24 h (2.80% vs 6.63%, respectively; adjusted odds ratio [OR]=0.287, 95% confidence interval [CI]=0.096-0.856, P=0.025). In addition, the direct MT group showed a trend toward a lower incidence of sICH (5.67% vs 10.06%, adjusted OR=0.453, P=0.061), procedure-related complications (7.12% vs 12.30%, adjusted OR=0.499, P=0.052) and distal or new territorial embolization (4.07% vs 6.95%, adjusted OR=0.450, P=0.093). Conclusion: Direct MT had similar efficacy to bridging MT in terms of the 90-day functional outcome in elderly patients, whereas bridging MT had a longer onset-to-puncture time and increased risk of hemorrhagic transformation and procedure-related complications.


Assuntos
Hemorragia Cerebral , Transtornos Cerebrovasculares , AVC Isquêmico , Trombectomia , Administração Intravenosa , Idoso , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/terapia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , AVC Isquêmico/cirurgia , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Melhoria de Qualidade , Trombectomia/efeitos adversos , Trombectomia/métodos , Terapia Trombolítica/métodos , Fluxo de Trabalho
16.
J Am Chem Soc ; 143(28): 10751-10759, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34232039

RESUMO

Mononuclear Pd(I) species are putative intermediates in Pd-catalyzed reactions, but our knowledge about them is limited due to difficulties in accessing them. Herein, we report the isolation of a Pd(I) amido complex, [(BINAP)Pd(NHArTrip)] (BINAP = 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene, ArTrip = 2,6-bis(2',4',6'-triisopropylphenyl)phenyl), from the reaction of (BINAP)PdCl2 with LiNHArTrip. This Pd(I) amido species has been characterized by X-ray crystallography, electron paramagnetic resonance, and multiedge Pd X-ray absorption spectroscopy. Theoretical study revealed that, while the three-electron-two-center π-interaction between Pd and N in the Pd(I) complex imposes severe Pauli repulsion in its Pd-N bond, pronounced attractive interligand dispersion force aids its stabilization. In accord with its electronic features, reactions of homolytic Pd-N bond cleavage and deprotonation of primary amines are observed on the Pd(I) amido complex.

17.
Org Lett ; 23(15): 5611-5615, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34240601

RESUMO

An efficient cascade reaction of 1-indanylidenemalononitrile with 3-benzylidenebenzofuran-2(3H)-one divergently promoted by DABCO or chiral organocatalyst was developed under mild reaction conditions, and various spiro-dihydrofluorene-benzofuranones were produced in gratifying results, respectively. It is worth noting that both the spiro and axially chiral products can be obtained by tuning the reaction conditions. The mechanism of the transformation was also studied by quantum chemical calculations.

18.
Chemosphere ; 282: 130982, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34111639

RESUMO

Our previous studies have shown that lactic acid bacteria (LABs) can bind and remove di-n-butyl phthalate (DBP), diethyl phthalate, and dioctyl phthalate; three ubiquitous environmental phthalate contaminants. In this study, Lactobacillus acidophilus NCFM was chosen to study the DBP binding mechanism. We found that the three-dimensional structure of the bacterial cell wall, including the carbohydrates and proteins, was essential for DBP adsorption. Peptidoglycan was the main binding component in the cell wall (80.71%), and binding sites exposed to DBP were C-N, N-H, O-H, and C-O bonds. Molecular dynamic (MD) studies demonstrated that hydrophobic interaction plays an important role in DBP adsorption, the chemical sites that influenced the binding in the peptidoglycan model were O2, O3>N1, N2, N3>O1, O4, and the form of adsorption force included hydrogen bonding force, electrostatic force, and van der Waals forces. These theoretical data from the MD simulation were consistent with the experimental results in terms of the ability of this bacterium to bind DBP, so the MD simulation proposed a new way to investigate the mechanisms of phthalate binding to LABs.


Assuntos
Lactobacillus acidophilus , Ácidos Ftálicos , Parede Celular , Dibutilftalato , Peptidoglicano
19.
mSphere ; 6(3): e0050021, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34160234

RESUMO

Klebsiella pneumoniae and the closely related species K. variicola and K. quasipneumoniae are common causes of health care-associated infections, and patients frequently become infected with their intestinal colonizing strain. To assess the association between Klebsiella colonization density and subsequent infections, a case-control study was performed. A multiplex quantitative PCR (qPCR) assay was developed and validated to quantify Klebsiella (K. pneumoniae, K. variicola, and K. quasipneumoniae combined) relative to total bacterial DNA copies in rectal swabs. Cases of Klebsiella infection were identified based on clinical definitions and having a clinical culture isolate and a preceding or coincident colonization isolate with the same wzi capsular sequence type. Controls were colonized patients without subsequent infection and were matched 2:1 to cases based on age, sex, and rectal swab collection date. qPCR from rectal swab samples was used to measure the association between the relative abundance of Klebsiella and subsequent infections. The Klebsiella relative abundance by qPCR was highly correlated with 16S sequencing (ρ = 0.79; P < 0.001). The median Klebsiella relative abundance was higher in cases (15.7% [interquartile range {IQR}, 0.93 to 52.6%]) (n = 83) than in controls (1.01% [IQR, 0.02 to 12.8%]) (n = 155) (P < 0.0001). Adjusting for multiple clinical covariates using inverse probability of treatment weighting, a Klebsiella relative abundance of >22% was associated with infection overall (odds ratio [OR], 2.87 [95% confidence interval {CI}, 1.64 to 5.03]) (P = 0.0003) and with bacteremia in a secondary analysis (OR, 4.137 [95% CI, 1.448 to 11.818]) (P = 0.0084). Measurement of colonization density by qPCR could represent a novel approach to identify hospitalized patients at risk for Klebsiella infection. IMPORTANCE Colonization by bacterial pathogens often precedes infection and offers a window of opportunity to prevent these infections in the first place. Klebsiella colonization is significantly and reproducibly associated with subsequent infection; however, factors that enhance or mitigate this risk in individual patients are unclear. This study developed an assay to measure the density of Klebsiella colonization, relative to total fecal bacteria, in rectal swabs from hospitalized patients. Applying this assay to 238 colonized patients, a high Klebsiella density, defined as >22% of total bacteria, was significantly associated with subsequent infection. Based on widely available PCR technology, this type of assay could be deployed in clinical laboratories to identify patients at an increased risk of Klebsiella infections. As novel therapeutics are developed to eliminate pathogens from the gut microbiome, a rapid Klebsiella colonization density assay could identify patients who would benefit from this type of infection prevention intervention.

20.
mSphere ; 6(3): e0013221, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34160237

RESUMO

Klebsiella commonly colonizes the intestinal tract of hospitalized patients and is a leading cause of health care-associated infections. Colonization is associated with subsequent infection, but the factors determining this progression are unclear. A cohort study was performed, in which intensive care and hematology/oncology patients with Klebsiella colonization based on rectal swab culture were enrolled and monitored for infection for 90 days after a positive swab. Electronic medical records were analyzed for patient factors associated with subsequent infection, and variables of potential significance in a bivariable analysis were used to build a final multivariable model. Concordance between colonizing and infecting isolates was assessed by wzi capsular gene sequencing. Among 2,087 hospitalizations from 1,978 colonized patients, 90 cases of infection (4.3%) were identified. The mean time to infection was 20.6 ± 24.69 (range, 0 to 91; median, 11.5) days. Of 86 typed cases, 68 unique wzi types were identified, and 69 cases (80.2%) were colonized with an isolate of the same type prior to infection. Based on multivariable modeling, overall comorbidities, depression, and low albumin levels at the time of rectal swab collection were independently associated with subsequent Klebsiella infection (i.e., cases). Despite the high diversity of colonizing strains of Klebsiella, there is high concordance with subsequent infecting isolates, and progression to infection is relatively quick. Readily accessible data from the medical record could be used by clinicians to identify colonized patients at an increased risk of subsequent Klebsiella infection. IMPORTANCE Klebsiella is a leading cause of health care-associated infections. Patients who are intestinally colonized with Klebsiella are at a significantly increased risk of subsequent infection, but only a subset of colonized patients progress to disease. Colonization offers a potential window of opportunity to intervene and prevent these infections, if the patients at greatest risk could be identified. To identify patient factors associated with infection in colonized patients, we studied 1,978 colonized patients. We found that patients with a higher burden of underlying disease in general, depression in particular, and low albumin levels in a blood test were more likely to develop infection. However, these variables did not completely predict infection, suggesting that other host and microbial factors may also be important. The clinical variables associated with infection are readily available in the medical record and could serve as the foundation for developing an integrated risk assessment of Klebsiella infection in hospitalized patients.

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