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BACKGROUND: Hearing loss is a prevalent issue resulting from loud noise exposure, aging, diseases, and genetic differences. As individuals age, the likelihood of experiencing hearing loss and depression escalates; yet, the link between hearing loss and the risk of depression remains ambiguous. This study explores the relationship between hearing and depression risk, taking into account sociodemographic and health-related factors. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018, a cross-sectional analysis was conducted, focusing on adult participants. It evaluated their hearing status and depression levels using the Patient Health Questionnaire-9 (PHQ-9). The study examined a range of variables, such as age, gender, socioeconomic status, lifestyle choices, and comorbidities, to understand their influence on the link between hearing loss and depression. RESULTS: Analysis indicated a significant association between moderate to severe hearing loss and an increased risk of depression, notably in older adults. This relationship remained significant even after adjusting for a variety of sociodemographic and health factors. LIMITATIONS: This is a study using the NHANES database using self-reported surveys. CONCLUSION: The findings of this study emphasize the need to integrate hearing health in the holistic assessment and treatment of depression, particularly advocating for combined care strategies for the elderly.
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Cardiac contractility modulation (CCM) is a novel device-based therapy used to treat patients with heart failure with reduced ejection fraction (HFrEF). In both randomized clinical trials and real-life studies, CCM has been shown to improve exercise tolerance and quality of life, reverse left ventricular remodeling, and reduce hospitalization in patients with HFrEF. In this case report, we describe for the first time the use of CCM combined with left bundle branch pacing (LBBP) cardiac resynchronization therapy pacemaker (CRT-P) implantation therapy in a female with a 22-year history of non-ischemic dilated cardiomyopathy. With the optimal medical therapy and cardiac resynchronization therapy (CRT) strategies, the patient's quality of life initially recovered to some extent, but began to deteriorate in the past year. Additionally, heart transplantation was not considered due to economic reasons and late stage systolic heart failure. This is the first case of CCM implantation in Fujian Province and the first report of a combined CCM and left bundle branch pacing CRT-P implantation strategy in a patient with non-ischemic etiology dilated cardiomyopathy in China.
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Terapia de Ressincronização Cardíaca , Cardiomiopatia Dilatada , Insuficiência Cardíaca , Marca-Passo Artificial , Disfunção Ventricular Esquerda , Humanos , Feminino , Insuficiência Cardíaca/terapia , Qualidade de Vida , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/terapia , Volume Sistólico , Resultado do Tratamento , Disfunção Ventricular Esquerda/terapia , Eletrocardiografia , Função Ventricular EsquerdaRESUMO
Studies have reported that Prosaposin (PSAP) is neuroprotective in cerebrovascular diseases. We hypothesized that PSAP would reduce infarct volume by attenuating neuronal apoptosis and promoting cell survival through G protein-coupled receptor 37(GPR37)/PI3K/Akt/ASK1 pathway in middle cerebral artery occlusion (MCAO) rats. Two hundred and thirty-five male and eighteen female Sprague-Dawley rats were used. Recombinant human PSAP (rPSAP) was administered intranasally 1 h (h) after reperfusion. PSAP small interfering ribonucleic acid (siRNA), GPR37 siRNA, and PI3K specific inhibitor LY294002 were administered intracerebroventricularly 48 h before MCAO. Infarct volume, neurological score, immunofluorescence staining, Western blot, Fluoro-Jade C (FJC) and TUNEL staining were examined. The expression of endogenous PSAP and GPR37 were increased after MCAO. Intranasal administration of rPSAP reduced brain infarction, neuronal apoptosis, and improved both short- and long-term neurological function. Knockdown of endogenous PSAP aggravated neurological deficits. Treatment with exogenous rPSAP increased PI3K expression, Akt and ASK1 phosphorylation, and Bcl-2 expression; phosphorylated-JNK and Bax levels were reduced along with the number of FJC and TUNEL positive neurons. GPR37 siRNA and LY294002 abolished the anti-apoptotic effect of rPSAP at 24 h after MCAO. In conclusion, rPSAP attenuated neuronal apoptosis and improved neurological function through GPR37/PI3K/Akt/ASK1 pathway after MCAO in rats. Therefore, further exploration of PSAP as a potential treatment option in ischemic stroke is warranted.
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Fármacos Neuroprotetores , Proteínas Proto-Oncogênicas c-akt , Ratos , Masculino , Feminino , Humanos , Animais , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt/metabolismo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Saposinas/metabolismo , Saposinas/farmacologia , Saposinas/uso terapêutico , Transdução de Sinais , Administração Intranasal , Apoptose , RNA Interferente Pequeno/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Dynamic polarity analysis is proposed herein as a general tool for investigating static polarity and transient polarity and revealing expanded reactivity patterns. Through this analysis formalism, polarity matching has been established for Rh(III)-catalyzed N-amino-directed C-H coupling with 3-methyleneoxetan-2-ones, providing efficient access to 1,2-dihydroquinoline-3-carboxylic acids. The identified reaction, by virtue of the internal oxidative mechanism, showcases mild reaction conditions (room temperature), a short reaction time (2 h), and a generally high product yield.
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A palladium catalytic method has been developed for the coupling of amides and cyclopropanols to γ-diketones, through simultaneous C-N and C-C activation. Heteroatom ligand exchange and heteroatom-to-carbon ligation mode switching enable the achievement of molecular cross-coupling in an amide N-atom structural context-dependent manner, avoiding any stoichiometric organometallic reagent or base.
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Adsorption is a green technology of treating heavy metal-contaminated strong acid wastewaters for the recycling of heavy metal and reuse of strong acid. Herein, three amine polymers (APs) with different alkalinities and electron donating abilities were prepared to investigate the adsorption-reduction processes of Cr(VI). It was found that the removal of Cr(VI) was controlled by the concentration of -NRH+ on the surface of APs at pH > 2, which relies on the alkalinity of APs. However, the high concentration of NRH+ significantly facilitated the adsorption of Cr(VI) on the surface of APs and accelerated the mass transfer between Cr(VI) and APs at strong acid environment (pH ≤ 2). More importantly, the reduction of Cr(VI) was enhanced at pH ≤ 2, due to the high reduction potential of Cr(VI) (E ≥ 0.437). The ratio of reduction to adsorption (α) of Cr(VI) was above 0.70, and the proportion of Cr(III) bonding on Ph-AP excessed 67.6 %. Finally, a proton-enhanced mechanism of Cr(VI) removal was verified by analyzing FTIR and XPS spectra as well as constructing DFT model. This study provides a theoretical basis for the removal of Cr(VI) in the strong acid wastewater.
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Organic metathesis reactions allow for expedient assembly of diverse molecular skeletons and appendages through the exchange of molecular fragments. The olefin-imine variant of this process, in particular, can expand the synthetic toolbox for manipulating carbon-carbon and carbon-nitrogen bonds but has thus far been achieved only on a stoichiometric metal-mediated basis. Herein, we report the development of a catalytic olefin-imine metathesis reaction, featuring cobalt-catalyzed amidine olefination with enaminones and a versatile product synthon enabling further structural diversification.
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BACKGROUND: Clostridium difficile (C. difficile) is a Gram-positive, anaerobic, spore-forming bacillus that can cause pseudomembranous colitis and other C. difficile-associated diseases, resulting in significant morbidity and mortality. The incidence and clinical features vary by geography. METHODS: In this cross-sectional study, we examined the incidence and clinical features of C. difficile infection (CDI) within a 2,900-bed academic medical center in a southern area of China from January 1, 2017, to December 31, 2020. All adult inpatients (aged ≥ 18 years) who submitted loose stool samples for C. difficile testing over this period were considered for the study. RESULTS: This cross-sectional study showed that the average incidence of CDI was 2.07 cases/100,000 hospital patient-days. The mean age of these inpatients was 71.21 ± 2.83 years (range 30 - 93 years), and 83.61% (51/61) were treated in medical units. We found that 85.25% (52/61) of inpatients with CDI were aged > 60 years. Multivariate logistic regression analysis revealed that age > 60 years, and admission to the geriatric treatment unit or neurosurgery treatment unit were indeed independent risk factors for CDI in inpatients. CONCLUSIONS: The incidence of CDI in the southern area of China was low. Age > 60 years, and treatment in geriatric or neurosurgery units were independent risk factors for CDI inpatients.
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Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Adulto , Humanos , Idoso , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos Transversais , Pacientes Internados , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , Fatores de Risco , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/induzido quimicamente , Antibacterianos/efeitos adversos , Infecção Hospitalar/tratamento farmacológicoRESUMO
Background: The global epidemiological situation of COVID-19 remains serious. The rapid hunting of SARS-CoV-2 infection is the key means for preventing transmission. Methods: A total of 40,689 consecutive overseas arrivals were screened for SARS-CoV-2 infection based on PCR and serologic testing. The yield and efficiency of different screening algorithms were evaluated. Result: Among the 40,689 consecutive overseas arrivals, 56 (0.14%) subjects were confirmed to have SARS-CoV-2 infection. The asymptomatic rate was 76.8%. When the algorithm based on PCR alone was used, the identification yield of a single round of PCR (PCR1) was only 39.3% (95% CI: 26.1-52.5%). It took at least four rounds of PCR to achieve a yield of 92.9% (95% CI: 85.9-99.8%). Fortunately, an algorithm based on a single round of PCR combined with a single round of serologic testing (PCR1+ Ab1) greatly improved the screening yield to 98.2% (95% CI: 94.6-100.0%) and required 42,299 PCR and 40,689 serologic tests that cost 6,052,855 yuan. By achieving a similar yield, the cost of PCR1+ Ab1 was 39.2% of that of four rounds of PCR. For hunting one case in PCR1+ Ab1, 769 PCR and 740 serologic tests were required, costing 110,052 yuan, which was 63.0% of that of the PCR1 algorithm. Conclusion: Comparing an algorithm based on PCR alone, PCR combined with a serologic testing algorithm greatly improved the yield and efficiency of the identification of SARS-CoV-2 infection.
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Teste para COVID-19 , COVID-19 , Humanos , Algoritmos , COVID-19/diagnóstico , COVID-19/epidemiologia , Reação em Cadeia da Polimerase , SARS-CoV-2RESUMO
Transition metal catalysis has revolutionized modern synthetic chemistry for its diverse modes of coordination reactivity. However, this versatility in reactivity is also the predominant cause of catalyst deactivation, a persisting issue that can significantly compromise its synthetic value. Homeostatic catalysis, a catalytic process that can sustain its productive catalytic cycle even when chemically disturbed, is proposed herein as an effective tactic to address the challenge. In particular, a cobalt homeostatic catalysis process has been developed for the water-tolerant coupling of enaminones and oxadiazolones to quinazolinones. Dynamic covalent bonding serves as a mechanistic handle for the preferred buffering of water onto enaminone and reverse exchange by a released secondary amine, thus securing reversible entry into cobalt's dormant and active states for productive catalysis. Through this homeostatic catalysis mode, a broad structural scope has been achieved for quinazolinones, enabling further elaboration into distinct pharmaceutically active agents.
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The incorporation of a naphthyl curing agent (NCA) can enhance the thermal stability of pressure-sensitive adhesives (PSAs). In this study, a PSA matrix was synthesized using a solution polymerization process and consisted of butyl acrylate, acrylic acid, and an ethyl acrylate within an acrylic copolymer. Benzoyl peroxide was used as an initiator during the synthesis. To facilitate the UV curing of the solvent-borne PSAs, glycidyl methacrylate was added to introduce unsaturated carbon double bonds. The resulting UV-curable acrylic PSA tapes exhibited longer holding times at high temperatures (150 °C) compared to uncross-linked PSA tapes, without leaving any residues on the substrate surface. The thermal stability of the PSA was further enhanced by adding more NCA and increasing the UV dosage. This may be attributed to the formation of cross-linking networks within the polymer matrix at higher doses. The researchers successfully balanced the adhesion performance and thermal stability by modifying the amount of NCA and UV radiation, despite the peel strength declining and the holding duration shortening. This research also investigated the effects of cross-linking density on gel content, molecular weight, glass transition temperature, and other properties of the PSAs.
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BACKGROUND: Preoperative conditions in pediatric liver transplant recipients are understandably complex. Compared with adults, children have lesser compensatory abilities and demand greater precision during procedural executions. In the setting of end-stage liver disease, the heightened perioperative risk of coexistent cardiovascular pathology may impact graft survival as well. Requirements for anesthesia and perioperative management are thus more rigorous, calling for individualized treatments that reflect specific cardiovascular constraints and proposed surgical plans. CASE SUMMARY: Reports of perioperative anesthesia management and liver transplant prognostication in pediatric patients with concurrent atrial septal defects are scarce. Herein, we detail the course of liver transplantation in a child with dual afflictions, focusing on perioperative anesthesia management and the important contributions of the anesthesiologist (pre- and perioperatively) to a positive therapeutic outcome, despite the clinical hurdles imposed. CONCLUSION: Children with atrial septal defects bear substantially more than customary perioperative risk during orthotopic liver transplants, given their compromised cardiopulmonary reserves and functional states. Comprehensive preoperative cardiovascular assessments, including use of agitated-saline contrast echocardiography (to characterize intracardiac shunting) and multidisciplinary deliberation, may offer insights into structural cardiac pathophysiologic effects and transplant-related hemodynamic changes that impact new grafts. At the same time, active and effective monitoring and other measures should be taken to maintain hemodynamic stability in the perioperative period, avoid entry of bubbles into the circulation, and ease congestion in newly grafted livers. Such efforts are crucial for transplantation success and graft survival.
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Introduction: Talaromyces marneffei is a life-threatening pathogen that causes systemic talaromycosis in immunocompromised and acquired immunodeficiency syndrome (AIDS) patients. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) as a tool to cluster T. marneffei isolates is rarely reported and the data on antifungal susceptibility of T. marneffei isolated in the southern region of China, especially in Fujian, is hardly found. Methods: MALDI-TOF MS was used to cluster 135 T. marneffei isolates, and the minimum inhibitory concentration (MIC) values of amphotericin B, itraconazole, posaconazole, voriconazole, fluconazole, anidulafungin, micafungin, caspofungin and 5-fluorocytosine with Sensititre YeastOne™ YO10 assay were measured during January 2017 to October 2020 in Fujian and Guangxi. Results: MALDI-TOF MS correctly identified 100% of the T. marneffei isolates. Hierarchical clustering of MALDI-TOF peak profiles identified four different clusters. MICs for itraconazole, posaconazole, voriconazole and amphotericin B were as follows: ≤0.015-0.03 µg/mL, ≤0.008-0.03 µg/mL, ≤0.008-0.06 µg/mL, ≤0.12-1 µg/mL, respectively. MICs for echinocandins and fluconazole were comparatively high. Conclusion: Since only simple sample preparation is required and since results are available in a short period of time, MALDI-TOF MS can be considered as a method for identification and clustering of T. marneffei. Itraconazole, posaconazole, voriconazole and amphotericin B can be used to treat T. marneffei infected patients due to the low MICs.
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Objective: Based on the postanesthesia recovery procedure for elderly patients with colorectal cancer, a care bundle program was conducted to validate its effectiveness. Method: According to the characteristics of elderly patients with colorectal cancer, five measures including respiratory management, circulatory stability, pain assessment, body temperature monitoring, and internal environment stability were integrated into one bundle. Postanesthesia care unit (PACU) care bundle program for elderly patients was developed and used to improve recovery care. The monitoring data of the pre-PACB group given care bundles were collected and compared with the data of the post-PACB group who were given conventional recovery care. Result: 222 patients in post-PACB group had shorter intubation time than 291 patients in pre-PACB group (37.7 ± 24.4 min vs. 42.1 ± 23.3 min, P < 0.05). The length of stay in PACU was longer in pre-PACB group (89.9 ± 33.5 min vs. 81.6 ± 31.1 min, P < 0.05). More adverse events were found in the post-PACB group than in the pre-PACB group (72.1% vs. 34.0%). Conclusion: After general anesthesia of patients with colorectal cancer, the application of the care bundles can improve the quality of recovery, shorten the intubation time and the length of stay in PACU, and reduce the complications caused by anesthesia.
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Período de Recuperação da Anestesia , Neoplasias Colorretais/terapia , Pacotes de Assistência ao Paciente , Idoso , Anestesia Geral/métodos , Temperatura Corporal , Sistema Cardiovascular , Neoplasias Colorretais/cirurgia , Humanos , Tempo de Internação , Medição da Dor , Reprodutibilidade dos Testes , Fenômenos Fisiológicos RespiratóriosRESUMO
The metabolite itaconate has both anti-inflammatory and immunomodulatory effects. However, its influence on chronic pain is unclear. Here, we demonstrated that intraperitoneal injection of the itaconate derivative dimethyl itaconate (DI) alleviated chronic pain symptoms, such as allodynia and hyperalgesia, in spinal nerve ligation (SNL) and inflammatory pain models. Moreover, intraperitoneal DI reduced the secretion of inflammatory cytokines (i.e., interleukin-1ß, tumour necrosis factor-alpha) in dorsal root ganglion (DRG), spinal cord and hind paw tissues, suppressed the activation of macrophages in the DRG and glial cells in the spinal dorsal horn and decreased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the DRG and spinal cord. DI boosted nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) levels in the DRG and spinal cord of SNL mice. Intraperitoneal administration of the Nrf2 inhibitor ML385 abolished the analgesic effect of DI and decreased the expression of Nrf2 in the DRG and spinal cord. Similarly, administration of DI potently reversed the lipopolysaccharide (LPS)-induced inflammatory effect in microglia. Reduction of endogenous itaconate levels by pretreatment with immune-responsive gene 1 (IRG1) siRNA blocked Nrf2 expression, which impaired the analgesic and anti-inflammatory effects of DI in vitro. Therefore, our findings revealed for the first time that intraperitoneal DI elicited anti-inflammatory effect and sustained chronic pain relief, which may be regarded as a promising therapeutic agent for chronic pain treatment.
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Dor Crônica , Neuralgia , Animais , Dor Crônica/tratamento farmacológico , Gânglios Espinais/metabolismo , Hiperalgesia/metabolismo , Camundongos , Neuralgia/metabolismo , Doenças Neuroinflamatórias , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal , SuccinatosRESUMO
ABSTRACT: The aim of this study was to compare the clinical efficacy of azithromycin and ceftizoxime (AC) and erythromycin and amoxicillin/sulbactam (EAS) in the treatment of children with Mycoplasma pneumoniae pneumonia (MPP).In this retrospective study, a total of 92 eligible children with MPP were included, and they were divided into a treatment group (nâ=â46) and a control group (nâ=â46). All patients were treated with intravenous ambroxol, and nebulized inhalation of budesonide and terbutaline. In addition, patients in the treatment group received AC. Patients in the control group underwent EAS. All patients in both groups were treated for a total of 10âdays. Outcomes consist of erythrocyte sedimentation rate, C-reactive protein, serum lactate dehydrogenase, and interleukin 6, fever clearance time, time of cough disappearance, time of rale disappearance, time of signs disappeared by X-ray, and adverse events. All outcomes were measured after 10-day treatment.After treatment, patients who received AC exerted better improvements in erythrocyte sedimentation rate (Pâ<â.01), C-reactive protein (Pâ<â.01), serum lactate dehydrogenase (Pâ<â.01), interleukin 6 (Pâ<â.01), fever clearance time (Pâ<â.01), time of cough disappearance (Pâ<â.01), time of rale disappearance (Pâ<â.01), and time of signs disappeared by X-ray (Pâ<â.01), than those in patients who received EAS. In addition, there were not significant differences in adverse events between 2 groups.The results of this study showed that AC may benefit more than EAS for the children with MPP.
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Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ceftizoxima/uso terapêutico , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/tratamento farmacológico , Criança , Eritromicina/uso terapêutico , Feminino , Febre/tratamento farmacológico , Humanos , Lactato Desidrogenases , Masculino , Mycoplasma pneumoniae/efeitos dos fármacos , Estudos Retrospectivos , Sulbactam/uso terapêutico , Resultado do TratamentoRESUMO
Background and Aims: Little is known about diet-related inflammation in chronic obstructive pulmonary disease (COPD). In this study, we aimed to explore the association between COPD and dietary inflammatory index (DII) scores in adults over 40 years old. Methods: Data were obtained from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES). In the present study, 9,929 participants were included and analyzed. The DII score was calculated and divided into tertiles. Logistic regression analysis was performed to determine the odds ratios of DII tertiles. Results: Participants were categorized into COPD (565, 5.69%) and non-COPD groups (9,364, 94.31%) according to interview information. COPD individuals had higher DII scores than non-COPD individuals (0.429 ± 1.809 vs. -0.191 ± 1.791, p < 0.001). The highest DII score tertile included 46.55% of COPD individuals was associated with lower family incomes and education and a higher smoking rate (p < 0.01). The odds ratios (95% CIs) of COPD according to logistic regression were 0.709 (0.512-0.982) for T1 and 0.645 (0.475-0.877) for T2 of the DII score (p = 0.011). Conclusion: Higher DII scores were positively correlated with COPD in participants over 40 years old. These results further support that diet can be used as an intervention strategy for COPD management.
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Enhancing the performance of adsorbents to the utmost extent is an objective but challenging in applying adsorption technology to wastewater treatment. In this work, novel quaternary ammonium polymers (QAPs) with high density adsorption site (i.e., quaternized N, confirmed by FT-IR results) were designed and prepared for rapid selective removal of Cr(VI) from water. The results of EDS analysis indicated the maximum exposure rate of N on the surface of QAPs was as high as 86.1%, which almost doubled comparing to that of Cr(VI) ions imprinted polymers (Cr(VI)-IIP) (46.2%). Interestingly, the maximum adsorption capacity (211.8 mg/g) and initial adsorption rate (h0, 66.6 mg/ (g·min)) of QAPs (i.e., 5:1(TRIM)) for Cr(VI) are about 3.6 times and 4.9 times those of Cr(VI)-IIP (63.0 mg/g and 13.5 mg/(g·min)), respectively. Impressively, flow-through adsorption experiments demonstrated 5:1(TRIM) can completely remove 5 mg/L of Cr(VI) within five seconds. Additionally, 5:1(TRIM) exhibited a remarkable selectivity for Cr(VI) adsorption, and high purity (100%) of chromium can be readily obtained. The proposed idea of high exposure effect of the adsorption site can provide a valuable guidance for designing rapid selective adsorbents to remove and reclaim Cr(VI) from wastewater.
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Compostos de Amônio , Poluentes Químicos da Água , Adsorção , Cromo/análise , Concentração de Íons de Hidrogênio , Cinética , Polímeros , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análiseRESUMO
Previous transition metal-catalyzed synthesis processes of δ-diketones are plagued by the high cost of the rhodium catalyst and harsh reaction conditions. Herein a low-cost, room temperature ruthenium catalytic method is developed based on the coupling of α-keto sulfoxonium ylides with cyclopropanols. The mild protocol features a broad substrate scope (47 examples) and a high product yield (up to 99%). Mechanistic studies argue against a radical pathway and support a cyclopropanol ring opening, sulfoxonium ylide-derived carbenoid formation, migratory insertion C-C bond formation pathway.
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Transition-metal-catalyzed, directed intermolecular C-H bond functionalization is synthetically useful but heavily underexplored in multiheteroatom heterocycle synthesis. Herein we report a cobalt catalytic method for the formation of a three-nitrogen-bearing benzotriazine scaffold via the coupling of arylhydrazine and oxadiazolone. This synthetic protocol features a low-cost base metal catalyst, a maximum number of heteroatoms built into a heterocycle, a distinct synthetic logic for benzotriazines, a superior step economy, and a broad substrate scope.