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1.
ChemSusChem ; : e202400796, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697941

RESUMO

Piezocatalysis-induced dye degradation has garnered significant attention as an effective method for addressing wastewater treatment challenges. In our study, we employed a room-temperature sonochemical method to synthesize piezoelectric barium titanate nanoparticles (BaTiO3: BTO) with varying levels of Li doping. This approach not only streamlined the sample preparation process but also significantly reduced the overall time required for synthesis, making it a highly efficient and practical method. One of the key findings was the exceptional performance of the Li-doped BTO nanoparticles. With 20 mg of Li additive, we achieved 90% removal of Rhodamine B (RhB) dye within a relatively short timeframe of 150 minutes, all while subjecting the sample to ultrasonic vibration. This rapid and efficient dye degradation was further evidenced by the calculated kinetic rate constant, which indicated seven times faster degradation rate compared to pure BTO. The enhanced piezoelectric performance observed in the Li-doped BTO nanoparticles can be attributed to the strategic substitution of Li atoms, which facilitated a more efficient transfer of charge charges at the interface. Overall, our study underscores the potential of piezocatalysis coupled with advanced materials like Li-doped BTO nanoparticles as a viable and promising solution for wastewater treatment, offering both efficiency and environmental sustainability.

2.
Liver Transpl ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38713020

RESUMO

INTRODUCTION: Psychiatric disorders after liver transplantation (LT) are associated with worse patient and graft outcomes, which may be amplified by inadequate treatment. We aimed to characterize the burden of psychiatric disorders, treatment patterns, and associated financial burden among LT recipients (LTRs). METHODS: IQVIA PharMetrics® Plus for Academics-a large health plan claims database representative of the commercially insured U.S. population-was used to identify psychiatric diagnoses among adult LTRs and assess treatment. Multivariable logistic regression analysis identified factors associated with post-LT psychiatric diagnoses and receipt of pharmacotherapy. Patient financial liability was estimated using adjudicated medical/pharmacy claims for LTRs with and without psychiatric diagnoses. RESULTS: Post-LT psychiatric diagnoses were identified in 395 (29.5%) of 1,338 LTRs, of which 106 (26.8%) were incident cases. Treatment varied, with 67.3% receiving pharmacotherapy, 32.1% psychotherapy, 21.0% combination therapy, and 21.5% no treatment. Among 340 LTRs on psychotropic medications before transplant, 24% did not continue them post-LT. Post-LT psychiatric diagnoses were independently associated with female sex, alcohol-associated liver disease (ALD), prolonged LT hospitalization (>2 weeks), and pre-LT psychiatric diagnosis. Incident psychiatric diagnoses were associated with female sex, ALD, and prolonged LT hospitalization. Patients with a post-LT psychiatric diagnosis had higher rates of hospitalization (89.6% vs 81.5%, p<0.001) and financial liability (median $5.5K vs $4.6K USD, p=0.006). Having a psychiatric diagnosis post-LT was independently associated with experiencing high financial liability >$5K. CONCLUSION: Over 1 in 4 LTRs had a psychiatric diagnosis in a large national cohort, yet nearly a quarter received no treatment. LTRs with psychiatric diagnoses experienced increased healthcare utilization and higher financial liability. Sociodemographic and clinical risk factors could inform high-risk subgroups who may benefit from screening and mitigation strategies.

3.
Aging (Albany NY) ; 162024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38709288

RESUMO

BMP9 has demonstrated significant osteogenic potential. In this study, we investigated the effect of Leptin on BMP9-induced osteogenic differentiation. Firstly, we found Leptin was decreased during BMP9-induced osteogenic differentiation and serum Leptin concentrations were increased in the ovariectomized (OVX) rats. Both in vitro and in vivo, exogenous expression of Leptin inhibited the process of osteogenic differentiation, whereas silencing Leptin enhanced. Exogenous Leptin could increase the malonylation of ß-catenin. However, BMP9 could increase the level of Sirt5 and subsequently decrease the malonylation of ß-catenin; the BMP9-induced osteogenic differentiation was inhibited by silencing Sirt5. These data suggested that Leptin can inhibit the BMP9-induced osteogenic differentiation, which may be mediated through reducing the activity of Wnt/ß-catenin signalling via down-regulating Sirt5 to increase the malonylation level of ß-catenin partly.

4.
Epidemiol Infect ; 152: e75, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38634450

RESUMO

This paper retrospectively analysed the prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in some parts of China. Between January 2013 and December 2019, we collected 4,145 respiratory samples, including pharyngeal swabs and alveolar lavage fluid. The highest PCR-positive rate of M. pneumoniae was 74.5% in Beijing, the highest resistance rate was 100% in Shanghai, and Gansu was the lowest with 20%. The highest PCR-positive rate of M. pneumoniae was 74.5% in 2013, and the highest MRMP was 97.4% in 2019; the PCR-positive rate of M. pneumoniae for adults in Beijing was 17.9% and the MRMP was 10.48%. Among the children diagnosed with community-acquired pneumonia (CAP), the PCR-positive and macrolide-resistant rates of M. pneumoniae were both higher in the severe ones. A2063G in domain V of 23S rRNA was the major macrolide-resistant mutation, accounting for more than 90%. The MIC values of all MRMP to erythromycin and azithromycin were ≥ 64 µg/ml, and the MICs of tetracycline and levofloxacin were ≤ 0.5 µg/ml and ≤ 1 µg/ml, respectively. The macrolide resistance varied in different regions and years. Among inpatients, the macrolide-resistant rate was higher in severe pneumonia. A2063G was the common mutation, and we found no resistance to tetracycline and levofloxacin.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Mycoplasma pneumoniae/efeitos dos fármacos , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Humanos , China/epidemiologia , Macrolídeos/farmacologia , Estudos Retrospectivos , Criança , Antibacterianos/farmacologia , Pré-Escolar , Adolescente , Adulto , Feminino , Masculino , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pessoa de Meia-Idade , Adulto Jovem , Testes de Sensibilidade Microbiana , Idoso , Lactente , Prevalência , RNA Ribossômico 23S/genética , Idoso de 80 Anos ou mais
5.
World J Surg ; 48(2): 427-436, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38686756

RESUMO

BACKGROUND: The McKeown minimally invasive esophagectomy (McMIE) procedure has various limitations, including surgical contraindications and a high rate of postoperative pulmonary complications. A novel mediastinoscopic esophagectomy procedure was described in this study by using esophageal invagination and a transhiatal and bilateral cervical approach (EITHBC). METHODS: According to the mode of operation, a total of 259 patients were divided into two groups, among which 106 underwent EITHBC and 153 underwent McMIE. The number of lymph nodes dissected, intraoperative outcomes, and postoperative outcomes were compared between the two groups of patients. RESULTS: The results revealed that the average number of resected lymph node in the EITHBC group was significantly higher in the recL106 and TbL106 stations (recL106: 1.75 vs. 1.51, p = 0.016, TbL106: 1.53 vs. 1.19, p = 0.016) and significantly lower in the 107 stations (1. 74 vs. 2. 07, p < 0.001) than in the McMIE group. The intraoperative blood loss in the EITHBC group was significantly lower than that in the McMIE group (63.30 vs. 80.45 mL, p < 0.001). The incidence of postoperative pulmonary complications in the EITHBC group was lower than that in the McMIE group (14.15% vs. 27.45%, p = 0.008). The incidence of recurrent laryngeal nerve paralysis in the EITHBC group was significantly higher than that in the McMIE group (26.41% vs. 10.46%, p = 0.003). CONCLUSION: Compared with the McMIE procedure, the EITHBC procedure has advantages in terms of removing the upper mediastinal lymph nodes and reducing postoperative pulmonary complications.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Mediastinoscopia , Humanos , Esofagectomia/métodos , Feminino , Estudos Retrospectivos , Masculino , Mediastinoscopia/métodos , Pessoa de Meia-Idade , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Idoso , Complicações Pós-Operatórias/epidemiologia , Excisão de Linfonodo/métodos , Resultado do Tratamento , Adulto , Estudos de Coortes
6.
Int J Biol Sci ; 20(6): 2027-2043, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617550

RESUMO

Metabolic-associated fatty liver disease (MAFLD) is a globally prevalent chronic hepatic disease. Previous studies have indicated that the activation of the signal transducer and activator of transcription3 (STAT3) plays a vital role in MAFLD progression at the very beginning. However, the specific association between STAT3 and abnormal hepatic metabolism remains unclear. In this study, activated inflammation was observed to induce abnormal glucolipid metabolic disorders in the hepatic tissues of high-fat diet (HFD)-fed ApoE-/- mice. Furthermore, we found that the activation of STAT3 induced by HFD might function as a transcriptional factor to suppress the expression of VAV3, which might participate in intracellular glucolipid metabolism and the regulation of glucose transporter 4 (GLUT4) storage vesicle traffic in the development of MAFLD both in vitro and in vivo. We verified that VAV3 deficiency could retard the GLUT4 membrane translocation and impair the glucose homeostasis. Additionally, VAV3 participates in cholesterol metabolism in hepatocytes, eventually resulting in the accumulation of intracellular cholesterol. Moreover, rAAV8-TBG-VAV3 was conducted to restore the expression of VAV3 in HFD-fed ApoE-/- mice. VAV3 overexpression was observed to improve glucose homeostasis as well as attenuate hepatic cholesterol accumulation in vivo. In conclusion, the STAT3/VAV3 signaling pathway might play a significant role in MAFLD by regulating glucose and cholesterol metabolism, and VAV3 might be a potential therapeutic strategy which could consequently ameliorate MAFLD.


Assuntos
Doenças Metabólicas , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Apolipoproteínas E/genética , Colesterol , Glucose
7.
Infect Drug Resist ; 17: 1459-1466, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628240

RESUMO

Objective: Salmonella enterica serovar Kentucky ST198 has emerged as a global threat to humans. In this study, we aimed to characterize the prolonged carriage of ciprofloxacin-resistant and extended-spectrum ß-lactamase (ESBL)-producing S. Kentucky ST198 in a single patient with inflammatory bowel disease (IBD). Methods: Three S. Kentucky strains were collected from a single patient with IBD on 11th January, 23rd January, and 8th February, 2022, respectively. Antimicrobial susceptibility testing, whole-genome sequencing, and phylogenetic analysis with 38 previously described Chinese S. Kentucky ST198 strains from patients and food were performed. Results: All three S. Kentucky isolates belonged to ST198. They carried identical 16 resistance genes, such as blaCTX-M-55, tet(A), and qnrS1, and had identical mutations within gyrA (S83F and D87N) and parC (S80I). Therefore, they exhibited identical multidrug-resistant profiles, including the clinically important antibiotics cephalosporins (ceftazidime and cefepime), fluoroquinolones (ciprofloxacin and levofloxacin), and third-generation tetracycline (tigecycline). Our three S. Kentucky strains were classified into the subclade ST198.2-2, and were genetically identical (2-6 SNPs) to each other. They exhibited a close genetic similarity (15-20 SNPs) to the isolate NT-h3189 from a patient and AH19MCS1 from chicken meat in China, indicating a possible epidemiological link between these S. Kentucky ST198 isolates from the patients and chicken meat. Conclusion: Long-term colonization of ciprofloxacin-resistant and ESBL-producing S. Kentucky ST198 in a single patient is a matter of concern. Due to the potential transfer of S. Kentucky ST198 from food sources to humans, ongoing surveillance of this particular clone in animals, animal-derived food products, and humans should be strengthened.

8.
Adv Mater ; : e2401349, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657644

RESUMO

Phonon polaritons, the hybrid quasiparticles resulting from the coupling of photons and lattice vibrations, have gained significant attention in the field of layered van der Waals heterostructures. Particular interest has been paid to hetero-bicrystals composed of molybdenum oxide (MoO3) and hexagonal boron nitride (hBN), which feature polariton dispersion tailorable via avoided polariton mode crossings. In this work, we systematically study the polariton eigenmodes in MoO3-hBN hetero-bicrystals self-assembled on ultrasmooth gold using synchrotron infrared nanospectroscopy. We experimentally demonstrate that the spectral gap in bicrystal dispersion and corresponding regimes of negative refraction can be tuned by material layer thickness, and we quantitatively match these results with a simple analytic model. We also investigate polaritonic cavity modes and polariton propagation along "forbidden" directions in our microscale bicrystals, which arise from the finite in-plane dimension of the synthesized MoO3 micro-ribbons. Our findings shed light on the unique dispersion properties of polaritons in van der Waals heterostructures and pave the way for applications leveraging deeply sub-wavelength mid-infrared light matter interactions. This article is protected by copyright. All rights reserved.

9.
Front Pharmacol ; 15: 1354806, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601461

RESUMO

Lung injury leads to respiratory dysfunction, low quality of life, and even life-threatening conditions. Circular RNAs (circRNAs) are endogenous RNAs produced by selective RNA splicing. Studies have reported their involvement in the progression of lung injury. Understanding the roles of circRNAs in lung injury may aid in elucidating the underlying mechanisms and provide new therapeutic targets. Thus, in this review, we aimed to summarize and discuss the characteristics and biological functions of circRNAs, and their roles in lung injury from existing research, to provide a theoretical basis for the use of circRNAs as a diagnostic and therapeutic target for lung injury.

10.
Heliyon ; 10(7): e28957, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601682

RESUMO

Background: Cushing disease (CD) is a rare clinical neuroendocrine disease. CD is characterized by abnormal hypercortisolism induced by a pituitary adenoma with the secretion of adrenocorticotropic hormone. Individuals with CD usually exhibit atrophy of gray matter volume. However, little is known about the alterations in topographical organization of individuals with CD. This study aimed to investigate the structural covariance networks of individuals with CD based on the gray matter volume using graph theory analysis. Methods: High-resolution T1-weighted images of 61 individuals with CD and 53 healthy controls were obtained. Gray matter volume was estimated and the structural covariance network was analyzed using graph theory. Network properties such as hubs of all participants were calculated based on degree centrality. Results: No significant differences were observed between individuals with CD and healthy controls in terms of age, gender, and education level. The small-world features were conserved in individuals with CD but were higher than those in healthy controls. The individuals with CD showed higher global efficiency and modularity, suggesting higher integration and segregation as compared to healthy controls. The hub nodes of the individuals with CD were Short insular gyri (G_insular_short_L), Anterior part of the cingulate gyrus and sulcus (G_and_S_cingul-Ant_R), and Superior frontal gyrus (G_front_sup_R). Conclusions: Significant differences in the structural covariance network of patients with CD were found based on graph theory. These findings might help understanding the pathogenesis of individuals with CD and provide insight into the pathogenesis of this CD.

12.
Curr Med Sci ; 44(2): 298-308, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619682

RESUMO

OBJECTIVE: In B-cell acute lymphoblastic leukemia (B-ALL), current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50% of cases, underscoring the urgent need for new therapeutic regimens for this patient population. The present study aimed to determine whether HZX-02-059, a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) and tubulin, is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients. METHODS: Cell proliferation, vacuolization, apoptosis, cell cycle, and in-vivo tumor growth were evaluated. In addition, Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL. RESULTS: HZX-02-059 was found to inhibit cell proliferation, induce vacuolization, promote apoptosis, block the cell cycle, and reduce in-vivo tumor growth. Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations. CONCLUSION: Overall, these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Tubulina (Proteína) , Humanos , Proliferação de Células , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêutico
13.
Arch Toxicol ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563870

RESUMO

The high incidence of colorectal cancer (CRC) is closely associated with environmental pollutant exposure. To identify potential intestinal carcinogens, we developed a cell transformation assay (CTA) using mouse adult stem cell-derived intestinal organoids (mASC-IOs) and assessed the transformation potential on 14 representative chemicals, including Cd, iPb, Cr-VI, iAs-III, Zn, Cu, PFOS, BPA, MEHP, AOM, DMH, MNNG, aspirin, and metformin. We optimized the experimental protocol based on cytotoxicity, amplification, and colony formation of chemical-treated mASC-IOs. In addition, we assessed the accuracy of in vitro study and the human tumor relevance through characterizing interdependence between cell-cell and cell-matrix adhesions, tumorigenicity, pathological feature of subcutaneous tumors, and CRC-related molecular signatures. Remarkably, the results of cell transformation in 14 chemicals showed a strong concordance with epidemiological findings (8/10) and in vivo mouse studies (12/14). In addition, we found that the increase in anchorage-independent growth was positively correlated with the tumorigenicity of tested chemicals. Through analyzing the dose-response relationship of anchorage-independent growth by benchmark dose (BMD) modeling, the potent intestinal carcinogens were identified, with their carcinogenic potency ranked from high to low as AOM, Cd, MEHP, Cr-VI, iAs-III, and DMH. Importantly, the activity of chemical-transformed mASC-IOs was associated with the degree of cellular differentiation of subcutaneous tumors, altered transcription of oncogenic genes, and activated pathways related to CRC development, including Apc, Trp53, Kras, Pik3ca, Smad4 genes, as well as WNT and BMP signaling pathways. Taken together, we successfully developed a mASC-IO-based CTA, which might serve as a potential alternative for intestinal carcinogenicity screening of chemicals.

14.
Plant Commun ; : 100891, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561965

RESUMO

Plants that grow in extreme environments represent unique sources of stress-resistance genes and mechanisms. Ammopiptanthus mongolicus (Leguminosae) is a xerophytic evergreen broadleaf shrub native to semi-arid and desert regions; however, its drought-tolerance mechanisms remain poorly understood. Here, we report the assembly of a reference-grade genome for A. mongolicus, describe its evolutionary history within the legume family, and examine its drought-tolerance mechanisms. The assembled genome is 843.07 Mb in length, with 98.7% of the sequences successfully anchored to the nine chromosomes of A. mongolicus. The genome is predicted to contain 47 611 protein-coding genes, and 70.71% of the genome is composed of repetitive sequences; these are dominated by transposable elements, particularly long-terminal-repeat retrotransposons. Evolutionary analyses revealed two whole-genome duplication (WGD) events at 130 and 58 million years ago (mya) that are shared by the genus Ammopiptanthus and other legumes, but no species-specific WGDs were found within this genus. Ancestral genome reconstruction revealed that the A. mongolicus genome has undergone fewer rearrangements than other genomes in the legume family, confirming its status as a "relict plant". Transcriptomic analyses demonstrated that genes involved in cuticular wax biosynthesis and transport are highly expressed, both under normal conditions and in response to polyethylene glycol-induced dehydration. Significant induction of genes related to ethylene biosynthesis and signaling was also observed in leaves under dehydration stress, suggesting that enhanced ethylene response and formation of thick waxy cuticles are two major mechanisms of drought tolerance in A. mongolicus. Ectopic expression of AmERF2, an ethylene response factor unique to A. mongolicus, can markedly increase the drought tolerance of transgenic Arabidopsis thaliana plants, demonstrating the potential for application of A. mongolicus genes in crop improvement.

15.
ACS Sens ; 9(4): 1866-1876, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38499997

RESUMO

Electromagnetic sensors with flexible antennas as sensing elements have attracted increasing attention in noninvasive continuous glucose monitoring for diabetic patients. The significant radiation performance loss of flexible antennas during mechanical deformation impairs the reliability of glucose monitoring. Here, we present flexible ultrawideband monopole antennas composed of Ti3C2 MXene and cellulose nanofibril (CNF) composite films for continuous glucose monitoring. The flexible MXene/CNF antenna with 20% CNF content can obtain a gain of up to 3.33 dBi and a radiation efficiency of up to 65.40% at a frequency range from 2.3 to 6.0 GHz. Compared with the pure MXene antenna, this antenna offers a comparable radiation performance and a lower performance loss in mechanical bending deformation. Moreover, the MXene/CNF antenna shows a stable response to fetal bovine serum/glucose, with a correlation of >0.9 at the reference glucose levels, and responds sensitively to the variations in blood glucose levels during human trials. The proposed strategy enhancing the mechanical robustness of MXene-based flexible antennas makes metallic two-dimensional nanomaterials more promising in wearable electromagnetic sensors.


Assuntos
Glicemia , Celulose , Titânio , Celulose/química , Titânio/química , Humanos , Glicemia/análise , Nanocompostos/química , Técnicas Biossensoriais/métodos , Dispositivos Eletrônicos Vestíveis , Animais , Nanofibras/química , Glucose/análise
17.
Org Biomol Chem ; 22(15): 3009-3018, 2024 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-38529785

RESUMO

Catalytic activity is undoubtedly a key focus in enzyme engineering. The complicated reaction conditions hinder some enzymes from industrialization even though they have relatively promising activity. This has occurred to some dehydrogenases. Hydroxysteroid dehydrogenases (HSDHs) specifically catalyze the conversion between hydroxyl and keto groups, and hold immense potential in the synthesis of steroid medicines. We underscored the importance of 7α-HSDH activity, and analyzed the overall robustness and underlying mechanisms. Employing a high-throughput screening approach, we comprehensively assessed a mutation library, and obtained a mutant with enhanced enzymatic activity and overall stability/tolerance. The superior mutant (I201M) was identified to harbor improved thermal stability, substrate susceptibility, cofactor affinity, as well as the yield. This mutant displayed a 1.88-fold increase in enzymatic activity, a 1.37-fold improvement in substrate tolerance, and a 1.45-fold increase in thermal stability when compared with the wild type (WT) enzyme. The I201M mutant showed a 2.25-fold increase in the kcat/KM ratio (indicative of a stronger binding affinity for the cofactor). This mutant did not exhibit the highest enzyme activity compared with all the tested mutants, but these improved characteristics contributed synergistically to the highest yield. When a substrate at 100 mM was present, the 24 h yield by I201M reached 89.7%, significantly higher than the 61.2% yield elicited by the WT enzyme. This is the first report revealing enhancement of the catalytic efficiency, cofactor affinity, substrate tolerance, and thermal stability of NAD(H)-dependent 7α-HSDH through a single-point mutation. The mutated enzyme reached the highest enzymatic activity of 7α-HSDH ever reported. High enzymatic activity is undoubtedly crucial for enabling the industrialization of an enzyme. Our findings demonstrated that, when compared with other mutants boasting even higher enzymatic activity, mutants with excellent overall robustness were superior for industrial applications. This principle was exemplified by highly active enzymes such as 7α-HSDH.


Assuntos
Hidroxiesteroide Desidrogenases , Mutação Puntual , Hidroxiesteroide Desidrogenases/genética , Hidroxiesteroide Desidrogenases/metabolismo , Mutação , Catálise , Cinética
18.
BMC Cancer ; 24(1): 321, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454345

RESUMO

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia , Quimioterapia de Consolidação , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto
19.
Adv Sci (Weinh) ; : e2309555, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502881

RESUMO

Photo-rechargeable zinc-ion batteries (PRZIBs) have attracted much attention in the field of energy storage due to their high safety and dexterity compared with currently integrated lithium-ion batteries and solar cells. However, challenges remain toward their practical applications, originating from the unsatisfactory structural design of photocathodes, which results in low photoelectric conversion efficiency (PCE). Herein, a flexible MoS2 /SnO2 -based photocathode is developed via constructing a sunflower-shaped light-trapping nanostructure with 3D hierarchical and self-supporting properties, enabled by the hierarchical embellishment of MoS2 nanosheets and SnO2 quantum dots on carbon cloth (MoS2 /SnO2 QDs@CC). This structural design provides a favorable pathway for the effective separation of photogenerated electron-hole pairs and the efficient storage of Zn2+ on photocathodes. Consequently, the PRZIB assembled with MoS2 /SnO2 QDs@CC delivers a desirable capacity of 366 mAh g-1 under a light intensity of 100 mW cm-2 , and achieves an ultra-high PCE of 2.7% at a current density of 0.125 mA cm-2 . In practice, an integrated battery system consisting of four series-connected quasi-solid-state PRZIBs is successfully applied as a wearable wristband of smartwatches, which opens a new door for the application of PRZIBs in next-generation flexible energy storage devices.

20.
Int J Pharm ; 655: 124030, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38521376

RESUMO

Disease-causing microorganisms such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are among the primary contributors to morbidity and mortality of diarrhea in humans. Considering the challenges associated with antibiotic use, including antimicrobial resistance, this study aimed to develop a novel zinc-based agent for bacterial inactivation. To this end, zinc caproate (ZnCA) was synthesized using caproic acid (CA) and zinc oxide (ZnO) in anhydrous ethanol via the solvothermal method. Structural characterization techniques, including Fourier-transform infrared spectroscopy, single crystal X-ray diffraction analysis, and nuclear magnetic resonance spectroscopy, revealed the bidentate bridging coordination of zinc atoms with CA. The resulting two-dimensional ZnCA network was found to be composed of a distinct lamellar pattern, without any evident inter-layer interactions. Powder X-ray diffraction analysis, elemental analysis, and melting point analysis confirmed that ZnCA had an average particle size of 1.320 µm, a melting point of 147.2 °C, and a purity exceeding 98 %. Remarkably, ZnCA demonstrated potent antibacterial activity against E. coli and S. aureus, which exceeded the antibacterial efficacy of ZnO. ZnCA exerted its antibacterial effects by inhibiting biofilm formation, disrupting cell membrane integrity, increasing cell membrane permeability, and altering intracellular Ca2+-Mg2+-ATPase activity. These findings highlight the potential of ZnCA as a promising antibiotic substitute for the treatment of diarrhea in humans.


Assuntos
Nanopartículas Metálicas , Óxido de Zinco , Humanos , Zinco , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Caproatos , Staphylococcus aureus , Escherichia coli , Difração de Raios X , Antibacterianos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química , Diarreia
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