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1.
J Biochem Mol Toxicol ; 38(8): e23800, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-39132781

RESUMO

Pyroglutamate (pE)-modified amyloid-ß (Aß) peptides play a crucial role in the development of Alzheimer's disease. pEAß3-42 can rapidly form oligomers that gradually elongate hydrophobic segments to form ß-sheet-rich amyloid intermediates, ultimately resulting in the formation of mature amyloid fibrils. pEAß3-42 can also catalyze the aggregation of Aß species and subsequently accelerate the formation of amyloid senile plaques. Considering the recent clinical success of the pEAß3-42-targeting antibody donanemab, molecules that strongly bind pEAß3-42 and prevent its aggregation and catalytic effect on Aßs may also provide potential therapeutic options for Alzheimer's disease. Here, we demonstrate that the natural antibiotic cyclopeptide tyrocidine A (TA) not only strongly inhibits the aggregation of Aß1-42 as previously reported, but also interacts with the hydrophobic C-terminus and middle domain of pEAß3-42 to maintain an unordered conformation, effectively impeding the formation of initial oligomers and subsequently halting the aggregation of pEAß3-42. Furthermore, TA can disrupt the "catalytic effect" of pEAß3-42 on amyloid aggregates, effectively suppressing Aß aggregation and ultimately preventing the pathological events induced by Aßs.


Assuntos
Peptídeos beta-Amiloides , Interações Hidrofóbicas e Hidrofílicas , Ácido Pirrolidonocarboxílico , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Ácido Pirrolidonocarboxílico/química , Ácido Pirrolidonocarboxílico/análogos & derivados , Ácido Pirrolidonocarboxílico/farmacologia , Humanos , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Agregados Proteicos/efeitos dos fármacos , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico
2.
J Chem Phys ; 161(1)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38949284

RESUMO

Layered manganese transition metal oxides, such as NaMnO2, have attracted great interest due to the low cost and high capacity. However, complex phase transitions in NaMnO2 lead to poor cycling stability. The introduction of Li doping has been confirmed to improve the performance of NaMnO2. O3-type NaLi1/3Mn2/3O2 (NLMO), synthesized in 2021, has demonstrated excellent electrochemical performance. Notably, irreversible Li interlayer migration (Li migrates from the transition metal layer to the alkali metal layer) has been observed during cycling, which is related to the electrochemical performance. Therefore, it is crucial to understand the mechanism underlying Li interlayer migration in O3-NLMO. However, the environment of Li interlayer migration on cycling is complex and involves interlayer spacing, Na-ion concentration, the degree of O-ion oxidation, and phase transition. Here, in this work, we utilized the first-principles method to decouple the coupling factors influencing the Li interlayer migration. Through analyzing the impact of the single-factor on Li interlayer migration, we aim to identify the crucial factors affecting this process. Our results show that a decrease in Na-ion concentration and an increase in O-ion oxidation degree promote the Li interlayer migration, while the O-P phase transition suppresses the Li interlayer migration. Interlayer spacing was found to play a less influential role in Li interlayer migration. Our investigations provide effective strategies for the subsequent regulation of Li interlayer migration.

3.
Mikrochim Acta ; 191(8): 451, 2024 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-38970693

RESUMO

Ti3C2Tx MXene/CuxO composites were prepared by acid etching combined with electrochemical technique. The abundant active sites on the surface of MXene greatly increase the loading of CuxO nanoparticles, and the synergistic effect between the different components of the composite can accelerate the oxidation reaction of glucose. The results indicate that at the working potential of 0.55 V (vs. Ag/AgCl), the glucose sensor based on Ti3C2Tx MXene/CuxO composite presents large linear concentration ranges from 1 µM to 4.655 mM (sensitivity of 361 µA mM-1 cm-2) and from 5.155 mM to 16.155 mM (sensitivity of 133 µA mM-1 cm-2). The limit of detection is 0.065 µM. In addition, the sensor effectively avoids the oxidative interference of common interfering species such as ascorbic acid, dopamine and uric acid. The sensor has good reproducibility, stability and acceptable recoveries for the detection of glucose in human sweat sample (97.5-103.3%) with RSD values less than 4%. Based on these excellent properties it has great potential for the detection of glucose in real samples.


Assuntos
Cobre , Técnicas Eletroquímicas , Glucose , Limite de Detecção , Titânio , Cobre/química , Humanos , Titânio/química , Glucose/análise , Glucose/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Suor/química , Eletrodos , Oxirredução , Reprodutibilidade dos Testes , Técnicas Biossensoriais/métodos , Nanocompostos/química
4.
Anal Chem ; 95(44): 16079-16088, 2023 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-37883745

RESUMO

The increasing pressure and unhealthy lifestyle are gradually eroding the physical and mental health of modern people. As a key hormone responsible for maintaining the normal functioning of human systems, cortisol plays a vital role in regulating physiological activities. Moreover, cortisol can serve as a marker for monitoring psychological stress. The development of cortisol detection sensors carries immense potential, as they not only facilitate timely adjustments and treatments by detecting abnormal physiological indicators but also provide comprehensive data for conducting research on the correlation between cortisol and several potential diseases. Here, we report a molecularly imprinted polymer (MIP) electrochemical biosensor that utilizes a porous composite (MXG) modified electrode. MXG composite is prepared by combining Ti3C2Tx-MXene sheets and graphene (Gr). MXG composite material with high conductive properties and large electroactive surface area promotes the charge transfer capability of the electrode surface, expands the effective surface area of the sensor, and increases the content of cortisol-imprinted cavities on the electrode, thereby improving the sensing ability of the sensor. By optimizing the preparation process, the prepared sensor has an ultralow lower limit of detection of 0.4 fM, a wide detection range of 1 fM-10 µM, and good specificity for steroid hormones and interfering substances with similar cortisol structure. The ability of the sensor to detect cortisol in saliva was also confirmed experimentally. This highly sensitive and selective cortisol sensor is expected to be widely used in the fields of physiological and psychological care.


Assuntos
Grafite , Impressão Molecular , Humanos , Polímeros/química , Hidrocortisona , Grafite/química , Técnicas Eletroquímicas , Limite de Detecção , Titânio , Eletrodos
5.
J Chem Phys ; 158(14): 144704, 2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37061471

RESUMO

The structural, mechanical, and electronic properties of Ni-Co-based layered transition oxide LiNixCo1-xO2 (x = 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, and 0.9) (LNCO) have been investigated using the first-principles method. The results show that the effect of Ni/Co mixing on the structural property is slight. For the case of the mechanical property, the elastic constant, elastic modulus, such as Young's modulus (Y), Poisson's ratio (v), Pugh's ratio (B/G), and Cauchy pressure (C') of LNCO have been carefully analyzed based on the strain-energy method. The results demonstrate that the mechanical strength of LNCO materials is weaker than that of pure LiCoO2 (LCO) and LiNiO2 (LNO). However, the B/G ratio and Poisson's ratio of LNCO are greater than that of the pure LCO and LNO, which means that Ni/Co mixing can improve the ductility of pure LCO and LNO. In addition, Cauchy pressure and anisotropy are also discussed, and as cathode materials, LNCO still exhibits good electrical conductivity. Our results provide a feasible way to realize mechanical property modulation by Ni-Co-based layered transition metal oxides LCO. Furthermore, our study is also helpful to reveal the formation mechanism of intra-lattice microcracks in electrode materials.

6.
Inorg Chem ; 60(14): 10109-10113, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34184871

RESUMO

Molecule-based crystalline materials with angle-dependent polarized emission have attracted considerable attention owing to their extensive applications in displays and anticounterfeiting. Herein, one anionic metal-organic framework (MOF) {[Zn2.5(µ3-OH)(NDC)2(HNDC)](HPIM)}n was constructed on the basis of an excellent photoactive ligand naphthalene-1,4-dicarboxylic acid (H2NDC). The protonated 2-propylimidazole (HPIM) guests residing in the nanochannels of MOF can be exchanged by a D-π-A cationic dye. The resulted host-guest system shows a rare example of ratiometric fluorescent polarizations and highly enhanced photoelectron performance in comparison with the pristine MOF.

7.
Inorg Chem ; 60(2): 846-851, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33406364

RESUMO

Metal-organic frameworks (MOFs) or coordination polymers (CPs)-based phosphorescence materials may provide a powerful route for photoelectric and optical recording devices. Herein, two phosphorescence ligands, iso-phthalic acid (IPA) and 2-methylimidazole (MIM), were selected to construct an nonporous CP {Zn(IPA)(MIM)2} (1) with a long-lived phosphorescence lifetime up to 552 ms. By the doping of Eosin Y (EY) dye molecules under an in situ process, the phosphorescence emission color of 1 can be expressly tuned from green to red. The light-harvesting range can also be vastly broadened from the UV to the visible region (550 nm). Photoelectron measurements reveal that the synergistic effect of bias voltage and illumination can greatly restrain electron-hole recombination for the generation of additional free charges.

8.
Inorg Chem ; 60(24): 18593-18597, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34822244

RESUMO

The relationship between the aggregation states of pyrene-based linkers and the photoluminescence/photoelectric performance was well studied by the formation of an anionic metal-organic framework, [BMI]2[Mg3(TBAPy)2(H2O)4]·2dioxane, which shows highly enhanced light-harvesting and photoelectric conversion efficiency by the encapsulation of D-π-A cation dyes.

9.
Angew Chem Int Ed Engl ; 60(1): 24-40, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-32592283

RESUMO

ß-Lactam antibiotics are generally perceived as one of the greatest inventions of the 20th century, and these small molecular compounds have saved millions of lives. However, upon clinical application of antibiotics, the ß-lactamase secreted by pathogenic bacteria can lead to the gradual development of drug resistance. ß-Lactamase is a hydrolase that can efficiently hydrolyze and destroy ß-lactam antibiotics. It develops and spreads rapidly in pathogens, and the drug-resistant bacteria pose a severe threat to human health and development. As a result, detecting and inhibiting the activities of ß-lactamase are of great value for the rational use of antibiotics and the treatment of infectious diseases. At present, many specific detection methods and inhibitors of ß-lactamase have been developed and applied in clinical practice. In this Minireview, we describe the resistance mechanism of bacteria producing ß-lactamase and further summarize the fluorogenic probes, inhibitors of ß-lactamase, and their applications in the treatment of infectious diseases. It may be valuable to design fluorogenic probes with improved selectivity, sensitivity, and effectiveness to further identify the inhibitors for ß-lactamases and eventually overcome bacterial resistance.


Assuntos
Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Corantes Fluorescentes/uso terapêutico , Resistência beta-Lactâmica/efeitos dos fármacos , Inibidores de beta-Lactamases/uso terapêutico , Humanos , Inibidores de beta-Lactamases/farmacologia
10.
Cancer Cell Int ; 20: 78, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190002

RESUMO

BACKGROUND: Non-small-cell lung cancer (NSCLC) is one of the common cancers in the world. Circular RNA 0072083 (circ_0072083, circZFR) has been reported to be associated with the progression of NSCLC. In this study, we intended to explore the role and the potential mechanism of circ_0072083 in NSCLC. METHODS: Quantitative real time polymerase chain reaction (qRT-PCR) was performed to detect the expression of circ_0072083, its matching linear RNA (zinc finger RNA binding protein (ZFR)) and microRNA-545-3p (miR-545-3p) in NSCLC cells. The ability of colony formation in NSCLC cells was detected by colony formation assay. The apoptosis and cell cycle were measured by flow cytometry. The metastasis was determined by transwell migration and invasion assays. The protein expression of E-cadherin, N-cadherin, Vimentin and Cbl proto-oncogene like 1 (CBLL1) was examined by western blot assay. The interaction between miR-545-3p and circ_0072083 or CBLL1 was predicted by starBase or Targetscan software. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate these interactions. Nude mice bearing tumors were used to confirm the role of circ_0072083 and cisplatin (DDP) in vivo. RESULTS: The level of circ_0072083 was higher in NSCLC tissues and cells relative to that in adjacent non-tumor tissues and normal lung cells. The transfection of si-circ_0072083 inhibited colony formation, cell cycle and metastasis while promoted the apoptosis of NSCLC cells stimulated by DDP. MiR-545-3p was a direct functional target of circ_0072083 in NSCLC cells. CBLL1 could bind to miR-545-3p in NSCLC cells. Circ_0072083 promoted the progression of NSCLC induced by DDP through sponging miR-545-3p and enhancing the enrichment of CBLL1 in vivo and in vitro. CONCLUSION: Circ_0072083 depletion contributed to DDP-triggered inhibition of NSCLC tumor through miR-545-3p/CBLL1 axis.

11.
Chembiochem ; 20(6): 831-837, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30485616

RESUMO

A fast-response fluorogenic probe-compound D1-for monitoring hypochlorite (ClO- ), based on specific ClO- cleavage of a C=N bond and producing results observable to the naked eye, has been developed. The response of the probe to ClO- increases linearly, and the fluorescence intensity was heightened by a factor of about 25. D1 responses to ClO- , with high selectivity and sensitivity, were observable by naked eye within 10 s. D1 can not only detect levels of hypochlorite in vitro, such as in urine, but is also capable of monitoring hypochlorite content under extremely cold conditions, as low as -78 °C. Meanwhile, its good biocompatibility permitted the use of D1 to detect intracellular ClO- by confocal microscopy. Moreover, D1 was successfully applied to monitor exogenous and endogenous ClO- in zebrafish through fluorescence imaging.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/urina , Naftóis/química , Oximas/química , Animais , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Naftóis/toxicidade , Oximas/toxicidade , Temperatura , Peixe-Zebra
12.
J Biochem Mol Toxicol ; 33(11): e22395, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31583774

RESUMO

Raloxifene, a selective estrogen receptor modulator, displays benefits for Alzheimer's disease (AD) prevention in postmenopausal women as hormonal changes during menopause have the potential to influence AD pathogenesis, but the underlying mechanism of its neuroprotection is not entirely clear. In this study, the effects of raloxifene on amyloid-ß (Aß) amyloidogenesis were evaluated. The results demonstrated that raloxifene inhibits Aß42 aggregation and destabilizes preformed Aß42 fibrils through directly interacting with the N-terminus and middle domains of Aß42 peptides. Consequently, raloxifene not only reduces direct toxicity of Aß42 in HT22 neuronal cells, but also suppresses expressions of tumor necrosis factor-α and transforming growth factor-ß induced by Aß42 peptides, and then alleviates microglia-mediated indirect toxicity of Aß42 to HT22 neuronal cells. Our results suggested an alternative possible explanation for the neuroprotective activity of raloxifene in AD prevention.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Agregados Proteicos/efeitos dos fármacos , Cloridrato de Raloxifeno/farmacologia , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Microglia/citologia , Microglia/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Fragmentos de Peptídeos/química , Agregação Patológica de Proteínas/metabolismo , Domínios Proteicos , Cloridrato de Raloxifeno/química , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/genética
13.
Nanotechnology ; 29(15): 155301, 2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29384492

RESUMO

Here we reported the fabrication of tungsten oxide (WO3-x ) nanowires by Ar+ ion irradiation of WO3 thin films followed by annealing in vacuum. The nanowire length increases with increasing irradiation fluence and with decreasing ion energy. We propose that the stress-driven diffusion of the irradiation-induced W interstitial atoms is responsible for the formation of the nanowires. Comparing to the pristine film, the fabricated nanowire film shows a 106-fold enhancement in electrical conductivity, resulting from the high-density irradiation-induced vacancies on the oxygen sublattice. The nanostructure exhibits largely enhanced surface-enhanced Raman scattering effect due to the oxygen vacancy. Thus, ion irradiation provides a powerful approach for fabricating and tailoring the surface nanostructures of semiconductors.

14.
Water Environ Res ; 96(9): e11112, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39245973

RESUMO

Root channel wetlands, as a new type of nature-imitating wetland system, provide a paradigm for micro-polluted water source purification; however, there is a knowledge gap on root channel wetlands' pollution removal effects and their main influencing factors after longtime operation. This study collected the turbidity, ammonia nitrogen (NH3-N), total nitrogen (TN), total phosphorus (TP), permanganate index (CODMn), dissolved oxygen (DO), and chemical oxygen demand (COD) at the inlet and outlet of Shijiuyang (SJY) wetland and Guanjinggang (GJG) wetland in Jiaxing City, China, from 2019 to 2021. The results showed that root channel wetlands had better water quality improvement effects. The SJY wetland had larger removal rates for DO, CODMn, and turbidity compared with the GJG wetland. In contrast, other water quality indexes have similar removal rates at both wetlands. The influencing factor analysis showed that water purification agent, flow, pH, and water temperature have large influences on the removal rates of pollutants for both wetlands. To address high turbidity and excessive DO, which are the primary pollutants affecting the two wetlands, implementing the diversion river before the pretreatment area and incorporating ecological floating beds in the deep purification area are recommended solutions to mitigate these issues. Compared with conventional general constructed wetlands, root channel wetlands are a more cost-effective and sustainable technology. The research is conducive to improving understanding of root channel wetland purification for micro-polluted water sources and enhancing water supply security capability in the plains water network area of the Yangtze River Delta region. PRACTITIONER POINTS: Compared with conventional general constructed wetlands, root channel wetlands are more cost-effective and sustainable technology. The SJY wetland demonstrated better removal rates for DO, CODMn, and turbidity, indicating a higher purification capacity compared to GJG wetland. Flow rate and pH are the primary factors influencing the GJG wetland, while the waterpurification agent and water temperature are the main factors affecting water quality in the SJY wetland.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Áreas Alagadas , China , Poluentes Químicos da Água/química , Purificação da Água/métodos , Fósforo/química , Nitrogênio , Qualidade da Água , Análise da Demanda Biológica de Oxigênio
15.
Front Neurol ; 15: 1357195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450079

RESUMO

Introduction: Positional vertigo and nystagmus are the main symptoms and signs of dizziness, respectively. Despite the clinical utility of the supine roll test (SRT) and null point (NP) in diagnosing light cupula, a type of positional vertigo, there exists a notable gap in the literature concerning the comprehensive evaluation of lateralization values based on various nystagmus characteristics and the intensity of direction-changing positional nystagmus (DCPN) in the SRT, particularly in comparison to the NP. Additionally, limited data on abnormal canal paresis (CP) in light cupula patients underscores the need for further research with a larger patient population to elucidate this mechanism. This study aims to investigate the characteristics of positional nystagmus and lateralization of the horizontal semicircular canal (HSCC) light cupula, which is a type of positional vertigo and nystagmus that is poorly understood. Methods: Eighty-five patients (17 males, 68 females; mean age, 60.9 years) with light cupula were reviewed. We summarized the characteristics of spontaneous nystagmus and positional nystagmus, including supine positioning nystagmus, bow nystagmus, and lean nystagmus. Then, the side of the NP was identified as the affected side, and the values of the fast phase direction of the spontaneous nystagmus, supine positioning nystagmus, bow nystagmus, and lean nystagmus, as well as the intensity of the DCPN in the SRT, were used to diagnose the affected sides. Caloric testing was also performed for some patients. Results: Light cupula was observed in 5.7% of the patients with positional nystagmus. The frequencies of supine positioning nystagmus (88.2%), bow nystagmus (90.6%), and lean nystagmus (83.5%) were higher than spontaneous nystagmus (61.2%) (p < 0.001). The second NP (NP2) (92.9%) and third NP (NP3) (83.5%) were readily detected, affecting the left and right sides in 38 and 47 patients, respectively. Lateralization through the fast phase directions of bow nystagmus and lean nystagmus did not significantly differ from that of NP (all p > 0.05). However, the accuracy rate of lateralization through the sides with more vigorous DCPN in the SRT was 63.5%, significantly lower than through NP (p < 0.001). Particularly in patients with supine positioning nystagmus (n = 75), the rate was only 58.7% (p < 0.001). However, the rate was 100% in patients without supine positioning nystagmus (n = 10). Among the 70 patients who underwent caloric testing, 37 had abnormal CP, and the sides of the reduced caloric reaction were ipsilateral to the affected sides of the light cupula in 83.8% of the patients. Conclusion: Besides utilizing the NP to determine the affected side, the fast phase direction of the bow nystagmus or lean nystagmus can also aid in identification. However, a simple comparison of the intensity of DCPN in SRT cannot provide accurate lateralization, especially in patients with supine positioning nystagmus. There is a high incidence of CP on the affected side of the light cupula.

16.
Clin Cancer Res ; 30(8): 1501-1508, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38372727

RESUMO

PURPOSE: Immune checkpoint inhibitors (ICI) have been a potential treatment option for patients with cervical cancer in several clinical studies. We investigated the safety and efficacy of cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, plus standard therapy for the first-line treatment of R/M CC (recurrent and/or metastatic cervical cancer). PATIENTS AND METHODS: Eligible patients were assigned to 3 cohorts: cohort A-15 (cadonilimab 15 mg/kg every 3 weeks (Q3W) plus chemotherapy), cohort A-10 (cadonilimb 10 mg/kg Q3W plus chemotherapy), and cohort B-10 (cadonilimab 10 mg/kg Q3W plus chemotherapy and bevacizumab). They received the corresponding treatments until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. The primary objective was safety; the secondary endpoints included objective overall response (ORR), duration of response, disease control rate, progression-free survival, and overall survival. This study is registered with ClinicalTrials.gov (NCT04868708). RESULTS: As of February 13, 2023, treatment-related adverse events (TRAE) occurred in 45 (100.0%) patients. Grade ≥3 TRAEs were reported in 33 (73.3%) patients. Immune-related adverse events (irAE) occurred in 29 (64.4%) patients and grade ≥3 irAEs were observed in 9 (20.0%) patients. Seven (15.6%) of 45 patients permanently discontinued cadonilimab treatment due to TRAEs. One death due to hemorrhagic shock occurred in cohort B-10. Among 44 patients who underwent at least one post-baseline tumor assessment, the ORR was 66.7% in cohort A-15, 68.8% in cohort A-10, 92.3% in cohort B-10, and 79.3% in cohorts A-10 and B-10 combined. CONCLUSIONS: Cadonilimab combined with standard therapy was acceptable, with encouraging antitumor activity in patients with R/M CC.


Assuntos
Benzenoacetamidas , Piperidonas , Neoplasias do Colo do Útero , Feminino , Humanos , Bevacizumab/efeitos adversos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/etiologia , Empatia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
17.
mSystems ; 8(3): e0102622, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37306481

RESUMO

The newly discovered complete ammonia-oxidizing (comammox) Nitrospira has been identified in different environments, including coastal environments, where salinity is one of the most important factors for the abundance and activity of nitrifiers. Here, we demonstrate the effect of salinity on comammox Nitrospira, canonical ammonia-oxidizing bacteria (AOB), and ammonia-oxidizing archaea (AOA) in the intertidal sediments of the Yangtze River estuary based on microcosm experiments, DNA stable-isotope probing (DNA-SIP), and potential ammonium-oxidation rate (PAR) tests for different groups of ammonia oxidizers with selective inhibitors. During microcosm incubations, the abundance of comammox Nitrospira was more sensitive to increased salinity than that of other ammonia oxidizers. The results obtained with DNA-SIP heavy fractions showed that the dominant phylotype in clade A.2 (containing genes involved in the adaptation to haloalkaline environments) had high proportions in comammox Nitrospira community under both freshwater (0.06% salinity) and highly saline water (3% salinity) conditions. In contrast, another phylotype of clade A.2 (which lacks these genes) was dominant only under freshwater conditions. The PARs confirmed that comammox Nitrospira presented greater contributions to nitrification under freshwater conditions with a PAR of 4.37 ± 0.53 mg N·day-1·kg soil-1 (54%) than under saline water conditions with a PAR of 0.60 ± 0.94 mg N·day-1·kg soil-1 (18%). Moreover, AOA were specific to saline water conditions, whereas AOB were common under both freshwater and saline water conditions (44% and 52%, respectively). The present study provided evidence that salinity markedly affects the activity of comammox Nitrospira, and that the salt sensitivity of different phylotypes varies. IMPORTANCE Complete ammonia oxidation (comammox) is a newly discovered type of nitrification through which ammonia is oxidized to nitrate in an organism. Comammox Nitrospira were abundantly found in coastal ecosystems and demonstrated high community diversity. Changes in salinity are considered one of the most important factors to comammox Nitrospira in coastal ecosystems; however, reports on the correlation between them remain inconsistent. Therefore, it is critical to experimentally determine the influence of salinity on comammox Nitrospira in the coastal ecosystem. This study demonstrated a clear effect of salinity on the abundance, activity, and relative contribution of different ammonia oxidizers, especially for comammox Nitrospira. To the best of our knowledge, this is the first study demonstrating comammox Nitrospira activity at seawater salinities, implying the existence of a salt-tolerant type comammox Nitrospira, despite its activity being much lower than in freshwater conditions. The indicated correlation between the activity of specific comammox Nitrospira and salinity is anticipated to provide insights into the distribution of comammox Nitrospira and their potential contributions in estuaries and coastal ecosystems.


Assuntos
Ecossistema , Nitrificação , Estuários , Amônia , Rios , Salinidade , Bactérias/genética , Oxirredução , Solo , DNA
18.
Front Microbiol ; 13: 1067939, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36687600

RESUMO

Astragalus sinicus (Chinese milk vetch) is a well-established resource of organic fertilizer widely used in paddy soil to partially replace chemical fertilizers. However, the influence of returning A. sinicus to fields on the soil bacterial community remains poorly understood. Here, we used different amounts of A. sinicus partially replacing chemical fertilizers and investigated the changes in soil physicochemical factors and the soil bacterial community structure responses. Returning A. sinicus to the field significantly increased the soil total nitrogen and available phosphorus content (p < 0.05). Weighted gene correlation network analysis (WGCNA) was applied to detect significant associations between the soil microbiome data and physicochemical factors. Two key ecological bacterial clusters (MEturquoise and MEgreen), mainly containing Acidobacteria, Proteobacteria, and Chloroflexi, were significantly correlated with soil nitrogen (N) levels. A. sinicus partially replacing chemical fertilizers reduced the normalized stochasticity ratio (NST) of rare amplicon sequence variants (ASVs), abundant ASVs, MEturquoise, and MEgreen (p < 0.05). Our results further indicated that a moderate amount of A. sinicus returned to the soil effectively mitigated the trend of reduced relative abundance of N fixation function of key ecological clusters caused by chemical fertilizer. However, a large amount of A. sinicus led to a significant increase in relative abundance of denitrification function and a significant decrease in relative abundance of N fixation function of key ecological clusters. This implies that the moderate substitution of A. sinicus returning for chemical fertilizer improves the N cycling function of key ecological bacterial clusters in soil. From the perspective of the bacterial community in paddy soil, this study provides new insight and a reference on how to find a good balance between the amount of A. sinicus returned to the soil and ecological safety.

19.
J Phys Condens Matter ; 34(40)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35882217

RESUMO

Due to the unique outermost orbitals of Sn, hole carriers in tin monoxide (SnO) possess small effective mass and high mobility among oxide semiconductors, making it a promising p-channel material for thin film field-effect transistors (TFTs). However, the Sn vacancy induced field-effect mobility deterioration and threshold voltage (Vth) shift in experiments greatly limit its application in complementary metal-oxide-semiconductor (CMOS) transistors. In this study, the internal mechanism of vacancy defect compensation by aluminum (Al) doping in SnOxfilm is studied combining experiments with the density functional theory (DFT). The doping is achieved by an argon (Ar) plasma treatment of Al2O3deposited onto the SnOxfilm, in which the Al2O3provides both the surface passivation and Al doping source. Experimental results show a wideVthmodulation range (6.08 to -19.77 V) and notable mobility enhancement (11.56 cm2V-1s-1) in the SnOxTFTs after the Al doping by Ar plasma. DFT results reveal that the most possible positions of Al in SnO and SnO2segments are the compensation to Sn vacancy and interstitial. The compensation will create an n-type doping effect and improve the hole carrier transport by reducing the hole effective mass (mh*), which is responsible for the device performance variation, while the interstitial in the SnO2segment can hardly affect the valence transport of the film. The defect compensation is suitable for the electronic property modulation of SnO towards the high-performance CMOS application.

20.
Front Microbiol ; 13: 1002459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225353

RESUMO

Multiple agricultural practices are being applied to increase crop yield in order to overcome the food shortage. Green manure has emerged as an appropriate practice to improve soil fertility and crop yield. However, the potential functions of arbuscular mycorrhizal fungi (AMF) in the below-ground ecosystems following the application of green manure in Ultisols remain largely unexplored. In this study, qPCR and high-throughput sequencing were used to investigate the response of AMF abundance and communities in different treatment groups, i.e., control (without fertilization), mineral fertilization (NPK), mineral fertilization with returning peanut straw (NPKS), and with green manure (hairy vetch; NPKG). The NPKG treatment significantly increased soil fertility compared to other treatment groups. Compared with control, the NPK, NPKS, and NPKG treatments increased peanut yield by 12.3, 13.1, and 25.4%, respectively. NPKS and NPKG treatments significantly altered the AMF community composition decreased the AMF diversity and increased AMF abundance compared to the control. The AMF network of the NPKG treatment group showed the highest complexity and stability compared to other treatment groups. The structural equation modeling revealed that the application of hairy vetch improved soil nutrients and peanut yield by increasing the soil AMF abundance and network stability. Overall, the results suggested that the application of hairy vetch might trigger positive feedback between the peanut and AMF community, contributing to fertility and yield improvement in the dryland of Ultisol.

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