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1.
Sci Total Environ ; 877: 162979, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36948316

RESUMO

Development of solar energy is one of the key solutions towards carbon neutrality in China. The output of solar energy is dependent on weather conditions and shows distinct spatiotemporal characteristics. Previous studies have explored the photovoltaic (PV) power potential in China but with single models and low-resolution radiation data. Here, we estimated the PV power potential in China for 2016-2019 using an ensemble of 11 PV models based on hourly solar radiation at the resolution of 5 km retrieved by the Himawari-8 geostationary satellite. On the national scale, the ensemble method revealed an annual average PV power potential of 242.79 kWh m-2 with the maximum in the west (especially the Tibetan Plateau) and the minimum in the southeast (especially the Sichuan Basin). The multi-model approach shows inter-model spreads of 6 %-7 % distributed uniformly in China, suggesting a robust spatial pattern predicted by these models. The seasonal variation in general shows the largest PV power generation in summer months except for Tibetan Plateau, where the peak value appears in spring because the high cloud coverage dampens the regional solar radiation in summer. On the national scale, the deseasonalized PV power potential shows a high correlation with cloud coverage (R2 = 0.71, p < 0.01) but a low correlation with aerosol optical depth (R2 = 0.08, p < 0.05). Sensitivity experiments show that national PV power potential increases by 0.55 % per 1 W m-2 increase of radiation and 0.79 % per 1 m s-1 increase of wind speed, but decreases by 0.46 % per 1 °C increase of air temperature. These sensitivities provide a solid foundation for the future projection of PV power potential in China under climate change.

2.
J Am Chem Soc ; 145(11): 6516-6525, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36913524

RESUMO

Electrochemical alkynol semi-hydrogenation has emerged as a sustainable and environmentally benign route for the production of high-value alkenols, featuring water as the hydrogen source instead of H2. It is highly challenging to design the electrode-electrolyte interface with efficient electrocatalysts and their matched electrolytes to break the selectivity-activity stereotype. Here, boron-doped Pd catalysts (PdB) and surfactant-modified interface are proposed to enable the simultaneous increase in alkenol selectivity and alkynol conversion. Typically, compared to pure Pd and commercial Pd/C catalysts, the PdB catalyst achieves both higher turnover frequency (139.8 h-1) and specific selectivity (above 90%) for the semi-hydrogenation of 2-methyl-3-butyn-2-ol (MBY). Quaternary ammonium cationic surfactants that are employed as electrolyte additives are assembled at the electrified interface in response to applied bias potential, establishing an interfacial microenvironment that can facilitate alkynol transfer and hinder water transfer suitably. Eventually the hydrogen evolution reaction is inhibited and alkynol semi-hydrogenation is promoted, without inducing the decrease of alkenol selectivity. This work offers a distinct perspective on creating a suitable electrode-electrolyte interface for electrosynthesis.

3.
J Med Chem ; 66(6): 4025-4044, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36912866

RESUMO

Bruton's tyrosine kinase (BTK) plays an essential role in B-cell receptor (BCR)-mediated signaling as well as the downstream signaling pathway for Fc receptors (FcRs). Targeting BTK for B-cell malignancies by interfering with BCR signaling has been clinically validated by some covalent inhibitors, but suboptimal kinase selectivity may lead to some adverse effects, which also makes the clinical development of autoimmune disease therapy more challenging. The structure-activity relationship (SAR) starting from zanubrutinib (BGB-3111) leads to a series of highly selective BTK inhibitors, in which BGB-8035 is located in the ATP binding pocket and has similar hinge binding to ATP but exhibits high selectivity over other kinases (EGFR, Tec, etc.). With an excellent pharmacokinetic profile as well as demonstrated efficacy studies in oncology and autoimmune disease models, BGB-8035 has been declared a preclinical candidate. However, BGB-8035 showed an inferior toxicity profile compared to that of BGB-3111.


Assuntos
Doenças Autoimunes , Neoplasias , Humanos , Tirosina Quinase da Agamaglobulinemia , Relação Estrutura-Atividade , Doenças Autoimunes/tratamento farmacológico , Neoplasias/tratamento farmacológico , Trifosfato de Adenosina , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética
5.
Heliyon ; 9(3): e13915, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36923844

RESUMO

Background: Rhesus macaques and humans are closely related genetically and share similar physiological and pathological characteristics. Exploring the impact of diet on the early establishment of gut microbiota in non-human primates can provide relevant clinical models for healthy infant growth and development. At present, few writers have focused on the composition and changes of the intestinal microbes of infant rhesus macaques throughout their progression from birth to formula feeding after weaning. In this study, we used 16S rRNA sequencing technology to explore the composition of the intestinal flora of rhesus macaques at different ages and analyzed the trends in the microbial changes. Results: The results showed that the relative abundance of Bifidobacterium and Lactobacillus in the intestinal flora of infant rhesus macaques significantly decreased, and Prevotella increased with age. Bifidobacterium longum and Bifidobacterium breve are effective biomarkers to predict grouping. The metabolic pathways enriched in early life mainly concentrated in glycosphingolipid biosynthesis (lacto and neolacto series) and the degradation and metabolism of alcohols and esters. Conclusions: We found that age was an important factor that affected the changes in the intestinal flora. This study revealed the change trend of flora in breastfed and formula-fed infant rhesus monkeys in different growth months, and found that the dominant flora changed greatly. This research provides a medically relevant theoretical basis for understanding the healthy development of infants.

6.
Anal Chim Acta ; 1251: 341000, 2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-36925308

RESUMO

Ionic current rectification (ICR) phenomena conventionally occurs in nanopores which dimensions are comparable to the thickness of their electrical double layers. However, the microscale ICR in a micropore can also exist under some conditions. Here, the charged hydrogel filled conical micropore was constructed to realize microscale ICR. To better understand the micropore ICR, the influences of space charge density of the hydrogel, micropore geometry, the hydrogel filling length as well as the electrolyte concentration and pH were investigated. Furthermore, we developed a PEGDA-based hydrogel filled micropore sensing platform which sensing performance was enhanced due to the weakly charged PEGDA. The promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARA) fusion genes and adenosine triphosphate (ATP) were respectively used as model analytes and the measured detection limits of 0.1 pM were achieved. The successful realization of microscale ICR in a homogenous and functional hydrogel filled micropore suggests that the fabrication, characterization and operation of ICR based devices can be more robust and facilitated for the wider applications.

7.
Oncol Lett ; 25(4): 157, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36936032

RESUMO

[This retracts the article DOI: 10.3892/ol.2018.9173.].

8.
Phys Chem Chem Phys ; 25(11): 8090-8102, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36876722

RESUMO

O-N-Acetylglucosamine transferase (OGT) can catalyze the O-GlcNAc modification of thousands of proteins. The holoenzyme formation of OGT and adaptor protein is the precondition for further recognition and glycosylation of the target protein, while the corresponding mechanism is still open. Here, static and dynamic schemes based on statistics can successfully screen the feasible identifying, approaching, and binding mechanism of OGT and its typical adaptor protein p38α. The most favorable interface, energy contribution of hotspots, and conformational changes of fragments were discovered. The hydrogen bond interactions were verified as the main driving force for the whole process. The distinct characteristic of active and inactive p38α is explored and demonstrates that the phosphorylated tyrosine and threonine will form strong ion-pair interactions with Lys714, playing a key role in the dynamic identification stage. Multiple method combinations from different points of view may be helpful for exploring other systems of the protein-protein interactions.


Assuntos
Simulação de Dinâmica Molecular , N-Acetilglucosaminiltransferases , N-Acetilglucosaminiltransferases/química , N-Acetilglucosaminiltransferases/metabolismo , Especificidade por Substrato , Glicosilação , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Acetilglucosamina/metabolismo
9.
Aquat Toxicol ; 257: 106443, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36863154

RESUMO

Neonicotinoids are widely used pesticides that contaminate aquatic environments. Although these chemicals can be photolyzed under sunlight radiation, it is unclear for the relationship between photolysis mechanism and toxicity change in aquatic organisms. This study aims to determine the photo-enhanced toxicity of four neonicotinoids with different main structures (acetamiprid, and thiacloprid for cyano-amidine structure, imidacloprid and imidaclothiz for nitroguanidine). To Achieve the goal, photolysis kinetics, effect of dissolved organic matter (DOM) and reactive oxygen species (ROSs) scavengers on photolysis rates, photoproducts, and photo-enhanced toxicity to Vibrio fischeri were investigated for four neonicotinoids. The results showed direct photolysis plays a key role in the photo-degradation of imidacloprid and imidaclothiz (photolysis rate constants are 7.85 × 10-3 and 6.48 × 10-3 min-1, respectively), while the photosensitization process of acetamiprid and thiacloprid was dominated by ·OH reactions and transformation (photolysis rate constants are 1.16 × 10-4 and 1.21 × 10-4 min-1, respectively). All four neonicotinoid insecticides exerted photo-enhanced toxicity to Vibrio fischeri, indicating photolytic product(s) posed greater toxicity than their parent compounds. The addition of DOM and ROS scavengers influenced photo-chemical transformation rates of parent compounds and their intermediates, leading to diverse effects on photolysis rates and photo-enhanced toxicity for the four insecticides as a result of different photo-chemical transformation processes. Based upon the detection of chemical structures of intermediates and Gaussian calculations, we observed different photo-enhanced toxicity mechanisms for the four neonicotinoid insecticides. Molecular docking was used to analyze the toxicity mechanism of parent compounds and photolytic products. A theoretical model was subsequently employed to describe the variability of toxicity response to each of the four neonicotinoids.


Assuntos
Inseticidas , Poluentes Químicos da Água , Inseticidas/química , Aliivibrio fischeri , Fotólise , Simulação de Acoplamento Molecular , Poluentes Químicos da Água/toxicidade , Neonicotinoides/toxicidade
10.
Ecotoxicol Environ Saf ; 254: 114728, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36889208

RESUMO

Tris(2-chloroethyl) phosphate (TCEP) has been detected all over the world as a typical refractory organic phosphate, especially in groundwater. This work applied a calcium-rich biochar derived from shrimp shell as a low-cost adsorbent for TCEP removal. Based on the kinetics and isotherm studies, the adsorption of TCEP on biochar was monolayer adsorbed on a uniform surface, with SS1000 (the biochar was prepared at the carbonization temperature of 1000 °C) achieving the maximum adsorption capacity of 264.11 mg·g-1. The prepared biochar demonstrated stable TCEP removal ability throughout a wide pH range, in the presence of co-existing anions, and in diverse water bodies. A rapid removal rate of TCEP was observed during the adsorption process. When the dosage of SS1000 was 0.2 g·L-1, 95% of TCEP could be removed within the first 30 min. The mechanism analysis indicated that the calcium species and basic functional groups on the SS1000 surface were highly involved in the TCEP adsorption process.


Assuntos
Cálcio , Poluentes Químicos da Água , Adsorção , Poluentes Químicos da Água/análise , Organofosfatos , Carvão Vegetal , Fosfatos , Cinética
11.
J Infect Chemother ; 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36921761

RESUMO

BACKGROUND: Our study aims to evaluate the performance of the combination of Sysmex urine dry chemistry analyzer UC-3500 and urine particle analyzer UF-5000 in screening bacterial urinary tract infection (UTI). METHODS: We analyzed 2000 urine specimens from patients with suspected UTI by using a urine dry chemistry analyzer (UC-3500) and a fully automated sediment analyzer (UF-5000). After being tested by the instrument, all specimens were sent to our clinical microbiology laboratory for culture. In addition, 600 urine specimens were selected to evaluate the accuracy of the six screening strategies established in this study. RESULTS: The consistency of UF-5000 bacterial classification and bacterial culture was fair (Kappa = 0.339). The counts of WBC and BACT elevated with sequential group designs (P < 0.001). The cut-off value of WBC was 32.20/µL for males (AUC, 0.942, 95%CI, 0.930-0.955) and 39.15/µL for females (AUC, 0.931, 95%CI, 0.914-0.948). The sensitivity and specificity of WBC were relatively higher than those of BACT. Strategy④ and Strategy⑥ in all six strategies had a good negative predictive value (NPV) which was 98.73%. CONCLUSION: UF-5000 bacterial classification cannot be used as a practical reference. 32.20/µL (male) and 39.15/µL (female) for WBC as well as 22.35/µL (male) and 127.25/µL (female) for BACT were used as cut-off values to effectively determine whether UTI occurs. WBC, BACT and LEU joint screening programs were suitable to rapidly and effectively exclude bacterial UTI.

13.
Biomed Opt Express ; 14(2): 987-1002, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36874482

RESUMO

Photoacoustic (PA) imaging provides unique advantages in peripheral vascular imaging due to its high sensitivity to hemoglobin. Nevertheless, limitations associated with handheld or mechanical scanning by stepping motor techniques have precluded photoacoustic vascular imaging from advancing to clinical applications. As clinical applications require flexibility, affordability, and portability of imaging equipment, current photoacoustic imaging systems developed for clinical applications usually use dry coupling. However, it inevitably induces uncontrolled contact force between the probe and the skin. Through 2D and 3D experiments, this study proved that contact forces during the scanning could significantly affect the vascular shape, size, and contrast in PA images, due to the morphology and perfusion alterations of the peripheral blood vessels. However, there is no available PA system that can control forces accurately. This study presented an automatic force-controlled 3D PA imaging system based on a six-degree-of-freedom collaborative robot and a six-dimensional force sensor. It is the first PA system that achieves real-time automatic force monitoring and control. This paper's results, for the first time, demonstrated the ability of an automatic force-controlled system to acquire reliable 3D PA images of peripheral blood vessels. This study provides a powerful tool that will advance PA peripheral vascular imaging to clinical applications in the future.

14.
Zhongguo Zhen Jiu ; 43(3): 299-303, 2023 Mar 12.
Artigo em Chinês | MEDLINE | ID: mdl-36858392

RESUMO

OBJECTIVE: To observe the effect of acupuncture at Weizhong (BL 40) with deqi on bladder urination function. METHODS: A total of 60 healthy subjects were randomized into an observation group and a control group, 30 subjects in each group. Under the guidance of ultrasound, acupuncture was applied Weizhong (BL 40) on both sides. In the observation group, the needling depth was reached to the tibial nerve, and lifting-thrusting twirling method was used to induce deqi. In the control group, the needling depth was reached to the superficial fascia, and no manipulation was operated to induce deqi. The needles were retained for 10 min and acupuncture was given once in both groups. The bilateral ureteral ejection frequency and volume of the bladder were observed by ultrasound before and after acupuncture, and the score of clinical evaluation scale of deqi sensation was observed in both groups. RESULTS: After acupuncture, the frequency of bilateral ureteral ejection in the observation group and the bladder volume in the two groups were increased compared before acupuncture (P<0.05), and the frequency of bilateral ureteral ejection, bladder volume and score of clinical evaluation scale of deqi sensation in the observation group were higher than those in the control group (P<0.05, P<0.01). CONCLUSION: Acupuncture at Weizhong (BL 40) with deqi improves the bladder urination function. Ultrasound visualization improves the standardization and safety of acupuncture, intuitively evaluates the acupuncture effect, and provides an objective basis for the correlation between meridian points specificity and zang-fu organs.


Assuntos
Terapia por Acupuntura , Meridianos , Humanos , Micção , Bexiga Urinária , Pontos de Acupuntura
15.
Food Res Int ; 165: 112542, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36869455

RESUMO

The preparation of emulsion films using pre-emulsification has received extensive attention due to the enhancement of oil binding capacity. However, the different effects of water in oil (W/O) and oil in water (O/W) pre-emulsions on the physicochemical properties of films are still unclear. Therefore, the soy protein isolate (SPI) based emulsion films were prepared by W/O or O/W pre-emulsion using sucrose esters with different hydrophile-lipophile balances to investigate the properties of SPI emulsion (SPIE) films. The viscosity, storage moduli, and loss moduli of film-forming solutions (FFSs) with O/W pre-emulsion were higher than those of FFSs with W/O pre-emulsion. The oil droplets of FFSs with W/O pre-emulsion were large and uneven, and the oil droplet size increased after drying. Phase separation and macroporous network appeared in cross-sectional of SPIE films with W/O pre-emulsion according to scanning electron microscope images. Meanwhile, the SPIE films with W/O pre-emulsion demonstrated higher oil concentration and hydrophobicity on the upper surface compared with the SPIE films with O/W pre-emulsion. Low tensile strength, glass transition temperature, and high elongation at break and transparency value of SPIE films with O/W pre-emulsions were founded. The water vapor permeability of SPIE films with W/O pre-emulsion increased with the addition of oil, whereas the opposite trend appeared in that with O/W pre-emulsion. In conclusion, the structure and porosity of emulsion films could be affected by the pre-emulsion types, which can determine the application ranges.


Assuntos
Ésteres , Proteínas de Soja , Emulsões , Estudos Transversais , Cetonas , Sacarose
16.
Molecules ; 28(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36903498

RESUMO

Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O2∙-) and singlet oxygen (1O2) in water under light irradiation, which were 2.6-fold and 15.4-fold higher than those of free PcSA, respectively. Furthermore, PcSA@Lip was able to accumulate selectively in tumors after intravenous injection with the fluorescence intensity ratio of tumors to livers was 4.1:1. The significant tumor inhibition effects resulted in a 98% tumor inhibition rate after PcSA@Lip was injected intravenously at an ultra-low PcSA@Lip dose (0.8 nmol g-1 PcSA) and light dose (30 J cm-2). Therefore, the liposomal PcSA@Lip is a prospective nanophotosensitizer possessing hybrid type I and type II photoreactions with efficient photodynamic anticancer effects.


Assuntos
Fotoquimioterapia , Zinco , Estudos Prospectivos , Fármacos Fotossensibilizantes/química , Isoindóis , Enxofre
17.
Artigo em Inglês | MEDLINE | ID: mdl-36901386

RESUMO

The coronavirus disease 2019 (COVID-19) poses a huge challenge to global public health. People with schizophrenia living in communities urgently need effective interventions to help them adjust to life and work, but they have not received enough attention. This study aims to assess the prevalence of anxiety and depression symptoms in community-dwelling patients with schizophrenia in China during the epidemic and to explore the possible influencing factors. METHODS: Using a cross-sectional survey, we collected 15,165 questionnaires. Assessments included demographic information, concern about COVID-19-related information, sleep status, anxiety and depressive symptoms, and accompanying illnesses. The 7-item Generalized Anxiety Disorder (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9) were used to evaluate depression and anxiety levels. Group comparison was conducted by t-test, ANOVA, or chi-square test wherever suitable, with Bonferroni pairwise correction. Multivariate logistic regression was performed to identify predictors for anxiety and depression. RESULTS: 16.9% of patients had at least moderate anxiety, and 34.9% had at least moderate depression. T-test showed that females scored higher on GAD-7 and PHQ-9 than males, and patients without accompanying long-standing diseases, who were not concerned about COVID-19, had lower GAD-7 and PHQ-9 scores. ANOVA showed that participants aged from 30 to 39, with higher education scored higher on GAD-7, and patients with better sleep, and having less concern about COVID-19, had lower GAD-7 and PHQ-9 scores. Regression analysis indicated that participant ages of 30-39 and 40-49 positively predicted anxiety, whereas patient ages of 30-39 years positively predicted depression. Patients with poor sleep, accompanying diseases, and concern about the COVID-19 pandemic were more likely to experience anxiety and depression. CONCLUSION: During the pandemic, Chinese community-dwelling patients with schizophrenia had high rates of anxiety and depression. These patients deserve clinical attention and psychological intervention, especially those with risk factors.


Assuntos
COVID-19 , Esquizofrenia , Masculino , Feminino , Humanos , Idoso , Adulto , COVID-19/epidemiologia , Pandemias , Depressão/epidemiologia , Esquizofrenia/epidemiologia , Estudos Transversais , Vida Independente , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , China/epidemiologia
18.
J Neurosci ; 43(12): 2090-2103, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36781221

RESUMO

The macaque middle temporal (MT) area is well known for its visual motion selectivity and relevance to motion perception, but the possibility of it also reflecting higher-level cognitive functions has largely been ignored. We tested for effects of task performance distinct from sensory encoding by manipulating subjects' temporal evidence-weighting strategy during a direction discrimination task while performing electrophysiological recordings from groups of MT neurons in rhesus macaques (one male, one female). This revealed multiple components of MT responses that were, surprisingly, not interpretable as behaviorally relevant modulations of motion encoding, or as bottom-up consequences of the readout of motion direction from MT. The time-varying motion-driven responses of MT were strongly affected by our strategic manipulation-but with time courses opposite the subjects' temporal weighting strategies. Furthermore, large choice-correlated signals were represented in population activity distinct from its motion responses, with multiple phases that lagged psychophysical readout and even continued after the stimulus (but which preceded motor responses). In summary, a novel experimental manipulation of strategy allowed us to control the time course of readout to challenge the correlation between sensory responses and choices, and population-level analyses of simultaneously recorded ensembles allowed us to identify strong signals that were so distinct from direction encoding that conventional, single-neuron-centric analyses could not have revealed or properly characterized them. Together, these approaches revealed multiple cognitive contributions to MT responses that are task related but not functionally relevant to encoding or decoding of motion for psychophysical direction discrimination, providing a new perspective on the assumed status of MT as a simple sensory area.SIGNIFICANCE STATEMENT This study extends understanding of the middle temporal (MT) area beyond its representation of visual motion. Combining multineuron recordings, population-level analyses, and controlled manipulation of task strategy, we exposed signals that depended on changes in temporal weighting strategy, but did not manifest as feedforward effects on behavior. This was demonstrated by (1) an inverse relationship between temporal dynamics of behavioral readout and sensory encoding, (2) a choice-correlated signal that always lagged the stimulus time points most correlated with decisions, and (3) a distinct choice-correlated signal after the stimulus. These findings invite re-evaluation of MT for functions outside of its established sensory role and highlight the power of experimenter-controlled changes in temporal strategy, coupled with recording and analysis approaches that transcend the single-neuron perspective.


Assuntos
Percepção de Movimento , Animais , Masculino , Feminino , Macaca mulatta , Percepção de Movimento/fisiologia , Comportamento de Escolha/fisiologia , Lobo Temporal/fisiologia , Estimulação Luminosa
19.
Chemistry ; : e202203363, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36826395

RESUMO

Acetylcholinesterase (AChE) is a key target for the current symptomatic treatment of Alzheimer's disease, and galantamine is a clinical anticholinesterase drug with transiently acting characteristic and good selectivity for AChE. The present theoretical-experimental work improves the drug's residence time without reducing the inhibition effect, thus providing a crucial breakthrough for modifying the inhibitor of AChE with better kinetic behavior. The static binding and dynamic delivery properties acquired from atomic view reveal that the galantamine simply occupies a catalytic anionic site, and its release from AChE needs only ∼8.6 kcal/mol. Both of these may cause the short residence time of galantamine. The hotspots and most favorable transport mechanism are identified, and the hydrogen bond and aromatic stacking interactions are observed to play crucial roles for galantamine binding and release in AChE. The typical peripheral anionic site arisen at the delivery process would provide another key occupation to enhance the anti-release ability for inhibitors. The compound with "specific-ring-chain-ring" framework with detailed beneficial modification scheme is summarized, which may improve the residence time of the inhibitor in AChE. The thermodynamic and dynamic properties of galantamine derivatives are also studied. Based on dictamnine, a natural alkaloid, two novel eligible derivatives are designed, synthesized and evaluated, which verifies our prediction. Multiple computational approaches and experimental combinations probably provide a train of thought from both static and dynamic views to modify or design appropriate inhibitors on the basis of specific binding and transportation features.

20.
Funct Integr Genomics ; 23(1): 61, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36792760

RESUMO

Breast cancer is the malignant tumor with the highest incidence in women worldwide. It is highly heterogeneous, has a high incidence of drug resistance, recurrence, and metastasis, and is one of the malignant tumors with the highest mortality rate. The early diagnosis, treatment monitoring, and prognosis assessment of breast cancer are the key factors affecting the survival of patients. However, due to the lack of specific biomarkers, breast cancer is still an essential factor affecting women's quality of life and physical and mental health. Long non-coding RNA can regulate various genes and different signaling pathways and plays an essential role in the occurrence and development of tumors. Recent studies have found that the abnormal expression of circulating long non-coding RNA in serum, saliva, and other biological body fluids plays a significant role in early diagnosis, pathological classification, stage, therapeutic effect monitoring, and prognosis evaluation of breast cancer. This article will review the potential application value of circulating lncRNA in breast cancer.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , RNA Longo não Codificante/metabolismo , Qualidade de Vida , Biomarcadores , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica
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