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1.
J Chem Inf Model ; 64(18): 6979-6992, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39230508

RESUMEN

RNA small molecule interactions play a crucial role in drug discovery and inhibitor design. Identifying RNA small molecule binding nucleotides is essential and requires methods that exhibit a high predictive ability to facilitate drug discovery and inhibitor design. Existing methods can predict the binding nucleotides of simple RNA structures, but it is hard to predict binding nucleotides in complex RNA structures with junctions. To address this limitation, we developed a new deep learning model based on spatial correlation, ZHmolReSTasite, which can accurately predict binding nucleotides of small and large RNA with junctions. We utilize RNA surface topography to consider the spatial correlation, characterizing nucleotides from sequence and tertiary structures to learn a high-level representation. Our method outperforms existing methods for benchmark test sets composed of simple RNA structures, achieving precision values of 72.9% on TE18 and 76.7% on RB9 test sets. For a challenging test set composed of RNA structures with junctions, our method outperforms the second best method by 11.6% in precision. Moreover, ZHmolReSTasite demonstrates robustness regarding the predicted RNA structures. In summary, ZHmolReSTasite successfully incorporates spatial correlation, outperforms previous methods on small and large RNA structures using RNA surface topography, and can provide valuable insights into RNA small molecule prediction and accelerate RNA inhibitor design.


Asunto(s)
Conformación de Ácido Nucleico , Nucleótidos , ARN , ARN/química , ARN/metabolismo , Nucleótidos/química , Nucleótidos/metabolismo , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/metabolismo , Aprendizaje Profundo , Modelos Moleculares , Propiedades de Superficie
2.
Radiat Oncol ; 19(1): 125, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304905

RESUMEN

BACKGROUND: To investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC). METHODS: During 2012-2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores. RESULTS: After a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant. CONCLUSION: Increases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.


Asunto(s)
Quimioradioterapia , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Calidad de Vida , Humanos , Masculino , Femenino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidad , Carcinoma Nasofaríngeo/patología , Persona de Mediana Edad , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/psicología , Adulto , Pronóstico , Anciano , Estudios Longitudinales , Tasa de Supervivencia , Adulto Joven , Estudios de Seguimiento
3.
J Chem Inf Model ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39265103

RESUMEN

The interaction between RNA and small molecules is crucial in various biological functions. Identifying molecules targeting RNA is essential for the inhibitor design and RNA-related studies. However, traditional methods focus on learning RNA sequence and secondary structure features and neglect small molecule characteristics, and resulting in poor performance on unknown small molecule testing. To overcome this limitation, we developed a double-layer stacking-based machine learning model called ZHMol-RLinter. This approach more effectively predicts RNA-small molecule binding preferences by learning RNA and small molecule features to capture their interaction information. ZHMol-RLinter also combines sequence and secondary structural features with structural geometric and physicochemical environment information to capture the specificity of RNA spatial conformations in recognizing small molecules. Our results demonstrate that ZHMol-RLinter has a success rate of 90.8% on the published RL98 testing set, representing a significant improvement over existing methods. Additionally, ZHMol-RLinter achieved a success rate of 77.1% on the unknown small molecule UNK96 testing set, showing substantial improvement over the existing methods. The evaluation of predicted structures confirms that ZHMol-RLinter is reliable and accurate for predicting RNA-small molecule binding preferences, even for challenging unknown small molecule testing. Predicting RNA-small molecule binding preferences can help in the understanding of RNA-small molecule interactions and promote the design of RNA-related drugs for biological and medical applications.

4.
J Am Chem Soc ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263905

RESUMEN

Asymmetric enamine alkylation represents a powerful tool for stereoselective C-C bond formation; in contrast, the development of enantioselective enamine acylation remains elusive. Here, we report that a chiral phosphoric acid can render an in-situ-formed enamine to undergo a stereoselective intramolecular α-carbon acylation, providing an alternative approach for the synthesis of useful pyrrolinones and indolinones bearing tetrasubstituted stereocenters. Utilizing an effective integration of the desymmetrization strategy and bifunctional organocatalysis, the first example of enantioselective enamine acylation is achieved by employing readily available aminomalonic esters and cyclic ketones. Instead of reactive and moisture-sensitive acyl chlorides, common esters with low electrophilicity were successfully used as efficient acylating reagents via hydrogen bonding interactions. The utility is demonstrated in the concise and enantioselective synthesis of (+)-LipidGreen I and II. Experimental studies and DFT calculations establish the reaction pathway and the origin of stereocontrol.

5.
Open Med (Wars) ; 19(1): 20240959, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38961882

RESUMEN

The aim of the present study was to explore the risk factors of postoperative airway complications in children with oral floor mass. The first choice of auxiliary examination method for children with oral floor mass is also proposed. This retrospective study included 50 children with floor-of-mouth (FOM) masses. Medical records were reviewed, and information on age of onset, functional impacts present, age at consultation, imaging findings, history of preoperative aspiration, pathology findings, properties of biopsied fluid, treatment modality, postoperative outcomes, and operation were recorded. A total of 20 patients exhibited functional impacts such as difficulty in breathing and feeding. Ultrasound examination was performed in 28 cases; and magnetic resonance imaging, in 38 cases. The diagnosis was lymphatic malformation in 12 cases, developmental cyst in 29 cases, and solid mass in 7 cases. There were 28 cases of surgical resection, 9 cases underwent multiple puncture volume reduction followed by surgery, 11 cases treated using sclerotherapy injection, and 1 case treated using sclerotherapy injection and surgical resection. Young age, functional impact, and high grade of lymphatic duct malformation increased the risk of surgical treatment. B-scan ultrasound is the first choice for the diagnosis of FOM masses in children.

6.
Radiother Oncol ; 197: 110324, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38735537

RESUMEN

PURPOSE: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders. METHODS: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia. RESULTS: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups. CONCLUSION: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice.


Asunto(s)
Ansiedad , Depresión , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Calidad de Vida , Humanos , Estudios Transversales , Masculino , Femenino , Carcinoma Nasofaríngeo/psicología , Carcinoma Nasofaríngeo/epidemiología , Persona de Mediana Edad , Depresión/epidemiología , Depresión/etiología , Ansiedad/epidemiología , Ansiedad/etiología , Neoplasias Nasofaríngeas/psicología , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/epidemiología , Incidencia , China/epidemiología , Adulto , Anciano , Prevalencia , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/etiología
7.
Cancer Immunol Immunother ; 73(7): 132, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38753055

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.


Asunto(s)
Adenocarcinoma , Protocolos de Quimioterapia Combinada Antineoplásica , Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico , Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor ErbB-2/metabolismo , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Ensayos Clínicos Fase III como Asunto , Biomarcadores de Tumor/metabolismo
8.
Expert Opin Drug Saf ; : 1-9, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38646719

RESUMEN

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

9.
Sci Rep ; 14(1): 5600, 2024 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454088

RESUMEN

Research has demonstrated the positive effect of natural environment on human restoration and well-being. Time spent in nature can often alleviate both physiological and psychological stress. However, few studies have discussed the environmental health effects of the nature's components and characteristics. Sixty volunteers were recruited and one manufactured environment and five different natural environments were randomly assigned to them, including coniferous forests (pure coniferous forest-PC and mixed coniferous forest-MC), broad-leaved forests (pure broad-leaved forest-PB and mixed broad-leaved forest-MB), and mixed forest (mixed coniferous and broad-leaved forest-MCB). Each volunteer sat in a built or natural environment and looked around the environment for 15 min. Physiological (HR, HRV, BP, pulse rate and salivary cortisol) and psychological indicators (POMS and STAI) were used to evaluate the changes in their stress level. Results indicated a strong difference in HR, HRV, POMS and STAI between the built and natural environment, which showed that natural environment can lower the stress level. MC had the best effect on relieving physiological stress, whereas MCB is most successful in improving emotional state and reducing anxiety. Broad-leaved forest and mixed forest significantly affected the DBP and vigor level of the subjects, respectively. While coniferous forest did significantly increase the concentration of salivary cortisol in subjects. The study confirmed that compared to the built environment, the natural environment can relieve the human body's physical and psychological stress and negative emotions, while significantly increasing vitality. And different plant communities also have different effects on the physiological and psychological indicators of the subjects. These results will provide scientific basis for the construction and improvement of urban green space environment.


Asunto(s)
Hidrocortisona , Tracheophyta , Humanos , Ansiedad , China , Emociones , Bosques , Árboles , Distribución Aleatoria
10.
Nat Commun ; 15(1): 949, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38297016

RESUMEN

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Síndrome Mano-Pie , Neoplasias Nasofaríngeas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina/uso terapéutico , Síndrome Mano-Pie/etiología , Carcinoma Nasofaríngeo/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología
11.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1020466

RESUMEN

Objective:To explore the current situation of binary coping in patients with perimenopausal syndrome and analyze its influencing factors, in order to provide a basis for improving the level of binary coping.Methods:Using convenience sampling method, a total of 210 patients with perimenopausal syndrome and their spouses from the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine were cross-sectional surveyed by a general data questionnaire, the Binary Coping Scale, and the Modified Kupperman Score Scale. The influencing factors of binary coping level in patients with perimenopausal syndrome were explored by univariate analysis and variance decomposition model analysis.Results:A total of 200 valid questionnaires were retrieved.The patients aged (50.52 ± 2.89) years old. The binary coping score was (79.64 ± 22.74) points. The variance decomposition model analysis showed that marriage age, type of medical insurance, number of children, education level, family monthly income, spouse′s education level, presence of major comorbidities in spouse, modified Kupperman score, presence of generalized anxiety in spouse were the main influencing factors of binary coping in patients with perimenopausal syndrome (all P<0.05). Conclusions:The binary coping scores of patients with perimenopausal syndrome are lower than normal, and considering the influence and involvement of patients' spouses, nursing staff should pay special attention to patients who are married relatively early, have more children, have lower education levels, and have lower family monthly incomes. Additionally, attention should be given to spouses who experience widespread anxiety, have a lower level of education, and suffer from major chronic diseases. By developing and implementing comprehensive intervention measures aimed at improving the Kupperman score and the level of binary coping, both parties can be encouraged to support each other more effectively, thereby improving the marital relationships of patients during the perimenopausal period.

12.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013345

RESUMEN

ObjectiveMyelodysplastic syndromes (MDS) is a group of clonal hematopoietic stem cell disorders,and this study aims to investigate the expression of hypoxia-inducible factor-1α(HIF-1α) in the bone marrow cells of patients with MDS and its correlation with the clinical features of MDS,the therapeutic efficacy of arsenic-containing Chineseherbal compound,and the survival prognosis. MethodAccording to the inclusion and exclusion criteria,27 MDS patients treated with arsenic-containing Chinese herbal compound in the Department of Hematology,Xiyuan Hospital,China Academy of Chinese Medical Sciences from January 2022 to September 2022 were included,and their bone marrow samples were collected by myelotomy. HIF-1α expression level in bone marrow cells was detected by real-time polymerase chain reaction (PCR) to analyze its correlation with clinical features,and logistic and Cox regression was used to analyze the risk factors affecting the efficacy and prognostic survival of MDS patients. ResultThe HIF-1α mRNA expression level was lower in bone marrow cells of MDS patients than in healthy subjects. HIF-1α was positively correlated with the degree of myelodysplasia(r=0.384,P<0.05) and bone marrow granulocytic system%(G%)(r=0.560,P<0.01). Logistic regression showed that HIF-1α was a risk factor for the prognosis in the follow-up of the efficacy of treatment(P<0.05)and Cox regression showed that HIF-1α was an independent factor affecting the survival prognosis of MDS patients [odds ratio(OR)=398.968,95% confidence interval(CI)(1.281,116 858.743),P<0.05]. ConclusionThe level of HIF-1α expression in bone marrow cells of MDS patients was closely related to the degree of clinical myelodysplasia and G%,and HIF-1α was a risk factor for the efficacy for and survival prognosis of MDS patients.

13.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1009507

RESUMEN

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.


Asunto(s)
Humanos , Antígeno B7-H1/metabolismo , Células Madre Mesenquimatosas/inmunología , Linfocitos T/metabolismo , Inmunomodulación
14.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1024304

RESUMEN

Periapical periodontitis arises from the interaction between microbial factors and the inflammatory response of the host's periapical tissues. In this process, bacteria and their byproducts serve as the primary drivers for the initiation, progression, and spread of the disease. Pulp infections and periapical lesions are primarily dominated by gram-negative bacteria. The endotoxin lipopolysaccharide component of these bacteria plays a crucial role in pulp infection, triggering clinical symptoms, inflammatory reactions, and bone tissue resorption. Similarly, lipoteichoic acid and lipopolysaccharide from gram-positive bacteria exhibit similar pathogenic characteristics, causing damage to pulp and periapical tissues. The aim of this review is to delve deeper into the distribution patterns and pathogenesis of periapical microorganisms in chronic periapical periodontitis.

15.
Phys Chem Chem Phys ; 26(1): 130-143, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-38063012

RESUMEN

Biological processes such as transcription, repair, and regulation require interactions between DNA and proteins. To unravel their functions, it is imperative to determine the high-resolution structures of DNA-protein complexes. However, experimental methods for this purpose are costly and technically demanding. Consequently, there is an urgent need for computational techniques to identify the structures of DNA-protein complexes. Despite technological advancements, accurately identifying DNA-protein complexes through computational methods still poses a challenge. Our team has developed a cutting-edge deep-learning approach called DDPScore that assesses DNA-protein complex structures. DDPScore utilizes a 4D convolutional neural network to overcome limited training data. This approach effectively captures local and global features while comprehensively considering the conformational changes arising from the flexibility during the DNA-protein docking process. DDPScore consistently outperformed the available methods in comprehensive DNA-protein complex docking evaluations, even for the flexible docking challenges. DDPScore has a wide range of applications in predicting and designing structures of DNA-protein complexes.


Asunto(s)
Aprendizaje Profundo , Proteínas/química , Redes Neurales de la Computación , Proyectos de Investigación , ADN/química , Unión Proteica
16.
Angew Chem Int Ed Engl ; 62(48): e202313797, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-37814442

RESUMEN

The Biltz synthesis establishes straightforward access to 5,5-disubstituted (thio)hydantoins by combining a 1,2-diketone and a (thio)urea. Its appealing features include inherent atom and step economy together with the potential to generate structurally diverse products. However, control of the stereochemistry of this reaction has proven to be a daunting challenge. Herein, we describe the first example of enantioselective catalytic Biltz synthesis which affords more than 40 thiohydantoins with high stereo- and regio-control, irrespective of the symmetry of thiourea structure. A one pot synthesis of corresponding hydantoins is also documented. Remarkably, experimental studies and DFT calculations establish the reaction pathway and origin of stereoselectivity.

17.
Micromachines (Basel) ; 14(9)2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37763905

RESUMEN

Biomimetic switchable adhesion interfaces (BSAIs) with dynamic adhesion states have demonstrated significant advantages in micro-manipulation and bio-detection. Among them, gecko-inspired adhesives have garnered considerable attention due to their exceptional adaptability to extreme environments. However, their high adhesion strength poses challenges in achieving flexible control. Herein, we propose an elegant and efficient approach by fabricating three-dimensional mushroom-shaped polydimethylsiloxane (PDMS) micropillars on a flexible PDMS substrate to mimic the bending and stretching of gecko footpads. The fabrication process that employs two-photon polymerization ensures high spatial resolution, resulting in micropillars with exquisite structures and ultra-smooth surfaces, even for tip/stem ratios exceeding 2 (a critical factor for maintaining adhesion strength). Furthermore, these adhesive structures display outstanding resilience, enduring 175% deformation and severe bending without collapse, ascribing to the excellent compatibility of the micropillar's composition and physical properties with the substrate. Our BSAIs can achieve highly controllable adhesion force and rapid manipulation of liquid droplets through mechanical bending and stretching of the PDMS substrate. By adjusting the spacing between the micropillars, precise control of adhesion strength is achieved. These intriguing properties make them promising candidates for various applications in the fields of microfluidics, micro-assembly, flexible electronics, and beyond.

18.
Sci Total Environ ; 900: 165782, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37495152

RESUMEN

Large-scale wind energy development is one of the main paths to achieving China's carbon peak and neutrality goals. How will the wind power and corresponding carbon abatement potential (CAP) in China change when China reaches the timing of its reduction carbon targets? This issue has not been well addressed. In this paper, a weighted multi-model ensemble with 14 global climate models from Phase 6 of the Coupled Model Intercomparison Project (CMIP6) is used to evaluate the spatio-temporal characteristics of wind speed over China during the baseline period (2004-2014). Then, we further analyze the changes in wind power and corresponding CAP due to the climate change over China in the two-level years (2030 and 2060) under the SSP2-4.5 and SSP5-8.5 scenarios. The results show that the wind capacity factor over China will have a trend of decreasing in most regions of China and increasing in the southeast in 2060. Overall, climate change will have a slight impact on the CAP of wind power in 2030, with an increase in some southern provinces. However, the CAP of wind power will decrease significantly in most regions of China in 2060 under the SSP2-4.5 scenario, especially in Shanxi, Inner Mongolia, Ningxia, and Liaoning, by more than 5 %. Under the SSP5-8.5 scenario, the CAP will decrease significantly in the southwest and northwest regions, such as Sichuan and Qinghai, by 9.86 % and 8.19 % respectively. Central and South provinces such as Hunan and Hubei will increase by about 5 %. In terms of seasonal changes, the CAP of wind power will decrease significantly in summer under the SSP2-4.5 scenario (about -5.24 %) and SSP5-8.5 scenario (about -6.50 %).These findings can help policymakers make decisions as they establish plans for wind power expansion while taking the effects of climate change into account as they work toward China's carbon neutrality goal.

19.
Lipids Health Dis ; 22(1): 81, 2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37365637

RESUMEN

BACKGROUND: Dysregulation of lipid metabolism is closely associated with cancer progression. The study aimed to establish a prognostic model to predict distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC), based on lipidomics. METHODS: The plasma lipid profiles of 179 patients with locoregionally advanced NPC (LANPC) were measured and quantified using widely targeted quantitative lipidomics. Then, patients were randomly split into the training (125 patients, 69.8%) and validation (54 patients, 30.2%) sets. To identify distant metastasis-associated lipids, univariate Cox regression was applied to the training set (P < 0.05). A deep survival method called DeepSurv was employed to develop a proposed model based on significant lipid species (P < 0.01) and clinical biomarkers to predict DMFS. Concordance index and receiver operating curve analyses were performed to assess model effectiveness. The study also explored the potential role of lipid alterations in the prognosis of NPC. RESULTS: Forty lipids were recognized as distant metastasis-associated (P < 0.05) by univariate Cox regression. The concordance indices of the proposed model were 0.764 (95% confidence interval (CI), 0.682-0.846) and 0.760 (95% CI, 0.649-0.871) in the training and validation sets, respectively. High-risk patients had poorer 5-year DMFS compared with low-risk patients (Hazard ratio, 26.18; 95% CI, 3.52-194.80; P < 0.0001). Moreover, the six lipids were significantly correlated with immunity- and inflammation-associated biomarkers and were mainly enriched in metabolic pathways. CONCLUSIONS: Widely targeted quantitative lipidomics reveals plasma lipid predictors for LANPC, the prognostic model based on that demonstrated superior performance in predicting metastasis in LANPC patients.


Asunto(s)
Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/patología , Pronóstico , Carcinoma/patología , Lipidómica , Lípidos
20.
BMC Cancer ; 23(1): 410, 2023 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-37149594

RESUMEN

BACKGROUND: To develop and validate a predictive nomogram for tumor residue 3-6 months after treatment based on postradiotherapy plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA), clinical stage, and radiotherapy (RT) dose in patients with stage II-IVA nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). METHODS: In this retrospective study, 1050 eligible patients with stage II-IVA NPC, who completed curative IMRT and underwent pretreatment and postradiotherapy (-7 to +28 days after IMRT) EBV DNA testing, were enrolled from 2012 to 2017. The prognostic value of the residue was explored using Cox regression analysis in patients (n=1050). A nomogram for predicting tumor residues after 3-6 months was developed using logistic regression analyses in the development cohort (n=736) and validated in an internal cohort (n=314). RESULTS: Tumor residue was an independent inferior prognostic factor for 5-year overall survival, progression-free survival, locoregional recurrence-free survival and distant metastasis-free survival (all P<0.001). A prediction nomogram based on postradiotherapy plasma EBV DNA level (0 vs. 1-499 vs. ≥500 copies/ml), clinical stage (II vs. III vs. IVA), and RT dose (68.00-69.96 vs. 70.00-74.00 Gy) estimated the probability of residue development. The nomogram showed better discrimination (area under the curve (AUC): 0.752) than either the clinical stage (0.659) or postradiotherapy EBV DNA level (0.627) alone in the development and validation cohorts (AUC: 0.728). CONCLUSIONS: We developed and validated a nomogram model integrating clinical characteristics at the end of IMRT for predicting whether tumor will residue or not after 3-6 months. Thus, high-risk NPC patients who might benefit from immediate additional intervention could be identified by the model, and the probability of residue can be reduced in the future.


Asunto(s)
Carcinoma , Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Carcinoma Nasofaríngeo/patología , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/radioterapia , Carcinoma/patología , Estudios Retrospectivos , Nomogramas , Neoplasias Nasofaríngeas/patología , ADN Viral , Pronóstico
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