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2.
Nat Commun ; 15(1): 7317, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39183335

RESUMO

N-oxides play a pivotal role in natural products and emerging drug design, while also serving as valuable ligand scaffolds in organometallic chemistry. Among heteroatom oxidations, the conversion of amines to N-oxides is a critical and challenging facet. We present here a highly enantioselective N-oxidation methodology for both cyclic and acyclic amines. The method employs an ion-pair catalyst comprising a chiral bisguanidinium [BG]2+ cation and an achiral oxodiperoxomolybdosulfate anion [(µ-SO4)2Mo2O2(µ-O2)2(O2)2]2-. Notably, the bisguanidinium cation undergoes modification through silyl group incorporation and is elucidated by X-ray crystallography. Our findings underscore the crucial role of the side chain in the determination of the chiral pocket size, allowing for the oxidation of diverse tertiary amines with enantioselectivities. Comprehensive mechanistic investigations are conducted to explain the catalytic system's efficacy in achieving dynamic kinetic resolution (DKR) with high efficiency.

3.
Hum Brain Mapp ; 45(12): e26814, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39163575

RESUMO

Subjective cognitive decline (SCD) is a high-risk population in the preclinical stage of Alzheimer's disease (AD), and olfactory dysfunction is a risk factor for dementia progression. The present study aimed to explore the patterns of functional connectivity (FC) changes in the olfactory neural circuits during olfactory stimulation in SCD subjects. A total of 56 SCD subjects and 56 normal controls (NCs) were included. All subjects were assessed with a cognitive scale, an olfactory behavior test, and olfactory task-based functional magnetic resonance imaging scanning. The FC differences in olfactory neural circuits between the two groups were analyzed by the generalized psychophysiological interaction. Additionally, we calculated and compared the activation of brain regions within the olfactory neural circuits during odor stimulation, the volumetric differences in brain regions showing FC differences between groups, and the correlations between neuroimaging indicators and olfactory behavioral and cognitive scale scores. During odor stimulation, the FC between the bilateral primary olfactory cortex (bPOC) and the right hippocampus in the SCD group was significantly reduced; while the FC between the right hippocampus and the right frontal cortex was significantly increased in the SCD group. The bPOC of all subjects showed significant activation, but no significant difference in activation between groups was found. No significant differences were observed in the volume of the brain regions within the olfactory neural circuits or in olfactory behavior between groups. The volume of the bPOC and right frontal cortex was significantly positively correlated with olfactory identification, and the volume of the right frontal cortex and right hippocampus was significantly correlated with cognitive functions. Furthermore, a significant correlation between the activation of bPOC and the olfactory threshold was found in the whole cohort. These results suggested that while the structure of the olfactory neural circuits and olfactory behavior in SCD subjects remained stable, there were significant changes observed in the FC of the olfactory neural circuits (specifically, the POC-hippocampus-frontal cortex neural circuits) during odor stimulation. These findings highlight the potential of FC alterations as sensitive imaging markers for identifying high-risk individuals in the early stage of AD.


Assuntos
Disfunção Cognitiva , Lobo Frontal , Hipocampo , Imageamento por Ressonância Magnética , Córtex Olfatório , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Córtex Olfatório/diagnóstico por imagem , Córtex Olfatório/fisiologia , Córtex Olfatório/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiopatologia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Percepção Olfatória/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/fisiologia , Conectoma , Odorantes
4.
Opt Lett ; 49(15): 4294-4297, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090917

RESUMO

To realize compact and denser photonic integrated circuits, three-dimensional integration has been widely accepted and researched. In this article, we demonstrate the operation of a 3D integrated silicon photonic platform fabricated through wafer bonding. Benefiting from the wafer bonding process, the material of all layers is c-Si, which ensures that the mobility is high enough to achieve a nanosecond response via the p-i-n diode shifter. Optical components, including multimode interferences (MMIs), waveguide crossing, and Mach-Zehnder interferometer (MZI)-based switch, are fabricated in different layers and exhibit great performance. The interlayer coupler and crossing achieve a 0.98 dB coupling loss and <-43.58 dB cross talk, while the crossing fabricated in the same layer shows <-36.00 dB cross talk. A nanosecond-order switch response is measured in different layers.

5.
Pharmaceuticals (Basel) ; 17(8)2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39204153

RESUMO

The establishment and utilization of preclinical animal models constitute a pivotal aspect across all facets of cancer research, indispensably contributing to the comprehension of disease initiation and progression mechanisms, as well as facilitating the development of innovative anti-cancer therapeutic approaches. These models have emerged as crucial bridges between basic and clinical research, offering multifaceted support to clinical investigations. This study initially focuses on the importance and benefits of establishing preclinical animal models, discussing the different types of preclinical animal models and recent advancements in cancer research. It then delves into cancer treatment, studying the characteristics of different stages of tumor development and the development of anti-cancer drugs. By integrating tumor hallmarks and preclinical research, we elaborate on the path of anti-cancer drug development and provide guidance on personalized cancer therapy strategies, including synthetic lethality approaches and novel drugs widely adopted in the field. Ultimately, we summarize a strategic framework for selecting preclinical safety experiments, tailored to experimental modalities and preclinical animal species, and present an outlook on the prospects and challenges associated with preclinical animal models. These models undoubtedly offer new avenues for cancer research, encompassing drug development and personalized anti-cancer protocols. Nevertheless, the road ahead continues to be lengthy and fraught with obstacles. Hence, we encourage researchers to persist in harnessing advanced technologies to refine preclinical animal models, thereby empowering these emerging paradigms to positively impact cancer patient outcomes.

6.
Front Pediatr ; 12: 1372514, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39170601

RESUMO

Objective: The aim of the study was to develop a prediction nomogram based on clinical factors to assess the risk of postoperative complications in children with congenital choledochal cyst. Methods: The clinical data from 131 children who underwent choledochal cyst resection and Roux-en-Y hepaticojejunostomy in our hospital between January 2016 and December 2022 were retrospectively analyzed. The general information, clinical symptoms, procedure, biochemical indicators, and imaging data were recorded. A prolonged hospital stay induced by postoperative complications or a follow-up over 6 months was assessed as the event outcome. A logistics regression analysis was performed to screen for risk factors with statistical significance in inducing postoperative complications. Then, with the dataset split into the training group and internal validation group, the nomogram for the prediction of postoperative complications was developed based on a computer algorithm. In addition, the receiver operating characteristic (ROC) curve and calibration curve were performed for nomogram verification. Results: Of 131 children, the multivariate logistics regression analysis suggested that age ≤2 years [odds ratio (OR) 0.93; 95% confidence interval (CI) 0.15-5.65; p = 0.938], Todani classification type 1 (OR 36.58; 95% CI 4.14-871.74; p = 0.005), cyst wall thickness >0.4 cm (OR 10.82; 95% CI 2.88-49.13; p < 0.001), with chronic cholecystitis (OR 7.01; 95% CI 1.62-38.52; p = 0.014), and choledochal cyst diameter (OR 1.01; 95% CI 0.99-1.03; p = 0.370) were predictors associated with the postoperative complications of choledochal cysts. The data were randomly divided into the training group (n = 92) and internal validation group (n = 39) to build the prediction nomogram including the appeal factors. The accuracy and discrimination of the model were evaluated using a ROC curve and calibration curve. The results showed that the nomogram area under the ROC curve [area under the curve (AUC) = 0.894; 95% CI 0.822-0.966; p < 0.001], validation (AUC = 0.844; 95% CI 0.804-0.952; p < 0.001), and Brier = 0.120 (95% CI 0.077-0.163p; p < 0.001) were indicative of the good stability and calibration of the predictive nomogram. Conclusion: The prognosis of congenital choledochal cysts was associated with multiple aspects of clinical factors. Combined with the internal validation, the novel prediction nomogram was suitable for evaluating the individualized risk of postoperative complications of choledochal cysts. The prediction nomogram could provide a more accurate strategy of procedure and postoperative follow-up for children with choledochal cysts.

7.
Org Lett ; 26(29): 6241-6246, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38996353

RESUMO

In this work, we describe an enantioselective reduction and sulfenylation of isoflavanone derivatives by an ion pair strategy. The chiral cationic catalyst bisguanidinium (BG) is capable of chiral induction in catalytic systems. Silane hydride works as a reductant and helps to form an anionic hypervalent silicate complex and intermediates with substrates to pair with chiral catalyst. A series of umpolung sulfur reagents accomplish electrophilic attack in the presence of a silicate anion. Both chemoselectivity and enantioselectivity are good to excellent to afford a wide scope of 4-oxo-4H-chromene-3-carbonitrile and S-electrophilic reagents. Further transformations were completed to introduce more applications.

8.
Materials (Basel) ; 17(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38894013

RESUMO

Advanced oxidation processes (AOPs) represent one of the most promising strategies to generate highly reactive species to deal with organic dye-contaminated water. However, developing green and cost-effective catalysts is still a long-term goal for the wide practical application of AOPs. Herein, we demonstrated doping cobalt in porous carbon to efficiently catalyze the oxidation of the typically persistent organic pollutant rhodamine B, via multiple reactive species through the activation of peroxymonosulfate (PMS). The catalysts were prepared by facile pyrolysis of nanocomposites with a core of cobalt-loaded silica and a shell of phenolic resin (Co-C/SiO2). It showed that the produced 1O2 could effectively attack the electron-rich functional groups in rhodamine B, promoting its molecular chain breakage and accelerating its oxidative degradation reaction with reactive oxygen-containing radicals. The optimized Co-C/SiO2 catalyst exhibits impressive catalytic performance, with a degradation rate of rhodamine B up to 96.7% in 14 min and a reaction rate constant (k) as high as 0.2271 min-1, which suggested promising potential for its practical application.

9.
Zhongguo Gu Shang ; 37(6): 6165-21, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38910386

RESUMO

OBJECTIVE: To explore clnical efficacy of modified Frosch approach for Schatzker typeⅡtibial plateau fracture with posterolateral column. METHODS: From January 2019 to September 2020, totally 11 patients with Schatzker typeⅡtibial plateau fractures with posterolateral column were treated, including 7 males and 4 females, aged from 21 to 49 years old. Modified Frosch approach was adopted for lateral decubitus position, and posterolateral fractures were fixed with support plates or posterolateral screws. Anterolateral fixation with conventional tibial plateau lateral locking plate. Tibial plateau varus angle and posterior inclination angle were measured by X-ray immediately and 12 months after operation, as well as knee motion at 12 months after operation. Knee function at 12 months after operation was evaluated by knee score of Hospital for Special Surgery(HSS). RESULTS: Eleven patients were followed up for 12 to 15 months. Varus angle and inclination angle at immediately after operation ranged from 76° to 86° and 6° to 10°, respectively, and 79° to 88° and 6° to 10°, respectively at 12 months after operation. The range of extension of knee ranged from 0° to 5°, and flexion was 106° to 137° at 12 months after operation. Postoperative HSS knee score at 12 months ranged from 74 to 94 scores, 8 patients were excellent and 3 good. CONCLUSION: Modified Frosch approach is an effective surgical method for Schatzker typeⅡtibial plateau fracture with posterolateral column. A single incision is used to complete fracture exposure and fixation at two sites, avoiding use of combined incisions, and could obtain good postoperative knee joint function. During operation, popliteal fossa structure should be familiar, and the common peroneal nerve should be protected to avoid injury.


Assuntos
Fixação Interna de Fraturas , Fraturas da Tíbia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fraturas da Tíbia/cirurgia , Fixação Interna de Fraturas/métodos , Adulto Jovem , Placas Ósseas
10.
New Microbiol ; 47(1): 68-79, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38700886

RESUMO

We aimed to investigate the role of Synbiotic preparations on the interaction of gut microbiota with AD development. APP/PS1 mice were randomized into APP/PS1 and Synbiotics groups, and C57BL/6J mice were used as wild type (WT) control group. The mice in the Synbiotics group and the APP/PS1 group were given Synbiotics and xylo-oligosaccharides for 3 months, respectively. The mice in the WT group were given the same amount of normal saline. Cognitive function was measured. Positron emission computed tomography/magnetic resonance imaging (PET/MRI) was used to detect fasting blood glucose level. Immunohistochemical assay, ELISA, western blot and qRT-PCR were carried out to detect inflammatory factors. DNA extraction of fecal sample was performed to carry out sequencing. Bioinformatics analysis, metabolites sample preparation and Liquid Chromatograph Mass Spectrometer (LC/MS) analysis were also performed. Synbiotics treatment can significantly ameliorate learning and memory competence by inhibiting Aß protein deposition. Different bacteria in the intestine were significantly improved and changes in gut microbiota can affect the intestinal metabolism to affect multiple potential pathways after Synbiotics treatment. Synbiotics treatment can activate peroxisome proliferator activated receptor (PPARs) signaling pathway and significantly reduce neuroinflammation in APP/PS1 mice brains. Synbiotics treatment can effectively reduce neuro-inflammatory response through the regulation of intestinal microflora to delay AD development.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Receptores Ativados por Proliferador de Peroxissomo , Simbióticos , Animais , Camundongos , Simbióticos/administração & dosagem , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Progressão da Doença , Transdução de Sinais , Masculino , Camundongos Transgênicos
11.
Food Chem ; 453: 139672, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38805941

RESUMO

The structure and functional properties of protein fibrils are closely related to environmental factors in fibrillation. Herein, soy protein isolate fibrils (SPIFs, 22 mg/mL) were prepared under acid-heating conditions in the presence of 100 mM metal ions (K+, Na+, Ca2+, Mg2+, and Fe3+). Except for Fe3+, fibrillation and subsequent larger fibril aggregates were promoted, ultimately leading to gel formation. Compared with K+ or Na+, the addition of Ca2+ or Mg2+ resulted in more organized SPIF structures with increased ß-sheet contents and higher ThT fluorescence intensities. Furthermore, both of them resulted in longer fibrils with an average contour length of 700-800 nm, which significantly enhanced the storage modulus. However, the presence of Fe3+ accelerated protein hydrolysis and inhibited SPIF formation, resulting in samples consistently exhibited liquid behavior. These findings provide a foundation for understanding the influence of metal ions on regulating the fibrillation and gelling properties of SPIFs.


Assuntos
Géis , Metais , Proteínas de Soja , Proteínas de Soja/química , Géis/química , Metais/química , Íons/química , Hidrólise
12.
Mikrochim Acta ; 191(6): 350, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806865

RESUMO

Gold nanomaterials have been widely explored in electrochemical sensors due to their high catalytic property and good stability in multi-medium. In this paper, the reproducibility of the signal among batches of gold nanorods (AuNRs)-modified electrodes was investigated to improve the data stabilization and repeatability. Ordered and random self-assembled AuNRs-modified electrodes were used as electrochemical sensors for the simultaneous determination of dopamine (DA) and topotecan (TPC), with the aim of obtaining an improved signal stability in batches of electrodes and realizing the simultaneous determination of both substances. The morphology and structure of the assemblies were analyzed and characterized by UV-Vis spectra, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray powder diffraction (XRD). Electrochemical studies showed that the ordered AuNRs/ITO electrodes have excellent signal reproducibility among several individuals due to the homogeneous mass transfer in the ordered arrangement of the AuNRs. Under the optimized conditions, the simultaneous detection results of DA and TPC showed good linearity in the ranges 1.75-45 µM and 1.5-40 µM, and the detection limits of DA and TPC were 0.06 µM and 0.17 µM, respectively. The results showed that the prepared ordered AuNR/ITO electrode had high sensitivity, long-term stability, and reproducibility for the simultaneous determination of DA and TPC, and it was expected to be applicable for real sample testing.


Assuntos
Dopamina , Técnicas Eletroquímicas , Eletrodos , Ouro , Limite de Detecção , Nanotubos , Topotecan , Dopamina/análise , Ouro/química , Topotecan/análise , Topotecan/química , Reprodutibilidade dos Testes , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Nanotubos/química , Humanos
13.
Org Lett ; 26(21): 4514-4519, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38758611

RESUMO

An efficient protocol of enantioselective thiolative azidation of sulfone-tethered alkenes via a chiral chalcogenide catalyzed electrophilic reaction is disclosed. A series of enantioenriched sulfones bearing remote stereogenic centers was achieved with good yields and high enantioselectivities with linear unsaturated sulfones and cyclic unsaturated sulfones. Mechanistic studies revealed the importance of the sulfone group in the improvement of the reactivity and enantioselectivity of the reaction.

14.
Eur J Med Res ; 29(1): 274, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720334

RESUMO

PURPOSE: To compare the effects of a single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple approach and traditional laparoscopic Cohen in treating pediatric primary obstructive megaureter. MATERIALS AND METHODS: The clinical data of 24 children with primary obstructive megaureter from January 2021 to November 2021 were analyzed retrospectively. Among them, 12 children (8 boys and 4 girls, the average age were 17.17 ± 6.31 months) treated with the laparoscopic Cohen method were defined as group C. The remaining 12 children (7 boys and 5 girls, the average age was 17.33 ± 6.99 months) underwent single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple ureteral extravesical reimplantation were defined as group L. The parameters of pre-operation, intraoperative and postoperative were compared. RESULTS: There were no differences in the patient characteristics and average follow-up time between the two groups (P > 0.05).The obstruction resolution rate was 100% in both groups. The total operation time in group L is slightly longer than that in group C(P < 0.001),but the intraperitoneal operation time of the two groups was comparable(P > 0.05). The postoperative parameters included blood loss, gross haematuria time, indwelling catheterization time and hospitalization time in group L is shorter than group C(P < 0.05). One year post-operation, decreasing in ureteral diameter and APRPD, and increasing in DRF were remarkably observed in both two groups(P < 0.05). Ureteral diameter, APRPD, and DRF were not significantly different both in pre-operation and post-operation between Group L and Group C(P > 0.05). CONCLUSION: Single-port-plus-one robot-assisted laparoscopic-modified Lich-Gregoir direct nipple approach and traditional laparoscopic Cohen are both dependable techniques for ureteral reimplantation in the treatment of pediatric primary obstructive megaureter. Since Lich-Gregoir can preserve the physiological direction of the ureter and direct nipple reimplantation enhances the effect of anti-refluxing, this technique is favorable for being promoted and applied in robot surgery.


Assuntos
Laparoscopia , Reimplante , Procedimentos Cirúrgicos Robóticos , Ureter , Obstrução Ureteral , Humanos , Feminino , Masculino , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/métodos , Obstrução Ureteral/cirurgia , Ureter/cirurgia , Reimplante/métodos , Estudos Retrospectivos , Pré-Escolar , Lactente , Criança , Duração da Cirurgia , Resultado do Tratamento
15.
BMC Urol ; 24(1): 81, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589861

RESUMO

OBJECTIVE: To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux. METHODS: The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients' characteristics as well as their perioperative and follow-up data were collected and evaluated. RESULTS: There was no significant difference in the data regarding patients' characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P < 0.0001). Also, the peri-operative data, including the volume of blood loss, fasting time, hospitalization, and length of time that a ureteral catheter remained in place, and the number of postoperative complications demonstrate no difference. In addition, the SFU grade and VCUG grade at the following time point also show no difference between the two groups. CONCLUSION: The study demonstrates that SR in robotic-assisted Lich-Gregoir ureteral reimplantation has reached the same surgical effects as MR. In addition, the single-port plus one trocar placement receives a higher cosmetic satisfaction score from parents and did not increase the surgical time and complexity.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Ureter , Refluxo Vesicoureteral , Criança , Humanos , Refluxo Vesicoureteral/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Urológicos , Resultado do Tratamento , Ureter/cirurgia , Reimplante
16.
Molecules ; 29(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474696

RESUMO

Heavy crude oil poses challenges in terms of extraction and transportation due to its high viscosity. In the pursuit of effective methods to reduce viscosity in heavy crude oil, this study investigates the potential of imidazolium chloride ionic liquids with varying alkyl chain lengths as viscosity reducers. The experimental results demonstrate that the addition of 1-dodecyl-3-methylimidazole chloride ([C12-MIM]Cl) leads to a maximum viscosity reduction of 49.87%. Solubility parameters were calculated based on characterization of the average molecular structure of the asphaltenes. The viscosity reduction effect is enhanced when the solubility parameter of the ionic liquid closely matches that of the asphaltene. The initial asphaltene deposition point of heavy crude oil is increased from 63% to 68% with the addition of 150 mg/L [C12-MIM]Cl. Furthermore, the average particle size of asphaltene deposits decreases from 79.35 µm to 48.54 µm. The viscosity of heavy crude oil is influenced by the aggregation of asphaltenes. The ability of ionic liquids, especially those with longer alkyl chains, to disperse asphaltene molecules and reduce viscosity has been confirmed through molecular dynamics and quantum mechanical simulations.

17.
Comput Biol Med ; 170: 108066, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38310806

RESUMO

Synthetic lethality (SL) occurs when the inactivation of two genes results in cell death while the inactivation of either gene alone is non-lethal. SL-based therapy has become a promising anti-cancer treatment option with the increasing researches and applications in clinical practice, while the specific therapeutic opportunities for various cancers have not yet been comprehensively investigated. Herein, we described a computational approach based on machine learning and statistical inference to discover the cancer-specific synthetic lethal interactions. First, Random Forest and One-Class SVM were used to perform cancer unbiased prediction of synthetic lethality. Then, two strategies, including mutual exclusivity and differential expression, were used to screen cancer-specific synthetic lethal interactions, resulting in 14,582 SL gene pairs in 33 cancer types. Finally, we developed a freely available database of CSSLdb (Cancer Specific Synthetic Lethality Database, http://www.tmliang.cn/CSSL/) to present cancer-specific synthetic lethal genetic interactions, which would enrich the relevant research and contribute to underlying therapy strategies based on synthetic lethality.


Assuntos
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Genes Letais , Bases de Dados Factuais , Aprendizado de Máquina
19.
Small ; 20(23): e2309366, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38150620

RESUMO

Nanocatalytic-based wound therapeutics present a promising strategy for generating reactive oxygen species (ROS) to antipathogen to promote wound healing. However, the full clinical potential of these nanocatalysts is limited by their low reactivity, limited targeting ability, and poor biodegradability in the wound microenvironment. Herein, a bio-organic nanozyme is developed by encapsulating a FeZn-based bimetallic organic framework (MOF) (MIL-88B-Fe/Zn) in platelet membranes (PM@MIL-88B-Fe/Zn) for antimicrobial activity during wound healing. The introduction of Zn in MIL-88B-Fe/Zn modulates the electronic structure of Fe thus accelerating the catalytic kinetics of its peroxidase-like activity to catalytically generate powerful ROS. The platelet membrane coating of MOF innovatively enhanced the interaction between nanoparticles and the biological environment, further developing bacterial-targeted therapy with excellent antibacterial activity against both gram-positive and gram-negative bacteria. Furthermore, this nanozyme markedly suppressed the levels of inflammatory cytokines and promoted angiogenesis in vivo to effectively treat skin surface wounds and accelerate wound healing. PM@MIL-88B-Fe/Zn exhibited superior biodegradability, favourable metabolism and non-toxic accumulation, eliminating concerns regarding side effects from long-term exposure. The high catalytic reactivity, excellent targeting features, and biodegradability of these nanoenzymes developed in this study provide useful insights into the design and synthesis of nanocatalysts/nanozymes for practical biomedical applications.


Assuntos
Antibacterianos , Estruturas Metalorgânicas , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Plaquetas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Humanos
20.
Bioresour Technol ; 394: 130232, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38141881

RESUMO

Microalgae, known for rapid growth and lipid richness, hold potential in biofuels and high-value biomolecules. The symbiotic link with bacteria is crucial in large-scale open cultures. This study explores algal-bacterial interactions using a symbiotic model, evaluating acid-resistant Lactic acid bacteria (LAB), stress-resilient Bacillus subtilis and Bacillus licheniformis, and various Escherichia coli strains in the Aurantiochytrium sp. SW1 system. It was observed that E. coli SUC significantly enhanced the growth and lipid production of Aurantiochytrium sp. SW1 by increasing enzyme activity (NAD-IDH, NAD-ME, G6PDH) while maintaining sustained succinic acid release. Optimal co-culture conditions included temperature 28 °C, a 1:10 algae-to-bacteria ratio, and pH 8. Under these conditions, Aurantiochytrium sp. SW1 biomass increased 3.17-fold to 27.83 g/L, and total lipid content increased 2.63-fold to 4.87 g/L. These findings have implications for more efficient microalgal lipid production and large-scale cultivation.


Assuntos
Microalgas , Escherichia coli , Ácido Succínico , Biomassa , Simbiose , NAD , Lipídeos , Biocombustíveis
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