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1.
BMC Infect Dis ; 24(1): 442, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671376

RESUMEN

BACKGROUND: Urinary tract infection (UTI) is a common cause of sepsis. Elderly patients with urosepsis in intensive care unit (ICU) have more severe conditions and higher mortality rates owing to factors such as advanced age, immunosenescence, and persistent host inflammatory responses. However, comprehensive studies on nomograms to predict the in-hospital mortality risk in elderly patients with urosepsis are lacking. This study aimed to construct a nomogram predictive model to accurately assess the prognosis of elderly patients with urosepsis and provide therapeutic recommendations. METHODS: Data of elderly patients with urosepsis were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV 2.2 database. Patients were randomly divided into training and validation cohorts. A predictive nomogram model was constructed from the training set using logistic regression analysis, followed by internal validation and sensitivity analysis. RESULTS: This study included 1,251 patients. LASSO regression analysis revealed that the Glasgow Coma Scale (GCS) score, red cell distribution width (RDW), white blood count (WBC), and invasive ventilation were independent risk factors identified from a total of 43 variables studied. We then created and verified a nomogram. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) of the nomogram were superior to those of the traditional SAPS-II, APACHE-II, and SOFA scoring systems. The Hosmer-Lemeshow test results and calibration curves suggested good nomogram calibration. The IDI and NRI values showed that our nomogram scoring tool performed better than the other scoring systems. The DCA curves showed good clinical applicability of the nomogram. CONCLUSIONS: The nomogram constructed in this study is a convenient tool for accurately predicting in-hospital mortality in elderly patients with urosepsis in ICU. Improving the treatment strategies for factors related to the model could improve the in-hospital survival rates of these patients.


Asunto(s)
Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Nomogramas , Sepsis , Infecciones Urinarias , Humanos , Anciano , Femenino , Masculino , Infecciones Urinarias/mortalidad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Sepsis/mortalidad , Anciano de 80 o más Años , Factores de Riesgo , Pronóstico , Curva ROC , Estudios Retrospectivos
2.
Bioorg Chem ; 143: 107044, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38134522

RESUMEN

Musashi1 and Musashi2 are RNA-binding proteins originally found in drosophila, in which they play a crucial developmental role. These proteins are pivotal in the maintenance and differentiation of stem cells in other organisms. Research has confirmed that the Musashi proteins are highly involved in cell signal-transduction pathways such as Notch and TGF-ß. These signaling pathways are related to the induction and development of cancers, such as breast cancer, leukemia, hepatoma and liver cancer. In this review we focus on how Musashi proteins interact with molecules in different signaling pathways in various cancers and how they affect the physiological functions of these pathways. We further illustrate the status quo of Musashi proteins-targeted therapies and predict the target RNA regions that Musashi proteins interact with, in the hope of exploring the prospect of the design of Musashi protein-targeted medicines.


Asunto(s)
Química Farmacéutica , Neoplasias , Humanos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Unión al ARN/metabolismo , Neoplasias/tratamiento farmacológico , ARN
3.
Curr Issues Mol Biol ; 45(2): 1570-1586, 2023 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-36826046

RESUMEN

ATP-binding cassette (ABC) transporters are involved in transporting multiple substrates, such as toxins, and may be important for the survival of Trichoderma when encountering biotic toxins. In this study, genome searching revealed that there are 44 ABC transporters encoded in the genome of Trichoderma asperellum. These ABC transporters were divided into six types based on three-dimensional (3D) structure prediction, of which four, represented by 39 ABCs, are involved in transport and the remaining two, represented by 5 ABCs, are involved in regulating translation. The characteristics of nucleotide-binding domain (NBD) are important in the identification of ABC proteins. Even though the 3D structures of the 79 NBDs in the 44 ABCs are similar, multiple sequence alignment showed they can be divided into three classes. In total, 794 motifs were found in the promoter regions of the 44 ABC genes, of which 541 were cis-regulators related to stress responses. To characterize how their ABCs respond when T. asperellum interact with fungi or plants, T. asperellum was cultivated in either minimal media (MM) control, C-hungry, N-hungry, or poplar medium (PdPap) to simulate normal conditions, competition with pathogens, interaction with pathogens, and interaction with plants, respectively. The results show that 17 of 39 transport ABCs are highly expressed in at least one condition, whereas four of the five translation-regulating ABCs are highly expressed in at least one condition. Of these 21 highly expressed ABCs, 6 were chosen for RT-qPCR expression under the toxin stress of phytopathogen Alternaria alternata, and the results show ABC01, ABC04, ABC05, and ABC31 were highly expressed and may be involved in pathogen interaction and detoxifying toxins from A. alternata.

4.
Br J Anaesth ; 131(2): 253-265, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37474241

RESUMEN

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).


Asunto(s)
Anestésicos por Inhalación , Delirio del Despertar , Neoplasias , Propofol , Humanos , Femenino , Anciano , Masculino , Propofol/efectos adversos , Sevoflurano/efectos adversos , Anestésicos por Inhalación/efectos adversos , Estudios de Seguimiento , Anestesia General/efectos adversos , Delirio del Despertar/inducido químicamente , Neoplasias/cirugía
5.
Br J Anaesth ; 131(2): 266-275, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37474242

RESUMEN

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.


Asunto(s)
Neoplasias , Propofol , Sevoflurano , Propofol/efectos adversos , Sevoflurano/efectos adversos , Neoplasias/cirugía , Humanos , Masculino , Femenino , Anciano , Estudios de Seguimiento , Anestésicos Intravenosos , Anestesia por Inhalación , Supervivientes de Cáncer
6.
Bioorg Chem ; 139: 106686, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37399616

RESUMEN

Since most tumors become resistant to drugs in a gradual and irreversible manner, making treatment less effective over time, anticancer drugs require continuous development. Peptoids are a class of peptidomimetics that can be easily synthesized and optimized. They exhibit a number of unique characteristics, including protease resistance, non-immunogenicity, do not interfere with peptide functionality and skeleton polarity, and can adopt different conformations. They have been studied for their efficacy in different cancer therapies, and can be considered as a promising alternative molecular category for the development of anticancer drugs. Herein, we discuss the extensive recent advances in peptoids and peptoid hybrids in the treatment of cancers such as prostate, breast, lung, and other ones, in the hope of providing a reference for the further development of peptoid anticancer drugs.


Asunto(s)
Antineoplásicos , Peptoides , Masculino , Humanos , Peptoides/farmacología , Peptoides/química , Péptidos , Conformación Molecular , Antineoplásicos/química , Péptido Hidrolasas
7.
Mol Divers ; 2023 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-37268742

RESUMEN

Influenza is a seasonal respiratory illness that kills hundreds of thousands of people every year. Currently, neuraminidase inhibitors and endonuclease inhibitors are used in antiviral therapy. However, both drug types have encountered drug-resistant influenza strains in the human body. Fortunately, there is currently no resistance to endonuclease inhibitors in wild strains of influenza. We obtained the molecules with endonuclease inhibitor activity independent of the existing drug-resistant strains through computer-aided drug design, and we hope the obtained results can lay a theoretical foundation for the development of high-activity endonucleases. Combining a traditional fragment-based drug discovery approach with AI-directed fragment growth, we selected and designed a compound that achieved antiviral activity on drug-resistant strains by avoiding mutable residues and drug-resistant residues. We predicted the related properties using an ADMET model. Finally, we obtained a compound similar to baloxavir in terms of binding free energy but not affected by baloxavir resistance.

8.
Eur Spine J ; 32(3): 1021-1028, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36715756

RESUMEN

OBJECTIVE: The purpose of our study is to identify the effect of short-term and high-dose use of erythropoietin (EPO) in spinal isolated metastatic patients with Total en bloc spondylectomy (TES) surgery by assessing hematological parameters, transfusion volume, postoperative complications, recurrence-free survival (RFS), and overall survival (OS). METHODS: From January 2015 and January 2022, 93 isolated spinal metastasis patients were selected and separated into 2 groups based on the treatment method used (EPO + TXA (Tranexamic acid) group, n = 47; and TXA group, n = 46). Indexes for evaluation included hemoglobin (Hb), hematocrit (Hct), red blood cells (RBC), RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, transfusion rate, and mean units transfused. RESULTS: The average follow-up duration was 38.13 months. There was no significant difference (P > 0.05) in RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, and transfusion rate between the two groups. However, patients in EPO + TXA group have significantly higher Hb, Hct, and RBC values than those in the TXA group on postoperative days 1, 2, 3, and 5. Moreover, the mean transfusion volume in EPO + TXA group was significantly lower than those in the TXA group (P = 0.011). CONCLUSIONS: Perioperative short-term and high-dose administration of EPO could improve the anemia-related hematological parameters and reduce the requirement for blood transfusion without increasing the risk of deep vein thrombosis and tumor progression in solitary spinal metastatic patients with TES surgery.


Asunto(s)
Antifibrinolíticos , Eritropoyetina , Neoplasias de la Columna Vertebral , Humanos , Antifibrinolíticos/uso terapéutico , Estudios de Casos y Controles , Pérdida de Sangre Quirúrgica/prevención & control , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico
9.
World J Surg Oncol ; 21(1): 11, 2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36647119

RESUMEN

BACKGROUND: This study aimed to assess changes in quality of sleep (QoS) in isolated metastatic patients with spinal cord compression following two different surgical treatments and identify potential contributing factors associated with QoS improvement. METHODS: We reviewed 49 patients with isolated spinal metastasis at our spinal tumor center between December 2017 and May 2021. Total en bloc spondylectomy (TES) and palliative surgery with postoperative stereotactic radiosurgery (PSRS) were performed on 26 and 23 patients, respectively. We employed univariate and multivariate analyses to identify the potential prognostic factors affecting QoS. RESULTS: The total Pittsburgh Sleep Quality Index (PSQI) score improved significantly 6 months after surgery. Univariate analysis indicated that age, pain worsening at night, decrease in visual analog scale (VAS), increase in Eastern Cooperative Oncology Group performance score (ECOG-PS), artificial implant in focus, and decrease in epidural spinal cord compression (ESCC) scale values were potential contributing factors for QoS. Multivariate analysis indicated that the ESCC scale score decreased as an independent prognostic factor. CONCLUSIONS: Patients with spinal cord compression caused by the metastatic disease had significantly improved QoS after TES and PSRS treatment. Moreover, a decrease in ESCC scale value of > 1 was identified as a favorable contributing factor associated with PSQI improvement. In addition, TES and PSRS can prevent recurrence by achieving efficient local tumor control to improve indirect sleep. Accordingly, timely and effective surgical decompression and recurrence control are critical for improving sleep quality.


Asunto(s)
Compresión de la Médula Espinal , Neoplasias de la Médula Espinal , Neoplasias de la Columna Vertebral , Humanos , Estudios Retrospectivos , Calidad del Sueño , Compresión de la Médula Espinal/cirugía , Compresión de la Médula Espinal/complicaciones , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/secundario , Resultado del Tratamiento
10.
Chem Biodivers ; 20(3): e202201100, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36808685

RESUMEN

The 3C protease (3C Pro) plays a significant role in the life cycle of picornaviruses from replication to translation, making it an attractive target for structure-based design of drugs against picornaviruses. The structurally related 3C-like protease (3CL Pro) is an important protein involved in the replication of coronaviruses. With the emergence of COVID-19 and consequent intensive research into 3CL Pro, development of 3CL Pro inhibitors has emerged as a popular topic. This article compares the similarities of the target pockets of various 3C and 3CL Pros from numerous pathogenic viruses. This article also reports several types of 3C Pro inhibitors that are currently undergoing extensive studies and introduces various structural modifications of 3C Pro inhibitors to provide a reference for the development of new and more effective inhibitors of 3C Pro and 3CL Pro.


Asunto(s)
COVID-19 , Picornaviridae , Humanos , Proteasas Virales 3C , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Péptido Hidrolasas , Antivirales/farmacología
11.
BMC Immunol ; 23(1): 15, 2022 04 02.
Artículo en Inglés | MEDLINE | ID: mdl-35366796

RESUMEN

BACKGROUND: Identifying immunogens which can elicit effective T cell responses against human immunodeficiency virus type 1 (HIV-1) is important for developing a T-cell based vaccine. It has been reported that human leukocyte antigen (HLA)-B*13-restricted T-cell responses contributed to HIV control in subtype B' and C infected individuals. However, the kinetics of B*13-restricted T-cell responses, viral evolution within epitopes, and the impact on disease progression in CRF01_AE subtype HIV-1-infected men who have sex with men (MSM) are not known. RESULTS: Interferon-γ ELISPOT assays and deep sequencing of viral RNAs were done in 14 early HLA-B*13-positive CRF01_AE subtype HIV-1-infected MSM. We found that responses to RQEILDLWV (Nef106-114, RV9), GQMREPRGSDI (Gag226-236, GI11), GQDQWTYQI (Pol487-498, GI9), and VQNAQGQMV (Gag135-143, VV9) were dominant. A higher relative magnitude of Gag-specific T-cell responses, contributed to viral control, whereas Nef-specific T-cell responses were associated with rapid disease progression. GI11 (Gag) was conserved and strong GI11 (Gag)-specific T-cell responses showed cross-reactivity with a dominant variant, M228I, found in 3/12 patients; GI11 (Gag)-specific T-cell responses were positively associated with CD4 T-cell counts (R = 0.716, P = 0.046). Interestingly, the GI9 (Pol) epitope was also conserved, but GI9 (Pol)-specific T-cell responses did not influence disease progression (P > 0.05), while a D490G variant identified in one patient did not affect CD4 T-cell counts. All the other epitopes studied [VV9 (Gag), RQYDQILIEI (Pol113-122, RI10), HQSLSPRTL (Gag144-152, HL9), and RQANFLGRL (Gag429-437, RL9)] developed escape mutations within 1 year of infection, which may have contributed to overall disease progression. Intriguingly, we found early RV9 (Nef)-specific T-cell responses were associated with rapid disease progression, likely due to escape mutations. CONCLUSIONS: Our study strongly suggested the inclusion of GI11 (Gag) and exclusion of RV9 (Nef) for T-cell-based vaccine design for B*13-positive CRF01_AE subtype HIV-1-infected MSM and high-risk individuals.


Asunto(s)
Infecciones por VIH , VIH-1 , Minorías Sexuales y de Género , VIH-1/fisiología , Antígenos HLA-B , Homosexualidad Masculina , Humanos , Masculino , Linfocitos T
12.
Small ; 18(42): e2203715, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36058648

RESUMEN

Limited by the insufficient active sites and the interference from breath humidity, designing reliable gas sensing materials with high activity and moisture resistance remains a challenge to analyze human exhaled breath for the translational application of medical diagnostics. Herein, the dual sensing and cooperative diagnosis is achieved by utilizing metal-organic frameworks (MOFs) and its derivative. The Fe-MIL-101-NH2 serves as the quartz crystal microbalance humidity sensing layer, which exhibits high selectivity and rapid response time (16 s/15 s) to water vapor. Then, the Co2+ and Ni2+ cations are further co-doped into Fe-MIL-101-NH2 host to obtain the derived Co/Ni/Fe trimetallic  oxides (CoNiFe-MOS-n). The chemiresistive CoNiFe-MOS-n sensor displays the high sensitivity (560) and good selectivity to acetone, together with a lower original resistance compared with Fe2 O3 and NiFe2 O4 . Moreover, as a proof-of-concept application, synergistic integration of Fe-MIL-101-NH2 and derived CoNiFe-MOS-n is carried out. The Fe-MIL-101-NH2 is applied as moisture sorbent materials, which realize a sensitivity compensation of CoNiFe-MOS-n sensors for the detection of acetone (biomarker gas of diabetes). The findings provide an insight for effective utilization of MOFs and the derived materials to achieve a trace gas detection in exhaled breath analysis.


Asunto(s)
Estructuras Metalorgánicas , Materiales Inteligentes , Humanos , Estructuras Metalorgánicas/química , Óxidos , Acetona/química , Vapor , Cationes , Biomarcadores
13.
Cerebrovasc Dis ; 51(3): 304-312, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34856549

RESUMEN

INTRODUCTION: Serum potassium abnormality is a risk factor of incident stroke, but whether it is associated with recurrent stroke in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA) remains unknown. This study aimed to investigate the association of serum potassium with the risk of recurrent stroke in patients with AIS or TIA. METHODS: We included 12,425 patients from the China National Stroke Registry III. Patients were classified into 3 groups according to tertiles of potassium. The outcomes were recurrence of stroke and combined vascular events at 1 year. Cox proportional hazards regression was adopted to explore the associations by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs). RESULTS: Among 12,425 enrolled patients, the median (interquartile range) of potassium was 3.92 (3.68-4.19) mmol/L. Compared with the highest tertile, after adjusted for confounding factors, the lowest tertile potassium was associated with increased risk of recurrent stroke at 1 year. The adjusted HR with 95% CI was 1.21 (1.04-1.41). There was an independent, linear association between serum potassium and stroke recurrence. Per 1 mmol/L decrease of potassium was associated with 19% higher risk of recurrent stroke (HR, 1.19; 95% CI, 1.04-1.37). Similar trends were found in ischemic stroke and combined vascular events. CONCLUSIONS: Lower serum potassium level was independently associated with elevated risk of recurrent stroke in patients with AIS or TIA. The finding suggested that monitoring serum potassium may help physicians to identify patients at high risk of recurrent stroke and to stratify risk for optimal management.


Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Infarto Cerebral/complicaciones , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Potasio , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología
14.
Macromol Rapid Commun ; 43(17): e2200238, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35510985

RESUMEN

Generally, a single enantiomer can induce a foldamer into a preferred-handed helix, while another condition is required for the helical inversion. Herein, it is found that the helix induction and subsequent inversion of poly(m-phenylene diethynylene)-based foldamer bearing aza-18-crown-6 pendants (Poly-1) can be realized by increasing the concentration of sterically hindered l-amino acid perchlorate salts. When the amount of chiral enantiomers is small, one enantiomer tends to complex with two non-adjacent aza-18-crown-6 rings via three N+ H···O hydrogen bonds in a sandwich mode. Notably, the transition dipole moment is perpendicular to the aza-18-crown-6 ring, so that the induced helical chirality in Poly-1 backbone is opposite to the chirality of enantiomers. When the amount of chiral enantiomers is large enough, each aza-18-crown-6 is occupied by one enantiomer, which causes the transition dipole moment in a parallel direction to aza-18-crown-6 ring. In this case, the increased steric hindrance can facilitate the inversion of screw sense of Poly-1 backbone, which is directed by chiral center of enantiomers. As a result, a helix inversion has been achieved successfully. This work not only provides a novel strategy for regulating the two-stage folded helical conformations by the single enantiomers, but opens a window to develop chiral recognition materials.


Asunto(s)
Aminoácidos , Polímeros , Dicroismo Circular , Conformación Molecular , Polímeros/química , Estereoisomerismo
15.
BMC Pregnancy Childbirth ; 22(1): 642, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35971117

RESUMEN

BACKGROUND: Physiological changes that occur during pregnancy can influence serum lipid levels and laboratory tests for renal function. Therefore, we established consecutive and reliable RIs for serum lipid and renal function indices for pregnant women in China throughout the entirety of pregnancy. METHODS: We included 120 healthy pregnant women who underwent a naturally conceived and uncomplicated pregnancy and delivered a healthy singleton neonate. Serum samples were collected at ten time points (pre-pregnancy, gestational age ≤ 8 weeks (W), 8 W+1 to 12 W, 12 W+1 to 16 W, 16 W+1 to 20 W, 20 W+1 to 24 W, 24 W+1 to 28 W, 28 W+1 to 32 W, 32 W+1 to 36 W, and 36 W+1 to 40 W) and analyzed for ten common serum lipid and renal function analytes. RIs were calculated according to the International Federation of Clinical Chemistry and Laboratory Medicine recommendations and compared with the established RIs for healthy adult women. RESULTS: During pregnancy, we observed significant increases in total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), cystatin C (Cys-C), and estimated glomerular filtration rate (eGFR). We also observed clear reductions in urea, creatinine (Crea), and uric acid (UA). Compared with the previously established RIs, the most significant misclassifications were recorded for TG, Apo-A1, Crea, and eGFR. CONCLUSIONS: We successfully described key changes in serum lipid levels and renal function indices throughout pregnancy. It is important to establish RIs for blood indices in women undergoing normal pregnancies during different period of pregnancy to avoid the misdiagnosis of disease states.


Asunto(s)
Colesterol , Lípidos , Adulto , HDL-Colesterol , Creatinina , Femenino , Humanos , Lactante , Recién Nacido , Riñón/fisiología , Embarazo , Triglicéridos
16.
J Enzyme Inhib Med Chem ; 37(1): 606-615, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35067153

RESUMEN

Type 2 diabetes mellitus is a metabolic disorder with complicated pathogenesis, and mono-target therapy often fails to effectively manage the levels of blood glucose. In recent years, the anti-diabetes target glucokinase (GK) has attracted the attention of researchers. It acts as a glucose sensor, triggering counter regulatory responses following a change in glucose levels to aid restoration of normoglycemia. Activation of GK induces glucose metabolism and reduces glucose levels for the treatment of type 2 diabetes. GK agonists (GKA) are a new class of antidiabetic drugs. Among these agents, dorzagliatin is currently being investigated in phase III clinical trials, while PB-201 and AZD-1656 have reached phase II clinical trials. This article describes the mechanism of action of GK in diabetes and of action of GKA at the protein level, and provides a review of the research, trends, and prospects regarding the use of GKA in this setting.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucoquinasa/metabolismo , Hipoglucemiantes/farmacología , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Desarrollo de Medicamentos , Humanos , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química
17.
Eur Spine J ; 31(6): 1583-1589, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34668050

RESUMEN

OBJECTIVE: The aim of the study was to compare total en bloc spondylectomy (TES) and separation surgery with postoperative stereotactic radiosurgery (SSRS) for isolated metastatic patients with spinal cord compression by assessing recurrence-free survival (RFS), overall survival (OS), postoperative complications, and quality of life scores (QoL). METHODS: From October 2013 to December 2020, 52 isolated spinal metastasis patients with cord compression were selected and separated into two groups based on the surgical method used (TES group, n = 26; and SSRS group, n = 26). Indexes for evaluation included postoperative Frankel grade, postoperative ECOG-PS, RFS, OS, postoperative complications, operation time, intraoperative blood loss, and QoL. RESULTS: The average follow-up duration was 31.44 months. There was no significant difference (P > 0.05) in postoperative complications and OS between the two groups. However, a significant difference in operation time, intraoperative blood loss, postoperative ECOG-PS, RFS, and mental health domain (6 months after surgery) was found between the two groups (P < 0.05). According to The Spine Oncology Study Group Outcomes Questionnaire assessment, the total pain and physical function domains scores were also elevated after surgery in both groups. However, no significant difference was observed between groups A and B (p = 0.450 and 0.446, respectively). CONCLUSIONS: TES and SSRS were efficient methods for treating solitary spinal metastasis patients with metastatic spinal cord compression. Better local tumor control and mental health were found in the TES group, and most patients felt as if they were free of spinal tumors. Compared with TES, the SSRS caused less operation-related trauma. However, there was no significant difference in OS between the two groups.


Asunto(s)
Compresión de la Médula Espinal , Neoplasias de la Columna Vertebral , Pérdida de Sangre Quirúrgica , Estudios de Casos y Controles , Humanos , Complicaciones Posoperatorias , Calidad de Vida , Estudios Retrospectivos , Compresión de la Médula Espinal/complicaciones , Compresión de la Médula Espinal/cirugía , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/cirugía , Resultado del Tratamiento
18.
Anal Chem ; 93(41): 13807-13814, 2021 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34613712

RESUMEN

Transmembrane signal transduction is of profound significance in many biological processes. The dimerization of cell-surface receptors is one prominent mechanism by which signals are transmitted across the membrane and trigger intracellular cascade amplification reactions. Recreating such processes in artificial systems has potential applications in sensing, drug delivery, bioengineering, and providing a new route for a deep understanding of fundamental biological processes. However, it remains a challenge to design artificial signal transduction systems working by the receptor dimerization mechanism in a predictable and smart manner. Here, benefitting from DNA with features of programmability, controllability, and flexible design, we use DNA as a building material to construct an artificial system mimicking dimerization of receptors for signal transduction and cascade amplification. DNA-based membrane-spanning receptor analogues are designed to recognize external signals, which drives two receptors into close spatial proximity to activate DNAzymes inside the cell-mimicking system. The activation of the DNAzyme initiates the catalyzed cleavage of encapsulated substrates and leads to the release of fluorescent second messengers for signal amplification. Such an artificial signal transduction system extends the range of biomimetic DNA-based signaling systems, providing a new avenue to study natural cell signaling processes and artificially regulate biological processes.


Asunto(s)
Fenómenos Biológicos , ADN Catalítico , ADN/genética , ADN/metabolismo , ADN Catalítico/metabolismo , Dimerización , Transducción de Señal
19.
Soft Matter ; 17(11): 3216-3221, 2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33624662

RESUMEN

Photo-responsive cholesteric liquid crystals (CLCs) have attracted much attention due to the dynamic tunability of their unique helical superstructure. However, it is still a challenge to endow the mechanical properties and to regulate the reflection colors at the same time. In this work, a simple strategy is developed for the construction of thermo-responsive CLC physical gels via the direct mixing of photo-responsive dopants and a gelator with nematic LCs. The reflection colors of CLCs and the mechanical properties of gels can be independently regulated due to the separation of the photo-responsive chiral group from the gelator. In addition, the CLC reflection colors can be regulated via visible light in the range of RGB with long-lived thermal stability. Finally, the information storage properties of this kind of CLC gel have been investigated.

20.
Nanotechnology ; 32(47)2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-33957609

RESUMEN

Methane (CH4) gas sensors play an important role in industrial safety and detection of indoor gas quality. In general, metal oxide semiconductor sensing materials with nano-structure have high responses to the target gas. However, the sensor resistance is usually very high. Considering the practical application, it is vital to reduce base resistance and improve sensitivity for gas sensors. Herein, Pd-doped SnO2nanoparticles were prepared as the basis material by a simple sol-gel method. In order to adjust the resistance, the pentavalent metal element (Sb) was introduced via a simple doping route. As CH4sensing layers, the prepared SnO2-sensors doped with Pd and Sb exhibited the most obvious resistance reduction effect. Meantime, excellent sensing performances including high response, fast response/recovery time, excellent reproducibility and great stability were also obtained. In-depth research has shown that the ability to reduce resistance depends on the effective internal doping of cation with high valence. The enhanced sensing capability can be attributed to the 'synergistic effects' including catalytic effects of novel metals, increased oxygen vacancies and decreased band gap energy. This work can provide a new opportunity to design metal oxide sensing materials with low resistance and high sensitivity.

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