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1.
Cell ; 179(2): 561-577.e22, 2019 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-31585088

RESUMEN

We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacent liver tissues from 159 patients. Integrated proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related HCC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct features in metabolic reprogramming, microenvironment dysregulation, cell proliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated signaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and cell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.


Asunto(s)
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virología , Fructosa-Bifosfato Aldolasa/genética , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virología , Proteogenómica/métodos , beta Catenina/genética , Animales , Proliferación Celular , Estudios de Cohortes , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Microambiente Tumoral/genética
3.
J Am Chem Soc ; 146(26): 17728-17737, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38899504

RESUMEN

Targeted protein degradation technology holds great potential in biomedicine, particularly in treating tumors and other protein-related diseases. Research on intracellular protein degradation using molecular glues and PROTAC technology is leading, while research on the degradation of membrane proteins and extracellular proteins through the lysosomal pathway is still in the preclinical stage. The scarcity of useful targets is an immense limitation to technological advancement, making it essential to explore novel, potentially effective approaches for targeted lysosomal degradation. Here, we employed the glucose transporter Glut1 as an innovative lysosome-targeting receptor and devised the Glut1-Facilitated Lysosomal Degradation (GFLD) strategy. We synthesized potential Glut1 ligands via reversible addition-fragmentation chain transfer (RAFT) polymerization and acquired antibody-glycooligomer conjugates through bioorthogonal reactions as lysosome-targeting protein degradation molecules, utilized in the management of PD-L1 high-expressing triple-negative breast cancer. The glucose transporter Glut1 as a lysosome-targeting receptor exhibits potential for the advancement of a broader array of medications in the future.


Asunto(s)
Transportador de Glucosa de Tipo 1 , Lisosomas , Proteolisis , Lisosomas/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Línea Celular Tumoral , Ligandos
4.
Hum Genet ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833008

RESUMEN

The long noncoding RNA CDKN2B-AS1 harbors a major coronary artery disease risk haplotype, which is also associated with progressive forms of the oral inflammatory disease periodontitis as well as myocardial infarction (MI). Despite extensive research, there is currently no broad consensus on the function of CDKN2B-AS1 that would explain a common molecular role of this lncRNA in these diseases. Our aim was to investigate the role of CDKN2B-AS1 in gingival cells to better understand the molecular mechanisms underlying the increased risk of progressive periodontitis. We downregulated CDKN2B-AS1 transcript levels in primary gingival fibroblasts with LNA GapmeRs. Following RNA-sequencing, we performed differential expression, gene set enrichment analyses and Western Blotting. Putative causal alleles were searched by analyzing associated DNA sequence variants for changes of predicted transcription factor binding sites. We functionally characterized putative functional alleles using luciferase-reporter and antibody electrophoretic mobility shift assays in gingival fibroblasts and HeLa cells. Of all gene sets analysed, collagen biosynthesis was most significantly upregulated (Padj=9.7 × 10- 5 (AUC > 0.65) with the CAD and MI risk gene COL4A1 showing strongest upregulation of the enriched gene sets (Fold change = 12.13, Padj = 4.9 × 10- 25). The inflammatory "TNFA signaling via NFKB" gene set was downregulated the most (Padj=1 × 10- 5 (AUC = 0.60). On the single gene level, CAPNS2, involved in extracellular matrix organization, was the top upregulated protein coding gene (Fold change = 48.5, P < 9 × 10- 24). The risk variant rs10757278 altered a binding site of the pathogen responsive transcription factor STAT1 (P = 5.8 × 10- 6). rs10757278-G allele reduced STAT1 binding 14.4% and rs10757278-A decreased luciferase activity in gingival fibroblasts 41.2% (P = 0.0056), corresponding with GTEx data. CDKN2B-AS1 represses collagen gene expression in gingival fibroblasts. Dysregulated collagen biosynthesis through allele-specific CDKN2B-AS1 expression in response to inflammatory factors may affect collagen synthesis, and in consequence tissue barrier and atherosclerotic plaque stability.

5.
N Engl J Med ; 385(12): 1067-1077, 2021 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-34459569

RESUMEN

BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).


Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Dieta Hiposódica , Hipertensión/dietoterapia , Accidente Cerebrovascular/prevención & control , Anciano , Enfermedades Cardiovasculares/epidemiología , China , Dieta Hiposódica/efectos adversos , Femenino , Humanos , Hiperpotasemia/complicaciones , Hipertensión/complicaciones , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Mortalidad , Potasio en la Dieta/efectos adversos , Prevención Secundaria , Accidente Cerebrovascular/epidemiología
6.
Blood ; 139(3): 357-368, 2022 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-34855941

RESUMEN

Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, -5.7%; adjusted 95% CI, -8.8% to -2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.


Asunto(s)
Hematopoyesis Clonal , Enfermedad Pulmonar Obstructiva Crónica/genética , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Oportunidad Relativa , Enfermedad Pulmonar Obstructiva Crónica/etiología , Factores de Riesgo , Fumar/efectos adversos , Secuenciación del Exoma
7.
BMC Cancer ; 24(1): 100, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38233798

RESUMEN

BACKGROUND: Immunotherapy targeting PD-1/PD-L1 has revolutionized the treatment of extensive-stage small cell lung cancer (ES-SCLC). However, clinical trials suggest differential efficacy of anti-PD-1 agents and anti-PD-L1 agents in first-line treatment of ES-SCLC. This retrospective multicenter study aimed to compare the efficacy and safety of anti-PD-1 agents versus anti-PD-L1 agents in first-line treatment of ES-SCLC in real-world practice. METHODS: Patients with pathologically or cytologically confirmed ES-SCLC treated with platinum plus etoposide combined with anti-PD-1 or PD-L1 agents as first-line treatment in different centers of PLA General Hospital between January 2017 and October 2021 were included for this study. Survival outcomes and safety were compared between patients receiving anti-PD-1 and PD-L1 agents. RESULTS: Of the total 154 included patients, 68 received anti-PD-1 agents plus chemotherapy (PD-1 group), and 86 received anti-PD-L1 agents plus chemotherapy (PD-L1 group). Progression-free survival (PFS) and overall survival (OS) in the entire cohort were 7.6 months (95% confidence interval [CI]: 6.5-8.2 months) and 17.4 months (95% CI: 15.3-19.3 months), respectively. Median PFS and OS were comparable between the PD-1 group and PD-L1 group (PFS: 7.6 months vs. 8.3 months, HR = 1.13, 95% CI: 0.79-1.62, p = 0.415; OS: 26.9 months vs. 25.6 months, HR = 0.96, 95% CI: 0.63-1.47, p = 0.859. The objective response rate and disease control rate were comparable between the two groups: 79.4% vs. 79.1% and 92.6% vs. 94.2%, respectively. The 6-month, 12-month, and 18-month PFS and OS rates were slightly higher in the PD-L1 group than in the PD-1 group, while the 24-month PFS rate was slightly higher in the PD-1 group than in the PD-L1 group. Stratified analysis showed that locoregional thoracic radiotherapy and normal lactate dehydrogenase level were independent predictors of better OS in ES-SCLC patients treated with first-line chemotherapy plus ICI. Adverse events were not significantly different between the two groups. CONCLUSIONS: Anti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Antígeno B7-H1 , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Receptor de Muerte Celular Programada 1 , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico
8.
Artículo en Inglés | MEDLINE | ID: mdl-38581316

RESUMEN

Objective: To explore and evaluate the effect of the accountability rehabilitation nursing model in the care of patients with ischemic stroke and the impact on nursing satisfaction, in order to improve the quality of care for patients with ischemic stroke. Design: This study selected 92 patients with ischemic stroke who met the inclusion criteria as the study objects, and divided them equally into the control group (46 cases) and the research group (46 cases) using a random number table. Data were collected by questionnaire. Interventions: The control group received standard routine rehabilitation nursing care, while the study group underwent an accountable rehabilitation care model. In the accountable rehabilitation care model, distinct nursing practices and strategies were employed to enhance clinical outcomes, limb function, neurological function, quality of life, and nursing satisfaction. Key elements of this model may include personalized care plans, increased emphasis on patient engagement, targeted therapeutic interventions, and a systematic approach to care coordination. A comparative analysis was conducted before and after the intervention to highlight the nuanced differences in outcomes between the two groups, shedding light on the specific benefits and effectiveness of the accountable rehabilitation care model as opposed to routine rehabilitation care. Results: In terms of clinical outcomes, the ESS score of the study group after intervention was significantly higher than that of the control group, indicating a positive impact on overall health (P < .05); limb function assessed by upper and lower limb muscle strength scores improved in both groups after the intervention. There was a significant enhancement, in which the score of the study group was significantly higher than that of the control group (P < .05); the NIHSS score showed that compared with the control group, the neurological function of the study group was significantly improved (P < .05); the SS-QOL score was used The assessed quality of life also improved significantly in the study group, exceeding the scores in the control group (P < .05). In addition, the nursing satisfaction of the study group was significantly higher compared with the control group, which highlighted the positive acceptance of the responsible rehabilitation nursing model by nursing staff (P < .05). Together, these findings highlight the combined benefits of the intervention in enhancing clinical, functional, and subjective outcomes. Discussion: The study underscores the promising clinical benefits of the responsibility system rehabilitation nursing model for patients with ischemic stroke. Marked enhancements in clinical outcomes, limb and nerve function, quality of life, and nursing satisfaction indicate its potential to significantly improve patient care. The personalized and accountable approach, featuring tailored care plans and heightened emphasis on patient engagement, holds promise for fostering positive health outcomes and enhancing overall patient experiences. Integrating this model into routine stroke care protocols emerges as a pivotal strategy for optimizing rehabilitation processes and adopting a patient-centered approach. Despite these advantages, acknowledging study limitations, such as non-randomized participant allocation and the absence of blinding, is crucial to recognizing potential biases. The study's sample size and single-center focus may impact generalizability. Beyond ischemic stroke, the model's broader significance aligns with contemporary healthcare trends, emphasizing accountability, personalized care plans, and enhanced care coordination. Its potential adaptation to various healthcare settings, chronic disease management, and preventive care could contribute to improved patient outcomes and healthcare quality. Future research should explore scalability and sustainability across diverse healthcare settings, investigating applicability to different patient populations and medical conditions. Assessing long-term effects, including healthcare cost-effectiveness and patient adherence, is essential for a comprehensive understanding of impact. Furthermore, delving into the perspectives of healthcare providers and patients can refine and tailor implementation strategies for optimal outcomes. Results: After the intervention, The European Stroke Scale (ESS) score of the study group was higher than that of the control group. After the intervention, the muscle strength scores of the upper and lower limbs of the study group were significantly higher than those of the control group. After intervention, the National Institutes of Health Stroke Scale (NIHSS) score of the study group was lower than that of the control group. After intervention, the stroke-specific quality of life scale (SS-QOL) score of the study group was higher than that of the control group. The nursing satisfaction of the study group was higher than that of the control group after intervention (all P < .05). Conclusion: The results of the study showed that the responsibility system rehabilitation nursing mode showed significant effects in improving the limb function, neurological function and quality of life of patients with ischemic stroke, which could promote the disease outcome of patients, and the nursing satisfaction of patients was high, which was worthy of promotion.

9.
Angew Chem Int Ed Engl ; 63(9): e202313640, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38193587

RESUMEN

D-peptide ligands can be screened for therapeutic potency and enzymatic stability using synthetic mirror-image proteins (D-proteins), but efficient acquisition of these D-proteins can be hampered by the need to accomplish their in vitro folding, which often requires the formation of correctly linked disulfide bonds. Here, we report the finding that temporary installation of natural O-linked-ß-N-acetyl-D-glucosamine (O-GlcNAc) groups onto selected D-serine or D-threonine residues of the synthetic disulfide-bonded D-proteins can facilitate their folding in vitro, and that the natural glycosyl groups can be completely removed from the folded D-proteins to afford the desired chirally inverted D-protein targets using naturally occurring O-GlcNAcase. This approach enabled the efficient chemical syntheses of several important but difficult-to-fold D-proteins incorporating disulfide bonds including the mirror-image tumor necrosis factor alpha (D-TNFα) homotrimer and the mirror-image receptor-binding domain of the Omicron spike protein (D-RBD). Our work establishes the use of O-GlcNAc to facilitate D-protein synthesis and folding and proves that D-proteins bearing O-GlcNAc can be good substrates for naturally occurring O-GlcNAcase.


Asunto(s)
Acetilglucosaminidasa , Proteínas , Péptidos , Polisacáridos , Glucosamina
10.
Angew Chem Int Ed Engl ; 63(14): e202318897, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38326236

RESUMEN

Mirror-image proteins (D-proteins) are useful in biomedical research for purposes such as mirror-image screening for D-peptide drug discovery, but the chemical synthesis of many D-proteins is often low yielding due to the poor solubility or aggregation of their constituent peptide segments. Here, we report a Lys-C protease-cleavable solubilizing tag and its use to synthesize difficult-to-obtain D-proteins. Our tag is easily installed onto multiple amino acids such as DLys, DSer, DThr, and/or the N-terminal amino acid of hydrophobic D-peptides, is impervious to various reaction conditions, such as peptide synthesis, ligation, desulfurization, and transition metal-mediated deprotection, and yet can be completely removed by Lys-C protease under denaturing conditions to give the desired D-protein. The efficacy and practicality of the new method were exemplified in the synthesis of two challenging D-proteins: D-enantiomers of programmed cell death protein 1 IgV domain and SARS-CoV-2 envelope protein, in high yield. This work demonstrates that the enzymatic cleavage of solubilizing tags under denaturing conditions is feasible, thus paving the way for the production of more D-proteins.


Asunto(s)
Péptidos , Proteínas , Proteínas/química , Péptidos/química , Aminoácidos/química , Técnicas de Química Sintética/métodos , Péptido Hidrolasas , Endopeptidasas
11.
Langmuir ; 39(30): 10553-10564, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37462155

RESUMEN

During COVID-19, personal protective equipment such as face masks was in urgent demand in the daily life. As the pandemic may have withdrawn from public attention, the disposal of face masks is a significant issue, especially plastic pollution. To address the degradation of the polymers in the marine environment, seven commercial masks were investigated via artificial weathering procedures in substitute ocean water. A suite of structural and chemical characterization techniques was employed, including scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, X-ray diffraction (XRD), and contact angle goniometry, to probe the treatment impact on commercially available N95, surgical, polyurethane, polyester, nylon, silk, and cotton masks. This work provides insights into the comprehensive analysis of material degradation in nature and raises public awareness of environmental issues post-pandemic.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias , Espectroscopía Infrarroja por Transformada de Fourier , Microscopía Electrónica de Rastreo , Nylons , Plásticos
12.
J Environ Manage ; 336: 117632, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36921474

RESUMEN

Although the fates of microplastics (0.1-5 mm) in marine environments and freshwater are increasingly studied, little is known about their vector effect in wastewater treatment plants (WWTPs). Previous studies have evaluated the accumulation of antibiotic resistance genes (ARGs) on microplastics, but there is no direct evidence for the selection and horizontal transfer of ARGs on different microplastics in WWTPs. Here, we show biofilm formation as well as bacterial community and ARGs in these biofilms grown on four kinds of microplastics via incubation in the aerobic and anaerobic tanks of a WWTP. Microplastics showed differential capacities for bacteria and ARGs enrichment, differing from those of the culture environment. Furthermore, ARGs in microplastic biofilms were horizontally transferred at frequencies higher than those in water samples in both tanks. Therefore, microplastics in WWTPs can act as substrates for horizontal transfer of ARGs, potentially causing a great harm to the ecological environment and adversely affecting human health.


Asunto(s)
Antibacterianos , Microplásticos , Humanos , Antibacterianos/farmacología , Plásticos , Genes Bacterianos , Aguas Residuales , Farmacorresistencia Microbiana/genética , Bacterias/genética
13.
Angew Chem Int Ed Engl ; 62(33): e202306270, 2023 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-37357888

RESUMEN

Membrane-associated D-proteins are an important class of synthetic molecules needed for D-peptide drug discovery, but their chemical synthesis using canonical ligation methods such as native chemical ligation is often hampered by the poor solubility of their constituent peptide segments. Here, we describe a Backbone-Installed Split Intein-Assisted Ligation (BISIAL) method for the synthesis of these proteins, wherein the native L-forms of the N- and C-intein fragments of the unique consensus-fast (Cfa) (i.e. L-CfaN and L-CfaC ) are separately installed onto the two D-peptide segments to be ligated via a removable backbone modification. The ligation proceeds smoothly at micromolar (µM) concentrations under strongly chaotropic conditions (8.0 M urea), and the subsequent removal of the backbone modification groups affords the desired D-proteins without leaving any "ligation scar" on the products. The effectiveness and practicality of the BISIAL method are exemplified by the synthesis of the D-enantiomers of the extracellular domains of T cell immunoglobulin and ITIM domain (TIGIT) and tropomyosin receptor kinase C (TrkC). The BISIAL method further expands the chemical protein synthesis ligation toolkit and provides practical access to challenging D-protein targets.


Asunto(s)
Inteínas , Proteínas , Péptidos/química , Empalme de Proteína
14.
Angew Chem Int Ed Engl ; 62(43): e202304483, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37670725

RESUMEN

Generating strong adhesion by engineered proteins has the potential for high technical applications. Current studies of adhesive proteins are primarily limited to marine organisms, e.g., mussel adhesive proteins. Here, we present a modular engineering strategy to generate a type of exotic protein adhesives with super strong adhesion behaviors. In the protein complexes, the lanmodulin (LanM) underwent α-helical conformational transition induced by lanthanides, thereby enhancing the stacking density and molecular interactions of adhesive protein. The resulting adhesives exhibited outstanding lap-shear strength of ≈31.7 MPa, surpassing many supramolecular and polymer adhesives. The extreme temperature (-196 to 200 °C) resistance capacity and underwater adhesion performance can significantly broaden their practical application scenarios. Ex vivo and in vivo experiments further demonstrated the persistent adhesion performance for surgical sealing and healing applications.

15.
Angew Chem Int Ed Engl ; 62(6): e202216365, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36515186

RESUMEN

Chemical synthesis of insulin superfamily proteins (ISPs) has recently been widely studied to develop next-generation drugs. Separate synthesis of multiple peptide fragments and tedious chain-to-chain folding are usually encountered in these studies, limiting accessibility to ISP derivatives. Here we report the finding that insulin superfamily proteins (e.g. H2 relaxin, insulin itself, and H3 relaxin) incorporating a pre-made diaminodiacid bridge at A-B chain terminal disulfide can be easily and rapidly synthesized by a single-shot automated solid-phase synthesis and expedient one-step folding. Our new H2 relaxin analogues exhibit almost identical structures and activities when compared to their natural counterparts. This new synthetic strategy will expediate production of new ISP analogues for pharmaceutical studies.


Asunto(s)
Relaxina , Relaxina/química , Relaxina/metabolismo , Disulfuros/química , Técnicas de Síntesis en Fase Sólida , Proteínas/química , Insulina/química , Receptores Acoplados a Proteínas G/metabolismo
16.
Zhongguo Yi Liao Qi Xie Za Zhi ; 47(6): 702-705, 2023 Nov 30.
Artículo en Zh | MEDLINE | ID: mdl-38086733

RESUMEN

OBJECTIVE: To analyze the medical equipment operation data of 44 clinical departments in the hospital from three aspects: materials and consumables, operation and maintenance depreciation, and operation management. METHODS: To formulate the evaluation standards and scoring criteria for the operation indicators, the lowest score is 0 points, and the highest score is 5 points. Based on the operation indicators of medical equipment, establish a hierarchical structure model, determine the criterion layer and sub-criteria layer, construct a judgment matrix, normalize it, and calculate the weight coefficient. RESULTS: Count equipment operation data in 2021 and 2022. Score according to the assessment standards, assign weights through the analytic hierarchy process, calculate the total score and sort, and making a special analysis on the top 10 departments and departments with a score below 4 points, and formulate a rectification plan. CONCLUSIONS: The establishment of index assessment standards and the weight distribution of AHP can effectively enhance the control of equipment operating costs.


Asunto(s)
Proceso de Jerarquía Analítica , Racionalización , Equipo Quirúrgico , Estándares de Referencia , Control de Costos
17.
J Am Chem Soc ; 144(1): 349-357, 2022 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-34978456

RESUMEN

Disulfide-rich proteins are useful as drugs or tool molecules in biomedical studies, but their synthesis is complicated by the difficulties associated with their folding. Here, we describe a removable glycosylation modification (RGM) strategy that expedites the chemical synthesis of correctly folded proteins with multiple or even interchain disulfide bonds. Our strategy comprises the introduction of simple O-linked ß-N-acetylglucosamine (O-GlcNAc) groups at the Ser/Thr sites that effectively improve the folding of disulfide-rich proteins by stabilization of their folding intermediates. After folding, the O-GlcNAc groups can be efficiently removed using O-GlcNAcase (OGA) to afford the correctly folded proteins. Using this strategy, we completed the synthesis of correctly folded hepcidin, an iron-regulating hormone bearing four pairs of disulfide-bonds, and the first total synthesis of correctly folded interleukin-5 (IL-5), a 26 kDa homodimer cytokine responsible for eosinophil growth and differentiation.


Asunto(s)
Acetilglucosamina
18.
Langmuir ; 38(29): 8890-8898, 2022 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-35830463

RESUMEN

The anisotropic adhesion behavior of the gecko is closely related to their feet and is comprised of keratinous hairs, setae, where van der Waals forces permit attachment and detachment during locomotion. Previous research either achieved only isotropic adhesion behaviors or involved the complicated photolithography method. Here, we reported a simple way to achieve the anisotropic adhesion behaviors of gecko-inspired adhesives, consisting of micropillars with asymmetrically tilted orientation via the 3D printing technique. The adhesive forces of structured polymer pillars achieved 4-fold stronger, compared to controls with the plain surface. The anisotropic adhesion behavior is presented on the patterned surface and is two times stronger along the gripping direction compared to the releasing direction on the adhesives, which is attributed to the asymmetric stress distributions at the edges, as well as the stresses resulting from the moment with the sheared top. The finite element analysis is applied to demonstrate the stress distributions and displacement variations. This work provides the insight into the design and fabrication of gecko-inspired adhesives with anisotropic adhesion behaviors in practical applications.


Asunto(s)
Adhesivos , Lagartos , Adhesividad , Animales , Análisis de Elementos Finitos , Locomoción
19.
J Environ Manage ; 307: 114557, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35066197

RESUMEN

In this study, two Cr(VI)-reducing functional bacterial strains (TJ-1 and TJ-5) were successfully isolated and screened from the chromium-contaminated soil from a real site. The 16S rRNA gene sequences were analysed, which showed high similarity (>99%) with Stenotrophomonas maltophilia (TJ-1) and Brucella intermedius (TJ-5) species. The optimum growth for the two bacteria to reduce Cr(VI) were achieved at pH 7.0 and initial inoculation amount of 5%. The two strains were applied to real contaminated soil samples and showed better Cr removal when external carbon sources were added. Using sawdust as a solid-phase carbon source supplement, both TJ-1 and TJ-5 showed higher remediation efficiency (99.77% and 93.86%) than using glucose as the carbon source (68.56% and 70.87%). Results of the stability of soil Cr(VI) bioremediation revealed that the water-soluble Cr(VI) content of bioremediated sample remained unchanged, indicating that Cr(VI) is not easily released after death of the strains. Solid-phase carbon source supplements may help the cells to attach and grow into biofilms, creating a better growth condition which improved the remediation efficiency. Column experiments showed that the total remediation efficiencies by the two strains were 34.23% and 20.63%, respectively, within a short time period (76 h). Therefore, the two strains showed great bioremediation potentials for chromium-contaminated sites and can be used in future application of in-situ bioremediation.


Asunto(s)
Cromo , Contaminantes del Suelo , Bacterias , Biodegradación Ambiental , ARN Ribosómico 16S/genética
20.
J Sci Food Agric ; 102(4): 1397-1404, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-34370306

RESUMEN

BACKGROUND: To improve the utilization rate of cinnamon essential oil and compensate for the shortcomings of its easy decomposition and oxidation, the microemulsion of cinnamon essential oil was prepared using Tween 80 and anhydrous ethanol as surfactant and cosurfactant, respectively. The effects of the surfactant type, Km value, preparation temperature and aqueous pH on the quality of the microemulsion were studied via a pseudo-ternary phase diagram. The slow-release performance of cinnamon essential oil microemulsion and the control performance of the insect repellent package on the rice weevil were characterized. RESULTS: The results showed that, when Tween 80 was used as a surfactant and anhydrous ethanol was used as a cosurfactant, the Km value was 3:1, preparation temperature was 40 °C, aqueous pH was 5 and prepared cinnamon essential oil microemulsion was of the O/W type. The microemulsion had strong stability and a 81.5-nm concentrated particle size distribution, and possessed excellent embedding and sustained-release effects. The prepared insect repellent active package prolongs the use time and the effect of cinnamon essential oil. The repellent rate of the rice weevil was as high as 100% after 48 h, and the contact mortality and fumigation mortality rates of the rice weevil also reached 96.67% and 86.67%, respectively, after 96 h. CONCLUSION: The prepared cinnamon essential oil microemulsion and active packaging had a good sustained-release effect. © 2021 Society of Chemical Industry.


Asunto(s)
Insecticidas , Aceites Volátiles , Cinnamomum zeylanicum , Preparaciones de Acción Retardada , Emulsiones , Solubilidad , Tensoactivos
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