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1.
Tzu Chi Med J ; 34(3): 310-317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912047

RESUMO

Objectives: Cardiovascular diseases are one of the primary causes of death. Cardiomyocyte loss is a significant feature of cardiac injury. Ferroptosis is iron-dependent cell death, which occurs due to excess iron and reactive oxygen species (ROS) accumulation causing lipid peroxidation, and subsequent cell death. Ferroptosis has been confirmed to mediate ischemia/reperfusion-induced cardiomyopathy and chemotherapy-induced cardiotoxicity. Berberine (BBR) has been proven to protect the heart from cardiomyopathies, including cardiac hypertrophy, heart failure, myocardial infarction, and arrhythmias. It protects cardiomyocytes from apoptosis and autophagy. However, the relation between BBR and ferroptosis is still unknown. This study aimed to confirm if BBR reduces cardiac cell loss via inhibiting ferroptosis. Materials and Methods: We used erastin and Ras-selective lethal small molecule 3 (RSL3) to establish a ferroptosis model in an H9c2 cardiomyoblast cell line and rat neonatal cardiomyocytes to prove that BBR has a protective effect on cardiac cells via inhibiting ferroptosis. Results: In H9c2 cardiomyoblasts, the results showed that BBR reduced erastin and RSL3-induced cell viability loss. Moreover, BBR decreased ROS accumulation and lipid peroxidation in cells induced with ferroptosis. Furthermore, quantitative polymerase chain reaction results showed that Ptgs2 mRNA was reduced in BBR-treated cells. In rat neonatal cardiomyocytes, BBR reduced RSL3-induced loss of cell viability. Conclusion: These results indicated that BBR inhibited ferroptosis via reducing ROS generation and reducing lipid peroxidation in erastin and RSL3-treated cardiac cells.

2.
Front Genet ; 13: 931562, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923692

RESUMO

Since the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, SARS-CoV-2 has led to a global coronavirus disease 2019 (COVID-19) pandemic. A better understanding of the SARS-CoV-2 receptor ACE2 at the genetic level would help combat COVID-19, particularly for long COVID. We performed a genetic analysis of ACE2 and searched for its common potential single nucleotide polymorphisms (SNPs) with minor allele frequency >0.05 in both European and Chinese populations that would contribute to ACE2 gene expression variation. We thought that the variation of the ACE2 expression would be an important biological feature that would strongly affect COVID-19 symptoms, such as "brain fog", which is highlighted by the fact that ACE2 acts as a major cellular receptor for SARS-CoV-2 attachment and is highly expressed in brain tissues. Based on the human GTEx gene expression database, we found rs2106809 exhibited a significant correlation with the ACE2 expression among multiple brain and artery tissues. This expression correlation was replicated in an independent European brain eQTL database, Braineac. rs2106809*G also displays significantly higher frequency in Asian populations than in Europeans and displays a protective effect (p = 0.047) against COVID-19 hospitalization when comparing hospitalized COVID-19 cases with non-hospitalized COVID-19 or SARS-CoV-2 test-negative samples with European ancestry from the UK Biobank. Furthermore, we experimentally demonstrated that rs2106809*G could upregulate the transcriptional activity of ACE2. Therefore, integrative analysis and functional experiment strongly support that ACE2 SNP rs2106809 is a functional brain eQTL and its potential involvement in long COVID, which warrants further investigation.

3.
Front Oncol ; 12: 911401, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924143

RESUMO

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer which typically exhibits a diverse progression trajectory. Our study sought to explore the cell differentiation trajectory of LUAD and its clinical relevance. Methods: Utilizing a single-cell RNA-sequencing dataset (GSE117570), we identified LUAD cells of distinct differential status along with differentiation-related genes (DRGs). DRGs were applied to the analysis of bulk-tissue RNA-sequencing dataset (GSE72094) to classify tumors into different subtypes, whose clinical relevance was further analyzed. DRGs were also applied to gene co-expression network analysis (WGCNA) using another bulk-tissue RNA-sequencing dataset (TCGA-LUAD). Genes from modules that demonstrated a significant correlation with clinical traits and were differentially expressed between normal tissue and tumors were identified. Among these, genes with significant prognostic relevance were used for the development of a prognostic nomogram, which was tested on TCGA-LUAD dataset and validated in GSE72094. Finally, CCK-8, EdU, cell apoptosis, cell colony formation, and Transwell assays were used to verify the functions of the identified genes. Results: Four clusters of cells with distinct differentiation status were characterized, whose DRGs were predominantly correlated with pathways of immune regulation. Based on DRGs, tumors could be clustered into four subtypes associated with distinct immune microenvironment and clinical outcomes. DRGs were categorized into four modules. A total of nine DRGs (SFTPB, WFDC2, HLA-DPA1, TIMP1, MS4A7, HLA-DQA1, VCAN, KRT8, and FABP5) with most significant survival-predicting power were integrated to develop a prognostic model, which outperformed the traditional parameters in predicting clinical outcomes. Finally, we verified that knockdown of WFDC2 inhibited proliferation, migration, and invasion but promoted the apoptosis of A549 cells in vitro. Conclusion: The cellular composition and cellular differentiation status of tumor mass can predict the clinical outcomes of LUAD patients. It also plays an important role in shaping the tumor immune microenvironment.

4.
ACS Nano ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35920687

RESUMO

The forthcoming wearable health care devices garner considerable attention because of their potential for monitoring, treatment, and protection applications. Herein, a self-powered triboelectric patch was developed using polytetrafluoroethylene rubbed with nylon fabric. The triboelectric patch can maintain a stable electrostatic field, due to the excess electrification on the surface of the triboelectric layer. The designed triboelectric nanogenerator (TENG) output watt density can reach about 485 mW/m2 with added resistance of 11 kΩ. Additionally, the performance of the triboelectric patch allowed eye movement monitoring. The maximum voltage could reach 80 V at the vertical distance of 20 mm between the frictional layer and collector. The triboelectric patch not only can power a digital watch for potential wearable applications but also can be integrated to monitor eye movements during sleep. This work proposed a mechanism for human movement energy harvesting, which may be used for self-powered smart wearable health equipment and Maxwell displacement current wireless sensors.

5.
Mol Cell Proteomics ; : 100276, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35931320

RESUMO

Lysine acetylation is a reversible and dynamic post-translational modification that play vital roles in regulating multiple cellular processes including aging. However, acetylome-wide analysis in the aging process remains poorly studied in mammalian tissues. Nicotinamide adenine dinucleotide (NAD+), a hub metabolite, benefits healthspan at least in part due to the activation of Sirtuins, a family of NAD+-consuming deacetylases, indicating changes in acetylome. Here, we combine two antibodies for the enrichment of acetylated peptides and perform label-free quantitative acetylomic analysis of mouse livers during natural aging and upon the treatment of beta-nicotinamide mononucleotide (NMN), a NAD+ booster. Our study describes previously unknown acetylation sites and reveals the acetylome-wide dynamics with age as well as upon the treatment of NMN. We discover protein acetylation events as potential aging biomarkers. We demonstrate that the life-beneficial effect of NMN could be partially reflected by the changes in age-related protein acetylation. Our quantitative assessment indicates that NMN has mild effects on acetylation sites previously reported as substrates of Sirtuins. Collectively, our data analyzes protein acetylation with age, laying critical foundation for the functional study of protein post-translational modification essential for healthy aging and perhaps disease conditions.

6.
Nat Commun ; 13(1): 4560, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931776

RESUMO

On-chip polarimeters are highly desirable for the next-generation ultra-compact optical and optoelectronic systems. Polarization-sensitive photodetectors relying on anisotropic absorption of natural/artificial materials have emerged as a promising candidate for on-chip polarimeters owing to their filterless configurations. However, these photodetectors can only be applied for detection of either linearly or circularly polarized light, not applicable for full-Stokes detection. Here, we propose and demonstrate three-ports polarimeters comprising on-chip chiral plasmonic metamaterial-mediated mid-infrared photodetectors for full-Stokes detection. By manipulating the spatial distribution of chiral metamaterials, we could convert polarization-resolved absorptions to corresponding polarization-resolved photovoltages of three ports through the photothermoelectric effect. We utilize the developed polarimeter in an imaging demonstration showing reliable ability for polarization reconstruction. Our work provides an alternative strategy for developing polarization-resolved photodetectors with a bandgap-independent operation range in the mid-infrared.

7.
BMC Pulm Med ; 22(1): 298, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922772

RESUMO

BACKGROUND: The provinces in western China have undergone rapid urbanization and industrialization, particularly since the Chinese government launched the Great Western Development Strategy in 2000. We examined the time trends and contributions of age, period, and cohort effects to asthma incidence and mortality in Sichuan Province, a populous province in western China, from 1990 to 2019. METHODS: The data of Sichuan Province from 1990 to 2019 were extracted from the Global Burden of Disease study 2019. Trends and average annual percentage change were estimated using joinpoint regression. Age, period, and cohort effects were estimated using an age-period-cohort model with the intrinsic estimator method. RESULTS: In the latest period (2015-2019), the highest incidence of asthma was 2004.49/100,000 in children aged < 5 years, and the highest mortality rate was 22.04/100,000 for elderly people aged > 80 years. Age-standardized rates generally remained stable (95% confidence interval [CI] - 0.21, 0.11) for incidence and declined by 4.74% (95% CI - 5.09, - 4.39) for mortality over the last 30 years. After controlling for other effects, the age effect on asthma showed that the incidence rate ratio (RR) was highest in the < 5 years age group, and the mortality RR was highest in the > 80 years age group. The period effect on incidence and mortality decreased from 1990 to 2019, respectively. A cohort effect was found the incidence RR increased slowly from the early birth cohorts to the later birth cohorts, especially after the 2005 birth cohort, whereas the mortality RR continued to decline. CONCLUSIONS: There was a significant effect of older age on the asthma mortality rate over the last 30 years, and the incidence rate in children aged < 5 years increased. The relative risk of asthma incidence in the later birth cohorts increased. Effective preventive measures and public health policies should be to protect children and elderly people from potentially harmful chronic diseases.


Assuntos
Asma , Idoso , Idoso de 80 Anos ou mais , Asma/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Efeito de Coortes , Estudos de Coortes , Humanos , Incidência , Mortalidade
8.
Cell Biol Toxicol ; 2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35809138

RESUMO

DDI2 and DDI3 (DDI2/3) are two identical genes in Saccharomyces cerevisiae encoding cyanamide (CY) hydratase. They are not only highly induced by CY, but also by a DNA-damaging agent methyl methanesulfonate (MMS), and the regulatory mechanism is unknown. In this study, we performed a modified genome-wide genetic synthetic array screen and identified Fzf1 as a zinc-finger transcriptional activator required for CY/MMS-induced DDI2/3 expression. Fzf1 binds to a DDI2/3 promoter consensus sequence CS2 in vivo and in vitro, and this interaction was enhanced in response to the CY treatment. Indeed, experimental over production of Fzf1 alone was sufficient to induce DDI2/3 expression; however, CY and MMS treatments did not cause the accumulation or apparent alteration in migration of cellular Fzf1. To test a hypothesis that Fzf1 is activated by covalent modification of CY and MMS, we performed mass spectrometry of CY/MMS-treated Fzf1 and detected a few modified lysine residues. Amino acid substitutions of these residues revealed that Fzf1-K70A completely abolished MMS-induced and reduced CY-induced DDI2/3 expression, indicating that the Fzf1-K70 methylation activates Fzf1. This study collectively reveals a novel regulatory mechanism by which Fzf1 is activated by chemical modifications and in turn induces the expression of its target genes for detoxification.

9.
Sci Total Environ ; : 157199, 2022 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-35810896

RESUMO

The temporal heterogeneity of nitrogen availability in soils is increasing due to agricultural deposition. We here compared the effects of gradually increasing nitrogen deposition rate and its increasing temporal heterogeneity patterns on the functional traits of seedlings of exotic species Rhus typhina and the native species Rhus chinensis. Nitrogen deposition rates of 0, 8, 20 g N m-2 year-1 and constant, single-peak, and double-peak nitrogen were added to simulate deposition rate and temporal heterogeneity. After 60 days of treatment, R. typhina seedlings had several advantageous growth trait values, such as higher total biomass production, but lower phenotypic plasticity than R. chinensis seedlings. R. typhina seedlings also had higher phenotypic integration, measured as the correlation among functional traits. The increased nitrogen deposition rate affected several traits of the two species differently. Thus, while R. chinensis seedlings allocated more biomass to leaves and less to roots with increasing N deposition, R. typhina seedlings had stable biomass allocation among all N treatments. Chlorophyll content, leaf phosphorus concentration, and water use efficiency increased, but the maximum net photosynthetic rate decreased, with N availability in R. chinensis, but not in R. typhina. Temporal heterogeneity had no significant effect on the total biomass of R. typhina and R. chinensis seedlings. Overall, the performance of R. typhina is better than that of R. chinensis seedlings under different nitrogen deposition treatments, which is due to the significantly advantageous trait values and greater phenotypic integration of R. typhina seedlings, whereas R. chinensis seedlings have higher phenotypic plasticity.

10.
Cell Prolif ; : e13293, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35822247

RESUMO

OBJECTIVES: As a result of the current limitation of therapeutic strategies, the repair and regeneration of oviduct injuries required an alternative treatment. We present a novel approach to treat oviduct injuries through a dental pulp stem cells (DPSCs)-based therapy. MATERIALS AND METHODS: In vitro and in vivo models have been established. Immunofluorescence staining, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to investigate the features and angiogenic properties of DPSCs, as well as their impact on macrophages, in vitro. For the in vivo experiment with female SD rat model, immunohistochemical staining and ELISA analysis were used to assess the effects of DPSCs on the repair and regeneration of damaged oviducts. RESULTS: The present data showed that intraperitoneal injection of DPSCs reduced the expression of IL-6 and TNF-α to inhibit the immunoreaction in injured sites, as well as increased the expression of VEGF to promote the in situ formation of vessel-like structures, thus the repair and recovery process could be initiated. CONCLUSIONS: We concluded that DPSCs-based therapy could be a novel potential technique for restoring the structure and function of damaged oviduct by enhancing immuno-regulated effect and promoting angiogenic property.

11.
Front Neurosci ; 16: 893239, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812240

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders characterized in current diagnostic criteria by two dominant symptoms, inattention and hyperactivity/impulsivity. Here, we show that task-related alpha (8-12 Hz) interhemispheric connectivity changes, as assessed during a unimanual finger-tapping task, is correlated with inattentive symptom severity (r = 0.55, p = 0.01) but not with severity of hyperactive/impulsive symptoms. Prior published analyses of the same dataset have already show that alpha event-related desynchronization (ERD) in the hemisphere contralateral to unimanual tapping is related to hyperactive/impulsive symptom severity (r = 0.43, p = 0.04) but not to inattentive symptom severity. Our findings demonstrate a neurobiological dissociation in ADHD symptom severity, with implications for understanding the structure of endophenotypes in the disorder as well as for biomarker development.

12.
Ann Med ; 54(1): 1977-1987, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35838186

RESUMO

BACKGROUND: To figure out the efficacy, effects, safety and patient's subjective perceptions of phacoemulsification with the active-fluidics system (AFS). PATIENTS AND METHODS: This was a prospective, randomized, double-masked, controlled clinical study. Age-related cataract patients were recruited and randomly assigned to the AFS group and gravity-fluidics system (GFS) group in a ratio of 1:1 to have phacoemulsification. Participants were followed up at one day, one week, one month and three months postoperatively (Chinese Clinical Trial Registry, ChiCTR2100044409). RESULTS: The overall included participants were 107 finally. The total aspiration time of the AFS group was significantly less than that of the GFS group (p = .020), while no significant difference existed in cumulative dissipated energy and estimated fluid usage between the two groups. The best corrected visual acuity was significantly better in the AFS group at one day and one week postoperatively (p = .002, p = .038 respectively). The recovery of central corneal thickening and macular superficial vasculature increase was earlier in the AFS group. The central retinal thickness was significantly higher in the GFS group at one month and three months postoperatively (p = .029, p = .016 respectively). The incidence of corneal adverse events was higher in GFS group (p = .035). No serious adverse events occurred in either group. Pain scores and the scores of Cat-PROM5 questionnaire of the AFS group were significantly lower than that of the GFS group (p = .011, p = .002 respectively). CONCLUSION: AFS improves the efficiency, effects, safety and patients' subjective perceptions of phacoemulsification compared with GFS. It is worthwhile to promote its application in cataract surgery.KEY MESSAGESThe active-fluidics system automatically detects and maintains stable intraocular pressure at the set value.The active-fluidics system improves the efficiency, effects, safety and patients' subjective perceptions in phacoemulsification.


Assuntos
Extração de Catarata , Catarata , Facoemulsificação , Catarata/etiologia , Extração de Catarata/efeitos adversos , Humanos , Facoemulsificação/efeitos adversos , Estudos Prospectivos , Acuidade Visual
13.
Adv Sci (Weinh) ; : e2200538, 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35863914

RESUMO

As one of leading technologies in detecting relativistic particles, Cherenkov radiation plays an essential role in modern high-energy and particle physics. However, the limited photon yield in transparent dielectrics makes efficient Cherenkov radiation only possible with high-energy particles (at least several MeV). This restriction hinders applications of Cherenkov radiation in free-electron light source, bio-imaging, medical therapy, etc. Broadband enhancement of Cherenkov radiation is highly desired for all these applications, but still widely acknowledged as a scientific challenge. To this end, a general approach is reported to enhance the photon yield of Cherenkov radiation using dispersionless plasmons. Broadband dispersionless plasmons can be realized by exploiting either the acoustic nature of terahertz plasmons in a graphene-based heterostructure or the nonlocal property of optical plasmons in a metallodielectric structure. When coupled to moving electrons, such dispersionless plasmons give rise to a radiation enhancement rate more than two orders of magnitude (as compared with conventional Cherenkov radiation) over an ultrabroad frequency band. Moreover, since the phase velocity of dispersionless plasmons can be made as small as the Fermi velocity, giant radiation enhancements can be readily induced by ultralow-energy free electrons (e.g., with a kinetic energy down to 3 eV), without resorting to relativistic particles.

14.
Biomed Res Int ; 2022: 9352735, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35845933

RESUMO

Background: The PDCA cycle consists of four stages: P (plan), D (design), C (check), and A (action). With the wide acceptance of PDCA cycle, there is an urgent need to verify the effect of combining this concept with clinical nursing work. Therefore, on the basis of in-depth study of a large number of related literature, the influence of PDCA cycle management mode on nurses' work efficiency, work enthusiasm, and teamwork ability was explored, so as to provide reference experience for exploring the nursing quality management model adapted to the development of medicine. Objective: To explore the application of PDCA circulation management mode in clinical nursing work and to explore its influence on the work efficiency, enthusiasm, and team cooperation ability of nurses. Methods: From January 2019 to January 2021, the patients were divided into two groups. The control group received routine nursing care, and the research group received the PDCA circulation management mode. Both groups of nurses received one-year training. The nursing quality, the ability of teamwork, the scores of personal quality control in clinical departments, the scores of nursing satisfaction, the number of problems in nursing document quality management, and nurses' enthusiasm were compared between the two groups. Results: The scores of relationships and family and work balance were greater than those of the control group. The nursing quality result suggested the nursing quality of gynecological operation area, emergency operation area, comprehensive operation area, and surgical operation area in research nurses was significantly better than the control cases (P < 0.05). The quality management of nursing documents showed that the number of problems in nursing documents such as nursing record displayed fewer than control group (P < 0.05). The personal quality-controlled checking in medical department showed that the points of ward governance, head nurse management quality control examination, first-level nursing, recovery, publications on therapeutics, pill governance, and healthcare documentation in the research group were higher than control group (P < 0.05). The teamwork ability implied the scores of interpersonal communications, problem definition, project division, team evaluation assistance and motivation, data collection, interpretation, and extraction of results in the observation group were remarkably greater than those of control group (P < 0.05). The satisfaction mark showed that the scores of care information exchange, advanced technologies, attitude towards care providing, healthcare establishing, knowledge publicity, and learning in the researches were markedly more than those of the control group (P < 0.05). Conclusion: Compared with the traditional clinical nursing management, the use of the PDCA circulation management mode can effectively improve the quality of hospital nursing work, strengthen nurses' ability of teamwork, improve nurses' work efficiency and enthusiasm, enhance their sense of achievement of clinical nursing work, then improve patient satisfaction, and enhance the reputation and competitiveness of hospitals. Therefore, the PDCA management model is worth popularizing and applying in clinic.


Assuntos
Comunicação , Enfermeiras e Enfermeiros , Hospitais , Humanos , Satisfação do Paciente
15.
J Oncol ; 2022: 7319641, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847360

RESUMO

Aim: To explore the role of Rac1 on sorafenib resistance in hepatocellular carcinoma. Methods: CCK-8, wound healing assay, Transwell, and cell cycle assay were used to detect the tumor cells development. Cell viability was assessed by MTT. The glycolytic pathway was revealed by cellular metabolism assays. Result: We recovered that Rac1 upregulation was related to HCC patients' poorer prognosis. Forced expression of Rac1 promoted cell development and sorafenib chemoresistance in HCC cells. Rac1 inhibitor EHop-016 and sorafenib combination markedly prevented cell viability, G2/M phase cycle arrest, and apoptosis than single therapy. Furthermore, combination therapy decreased glycolysis in HCC cells. In vivo, the tumor growth was significantly prevented by combination therapy single therapy. Conclusion: Our research declares that Rac1 inhibition could block sorafenib resistance in HCC by decreasing glycolysis, which would provide an underlying target for HCC therapy.

16.
J Biomed Nanotechnol ; 18(4): 1164-1171, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35854466

RESUMO

Gingival fibroblasts play an important role in the constitution of soft tissue attachment. This study aims to investigate whether porous zirconia coating has a positive effect on promoting human gingival fibroblast attachment. The porous zirconia coating was loaded on zirconia surface by the dip coating method, surface morphology and composition were confirmed by scanning electron microscope and energy dispersive spectrometer; Tested the tensile bond strength by universal testing machine; Tested the surface roughness by roughness analyzer; Human gingival fibroblast proliferation, integrin ß1 and F-actin immunofluorescence staining explored the influence of porous zirconia on the adhesion and proliferation of human gingival fibroblast. Zirconia0.2 group showed spherical zirconia particles with diameters of 3-8 µm are distributed on the surface; The bonding strength of zirconia particle coating group reached 16.1±0.1 MPa, and the surface roughness was 0.715±0.091 µm; In comparison with control group (P < 0.01), the percentage of human gingival fibroblasts adhering to zirconia was markedly higher. In zirconia group, integrin-ß1 and F-actin fluoresced more obvious than in control group. Porous zirconia coating can form a porous structure on the surface and the porous structure can promote the attachment and proliferation of human gingival fibroblast, it will be more beneficial for soft tissue early sealing.


Assuntos
Actinas , Zircônio , Fibroblastos , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Porosidade , Propriedades de Superfície , Zircônio/química
17.
Int J Antimicrob Agents ; : 106631, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35787920

RESUMO

Real-world experience with low-level viraemia (LLV) and its impact remain less reported among people living with HIV (PLWH) who receive antiretroviral therapy (ART) containing second-generation integrase strand transferase inhibitors, including dolutegravir and bictegravir. This retrospective cohort study included virally suppressed PLWH who achieved plasma HIV-RNA viral load (PVL) <50 copies/mL for ≥6 months and were switched to either dolutegravir- or bictegravir-based ART. Incidence rates of developing LLV events (PVL, 50-200 copies/mL) and virologic failure (VF) (PVL ≥1000 copies/mL) were compared between the dolutegravir and bictegravir cohorts. A total of 623 and 862 PLWH switched to dolutegravir-based and bictegravir-based ART, respectively, were included. The incidence rate of developing LLV was 6.2 per 100 person-years of follow-up (PYFU) in the bictegravir cohort and 3.8 per 100 PYFU in the dolutegravir cohort [incidence rate ratio (IRR) = 1.63, 95% confidence interval (CI), 0.90-2.95; P = 0.08], while rates of VF were 0.69 per 100 PYFU and 0.95 per 100 PYFU, respectively, in the bictegravir and dolutegravir cohorts (IRR = 0.72, 95% CI 0.12-3.39; P = 0.34). Presence of LLV events was not associated with subsequent VF in multivariate analysis. Secondary analysis also demonstrated that resistance-associated mutations (RAMs) to nucleoside reverse transcriptase inhibitors (NRTIs) before switch were not associated with adverse virologic outcomes in either cohort. In conclusion, among virally suppressed PLWH, the incidences of developing LLV or VF were similar after switch to dolutegravir- or bictegravir-based ART. Pre-existing RAMs to NRTIs or LLV events were not associated with subsequent VF.

18.
Diagnostics (Basel) ; 12(7)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35885568

RESUMO

BACKGROUND: Accurate outcome prediction is of great clinical significance in customizing personalized treatment plans, reducing the situation of poor recovery, and objectively and accurately evaluating the treatment effect. This study intended to evaluate the performance of clinical text information (CTI), radiomics features, and survival features (SurvF) for predicting functional outcomes of patients with ischemic stroke. METHODS: SurvF was constructed based on CTI and mRS radiomics features (mRSRF) to improve the prediction of the functional outcome in 3 months (90-day mRS). Ten machine learning models predicted functional outcomes in three situations (2-category, 4-category, and 7-category) using seven feature groups constructed by CTI, mRSRF, and SurvF. RESULTS: For 2-category, ALL (CTI + mRSRF+ SurvF) performed best, with an mAUC of 0.884, mAcc of 0.864, mPre of 0.877, mF1 of 0.86, and mRecall of 0.864. For 4-category, ALL also achieved the best mAuc of 0.787, while CTI + SurvF achieved the best score with mAcc = 0.611, mPre = 0.622, mF1 = 0.595, and mRe-call = 0.611. For 7-category, CTI + SurvF performed best, with an mAuc of 0.788, mPre of 0.519, mAcc of 0.529, mF1 of 0.495, and mRecall of 0.47. CONCLUSIONS: The above results indicate that mRSRF + CTI can accurately predict functional outcomes in ischemic stroke patients with proper machine learning models. Moreover, combining SurvF will improve the prediction effect compared with the original features. However, limited by the small sample size, further validation on larger and more varied datasets is necessary.

19.
Cell Rep ; 40(4): 111137, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35905716

RESUMO

In addition to neuroprotective strategies, neuroregenerative processes could provide targets for stroke recovery. However, the upregulation of inhibitory chondroitin sulfate proteoglycans (CSPGs) impedes innate regenerative efforts. Here, we examine the regulatory role of PTPσ (a major proteoglycan receptor) in dampening post-stroke recovery. Use of a receptor modulatory peptide (ISP) or Ptprs gene deletion leads to increased neurite outgrowth and enhanced NSCs migration upon inhibitory CSPG substrates. Post-stroke ISP treatment results in increased axonal sprouting as well as neuroblast migration deeply into the lesion scar with a transcriptional signature reflective of repair. Lastly, peptide treatment post-stroke (initiated acutely or more chronically at 7 days) results in improved behavioral recovery in both motor and cognitive functions. Therefore, we propose that CSPGs induced by stroke play a predominant role in the regulation of neural repair and that blocking CSPG signaling pathways will lead to enhanced neurorepair and functional recovery in stroke.


Assuntos
Células-Tronco Neurais , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Regeneração Nervosa/fisiologia , Células-Tronco Neurais/metabolismo , Peptídeos , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo
20.
J Chromatogr A ; 1677: 463300, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35810643

RESUMO

In this work, a new strategy of simultaneously grafting two different functional ligands onto the silica surface was adopted to prepare a carbonyldiimidazolium/dodecyl dual-functionalized silica stationary phase (Sil-CDI-DD) by recycling the discarded commercial C18 columns as the raw materials. A full characterization of the waste silica-C18, the calcined silica, the acidified silica and the new packing materials was done to explore the feasibility of recycling the waste chromatographic columns. Hydrophobic and hydrophilic selectivity of the obtained Sil-CDI-DD was specifically investigated, and retention mechanisms in reversed-phase and hydrophilic interaction chromatography modes were discussed. The experimental results showed that the perfect combination of carbonyldiimidazolium and long-chain alkyl groups commendably enhanced the separation selectivity and efficiency of the versatile Sil-CDI-DD, which could provide multiple interaction sites for diverse target analytes, thereby contributing to the favorable resolution of hydrophilic nucleosides/nucleobases and weak polar environmental endocrine disruptors, including alkylphenols, bisphenols, steroid hormones and phthalates.


Assuntos
Nucleosídeos , Dióxido de Silício , Cromatografia , Interações Hidrofóbicas e Hidrofílicas , Nucleosídeos/química , Dióxido de Silício/química
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