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1.
Sci Total Environ ; 946: 174453, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964410

RESUMO

BACKGROUND: Despite evidence linking fine particulate matter (PM2.5) to cardiometabolic multimorbidity (CMM), the impact of its components remains unclear. Socioeconomic status (SES) and regional disparities may confound their association. We aim to evaluate the associations between PM2.5 components and CMM and explore how socioeconomic status and regional disparities affect these relationships. METHODS: We recruited 108,941 participants aged 35-76 years from ten cities in eastern China. Individual exposure was assessed using Tracking Air Pollution in China (TAP) data, including PM2.5 and five components: ammonium (NH4+), black carbon (BC), nitrates (NO3-), organic matter (OM), and sulfates (SO42-). Generalized linear models and quantile g-computation models were employed to quantify the effects of PM2.5 components on CMM and to identify key components. Stratified analyses were performed to investigate the modifying effect of SES and regional disparities. RESULTS: For each increase in interquartile range (IQR), BC (odds ratio [OR] 1.37, 95 % CI 1.29-1.47), OM (1.38, 1.29-1.48), NH4+ (1.31, 1.21-1.40), NO3- (1.34, 1.25-1.44), and SO42- (1.28, 1.20-1.38) were positively associated with CMM. Joint exposure to five components was significantly positively associated with CMM (OR: 1.27, 95 % CI: 1.21-1.33), with SO42- having the highest estimated weight, followed by NO3- and BC. These associations were stronger for participants from low socio-economic status and poor regions. CONCLUSION: In summary, we found a stronger hazard effect of PM2.5 and its components on CMM, compared to those suffering from CMDs, particularly among participants with low socioeconomic status and in poor regions. SO42- may be a primary contributor to the association between PM2.5 components and CMM. These findings underscore the importance of prioritizing CMM and targeting SO42-related pollution sources in health policies, particularly amid China's aging population, reducing environmental health inequalities is critical.

2.
Drug Des Devel Ther ; 18: 1855-1864, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828023

RESUMO

Purpose: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ. Methods: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated. Results: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80-1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported. Conclusion: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing. Trial Registration: ClinicalTrials.gov NCT06083116.


Assuntos
Interações Medicamentosas , Voluntários Saudáveis , Hidroclorotiazida , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/farmacocinética , Hidroclorotiazida/farmacologia , Adulto , Masculino , Adulto Jovem , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Glucosídeos/farmacologia , Povo Asiático , Relação Dose-Resposta a Droga , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , População do Leste Asiático
3.
J Neuroeng Rehabil ; 21(1): 102, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877589

RESUMO

BACKGROUND: Investigating the spatial distribution of muscle activity would facilitate understanding the underlying mechanism of spasticity. The purpose of this study is to investigate the characteristics of spastic muscles during passive stretch and active contraction by high-density surface electromyography (HD-sEMG). METHODS: Fourteen spastic hemiparetic subjects and ten healthy subjects were recruited. The biceps brachii (BB) muscle activity of each subject was recorded by HD-sEMG during passive stretch at four stretch velocities (10, 60, 120, 180˚/s) and active contraction at three submaximal contraction levels (20, 50, 80%MVC). The intensity and spatial distribution of the BB activity were compared by the means of two-way analysis of variance, independent sample t-test, and paired sample t-test. RESULTS: Compared with healthy subjects, spastic hemiparetic subjects showed significantly higher intensity with velocity-dependent heterogeneous activation during passive stretch and more lateral and proximal activation distribution during active contraction. In addition, spastic hemiparetic subjects displayed almost non-overlapping activation areas during passive stretch and active contraction. The activation distribution of passive stretch was more distal when compared with the active contraction. CONCLUSIONS: These alterations of the BB activity could be the consequence of deficits in the descending central control after stroke. The complementary spatial distribution of spastic BB activity reflected their opposite motor units (MUs) recruitment patterns between passive stretch and active contraction. This HD-sEMG study provides new neurophysiological evidence for the spatial relationship of spastic BB activity between passive stretch and active contraction, advancing our knowledge on the mechanism of spasticity. TRIAL REGISTRATION: ChiCTR2000032245.


Assuntos
Eletromiografia , Contração Muscular , Espasticidade Muscular , Músculo Esquelético , Acidente Vascular Cerebral , Humanos , Masculino , Espasticidade Muscular/fisiopatologia , Espasticidade Muscular/etiologia , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/complicações , Músculo Esquelético/fisiopatologia , Contração Muscular/fisiologia , Adulto , Idoso
4.
Sci Total Environ ; 945: 174055, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38889814

RESUMO

BACKGROUND: Dyslipidemia in schizophrenia causes a serious loss of healthy life expectancy, making it imperative to explore key environmental risk factors. We aimed to assess the effect of PM2.5 and its constituents on dyslipidemia in schizophrenia, identify the critical hazardous components, and investigate the role of impaired thyroid hormones (THs) sensitivity in this association. METHODS: We collected disease data on schizophrenia from the Anhui Mental Health Center from 2019 to 2022. Logistic regression was constructed to explore the effect of average annual exposure to PM2.5 and its components [black carbon (BC), organic matter (OM), sulfate (SO42-), ammonium (NH4+), and nitrate (NO3-)] on dyslipidemia, with subgroup analyses for age and gender. The degree of impaired THs sensitivity in participants was reflected by the Thyroid Feedback Quantile-based Index (TFQI), and its role in the association of PM2.5 components with dyslipidemia was explored. RESULTS: A total of 5125 patients with schizophrenia were included in this study. Exposure to PM2.5 and its components (BC, OM, SO42-, NH4+, and NO3-) were associated with dyslipidemia with the odds ratios and 95 % confidence interval of 1.13 (1.04, 1.23), 1.16 (1.07, 1.26), 1.15 (1.06, 1.25), 1.11 (1.03, 1.20), 1.09 (1.00, 1.18), 1.12 (1.04, 1.20), respectively. Mixed exposure modeling indicated that BC played a major role in the effects of the mixture. More significant associations were observed in males and groups <45 years. In addition, we found that the effect of PM2.5 and its components on dyslipidemia was exacerbated as impaired THs sensitivity in the patients. CONCLUSIONS: Exposure to PM2.5 and its components is associated with an increased risk of dyslipidemia in schizophrenia, which may be exacerbated by impaired THs sensitivity. Our results suggest a new perspective for the management of ambient particulate pollution and the protection of thyroid function in schizophrenia.


Assuntos
Poluentes Atmosféricos , Dislipidemias , Material Particulado , Esquizofrenia , Hormônios Tireóideos , Humanos , Dislipidemias/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Exposição Ambiental/estatística & dados numéricos , China , Poluição do Ar/estatística & dados numéricos
5.
Nat Commun ; 15(1): 5484, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942769

RESUMO

The tunable properties of halide perovskite/two dimensional (2D) semiconductor mixed-dimensional van der Waals heterostructures offer high flexibility for innovating optoelectronic and photonic devices. However, the general and robust growth of high-quality monocrystalline halide perovskite/2D semiconductor heterostructures with attractive optical properties has remained challenging. Here, we demonstrate a universal van der Waals heteroepitaxy strategy to synthesize a library of facet-specific single-crystalline halide perovskite/2D semiconductor (multi)heterostructures. The obtained heterostructures can be broadly tailored by selecting the coupling layer of interest, and can include perovskites varying from all-inorganic to organic-inorganic hybrid counterparts, individual transition metal dichalcogenides or 2D heterojunctions. The CsPbI2Br/WSe2 heterostructures demonstrate ultrahigh optical gain coefficient, reduced gain threshold and prolonged gain lifetime, which are attributed to the reduced energetic disorder. Accordingly, the self-organized halide perovskite/2D semiconductor heterostructure lasers show highly reproducible single-mode lasing with largely reduced lasing threshold and improved stability. Our findings provide a high-quality and versatile material platform for probing unique optoelectronic and photonic physics and developing further electrically driven on-chip lasers, nanophotonic devices and electronic-photonic integrated systems.

6.
Comp Cytogenet ; 18: 73-95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38798789

RESUMO

To characterize the chromosomes of the four species of Polygonatum Miller, 1754, used in traditional Chinese medicine, P.cyrtonema Hua, 1892, P.kingianum Collett et Hemsley, 1890, P.odoratum (Miller, 1768) Druce, 1906, and P.sibiricum Redouté, 1811, and have an insight into the karyotype variation of the genus Polygonatum, fluorescence in situ hybridization (FISH) with 5S and 45S rDNA oligonucleotide probes was applied to analyze the karyotypes of 9 populations of the four species. Detailed molecular cytogenetic karyotypes of the 9 populations were established for the first time using the dataset of chromosome measurements and FISH signals of 5S and 45S rDNA. Four karyotype asymmetry indices, CVCI, CVCL, MCA and Stebbins' category, were measured to elucidate the asymmetry of the karyotypes and karyological relationships among species. Comparison of their karyotypes revealed distinct variations in the karyotypic parameters and rDNA patterns among and within species. The basic chromosome numbers detected were x = 9, 11 and 13 for P.cyrtonema, x = 15 for P.kingianum, x = 10 and 11 for P.odoratum, and x = 12 for P.sibiricum. The original basic chromosome numbers of the four species were inferred on the basis of the data of this study and previous reports. All the 9 karyotypes were of moderate asymmetry and composed of metacentric, submetacentric and subtelocentric chromosomes or consisted of two of these types of chromosomes. Seven populations have one locus of 5S rDNA and two loci of 45S rDNA, and two populations added one 5S or 45S locus. The karyological relationships among the four species revealed by comparison of rDNA patterns and PCoA based on x, 2n, TCL, CVCI, MCA and CVCL were basically accordant with the phylogenetic relationships revealed by molecular phylogenetic studies. The mechanisms of both intra- and inter-specific dysploidy in Polygonatum were discussed based on the data of this study and literature.

7.
Clin Immunol ; 263: 110223, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636890

RESUMO

Idiopathic severe aplastic anemia (SAA) is a disease of bone marrow failure caused by T-cell-induced destruction of hematopoietic stem and progenitor cells (HSPCs), however the mechanism remains unclear. We performed single-cell RNA sequencing of PBMCs and BMMCs from SAA patients and healthy donors and identified a CD8+ T cell subset with a tissue residency phenotype (Trm) in bone marrow that exhibit high IFN-γ and FasL expression and have a higher ability to induce apoptosis in HSPCs in vitro through FasL expression. CD8+ Trm cells were induced by IL-15 presented by IL-15Rα on monocytes, especially CD16+ monocytes, which were increased in SAA patients. CD16+ monocytes contributed to IL-15-induced CD38+CXCR6+ pre-Trm differentiation into CD8+ Trm cells, which can be inhibited by the CD38 inhibitor 78c. Our results demonstrate that IL-15-induced CD8+ Trm cells are pathogenic cells that mediate HSPC destruction in SAA patients and are therapeutic targets for future treatments.


Assuntos
Anemia Aplástica , Linfócitos T CD8-Positivos , Proteínas Ligadas por GPI , Células-Tronco Hematopoéticas , Interleucina-15 , Monócitos , Receptores de IgG , Humanos , Anemia Aplástica/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Interleucina-15/farmacologia , Interleucina-15/imunologia , Receptores de IgG/metabolismo , Receptores de IgG/imunologia , Monócitos/imunologia , Monócitos/efeitos dos fármacos , Feminino , Masculino , Adulto , Células-Tronco Hematopoéticas/imunologia , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/imunologia , Pessoa de Meia-Idade , Proteína Ligante Fas/metabolismo , Proteína Ligante Fas/imunologia , Adulto Jovem , Adolescente , Interferon gama/imunologia , Interferon gama/metabolismo , Receptores de Interleucina-15/metabolismo , Receptores de Interleucina-15/imunologia , Apoptose/efeitos dos fármacos , Diferenciação Celular/imunologia
8.
J Ethnopharmacol ; 330: 118214, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38641076

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ferroptosis, a recently identified non-apoptotic form of cell death reliant on iron, is distinguished by an escalation in lipid reactive oxygen species (ROS) that are iron-dependent. This phenomenon has a strong correlation with irregularities in iron metabolism and lipid peroxidation. Salvia miltiorrhiza Bunge (DS), a medicinal herb frequently utilized in China, is highly esteemed for its therapeutic effectiveness in enhancing blood circulation and ameliorating blood stasis, particularly during the treatment of cardiovascular diseases (CVDs). Numerous pharmacological studies have identified that DS manifests antioxidative stress effects as well as inhibits lipid peroxidation. However, ambiguity persists regarding the potential of DS to impede ferroptosis in cardiomyocytes and subsequently improve myocardial damage post-myocardial infarction (MI). AIM OF THE STUDY: The present work focused on investigating whether DS could be used to prevent the ferroptosis of cardiomyocytes and improve post-MI myocardial damage. MATERIALS AND METHODS: In vivo experiments: Through ligation of the left anterior descending coronary artery, we constructed both a wild-type (WT) and NF-E2 p45-related factor 2 knockout (Nrf2-/-) mouse model of MI. Effects of DS and ferrostatin-1 (Fer-1) on post-MI cardiomyocyte ferroptosis were examined through detecting ferroptosis and myocardial damage-related indicators as well as Nrf2 signaling-associated protein levels. In vitro experiments: Erastin was used for stimulating H9C2 cardiomyocytes to construct an in vitro ferroptosis cardiomyocyte model. Effects of DS and Fer-1 on cardiomyocyte ferroptosis were determined based on ferroptosis-related indicators and Nrf2 signaling-associated protein levels. Additionally, inhibitor and activator of Nrf2 were used for confirming the impact of Nrf2 signaling on DS's effect on cardiomyocyte ferroptosis. RESULTS: In vivo: In comparison to the model group, DS suppressed ferroptosis in cardiomyocytes post-MI and ameliorated myocardial damage by inducing Nrf2 signaling-related proteins (Nrf2, xCT, GPX4), diminishing tissue ferrous iron and malondialdehyde (MDA) content. Additionally, it enhanced glutathione (GSH) levels and total superoxide dismutase (SOD) activity, effects that are aligned with those of Fer-1. Moreover, the effect of DS on alleviating cardiomyocyte ferroptosis after MI could be partly inhibited through Nrf2 knockdown. In vitro: Compared with the erastin group, DS inhibited cardiomyocyte ferroptosis by promoting the expression of Nrf2 signaling-related proteins, reducing ferrous iron, ROS, and MDA levels, but increasing GSH content and SOD activity, consistent with the effect of Fer-1. Additionally, Nrf2 inhibition increased erastin-mediated ferroptosis of cardiomyocytes through decreasing Nrf2 signaling-related protein expressions. Co-treatment with DS and Nrf2 activator failed to further enhance the anti-ferroptosis effect of DS. CONCLUSION: MI is accompanied by cardiomyocyte ferroptosis, whose underlying mechanism is probably associated with Nrf2 signaling inhibition. DS possibly suppresses ferroptosis of cardiomyocytes and improves myocardial damage after MI through activating Nrf2 signaling.


Assuntos
Ferroptose , Infarto do Miocárdio , Miócitos Cardíacos , Salvia miltiorrhiza , Transdução de Sinais , Animais , Masculino , Camundongos , Ratos , Linhagem Celular , Modelos Animais de Doenças , Ferroptose/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos
9.
Opt Express ; 32(6): 9297-9305, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571167

RESUMO

We perform measurements of microwave spectra of cesium Rydberg 51S1/2 → 51PJ transitions with the linewidth approaching the Fourier limit. A two-photon scheme excites the ground-state atoms to the Rydberg 51S1/2 state, and a weak microwave photon couples the Rydberg transition of 51S1/2 → 51PJ. The hyperfine structure of 51P1/2 can be clearly resolved with a narrow linewidth microwave spectra by using the method of ion detection. Furthermore, we investigate the Zeeman effect of the 51P1/2,3/2 state. The theoretical calculations reproduce the measurement well. Our experimental measurements provide a reliable technical solution for the investigation of high angular momentum Rydberg states, which is conducive to further realizing the coherent manipulation of Rydberg energy levels and improving the sensitivity of electromagnetic field measurement.

10.
Nano Lett ; 24(12): 3768-3776, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38477579

RESUMO

The reduced dimensionality and interfacial effects in magnetic nanostructures open the feasibility to tailor magnetic ordering. Here, we report the synthesis of ultrathin metallic Co2Si nanoplates with a total thickness that is tunable to 2.2 nm. The interfacial magnetism coupled with the highly anisotropic nanoplate geometry leads to strong perpendicular magnetic anisotropy and robust hard ferromagnetism at room temperature, with a Curie temperature (TC) exceeding 950 K and a coercive field (HC) > 4.0 T at 3 K and 8750 Oe at 300 K. Theoretical calculations suggest that ferromagnetism originates from symmetry breaking and undercoordinated Co atoms at the Co2Si and SiO2 interface. With protection by the self-limiting intrinsic oxide, the interfacial ferromagnetism of the Co2Si nanoplates exhibits excellent environmental stability. The controllable growth of ambient stable Co2Si nanoplates as 2D hard ferromagnets could open exciting opportunities for fundamental studies and applications in Si-based spintronic devices.

12.
Anal Bioanal Chem ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457006

RESUMO

With the rapid development of society, it is of paramount importance to expeditiously assess environmental pollution and provide early warning of toxicity risks. Microbial fuel cell-based self-powered biosensors (MFC-SPBs) have emerged as a pivotal technology, obviating the necessity for external power sources and aligning with the prevailing trends toward miniaturization and simplification in biosensor development. In this case, vigorous advancements in MFC-SPBs have been acquired in past years, irrespective of whether the target identification event transpires at the anode or cathode. The present article undertakes a comprehensive review of developed MFC-SPBs, categorizing them into substrate effect and microbial activity effect based on the nature of the target identification event. Furthermore, various enhancement strategies to improve the analytical performance like accuracy and sensitivity are also outlined, along with a discussion of future research trends and application prospects of MFC-SPBs for their better developments.

13.
Exp Neurol ; 376: 114758, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38513970

RESUMO

Impaired long-term memory, a complication of traumatic stress including hemorrhage shock and resuscitation (HSR), has been reported to be associated with multiple neurodegenerations. The ventral tegmental area (VTA) participates in both learned appetitive and aversive behaviors. In addition to being prospective targets for the therapy of addiction, depression, and other stress-related diseases, VTA glutamatergic neurons are becoming more widely acknowledged as powerful regulators of reward and aversion. This study revealed that HSR exposure induces memory impairments and decreases the activation in glutamatergic neurons, and decreased ß power in the VTA. We also found that optogenetic activation of glutamatergic neurons in the VTA mitigated HSR-induced memory impairments, and restored ß power. Moreover, hydrogen sulfide (H2S), a gasotransmitter with pleiotropic roles, has neuroprotective functions at physiological concentrations. In vivo, H2S administration improved HSR-induced memory deficits, elevated c-fos-positive vesicular glutamate transporters (Vglut2) neurons, increased ß power, and restored the balance of γ-aminobutyric acid (GABA) and glutamate in the VTA. This work suggests that glutamatergic neuron stimulation via optogenetic assay and exogenous H2S may be useful therapeutic approaches for improving memory deficits following HSR.


Assuntos
Modelos Animais de Doenças , Ácido Glutâmico , Sulfeto de Hidrogênio , Transtornos da Memória , Camundongos Endogâmicos C57BL , Neurônios , Animais , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêutico , Camundongos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/terapia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ácido Glutâmico/metabolismo , Ácido Glutâmico/toxicidade , Choque Hemorrágico , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/metabolismo , Optogenética/métodos
14.
Clin Transl Sci ; 17(3): e13750, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38451110

RESUMO

This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin-A (ETA ) receptor antagonist, in healthy subjects. The primary objectives of this first-in-human phase I study, comprised of single-ascending-dose, multiple-ascending-dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin-1 (ET-1) and total bile acids (TBA). Single doses of 10 to 100 mg and multiple daily doses of 20 and 50 mg for 6 days were well tolerated. SC0062 was rapidly absorbed and plasma exposure of SC0062 and M18 increased disproportionately with dose, achieving steady state by day 3, with accumulation ratios of 1.22 and 1.89 on day 6 for SC0062 and M18, respectively. The geometric mean (geometric standard deviation) terminal elimination half-life (t1/2 ) values of SC0062 and M18 were 7.25 (1.70) h and 13.73 (1.32) h, respectively. Plasma ET-1 concentrations were dose-proportional, whereas plasma TBA concentrations behaved erratically. Following a single 50 mg dose of SC0062 after a high-fat meal, Cmax values for SC0062 and M18 increased by 41% and 32%, respectively, and median Tmax values for SC0062 were 3 h longer than fasting values; exposure was unaffected. These favorable safety, PK, and PD results provide a foundation for further studies of SC0062 in pulmonary arterial hypertension, chronic kidney disease, and other relevant indications.


Assuntos
Povo Asiático , Humanos , Ácidos e Sais Biliares , China , Jejum , Voluntários Saudáveis
15.
J Agric Food Chem ; 72(13): 7374-7382, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38526016

RESUMO

Brazzein (Brz) is a sweet-tasting protein composed of 54 amino acids and is considered as a potential sugar substitute. The current methods for obtaining brazzein are complicated, and limited information is available regarding its thermal stability. In this study, we successfully expressed recombinant brazzein, achieving a sweetness threshold of 15.2 µg/mL. Subsequently, we conducted heat treatments at temperatures of 80, 90, 95, and 100 °C for a duration of 2 h to investigate the structural changes in the protein. Furthermore, we employed hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) to analyze the effect of heating on the protein structure-sweetness relationships. Our results indicated that the thermal inactivation process primarily affects residues 6-14 and 36-45 of brazzein, especially key residues Tyr8, Tyr11, Ser14, Glu36, and Arg43, which are closely associated with its sweetness. These findings have significant implications for improving the thermal stability of brazzein.


Assuntos
Proteínas de Plantas , Edulcorantes , Proteínas de Plantas/metabolismo , Edulcorantes/química , Paladar
16.
J Biomech ; 165: 111997, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38377742

RESUMO

The ankle mechanics (stiffness and moment) are modulated continuously when interacting with the environment during human walking. However, it remains unclear how ankle mechanics vary with walking speeds, and how they are affected by stroke. This study aimed to determine time-varying ankle stiffness and moment in stroke participants during walking, comparing them with healthy participants at matched speeds. A motion capture system, surface electromyography (EMG) system and force plates were used to measure biomechanics of seven healthy participants walking at 5 controlled speeds and ten patients with stroke at self-selected speeds. The ankle moment and stiffness during the stance phase were calculated using an EMG-driven musculoskeletal model. Surface equations of ankle moment and stiffness in healthy participants, with walking speed and stance phase as variables, were proposed based on polynomial fitting. Results showed that as walking speed increased, there was an increase in the ankle stiffness and moment of healthy participants during 77 %-89 % and 63 %-91 % of stance phase, respectively. Patients with stroke had lower ankle stiffness and moment at self-selected walking speed than healthy participants at 1.04 m/s walking speed during 52 %-87 % and 52 %-91 % of stance phase, respectively. At matched walking speed, the peak values of ankle stiffness and moment in patients with stroke were significantly less than those in healthy participants (p = 0.007; p = 0.028, respectively). This study proposes a novel approach to evaluate the ankle mechanics of patients with stroke using the speed-matched model of healthy participants and may provide insights into understanding speed-dependent movement mechanisms of human walking.


Assuntos
Tornozelo , Acidente Vascular Cerebral , Humanos , Marcha , Articulação do Tornozelo , Caminhada , Velocidade de Caminhada , Fenômenos Biomecânicos
17.
Artigo em Inglês | MEDLINE | ID: mdl-38421838

RESUMO

Modeling the muscle response to functional electrical stimulation (FES) is an important step during model-based FES control system design. The Hammerstein structure is widely used in simulating this nonlinear biomechanical response. However, a fixed relationship cannot cope well with the time-varying property of muscles and muscle fatigue. In this paper, we proposed an adaptive Hammerstein model to predict ankle joint torque induced by electrical stimulation, which used variable forgetting factor recursive least squares (VFFRLS) method to update the model parameters. To validate the proposed model, ten healthy individuals were recruited for short-duration FES experiments, ten for long-duration FES experiments, and three stroke patients for both. The isometric ankle dorsiflexion torque induced by FES was measured, and then the test performance of the fixed-parameter Hammerstein model, the adaptive Hammerstein model based on fixed forgetting factor recursive least squares (FFFRLS) and the adaptive Hammerstein model based on VFFRLS was compared. The goodness of fit, root mean square error, peak error and success rate were applied to evaluate the accuracy and stability of the model. The results indicate a significant improvement in both the accuracy and stability of the proposed adaptive model compared to the fixed-parameter model and the adaptive model based on FFFRLS. The proposed adaptive model enhances the ability of the model to cope with muscle changes.


Assuntos
Algoritmos , Terapia por Estimulação Elétrica , Humanos , Análise dos Mínimos Quadrados , Torque , Músculo Esquelético/fisiologia , Estimulação Elétrica/métodos , Terapia por Estimulação Elétrica/métodos
18.
IEEE Trans Biomed Eng ; PP2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381630

RESUMO

OBJECTIVE: electromyogram (EMG)-driven musculoskeletal models have been widely used to investigate human movements while existing EMG-driven models commonly neglect regional heterogeneity in anatomy and activation within a skeletal muscle. To consider neuromuscular compartment anatomy and activation, a subject- and compartment-specific EMG-driven model was developed for isometric plantarflexion moment prediction. METHODS: the model was hill-type consisting of gastrocnemius medialis, gastrocnemius lateralis, and soleus around the ankle joint, and each muscle was discretised into four compartments. The moment arms of each compartment were determined using magnetic resonance imaging and the compartment activation was calculated based on high-density surface EMG signals. And the hill-type compartment parameters were tuned in a calibration process. The developed compartment-specific model and a generic EMG-driven model were examined by comparing their predicted net ankle moments with measurements obtained while subjects performed isometric plantarflexion tasks at different contraction levels. RESULTS: compared to the generic EMG-driven model, the isometric plantarflexion moment prediction using the compartment-specific model was more accurate at all contraction levels, with the average prediction error decreasing from average 13.81% to 10.11%. The contraction of each compartment was found to be generally non-uniform at all contraction levels. CONCLUSION: the developed compartment-specific model enabled accurate prediction of isometric plantarflexion moment and the simulation of non-uniform muscular contraction, which is more physiologically appropriate than the existing EMG-driven models. SIGNIFICANCE: the proposed compartment-specific formulation opens new perspectives for subject-specific musculoskeletal modelling, which has great potential in understanding regional characteristics of the neuromuscular activities.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38165796

RESUMO

Adaptive compliance control is critical for rehabilitation robots to cope with the varying rehabilitation needs and enhance training safety. This article presents a trajectory deformation-based multi-modal adaptive compliance control strategy (TD-MACCS) for a wearable lower limb rehabilitation robot (WLLRR), which includes a high-level trajectory planner and a low-level position controller. Dynamic motion primitives (DMPs) and a trajectory deformation algorithm (TDA) are integrated into the high-level trajectory planner, generating multi-joint synchronized desired trajectories through physical human-robot interaction (pHRI). In particular, the amplitude modulation factor of DMPs and the deformation factor of TDA are adapted by a multi-modal adaptive regulator, achieving smooth switching of human-dominant mode, robot-dominant mode, and soft-stop mode. Besides, a linear active disturbance rejection controller is designed as the low-level position controller. Four healthy participants and two stroke survivors are recruited to conduct robot-assisted walking experiments using the TD-MACCS. The results show that the TD-MACCS can smoothly switch three control modes while guaranteeing trajectory tracking accuracy. Moreover, we find that appropriately increasing the upper bound of the deformation factor can enhance the average walking speed (AWS) and root mean square of trajectory deviation (RMSTD).


Assuntos
Robótica , Acidente Vascular Cerebral , Dispositivos Eletrônicos Vestíveis , Humanos , Robótica/métodos , Extremidade Inferior , Algoritmos
20.
Ecotoxicol Environ Saf ; 271: 115973, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219619

RESUMO

BACKGROUND: In the era characterized by global environmental and climatic changes, understanding the effects of PM2.5 components and heatwaves on schizophrenia (SCZ) is essential for implementing environmental interventions at the population level. However, research in this area remains limited, which highlights the need for further research and effort. We aim to assess the association between exposure to PM2.5 components and hospitalizations for SCZ under different heatwave characteristics. METHODS: We conducted a 16 municipalities-wide, individual exposure-based, time-stratified, case-crossover study from January 1, 2017, to December 31, 2020, encompassing 160736 hospitalizations in Anhui Province, China. Daily concentrations of PM2.5 components were obtained from the Tracking Air Pollution in China dataset. Conditional logistic regression models were used to investigate the association between PM2.5 components and hospitalizations. Additionally, restricted cubic spline models were used to identify protective thresholds of residential environment in response to environmental and climate change. RESULTS: Our findings indicate a positive correlation between PM2.5 and its components and hospitalizations. Significantly, a 1 µg/m3 increase in black carbon (BC) was associated with the highest risk, at 1.58% (95%CI: 0.95-2.25). Exposure to heatwaves synergistically enhanced the impact of PM2.5 components on hospitalization risks, and the interaction varied with the intensity and duration of heatwaves. Under the 99th percentile heatwave events, the impact of PM2.5 and its components on hospitalizations was most pronounced, which were PM2.5 (2-4d: 4.59%, 5.09%, and 5.09%), sulfate (2-4d: 21.73%, 23.23%, and 25.25%), nitrate (2-4d: 17.51%, 16.93%, and 20.31%), ammonium (2-4d: 27.49%, 31.03%, and 32.41%), organic matter (2-4d: 32.07%, 25.42%, and 24.48%), and BC (2-4d: 259.36%, 288.21%, and 152.52%), respectively. Encouragingly, a protective effect was observed when green and blue spaces comprised more than 17.6% of the residential environment. DISCUSSION: PM2.5 components and heatwave exposure were positively associated with an increased risk of hospitalizations, although green and blue spaces provided a mitigating effect.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Esquizofrenia , Humanos , Poluição do Ar/efeitos adversos , China/epidemiologia , Estudos Cross-Over , Exposição Ambiental , Hospitalização , Material Particulado , Fuligem
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