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1.
J Am Chem Soc ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38853359

RESUMO

Aminoboronic acids represent a class of significant compounds that have attracted significant attention in the fields of drug discovery and organic synthesis. Despite notable progress in their synthesis, the efficient construction of chiral ß-aminoboronic acids with alkyl side chains remains a challenging endeavor. Here, we introduce an unprecedented nickel-catalyzed asymmetric borylalkylation of enamides, employing a simple chiral diamine ligand, readily available B2pin2, and alkyl halides as coupling partners. This reaction serves as an efficient platform for assembling a diverse range of ß-aminoboronic acid derivatives with flexible alkyl side chains, displaying exceptional regio-, stereo-, and enantioselectivities. Moreover, this transformation exhibits a broad substrate scope and remarkable tolerance toward various functional groups. Theoretical calculations demonstrate that the benzyl group on the ligand is the key to the high enantiocontrol in this transformation. Additionally, we exemplify the practical application of this strategy through the concise synthesis of complex bioactive molecules.

2.
Angew Chem Int Ed Engl ; : e202405520, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896428

RESUMO

Functionalization of Si-bound methyl group provides an efficient access to diverse organosilanes. However, the asymmetric construction of silicon-stereogenic architectures by functionalization of Si-bound methyl group has not yet been described despite recent significant progress in producing chiral silicon. Herein, we disclosed the enantioselective silylmethyl functionalization involving the aryl to alkyl 1,5-palladium migration to access diverse naphthalenes possessing an enantioenriched stereogenic silicon center, which are inaccessible before. It is worthy to note that the realization of asymmetric induction at the step of metal migration itself remains challenging. Our study constitutes the first enantioselective aryl to alkyl 1,5-palladium migration reaction. The key to the success is the discovery and fine-tuning of the different substituents of α,α,α,α-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL)-based phosphoramidites, which ensure the enantioselectivity and desired reactivity.

3.
Cell Biosci ; 14(1): 86, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937838

RESUMO

BACKGROUND: Neurodevelopmental disorders (NDD), such as autism spectrum disorders (ASD) and intellectual disorders (ID), are highly debilitating childhood psychiatric conditions. Genetic factors are recognized as playing a major role in NDD, with a multitude of genes and genomic regions implicated. While the functional validation of NDD-associated genes has predominantly been carried out using mouse models, the significant differences in brain structure and gene function between mice and humans have limited the effectiveness of mouse models in exploring the underlying mechanisms of NDD. Therefore, it is important to establish alternative animal models that are more evolutionarily aligned with humans. RESULTS: In this study, we employed CRISPR/Cas9 and somatic cell nuclear transplantation technologies to successfully generate a knockout miniature pig model of the MIR137 gene, which encodes the neuropsychiatric disorder-associated microRNA miR-137. The homozygous knockout of MIR137 (MIR137-/-) effectively suppressed the expression of mature miR-137 and led to the birth of stillborn or short-lived piglets. Transcriptomic analysis revealed significant changes in genes associated with neurodevelopment and synaptic signaling in the brains of MIR137-/- miniature pig, mirroring findings from human ASD transcriptomic data. In comparison to miR-137-deficient mouse and human induced pluripotent stem cell (hiPSC)-derived neuron models, the miniature pig model exhibited more consistent changes in critical neuronal genes relevant to humans following the loss of miR-137. Furthermore, a comparative analysis identified differentially expressed genes associated with ASD and ID risk genes in both miniature pig and hiPSC-derived neurons. Notably, human-specific miR-137 targets, such as CAMK2A, known to be linked to cognitive impairments and NDD, exhibited dysregulation in MIR137-/- miniature pigs. These findings suggest that the loss of miR-137 in miniature pigs affects genes crucial for neurodevelopment, potentially contributing to the development of NDD. CONCLUSIONS: Our study highlights the impact of miR-137 loss on critical genes involved in neurodevelopment and related disorders in MIR137-/- miniature pigs. It establishes the miniature pig model as a valuable tool for investigating neurodevelopmental disorders, providing valuable insights for potential applications in human research.

4.
J Pain Res ; 17: 1785-1792, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799272

RESUMO

Sleep is crucial for human health, insufficient sleep or poor sleep quality may negatively affect sleep function and lead to a state of sleep deprivation. Sleep deprivation can result in various health problems, including chronic pain. The intricate relationship between sleep and pain is complex and intertwined, with daytime pain affecting sleep quality and poor sleep increasing pain intensity. The article first describes the influence of sleep on the onset and development of pain, and then explores the impact of daytime pain intensity on nighttime sleep quality and subsequent pain thresholds. However, the primary emphasis is placed on the pivotal role of oxidative stress in this bidirectional relationship. Although the exact mechanisms underlying sleep and chronic pain are unclear, this review focuses on the role of oxidative stress. Numerous studies on sleep deprivation have demonstrated that it can lead to varying degrees of increased pain sensitivity, while chronic pain leads to sleep deprivation and further exacerbates pain. Further research on the role of oxidative stress in the mechanism of sleep deprivation-induced pain sensitization seems reasonable. This article comprehensively reviews the current research on the interrelationship between sleep deprivation, pain and the crucial role of oxidative stress.

5.
J Biomed Res ; : 1-14, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38808570

RESUMO

The abnormality of p53 tumor suppressor is crucial in lung cancer development, and p53 may regulate target gene promoters to combat cancer. Recent studies have shown extensive p53 binding to enhancer elements. However, whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood. In the current study, we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout human bronchial epithelial cells (BEAS-2B). A total of 943 active regular enhancers and 370 super-enhancers (SEs) disappeared upon the deletion of p53, indicating that p53 modulates the activity of hundreds of enhancer elements. We found that one p53-dependent SE, located on chromosome 9 and designated as KLF4-SE, regulated the expression of the Krüppel-like factor 4 ( KLF4) gene. Furthermore, deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression, but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model. Subsequently, in TP53 knockout cells, the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency. Consistently, KLF4 expression also decreased in lung cancer tissues and cell lines. Overexpression of KLF4 significantly suppressed lung cancer cell proliferation and migration. Collectively, our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function. Therefore, our findings offer novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.

6.
Adv Mater ; : e2404485, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760003

RESUMO

Achieving bacterial killing and osteogenic formation on an implant surface rarely occurs. In this study, a novel surface design-a palladium hydride (PdHx) film that enables these two distinct features to coexist is introduced. The PdHx lattice captures protons in the extracellular microenvironment of bacteria, disrupting their normal metabolic activities, such as ATP synthesis, nutrient co-transport, and oxidative stress. This disruption leads to significant bacterial death, as evidenced by RNA sequence analysis. Additionally, the unique enzymatic activity and hydrogen-loading properties of PdHx activate the human antioxidant system, resulting in the rapid clearance of reactive oxygen species. This process reshapes the osteogenic immune microenvironment, promoting accelerated osteogenesis. These findings reveal that the downregulation of the NOD-like receptor signaling pathway is critical for activating immune cells toward M2 phenotype polarization. This novel surface design provides new strategies for modifying implant coatings to simultaneously prevent bacterial infection, reduce inflammation, and enhance tissue regeneration, making it a noteworthy contribution to the field of advanced materials.

7.
Adv Sci (Weinh) ; : e2403107, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38704679

RESUMO

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5-year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe-layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.

8.
JAMA Netw Open ; 7(4): e243127, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558142

RESUMO

Importance: Polybrominated diphenyl ethers (PBDEs) are an important group of persistent organic pollutants with endocrine-disrupting properties. However, prospective cohort studies regarding the association of PBDE exposure with long-term health outcomes, particularly mortality, are lacking. Objective: To examine the association of environmental exposure to PBDEs with risk of all-cause and cause-specific mortality. Design, Setting, and Participants: This nationally representative cohort study used data from the National Health and Nutrition Examination Survey 2003 to 2004 and linked mortality information through December 31, 2019. Adults aged 20 years or older with available data on PBDE measurements and mortality were included. Statistical analysis was performed from February 2022 to April 2023. Exposures: PBDE analytes in serum samples were measured using solid phase extraction and isotope dilution gas chromatography high-resolution mass spectrometry. Main Outcomes and Measures: All-cause mortality, cancer mortality, and cardiovascular mortality. Results: This study included 1100 participants (mean [SE] age, 42.9 [0.6] years; proportion [SE] female, 51.8% [1.6%]; proportion [SE] Hispanic, 12.9% [2.7%]; proportion [SE] non-Hispanic Black, 10.5% [1.6%]; proportion [SE] non-Hispanic White, 70.8% [3.7%]; proportion [SE] other race and ethnicity, 5.8% [1.1%]). During 16 162 person-years of follow-up (median [IQR] follow-up, 15.8 [15.2-16.3] years; maximum follow-up, 17 years), 199 deaths occurred. Participants with higher serum PBDE levels were at higher risk for death. After adjustment for age, sex, and race and ethnicity, lifestyle and socioeconomic factors, and body mass index, participants with the highest tertile of serum PBDE levels had an approximately 300% increased risk of cancer mortality (HR, 4.09 [95% CI, 1.71-9.79]) compared with those with the lowest tertile of serum PBDE levels. No significant association of PBDE exposure with all-cause mortality (HR, 1.43 [95% CI, 0.98-2.07]) or cardiovascular mortality (HR, 0.92 [95% CI, 0.41-2.08]) was observed. Conclusions and Relevance: In this nationally representative cohort study, PBDE exposure was significantly associated with an increased risk of cancer mortality. Further studies are needed to replicate the findings and determine the underlying mechanisms.


Assuntos
Doenças Cardiovasculares , Neoplasias , Adulto , Humanos , Feminino , Éteres Difenil Halogenados , Estudos de Coortes , Causas de Morte , Estudos Prospectivos , Inquéritos Nutricionais
9.
Drug Des Devel Ther ; 18: 1025-1034, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585256

RESUMO

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.


Assuntos
Anestesia , Fragilidade , Hipotensão , Idoso , Humanos , Fragilidade/tratamento farmacológico , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Dor , Inconsciência
10.
Front Pediatr ; 12: 1343211, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38560400

RESUMO

Aim: We aimed to investigate the short-term efficacy and safety of laparoscopic pyeloplasty for treating newborns with severe hydronephrosis due to ureteropelvic junction obstruction (UPJO). Methods: A retrospective analysis was performed on 16 newborn patients with severe neonatal hydronephrosis who underwent laparoscopic pyeloplasty at our hospital from January 2021 to November 2022. All patients were regularly followed up. Laparoscopic pyeloplasty with double J stent placement was performed after the presence of severe hydronephrosis was confirmed. Results: Among the 16 pediatric patients (13 males, 3 females), the left side was affected in 13 cases and the right side in 3. The average age at surgery was 9.50 (8.50-12.00) days, with an average weight of 3.30 ± 0.95 kg. Laparoscopic pyeloplasty was performed in all cases without the need for open conversion. The mean surgery duration was 292.06 ± 73.60 min, with minimal blood loss (2.50, 2.00-5.00 ml). Postoperative hospital stays averaged 13.44 ± 4.70 days. No anastomotic leakage occurred, and follow-ups at 1, 3, 6, and 12 months showed no stent displacement, except for one case where the stent was removed at 1 month, and the others at 3 months. There were no cases of worsened hydronephrosis, except for one with renal atrophy at the 6-month follow-up. Changes in renal pelvis anteroposterior diameter exhibited a time effect (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Notably, differences were observed between 6 and 3 months, as well as between 12 and 3 months postoperatively (P < 0.05). Similarly, renal parenchymal thickness changes showed a time effect Pediatric urology, Guangdong Women and Children Hospital, Guangzhou, China (F = 49.281, P < 0.001), with significant differences at 1, 3, 6, and 12 months postoperatively compared to preoperative values (P < 0.05). Significant differences were also noted between 6 and 1 month, as well as between 12 and 1 month postoperatively (P < 0.05). There was one case of urinary tract infection after surgery, and no case of recurrence was observed. Conclusion: Severe neonatal hydronephrosis must be treated promptly. Laparoscopic pyeloplasty is a safe and feasible treatment with minimal complications for newborn patients with severe hydronephrosis due to UPJO.

11.
Front Pharmacol ; 15: 1355169, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38533257

RESUMO

Introduction: Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Recanalization of blocked blood vessels and restoring blood supply to ischemic brain tissue are crucial for post-stroke rehabilitation. The decoction Naodesheng (NDS) composed of five Chinese botanical drugs, including Panax notoginseng (Burk.) F. H. Chen, Ligusticum chuanxiong Hort., Carthamus tinctorius L., Pueraria lobata (Willd.) Ohwi, and Crataegus pinnatifida Bge., is a blood-activating and stasis-removing herbal medicine commonly used for the clinical treatment of cerebrovascular diseases in China. However, the material basis of NDS on the effects of blood circulation improvement and vascular tone regulation remains unclear. Methods: A database comprising 777 chemical metabolites of NDS was constructed. Then, the interactions between various herbal metabolites of NDS and five vascular tone modulation G-protein-coupled receptors (GPCRs), including 5-HT1AR, 5-HT1BR, ß2-AR, AT1R, and ETBR, were assessed by molecular docking. Using network analysis and vasomotor experiment of the cerebral basilar artery, the potential material basis underlying the vascular regulatory effects of NDS was further explored. Results: The Naodesheng Effective Component Group (NECG) was found to induce relaxation of rat basilar artery rings precontracted using Endothelin-1 (ET-1) and KCl in vitro in a dose-dependent manner. Several metabolites of NDS, including C. tinctorius, C. pinnatifida, and P. notoginseng, were found to be the main plant resources of metabolites with high docking scores. Furthermore, several metabolites in NDS, including formononetin-7-glucoside, hydroxybenzoyl-coumaric anhydride, methoxymecambridine, puerarol, and pyrethrin II, were found to target multiple vascular GPCRs. Metabolites with moderate-to-high binding energy were verified to have good rat basilar artery-relaxing effects, and the maximum artery relaxation effects of all three metabolites, namely, isorhamnetin, kaempferol, and daidzein, were found to exceed 90%. Moreover, metabolites of NDS were found to exert a synergistic effect by interacting with vascular GPCR targets, and these metabolites may contribute to the cerebrovascular regulatory function of NDS. Discussion: The study reports that various metabolites of NDS contribute to its vascular tone regulating effects and demonstrates the multi-component and multi-target characteristics of NDS. Among them, metabolites with moderate-to-high binding scores in NDS may play an important role in regulating vascular function.

12.
BMC Anesthesiol ; 24(1): 65, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360531

RESUMO

BACKGROUND: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. METHODS: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. RESULTS: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). CONCLUSIONS: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).


Assuntos
Analgesia Controlada pelo Paciente , Hidromorfona , Ketamina , Humanos , Criança , Estudos Prospectivos , Analgesia Controlada pelo Paciente/efeitos adversos , Dor Pós-Operatória/etiologia , Analgésicos
13.
J Mater Chem B ; 12(10): 2481-2485, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38375678

RESUMO

6-Nitrobenzo[cd]indole-2(1H)-ketone (compound C2) exhibits an excellent germicidal effect against methicillin-resistant Staphylococcus aureus (MRSA). Mechanism studies show that C2 induces ROS over-production, cell membrane damage, and ATP and virulence factor down-regulation in bacteria. More importantly, C2 can inhibit biofilm formation and accelerate wound healing in a mouse infection model induced by MRSA.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Camundongos , Staphylococcus aureus , Antibacterianos/farmacologia , Cetonas/farmacologia , Biofilmes , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Modelos Animais de Doenças , Indóis/farmacologia
14.
Mol Cancer Res ; 22(3): 227-239, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38047807

RESUMO

Cancer risk loci provide special clues for uncovering pathogenesis of cancers. The TNFRSF19 gene located within the 13q12.12 lung cancer risk locus encodes TNF receptor superfamily member 19 (TNFRSF19) protein and has been proved to be a key target gene of a lung tissue-specific tumor suppressive enhancer, but its functional role in lung cancer pathogenesis remains to be elucidated. Here we showed that the TNFRSF19 gene could protect human bronchial epithelial Beas-2B cells from pulmonary carcinogen nicotine-derived nitrosamine ketone (NNK)-induced malignant transformation. Knockout of the TNFRSF19 significantly increased NNK-induced colony formation rate on soft agar. Moreover, TNFRSF19 expression was significantly reduced in lung cancer tissues and cell lines. Restoration of TNFRSF19 expression in A549 lung cancer cell line dramatically suppressed the tumor formation in xenograft mouse model. Interestingly, the TNFRSF19 protein that is an orphan membrane receptor could compete with LRP6 to bind Wnt3a, thereby inhibiting the Wnt/ß-catenin signaling pathway that is required for NNK-induced malignant transformation as indicated by protein pulldown, site mutation, and fluorescence energy resonance transfer experiments. Knockout of the TNFRSF19 enhanced LRP6-Wnt3a interaction, promoting ß-catenin nucleus translocation and the downstream target gene expression, and thus sensitized the cells to NNK carcinogen. In conclusion, our study demonstrated that the TNFRSF19 inhibited lung cancer carcinogenesis by competing with LRP6 to combine with Wnt3a to inhibit the Wnt/ß-catenin signaling pathway. IMPLICATIONS: These findings revealed a novel anti-lung cancer mechanism, highlighting the special significance of TNFRSF19 gene within the 13q12.12 risk locus in lung cancer pathogenesis.


Assuntos
Neoplasias Pulmonares , Animais , Humanos , Camundongos , beta Catenina/genética , Carcinógenos , Modelos Animais de Doenças , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Camundongos Knockout , Receptores do Fator de Necrose Tumoral , Via de Sinalização Wnt
15.
Artigo em Inglês | MEDLINE | ID: mdl-38088991

RESUMO

Prosthetic hands are frequently rejected due to frustrations in daily uses. By adopting principles of human neuromuscular control, it could potentially achieve human-like compliance in hand functions, thereby improving functionality in prosthetic hand. Previous studies have confirmed the feasibility of real-time emulation of neuromuscular reflex for prosthetic control. This study further to explore the effect of feedforward electromyograph (EMG) decoding and proprioception on the biomimetic controller. The biomimetic controller included a feedforward Bayesian model for decoding alpha motor commands from stump EMG, a muscle model, and a closed-loop component with a model of muscle spindle modified with spiking afferents. Real-time control was enabled by neuromorphic hardware to accelerate evaluation of biologically inspired models. This allows us to investigate which aspects in the controller could benefit from biological properties for improvements on force control performance. 3 non-disabled and 3 amputee subjects were recruited to conduct a "press-without-break" task, subjects were required to press a transducer till the pressure stabilized in an expected range without breaking the virtual object. We tested whether introducing more complex but biomimetic models could enhance the task performance. Data showed that when replacing proportional feedback with the neuromorphic spindle, success rates of amputees increased by 12.2% and failures due to breakage decreased by 26.3%. More prominently, success rates increased by 55.5% and failures decreased by 79.3% when replacing a linear model of EMG with the Bayesian model in the feedforward EMG processing. Results suggest that mimicking biological properties in feedback and feedforward control may improve the manipulation of objects by amputees using prosthetic hands. Clinical and Translational Impact Statement: This control approach may eventually assist amputees to perform fine force control when using prosthetic hands, thereby improving the motor performance of amputees. It highlights the promising potential of the biomimetic controller integrating biological properties implemented on neuromorphic models as a viable approach for clinical application in prosthetic hands.


Assuntos
Membros Artificiais , Humanos , Teorema de Bayes , Desenho de Prótese , Mãos/fisiologia , Eletromiografia/métodos
16.
Environ Sci Pollut Res Int ; 30(57): 119925-119934, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37932615

RESUMO

Fossil fuels are the primary energy sources of China, which are not only expensive but have adverse environmental impacts. To cope with this situation, the Chinese government wants to fulfil 25% of its energy consumption by non-fossil fuels by 2030. In this perspective, we selected the solar sources of the country and collected solar irradiation data for one year in the six big cities of China in 2022. For the analysis of data and assessing the effectiveness of photovoltaic (PV), RETScreen and MATLAB were utilized. A further step was taken by performing the life cycle assessment (LCA) to scrutinize the different features of solar energy, including fuel consumption, price, average lifetime, maintenance and operation expenses, land requirements, and greenhouse gas emissions. Results reveal that all these cities have enormous solar power potential. However, the highest solar power (0.27 kW) is generated in Nanchang city, while the lowest power (0.21 kW) is generated in Sanya city. Solar energy is durable and has a good average lifespan but can be costly, as PV panels lose efficiency due to dust and pollution. The regular cleaning of PV panels, in turn, demands substantial cost. Based on research results, significant policy suggestions have been recommended to fulfil the country's energy demand on its way to a future of sustainable development.


Assuntos
Energia Solar , Meio Ambiente , Cidades , Combustíveis Fósseis , China
17.
PLoS One ; 18(10): e0293505, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37883369

RESUMO

This study employs a multilevel model, nesting firm observations within industry and province groups, to investigate the influences on corporate contributions to poverty alleviation while considering the industrial and provincial contexts. Using a sample of Chinese firms listed in Shanghai and Shenzhen Stock Exchanges between 2016 and 2019, we find that Herfindah-Hirschman Index (HHI) does not affect corporate contribution. The results show a significantly negative relationship between industry dynamism and a firm's substantial poverty contributions, as well as a significantly positive relationship between number of state-owned enterprises (SOEs) in industry and the likelihood and extent of a firm's contributions. Moreover, a firm's likelihood to participate in anti-poverty activities and make substantial contributions is affected by more intense government intervention and lower per capita GDP. A province's poverty rate is positively associated with the extent of corporate investments in poverty alleviation. Additional analyses note that firms competitive in an industry that is less dynamic environment are more likely to invest funds into poverty alleviation instead of material contribution. Moreover, for firms headquartered in an industry with more SOEs and in provinces with a stronger government, a higher poverty rate and lower per capita GDP mean it is more likely for them to make both monetary and material contributions for anti-poverty campaigns.


Assuntos
Indústrias , Organizações , Análise Multinível , China , Pobreza
18.
Micromachines (Basel) ; 14(10)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37893247

RESUMO

The effect of graphite powder on the machining characteristics in graphite-powder-mixed electrochemical discharge machining of microholes was still not clear. How the discharge mechanism changed with the addition of graphite powder into the electrolyte, which further led to changes in the morphology of the machined holes, remained to be revealed. In this study, a series of microhole machining experiments were conducted in glass. Comparisons of the discharge energy, microhole entrance diameter, hole taper, and tool electrode morphology after machining were made when machining in the electrolytes with and without graphite powder. Experimental results revealed that there were a lot of small pulse currents distributed on the current waveform when machining with the graphite-powder-mixed electrolyte. The average discharge energy of the small pulse current was 2.8 times as much as that of the general electrochemical discharge. After introducing graphite powder into the electrolyte, the entrance diameter of the hole became larger when the hole depth was deeper than 200 µm. The HAZ width increased with increasing hole depth at the voltage of 37-41 V, while it decreased at the voltage of 43 V. A reduction in hole taper angle with a range of 0.5° to 2.3° was achieved. In addition, after machining in electrolytes with and without graphite powder, the tool electrode surfaces showed different morphologies due to different discharges.

19.
J Agric Food Chem ; 71(36): 13518-13526, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37658470

RESUMO

A figure-actuated microfluidic biosensor was developed for the rapid and sensitive detection of Salmonella typhimurium using immunomagnetic separation to separate target bacteria and rolling circle amplification (RCA) combined with CRISPR/Cas12a to amplify the detection signal. The magnetic nanoparticles (MNPs) modified with the capture antibodies (MNPs@Ab1) and RCA primer linked with recognized antibodies (primer@Ab2) were first used to react with S. typhimurium, resulting in the formation of MNPs@Ab1-S. typhimurium-primer@Ab2 complexes. Then, the RCA and CRISPR/Cas12a reagents were successively pumped into the chamber and incubated at the appropriate conditions. With the help of a 3D-printed signal detector, the fluorescence signal was collected and analyzed using the smartphone APP for the determination of bacterial concentration. This biosensor exhibited a wide linear range for the detection of S. typhimurium with a low limit of detection of 1.93 × 102 CFU/mL and a mean recovery of about 106% in the spiked milk sample.


Assuntos
Separação Imunomagnética , Salmonella typhimurium , Salmonella typhimurium/genética , Sistemas CRISPR-Cas , Microfluídica , Anticorpos
20.
PLoS One ; 18(8): e0290548, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37616251

RESUMO

Product-harm crises have detrimental effects on firm's sales, reputation, and financial value, requiring crisis managers to promptly adopt appropriate response strategies to mitigate these impacts. Situational Crisis Communication Theory (SCCT) guides managers to align responsibility attribution with response strategies. Using Chinese listed firms' product-harm crises sample from 2015 to 2021, this study analyzes the stock market's reaction to different response strategies. The event study method reveals that a passive strategy is more effective during the disclosure stage, and accept+no recall and deny+recall are conforming strategies during the initial response stage. Additionally, firms with a crisis history should assume greater responsibility when developing response strategies for product-harm crises, as crisis history amplifies negative effects. The results provide recommendations to help managers formulate appropriate strategies.


Assuntos
Comércio , Recall e Retirada de Produto , Revelação , Percepção Social , Qualidade de Produtos para o Consumidor , Setor Privado , Opinião Pública , Revelação da Verdade , China
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