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1.
Neural Regen Res ; 20(3): 836-844, 2025 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38886956

RESUMEN

JOURNAL/nrgr/04.03/01300535-202503000-00028/figure1/v/2024-06-17T092413Z/r/image-tiff Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

2.
Neural Regen Res ; 20(5): 1467-1482, 2025 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-39075913

RESUMEN

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

3.
J Environ Sci (China) ; 148: 650-664, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39095197

RESUMEN

China is the most important steel producer in the world, and its steel industry is one of the most carbon-intensive industries in China. Consequently, research on carbon emissions from the steel industry is crucial for China to achieve carbon neutrality and meet its sustainable global development goals. We constructed a carbon dioxide (CO2) emission model for China's iron and steel industry from a life cycle perspective, conducted an empirical analysis based on data from 2019, and calculated the CO2 emissions of the industry throughout its life cycle. Key emission reduction factors were identified using sensitivity analysis. The results demonstrated that the CO2 emission intensity of the steel industry was 2.33 ton CO2/ton, and the production and manufacturing stages were the main sources of CO2 emissions, accounting for 89.84% of the total steel life-cycle emissions. Notably, fossil fuel combustion had the highest sensitivity to steel CO2 emissions, with a sensitivity coefficient of 0.68, reducing the amount of fossil fuel combustion by 20% and carbon emissions by 13.60%. The sensitivities of power structure optimization and scrap consumption were similar, while that of the transportation structure adjustment was the lowest, with a sensitivity coefficient of less than 0.1. Given the current strategic goals of peak carbon and carbon neutrality, it is in the best interest of the Chinese government to actively promote energy-saving and low-carbon technologies, increase the ratio of scrap steel to steelmaking, and build a new power system.


Asunto(s)
Dióxido de Carbono , Huella de Carbono , Acero , China , Dióxido de Carbono/análisis , Contaminantes Atmosféricos/análisis , Metalurgia , Monitoreo del Ambiente , Industrias , Contaminación del Aire/estadística & datos numéricos , Contaminación del Aire/prevención & control
4.
BMC Geriatr ; 24(1): 770, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300333

RESUMEN

OBJECTIVE: Cognitive dysfunction is a common complication of diabetes after central nervous system involvement. The impact of exercise, as an important non-pharmacological intervention strategy, on cognitive function remains controversial. Thus, we conducted a meta-analysis to assess the impact of exercise on cognitive function of elderly patients with type2 diabetes mellitus (T2DM). METHODS: We computer searched PubMed, Web of Science, Embase, CINAHL, Cochrane Library, CNKI, Wanfang date, and VIP, and traced back the references included in the literature from 1974 to July 2024. We used RevMan5.4 software for data analysis, and also conducted sensitivity, subgroup, and publication bias analyses. RESULTS: Eight eligible studies with a combined total of 747 elderly patients with T2DM were included. Meta-analysis showed that the combined effect size of exercise intervention on cognitive improvement in elderly patients with T2DM was significant [SMD = 0.65, 95% CI (0.48, 0.82), P < 0.01]. The following three factors had significant effects on the overall cognitive function of participants: subgroups (MoCA group [MD = 2.22 95% CI (1.26, 3.18), P < 0.01] and MMSE group [MD = 1.81, 95% CI (0.71,2.90), P = 0.001]); intervention times (3-month intervention [MD = 3.14, 95% CI (2.50, 3.78), P < 0.01], 6-month intervention [SMD = 0.32, 95% CI (0.12. 0.52), P = 0.002], and > 6 month intervention [SMD = 0.21, 95% CI (0.45, 0.81), P < 0.01]); intervention forms (single exercise [SMD = 0.21, 95% CI (0.45, 0.81), P < 0.01] and multiple exercise [SMD = 0.86, 95% CI ( 0.39,1.33), P < 0.0001]). CONCLUSION: Exercise intervention may improve cognitive function in elderly patients with T2DM.


Asunto(s)
Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Terapia por Ejercicio , Humanos , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/psicología , Diabetes Mellitus Tipo 2/complicaciones , Anciano , Disfunción Cognitiva/terapia , Disfunción Cognitiva/psicología , Disfunción Cognitiva/etiología , Terapia por Ejercicio/métodos , Cognición/fisiología , Ejercicio Físico/fisiología , Ejercicio Físico/psicología
5.
Nat Metab ; 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39322747

RESUMEN

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8+ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8+ T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8+ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

6.
Drug Discov Today ; 29(11): 104182, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39284523

RESUMEN

Diabetes is a complex, multifactorial disease that is caused by a pathological combination of insulin resistance and pancreatic islet dysfunction. Polysaccharides are extensively dispersed in nature and have a very complicated structure with various biological properties. Natural polysaccharides have potentially extraordinary beneficial health effects on managing metabolic diseases such as diabetes, obesity and cardiovascular disease. Thus, a systematic review of the latest research into and possible regulatory mechanisms of natural polysaccharides for type 2 diabetes mellitus treatment is of great significance for a better understanding of their pharmaceutical value. We discuss the regulatory mechanisms of natural polysaccharides for the treatment of diabetes, and especially their role in reshaping dysfunctional gut microbiota. Natural polysaccharides could be developed as new and safe antidiabetic drugs, and detailed mechanistic studies could further clarify the molecular targets of polysaccharides in the treatment of diabetes.

7.
Diabetes Obes Metab ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313920

RESUMEN

AIM: To assess the variation in patterns of use of insulin and other antidiabetic medicines across China, both geographically and over time. MATERIALS AND METHODS: Nationally, we calculated the relative change in antidiabetic medicine purchases between the first and last quarters of 2020 through 2022 based on the number of defined daily doses procured per quarter. We used annual data to analyse differences in antidiabetic medicine use and patterns across seven regions of China. Considering large regional variations, we used multifactor linear regression to preliminarily explore the possible factors influencing this variation. RESULTS: Nationally, the procurement of antidiabetic medicines and insulin increased from 2020 to 2022, while the proportion of insulin among antidiabetic medicines remained stable at approximately 22%. Among all insulins, premixed insulin (human) was ranked first. Of the three subgroups of insulin, analogues were the most preferred and had the largest procurement, but different categories showed different trends in terms of purchases and proporation. Regionally, the growth rate of antidiabetic medicines, the proportion of insulin procurement and the preferred types of insulin across the seven regions were different. Regarding preliminary influencing factors, the level of education and owning a domestically funded producer had a positive effect on insulin procurement. CONCLUSIONS: From 2020 to 2022, the procurement of insulin increased, which may be due to the increased attention for diabetes from the country and residents.However, the proportion of insulin among all antidiabetic medicines was essentially unchanged, while the use of some non-insulin hypoglycemic drugs increased significantly, especially the SGLT2i and GLP-1 RA. Given the economic and cultural diversity, Insulin procurement and utilization patterns varied greatly across the regions. Owning domestic enterprises potentially influences the procurement of insulin. Enhancing education to further improve the self-management of patients with diabetes is essential.

8.
Mol Neurobiol ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39316356

RESUMEN

The benefits of exercise on neuropathic pain (NP) have been demonstrated in numerous studies. In recent studies, inflammation, neurotrophins, neurotransmitters, and endogenous opioids are considered as the main mechanisms. However, the role of exercise in alleviating NP remains unclear. Neuroglia, widely distributed in both the central and peripheral nervous systems, perform functions such as support, repair, immune response, and maintenance of normal neuronal activity. A large number of studies have shown that neuroglia play an important role in the occurrence and development of NP, and exercise can alleviate NP by regulating neuroglia. This article reviewed the involvement of neuroglia in the development of NP and their role in the exercise treatment of NP, intending to provide a theoretical basis for the exercise treatment strategy of NP.

9.
Plant Physiol ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39268871

RESUMEN

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system allows precise and easy editing of genes in many plant species. However, this system has not yet been applied to any fern species through gametophytes due to the complex characteristics of fern genomes, genetics, and physiology. Here, we established a protocol for gametophyte-based screening of single-guide RNAs (sgRNAs) with high efficiency for CRISPR/Cas9-mediated gene knockout in a model fern species, Ceratopteris richardii. We utilized the C. richardii ACTIN promoter to drive sgRNA expression and the enhanced CaMV 35S promoter to drive the expression of Streptococcus pyogenes Cas9 in this CRISPR-mediated editing system, which was employed to successfully edit a few genes, such as Nucleotidase/phosphatase 1 (CrSAL1) and Phytoene Desaturase (CrPDS), which resulted in an albino phenotype in C. richardii. Knockout of CrSAL1 resulted in significantly (P<0.05) reduced stomatal conductance (gs), leaf transpiration rate (E), guard cell length, and abscisic acid (ABA)-induced reactive oxygen species (ROS) accumulation in guard cells. Moreover, CrSAL1 overexpressing plants showed significantly increased net photosynthetic rate (A), gs, and E as well as most of the stomatal traits and ABA-induced ROS production in guard cells compared to the wild-type (WT) plants. Taken together, our optimized CRISPR/Cas9 system provides a useful tool for functional genomics in a model fern species, allowing the exploration of fern gene functions for evolutionary biology, herbal medicine discovery, and agricultural applications.

10.
J Am Heart Assoc ; 13(18): e036109, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39258531

RESUMEN

BACKGROUND: This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS AND RESULTS: ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. CONCLUSIONS: In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. REGISTRATION: URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.


Asunto(s)
Fibrinolíticos , Accidente Cerebrovascular Isquémico , Recuperación de la Función , Terapia Trombolítica , Activador de Tejido Plasminógeno , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico , Anciano , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Tejido Plasminógeno/uso terapéutico , Fibrinolíticos/uso terapéutico , Fibrinolíticos/administración & dosificación , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Pronóstico , Índice de Severidad de la Enfermedad , Estado Funcional , Evaluación de la Discapacidad , Anciano de 80 o más Años
11.
J Orthop Translat ; 48: 163-175, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39257437

RESUMEN

Background: In the recent decade, there has been substantial progress in the technologies and philosophies associated with diagnosing and treating anterior cruciate ligament (ACL) injuries in China. The therapeutic efficacy of ACL reconstruction in re-establishing the stability of the knee joint has garnered widespread acknowledgment. However, the path toward standardizing diagnostic and treatment protocols remains to be further developed and refined. Objective: In this context, the Chinese Association of Orthopaedic Surgeons (CAOS) and the Chinese Society of Sports Medicine (CSSM) collaboratively developed an expert consensus on diagnosing and treating ACL injury, aiming to enhance medical quality through refining professional standards. Methods: The consensus drafting team invited experts across the Greater China region, including the mainland, Hong Kong, Macau, and Taiwan, to formulate and review the consensus using a modified Delphi method as a standardization approach. As members of the CSSM Lower Limb Study Group and the CAOS Arthroscopy and Sports Medicine Study Group, invited experts concentrated on two pivotal issues: "Graft Selection" and "Clinical Outcome Evaluation" during the second part of the consensus development. Results: This focused discussion ultimately led to a strong consensus on nine specific consensus terms. Conclusion: The consensus clearly states that ACL reconstruction has no definitive "gold standard" graft choice. Autografts have advantages in healing capability but are limited in availability and have potential donor site morbidities; allografts reduce surgical trauma but incur additional costs, and there are concerns about slow healing, quality control issues, and a higher failure rate in young athletes; synthetic ligaments allow for early rehabilitation and fast return to sport, but the surgery is technically demanding and incurs additional costs. When choosing a graft, one should comprehensively consider the graft's characteristics, the doctor's technical ability, and the patient's needs. When evaluating clinical outcomes, it is essential to ensure an adequate sample size and follow-up rate, and the research should include patient subjective scoring, joint function and stability, complications, surgical failure, and the return to sport results. Medium and long-term follow-ups should not overlook the assessment of knee osteoarthritis.

13.
JMIR Serious Games ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288282

RESUMEN

BACKGROUND: EmergenCSimTM, is a novel researcher-developed serious game (SG) with an embedded scoring and feedback tool that reproduces an obstetric operating room environment. The learner must perform general anesthesia (GA) for emergent cesarean delivery (CD) for umbilical cord prolapse. The game was developed as an alternative teaching tool because of diminishing real-world exposure of anesthesiology trainees to this clinical scenario. Traditional debriefing (facilitator-guided reflection) is considered to be integral to experiential learning but requires the participation of an instructor. The optimal debriefing methods for SGs have not been well-studied. Electronic feedback is commonly provided at the conclusion of SGs, so we aimed to compare the effectiveness of learning when an in-person debrief is added to electronic feedback compared to using electronic feedback alone. OBJECTIVE: We hypothesized that an in-person debriefing in addition to the SG-embedded electronic feedback will provide superior learning than electronic feedback alone. METHODS: Novice 1st year anesthesiology residents (CA-1) (n=51) (i) watched a recorded lecture on GA for emergent CD, (ii) took a 26-item multiple-choice question (MCQ) pre-test, and (iii) played EmergenCSimTM (maximum score 196.5). They were randomized to either the control group which experienced the electronic feedback alone (Group EF, n=26) or the intervention group, which experienced the SG-embedded electronic feedback and an in-person debriefing (Group IPD+EF, n=25). All subjects played the SG a 2nd time, with instructions to try to increase their score, then they took a 26-item MCQ post-test. Pre-and post-tests (maximum score of 26 points each), were validated parallel forms. RESULTS: For Groups EF and IPD+EF respectively, mean pre-test scores were18.6 (SD 2.5) and 19.4 (SD 2.3), and mean post-test scores were 22.6 (SD 2.2) and 22.1 (SD 1.6); F=1.8, P =.19. SG scores for Groups EF and IPD+EF respectively were - mean 1st play SG scores of 135 (SE 4.4) and 141 (SE 4.5), and mean 2nd play SG scores were 163.1 (SE 2.9) and 173.3 (SE 2.9); F= 137.7, P < .001. CONCLUSIONS: Adding an in-person debriefing experience led to greater improvement in SG scores, emphasizing the learning benefits of this practice. Improved SG performance in both groups suggests that SGs have a role as independent, less resource-intensive educational tools. CLINICALTRIAL: None.

14.
Br J Radiol ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39288312

RESUMEN

OBJECTIVES: To evaluate the performance of ultrasound-based deep learning (DL) models in distinguishing breast phyllodes tumors (PTs) from fibroadenomas (FAs) and their clinical utility in assisting radiologists with varying diagnostic experiences. METHODS: We retrospectively collected 1180 ultrasound images from 539 patients (247 PTs and 292 FAs). Five DL network models with different structures were trained and validated using nodule regions annotated by radiologists on breast ultrasound images. DL models were trained using the methods of transfer learning and 3-fold cross-validation. The model demonstrated the best evaluation index in the 3-fold cross-validation was selected for comparison with radiologists' diagnostic decisions. Two-round reader studies were conducted to investigate the value of DL model in assisting six radiologists with different levels of experience. RESULTS: Upon testing, Xception model demonstrated the best diagnostic performance (AUC: 0.87, 95%CI: 0.81-0.92), outperforming all radiologists (all p < 0.05). Additionally, the DL model enhanced the diagnostic performance of radiologists. Accuracy demonstrated improvements of 4%, 4%, and 3% for senior, intermediate, and junior radiologists, respectively. CONCLUSIONS: The DL models showed superior predictive abilities compared to experienced radiologists in distinguishing breast PTs from FAs. Utilizing the model led to improved efficiency and diagnostic performance for radiologists with different levels of experience (6-25 years of work). ADVANCES IN KNOWLEDGE: We developed and validated a DL model based on the largest available dataset to assist in diagnosing PTs. This model has the potential to allow radiologists to discriminate two types of breast tumors which are challenging to identify with precision and accuracy, and subsequently to make more informed decisions about surgical plans.

15.
Heliyon ; 10(17): e37033, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296138

RESUMEN

It is vital and challenging to coordinate the protection of natural reserves with rural construction. The rural structure and function were divided during the creation of natural reserves on the Qinghai Tibet Plateau (QTP), throwing the rural structure and functional system and its constituent parts out of balance. According to current research results on the construction mode of rural landscapes, the creation of rural landscapes is unable to address the requirements of villages and encourage the creation of protected areas. Therefore, it has become urgently necessary to conduct research on the rural landscape construction model of the QTP natural reserve. This study focuses on the case study of the construction mode of rural landscapes in the Mengda National Nature Reserve (MNNR) in the QTP. The inherent hierarchical structure relationships between rural landscape types, units and elements were identified. The basic characteristics of residential, production and cultural landscapes and their interdependent structural relationships were described. According to the evidence collected from literature, the rural landscape complex model and spatial optimisation strategy in the MNNR were proposed. It is believed that the rural residential, production and cultural landscape structures of the MNNR cannot effectively realise its living, production and culture function. From a spatial structure level, a rural landscape construction model was proposed based on production landscapes, residential landscapes as characteristics and cultural landscapes as the source. This model is based on agricultural landscapes, features the village and village dwellings and originates from temple landscapes, forming a comprehensive landscape unit that relies on and supports each other among production, residential and cultural landscapes. Emphasising the structural construction of infrastructure, such as transportation roads, network routes, tourism routes and water and electricity networks between the system and the external environment, is essential for promoting the circular relationship between the agricultural community complex in Dazhuang Village and the external system. The model is beneficial to balance the relationship between the rural landscape structure and MNNR function and promote the sustainable development of the relationship between the nature reserve and rural areas.

16.
Heliyon ; 10(17): e37066, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39296204

RESUMEN

Objective: This study explores the correlation between Forkhead box M1 (FOXM1) and ATP-binding cassette subfamily C member 5 (ABCC5) in relation to paclitaxel resistance in cervical cancer. It aims to identify potential cervical cancer stem cell markers, offering fresh perspectives for developing therapeutic strategies to overcome paclitaxel chemoresistance in cervical cancer. Methods: Paclitaxel-resistant Hela cells (Hela/Taxol) were developed by intermittently exposing Hela cells to progressively increasing concentrations of paclitaxel. We assessed the biological properties of both Hela and Hela/Taxol cells using various assays: cell proliferation, clonogenic, cell cycle, apoptosis, scratch, and transwell. To determine which markers better represent tumor stem cells, we analyzed various known and potential stem cell markers in combination. Flow cytometry was employed to measure the proportion of positive markers in both parental and drug-resistant cell lines. Following statistical analysis to establish relative stability, CD133+ABCC5+ cells were sorted for further examination. Subsequent tests included sphere-forming assays and Western blot analysis to detect the presence of the stem cell-specific protein Sox2, aiding in the identification of viable cervical cancer stem cell markers. Results: The Hela/Taxol cell line exhibited significantly enhanced proliferation, migration, and invasion capabilities compared to the Hela cell line, alongside a marked reduction in apoptosis rates (P < 0.01). Notably, proportions of CD44+, CD24+CD44+, ABCC5+, CD24+CD44+ABCC5+, CD44+ABCC5+, CD24+CD44+FOXM1+, CD44+FOXM1+, CD133+ABCC5+, and CD133+FOXM1+ were significantly higher (P < 0.05). Furthermore, the size and number of spheres formed byCD133+ABCC5+ cells were greater in the sorted Hela/Taxol line (P < 0.01), with increased expression of the stem cell marker Sox2 (P < 0.001). Conclusion: The Hela/Taxol cells demonstrate increased tumoral stemness, suggesting that CD133+ABCC5+ may serve as a novel marker for cervical cancer stem cells.

17.
J Hazard Mater ; 480: 135870, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39298961

RESUMEN

Environmental persistent free radicals (EPFRs) derived from chlorophenols, triggered by light or heat exposure, pose significant ecological concerns, yet the impact of chlorine substituents on EPFRs formation and reactivity remains inadequately understood. Through an intentional synthesis of chlorophenol-derived EPFRs with varying chlorine contents and positioning, we elucidated the role of chlorine in the photoactivation of molecular oxygen. Our combined experimental and theoretical analysis reveals that these EPFRs are primarily oxygen-centered phenoxy radicals, establishing a direct link between chlorine substitution patterns and their ability to activate molecular oxygen under visible light. Increased chlorine content enhances EPFRs formation by elevating the positive charge on the phenolic hydroxyl group's hydrogen atom, facilitating its removal. Moreover, the capability of EPFRs to activate molecular oxygen was directly correlated with chlorine content, with 2,3,5,6-tetrachlorophenol-derived EPFRs showcasing the highest activity. This activity is attributed to their structural propensity for TCSQ·- species generation. Furthermore, our study established a significant correlation between the toxicity and activity of EPFRs, emphasizing the critical role of halogen substituents in determining the reactivity of EPFRs. These insights contribute to our understanding of their environmental and toxicological ramifications, underscoring the imperative for continued research aimed at mitigating their detrimental impacts.

18.
Sports Biomech ; : 1-16, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39279564

RESUMEN

This study aims to explore the effects of 8 weeks of lateral entry training on the start performance of elite athletes and its impact on ordinary entry performance. Data were collected from 12 elite-level participants before and after the training using Kistler(9691A1) system with 3D force platform and high-speed cameras. 19 parameters of ordinary and lateral entry were assessed and analysed using paired samples t-tests. Compared to ordinary entry, the lateral entry performance was characterised by: decrease of both vertical force (5.77%) and maximum depth (6.09%) at a significance level (p < .01), and increase of flight distance (4.33%), first kick distance (3.90%) and push force (14.06%) at (p < .05). The results show that, compared to an ordinary entry technique, the lateral entry technique provides a 3.93%, 6.14%, and 8.29% reduction in time to reaching a 5 m, 10 m and 15 m distance (p ≤ .01), showing performance improvements at start times. The 8-week training on the lateral entry technique did not have a significant impact on the time performance of the ordinary entry technique (p > .050). The findings presented herein offer pertinent insights for elite-level athletes, coaches and future investigations aimed at enhancing swimming start techniques and performance.

19.
Biotechnol Bioeng ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39279638

RESUMEN

We report the integration of 3D printing, electrobiofabrication, and protein engineering to create a device that enables near real-time analysis of monoclonal antibody (mAb) titer and quality. 3D printing was used to create the macroscale architecture that can control fluidic contact of a sample with multiple electrodes for replicate measurements. An analysis "chip" was configured as a "snap-in" module for connecting to a 3D printed housing containing fluidic and electronic communication systems. Electrobiofabrication was used to functionalize each electrode by the assembly of a hydrogel interface containing biomolecular recognition and capture proteins. Specifically, an electrochemical thiol oxidation is used to assemble a thiolated polyethylene glycol hydrogel, that in turn is covalently coupled to either a cysteine-tagged protein G that binds the antibody's Fc region or a lectin that binds the glycans of target mAb analytes. We first show the design, assembly, and testing of the hardware device. Then, we show the transition of a step-by-step sensing methodology (e.g., mix, incubate, wash, mix, incubate, wash, measure) into the current method where functionalization, antibody capture, and assessment are performed in situ and in parallel channels. Both titer and glycan analyses were found to be linear with antibody concentration (to 0.2 mg/L). We further found the interfaces could be reused with remarkably similar results. Because the interface assembly and use are simple, rapid, and robust, we suggest this assessment methodology will be widely applicable, including for other biomolecular process development and manufacturing environments.

20.
Curr Gene Ther ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39279703

RESUMEN

INTRODUCTION: Lung cancer stands as one of the most prevalent malignant neoplasms, with microRNAs (miRNAs) playing a pivotal role in the modulation of gene expression, impacting cancer cell proliferation, invasion, metastasis, immune escape, and resistance to therapy. METHOD: The intricate role of miRNAs in lung cancer underscores their significance as biomarkers for early detection and as novel targets for therapeutic intervention. Traditional approaches for the identification of miRNAs related to lung cancer, however, are impeded by inefficiencies and complexities. RESULTS: In response to these challenges, this study introduced an innovative deep-learning strategy designed for the efficient and precise identification of lung cancer-associated miRNAs. Through comprehensive benchmark tests, our method exhibited superior performance relative to existing technologies. CONCLUSION: Further case studies have also confirmed the ability of our model to identify lung cancer-associated miRNAs that have undergone biological validation.

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