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1.
Front Public Health ; 12: 1329768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737867

RESUMO

Objectives: This study aimed to analyze the influencing factors of hospitalization cost of hypertensive patients in TCM (traditional Chinese medicine, TCM) hospitals, which can provide a scientific basis for hospitals to control the hospitalization cost of hypertension. Methods: In this study, 3,595 hospitalized patients with a primary diagnosis of tertiary hypertension in Tianshui City Hospital of TCM, Gansu Province, China, from January 2017 to June 2022, were used as research subjects. Using univariate analysis to identify the relevant variables of hospitalization cost, followed by incorporating the statistically significant variables of univariate analysis as independent variables in multiple linear regression analysis, and establishing the path model based on the results of the multiple linear regression finally, to explore the factors influencing hospitalization cost comprehensively. Results: The results showed that hospitalization cost of hypertension patients were mainly influenced by length of stay, age, admission pathways, payment methods of medical insurance, and visit times, with length of stay being the most critical factor. Conclusion: The Chinese government should actively exert the characteristics and advantages of TCM in the treatment of chronic diseases such as hypertension, consistently optimize the treatment plans of TCM, effectively reduce the length of stay and steadily improve the health literacy level of patients, to alleviate the illnesses pain and reduce the economic burden of patients.


Assuntos
Hospitalização , Hipertensão , Medicina Tradicional Chinesa , Humanos , Feminino , Hipertensão/economia , Masculino , Pessoa de Meia-Idade , Medicina Tradicional Chinesa/economia , Medicina Tradicional Chinesa/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , China , Idoso , Tempo de Internação/estatística & dados numéricos , Tempo de Internação/economia , Adulto , Custos Hospitalares/estatística & dados numéricos
2.
Sensors (Basel) ; 24(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38732815

RESUMO

The properties of small size, low noise, high performance and no wear-out have made the hemispherical resonator gyroscope a good choice for high-value space missions. To enhance the precision of the hemispherical resonator gyroscope for use in tasks with large angular velocities and angular accelerations, this paper investigates the standing wave precession of a non-ideal hemispherical resonator under nonlinear high-intensity dynamic conditions. Based on the thin shell theory of elasticity, a dynamic model of a hemispherical resonator is established by using Lagrange's second kind equation. Then, the dynamic model is equivalently transformed into a simple harmonic vibration model of a point mass in two-dimensional space, which is analyzed using a method of averaging that separates the slow variables from the fast variables. The results reveal that taking the nonlinear terms about the square of the angular velocity and the angular acceleration in the dynamic equation into account can weaken the influence of the 4th harmonic component of a mass defect on standing wave drift, and the extent of this weakening effect varies with the dimensions of the mass defects, which is very important for steering the development of the high-precision hemispherical resonator gyroscope.

3.
Surg Endosc ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777891

RESUMO

BACKGROUND: Anastomotic stricture significantly impacts patients' quality of life and long-term prognosis. However, current clinical practice lacks accurate tools for predicting anastomotic stricture. This study aimed to develop a nomogram to predict anastomotic stricture in patients with rectal cancer who have undergone anterior resection. METHODS: A total of 1542 eligible patients were recruited for the study. Least absolute shrinkage selection operator (Lasso) analysis was used to preliminarily select predictors. A prediction model was constructed using multivariate logistic regression and presented as a nomogram. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration diagrams, and decision curve analysis (DCA). Internal validation was conducted by assessing the model's performance on a validation cohort. RESULTS: 72 (4.7%) patients were diagnosed with anastomotic stricture. Participants were randomly divided into training (n = 1079) and validation (n = 463) sets. Predictors included in this nomogram were radiotherapy, diverting stoma, anastomotic leakage, and anastomotic distance. The area under the ROC curve (AUC) for the training set was 0.889 [95% confidence interval (CI) 0.840-0.937] and for the validation set, it was 0.930 (95%CI 0.879-0.981). The calibration curve demonstrated a strong correlation between predicted and observed outcomes. DCA results showed that the nomogram had clinical value in predicting anastomotic stricture in patients after anterior resection of rectal cancer. CONCLUSION: We developed a predictive model for anastomotic stricture following anterior resection of rectal cancer. This nomogram could assist clinicians in predicting the risk of anastomotic stricture, thus improving patients' quality of life and long-term prognosis.

4.
Exp Ther Med ; 27(6): 265, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38756905

RESUMO

Sphingosine 1-phosphate receptor 3 (S1PR3) participates in the inflammatory response in multiple types of diseases. However, the biological role of S1PR3 in intervertebral disc degeneration and the underlying mechanism are unclear. The aim of the present study was to investigate the functional role and the mechanism of S1PR3 in lipopolysaccharide (LPS)-induced human nucleus pulposus cells. The expression of S1PR3 and Toll-like receptor (TLR) 2 in LPS-induced nucleus pulposus (NP) cells was investigated using western blotting. The Cell Counting Kit-8 assay was used to detect cell proliferation, and the levels of inflammatory factors were detected using ELISA. Flow cytometry and western blotting were used for the assessment of apoptosis. The deposition of extracellular matrix (ECM) proteins was investigated using reverse transcription-quantitative PCR and western blotting. In addition, western blotting was used to investigate the protein expression levels of phosphorylated (p)-STAT3, STAT3, p-JNK, JNK, p-ERK, ERK, p-p38 and p38associated with STAT3 and MAPK signaling. S1PR3 expression was reduced, while TLR2 expression was elevated in LPS-induced human nucleus pulposus cells (HNPC). S1PR3 overexpression increased HNPC viability, inhibited the inflammatory response and suppressed apoptosis. Meanwhile, S1PR3 overexpression regulated the expression of ECM-related proteins. Additionally, overexpression of S1PR3 inhibited the expression of the TLR2-regulated STAT3 and MAPK pathways in LPS-induced HNPCs. Furthermore, TLR2 overexpression partially offset the impacts of S1PR3 overexpression on HNPC viability, apoptosis level, inflammation and as ECM degradation. In conclusion, STAT3 overexpression suppressed viability injury, the inflammatory response and the level of apoptosis and alleviated ECM protein deposition in HNPCs through the TLR2/STAT3 and TLR2/MAPK pathways, which may offer a promising candidate for the amelioration of intervertebral disc degeneration.

5.
Photoacoustics ; 38: 100614, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38764523

RESUMO

Microscopic defects in flip chips, originating from manufacturing, significantly affect performance and longevity. Post-fabrication sampling methods ensure product functionality but lack in-line defect monitoring to enhance chip yield and lifespan in real-time. This study introduces a photoacoustic remote sensing (PARS) system for in-line imaging and defect recognition during flip-chip fabrication. We first propose a real-time PARS imaging method based on continuous acquisition combined with parallel processing image reconstruction to achieve real-time imaging during the scanning of flip-chip samples, reducing reconstruction time from an average of approximately 1134 ms to 38 ms. Subsequently, we propose improved YOLOv7 with space-to-depth block (IYOLOv7-SPD), an enhanced deep learning defect recognition method, for accurate in-line recognition and localization of microscopic defects during the PARS real-time imaging process. The experimental results validate the viability of the proposed system for enhancing the lifespan and yield of flip-chip products in chip manufacturing facilities.

6.
Surg Endosc ; 38(5): 2756-2769, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38575830

RESUMO

BACKGROUND: The appropriateness of laparoscopic gastrectomy (LG) for super-geriatric patients with locally advanced gastric cancer (LAGC) is inconclusive, and the prognostic factors are also yet to be elucidated. Herein, we aimed to investigate the surgical and oncological outcomes of LG versus open gastrectomy (OG) for geriatric patients with LAGC who have outlived the average lifespan of the Chinese population (≥ 78 years). METHODS: This is a monocentric, retrospective, comparative study. A 1:1 propensity score matching (PSM) was performed to minimize selection bias and ensure well-balanced characteristics. The primary endpoint of interest was 3-year overall survival, while secondary endpoints included procedure-related variables, postoperative recovery indices, and complications. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify unfavorable prognostic factors. RESULTS: Of 196 eligible individuals, 107 underwent LG and 89 underwent OG, with a median age (interquartile range [IQR]) of 82 [79, 84] years. PSM yielded 61 matched pairs, with comparable demographic and tumor characteristics. The LG group had a significantly lower overall complication rate than the OG group (31.1% vs. 49.2%, P = 0.042), as well as shorter duration of postoperative hospital stay [12 (11, 13) vs. 13 (12, 15.5) d, P < 0. 001], less intraoperative blood loss [95 (75, 150) vs. 230 (195, 290) mL, P < 0.001], but a longer operative time [228 (210, 255.5) vs. 196 (180, 219.5) min, P < 0.001]. The times to first aerofluxus, defecation, liquid diet, and half-liquid diet were comparable. Kaplan-Meier analyses revealed no significant difference in 3-year overall survival between the groups, either in the entire cohort or in subgroups with different TNM staging. Moreover, Age-adjusted Charlson Comorbidity Index scores of > 6 [hazard ratio (HR) 4.003; P = 0.021] and pathologic TNM stage III (HR 3.816, P = 0.023) were independent unfavorable prognostic factors for long-term survival. CONCLUSIONS: LG performed by experienced surgeons offers the benefits of comparable or better surgical and oncological safety profiles than OG for super-geriatric patients with LAGC.


Assuntos
Gastrectomia , Laparoscopia , Pontuação de Propensão , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Masculino , Gastrectomia/métodos , Feminino , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Prognóstico , Laparoscopia/métodos , Idoso , Taxa de Sobrevida , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Tempo de Internação/estatística & dados numéricos
7.
Microbiol Spectr ; : e0216423, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563791

RESUMO

African swine fever (ASF) is a highly fatal viral disease that poses a significant threat to domestic pigs and wild boars globally. In our study, we aimed to explore the potential of a multiplexed CRISPR-Cas system in suppressing ASFV replication and infection. By engineering CRISPR-Cas systems to target nine specific loci within the ASFV genome, we observed a substantial reduction in viral replication in vitro. This reduction was achieved through the concerted action of both Type II and Type III RNA polymerase-guided gRNA expression. To further evaluate its anti-viral function in vivo, we developed a pig strain expressing the multiplexable CRISPR-Cas-gRNA via germline genome editing. These transgenic pigs exhibited normal health with continuous expression of the CRISPR-Cas-gRNA system, and a subset displayed latent viral replication and delayed infection. However, the CRISPR-Cas9-engineered pigs did not exhibit a survival advantage upon exposure to ASFV. To our knowledge, this study represents the first instance of a living organism engineered via germline editing to assess resistance to ASFV infection using a CRISPR-Cas system. Our findings contribute valuable insights to guide the future design of enhanced viral immunity strategies. IMPORTANCE: ASFV is currently a devastating disease with no effective vaccine or treatment available. Our study introduces a multiplexed CRISPR-Cas system targeting nine specific loci in the ASFV genome. This innovative approach successfully inhibits ASFV replication in vitro, and we have successfully engineered pig strains to express this anti-ASFV CRISPR-Cas system constitutively. Despite not observing survival advantages in these transgenic pigs upon ASFV challenges, we did note a delay in infection in some cases. To the best of our knowledge, this study constitutes the first example of a germline-edited animal with an anti-virus CRISPR-Cas system. These findings contribute to the advancement of future anti-viral strategies and the optimization of viral immunity technologies.

8.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38622356

RESUMO

Identifying disease-associated microRNAs (miRNAs) could help understand the deep mechanism of diseases, which promotes the development of new medicine. Recently, network-based approaches have been widely proposed for inferring the potential associations between miRNAs and diseases. However, these approaches ignore the importance of different relations in meta-paths when learning the embeddings of miRNAs and diseases. Besides, they pay little attention to screening out reliable negative samples which is crucial for improving the prediction accuracy. In this study, we propose a novel approach named MGCNSS with the multi-layer graph convolution and high-quality negative sample selection strategy. Specifically, MGCNSS first constructs a comprehensive heterogeneous network by integrating miRNA and disease similarity networks coupled with their known association relationships. Then, we employ the multi-layer graph convolution to automatically capture the meta-path relations with different lengths in the heterogeneous network and learn the discriminative representations of miRNAs and diseases. After that, MGCNSS establishes a highly reliable negative sample set from the unlabeled sample set with the negative distance-based sample selection strategy. Finally, we train MGCNSS under an unsupervised learning manner and predict the potential associations between miRNAs and diseases. The experimental results fully demonstrate that MGCNSS outperforms all baseline methods on both balanced and imbalanced datasets. More importantly, we conduct case studies on colon neoplasms and esophageal neoplasms, further confirming the ability of MGCNSS to detect potential candidate miRNAs. The source code is publicly available on GitHub https://github.com/15136943622/MGCNSS/tree/master.


Assuntos
Neoplasias do Colo , MicroRNAs , Humanos , MicroRNAs/genética , Algoritmos , Biologia Computacional/métodos , Software , Neoplasias do Colo/genética
9.
Cancer Imaging ; 24(1): 52, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627828

RESUMO

BACKGROUND: Combining conventional radiomics models with deep learning features can result in superior performance in predicting the prognosis of patients with tumors; however, this approach has never been evaluated for the prediction of metachronous distant metastasis (MDM) among patients with retroperitoneal leiomyosarcoma (RLS). Thus, the purpose of this study was to develop and validate a preoperative contrast-enhanced computed tomography (CECT)-based deep learning radiomics model for predicting the occurrence of MDM in patients with RLS undergoing complete surgical resection. METHODS: A total of 179 patients who had undergone surgery for the treatment of histologically confirmed RLS were retrospectively recruited from two tertiary sarcoma centers. Semantic segmentation features derived from a convolutional neural network deep learning model as well as conventional hand-crafted radiomics features were extracted from preoperative three-phase CECT images to quantify the sarcoma phenotypes. A conventional radiomics signature (RS) and a deep learning radiomics signature (DLRS) that incorporated hand-crafted radiomics and deep learning features were developed to predict the risk of MDM. Additionally, a deep learning radiomics nomogram (DLRN) was established to evaluate the incremental prognostic significance of the DLRS in combination with clinico-radiological predictors. RESULTS: The comparison of the area under the curve (AUC) values in the external validation set, as determined by the DeLong test, demonstrated that the integrated DLRN, DLRS, and RS models all exhibited superior predictive performance compared with that of the clinical model (AUC 0.786 [95% confidence interval 0.649-0.923] vs. 0.822 [0.692-0.952] vs. 0.733 [0.573-0.892] vs. 0.511 [0.359-0.662]; both P < 0.05). The decision curve analyses graphically indicated that utilizing the DLRN for risk stratification provided greater net benefits than those achieved using the DLRS, RS and clinical models. Good alignment with the calibration curve indicated that the DLRN also exhibited good performance. CONCLUSIONS: The novel CECT-based DLRN developed in this study demonstrated promising performance in the preoperative prediction of the risk of MDM following curative resection in patients with RLS. The DLRN, which outperformed the other three models, could provide valuable information for predicting surgical efficacy and tailoring individualized treatment plans in this patient population. TRIAL REGISTRATION: Not applicable.


Assuntos
Aprendizado Profundo , Leiomiossarcoma , Neoplasias Retroperitoneais , Sarcoma , Humanos , Leiomiossarcoma/diagnóstico por imagem , Leiomiossarcoma/cirurgia , Radiômica , Estudos Retrospectivos , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/cirurgia
10.
Int J Cardiol Heart Vasc ; 51: 101395, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628294

RESUMO

Background: In this study, we investigated clinical prediction factors of nonchronic total occlusion lesion (NCTOL) progression in patients who underwent percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions. Methods: In total, 450 patients with unstable angina (mean age = 57.1 ± 9.2 years) who underwent PCI for CTO lesions between January 2016 and December 2018 at Beijing Anzhen Hospital were enrolled in this study. A clinical and angiographic follow-up examination was performed 12 months postoperatively. The patients were divided into NCTOL progression (145 cases) and control (305 cases) groups based on the outcome of the 12-month angiographic follow-up. The clinical and angiographic features of the participants were analyzed. Results: The adenosine diphosphate-induced platelet aggregation (ADP-IPA) rate and levels of lipoprotein (a) (Lp(a)) in the NCTOL progression group were significantly higher than those in the control group (51.89 ± 14.81 vs. 39.63 ± 17.12, P < 0.01; 0.22 ± 0.26 vs. 0.14 ± 0.18, P < 0.05, respectively). Logistic regression showed that the ADP-IPA rate (odds ratio = 1.047, 95 % confidence interval: 1.014-1.082, P = 0.005) and Lp(a) (odds ratio = 11.972, 95 % confidence interval: 1.230-116.570, P = 0.033) were independent predictors of NCTOL progression. Partial correlation analysis demonstrated that the ADP-IPA rate was positively correlated with NCTOL progression (r = 0. 351, P < 0.001). Receiver operating characteristic curve showed that the boundary point of the ADP-IPA rate to predict NCTOL progression was 30 % (sensitivity, 86.2 %; specificity, 68.9 %). Conclusions: NCTOL progression is an important cause of recurrent PCI in patients with coronary artery disease after PCI for CTO lesions. The ADP-IPA rate is a useful predictor for NCTOL progression in patients with unstable angina who undergo PCI for CTO lesions.

11.
Opt Express ; 32(6): 9958-9966, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571219

RESUMO

In this study, a three-dimensional (3D) laser micromachining system with an integrated sub-100 nm resolution in-situ measurement system was proposed. The system used the same femtosecond laser source for in-situ measurement and machining, avoiding errors between the measurement and the machining positions. It could measure the profile of surfaces with an inclination angle of less than 10°, and the measurement resolution was greater than 100 nm. Consequently, the precise and stable movement of the laser focus could be controlled, enabling highly stable 3D micromachining. The results showed that needed patterns could be machined on continuous surfaces using the proposed system. The proposed machining system is of great significance for broadening the application scenarios of laser machining.

12.
J Colloid Interface Sci ; 665: 232-239, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38522162

RESUMO

The self-assembled aerogels are considered as an efficient strategy to address the aggregation and restacking of Ti3C2Tx MXene nanosheets for high-performance supercapacitors. However, the low mechanical strength of the MXene aerogel results in the structural collapse of the self-standing supercapacitor electrode materials. Herein, a low-cost melamine sponge (MS) absorbed different cations (H+, K+, Mg2+, Fe2+, Co2+, Ni2+ and Al3+), serves as a carrier and crosslinker for loading MXene hydrogel induced by the absorbed cations on the skeleton surface and the pores of MS, resulting in the high loading mass MXene aerogels with high mechanical strength. The experimental results show that the Mg-Ti3C2Tx@MS aerogel exhibits the maximum area capacitance of 702.22 mF cm-2 at 3 mA cm-2, and the area capacitance is still 603.12 mF cm-2 even at 100 mA cm-2, indicating the high rate capability with a capacitance retention of 85.89 %. It is worth noting that the constructed asymmetric supercapacitor with activated carbon achieves high energy densities of 104.53 µWh cm-2 and 93.87 µWh cm-2 at 800 µW cm-2 and 7999 µW cm-2, respectively. Furthermore, the asymmetric supercapacitor shows the high cycling stability with 90.2 % capacity retention after 10,000 cycles. This work provides a feasible strategy to prepare Ti3C2Tx MXene aerogels with large layer spacing and high strength for high-performance supercapacitors.

13.
J Agric Food Chem ; 72(11): 5690-5698, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38447177

RESUMO

There is currently a lack of effective olfaction-based techniques to control diamondback moth (DBM) larvae. Identifying behaviorally active odorants for DBM larvae and exploring their recognition mechanisms can provide insights into olfaction-based larval control strategies. Through the two-choice assay, (E,E)-2,6-farnesol (farnesol) was identified as a compound exhibiting significant attractant activity toward DBM larvae, achieving an attraction index of 0.48 ± 0.13. PxylGOBP1 and PxylGOBP2, highly expressed in the antennae of DBM larvae, both showed high affinity toward farnesol. RNAi technology was used to knock down PxylGOBP1 and PxylGOBP2, revealing that the attraction of DBM larvae to farnesol nearly vanished following the knockdown of PxylGOBP2, indicating its critical role in recognizing farnesol. Further investigation into the PxylGOBP2-farnesol interaction revealed the importance of residues like Thr9, Trp37, and Phe118 in PxylGOBP2's binding to farnesol. This research is significant for unveiling the olfactory mechanisms of DBM larvae and developing larval behavior regulation techniques.


Assuntos
Farneseno Álcool , Mariposas , Animais , Larva/genética , Farneseno Álcool/farmacologia , Farneseno Álcool/metabolismo , Odorantes , Mariposas/metabolismo , Olfato
14.
Phytomedicine ; 128: 155362, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38522312

RESUMO

BACKGROUND: Stroke is a leading cause of disability and death worldwide. Currently, there is a lack of clinically effective treatments for the brain damage following ischemic stroke. Catalpol is a bioactive compound derived from the traditional Chinese medicine Rehmannia glutinosa and shown to be protective in various neurological diseases. However, the potential roles of catalpol against ischemic stroke are still not completely clear. PURPOSE: This study aimed to further elucidate the protective effects of catalpol against ischemic stroke. METHODS: A rat permanent middle cerebral artery occlusion (pMCAO) and oxygen-glucose deprivation (OGD) model was established to assess the effect of catalpol in vivo and in vitro, respectively. Behavioral tests were used to examine the effects of catalpol on neurological function of ischemic rats. Immunostaining was performed to evaluate the proliferation, migration and differentiation of neural stem cells (NSCs) as well as the angiogenesis in each group. The protein level of related molecules was detected by western-blot. The effects of catalpol on cultured NSCs as well as brain microvascular endothelial cells (BMECs) subjected to OGD in vitro were also examined by similar methods. RESULTS: Catalpol attenuated the neurological deficits and improved neurological function of ischemic rats. It stimulated the proliferation of NSCs in the subventricular zone (SVZ), promoted their migration to the ischemic cortex and differentiation into neurons or glial cells. At the same time, catalpol increased the cerebral vessels density and the number of proliferating cerebrovascular endothelial cells in the infracted cortex of ischemic rats. The level of SDF-1α and CXCR4 in the ischemic cortex was found to be enhanced by catalpol treatment. Catalpol was also shown to promote the proliferation and migration of cultured NSCs as well as the proliferation of BMECs subjected to OGD insult in vitro. Interestingly, the impact of catalpol on cultured cells was inhibited by CXCR4 inhibitor AMD3100. Moreover, the culture medium of BMECs containing catalpol promoted the proliferation of NSCs, which was also suppressed by AMD3100. CONCLUSION: Our data demonstrate that catalpol exerts neuroprotective effects by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway, suggesting the therapeutic potential of catalpol in treating cerebral ischemia.


Assuntos
Quimiocina CXCL12 , Glucosídeos Iridoides , AVC Isquêmico , Neurogênese , Ratos Sprague-Dawley , Receptores CXCR4 , Rehmannia , Animais , Glucosídeos Iridoides/farmacologia , Receptores CXCR4/metabolismo , Neurogênese/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Masculino , Rehmannia/química , AVC Isquêmico/tratamento farmacológico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Células-Tronco Neurais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ratos , Fármacos Neuroprotetores/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Células Cultivadas , Angiogênese
15.
Mol Psychiatry ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503925

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions, communication deficits and repetitive behaviors. A study of autistic human subjects has identified RFWD2 as a susceptibility gene for autism, and autistic patients have 3 copies of the RFWD2 gene. The role of RFWD2 as an E3 ligase in neuronal functions, and its contribution to the pathophysiology of ASD, remain unknown. We generated RFWD2 knockin mice to model the human autistic condition of high gene dosage of RFWD2. We found that heterozygous knockin (Rfwd2+/-) male mice exhibited the core symptoms of autism. Rfwd2+/- male mice showed deficits in social interaction and communication, increased repetitive and anxiety-like behavior, and spatial memory deficits, whereas Rfwd2+/- female mice showed subtle deficits in social communication and spatial memory but were normal in anxiety-like, repetitive, and social behaviors. These autistic-like behaviors in males were accompanied by a reduction in dendritic spine density and abnormal synaptic function on layer II/III pyramidal neurons in the prelimbic area of the medial prefrontal cortex (mPFC), as well as decreased expression of synaptic proteins. Impaired social behaviors in Rfwd2+/- male mice were rescued by the expression of ETV5, one of the major substrates of RFWD2, in the mPFC. These findings indicate an important role of RFWD2 in the pathogenesis of autism.

16.
Oral Dis ; 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38462885

RESUMO

OBJECTIVE: Ferroptosis has been defined as a novel form of regulated cell death characterized by iron-dependent lipid peroxidation. Manganese has been used to induce ferroptosis in cancer cells recently. This study aims to investigate whether manganese can induce ferroptosis in oral squamous cell carcinoma (OSCC) and the underlying biological mechanisms. MATERIALS AND METHODS: Cancer cells with or without manganese treatment were analyzed by RNA-sequencing to identify ferroptosis-related genes. Next, the activation of YAP/TAZ/ACSL4-ferroptosis signaling pathway was detected. Bioinformatic analysis and immunofluorescence assay were used to explore the phase separation of YAP/TAZ. Finally, specimens of OSCC patients were applied to analyze the clinical significance of YAP/TAZ/ACSL4. RESULTS: RNA-sequencing analysis showed the ferroptosis-related genes and YAP/TAZ were upregulated after manganese treatment. The results of immunofluorescence, ELISA, western blotting, etc. further confirmed that manganese-induced ferroptosis depends on YAP/TAZ/ACSL4 signaling pathway. Moreover, the activation of ACSL4 was achieved by YAP/TAZ phase separation. The survival analysis in OSCC specimen suggested that the higher level of YAP/TAZ-ACSL4 axis expression indicates longer survival. CONCLUSIONS: Manganese induces YAP/TAZ phase separation and subsequent ACSL4 activation via YAP/TAZ nuclear translocation, which facilitates ferroptosis of OSCC. Then YAP/TAZ-ACSL4 axis can be used as a potential prognostic predictor of OSCC patients.

17.
Urol Int ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38432217

RESUMO

The incidence of urinary tract stones is increasing worldwide, with a notably high recurrence rate. Among upper urinary tract stones, a significant proportion comprises uric acid stones. This study aims to rapid and reliable identification of uric acid stones in the upper urethra by gathering comprehensive biochemical profiles, urinalysis, and CT scan data from 276 patients diagnosed with kidney and ureteral stones. Leveraging machine learning techniques, the goal is to establish multiple predictive models that can accurately identify uric acid stones.

18.
J Appl Clin Med Phys ; 25(5): e14308, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38368614

RESUMO

PURPOSE: Proton therapy is sensitive to anatomical changes, often occurring in head-and-neck (HN) cancer patients. Although multiple studies have proposed online adaptive proton therapy (APT), there is still a concern in the radiotherapy community about the necessity of online APT. We have performed a retrospective study to investigate the potential dosimetric benefits of online APT for HN patients relative to the current offline APT. METHODS: Our retrospective study has a patient cohort of 10 cases. To mimic online APT, we re-evaluated the dose of the in-use treatment plan on patients' actual treatment anatomy captured by cone-beam CT (CBCT) for each fraction and performed a templated-based automatic replanning if needed, assuming that these were performed online before treatment delivery. Cumulative dose of the simulated online APT course was calculated and compared with that of the actual offline APT course and the designed plan dose of the initial treatment plan (referred to as nominal plan). The ProKnow scoring system was employed and adapted for our study to quantify the actual quality of both courses against our planning goals. RESULTS: The average score of the nominal plans over the 10 cases is 41.0, while those of the actual offline APT course and our simulated online course is 25.8 and 37.5, respectively. Compared to the offline APT course, our online course improved dose quality for all cases, with the score improvement ranging from 0.4 to 26.9 and an average improvement of 11.7. CONCLUSION: The results of our retrospective study have demonstrated that online APT can better address anatomical changes for HN cancer patients than the current offline replanning practice. The advanced artificial intelligence based automatic replanning technology presents a promising avenue for extending potential benefits of online APT.


Assuntos
Neoplasias de Cabeça e Pescoço , Órgãos em Risco , Terapia com Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Humanos , Estudos Retrospectivos , Neoplasias de Cabeça e Pescoço/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Órgãos em Risco/efeitos da radiação , Tomografia Computadorizada de Feixe Cônico/métodos , Prognóstico
19.
Gene ; 908: 148281, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38360124

RESUMO

The upregulation of methyltransferase-like 3 (METTL3) has been associated with the progression of esophageal cancer. However, METTL3-induced N6-methyladenosine (m6A) alterations on the downstream target mRNAs in esophageal squamous cell carcinoma (ESCC) are not yet fully understood. Our study revealed that silencing METTL3 resulted in a significant decrease in ESCC cell proliferation and metastasis in vitro and in vivo. Additionally, the adhesion molecule with Ig like domain 2 (AMIGO2) was identified as a potential downstream target of both METTL3 and YTH Domain-Containing Protein 1 (YTHDC1) in ESCC cells. Functionally, AMIGO2 augmented the malignant behaviors of ESCC cells in vitro and in vivo, and its overexpression can rescue the inhibition of the proliferation and migration in ESCC cells induced by METTL3 or YTHDC1 knockdown. Furthermore, our findings revealed that knockdown of METTL3 decreased m6A modification in the 5'-untranslated regions (5'UTR) of AMIGO2 precursor mRNA (pre-mRNA), and YTHDC1 interacted with AMIGO2 pre-mRNA to regulate AMIGO2 expression by modulating the splicing process of AMIGO2 pre-mRNA in ESCC cells. These findings highlighted a novel role of the METTL3-m6A-YTHDC1-AMIGO2 axis in regulating ESCC cell proliferation and motility, suggesting its potential as a therapeutic target for ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Precursores de RNA/metabolismo , Proliferação de Células/genética , Regulação para Cima , Metiltransferases/genética , Metiltransferases/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fatores de Processamento de RNA/genética
20.
Sci Total Environ ; 919: 170916, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38350563

RESUMO

Biochar with adjustable redox activity is an effective strategy for immobilization of excess arsenic (As(III)) contaminated soil. However, biochar exhibits limitations in terms of electron transfer efficiency and immobilization efficiency due to insufficient activation energy. In this study, As(III) in the soil was rapidly immobilized by adding magnetic biochar (Fe-BC) and introducing microwave irradiation energy to enhance electron transport efficiency. The results showed that the pore structure and iron species (ZVI, Fe3O4) loaded onto the biochar could be modulated by controlling the temperature and time of microwave pyrolysis, which enhanced the microwave absorption capacity and the immobilization performance of As. After adding Fe-BC (10 wt%) and treating with microwave irradiation for 3 h, the content of As(III) in the soil was reduced to 54.56 %. Compared with the conventional heating treatment, the percentage of stabilized As (residual form) increased by 11.21 %. The localized hot spots formed through the absorption of microwave energy by biochar promote the formation of arsenic-containing mineral crystals (FeAsO4 and Fe3AsO7), thus enhancing the immobilization efficiency. In addition, microwave-induced electron transfer facilitated the oxidation of As(III) to As(V) by surface quinone and carbonyl groups on the Fe-BC. Density functional theory calculation further proved that the surface groups of the Fe-BC had a stronger electron-withdrawing ability under microwave irradiation, thereby promoting the adsorption and immobilization of As(III). This work provided a new perspective on the technology of rapid remediation of heavy metals contaminated soil using biochar.

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