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1.
Micromachines (Basel) ; 15(10)2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39459116

RESUMEN

A rotary vibration-assisted polishing device (RVAPD) is designed to enhance polishing force by converting PZT's linear motion into the rotary motion of a central platform via a flexible mechanism, improving material surface quality. The RVAPD is optimized, simulated, and tested to meet high-frequency and large-amplitude non-resonant vibration polishing requirements. Its structure, designed using theoretical models and finite element software, offers a wide range of polishing parameters. Performance parameters are validated through open-loop tests, confirming effectiveness in polishing experiments. The lever mechanism and Hoeckens connection enhance vibration parameters and motion efficiency, reducing surface flaws in SiC and improving uniformity. Adjusting the RVAPD structure and using the proposed method significantly improve SiC surface quality.

2.
Front Cardiovasc Med ; 11: 1433011, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39399511

RESUMEN

Background: Cardiopulmonary bypass (CPB) triggers a strong inflammatory response in cardiovascular surgery patients during the perioperative period. This article mainly focuses on the perioperative application of novel inflammatory biomarkers in cardiovascular surgeries involving CPB. Methods: Patients were divided into a CPB group and a non-CPB group according to whether they underwent CPB during cardiovascular surgery. Novel inflammatory biomarkers and clinical results were recorded. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), platelet × neutrophil/lymphocyte ratio (SII), and monocyte × platelet × neutrophil/lymphocyte ratio (PIV) were calculated. The primary outcomes were perioperative prognosis between the CPB and non-CPB groups. The secondary outcomes included perioperative alterations of novel inflammatory biomarkers in the CPB group and predictive values of novel inflammatory biomarkers for postoperative infection and acute kidney injury. Results: A total of 332 patients were initially included in the study. Before propensity score matching (PSM), there were 96 patients in the CPB group and 236 patients in the non-CPB group. After PSM, both groups included 58 patients each. Compared with the non-CPB group, the CPB group had a higher proportion of intraoperative transfusion of blood products (63.79% vs. 6.90%, P < 0.001), specifically for red blood cells (58.62% vs. 3.45%, P < 0.001) and plasma (41.38% vs. 1.72, P < 0.001), exhibited a higher drainage fluid volume within 24 h [380 (200-550) ml vs. 200 (24-330) ml, P = 0.002], and required longer durations of mechanical ventilation [14.3 (6.6-21.3) h vs. 5.75 (4.08-10.1) h, P < 0.001] and ICU stay [48.78 (44.92-89.38) h vs. 27.16 (21.67-46.25) h, P < 0.001]. After surgery, NLR [14.00 (9.93-23.08) vs. 11.55 (7.38-17.38), P = 0.043] was higher in the CPB group, while the PIV, PLR, and SII in the CPB group were lower than those in the non-CPB group on the first day after surgery. Conclusions: Cardiovascular surgeries involving CPB exhibit a poorer prognosis compared to non-CPB procedures. Novel inflammatory biomarkers, including PLR, PIV, and SII, may offer valuable insights into the degree of postoperative inflammation, with NLR emerging as a potentially reliable prognostic indicator.

3.
Int J Mol Sci ; 25(19)2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39409070

RESUMEN

Andrographis paniculata is known for its diterpenoid medicinal compounds with antibacterial and anti-inflammatory properties. However, it faces production and cultivation challenges due to low temperatures (LTs). Cytochrome P450 monooxygenases (CYPs) are key enzymes in diterpenoid accumulation. Nevertheless, the functions and LT-related expression patterns of diterpenoid pathway CYPs in Andrographis paniculata remain poorly understood. In this study, 346 CYPs were discovered in Andrographis paniculata. Among them, 328 CYPs belonged to 42 known subfamilies. The remaining 17 CYPs might have represented novel subfamilies unique to this species. A total of 65 candidate CYPs associated with diterpenoid modification were identified. Of these, 50 were transmembrane proteins, and 57 were localized to chloroplasts. The CYP71 subfamily was the most abundant and had the highest motif diversity. Promoters of all candidate CYPs commonly contained elements responsive to gibberellins (GAs), methyl jasmonate (MeJA), and abiotic stresses. Notably, the XP_051152769 protein, corresponding to a CYP gene over 40,000 bp in length, featured an extraordinarily long intron (40,751 nts). Functional elements within this intron were related to LT, GAs, and dehydration pathways. Based on the promoter element arrangement and subfamily classification, 10 representative candidate CYPs were selected. Under LT stress, significant expression changes were observed in three representative CYPs: CYP71D, ent-kaurenoic acid oxidase (KAO), and ent-kaurene oxidase (KO). KAO and KO were significantly upregulated during early LT stress. KAO and KO interacted with each other and jointly interacted with GA20OX2-like. CYP71D acted as a negative response factor to LT stress. Among the 37 proteins interacting with CYP71D, 95% were CYPs. This study provides a critical preliminary foundation for investigating the functions of diterpenoid pathway CYPs in Andrographis paniculata, thereby facilitating the development of LT-tolerant cultivars.


Asunto(s)
Andrographis , Sistema Enzimático del Citocromo P-450 , Diterpenos , Regulación de la Expresión Génica de las Plantas , Andrographis/genética , Andrographis/metabolismo , Diterpenos/metabolismo , Diterpenos/farmacología , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Regiones Promotoras Genéticas , Respuesta al Choque por Frío/genética , Frío , Estrés Fisiológico/genética , Perfilación de la Expresión Génica , Genoma de Planta
4.
Nanotechnology ; 36(1)2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39378893

RESUMEN

Using a first-principles approach, this study delves into the effects of strain and electrostatic doping on the electronic and magnetic properties of the GaN/VTe2van der Waals (vdW) heterostructure. The results reveal that when the GaN/VTe2vdW heterostructure is doped with 0.1h/0.2hof electrostatic charge, its magnetization direction undergoes a remarkable reversal, shifting from out-of-plane orientation to in-plane direction. Therefore, we conduct a thorough investigation into the influence of electron orbitals on magnetic anisotropy energy. In addition, as the strain changes from -1% to 1%, the 100% spin polarization region of the GaN/VTe2vdW heterostructure becomes smaller. It is worth noting that at a doping concentration of 0.1h, the GaN/VTe2vdW heterostructure has a Curie temperature of 30 K above room temperature. This comprehensive study provides valuable insights and provides a reference for analyzing the electronic and magnetic properties of low-dimensional systems.

5.
Adv Sci (Weinh) ; : e2410927, 2024 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-39435757

RESUMEN

Enriched environment (EE), characterized by multi-sensory stimulation, represents a non-invasive alternative for alleviating epileptic seizures. However, the mechanism by which EE exerts its therapeutic impact remains incompletely understood. Here, it is elucidated that EE mitigates seizure susceptibility through the augmentation of adult neurogenesis within the entorhinal cortex (EC) circuit. A substantial upregulation of adult hippocampal neurogenesis concomitant with a notable reduction in seizure susceptibility has been found following exposure to EE. EE-enhanced adult-born dentate granule cells (abDGCs) are functionally activated during seizure events. Importantly, the selective activation of abDGCs mimics the anti-seizure effects observed with EE, while their inhibition negates these effects. Further, whole-brain c-Fos mapping demonstrates increased activity in DG-projecting EC CaMKIIα+ neurons in response to EE. Crucially, EC CaMKIIα+ neurons exert bidirectional modulation over the proliferation and maturation of abDGCs that can activate local GABAergic interneurons; thus, they are essential components for the anti-seizure effects mediated by EE. Collectively, this study provides compelling evidence regarding the circuit mechanisms underlying the effects of EE treatment on epileptic seizures, shedding light on the involvement of the EC-DG circuit in augmenting the functionality of abDGCs. This may help for the translational application of EE for epilepsy management.

7.
Neuroimage Clin ; 44: 103681, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39368336

RESUMEN

The spatial distribution patterns of cerebral microbleeds are associated with different types of cerebral small vessel disease (CSVD). This study aims to examine the disparities in brain imaging markers of CSVD among patients diagnosed with possible amyloid and non-amyloid small vessel disease. The head MR scans including susceptibility-weighted imaging (SWI) sequences from 351 patients at our institute were collected for analysis. CSVD imaging markers were quantified or graded across various CSVD dimensions in the patient images. Patients were categorized into the cerebral amyloid angiopathy group (CAA), hypertensive arteriopathy group (HA), or mixed small vessel disease group (Mixed), based on the spatial distribution of microbleeds. White matter lesions (WML) were segmented using an artificial neural network and assessed via a voxel-wise approach. Significant differences were observed among the three groups in several indices: microbleed count, lacune count at the centrum semiovale and basal ganglia levels, grade of enlarged perivascular space (EPVS) at the basal ganglia, and white matter lesion volume. These indices were substantially higher in the Mixed group compared to the other groups. Additionally, the incidences of cerebral hemorrhages (χ2 = 7.659, P = 0.006) and recent small subcortical infarcts (χ2 = 4.660, P = 0.031) were significantly more frequent in the HA group than in the CAA group. These results indicate that mixed spatial distribution patterns of microbleeds demonstrated the highest burden of cerebral small vessel disease. Microbleeds located in the deep brain regions were associated with a higher incidence of recent small subcortical infarcts and cerebral hemorrhages compared to those in the cortical areas.

8.
Talanta ; 282: 126960, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39362038

RESUMEN

Accurate analysis of multiple microRNA (miRNA) levels is significantly valuable for early diagnosis of colorectal cancer noninvasively considering the miRNA expression is highly relevant to the occurrence and progression of cancer. However, the low abundance and high sequence homology of miRNAs make their precise determination extremely challenging. Here, we developed a universal and programmable diagnostic strategy allowing for analyzing multiple colorectal cancer-associated miRNAs. The system combined sequentially programmable rolling circle transcription (RCT) and the CRISPR/Cas12a system with high trans-cleavage activity to achieve highly sensitive and specific detection of four target miRNAs. Owing to the remarkable performance of universal RCT-Cas12a strategy, this biosensor could detect miR-21, miR-17, miR-31 and miR-92a with a LOD of 2.1, 1.6, 3.7 and 1.0 pM, respectively. This strategy had a unique advantage in distinguishing human normal colon epithelial cells lines (NCM460) from human colon cancer cells (HT29). In particular, the designed system exhibited superior analytical capability in distinguishing paracancerous and colorectal cancer tissues from patients undergoing colorectal cancer surgery. This arbitrarily programmable, scalable, fast and specific strategy potentially offered an attractive alternative to handle varied challenges encountered with CRISPR-based systems, and held immense promise in scientific research and clinical applications.

9.
Neural Netw ; 180: 106756, 2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39332210

RESUMEN

This study introduces an innovative neural network framework named spectral integrated neural networks (SINNs) to address both forward and inverse dynamic problems in three-dimensional space. In the SINNs, the spectral integration technique is utilized for temporal discretization, followed by the application of a fully connected neural network to solve the resulting partial differential equations in the spatial domain. Furthermore, the polynomial basis functions are employed to expand the unknown function, with the goal of improving the performance of SINNs in tackling inverse problems. The performance of the developed framework is evaluated through several dynamic benchmark examples encompassing linear and nonlinear heat conduction problems, linear and nonlinear wave propagation problems, inverse problem of heat conduction, and long-time heat conduction problem. The numerical results demonstrate that the SINNs can effectively and accurately solve forward and inverse problems involving heat conduction and wave propagation. Additionally, the SINNs provide precise and stable solutions for dynamic problems with extended time durations. Compared to commonly used physics-informed neural networks, the SINNs exhibit superior performance with enhanced convergence speed, computational accuracy, and efficiency.

10.
Waste Manag ; 190: 186-196, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39332347

RESUMEN

Tremendous amount of sludge is generated annually from freshwater treatment or sewage. The high temperature slagging co-gasification converts the sludge to slag showing the potential application for construction material. In this study, the physico-chemical properties of 4 types of slags generated from the co-gasification of municipal solid waste (MSW) with sludge from freshwater treatment or sewage, and ashes from sludge incineration are comprehensively analyzed. Leaching performance of the sludge-derived slag and mortar (with slag as the fine aggregate), as determined based on Toxicity Characteristic Leaching Procedure (TCLP), batch leaching and column leaching tests, indicates the slag can be considered safe for reutilization. Compressive strength test demonstrates that the mortars perform excellently and have the potential to replace sand in concrete production. The consolidation coefficient of slag (1.6 - 39.1 m2/year) is lower than the sandy silt but higher than clay. Additionally, the coefficient of permeability (∼1.96 × 10-3 m/s), angle of shearing resistance (∼39°), and undrained shear strength (375.5 ± 54.8 kPa) of the slag are comparable to sand. The life cycle assessment (LCA) is also conducted to evaluate the environmental impacts and benefits of reutilizing sludge-derived slag as an alternative material for concrete production and land reclamation.

11.
Curr Med Chem ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39248068

RESUMEN

BACKGROUND: Glioblastoma is the most common type of brain cancer, with a prognosis that is unfortunately poor. Despite considerable progress in the field, the intricate molecular basis of this cancer remains elusive. AIM: The aim of this study was to identify genetic indicators of glioblastoma and reveal the processes behind its development. OBJECTIVE: The advent and integration of supercomputing technology have led to a significant advancement in gene expression analysis platforms. Microarray analysis has gained recognition for its pivotal role in oncology, crucial for the molecular categorization of tumors, diagnosis, prognosis, stratification of patients, forecasting tumor responses, and pinpointing new targets for drug discovery. Numerous databases dedicated to cancer research, including the Gene Expression Omnibus (GEO) database, have been established. Identifying differentially expressed genes (DEGs) and key genes deepens our understanding of the initiation of glioblastoma, potentially unveiling novel markers for diagnosis and prognosis, as well as targets for the treatment of glioblastoma. METHODS: This research sought to discover genes implicated in the development and progression of glioblastoma by analyzing microarray datasets GSE13276, GSE14805, and GSE109857 from the GEO database. DEGs were identified, and a function enrichment analysis was performed. Additionally, a protein-protein interaction network (PPI) was constructed, followed by module analysis using the tools STRING and Cytoscape. RESULTS: The analysis yielded 88 DEGs, consisting of 66 upregulated and 22 downregulated genes. These genes' functions and pathways primarily involved microtubule activity, mitotic cytokinesis, cerebral cortex development, localization of proteins to the kinetochore, and the condensation of chromosomes during mitosis. A group of 27 pivotal genes was pinpointed, with biological process analysis indicating significant enrichment in activities, such as division of the nucleus during mitosis, cell division, maintaining cohesion between sister chromatids, segregation of sister chromatids during mitosis, and cytokinesis. The survival analysis indicated that certain genes, including PCNA clamp-associated factor (PCLAF), ribonucleoside- diphosphate reductase subunit M2 (RRM2), nucleolar and spindle-associated protein 1 (NUSAP1), and kinesin family member 23 (KIF23), could be instrumental in the development, invasion, or recurrence of glioblastoma. CONCLUSION: The identification of DEGs and key genes in this study advances our comprehension of the molecular pathways that contribute to the oncogenesis and progression of glioblastoma. This research provides valuable insights into potential diagnostic and therapeutic targets for glioblastoma.

12.
Hernia ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287831

RESUMEN

PURPOSE: This study aimed to develop, validate, and evaluate machine learning (ML) algorithms for predicting Surgical site infections (SSI) and surgical site occurrences (SSO) after elective open inguinal hernia surgery. METHODS: A cohort of 491 patients who underwent elective open inguinal hernia surgery at Fudan University Affiliated Huadong Hospital between December 2019 and December 2020 was enrolled. To create a strong prediction model, we employed five ML methods: generalized linear model, random forest (RF), support vector machines, neural network, and gradient boosting machine. Based on the best performing model, we devised online calculators to facilitate clinicians' access to a linear predictor for patients. The receiver operating characteristic curve was utilized to evaluate the model's discriminatory capability and predictive accuracy. RESULTS: The incidence rates of SSI and SSO were 4.68% and 13.44%, respectively. Four variables (diabetes, recurrence, antibiotic prophylaxis, and duration of surgery) were identified for SSI prediction, while four variables (diabetes, size of hernias, albumin levels, and antibiotic prophylaxis) were included for SSO prediction. In the test set, the RF model showed the best predictive ability (SSI: area under the curve (AUC) = 0.849, sensitivity = 0.769, specificity = 0.769, and accuracy = 0.769; SSO: AUC = 0.740, sensitivity = 0.513, specificity = 0.821, and accuracy = 0.667). Online calculators have been developed to assess patients' risk of SSI ( https://wuqian17.shinyapps.io/predictionSSI/ ) and SSO ( https://wuqian17.shinyapps.io/predictionSSO/ ) after surgery. CONCLUSIONS: This study developed a prediction model for SSI/SSO using ML methods. It holds the potential to facilitate the selection of appropriate treatment options following elective open inguinal hernia surgery.

13.
J Mater Chem B ; 12(39): 10054-10067, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39258439

RESUMEN

The application of patch methods for repairing abdominal wall wounds presents a variety of challenges, such as adhesion and limited mobility due to inadequate mechanical strength and nonabsorbable materials. Among these complications, postoperative visceral adhesion and wound infection are particularly serious. In this study, a bilayered composite patch with a gelatin methacryloyl (GelMA)/sodium alginate (SA)-vancomycin (Van)@polycaprolactone (PCL) (GelMA/SA-Van@PCL) antibacterial layer was prepared via coaxial 3D printing and a polycaprolactone (PCL)-silicon dioxide (SiO2) antiadhesive layer (PCL-SiO2) was prepared via electrospinning and electrostatic spray for hernia repair. The evaluation of the physicochemical properties revealed that the composite patch had outstanding tensile properties (16 N cm-1), excellent swelling (swelling rate of 243.81 ± 12.52%) and degradation (degradation rate of 53.14 ± 3.02%) properties. Furthermore, the composite patch containing the antibiotic Van exhibited good antibacterial and long-term drug release properties. Both in vivo and in vitro experiments indicated that the composite patch displayed outstanding biocompatibility and antiadhesive properties and could prevent postoperative infections. In summary, the bilayered composite patch can effectively prevent postoperative complications while promoting tissue growth and repair and holds significant application potential in hernia repair.


Asunto(s)
Pared Abdominal , Antibacterianos , Gelatina , Poliésteres , Impresión Tridimensional , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Poliésteres/química , Poliésteres/farmacología , Animales , Pared Abdominal/cirugía , Pared Abdominal/patología , Gelatina/química , Vancomicina/farmacología , Vancomicina/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Alginatos/química , Metacrilatos/química , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Adherencias Tisulares/prevención & control , Adherencias Tisulares/tratamiento farmacológico , Ratones , Tamaño de la Partícula
14.
BMC Genomics ; 25(1): 836, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237905

RESUMEN

BACKGROUND: The KT/HAK/KUP is the largest K+ transporter family in plants, playing crucial roles in K+ absorption, transport, and defense against environmental stress. Sweet watermelon is an economically significant horticultural crop belonging to the genus Citrullus, with a high demand for K+ during its growth process. However, a comprehensive analysis of the KT/HAK/KUP gene family in watermelon has not been reported. RESULTS: 14 KT/HAK/KUP genes were identified in the genomes of each of seven Citrullus species. These KT/HAK/KUPs in watermelon were unevenly distributed across seven chromosomes. Segmental duplication is the primary driving force behind the expansion of the KT/HAK/KUP family, subjected to purifying selection during domestication (Ka/Ks < 1), and all KT/HAK/KUPs exhibit conserved motifs and could be phylogenetically classified into four groups. The promoters of KT/HAK/KUPs contain numerous cis-regulatory elements related to plant growth and development, phytohormone response, and stress response. Under K+ deficiency, the growth of watermelon seedlings was significantly inhibited, with cultivated watermelon experiencing greater impacts (canopy width, redox enzyme activity) compared to the wild type. All KT/HAK/KUPs in C. lanatus and C. amarus exhibit specific expression responses to K+-deficiency and drought stress by qRT-PCR. Notably, ClG42_07g0120700/CaPI482276_07g014010 were predominantly expressed in roots and were further induced by K+-deficiency and drought stress. Additionally, the K+ transport capacity of ClG42_07g0120700 under low K+ stress was confirmed by yeast functional complementation assay. CONCLUSIONS: KT/HAK/KUP genes in watermelon were systematically identified and analyzed at the pangenome level and provide a foundation for understanding the classification and functions of the KT/HAK/KUPs in watermelon plants.


Asunto(s)
Citrullus , Sequías , Filogenia , Proteínas de Plantas , Estrés Fisiológico , Citrullus/genética , Citrullus/metabolismo , Citrullus/crecimiento & desarrollo , Estrés Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Potasio/metabolismo , Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Familia de Multigenes , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Deficiencia de Potasio/genética , Deficiencia de Potasio/metabolismo , Regiones Promotoras Genéticas
15.
Artículo en Chino | MEDLINE | ID: mdl-39198952

RESUMEN

Objective To explore the risk factors for the returning of pediatric liver transplant recipients to the intensive care unit (ICU) and provide reference for the clinical decision-making after surgery. Methods A retrospective analysis was conducted with the information of all the pediatric patients who underwent liver transplantation in Ren Ji Hospital,Shanghai Jiao Tong University School of Medicine and were returned to the ICU from 2019 to 2021.The patients returned to the ICU during hospitalization and the reasons for the return were recorded.Each patient of ICU return was matched with three pediatric patients who did not return to the ICU during hospitalization.The basic information,the vital signs and laboratory indicators on the day of transfer from ICU,immunosuppressants and drug concentrations were compared between the two groups.Multivariate Logistic regression analysis was performed to explore the risk factors for the returning of pediatric liver transplant recipients to the ICU. Results The returning rate of pediatric liver transplant recipients to the ICU was 4.36%,and it was 16.00% within 48 h.The main reasons for the return included respiratory complications,abdominal infections,and hepatic vascular occlusion.Multivariate Logistic regression analysis showed that post-operative red blood cell transfusion (OR=4.554,95%CI=1.743-11.901,P=0.002) and high serum level of uric acid (OR=1.005,95%CI=1.001-1.009,P=0.014) were the risk factors for returning to the ICU.High diastolic blood pressure (OR=0.922,95%CI=0.885-0.960,P<0.001) and high total protein level (OR=0.937,95%CI=0.891-0.986,P=0.012) were the protective factors for returning to the ICU. Conclusion Post-operative red blood cell transfusion and high serum level of uric acid are independent risk factors for the returning of pediatric liver transplant recipients to the ICU.

16.
Immunity ; 57(9): 2030-2042.e8, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39116878

RESUMEN

Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.


Asunto(s)
Hemodinámica , Hipertensión , Microglía , Núcleo Hipotalámico Paraventricular , Sistema Nervioso Simpático , Núcleo Hipotalámico Paraventricular/metabolismo , Animales , Microglía/metabolismo , Hipertensión/fisiopatología , Ratones , Sistema Nervioso Simpático/fisiopatología , Masculino , Ratones Endogámicos C57BL , Adenosina Trifosfato/metabolismo , Receptores Purinérgicos P2Y12/metabolismo , Inflamación/inmunología , Presión Sanguínea , Neuronas/metabolismo
17.
Transl Psychiatry ; 14(1): 325, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107319

RESUMEN

Understanding the neuropathogenesis of impaired social cognition in autism spectrum disorders (ASD) is challenging. Altered cortical parvalbumin-positive (PV+) interneurons have been consistently observed in ASD, but their roles and the underlying mechanisms remain poorly understood. In our study, we observed a downward-shifted spectrum of PV expression in the developing medial prefrontal cortex (mPFC) of ASD mouse models due to decreased activity of PV+ neurons. Surprisingly, chemogenetically suppressing PV+ neuron activity during postnatal development failed to induce ASD-like behaviors. In contrast, lowering excitatory activity in the developing mPFC not only dampened the activity state and PV expression of individual PV+ neurons, but also replicated ASD-like social deficits. Furthermore, enhancing excitation, but not PV+ interneuron-mediated inhibition, rescued social deficits in ASD mouse models. Collectively, our findings propose that reduced excitatory activity in the developing mPFC may serve as a shared local circuitry mechanism triggering alterations in PV+ interneurons and mediating impaired social functions in ASD.


Asunto(s)
Trastorno del Espectro Autista , Modelos Animales de Enfermedad , Interneuronas , Parvalbúminas , Corteza Prefrontal , Cognición Social , Trastorno del Espectro Autista/fisiopatología , Animales , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/metabolismo , Ratones , Interneuronas/metabolismo , Interneuronas/fisiología , Parvalbúminas/metabolismo , Masculino , Conducta Animal/fisiología , Conducta Social , Ratones Endogámicos C57BL , Femenino
18.
J Biomed Res ; 38(4): 307-321, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-39113127

RESUMEN

Liquid-liquid phase separation, a novel biochemical phenomenon, has been increasingly studied for its medical applications. It underlies the formation of membrane-less organelles and is involved in many cellular and biological processes. During transcriptional regulation, dynamic condensates are formed through interactions between transcriptional elements, such as transcription factors, coactivators, and mediators. Cancer is a disease characterized by uncontrolled cell proliferation, but the precise mechanisms underlying tumorigenesis often remain to be elucidated. Emerging evidence has linked abnormal transcriptional condensates to several diseases, especially cancer, implying that phase separation plays an important role in tumorigenesis. Condensates formed by phase separation may have an effect on gene transcription in tumors. In the present review, we focus on the correlation between phase separation and transcriptional regulation, as well as how this phenomenon contributes to cancer development.

19.
Front Endocrinol (Lausanne) ; 15: 1419913, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104813

RESUMEN

Like the ovaries and prostate, the thyroid exhibits characteristic hormone secretion and regulation. Thyroid cancer (TC), especially differentiated thyroid carcinoma, has typical sex-specific and age-specific hormone-driven clinical features. Previous research has primarily focused on the effects of thyroid stimulating hormone, thyroid hormones, and estrogens on the onset and progression of TC, while the roles of growth hormone (GH), androgens, and glucocorticoids have largely been overlooked. Similarly, few studies have investigated the interactions between hormones and hormone systems. In fact, numerous studies of patients with acromegaly have shown that serum levels of GH and insulin-like growth factor-1 (IGF-1) may be associated with the onset and progression of TC, although the influences of age, sex, and other risk factors, such as obesity and stress, remain unclear. Sex hormones, the GH/IGF axis, and glucocorticoids are likely involved in the onset and progression of TC by regulating the tumor microenvironment and metabolism. The aim of this review was to clarify the roles of hormones and hormone systems in TC, especially papillary thyroid carcinoma, as references for further investigations.


Asunto(s)
Sistema Hipotálamo-Hipofisario , Glándula Tiroides , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Sistema Hipotálamo-Hipofisario/metabolismo , Glándula Tiroides/metabolismo , Hormonas Tiroideas/metabolismo , Animales , Factor I del Crecimiento Similar a la Insulina/metabolismo
20.
Front Genet ; 15: 1372164, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39165753

RESUMEN

Background: Preeclampsia (PE) is a global pregnancy concern, characterized by hypertension with an unclear etiology. This study employs Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to clarify its genetic and molecular roots, offering insights into diagnosis and treatment avenues. Methods: We integrated PE-specific genome-wide association study (GWAS) data, expression and protein quantitative trait loci (eQTL and pQTL) data, and single-cell data from peripheral blood mononuclear cells (PBMCs). We identified highly variable genes using single-cell information and employed MR to determine potential causality. We also combined pQTL and GWAS data, discerned genes positively associated with PE through scRNA-seq, and leveraged the Enrichr platform to unearth drug-gene interactions. Results: Our scRNA-seq pinpointed notable cell type distribution variances, especially in T helper cells (Th cells), between PE and control groups. We unveiled 591 highly variable genes and 6 directly PE-associated genes. Although MR revealed correlations with PE risk, pQTL analysis was inconclusive due to data constraints. Using DSigDB, 93 potential therapeutic agents, like Retinoic acid targeting core genes (IFITM3, NINJ1, COTL1, CD69, and YWHAZ), emerged as prospective multi-target treatments. Conclusion: Utilizing MR and scRNA-seq, this study underscores significant cellular disparities, particularly in Th cells, and identifies crucial genes related to PE. Despite some limitations, these genes have been revealed in PE's underlying mechanism. Potential therapeutic agents, such as Retinoic acid, suggest promising treatment pathways.

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