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1.
Int J Mol Med ; 54(3)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38963054

RESUMO

PANoptosis, a complex form of proinflammatory programmed cell death, including apoptosis, pyroptosis and necroptosis, has been an emerging concept in recent years that has been widely reported in cancer, infectious diseases and neurological disorders. Cardiovascular diseases (CVDs) are an important global health problem, posing a serious threat to individuals' lives. An increasing body of research shows that inflammation has a pivotal role in CVDs, which provides an important theoretical basis for PANoptosis to promote the progression of CVDs. To date, only sporadic studies on PANoptosis in CVDs have been reported and its role in the field of CVDs has not been fully explored. Elucidating the various modes of cardiomyocyte death, the specific molecular mechanisms and the links among the various modes of death under various stressful stimuli is of notable clinical significance for a deeper understanding of the pathophysiology of CVDs. The present review summarizes the molecular mechanisms of apoptosis, pyroptosis, necroptosis and PANoptosis and their prospects in the field of CVDs.


Assuntos
Doenças Cardiovasculares , Necroptose , Piroptose , Humanos , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/metabolismo , Animais , Apoptose/fisiologia , Morte Celular Regulada , Inflamação/patologia , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo
2.
Bioact Mater ; 39: 287-301, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38827170

RESUMO

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

3.
Front Bioeng Biotechnol ; 12: 1400614, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887613

RESUMO

Background and objective: Our group has developed a novel artificial cervical joint complex (ACJC) as a motion preservation instrument for cervical corpectomy procedures. Through finite element analysis (FEA), this study aims to assess this prosthesis's mobility and stability in the context of physiological reconstruction of the cervical spine. Materials and methods: A finite element (FE)model of the subaxial cervical spine (C3-C7) was established and validated. ACJC arthroplasty, anterior cervical corpectomy and fusion (ACCF), and two-level cervical disc arthroplasty (CDA) were performed at C4-C6. Range of motion (ROM), intervertebral disc pressure (IDP), facet joint stress (FJS), and maximum von Mises stress on the prosthesis and vertebrae during loading were compared. Results: Compared to the intact model, the ROM in all three surgical groups demonstrated a decline, with the ACCF group exhibiting the most significant mobility loss, and the highest compensatory motion in adjacent segments. ACJC and artificial cervical disc prosthesis (ACDP) well-preserved cervical mobility. In the ACCF model, IDP and FJS in adjacent segments increased notably, whereas the index segments experienced the most significant FJS elevation in the CDA model. The ROM, IDP, and FJS in both index and adjacent segments of the ACJC model were intermediate between the other two. Stress distribution of ACCF instruments and ACJC prosthesis during the loading process was more dispersed, resulting in less impact on the adjacent vertebrae than in the CDA model. Conclusion: The biomechanical properties of the novel ACJC were comparable to the ACCF in constructing postoperative stability and equally preserved physiological mobility of the cervical spine as CDA without much impact on adjacent segments and facet joints. Thus, the novel ACJC effectively balanced postoperative stability with cervical motion preservation.

4.
Stem Cell Res ; 78: 103467, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38861774

RESUMO

Dilated cardiomyopathy (DCM) is one of the main causes of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation worldwide. Mutations in dozens of cardiac genes have been connected to the development of DCM including the Troponin T2 gene (TNNT2). Here, we generated a human induced pluripotent stem cells (hiPSCs) from a DCM patient with a familial history that carries a missense mutation in TNNT2. The hiPSCs show typical morphology of pluripotent stem cells, expression of pluripotency markers, normal karyotype, and in vitro capacity to differentiate into all three germ layers.


Assuntos
Cardiomiopatia Dilatada , Células-Tronco Pluripotentes Induzidas , Troponina T , Humanos , Cardiomiopatia Dilatada/patologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Troponina T/metabolismo , Troponina T/genética , Diferenciação Celular , Linhagem Celular , Masculino , Cariótipo
5.
Chemosphere ; 362: 142616, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906194

RESUMO

The water accommodated fraction (WAF) of spilled crude oil is a severe threat to the health of marine fish. This study was conducted to investigate the effects of short-term embryonic exposure to the WAF on the ovarian development and reproductive capability of F0 adult female marine medaka (Oryzias melastigma). Following embryonic exposure to the WAF with nominal total petroleum hydrocarbon concentrations of 0.5, 5, 50, and 500 µg/L for 7 days, the number of spawned eggs and gonadosomatic indices of F0 adult females were significantly reduced at 130 days postfertilization. In these F0 adult females, the proportion of mature oocytes was significantly lower, the level of 17ß-estradiol was lower, and the level of testosterone was greater than those in control group. The mRNA levels of the follicle-stimulating hormone ß subunit, luteinizing hormone ß subunit, cytochrome P450 aromatase 19b, estrogen receptor α and ß, and androgen receptor α and ß genes were upregulated, while the mRNA level of the salmon-type gonadotropin-releasing hormone was downregulated in F0 adult females exposed to the WAF during the embryonic stage. Additionally, the methylation level of vitellogenin (vtg) in F0 adult females was significantly elevated, this might have, in turn, downregulated the mRNA level of vtg. The mortality rate of the unexposed F1 embryos was significantly increased and the hatching success was significantly reduced. These results collectively indicated the necessity of incorporating and evaluating the effects of short-term early-life exposure to crude oil in the assessment of risks to the reproductive health of marine fish.

6.
Front Pharmacol ; 15: 1344786, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38783938

RESUMO

Introduction: Glycopyrrolate is commonly researched as a preoperative medication or in conjunction with cholinesterase inhibitors to counteract the lingering muscarinic effects of non-depolarizing muscarinic agents. However, studies have yielded inconsistent results regarding the superiority of glycopyrrolate over other anti-cholinergic drugs, such as atropine, particularly its effect on heart rate, blood pressure (BP), and glandular secretions. This study aimed to evaluate the differences in perioperative oral secretions, hemodynamics, and recovery quality with glycopyrrolate versus those with atropine before anesthesia induction in children undergoing tonsillectomy and adenoidectomy. Methods: In this prospective, single-center, randomized, double-blind, controlled trial, a total of 103 children were randomly assigned to group A (n = 51, glycopyrrolate 0.005 mg/kg) or B (n = 52, atropine 0.01 mg/kg). The follow-up anesthetic induction and maintenance protocols were the same in both groups. Vital signs, duration of surgery, extubation time, degree of wetness around the vocal cords during tracheal intubation, weight of oral secretions, and perioperative complications were recorded. Results: No significant differences were observed in the degree of wetness around the vocal cords during tracheal intubation, as well as in the weight of oral secretions, duration of surgery, or extubation time, between the two groups. The intraoperative and postoperative heart rates were lower in group A than in group B (110.18 ± 10.58 vs. 114.94 ± 11.14, p = 0.028; 96.96 ± 10.81 vs. 103.38 ± 10.09, p = 0.002). The differences observed in the intraoperative and preoperative heart rates were lower in group A than in group B (23.84 ± 9.62 vs. 29.65 ± 8.75, p = 0.002). The differences observed in the postoperative and preoperative heart rates were lower in group A than in group B (10.63 ± 9.97 vs. 18.09 ± 9.39, p = 0.000). Conclusion: Glycopyrrolate showed a smoother change in heart rate than atropine during and after tonsillectomy and adenoidectomy, with no effect on BP or recovery quality, and did not increase oral secretions. The findings indicate that glycopyrrolate can serve as an alternative to atropine to prevent secretions in anesthesia induction for tonsillectomy and adenoidectomy in children. Trial registration: This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR2200063578; Date of Registration: 12/09/2022).

7.
J Orthop Surg Res ; 19(1): 318, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807224

RESUMO

BACKGROUND: Nonfusion technologies, such as motion-preservation devices, have begun a new era of treatment options in spine surgery. Motion-preservation approaches mainly include total disc replacement for anterior cervical discectomy and fusion. However, for multisegment fusion, such as anterior cervical corpectomy and fusion, the options are more limited. Therefore, we designed a novel 3D-printed motion-preservation artificial cervical corpectomy construct (ACCC) for multisegment fusion. The aim of this study was to explore the feasibility of ACCC in a goat model. METHODS: Goats were treated with anterior C3 corpectomy and ACCC implantation and randomly divided into two groups evaluated at 3 or 6 months. Radiography, 3D CT reconstruction and MRI evaluations were performed. Biocompatibility was evaluated using micro-CT and histology. RESULTS: Postoperatively, all goats were in good condition, with free neck movement. Implant positioning was optimal. The relationship between facet joints was stable. The range of motion of the C2-C4 segments during flexion-extension at 3 and 6 months postoperatively was 7.8° and 7.3°, respectively. The implants were wrapped by new bone tissue, which had grown into the porous structure. Cartilage tissue, ossification centres, new blood vessels, and bone mineralization were observed at the porous metal vertebrae-bone interface and in the metal pores. CONCLUSIONS: The ACCC provided stabilization while preserving the motion of the functional spinal unit and promoting bone regeneration and vascularization. In this study, the ACCC was used for anterior cervical corpectomy and fusion (ACCF) in a goat model. We hope that this study will propel further research of motion-preservation devices.


Assuntos
Vértebras Cervicais , Cabras , Impressão Tridimensional , Fusão Vertebral , Animais , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Fusão Vertebral/métodos , Amplitude de Movimento Articular , Modelos Animais , Materiais Biocompatíveis , Teste de Materiais/métodos , Fatores de Tempo , Discotomia/métodos
8.
Front Mol Biosci ; 11: 1405339, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756532

RESUMO

Heat shock protein 90 (Hsp90) is a family of chaperone proteins that consists of four isoforms: Hsp90α, Hsp90ß, glucose-regulated protein 94 (Grp94), and tumor necrosis factor type 1 receptor-associated protein (TRAP1). They are involved in modulating the folding, maturation, and activation of their client proteins to regulate numerous intracellular signaling pathways. Previous studies demonstrated that pan-Hsp90 inhibitors reduce inflammatory signaling pathways resulting in a reduction of inflammation and pain but show toxicities in cancer-related clinical trials. Further, the role of Hsp90 isoforms in inflammation remains poorly understood. This study aimed to determine anti-inflammatory activities of Hsp90 isoforms selective inhibitors on the lipopolysaccharide (LPS)-induced inflammation in BV-2 cells, a murine microglial cell line. The production of inflammatory mediators such as nitric oxide (NO), interleukin 1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) was measured. We also investigated the impact of Hsp90 isoform inhibitors on the activation of nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitogen-activated protein kinases (MAPKs). We found that selective inhibitors of Hsp90ß reduced the LPS-induced production of NO, IL-1ß, and TNF-α via diminishing the activation of NF-κB and Extracellular signal-regulated kinases (ERK) MAPK. The Hsp90α, Grp94, TRAP1 inhibitors had limited effect on the production of inflammatory mediators. These findings suggest that Hsp90ß is the key player in LPS-induced neuroinflammation. Thereby providing a more selective drug target for development of medications involved in pain management that can potentially contribute to the reduction of adverse side effects associated with Hsp90 pan inhibitors.

9.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(2): 144-149, 2024 Mar 30.
Artigo em Chinês | MEDLINE | ID: mdl-38605612

RESUMO

Objective: A deep learning-based method for evaluating the quality of pediatric pelvic X-ray images is proposed to construct a diagnostic model and verify its clinical feasibility. Methods: Three thousand two hundred and forty-seven children with anteroposteric pelvic radiographs are retrospectively collected and randomly divided into training datasets, validation datasets and test datasets. Artificial intelligence model is conducted to evaluate the reliability of quality control model. Results: The diagnostic accuracy, area under ROC curve, sensitivity and specificity of the model are 99.4%, 0.993, 98.6% and 100.0%, respectively. The 95% consistency limit of the pelvic tilt index of the model is -0.052-0.072. The 95% consistency threshold of pelvic rotation index is -0.088-0.055. Conclusion: This is the first attempt to apply AI algorithm to the quality assessment of children's pelvic radiographs, and has significantly improved the diagnosis and treatment status of DDH in children.


Assuntos
Inteligência Artificial , Aprendizado Profundo , Criança , Humanos , Distribuição Aleatória , Reprodutibilidade dos Testes , Estudos Retrospectivos , Raios X
10.
Ecotoxicol Environ Saf ; 277: 116325, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38653019

RESUMO

The water accommodated fraction (WAF) of crude oil exerts considerable impacts on marine fish during embryonic stage. Clarifying changes in epigenetic modifications is helpful for understanding the molecular mechanism underlying the toxicity of embryonic WAF exposure. The aim of this study was to explore genome-wide DNA methylation changes in Oryzias melastigma embryos after exposure to the nominal total petroleum hydrocarbon concentration of 500 µg/L in WAF for 7 days. Whole-genome bisulfite sequencing revealed that 8.47 % and 8.46 % of all the genomic C sites were methylated in the control and WAF-exposed groups, respectively. Among the three sequence contexts, methylated CG site had the largest number in both the two groups. The sequence preferences of nearby methylated cytosines were consistent between the two groups. A total of 4798 differentially methylated regions (DMRs) were identified in the promoter region. Furthermore, Gene Ontology analysis revealed that DMR-related genes were enriched mainly for functions related to development and nervous system. Additionally, the Kyoto Encyclopedia of Genes and Genomes pathways enriched in DMR-related genes were related to nervous system and endocrine system. These novel findings provide comprehensive insights into the genome-wide DNA methylation landscape of O. melastigma following embryonic WAF exposure, shedding light on the epigenetic regulatory mechanisms underlying WAF-induced toxicity.


Assuntos
Metilação de DNA , Embrião não Mamífero , Petróleo , Poluentes Químicos da Água , Metilação de DNA/efeitos dos fármacos , Animais , Poluentes Químicos da Água/toxicidade , Petróleo/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos
11.
SAGE Open Med Case Rep ; 12: 2050313X241240097, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559411

RESUMO

Idiopathic multicentric Castleman disease is a rare and complex disease characterized by systemic inflammation, lymphadenopathy, and multiorgan involvement. This case report presents a 66-year-old Chinese man with idiopathic multicenter Castleman disease without significant lymphadenopathy and challenging diagnosis. Patients present with fever, fatigue, loss of appetite, weight loss, and acute kidney injury. Initially, a urinary tract infection was suspected, but despite anti-infective treatment, the patient's symptoms persisted. Lymph node biopsy, although there is no significant lymphadenopathy, confirms idiopathic multicenter Castleman disease. Treatment includes thalidomide, cyclophosphamide, and dexamethasone, as well as supportive measures and infection control. After 8 months of follow-up, the patient's clinical symptoms, inflammatory markers and renal function were significantly improved, and there was no symptomatic recurrence. This case underscores the importance of considering idiopathic multicenter Castleman's disease in patients with persistent fever and systemic inflammation, even in the absence of significant lymphadenopathy. Early identification and accurate diagnosis of idiopathic multicenter Castleman's disease can lead to the initiation of targeted therapy strategies that ultimately yield favorable outcomes.

12.
Cell Stress Chaperones ; 29(2): 300-311, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38508444

RESUMO

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies characterized by abnormal hematopoietic cell maturation, increased apoptosis of bone marrow cells, and anemia. They are the most common myeloid blood cancers in American adults. The full complement of gene mutations that contribute to the phenotypes or clinical symptoms in MDS is not fully understood. Around 10%-25% of MDS patients harbor an interstitial heterozygous deletion on the long arm of chromosome 5 [del(5q)], creating haploinsufficiency for a large set of genes, including HSPA9. The HSPA9 gene encodes for the protein mortalin, a highly conserved heat shock protein predominantly localized in mitochondria. Our prior study showed that knockdown of HSPA9 induces TP53-dependent apoptosis in human CD34+ hematopoietic progenitor cells. In this study, we explored the role of HSPA9 in regulating erythroid maturation using human CD34+ cells. We inhibited the expression of HSPA9 using gene knockdown and pharmacological inhibition and found that inhibition of HSPA9 disrupted erythroid maturation as well as increased expression of p53 in CD34+ cells. To test whether the molecular mechanism of HSPA9 regulating erythroid maturation is TP53-dependent, we knocked down HSPA9 and TP53 individually or in combination in human CD34+ cells. We found that the knockdown of TP53 partially rescued the erythroid maturation defect induced by HSPA9 knockdown, suggesting that the defect in cells with reduced HSPA9 expression is TP53-dependent. Collectively, these findings indicate that reduced levels of HSPA9 may contribute to the anemia observed in del(5q)-associated MDS patients due to the activation of TP53.


Assuntos
Anemia , Síndromes Mielodisplásicas , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Anemia/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo
13.
Heliyon ; 10(4): e25753, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390151

RESUMO

Background: Neglected congenital clubfoot (NCCF) is a birth deformity that remains untreated until the child begins to walk. Irrespective of the treatment protocols employed, children with NCCF face an elevated risk of recurrence following the initial correction. Predicting this recurrence could enable early intervention for high-risk children, ultimately diminishing the likelihood of invasive surgery. Methods: From January 2006 to January 2022, a total of 33 unilateral NCCF patients were enrolled in this study at Xijing Hospital. Pedobarographic tests were performed at three distinct time points: after the initial Ponseti treatment, before recurrence treatment, and after recurrence treatment. Four derivative parameters were developed for predicting recurrence, namely the difference of the contact time% (DCT%), difference of the contact area% (DCA%), difference of the peak pressure (DPP), and difference of the pressure-time integral (DPTI) between the two feet. ROC curves, Kaplan-Meier survival analysis, and Cox regression were employed to identify potential prognostic factors. Results: Out of the 33 unilateral NCCF patients, recurrence occurred in 8 individuals, with an average follow-up period of 109.8 months. The predictive parameter for recurrence is the midfoot (MF) zone's DCT% (MF-DCT%). When the contact time (CT)% of the affected side was 20.69% higher than that of the unaffected side, the hazard ratio (HR) of recurrence increased by 7.404 times. Another predictive plantar pressure parameter is the DPP in the MF zone (MF-DPP). If the PP of the affected side was 159% higher than that of the unaffected side, the HR of recurrence increased by 9.229 times. The MF-DCT% and MF-DPP of recurrence patients were assessed at three time points for comparisons, further validating their predictive ability for recurrence. Conclusion: Although satisfactory clinical outcomes were achieved in patients with unilateral NCCF after the initial Ponseti treatment, the plantar pressure distribution does not return to normal levels, which may indicate future recurrence. DCT% and DPP in the MF zone can be used as plantar pressure predictors of recurrence in patients with NCCF.

15.
Cancer Sci ; 115(3): 836-846, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38273817

RESUMO

Matrix stiffness potently promotes the malignant phenotype in various biological contexts. Therefore, identification of gene expression to participate in mechanical force signals transduced into downstream biochemical signaling will contribute substantially to the advances in nasopharyngeal carcinoma (NPC) treatment. In the present study, we detected that cortactin (CTTN) played an indispensable role in matrix stiffness-induced cell migration, invasion, and invadopodia formation. Advances in cancer research have highlighted that dysregulated alternative splicing contributes to cancer progression as an oncogenic driver. However, whether WT-CTTN or splice variants (SV1-CTTN or SV2-CTTN) regulate matrix stiffness-induced malignant phenotype is largely unknown. We proved that alteration of WT-CTTN expression modulated matrix stiffness-induced cell migration, invasion, and invadopodia formation. Considering that splicing factors might drive cancer progression through positive feedback loops, we analyzed and showed how the splicing factor PTBP2 and TIA1 modulated the production of WT-CTTN. Moreover, we determined that high stiffness activated PTBP2 expression. Taken together, our findings showed that the PTBP2-WT-CTTN level increases upon stiffening and then promotes cell migration, invasion, and invadopodia formation in NPC.


Assuntos
Neoplasias Nasofaríngeas , Podossomos , Humanos , Cortactina/genética , Cortactina/metabolismo , Carcinoma Nasofaríngeo/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Nasofaríngeas/genética , Invasividade Neoplásica
16.
Small ; 20(5): e2304518, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752744

RESUMO

Designing reliable and energy-efficient memristors for artificial synaptic arrays in neuromorphic computing beyond von Neumann architecture remains a challenge. Here, memristors based on emerging layered nickel phosphorus trisulfide (NiPS3 ) are reported that exhibit several favorable characteristics, including uniform bipolar nonvolatile switching with small operating voltage (<1 V), fast switching speed (< 20 ns), high On/Off ratio (>102 ), and the ability to achieve programmable multilevel resistance states. Through direct experimental evidence using transmission electron microscopy and energy dispersive X-ray spectroscopy, it is revealed that the resistive switching mechanism in the Ti/NiPS3 /Au device is related to the formation and dissolution of Ti conductive filaments. Intriguingly, further investigation into the microstructural and chemical properties of NiPS3 suggests that the penetration of Ti ions is accompanied by the drift of phosphorus-sulfur ions, leading to induced P/S vacancies that facilitate the formation of conductive filaments. Furthermore, it is demonstrated that the memristor, when operating in quasi-reset mode, effectively emulates long-term synaptic weight plasticity. By utilizing a crossbar array, multipattern memorization and multiply-and-accumulate (MAC) operations are successfully implemented. Moreover, owing to the highly linear and symmetric multiple conductance states, a high pattern recognition accuracy of ≈96.4% is demonstrated in artificial neural network simulation for neuromorphic systems.

17.
Mol Med Rep ; 29(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37997818

RESUMO

Breast cancer is the most common malignancy in women. Metastatic breast cancer is incurable and is a major cause of shortened patient survival. The different molecular types of breast cancer make targeted therapy difficult and a complex challenge. Aryl hydrocarbon receptor (AhR) is an evolutionarily conserved transcription factor that has been implicated in the metabolism of xenobiotic ligands. AhR is activated by numerous exogenous and endogenous ligands and participates in multiple physiological processes, including proliferation, migration, invasion and apoptosis. AhR expression is upregulated in certain breast cancer subtypes, including estrogen receptor­positive breast cancer, and has been implicated in the development and progression of breast cancer. Over the last two decades, AhR and its ligands have emerged as novel biological targets for the treatment of breast cancer. Both AhR agonists and antagonists may be effective in inhibiting critical activities of breast cancer. The present review evaluates the role and underlying mechanisms of AhR and its ligands in breast cancer and demonstrates the potential of exploiting AhR as a novel target for breast cancer therapy.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Ligantes
18.
Aquac Nutr ; 2023: 4912141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077279

RESUMO

The aim of this trial was to investigate the effects of apple polyphenols (AP) and taurine (TA) on the growth performance, tissue morphology, and lipid and glucose metabolism in rice field eel fed diets with high oxidized fish oil (OFO). A 10-week feeding experiment was conducted using juveniles (initial body weight 16.66 ± 0.02 g) fed five different diets. Three diets were formulated with various levels of OFO at 9.5, 600, and 800 meq·kg-1 and named as Control, POV600, and POV800 diet, respectively. The other two diets were POV600 and POV800 supplemented with 0.5% AP and 0.2% TA, respectively. Compared to the Control group, only the eels fed POV800 exhibited an increase in weight gain and specific growth rate along with a reduction in feed conversion ratio. AP and TA did not affect growth performance; juveniles fed AP, however, showed a decrease in liver weight. Both POV600 and POV800 decreased nuclei number and increased vacuoles size in the liver. POV800 damaged the intestinal structure integrity and reduced goblet cells number. AP repaired the liver damage on nuclei number and vacuoles size in fish fed with POV600 diet, while TA mitigated intestinal histopathological damage on intact structure and goblet cells number. The mRNA expression level of liver ampkα in fish fed AP was upregulated, while dietary TA upregulated the mRNA expression levels of liver ampkα and accα. In the muscle, POV600 downregulated mRNA expression levels of accα, cpt1, and lipin, whereas POV800 upregulated mRNA expression levels of accα, pparα, and lipin. Dietary AP and TA could counteract the effects of POV600 and POV800 diet on muscle lipid metabolism. Both POV600 and POV800 diets upregulated mRNA expression levels of liver pck1 and gsk3α. AP and TA both downregulated mRNA expression level of liver pck1, while only TA downregulated the expression of liver gsk3α. AP increased the mRNA expression level of gsk3α in muscle. In summary, inclusion of AP and TA did not affect growth performance but showed a potential to alleviate liver or intestinal damages induced by a high OFO diet. Dietary AP and TA were also found to regulate mRNA expression of genes related to lipid and glucose metabolism.

19.
J Med Case Rep ; 17(1): 525, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38057903

RESUMO

BACKGROUND: Tarlov's cyst is often underdiagnosed since it is difficult to identify without imaging assistance. Herein, we report the case of a young girl who presented with an 8-year history of chronic osteomyelitis of bilateral proximal phalanges and metatarsal bones caused by a Tarlov's cyst that did not contain a nerve root. The chronic wound in the forefoot is an unusual presentation and resulted from the Tarlov's cyst accompanied with tethered conus syndrome. CASE PRESENTATION: A 10-year-old Asian girl presented with an 8-year history of chronic osteomyelitis of bilateral proximal phalanges and metatarsal bones. She received sequestrectomy five times, however the immune function tests were all normal. A neurological examination revealed diminished sensation and a slapping gait pattern. Magnetic resonance imaging (MRI) demonstrated a lobulated cyst at the right aspect of the sacrum (S) 1 to sacrum (S) 3 canal near the dorsal root ganglion. Tethered conus syndrome was highly suspected. She received laminectomy of lumbar (L) 5 and S1-S2, which led to the diagnosis of a right S1-S3 epidural cyst. The final diagnosis from the histopathological examination was a right sacral Tarlov's cyst. The clinical conditions of diminished sensation and slapping gait pattern greatly improved after successful surgical treatment. CONCLUSION: In children who present with a recalcitrant chronic wound in the forefoot accompanied with a slapping gait pattern and foot hypoesthesia to pain, aggressive imaging examinations such as spine MRI should be arranged for further evaluation, especially in immunocompetent children.


Assuntos
Cistos , Osteomielite , Cistos de Tarlov , Feminino , Criança , Humanos , Cistos de Tarlov/complicações , Cistos de Tarlov/diagnóstico , Cistos de Tarlov/cirurgia , Cistos/cirurgia , Imageamento por Ressonância Magnética , Laminectomia , Osteomielite/diagnóstico por imagem , Osteomielite/complicações
20.
BMC Surg ; 23(1): 354, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37980464

RESUMO

BACKGROUNDS: This study aimed to compare whether Calcium phosphate cement (CPC) promotes the stability of osteoporotic lumbar pedicle screw by enhancer-injecters with different number of holes. METHODS: Through a self-designed bone cement injection device, the pedicle screw canal was strengthened with calcium phosphate bone cement, and divided into 4-hole group, 6-hole group, 8-hole group, straight pore group and the control group. The screw was inserted into the mechanical test module, the Maximum insertion torque and Maximum axial pull-out strength were recorded, and the distribution of calcium phosphate bone cement was analyzed by CT and X-ray. The data results were analyzed using SPSS19.0 statistical software package. RESULTS: The distribution of bone cement in different reinforcement groups was different and showed regularity. The bone cement in the 4-hole group was roughly located in the head 1/3 of the screw, the 6-hole group was located in the middle 1/3 of the screw, and the 8-hole group was located in the caudal 1/3 of the screw. Compared with the control group, the maximum axial pull-out force of screws in the lateral hole and full screw tunnel reinforcement group was significantly increased. There was no significant difference between the 4-hole, 6-hole and straight pore groups. There was no difference in the screw-in torque between the reinforcement groups, and they all increased significantly compared with the control group, and the difference was statistically significant. After the screw was pulled out, the interface between the bone cement and the polyurethane material was fractured, and a tight package was formed with the screw. CONCLUSIONS: Enhancer syringes with different hole numbers combined with CPC bone cement injection can significantly increase the maximum screw pull-out force. The 8-hole group has a smaller pull-out force and is relatively prone to leakage of reinforcing material, which lacks safety in use. The local reinforcement of 4-hole and 6-hole sheath can play a similar role to that of total nail tunnel reinforcement.


Assuntos
Cimentos Ósseos , Parafusos Pediculares , Humanos , Fenômenos Biomecânicos , Fosfatos de Cálcio , Vértebras Lombares/cirurgia
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