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Largemouth bass virus (LMBV) infections has resulted in high mortality and economic losses to the global largemouth bass industry and has seriously restricted the healthy development of the bass aquaculture industry. There are currently no antiviral therapies available for the control of this disease. In this study, we developed three types of vaccine against LMBV; whole virus inactivated vaccine (I), a subunit vaccine composed of the major viral capsid protein MCP (S) as well as an MCP DNA vaccine(D), These were employed using differing immunization and booster strategies spaced 2 weeks apart as follows: II, SS, DD and DS. We found that all vaccine groups induced humoral and cellular immune responses and protected largemouth bass from a lethal LMBV challenge to varying degrees and DD produced the best overall effect. Specifically, the levels of specific IgM in serum in all immunized groups were elevated and significantly higher than those in the control group. Moreover, the expression of humoral immunity (CD4 and IgM) and cellular immunity (MHC-1) as well as cytokines (IL-1ß) was increased, and the activity of immunity-related enzymes ACP, AKP, LZM, and T-SOD in the serum was significantly enhanced. In addition, the relative percent survival of fish following an LMBV lethal challenge 4 weeks after the initial immunizations were high for each group: DD(89.5%),DS(63.2%),SS(50%) and II (44.7%). These results indicated that the MCP DNA vaccine is the most suitable and promising vaccine candidate for the effective control of LMBV disease.
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STUDY DESIGN: Biomechanical testings and finite element analysis. OBJECTIVES: This study aims to investigate how annulus fibrosus (AF) incision size (RIS, Ratio of incision width to AF height) and shape affect intervertebral disc (IVD) biomechanics. METHODS: A validated finite element model of lumbar spines simulated various incisions in the middle-right posterior region of the AF, with different sizes and shapes. Simulations included axial compression, flexion, extension, bending, and rotation. Parameters assessed included stability, re-herniation, and IVD degeneration by analyzing stress, height, Intradiscal pressure (IDP), and the range of motion (ROM). RESULTS: Incision increased AF stress and ROM under 3 Nm moment, with values rising as RIS increased. RIS exceeding 40% resulted in a 20% AF stress increase during compression and extension, while RIS over 50% led to over 20% AF stress increase during other motions. Incision stress also increased with higher RIS, particularly surpassing 50% RIS. IDP rose across all incision shapes. Endplate stress increased (9.9%-48.9%) with larger incisions, with average increases of 12.8%, 12.7%, 30.5%, and 22.8% for circular, oval, square, and rectangular incisions. Compression and rotation minimally affected NP pressure (<15%), while flexion (19.8%-38.8%) and bending (18.5%-43.9%) had a more pronounced effect. ROM increased with RIS (20.0% â¼ 77.4%), especially with an incision RIS exceeding 40%. CONCLUSIONS: AF injury elevates AF stress, reduces spine stability, heightens degeneration risk with increasing RIS. Reherniation risk rises when RIS exceeds 40%. Circular or oval incisions maintain spine biomechanics better than square or rectangular ones.
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Background: Anthraquinone drugs are widely used in the treatment of tumors. However, multidrug resistance and severe cardiac toxicity limit its use, which have led to the discovery of new analogues. In this paper, 4-Deoxy-ε-pyrromycinone (4-Deo), belonging to anthraquinone compounds, was first been studied with the anti-tumor effects and the safety in vitro and in vivo as a new anti-tumor drug or lead compound. Methods: The quantitative analysis of 4-Deo was established by UV methodology. The anti-cancer effect of 4-Deo in vitro was evaluated by cytotoxicity experiments of H22, HepG2 and Caco2, and the anti-cancer mechanism was explored by cell apoptosis and cycle. The tumor-bearing mouse model was established by subcutaneous inoculation of H22 cells to evaluate the anti-tumor effect of 4-Deo in vivo. The safety of 4-Deo was verified by the in vitro safety experiments of healthy cells and the in vivo safety experiments of H22 tumor-bearing mice. Tumor tissue sections were labeled with CRT, HMGB1, IL-6 and CD115 to explore the preliminary anti-cancer mechanism by immunohistochemistry. Results: In vitro experiments demonstrated that 4-Deo could inhibit the growth of H22 by inducing cell necrosis and blocking cells in S phase, and 4-Deo has less damage to healthy cells. In vivo experiments showed that 4-Deo increased the positive area of CRT and HMGB1, which may inhibit tumor growth by triggering immunogenic cell death (ICD). In addition, 4-Deo reduced the positive area of CSF1R, and the anti-tumor effect may be achieved by blocking the transformation of tumor-associated macrophages (TAMs) to M2 phenotype. Conclusion: In summary, this paper demonstrated the promise of 4-Deo for cancer treatment in vitro and in vivo. This paper lays the foundation for the study of 4-Deo, which is beneficial for the further development anti-tumor drugs based on the lead compound of 4-Deo.
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Antineoplásicos , Apoptose , Proliferação de Células , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Camundongos , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Antraquinonas/farmacologia , Antraquinonas/química , Antraquinonas/síntese química , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade , Camundongos Endogâmicos BALB CRESUMO
AIMS/INTRODUCTION: We investigated the relationship of circulating TSP-1 mRNA and miR-194 with diabetic kidney disease's degree. MATERIALS AND METHODS: We enrolled 167 hospitalized type 2 diabetes patients in the endocrinology department. Patients were split into three groups according to urinary microalbumin: A, B and C. The control group comprised healthy outpatients (n = 163). The quantities of microribonucleic acid (miR)-194 and thrombospondin-1 (TSP-1) messenger ribonucleic acid (mRNA) in the participants' circulation were measured using a quantitative real-time polymerase chain reaction. RESULTS: Circulating TSP-1 mRNA (P = 0.024) and miR-194 (P = 0.029) expressions significantly increased in type 2 diabetes patients. Circulating TSP-1 mRNA (P = 0.040) and miR-194 (P = 0.007) expression levels differed significantly among the three groups; circulating TSP-1 mRNA expression increased with urinary microalbumin. However, miR-194 declined in group B and increased in group C. Circulating TSP-1 mRNA was positively correlated with cystatin-c (r = 0.281; P = 0.021) and microalbumin/creatinine ratio (UmALB/Cr; r = 0.317; P = 0.009); miR-194 was positively correlated with UmALB/Cr (r = 0.405; P = 0.003). Stepwise multivariate linear regression analysis showed cystatin-c (ß = 0.578; P = 0.021) and UmALB/Cr (ß = 0.001; P = 0.009) as independent factors for TSP-1 mRNA; UmALB/Cr (ß = 0.005; P = 0.028) as an independent factor for miR194. Areas under the curve for circulating TSP-1 mRNA and miR194 were 0.756 (95% confidence interval 0.620-0.893; sensitivity 0.69 and specificity 0.71, P < 0.01) and 0.584 (95% confidence interval 0.421-0.748; sensitivity 0.54 and specificity 0.52, P < 0.01), respectively. CONCLUSIONS: Circulating TSP-1 mRNA and miR-194 expressions significantly increased in type 2 diabetes patients. The microalbumin group had lower levels of miR-194 (a risk factor that is valuable for type 2 diabetes kidney disease evaluation).
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OBJECTIVE: With the increase in the prevalence rate and improvements in the survival of breast cancer patients, there is a growing interest in understanding the level of psychosocial adjustment in these patients. The study aimed to describe the illness perception and psychosocial adjustment levels of both breast cancer patients and their spouses, to use the Actor-Partner Interdependence Model (APIM) to clarify the actor-partner relationships between spouses, and to explore the impact of illness perception on psychosocial adjustment to the disease within the joint actions of both spouses. METHODS: A total of 216 female patients with breast cancer and their spouses participated in the study. They were selected from two tertiary hospitals in Guangdong Province, China from October 2022 to May 2023 using a convenience sampling method. The participants were assessed using the Brief Illness Perception Questionnaire and the Psychosocial Adjustment to Illness Scale to examine the relationship between illness perception and psychosocial adjustment. AMOS24.0 was used to test and analyze the actor-partner interdependence model. RESULTS: The illness perception score (57.75 ± 10.91) was slightly higher than that of the spouse (57.10 ± 11.00), and the psychosocial adjustment score (64.67 ± 6.33) was slightly lower than that of the spouse (64.76 ± 7.49). The results of the actor-partner interdependence model indicated that there was a couple partner between breast cancer patients and their spouses: the spouse's illness perception significantly affected the patient's psychosocial adjustment (ß = 0.095, p = 0.015); the patient's illness perception also significantly affected the spouse's psychosocial adjustment (ß = 0.106, p = 0.033). Among them, the patient's psychosocial adjustment was found to be related to the patient's illness comprehensibility or coherence of illness (ß = 0.433, p = 0.009), the spouse's emotional illness representation (ß = 0.218, p = 0.037), and the spouse's illness comprehensibility or coherence of illness (ß = 0.416, p = 0.007), while the spouse's psychosocial adjustment was only related to the spouse's illness comprehensibility or coherence of illness (ß = 0.528, p = 0.007). CONCLUSIONS: The psychosocial adjustment of breast cancer patients is affected by both their own and spouse's illness perception. Therefore, in the future, the healthcare staff can implement early psychological interventions for patients diagnosed with breast cancer and their spouses as a unit to promote the psychosocial adjustment of them.
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Adaptação Psicológica , Neoplasias da Mama , Cônjuges , Humanos , Feminino , Cônjuges/psicologia , Neoplasias da Mama/psicologia , Pessoa de Meia-Idade , Adulto , China , Masculino , Idoso , Inquéritos e Questionários , Modelos PsicológicosRESUMO
Cervical cancer, primarily squamous cell carcinoma, is the most prevalent gynecologic malignancy. Organoids can mimic tumor development in vitro, but current Matrigel inaccurately replicates the tissue-specific microenvironment. This limitation compromises the accurate representation of tumor heterogeneity. We collected para-cancerous cervical tissues from patients diagnosed with cervical squamous cell carcinoma (CSCC) and prepared uterine cervix extracellular matrix (UCEM) hydrogels. Proteomic analysis of UCEM identified several tissue-specific signaling pathways including human papillomavirus, phosphatidylinositol 3-kinase-AKT, and extracellular matrix receptor. Secreted proteins like FLNA, MYH9, HSPA8, and EEF1A1 were present, indicating UCEM successfully maintained cervical proteins. UCEM provided a tailored microenvironment for CSCC organoids, enabling formation and growth while preserving tumorigenic potential. RNA sequencing showed UCEM-organoids exhibited greater similarity to native CSCC and reflected tumor heterogeneity by exhibiting CSCC-associated signaling pathways including virus protein-cytokine, nuclear factor κB, tumor necrosis factor, and oncogenes EGR1, FPR1, and IFI6. Moreover, UCEM-organoids developed chemotherapy resistance. Our research provides insights into advanced organoid technology through native matrix hydrogels.
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Carcinoma de Células Escamosas , Matriz Extracelular , Hidrogéis , Organoides , Neoplasias do Colo do Útero , Humanos , Feminino , Organoides/metabolismo , Organoides/patologia , Organoides/efeitos dos fármacos , Matriz Extracelular/metabolismo , Hidrogéis/química , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Colo do Útero/patologia , Colo do Útero/metabolismo , Microambiente Tumoral , Transdução de Sinais , Animais , Proteômica/métodos , CamundongosRESUMO
PURPOSE: Osteonecrosis of the femoral head (ONFH) is a severe bone disease that can progressively lead to hip dysfunction. Accurately segmenting the necrotic lesion helps in diagnosing and treating ONFH. This paper aims at enhancing deep learning models for necrosis segmentation. METHODS: Necrotic lesions of ONFH are confined to the femoral head. Considering this domain knowledge, we introduce a preprocessing procedure, termed the "subtracting-adding" strategy, which explicitly incorporates this domain knowledge into the downstream deep neural network input. This strategy first removes the voxels outside the predefined volume of interest to "subtract" irrelevant information, and then it concatenates the bone mask with raw data to "add" anatomical structure information. RESULTS: Each of the tested off-the-shelf networks performed better with the help of the "subtracting-adding" strategy. The dice similarity coefficients increased by 10.93%, 9.23%, 9.38% and 1.60% for FCN, HRNet, SegNet and UNet, respectively. The improvements in FCN and HRNet were statistically significant. CONCLUSIONS: The "subtracting-adding" strategy enhances the performance of general-purpose networks in necrotic lesion segmentation. This strategy is compatible with various semantic segmentation networks, alleviating the need to design task-specific models.
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Necrose da Cabeça do Fêmur , Humanos , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Aprendizado Profundo , Redes Neurais de Computação , Tomografia Computadorizada por Raios X/métodos , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Masculino , Feminino , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND AND OBJECTIVE: Core decompression surgery is an effective treatment method for patients with pre-collapse osteonecrosis of the femoral head (ONFH). The treatment relies on accurately predrilling the wire into the necrotic lesion. However, the surgical planning of this drilling path remains unclear. This paper aims to develop a framework to automatically plan the drilling path and analyze its geometric parameters. METHODOLOGY: The proposed system consists of two stages. The first stage is to detect the key points. Besides the entry point and target point for the drilling path, the center of the femoral head (FH) and the boundary points of the necrotic lesion are also detected for the subsequent geometric analysis. In the second stage, the geometric parameters of the drilling path are analyzed, including the size of the necrotic lesion, the length from the entry point to the target point, the relative location between the FH center and the necrosis center, and the angular range of the drilling path in the anterior-posterior (AP) direction and superior-inferior (SI) direction. RESULTS: All of the drilling paths designed by the proposed system were considered successful, starting from the proximal subtrochanteric region, terminating at the center of the necrotic lesion, and remaining within the femoral neck. The relative coordinates of the centers of the femoral head and necrotic lesion were (-0.89,5.14,2.63) mm for the left femurs and (1.55,5.92,2.63) mm for the right femurs, on average. The angular range of the drilling path was 39.99±29.58 degrees in the SI direction and 46.18±40.73 degrees in the AP direction. CONCLUSION: This study develops a framework that allows for automatic planning and geometric analysis of the drilling path in core decompression surgery. The target point of the drilling path primarily resides in the lateral-anterior-superior region relative to the femoral head center. Surgeons and researchers can benefit from our unified framework while still maintaining the flexibility to adapt to variations in surgical cases.
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Previous studies on the advantages of binaural hearing have long been focused on sound localization and spatial stream segregation. The binaural advantages have also been observed in speech perception in reverberation. Both human speech and animal vocalizations contain temporal features that are critical for speech perception and animal communication. However, whether there are binaural advantages for sound temporal information processing in the central auditory system has not been elucidated. Gap detection threshold (GDT), the ability to detect the shortest silent interval in a sound, has been widely used to measure the auditory temporal resolution. In the present study, we determined GDTs of rat inferior collicular neurons under both monaural and binaural hearing conditions. We found that the majority of the inferior collicular neurons in adult rats exhibited binaural advantages in gap detection, i.e., better neural gap detection ability in binaural hearing conditions compared to monaural hearing condition. However, this binaural advantage in sound temporal information processing was not significant in the inferior collicular neurons of P14-21 and P22-30 rats. Additionally, we also observed age-related changes in neural temporal acuity in the rat inferior colliculus. These results demonstrate a new advantage of binaural hearing (i.e., binaural advantage in temporal processing) in the central auditory system in addition to sound localization and spatial stream segregation.
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Coal seam drilling is a simple, economical, and effective measure commonly used to prevent and control rock burst. Following rock burst, coal exhibits significant dynamic characteristics under high strain-rate loading. Our purpose was to determine the physical processes associated with impact damage to drilled coal rock, and its mitigation mechanism. An impact test was carried out on prefabricated borehole coal specimens, and the impulse signals of the incident and transmission rods were monitored. The crack initiation, expansion, and penetration of coal specimens were video-recorded to determine the mechanical properties, crack expansion, damage modes, fragmentation, and energy dissipation characteristics of coal specimens containing different boreholes. The dynamic compressive strength of the coal specimens was significantly weakened by boreholes under high strain-rate loading; the dynamic compressive strength and the dynamic modulus of elasticity of coal rock showed a decreasing trend, with increasing numbers of boreholes and a rising and decreasing trend with increasing borehole spacing; the number and spacing of boreholes appeared to be design parameters that could weaken coal-rock material under high strain-rate loading; during the loading of coal and rock, initial cracks appeared and expanded in the tensile stress zone of the borehole side, while secondary cracks, which appeared perpendicular to the main crack, expanded and connected, destroying the specimen. As the number of boreholes increased, the fractal dimension (D) and transmission energy decreased, while the reflection energy increased. As the borehole spacing was increased, D decreased while the reflective energy ratio decreased and increased, and the transmissive energy ratio increased and decreased. Drilling under high strain modifies the mechanical properties of impact damaged coal rock.
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Background: Postoperative complications following total hip arthroplasty (THA) often require revision surgery. X-rays are usually used to detect such complications, but manually identifying the location of the problem and making an accurate assessment can be subjective and time-consuming. Therefore, in this study, we propose a multi-branch network to automatically detect postoperative complications on X-ray images. Methods: We developed a multi-branch network using ResNet as the backbone and two additional branches with a global feature stream and a channel feature stream for extracting features of interest. Additionally, inspired by our domain knowledge, we designed a multi-coefficient class-specific residual attention block to learn the correlations between different complications to improve the performance of the system. Results: Our proposed method achieved state-of-the-art (SOTA) performance in detecting multiple complications, with mean average precision (mAP) and F1 scores of 0.346 and 0.429, respectively. The network also showed excellent performance at identifying aseptic loosening, with recall and precision rates of 0.929 and 0.897, respectively. Ablation experiments were conducted on detecting multiple complications and single complications, as well as internal and external datasets, demonstrating the effectiveness of our proposed modules. Conclusion: Our deep learning method provides an accurate end-to-end solution for detecting postoperative complications following THA.
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Background: Rheumatoid arthritis (RA) is an autoimmune disease leading to chronic joint inflammation. Bone erosion is the most serious pathological condition of RA and the main cause of joint deformities and disability. Melittin acupoint injection (MAI) is an effective traditional Chinese medicine (TCM) method for RA treatment. This study aimed to investigate the effect of MAI on RA bone erosion and to elucidate the underlying mechanism. Methods: A collagen-induced arthritis (CIA) mouse model was established as the experimental subject. MAI was administrated once every other day for 28 days to mice with CIA. The effects of MAI on joint diseases were assessed by body weight, arthritis index (AI) score, swollen joint count (SJC) score, and hind paw thickness. Ankle radiological changes were captured by micro-computed tomography (micro-CT) and histological changes were observed by pathological staining. Organ histological changes, spleen index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Crea) levels of serum were tested to evaluate the toxicity of MAI. Cytokine expression levels were confirmed by enzyme-linked immunosorbent assay (ELISA) to evaluate the immunity of CIA mice. Results: MAI administration markedly improved the clinical signs of CIA in mice, including hind paw thickness, AI, and the number of swollen paw joints (most of them P<0.05 or even <0.01). According to histopathological analysis, MAI ameliorated inflammatory cell infiltration, synovial hyperplasia, pannus formation, and bone erosion (all P<0.01). Micro-CT and tartrate-resistant acid phosphatase (TRAP) staining (P<0.01) also revealed that MAI could relieve bone erosion via reducing the formation of osteoclasts. Not only could MAI relieve the immunological boost [P<0.05 for the high-dose MAI (HM) group], but also it had no liver or kidney side effects (P>0.05). In addition, it decreased the serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) and increased the serum levels of IL-4 and IL-10 (the majority of P<0.05 or even <0.01). Transcriptome sequencing results indicated that MAI affected the expression of osteoclast differentiation pathway genes, which was connected with the receptor activator of the nuclear factor κB ligand/nuclear factor kappa B (RANKL/NF-κB) pathway. Conclusions: Based on our findings, MAI could suppress joint inflammation and inhibit RANKL/NF-κB-mediated osteoclast differentiation to rescue bone erosion in CIA mice, suggesting that MAI can be a potentially therapeutic substance for RA.
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Depression is a multifactorial syndrome with a variety of underlying pathological mechanisms. While ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, exhibits a rapid antidepressant action in the central never system (CNS), the potential addiction and psychotomimetic adverse effects of ketamine limit its chronic use in clinical practice. Therefore, it is necessary to discover an additional agent that shows a synergistic antidepressant activity with ketamine to sustain its therapeutic action so as to reduce its use frequency in depression treatment. The present study indicated that Dajianzhong decoction (DJZT), an empirical herbal formula used for the clinical treatment of several inflammation-related intestinal disorders, sustains behavioral and synaptic action of ketamine in depressive mouse models. Additionally, ketamine was also demonstrated to exert a synergistic action with DJZT to alleviate the chronic unpredictable mild stress (CUMS)-induced abnormalities in gut barrier proteins and colonic histology, and subsequently to normalize the diversity and composition of gut microbiota. Furthermore, DJZT was shown to possess an anti-inflammatory activity to prevent activation of NF-κB from releasing proinflammatory cytokines, specifically through inhibiting Th17 cells/IL-17A pathway. Our results uncovered the mechanism of action of DJZT in conjunction with ketamine in depression treatment by which these agents target different pathological factors across biological systems and exert a synergistic activity through a bidirectional communication in the gut-brain axis, and also provided new insights into the systematic treatment of depression.
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Ketamina , Camundongos , Animais , Ketamina/farmacologia , Ketamina/uso terapêutico , Depressão/tratamento farmacológico , Depressão/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Citocinas/metabolismo , NF-kappa B/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
OBJECTIVE: As a gate-keeper enzyme link, pyruvate dehydrogenase E1 subunit alpha (PDHA1) functions as a key regulator during glycolysis and the mitochondrial citric acid cycle, which has been reported in several tumors. Nevertheless, the effects of PDHA1 on biological behaviors and metabolism remain unclear in cervical cancer (CC) cells. The study aims to explore the PDHA1 effects on glucose metabolism in CC cells and its possible mechanism. METHODS: We first determined the expression levels of PDHA1 and activating protein 2 alpha (AP2α) as a PDHA1 potential transcription factor. The effects of PDHA1 in vivo were evaluated through a subcutaneous xenograft mouse model. Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) labeling assay, Transwell invasion assay, wound healing assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and flow cytometry were performed in CC cells. Oxygen consumption rate (OCR) levels were determined to reflect aerobic glycolysis level in gastric cancer cells. Reactive oxygen species (ROS) level was measured with 2', 7'-dichlorofluorescein diacetate kit. The relationship between PDHA1 and AP2α was examined by conducting chromatin immunoprecipitation assay and electrophoretic mobility shift assay. RESULTS: In CC tissues and cell lines, PDHA1 was downregulated, while AP2α was upregulated. Overexpression of PDHA1 remarkedly inhibited the proliferation, invasion and migration of CC cells, and tumor growth in vivo, as well as promoted OCR, apoptosis and ROS production. Moreover, AP2α directly bound to PDHA1 within suppressor of cytokine signaling 3 promoter region to negatively regulate PDHA1 expression level. What is more, PDHA1 knockdown could effectively reversed the AP2α silencing-mediated suppressive effects on cell proliferation, invasion, migration, and the promotive effects of AP2α knockdown on OCR, apoptosis and ROS production. CONCLUSIONS: Our findings demonstrate that AP2α negatively regulated PDHA1 via binding to PDHA1 gene promoter to promote malignant CC cell behaviors, which may provide a potential approach for CC therapeutics.
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Neoplasias do Colo do Útero , Feminino , Humanos , Camundongos , Animais , Neoplasias do Colo do Útero/genética , Ciclo do Ácido Cítrico , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Glicólise , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Growing evidence suggests that gut microbiota can affect depression-like behavior, and electroacupuncture (EA) can regulate the composition and abundance of gut microbiota. At the same time, not a lot of research has been done on how EA affects gut microbiota to depression-like behavior. The objective of this study was to study the associated mechanisms by which EA exerts antidepressant effects by modulating gut microbiota. METHODS: Twenty-four C57BL/6 male mice were randomly divided into three groups, one group (n = 8) was the normal control group (NC). And the other two groups was chronic unpredictable mild stress for modeling + electroacupuncture group (CUMS + EA) (n = 8) and chronic unpredictable mild stress for modeling group (CUMS) (n = 8). Both CUMS and EA groups were subjected to 28 days of CUMS, but only the EA group received an additional 14 days of EA procedure. Behavior tests were used to determine the antidepressant effect of EA. Sequencing of the 16S ribosomal RNA (rRNA) gene was applied to examine alterations in the intestinal microbiome between groups. RESULTS: The findings were compared to those of the NC group, the sucrose preference rate and the total distance of Open Field Test (OFT) in CUMS group decreased, the abundance of Lactobacillus decreased, while the abundance of staphylococci increased. After the intervention of EA, the sucrose preference index and the total distance of OFT increased, the abundance of Lactobacillus increased, while the abundance of staphylococci decreased. CONCLUSIONS: These findings indicated EA may play an antidepressant effect by adjusting the abundance of Lactobacillus and staphylococci.
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Depressão , Eletroacupuntura , Camundongos , Masculino , Animais , Depressão/terapia , Lactobacillus , Staphylococcus , Camundongos Endogâmicos C57BL , Antidepressivos/farmacologia , Estresse Psicológico , Modelos Animais de Doenças , Comportamento AnimalRESUMO
Data on the dynamic changes in chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD) during antiviral therapy are scarce. We aimed to investigate the evolution of NAFLD status change in CHB patients treated with nucleos(t)ide analogues (NAs) and its influence on therapeutic outcomes. This retrospective study included 164 HBeAg-positive CHB patients from a randomized controlled trial who were treated with NAs for 104 weeks and underwent paired liver biopsies. Histological evaluation was performed at baseline and Week 104. The patients were divided into four groups according to NAFLD status changes. From baseline to Week 104, the overall percentage of CHB patients with concurrent NAFLD increased from 17.1% to 26.2% (p = 0.044). Among them, 7 of 28 patients (25.0%) with NAFLD at baseline showed NAFLD remission at week 104, while 22 of 136 patients (16.2%) without NAFLD at baseline developed new-onset NAFLD. In subgroup analyses, the new-onset and sustained NAFLD groups showed significantly lower rates of biochemical response at week 104 as compared to the sustained non-NAFLD group (77.3% and 57.1% vs. 93.9%, respectively; all p < 0.05), as well as fibrosis improvement (31.8% and 42.9% vs. 69.3%, respectively; all p < 0.05). NAFLD status changes did not influence the virological response, HBeAg seroconversion, and necroinflammation improvement (all p > 0.05). In HBeAg-positive CHB patients receiving NAs therapy, new-onset and sustained NAFLD may counteract the benefits of antiviral therapy, reducing the rate of biochemical response and fibrosis improvement.
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Hepatite B Crônica , Hepatopatia Gordurosa não Alcoólica , Humanos , Antivirais/uso terapêutico , Antígenos E da Hepatite B/análise , Hepatite B Crônica/tratamento farmacológico , Resultado do Tratamento , Estudos Retrospectivos , Fibrose , Vírus da Hepatite BRESUMO
Background: With the increasing popularity of traditional Chinese medicine (TCM) by the global community, how to teach basic knowledge of TCM to international students and improve the teaching quality are important issues for teachers of TCM. The present study was to analyze the perceptions from both students and teachers on how to improve TCM learning internationally. Methods: A cross-sectional national survey was conducted at 23 universities/colleges across China. A structured, self-reported on-line questionnaire was administered to 34 Chinese teachers who taught TCM course in English and to 1016 international undergraduates who were enrolled in the TCM course in China between 2017 and 2021. Results: Thirty-three (97.1%) teachers and 900 (88.6%) undergraduates agreed Chinese culture should be fully integrated into TCM courses. All teachers and 944 (92.9%) undergraduates thought that TCM had important significance in the clinical practice. All teachers and 995 (97.9%) undergraduates agreed that modern research of TCM is valuable. Thirty-three (97.1%) teachers and 959 (94.4%) undergraduates thought comparing traditional medicine in different countries with TCM can help the students better understand TCM. Thirty-two (94.1%) teachers and 962 (94.7%) undergraduates agreed on the use of practical teaching method with case reports. From the perceptions of the undergraduates, the top three beneficial learning styles were practice (34.3%), teacher's lectures (32.5%), case studies (10.4%). The first choice of learning mode was attending to face-to-face teaching (82.3%). The top three interesting contents were acupuncture (75.5%), Chinese herbal medicine (63.8%), and massage (55.0%). Conclusion: To improve TCM learning among international undergraduates majoring in conventional medicine, integration of Chinese culture into TCM course, comparison of traditional medicine in different countries with TCM, application of the teaching method with case reports, and emphasization of clinical practice as well as modern research on TCM should be fully considered.
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An increasing number of studies have shown that cross-modal interaction can occur in early sensory cortices. Yet, how neurons in sensory cortices integrate multisensory cues in perceptual tasks and to what extent this influences behavior is largely unclear. To investigate, we examined visual modulation of auditory responses in the primary auditory cortex (A1) in a two-alternative forced-choice task. During the task, male rats were required to make a behavioral choice based on the pure tone frequency (low vs high) of the self-triggered stimulus to get a water reward. The result showed that the presence of a noninformative visual cue did not uniformly influence auditory response, with frequently enhancing just one of them. Closely correlated with behavioral choice, the visual cue mainly enhanced responsiveness to the auditory cue indicating a movement direction contralateral to A1 being recorded. Operating in this fashion provided A1 neurons a superior capability to discriminate sound during multisensory trials. Concomitantly, behavioral data and decoding analysis revealed that visual cue presence could speed the process of sound discrimination. We also observed this differential multisensory integration effect in well-trained rats when tested with passive stimulation and under anesthesia, albeit to a much lesser extent. We did not see this differentially integrative effect while recording in A1 in another similar group of rats performing a free-choice task. These data suggest that auditory cortex can engage in meaningful audiovisual processing, and perceptual learning can modify its multisensory integration mechanism to meet task requirements.SIGNIFICANCE STATEMENT In the natural environment, visual stimuli are frequently accompanied by auditory cues. Although multisensory integration has traditionally been seen as a feature of associational cortices, recent studies have shown that cross-modal inputs can also influence neuronal activity in primary sensory cortices. However, exactly how neurons in sensory cortices integrate multisensory cues to guide behavioral choice is still unclear. Here, we describe a novel model of multisensory integration used by A1 neurons to shape auditory representations when rats performed a cue-guided task. We found that a task-irrelevant visual cue could specifically enhance the response of neurons in sound guiding to the contralateral choice. This differentially integrative model facilitated sound discrimination and behavioral choice. This result indicates that task engagement can modulate multisensory integration.
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Córtex Auditivo , Masculino , Ratos , Animais , Córtex Auditivo/fisiologia , Estimulação Acústica , Estimulação Luminosa , Percepção Auditiva/fisiologia , Discriminação Psicológica , Percepção Visual/fisiologiaRESUMO
Currently, little is known about the mechanism of how university students' attitudes toward entrepreneurship education (ATEE) affect entrepreneurial self-efficacy (ESE) in the post-pandemic entrepreneurial environment. Based on the existing research, this study explores the relationship between ATEE, the post-pandemic entrepreneurship environment, and ESE through a questionnaire survey. A total of 910 university students from three universities in Zhejiang Province, China participated, with an effective rate of 92.9%. The data collection focused on the period from August to December 2020. In this study, Stepwise Multiple regression analysis was used to analyze university students' ATEE and its impact on ESE, as well as the moderating effect of the post-pandemic entrepreneurial environment. The results show that the gender of university students and the entrepreneurial experience of their family members exist significant differences in their ATEE and also on their ESE. Furthermore, ATEE exert a significant and positive impact on their entrepreneurial self-efficacy, while the post-pandemic entrepreneurial environment plays a positively moderating role in this influential process.
RESUMO
Interventions for extrinsic aging can be implemented, but these must address photoaging, which is the primary cause of extrinsic aging. Pigmentation due to photoaging depends on the duration and intensity of sun exposure. This study investigated the relationship between adipose-derived mesenchymal stem cells (ASCs) and photoaging pigmentation, and the underlying mechanism of action by establishing a photoaging pigmentation model using various treatments and exposure options in a guinea pigs. The energy dose of each UVB irradiation was 120 mJ/cm2 and the total dose of irradiation was 360 mJ/cm2. After successfully establishing the photoaging model, ASCs (1×106) in an balanced salt solution (0.9 ml), balanced salt solution (0.9 ml), and bFGF (9 µg) mixed with an balanced salt solution (0.9 ml) were injected intradermally in ten guinea pigs. ELISA, macroscopic skin and histological observations, and Masson-Fontana staining were done. At 2 and 4 weeks post-injection, noticeable changes were observed. Guinea pigs receiving ASCs injections displayed significantly lower visible skin scores while the melanin content continued to decrease. Somewhat improved histopathological morphology, including epidermal thinning, dermal thickening, and little inflammatory cell infiltration was observed immediately after and up to 4 weeks of ASCs injection. Melanocortin 1 receptor (MC1R) and alpha-melanocyte test hormone (alpha-MSH) levels reduced significantly, and basic fibroblast growth factor (bFGF) levels increased significantly immediately after and up to 4 weeks of ASCs injection. The MC1R and alpha-MSH levels reduced significantly immediately after and up to 4 weeks of bFGF injection. Briefly, intradermal ASCs injection can notably eliminate pigmentation in a guinea pig photoaging pigmentation model. This may be related to the fact that bFGF secreted by ASCs lowers MC1R and alpha-MSH levels, blocks the cAMP signalling pathway, and inhibits melanin synthesis. This finding may present new options for treating photoaging pigmentation.Level of Evidence: N/A.