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Previous studies have shown that men who have sex with men (MSM) with different anal sexual roles, namely bottom, versatile, and top, are at different risk of HIV infection and psychological distress. However, the evidence was primarily derived from cross-sectional designs from Western countries, and it remains unclear how anal sexual roles change over a long time and their health impacts among MSM from Eastern countries. We aimed to describe the changes in anal sexual roles among a Chinese sample of MSM over 14 years and explore their effects on HIV infection, depression, anxiety, and suicidal ideation. Between 2009 and 2023, a longitudinal study was conducted on 373 MSM in Changsha, China, to assess their anal sexual roles, HIV infection, and psychological distress, including depression, anxiety, and suicidal ideation. Generalized linear models with a binomial probability was used to analyze the predictive effect of anal sexual roles on HIV infection and psychological distress. At baseline, 30.3% of MSM self-identified as bottom, 32.2% as versatile, and 37.5% as top, and these numbers changed slightly to 35.9%, 33.0%, and 31.1%, respectively, at follow-up (p = 0.131). From baseline to follow-up, 48 (12.9%) new HIV cases were identified. The prevalence of depression increased from 23.1 to 38.1% (p < 0.001), anxiety increased from 25.5% to 35.4% (p = 0.003), and suicidal ideation increased from 30.8 to 38.9% (p = 0.021). MSM with bottom and versatile roles were more likely to have HIV infection, depression, anxiety, and suicidal ideation than those with top roles. MSM's risk of HIV infection and psychological distress varies according to their anal sexual roles, suggesting that future HIV prevention and mental health improvement programs for MSM may benefit from providing targeted and individualized support based on their anal sexual roles, with a particular focus on those with bottom and versatile roles.
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BACKGROUND: Medication adherence is essential for chronic disease management among older adults. Previous studies have shown significant links among social isolation, social support, loneliness, and medication adherence, yet most were based on cross-sectional designs. PURPOSE: We conducted a longitudinal cohort study among Chinese older adults with chronic diseases to explore the mediating effects of social support and loneliness in the association between social isolation and medication adherence. METHODS: This study followed a cohort of 797 older adults with chronic diseases in China from 2022 to 2023. The serial mediation model was examined via bootstrapping techniques to evaluate the mediating effect of social support and loneliness in the association between social isolation and medication adherence. RESULTS: From baseline to follow-up, there were significant decreases in social support (from 26.6 ± 6.2 to 23.5 ± 6.7) and medication adherence (from 6.7 ± 1.2 to 6.0 ± 1.5) and significant increases in social isolation (from 1.8 ± 1.3 to 2.5 ± 1.4) and loneliness (13.2 ± 4.1 to 23.5 ± 6.7), all with p < .001. A serial mediation model was confirmed, where social support and loneliness serially and partially mediated the association between social isolation and medication adherence (total effect c = -0.216, 95% CI = -0.296 to -0.136; direct effect c' = -0.094, 95% CI = -0.171 to -0.017; total indirect effect ab = -0.122, 95% CI = -0.179 to -0.070). CONCLUSIONS: Our findings yield critical insights into the relationship between social isolation and medication adherence through various mediating mechanisms. These findings hold significant implications for devising psychosocial interventions to enhance medication adherence among older adults with chronic diseases, underscoring the pivotal role of bolstering social support and alleviating loneliness.
This study investigated the relationship between social isolation, medication adherence, and psychosocial factors (social support and loneliness) in Chinese older adults with chronic diseases. We observed decreases in social support and medication adherence and increases in social isolation and loneliness from baseline to follow-up. The findings revealed that social support and loneliness sequentially and partially mediated the association between social isolation and medication adherence. These results highlight the importance of psychosocial interventions to improve medication adherence among older adults by enhancing social support and addressing feelings of loneliness. This study contributes to our understanding of the complex factors influencing medication adherence in this population and offers insights for designing effective interventions.
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ABSTRACT: The desires for marriage and fertility among people living with HIV (PLWH) are increasing worldwide because of improved treatment and prognosis; yet they remain understudied in China, which has a family-oriented culture. This study aimed to investigate these desires for marriage and fertility among Chinese PLWH and explore their correlates. A cross-sectional study was conducted among 1,504 Chinese PLWH to assess their desires for marriage, fertility, and other variables through an online questionnaire. Logistic regression models were used to analyze factors associated with desires for marriage and fertility. Among the 1,504 participants, 53.9% aspired to marry at 34.76 ± 5.26 years old, whereas 62.0% desired parenthood at 36.43 ± 5.11 years old. Factors associated with these desires included age, gender, residence, education level, HIV transmission route, CD4 + T-cell count, time since HIV diagnosis, disclosure of HIV status, social support, and mental health indicators.
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OBJECTIVE: Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients. METHODS: First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes. CONCLUSION: Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.
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PURPOSE: Immunotherapy using PD-L1 blockade is effective in only a small group of cancer patients, and resistance is common. This emphasizes the importance of understanding the mechanisms of cancer immune evasion and resistance. METHODS: A genome-scale CRISPR-Cas9 screen identified Bap1 as a regulator of PD-L1 expression. To measure tumor size and survival, tumor cells were subcutaneously injected into both syngeneic WT mice and immunocompromised mice. The phenotypic and transcriptional characteristics of Bap1-deleted tumors were examined using flow cytometry, RNA-seq, and CUT&Tag-seq analysis. RESULTS: We found that loss of histone deubiquitinase Bap1 in cancer cells activates a cDC1-CD8+ T cell-dependent anti-tumor immunity. The absence of Bap1 leads to an increase in genes associated with anti-tumor immune response and a decrease in genes related to immune evasion. As a result, the tumor microenvironment becomes inflamed, with more cDC1 cells and effector CD8+ T cells, but fewer neutrophils and regulatory T cells. We also found that the elimination of Bap1-deleted tumors depends on the tumor MHCI molecule and Fas-mediated CD8+ T cell cytotoxicity. Our analysis of TCGA data further supports these findings, showing a reverse correlation between BAP1 expression and mRNA signatures of activated DCs and T-cell cytotoxicity in various human cancers. CONCLUSION: The histone deubiquitinase Bap1 could be used as a biomarker for tumor stratification and as a potential therapeutic target for cancer immunotherapies.
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Thermal or burn injury results in profound metabolic changes in the body. This can contribute to muscle atrophy, bone loss, as well as suppression of the immune system. While the mechanisms that underlie this hypermetabolic response remain unclear, patients with burn injury often have low circulating levels of vitamin D. Vitamin D has been shown to regulate bone formation as well as regulate muscle function. We sought to clarify the effects of vitamin D administration on skeletal muscle function following thermal injury using a mouse model. We found that thermal injury resulted in decreased vitamin D levels as well as decreased bone mineral density. Branched chain amino acid (BCAA)s levels were also significantly enhanced in the serum following burn injury. Vitamin D administration reversed the decrease in bone marrow-derived mesenchymal stem cell (BM-MSC)s observed post burn injury. Interestingly, vitamin D administration also resulted in increased tricarboxylic acid cycle (TCA) cycle metabolites in muscle which was decreased after burn conditions, enhanced the supply of alanine and glutamine in the blood which could contribute to gluconeogenesis and wound healing. Therefore, vitamin D supplementation after burn injury may have effects not only in bone metabolism, but may affect substrate metabolism in other organs/tissues.
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BACKGROUND AND OBJECTIVES: The percutaneous full-endoscopic C2 ganglionectomy (PEC2G), an innovative procedure developed for the surgical treatment of intractable occipital neuralgia, was firstly reported by us in 2021. However, a universally accepted and well-articulated protocol modality remains elusive. The primary objective of this anatomic investigation was to meticulously elucidate the standard procedural steps of PEC2G and assess the anatomic features supporting the safe implementation of PEC2G. METHODS: Eighteen fresh adult cadavers were incorporated into this study. From this sample, 3 cadavers were subjected to bilateral PEC2G. Each procedure was documented and assessed, leading to the formulation of standard procedure criteria for PEC2G. Subsequently, 10 sets of anatomic parameters pertinent to this procedure were identified, quantified, and analyzed in 15 cadavers after complete bilateral endoscopic exposure of the C2 ganglion. An assessment of the technical feasibility and potential constraints associated with PEC2G was conducted, providing invaluable insights into the procedure's anatomic considerations. RESULTS: All 3 cadavers successfully underwent the PEC2G without any observed complications, such as dura tears or vertebral artery injuries. The C2 inferior articular process emerged as the optimal bony target for puncture, with the C2 pedicle serving as the standard guiding landmark en route to the C2 ganglion. In the 15 cadavers subjected to the planned procedure, 10 sets of anatomic parameters were quantified, establishing a foundational understanding of the anatomy in the context of PEC2G procedure. The results demonstrated that the characteristic of anatomic data pertinent to surgical site supported the safe implementation of PEC2G. CONCLUSION: This study contributes the standard surgical steps and crucial anatomic parameters relevant to PEC2G. The characteristic of anatomic data bolsters the safety credentials of this technique, which offers a reliable approach to achieve C2 ganglionectomy. These insights undeniably establish a robust foundation for the ongoing refinement and broader adoption of PEC2G.
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Fat greatly impacts the overall texture and flavor of pork belly. Twice-cooked pork bellies (TPB), typically boiled and sliced before "back to pot" being stir-fried, is a classic Sichuan cuisine among stir-fried dishes. In this study, the effects of substituting conventional pan-frying (PCV) with superheated steam (SHS) technology on the sensory, texture, microstructure and flavor of the fat layers were investigated. SHS was used as an alternative to boiling (120 °C for 15, 20, 25, and 30 min), and "back to pot" stir-frying was also by SHS. TPB precooked for 25 min (P25) with SHS performed better quality characteristics than PCV, with less collagen fiber disruption and lipid droplet area, resulting in a lower hardness and higher shear force. Besides, the low-oxygen environment of SHS retarded the lipid peroxidation, showing a significantly lower MDA content than PCV. Differently, PCV exhibited more grassy and fatty flavors, while P25 exhibited a unique aroma of fruity and creamy due to its higher UFA/SFA ratios in the pre-cooking stage. Overall, the sensory scores of P25 were comparable to those of PCV (with no significant difference), revealing that SHS is expected to be applied to the industrial production of stir-fried dishes.
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BACKGROUND: Spinal cord stimulation is an established technique wherein diverse electrode types are strategically implanted within the spinal epidural space for neuromodulation. Traditional percutaneous puncture cylindrical electrodes (PEs) are predominantly implanted by interventionalists utilizing a percutaneous technique under the monitor of radiation, which is a nonvisualized procedure. OBJECTIVE: Our study aimed to assess the feasibility of percutaneous endoscope-assisted visualized implantation approach for PEs, delineating its specific merits and demerits compared to the traditional method. STUDY DESIGN: Laboratory study with Institutional Review Board Number B2023-056SETTING: Clinical Anatomy Research Center, Fudan University. METHODS: Eight freshly procured adult cadavers (4 women and 4 men) were operated on in this study. They were divided into either Group A or Group B, each encompassing 4 cadavers. Group A was subjected to endoscope-assisted PEs implantation, whereas Group B followed the conventional PEs implantation route.In both groups the operative time of introducer needles placement (OTNP), total operative time (TOT), fluoroscopy time of introducer needles placement (FTNP), and total fluoroscopy time (TFT) were documented and analyzed. Furthermore, the precise positioning of the PEs and any ensuing complications were systematically examined. RESULTS: Both Group A and Group B successfully executed all predetermined surgical steps. A total of 16 PEs were implanted (dual electrodes in each cadaver): 8 using the percutaneous endoscope-assisted visualized approach (Group A) and 8 via the traditional methodology (Group B). Group A's mean ± SD durations for OTNP, TOT, FTNP, and TFT were 10.25 ± 1.03 minutes, 31.63 ± 5.87 minutes, 4.58 ± 1.35 seconds, and 43.73 ± 14.46 seconds, respectively. In contrast, Group B exhibited mean ± SD times of 11.55 ± 2.81 minutes, 44.75 ± 7.85 minutes, 23.53 ± 4.16 seconds, and 66.30 ± 6.35 seconds for the same metrics. No discernible statistical difference in OTNP and TOT emerged between the groups. However, Group A demonstrated reduced durations for both FTNP and TFT compared to Group B. The optimal position of the PEs was verified via fluoroscopy, with no recorded instances of dura rupture. These outcomes suggest that this endoscope-assisted technique neither increases surgical time nor compromises efficacy. Instead, it leads to a marked reduction in fluoroscopic duration relative to the traditional methodology. LIMITATIONS: Anatomical study on a human cadaver, the quantity of cadavers, and the procedure's steep learning curve. CONCLUSION: With the assistance of percutaneous spinal endoscopy, introducer needles can be punctured through the ligamentum flavum at the anticipated interlaminar window locus under direct visualization, improving the convenience of the puncture and reducing fluoroscopic exposure. It is a viable alternative for surgeons from diverse training backgrounds to implant PEs, particularly benefiting those well-versed in endoscopic spine surgery techniques.
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Cadáver , Electrodos Implantados , Estudios de Factibilidad , Estimulación de la Médula Espinal , Humanos , Estimulación de la Médula Espinal/métodos , Estimulación de la Médula Espinal/instrumentación , Femenino , Masculino , Endoscopía/métodos , Endoscopía/instrumentaciónRESUMEN
BACKGROUND: Minimally invasive treatments for spinal cord tumours are common. The aim of this study was to compare the perioperative outcomes of patients with thoracic extramedullary spinal tumours (TEST) treated by microendoscopic minimally invasive surgery-hemilaminectomy through a homemade tubular retractor (MIS-TR) and microscopic full laminectomy (open surgery). METHODS: Between February 2016 and February 2021, 51 patients with TEST were included. According to their clinical data, patients were classified into the MIS-TR group (n = 30) and the open surgery group (n = 21) and assessed. RESULTS: In both groups, the mean operation time, change in perioperative ASIA score, and modified Macnab score were comparable. The average postoperative hospital stay in the MIS-TR group was substantially shorter than that in the open surgery group (p < 0.0001). The mean blood loss volume in the MIS-TR group was substantially lower than that in the open surgery group (p = 0.001). The perioperative complication rate in the MIS-TR group was considerably lower than that in the open surgery group (p < 0.0001). At the 3-month follow-up, there was no substantial difference in the Oswestry Disability Index (ODI) score improvement between the two groups. Nonetheless, at the 12-month follow-up, the average ODI in the MIS-TR group was considerably lower than that in the open surgery group (p = 0.023). The main influencing factors for complete postoperative recovery were preoperative ASIA score (OR 7.848, P = 0.002), surgical complications (OR 0.017, P = 0.008) and age (OR 0.974, P = 0.393). CONCLUSIONS: MIS-TR is safer and more effective than open surgery for treating TEST, but the long-term recovery of MIS-TR is not better than that of open surgery.
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Endoscopía , Laminectomía , Procedimientos Quirúrgicos Mínimamente Invasivos , Vértebras Torácicas , Humanos , Laminectomía/métodos , Femenino , Masculino , Persona de Mediana Edad , Vértebras Torácicas/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Endoscopía/métodos , Adulto , Neoplasias de la Médula Espinal/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Anciano , Tempo Operativo , Microcirugia/métodos , Tiempo de InternaciónRESUMEN
Flexible multiplexing chips that permit reconfigurable multidimensional channel utilization are indispensable for revolutionary 6G terahertz communications, but the insufficient manipulation capability of terahertz waves prevents their practical implementation. Herein, we propose the first experimental demonstration of a flexible multiplexing chip for terahertz communication by revealing the unique mechanism of topological phase (TP) transition and perseveration in a heterogeneously coupled bilayer valley Hall topological photonic system. The synthetic and individual TPs operated in the coupled and decoupled states enable controllable on-chip modular TP transitions and subchannel switching. Two time-frequency interleaved subchannels support 10- and 12-Gbit/s QAM-16 high-speed data streams along corresponding paths over carriers of 120 and 130 GHz with 2.5- and 3-GHz bandwidths, respectively. This work unlocks interlayer heterogeneous TPs for inspiring ingenious on-chip terahertz-wave regulation, allowing functionality-reconfigurable, compactly integrated and CMOS-compatible chips.
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Atmospheric transport drives the widespread distribution of microplastic (MP) in various ecosystems, posing a growing potential threat to environmental safety and human health. Understanding the source and fate of atmospheric MPs is thus crucial to constrain MP's widespread exposure. However, the source-sink dynamics of atmospheric MPs, especially in remote areas, are uncertain, and their transport routes have yet to be identified. Here, we conducted a 13-month monitoring of the atmospheric MPs in the uninhabited area of Mount Taibai, estimated the potential risk of MP exposure to the environment, and modeled the MP trajectory to analyze their transportation. We first found that as many as 15 polymer types of MPs, whose shapes mainly include fiber, fragments, films, and granules, maintained abundance (0.7 and 0.3 particle/m3 for PM10 and PM2.5, respectively) in the mountain atmosphere at respirable sizes. It is worth noting that the risk assessment results that comprehensively consider the influences of abundance and morphological characteristics suggest that the exposure level of MPs exhibits a risk even in this remote mountainous area that is not disturbed by frequent human activities. Backward trajectories revealed the likely source of MPs in the sparsely populated Liupan Mountains and Qinling Mountains of short-range transport. Further, polymer characteristics of MPs and airflow-based source analysis indicated the emission source of MPs in southern Xianyang in a longer-range transport. MPs were directionally transported to Mount Taibai through atmospheric transport under the premise of stable climate and geographical conditions. These suggest that MPs inevitably occur in remote mountainous areas driven by atmospheric transport, and the mountainous areas are persistently bearing the environmental impact of MP exposure. This study reveals the risk impacts of MP exposure and the transport dynamics of atmospheric MPs in a mountain ecosystem.
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Colorectal cancer (CRC) is a common digestive system tumor with high morbidity and mortality worldwide. At present, the use of computer-assisted colonoscopy technology to detect polyps is relatively mature, but it still faces some challenges, such as missed or false detection of polyps. Therefore, how to improve the detection rate of polyps more accurately is the key to colonoscopy. To solve this problem, this paper proposes an improved YOLOv5-based cancer polyp detection method for colorectal cancer. The method is designed with a new structure called P-C3 incorporated into the backbone and neck network of the model to enhance the expression of features. In addition, a contextual feature augmentation module was introduced to the bottom of the backbone network to increase the receptive field for multi-scale feature information and to focus on polyp features by coordinate attention mechanism. The experimental results show that compared with some traditional target detection algorithms, the model proposed in this paper has significant advantages for the detection accuracy of polyp, especially in the recall rate, which largely solves the problem of missed detection of polyps. This study will contribute to improve the polyp/adenoma detection rate of endoscopists in the process of colonoscopy, and also has important significance for the development of clinical work.
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Algoritmos , Pólipos del Colon , Colonoscopía , Neoplasias Colorrectales , Humanos , Colonoscopía/métodos , Pólipos del Colon/diagnóstico , Pólipos del Colon/diagnóstico por imagen , Pólipos del Colon/patología , Neoplasias Colorrectales/diagnóstico , Redes Neurales de la Computación , Semántica , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
Innovations in wearable sweat sensors hold great promise to provide deeper insights into molecular level health information non-invasively. Lactate, a key metabolite present in sweat, holds immense significance in assessing physiological conditions and performance in sports physiology and health sensing. This paper presents the development and characterization of stretchable electrodes with ultrahigh active surface area of 648% for lactate sensing. The as-printed stretchable electrodes were functionalized with an electron transfer layer comprising of Toluidine Blue O and multi-walled carbon nanotubes (MWCNTs), and an enzymatic layer consisting of lactate dehydrogenase with ß-Nicotinamide adenine dinucleotide as the cofactor for lactate selectivity. This sensor achieves a dual-signal read-out in which both electrochemical and fluorescence signals were obtained during lactate detection, demonstrating promising sensor performance in terms of sensitivity and reliability. We demonstrate the robustness of the dual-signal sensor under simulated conditions of physical deformation and shifted excitation. Under these compromised conditions, the performance of the stretchable electrodes remained largely unaffected, showcasing their potential for robust and adaptable sensing platforms in wearable health monitoring applications.
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The production and application of materials are evolving towards the low-dimensional micro-nano scale. Nevertheless, the fabrication of micron-scale alloy fibers remains a challenge. Herein, a novel Ni-Co-Cr-Fe-Mo high-entropy alloy (HEA) fiber with a cold-drawn reduction rate of 99.9995% and a strain (É) of 12.19 is presented without requiring intermediate annealing. The exceptional deformation strain of 11.62 within the fiber leads to extraordinary tensile strengths of 2.8 GPa at room temperature and 3.6 GPa at 123 K. The in-depth investigation of the microstructure of fibers has revealed the cold drawing deformation mechanisms mediated by the synergistic effects of plane defects. Specifically, various geometrically necessary dislocation interfaces, such as dislocation walls and microbands, along with deformation twins and long-period 9R structures, form in response to external stress when É≤2.7. As the strain increases, the saturated layered structure emerges and progressively evolves into a 3D equiaxed crystal. Moreover, the formation and evolution of the 9R structure (i.e., the migration of incoherent twin boundaries), coupled with the interaction of partial dislocations and the role of deformation twins, are crucial factors determining the fiber's plastic response. This work provides a novel approach to discovering new high-strength metallic fibers with excellent deformability through plane defects engineering.
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Catechin is a kind of flavonoids, mainly derived from the plant Camellia sinensis. It has a strong antioxidant effect, and it also has significant therapeutic effects on anti-cancer, anti-diabetes, and anti-infection. This study was intended to look at how catechin affected the malignant biological activity of gastric cancer cells. We used databases to predict the targets of catechin and the pathogenic targets of gastric cancer. Venn diagram was used to find the intersection genes, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed on intersection genes. Using the STRING database, the Protein-Protein Interaction (PPI) network was built. The top 8 genes were screened by Cytoscape 3.9.1, then their binding was verified by molecular docking. The proliferation ability, cell cycle, apoptosis and migration of gastric cancer cells were detected, as well as the protein expression levels of PI3K, p-AKT, and AKT and the mRNA expression levels of AKT1, VEGFA, EGFR, HRAS, and HSP90AA1 in gastric cancer cells. Our research revealed that different concentrations of catechin could effectively inhibit the proliferation and migration of gastric cancer cells, regulate the cell cycle, and promote the death of these cells, and it's possible that the PI3K/Akt pathway was crucial in mediating this impact. Moreover, adding the PI3K/Akt pathway agonist significantly reduced the promoting effect of catechin on the apoptosis of gastric cancer cells. This study suggested that catechin was a potential drug for the treatment of gastric cancer.
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Apoptosis , Catequina , Movimiento Celular , Proliferación Celular , Simulación del Acoplamiento Molecular , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Catequina/farmacología , Catequina/análogos & derivados , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Mapas de Interacción de Proteínas , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Antineoplásicos Fitogénicos/farmacología , Fosfatidilinositol 3-Quinasa/metabolismoRESUMEN
Streptococcus suis is an important zoonotic pathogen, causing cytokine storms of Streptococcal toxic shock-like syndrome amongst humans after a wound infection into the bloodstream. To overcome the challenges of fever and leukocyte recruitment, invasive S. suis must deploy multiple stress responses forming a network and utilize proteases to degrade short-lived regulatory and misfolded proteins induced by adverse stresses, thereby adapting and evading host immune responses. In this study, we found that S. suis encodes multiple ATP-dependent proteases, including single-chain FtsH and double-subunit Clp protease complexes ClpAP, ClpBP, ClpCP, and ClpXP, which were activated as the fever of infected mice in vivo. The expression of genes ftsH, clpA/B/C, and clpP, but not clpX, were significantly upregulated in S. suis in response to heat stress, while were not changed notably under the treatments with several other stresses, including oxidative, acidic, and cold stimulation. FtsH and ClpP were required for S. suis survival within host blood under heat stress in vitro and in vivo. Deletion of ftsH or clpP attenuated the tolerance of S. suis to heat, oxidative and acidic stresses, and significantly impaired the bacterial survival within macrophages. Further analysis identified that repressor CtsR directly binds and controls the clpA/B/C and clpP operons and is relieved by heat stress. In summary, the deployments of multiple ATP-dependent proteases form a flexible heat stress response network that appears to allow S. suis to fine-tune the degradation or refolding of the misfolded proteins to maintain cellular homeostasis and optimal survival during infection.
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Lysosomal acidity relies on H+ inflow, which requires counter-ion flows (Cl- and K+) to balance charge. A lysosome targeting ternary recognition fluorescent probe for Cl-, K+, and pH was developed for lysosome acidification counter-ion research. The probe was used to study counter-ion changes when the Cl- channel was blocked and under oxidative pressure.
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Cholesterol homeostasis in neurons is critical for synapse formation and maintenance. Neurons with impaired cholesterol uptake undergo progressive synapse loss and eventual degeneration. To investigate the molecular mechanisms of neuronal cholesterol homeostasis and its role during synapse development, we studied motor neurons of Caenorhabditis elegans because these neurons rely on dietary cholesterol. Combining lipidomic analysis, we discovered that NCR-1, a lysosomal cholesterol transporter, promotes cholesterol absorption and synapse development. Loss of ncr-1 causes smaller synapses, and low cholesterol exacerbates the deficits. Moreover, NCR-1 deficiency hinders the increase in synapses under high cholesterol. Unexpectedly, NCR-2, the NCR-1 homolog, increases the use of cholesterol and sphingomyelins and impedes synapse formation. NCR-2 deficiency causes an increase in synapses regardless of cholesterol concentration. Inhibiting the degradation or synthesis of sphingomyelins can induce or suppress the synaptic phenotypes in ncr-2 mutants. Our findings indicate that neuronal cholesterol homeostasis is differentially controlled by two lysosomal cholesterol transporters and highlight the importance of neuronal cholesterol homeostasis in synapse development.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Colesterol , Lisosomas , Animales , Caenorhabditis elegans/metabolismo , Lisosomas/metabolismo , Colesterol/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Unión Neuromuscular/metabolismo , Homeostasis , Neuronas Motoras/metabolismo , Sinapsis/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas de Transporte de Membrana/genéticaRESUMEN
Timely diagnosis, monitoring, and management of chronic wounds play crucial roles in improving patients' quality of life, but clinical evaluation of chronic wounds is still ambiguous and relies heavily on the experience of clinician, resulting in increased social and financial burden and delay of optimal treatment. During the different stages of the healing process, specific and dynamic changes of pH values in the wound exudate can be used as biomarkers to reflect the wound status. Herein, a pH-responsive agent with well-behaved photoacoustic (PA) properties, nitrazine yellow (NY), was incorporated in poly(vinyl alcohol)/sucrose (PVA/Suc) hydrogel to construct a wearable pH-sensing patch (PVA/Suc/NY hydrogel) for monitoring of pH values during chronic wound healing. According to Rosencwaig-Gersho theory and the combination of 3D printing technology, the PA chamber volume and chopping frequency were systematically optimized to improve the sensitivity of the PA analytical system. The prepared PVA/Suc/NY hydrogel patch had excellent mechanical properties and flexibility and could maintain conformal contact with skin. Moreover, combined with the miniaturized PA analytical device, it had the potential to detect pH values (5.0-9.0) free from the color interference of blood and therapeutic drugs, which provides a valuable strategy for wound pH value monitoring by PA quantitation. This strategy of combining the wearable hydrogel patch with portable PA analysis offers broad new prospects for the treatment and management of chronic wounds due to its features of simple operation, time savings, and anti-interference.