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ETHNOPHARMACOLOGICAL RELEVANCE: Within Anemarrhena asphodeloides Bunge (AAB), the pivotal bioactive constituents are identified as Anemarrhena asphodeloides Bunge total saponins (ABS). In traditional pharmacology, ABS has exhibited notable anti-inflammatory, hypoglycemic, and cardioprotective properties. Despite these observed effects, the specific protective mechanisms of ABS against metabolic diseases and improving the endocrine system remain largely uncharted. AIM TO STUDY: This work intends to shed light on the effects and intrinsic mechanisms of ABS on metabolic diseases. MATERIALS AND METHODS: The characterization of ABS components was achieved through High-Performance Liquid Chromatography/Mass Spectrometry (HPLC/MS). To evaluate ABS's anti-inflammatory efficacy, mouse macrophages underwent analysis using the Griess method. Induced differentiation of mouse fibroblasts was assessed through Oil Red O staining. In an obesity model with C57BL/6 N mice, ABS administration prompted measurements of glucose and insulin tolerance. Western blot analysis quantified lipolysis and anti-inflammatory protein expression. Nile red staining gauged body fat content in C. elegans post-ABS treatment. The mechanism of ABS action was elucidated through mRNA sequencing, further validated using RNA interference technology, and nematode mutants. RESULTS: ABS showcased the ability to diminish Nitric Oxide (NO) production in inflammatory macrophages and shrink adipocyte lipid droplets. In mice experiments, ABS was effective in alleviating fat accumulation and affecting serum lipid metabolism in diabetic mice. It enhanced oral glucose tolerance and insulin tolerance while increasing lipolysis-associated protein expression. ABS notably reduced fat content in C. elegans. Mechanistically, ABS downregulated NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and monoamine oxidase A (MAOA) expression while enhancing UGT, ilys-2, and ilys-3. Lipolysis emerged as a pivotal pathway for ABS in the therapeutic intervention of metabolic diseases. CONCLUSIONS: Our investigation has revealed that ABS exert a role in combating metabolic diseases by enhancing the body's defense mechanisms. ABS activate the NLRP3-neurotransmitter-visceral adipose pathway in mice, thereby bolstering resistance and diminishing fat accumulation. In C. elegans, ABS downregulated the expression of MAOA, bolstered resistance, and augmented glucuronidase activity, consequently leading to a reduction in fat content.
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Bensulfuron methyl (BSM), a typical sulfonylurea herbicide, has been widely used worldwide for weed suppression and crop protection. Nevertheless, the long-term and prolonged usage led to residues in environment, resulting in the reduction of crop yields and even threatening food security. In this study, the nitrogen/magnesium codoped biochar (NMg-BC) was prepared via two-step pyrolysis method to activate periodate (PI) for BSM degradation. The results demonstrated BSM degradation rate was 87.9 % within 10 min by NMg-BC/PI system at 15 â. The system exhibited the favorable tolerance to environmental changes (pH, temperature, anions, and humic acids), presenting high removal efficiency of BSM. Radicals (IO3â¢) and non-radicals (1O2 and electron transfer) pathways contributed to the degradation of BSM, while the latter performed a crucial role in BSM degradation. Theoretical calculations further confirmed doped of N and Mg changed the electron configuration and electrostatic potential (ESP) distribution of biochar, which was beneficial to provide more active sites for PI activation. Hydroponic experiments showed that NMg-BC/PI system could effectively degrade BSM, and its residue had no significant effect on the length and weight of soybean. The study provides a promising approach for the pollutant remediation in cold regions.
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Bensulfuron-methyl (BSM) is a typical broad-spectrum sulfonylurea herbicide and the runoff of BSM residues from agricultural regions poses a significant threat to the ecosystem. Here we develop a bacteria-material hybrid system constructed by Acinetobacter YH0317 and Mg(NO3)2 modified biochar (MBC) for efficiently degrading BSM under various conditions including pH and temperature. Results showed that BSM biodegradation efficiency by YH0317&MBC (96.7 %) was significantly higher than YH0317&BC (79.5 %) and YH0317 (43.9 %) at 15 °C after 7 d of incubation. The addition of MBC significantly increased the reactive oxygen species (ROS) level, which was significantly higher than group YH0317. Moreover, the bacterial viability, extracellular polymeric substances (EPS) production, and membrane permeability of YH0317 were also enhanced with the addition of MBC. The electron paramagnetic resonance (EPR) and quenching experiments revealed that singlet oxygen (1O2) was the dominant active substance produced by MBC. The YH0317&MBC could effectively remove the BSM, and reduce the oxidative stress to soybean, which was beneficial to the growth of soybean through hydroponic experiment. This study establishes a microorganism-material system that efficiently removes BSM in aquatic environments and emphasizes the importance of ROS in pollution removal by the hybrid system.
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BACKGROUND: Sepsis is a life-threatening severe inflammatory reaction caused by the host's dysregulated response to infection. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to occur in 50 % of patients with septic shock. Currently, the pathophysiological mechanism of SIMD is complex, and there is no targeted treatment. Elabela is another endogenous ligand of Aplnr (APJ). The protective effect of APJ on the heart has been proven. Elabela (Ela) has been shown to have a variety of cardiovascular protective effects. However, there are no studies demonstrating the protective effect of Ela-APJ axis on SIMD. MATERIALS AND METHODS: In vivo, C57BL/J mice were injected subcutaneously with 1 mg/kg/d Ela for 2 weeks, and in vitro, AC16 cells were treated with 1 µM Ela for 24 h. A 7-0 thread was used to ligate the distal end of the cecum, followed by puncture with a 20-gauge needle. Once a small amount of fluid leaks out, release the cecum back into the abdominal cavity. We measured the survival rates of the mice, performed ultrasound on their hearts, and evaluated the effects of the treatments. The serum and cell supernatant were extracted to detect myocardial injury markers and pyroptosis-related indicators. Western blotting was used to detect autophagy and pyroptosis-related protein. Molecular docking and other experiments were also used to detect changes in related proteins. RESULTS: In vivo, Ela significantly improved the survival rate of septic mice, improved cardiac function, and reduced the production of myocardial injury markers, oxidative stress and pyroptosis. In vitro, Ela unblocked autophagy flow by affecting TFEB transcription. Autophagy reduces inflammation and oxidative stress by selectively degrading inflammatory bodies and ultimately alleviates pyroptosis. CONCLUSION: We had demonstrated for the first time that in sepsis, Ela promoted the degradation of inflammasomes, reduced oxidative stress, and inhibited the occurrence of pyroptosis by unblocking autophagy flow.
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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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Fertilidad , Infecciones por VIH , Matrimonio , Persona Soltera , Humanos , Estudios Transversales , Femenino , Masculino , Adulto , Infecciones por VIH/psicología , China/epidemiología , Matrimonio/psicología , Persona Soltera/psicología , Encuestas y Cuestionarios , Persona de Mediana Edad , Apoyo Social , Recuento de Linfocito CD4RESUMEN
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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Culinaria , Carne de Cerdo , Vapor , Culinaria/métodos , Calor , Peroxidación de Lípido , Carne de Cerdo/análisis , GustoRESUMEN
Tumor cell-derived extracellular vesicles (TEVs) contain numerous cellular molecules and are considered potential biomarkers for non-invasive liquid biopsy. However, due to the low abundance of TEVs secreted by tumor cells and their phenotypic heterogeneity, there is a lack of sensitive and specific methods to quantify TEVs. Here, we developed a dual-aptamer proximity ligation-coupled hybridization chain reaction (HCR) method for tracing TEVs, exploiting CRISPR to achieve highly sensitive detection. Taking advantage of the high binding affinity of aptamers, the two aptamers (AptEpCAM, AptHER2) exhibited the high selectivity for TEVs recognition. HCR generated long-repeated sequence containing multiple crRNA targetable barcodes, and the signals were further amplified by CRISPR upon recognizing the HCR sequences, thereby enhancing the sensitivity. Under optimal conditions, the developed method demonstrated a favorable linear relationship in the range of 2 × 103-107 particles/µL, with a limit of detection (LOD) of 3.3 × 102 particles/µL. We directly applied our assay to clinical plasma analysis, achieving 100 % accuracy in cancer diagnosis, thus demonstrating the potential clinical applications of TEVs. Due to its simplicity and rapidity, excellent sensitivity and specificity, this method has broad applications in clinical medicine.
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Aptámeros de Nucleótidos , Vesículas Extracelulares , Neoplasias , Hibridación de Ácido Nucleico , Humanos , Vesículas Extracelulares/química , Aptámeros de Nucleótidos/química , Neoplasias/diagnóstico , Neoplasias/genética , Límite de Detección , Sistemas CRISPR-Cas/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genéticaRESUMEN
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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Soledad , Cumplimiento de la Medicación , Aislamiento Social , Apoyo Social , Humanos , Soledad/psicología , Aislamiento Social/psicología , Anciano , Masculino , Femenino , Cumplimiento de la Medicación/psicología , Cumplimiento de la Medicación/estadística & datos numéricos , Enfermedad Crónica/tratamiento farmacológico , China , Estudios Longitudinales , Persona de Mediana Edad , Anciano de 80 o más Años , Pueblos del Este de AsiaRESUMEN
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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Depresión , Infecciones por VIH , Homosexualidad Masculina , Distrés Psicológico , Conducta Sexual , Ideación Suicida , Humanos , Masculino , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Homosexualidad Masculina/psicología , Homosexualidad Masculina/estadística & datos numéricos , Estudios Longitudinales , China/epidemiología , Adulto , Conducta Sexual/psicología , Conducta Sexual/estadística & datos numéricos , Depresión/epidemiología , Depresión/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Adulto Joven , AdolescenteRESUMEN
Freeze-thaw (FT) aging can change the physicochemical characteristics of microplastics (MPs). The toxic impacts of FT-aged-MPs to soil invertebrates are poorly understood. Here the toxic mechanisms of FT-aged-MPs were investigated in earthworms after 28 d exposure. Results showed that FT 50 µm PE-MPs significantly increased reactive oxygen species (ROS) by 5.78-9.04 % compared to pristine 50 µm PE-MPs (41.80-45.05 ng/mgprot), whereas FT 500 µm PE-MPs reduced ROS by 7.52-7.87 % compared to pristine 500 µm PE-MPs (51.44-54.46 ng/mgprot). FT-PP-MPs significantly increased ROS and malondialdehyde (MDA) content in earthworms by 14.82-44.06 % and 46.75-110.21 %, respectively, compared to pristine PP-MPs (40.56-44.66 ng/mgprot, 0.41-2.53 nmol/mgprot). FT-aged PE- and PP-MPs caused more severe tissue damage to earthworms. FT-aged PE-MPs increased the alpha diversity of the gut flora of earthworms compared to pristine MPs. Earthworm guts exposed to FT-aged-MPs were enriched with differential microbial genera of contaminant degradation capacity. FT-PE-MPs affected membrane translocation by up-regulating lipids and lipid-like molecules, whereas FT-PP-MPs changed xenobiotic biodegradation and metabolism by down-regulating organoheterocyclic compounds compared to the pristine PE- and PP-MPs. This study concludes that FT-aged MPs cause greater toxicity to earthworms compared to pristine MPs.
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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
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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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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Proteínas Bacterianas , Infecciones Estreptocócicas , Streptococcus suis , Streptococcus suis/enzimología , Streptococcus suis/genética , Streptococcus suis/patogenicidad , Animales , Ratones , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Infecciones Estreptocócicas/microbiología , Respuesta al Choque Térmico , Proteasas ATP-Dependientes/metabolismo , Proteasas ATP-Dependientes/genética , Regulación Bacteriana de la Expresión Génica , Macrófagos/microbiología , Macrófagos/inmunología , Endopeptidasa Clp/metabolismo , Endopeptidasa Clp/genética , FemeninoRESUMEN
Long-term mortality effects of particulate air pollution have been investigated in a causal analytic frame, while causal evidence for associations with gaseous air pollutants remains extensively lacking, especially for carbon monoxide (CO) and sulfur dioxide (SO2). In this study, we estimated the causal relationship of long-term exposure to nitrogen dioxide (NO2), CO, SO2, and ozone (O3) with mortality. Utilizing the data from National Morbidity, Mortality, and Air Pollution Study, we applied a variant of difference-in-differences (DID) method with conditional Poisson regression and generalized weighted quantile sum regression (gWQS) to investigate the independent and joint effects. Independent exposures to NO2, CO, and SO2 were causally associated with increased risks of total, nonaccidental, and cardiovascular mortality, while no evident associations with O3 were identified in the entire population. In gWQS analyses, an interquartile range-equivalent increase in mixture exposure was associated with a relative risk of 1.067 (95% confidence interval: 1.010-1.126) for total mortality, 1.067 (1.009-1.128) for nonaccidental mortality, and 1.125 (1.060-1.193) for cardiovascular mortality, where NO2 was identified as the most significant contributor to the overall effect. This nationwide DID analysis provided causal evidence for independent and combined effects of NO2, CO, SO2, and O3 on increased mortality risks among the US general population.
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Contaminantes Atmosféricos , Contaminación del Aire , Exposición a Riesgos Ambientales , Dióxido de Nitrógeno , Ozono , Dióxido de Azufre , Humanos , Estados Unidos/epidemiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/efectos adversos , Dióxido de Azufre/análisis , Dióxido de Azufre/efectos adversos , Ozono/análisis , Ozono/efectos adversos , Ozono/toxicidad , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/efectos adversos , Dióxido de Nitrógeno/toxicidad , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Mortalidad , Monóxido de Carbono/análisis , Monóxido de Carbono/efectos adversos , Enfermedades Cardiovasculares/mortalidad , Material Particulado/efectos adversos , Material Particulado/análisis , Adolescente , Adulto JovenRESUMEN
BACKGROUND: This study explores the diagnostic value of combining fractional-order calculus (FROC) diffusion-weighted model with simultaneous multi-slice (SMS) acceleration technology in distinguishing benign and malignant breast lesions. METHODS: 178 lesions (73 benign, 105 malignant) underwent magnetic resonance imaging with diffusion-weighted imaging using multiple b-values (14 b-values, highest 3000 s/mm2). Independent samples t-test or Mann-Whitney U test compared image quality scores, FROC model parameters (D,, ), and ADC values between two groups. Multivariate logistic regression analysis identified independent variables and constructed nomograms. Model discrimination ability was assessed with receiver operating characteristic (ROC) curve and calibration chart. Spearman correlation analysis and Bland-Altman plot evaluated parameter correlation and consistency. RESULTS: Malignant lesions exhibited lower D, and ADC values than benign lesions (P < 0.05), with higher values (P < 0.05). In SSEPI-DWI and SMS-SSEPI-DWI sequences, the AUC and diagnostic accuracy of D value are maximal, with D value demonstrating the highest diagnostic sensitivity, while value exhibits the highest specificity. The D and combined model had the highest AUC and accuracy. D and ADC values showed high correlation between sequences, and moderate. Bland-Altman plot demonstrated unbiased parameter values. CONCLUSION: SMS-SSEPI-DWI FROC model provides good image quality and lesion characteristic values within an acceptable time. It shows consistent diagnostic performance compared to SSEPI-DWI, particularly in D and values, and significantly reduces scanning time.
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Neoplasias de la Mama , Imagen de Difusión por Resonancia Magnética , Humanos , Femenino , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias de la Mama/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Anciano , Curva ROC , Sensibilidad y Especificidad , Diagnóstico Diferencial , Estudios Retrospectivos , Interpretación de Imagen Asistida por Computador/métodos , Adulto JovenRESUMEN
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.