RESUMO
Target: We executed a Mendelian randomization (MR) investigation employing two distinct cohorts of genetic instrumental variables to elucidate the causal nexus between age at menarche (AAM) and the incidence of disparate breast cancer (BC) subtypes, in addition to the incidence of BC among first-degree kin. Methods: We aggregated statistical data pertaining to AAM and BC from various consortia representing a homogenous population cohort. MR analysis was conducted employing inverse variance weighted (IVW) methodology as the principal approach, complemented by weighted median and MR-Egger regression techniques for an exhaustive evaluation. To evaluate the presence of pleiotropy, we applied the MR-Egger intercept test, MR-PRESSO, and leave-one-out sensitivity analysis. Results: Upon exclusion of confounding SNP, an increment of one standard deviation in AAM was inversely correlated with the incidence of BC. (odds ratio [OR] 0.896, 95% confidence interval [CI] 0.831-0.968)/(OR 0.998, 95% CI 0.996-0.999) and estrogen receptor-positive (ER+) BC incidence (OR 0.895, 95% CI 0.814-0.983). It was also associated with reducing the risk of maternal BC incidence (OR 0.995, 95% CI 0.990-0.999) and sibling BC incidence (OR 0.997, 95% CI 0.994-0.999). No significant association was found between AAM and estrogen receptor-negative (ER-) BC incidence (OR 0.936, 95% CI 0.845-1.037). Conclusion: Our study substantiated the causal relationship between a delayed AAM and a diminished risk of BC in probands, as well as in their maternal progenitors and siblings. Furthermore, the analysis suggests that AAM exerts a considerable potential causal influence on the risk of developing Luminal-a/b subtype of BC.
RESUMO
The dissociation of H2O onγ-U (110) andγ-U (100) surfaces has been studied by usingab initiomolecular dynamics simulations at an elevated temperature of 800 K. The simulation results show the dissociation of H2O into the OH group and H atom, which are finally adsorbed on the uranium surface. The dissociation results from electronic interactions between surface uranium 6d/5 f states and the s orbitals of H and the 2p orbitals of O. Additionally, the hybridization between the 6d orbital of surface uranium and the 2p orbital of oxygen plays a dominant role in dissociative adsorption. A significant charge transfer from the uranium surface to the O and H atoms is observed, indicating the formation of U-O and U-H chemical bonds. Specifically, forγ-U (110) surface, the most preferred site for OH is the 3-fold hollow site and H occupies the bridge site or the 3-fold hollow site. On the other hand, forγ-U (100) surface, OH prefers to adsorb on the bridge site and H occupies the 3-fold hollow site or the bridge site. Furthermore, when H2O is placed on the TOP site, its initial dissociation on theγ-U (110) surface is easier compared to theγ-U (100) surface.
RESUMO
In recent years, CO2 flooding has become one of the main enhanced oil recovery (EOR) methods, especially for tight formations in different oilfields around the world. Most of the CO2 flooding projects carried out in the world are based on miscible flooding, however, this technique is less effective in China because of the depth of the reservoirs and the heavy components of the crude oil. Near-miscible flooding and immiscible flooding have also been gradually applied to China's domestic oil fields, and have achieved certain oil increase effects, but there are still some challenges such as gas channeling, corrosion, and solid phase deposition in the process of CO2 flooding. In this paper, through a detailed review of recent domestic and foreign cases of enhanced oil recovery, the effects of development methods of low permeability and ultralow permeability reservoirs under different miscible degrees are analyzed, and the solutions to some of the existing problems in field tests and experience are systematically summarized. According to the results of field tests, both miscible flooding and near-miscible flooding have similar effects and can achieve better recovery increment, with a long effect period and slow gas breakthrough speed. In addition, the problems of gas channeling, corrosion, and solid phase deposition occurring in the process of CO2 flooding are analyzed, and solutions such as a change in injection methods and coatings are put forward, which effectively promote the development of CO2 flooding technology. Those suggestions are of great significance for improving the oil recovery rate of unconventional oil reservoirs, ensuring the national energy supply, and low-carbon emissions reduction in China.
RESUMO
The normal aging process is accompanied by cognitive decline, and previous studies have indicated the crucial role of the hypothalamus in regulating both aging and cognition. However, the precise molecular mechanism underlying this relationship remains unclear. Therefore, this present study aimed to identify potential predictors of cognitive decline associated with aging specifically within the hypothalamus. To achieve this, we employed Morris water maze (MWM) testing to assess learning and memory differences between young and aged mice. Additionally, transcriptome sequencing was conducted on the hypothalamus of young and aged mice to identify potential genes. Subsequently, GO and KEGG analyses were performed to investigate the functions of differentially expressed genes (DEGs) and their associated biological pathways. Finally, the results obtained from sequencing analysis were further validated using qRT-PCR. Notably, MWM testing revealed a significant decrease in spatial learning and memory ability among aged mice. According to KEGG analysis, the DEGs primarily encompassed various biochemical signaling pathways related to immune system (e.g., C3; C4b; Ccl2; Ccl7; Cebpb; Clec7a; Col3a1; Cxcl10; Cxcl2; Fosb; Fosl1; Gbp5; H2-Ab1; Hspa1a; Hspa1b; Icam1; Il1b; Itga5; Itgax; Lilrb4a; Plaur; Ptprc; Serpine1; Tnfrsf10b; Tnfsf10), neurodegenerative disease (e.g., Atp2a1; Creb5; Fzd10; Hspa1a; Hspa1b; Il1b; Kcnj10; Nxf3; Slc6a3; Tubb6; Uba1y; Wnt9b), nervous system function (e.g., Chrna4; Chrna6; Creb5; Slc6a3),and aging (e.g., Creb5; Hspa1a; Hspa1b) among others. These identified genes may serve as potential predictors for cognitive function in elderly individuals and will provide a crucial foundation for further exploration into the underlying molecular mechanisms.
Assuntos
Disfunção Cognitiva , Doenças Neurodegenerativas , Humanos , Camundongos , Animais , Idoso , Perfilação da Expressão Gênica , Envelhecimento/genética , Disfunção Cognitiva/genética , Hipotálamo , TranscriptomaRESUMO
Theoretical calculations are performed to elucidate the adsorption behaviors and poisoning effects of CO gas on the ZrCo surface, which drastically limits its application in hydrogen isotopic storage. Specifically, the ionic Zr-Co bond on the surface leads to unique CO adsorption structures on different sites. The CO molecule tends to prefer a tilted adsorption configuration on the Co-Co bridge site. The electronic structures, charge distributions, and bonding characteristics are further explored to study the CO adsorption properties, which obey the electron density donation and back-donation mechanism. For different CO coverages, the stepwise adsorption energies of CO increase with the increasing of coverage, reaching the saturated coverage at nCO = 11. Then, the effects of temperature and partial pressure on CO coverage are evaluated using atomic thermodynamics. The computed phase diagram shows that the ZrCo(110) surface has a stable coverage of nCO = 6 at ambient temperature under ultrahigh vacuum conditions. The pre-adsorbed CO molecules lead to the charge redistribution and the d-band center downshift on the surface, which significantly affect hydrogen adsorption and dissociation. Our results provide insights into the poisoning mechanisms of the impurity gas on ZrCo alloys, which can be beneficial for designing high-performance ZrCo-based alloys with improved poisoning tolerance.
RESUMO
Intestinal ischemia/reperfusion (I/R) injury is a typical pathological course in the clinic with a high morbidity rate. Recent research has pointed out the critical role of ubiquitination during the occurrence and development of intestinal I/R by precisely mediating protein quality control and function. Here, we conducted an integrated multiomic analysis to identify critical ubiquitination-associated molecules in intestinal I/R and identified endoplasmic reticulum-located HRD1 as a candidate molecule. During intestinal I/R, excessive ER stress plays a central role by causing apoptotic pathway activation. In particular, we found that ER stress-mediated apoptosis was mitigated by HRD1 knockdown in intestinal I/R mice. Mechanistically, TMEM2 was identified as a new substrate of HRD1 in intestinal I/R by mass spectrometry analysis, which has a crucial role in attenuating apoptosis and promoting non-canonical ER stress resistance. A strong negative correlation was found between the protein levels of HRD1 and TMEM2 in human intestinal ischemia samples. Specifically, HRD1 interacted with the lysine 42 residue of TMEM2 and reduced its stabilization by K48-linked polyubiquitination. Furthermore, KEGG pathway analysis revealed that TMEM2 regulated ER stress-mediated apoptosis in association with the PI3k/Akt signaling pathway rather than canonical ER stress pathways. In summary, HRD1 regulates ER stress-mediated apoptosis through a non-canonical pathway by ubiquitinating TMEM2 and inhibiting PI3k/Akt activation during intestinal I/R. The current study shows that HRD1 is an intestinal I/R critical regulator and that targeting the HRD1/TMEM2 axis may be a promising therapeutic approach.
Assuntos
Estresse do Retículo Endoplasmático , Ubiquitina-Proteína Ligases , Animais , Humanos , Camundongos , Apoptose , Estresse do Retículo Endoplasmático/fisiologia , Isquemia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reperfusão , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , UbiquitinaçãoRESUMO
High entropy materials offer almost unlimited catalytic possibilities due to their variable composition, unique structure, and excellent electrocatalytic performance. However, due to the strong tendency of nanoparticles to coarsen and agglomerate, it is still a challenge to synthesize nanoparticles using simple methods to precisely control the morphology and size of the nanoparticles in large quantities, and their large-scale application is limited by high costs and low yields. Herein, a series of high-entropy oxides (HEOs) nanoparticles with high-density and ultrasmall size (<5 nm) loaded on carbon nanosheets with large quantities are prepared by Joule-heating treatment of gel precursors in a short period of time (≈60 s). Among them, the prepared (FeCoNiRuMn)3O4-x catalyst shows the best electrocatalytic activity for oxygen evolution reaction, with low overpotentials (230 mV @10 mA cm-2, 270 mV @100 mA cm-2), small Tafel slope (39.4 mV dec-1), and excellent stability without significant decay at 100 mA cm-2 after 100 h. The excellent performance of (FeCoNiRuMn)3O4-x can be attributed to the synergistic effect of multiple elements and the inherent structural stability of high entropy systems. This study provides a more comprehensive design idea for the preparation of efficient and stable high entropy catalysts.
RESUMO
BACKGROUND: It has been reported that patients with cholelithiasis may have changes in levels of cytokines and growth factors, while their causal relationships were still unclear. METHODS: This study was a bidirectional Mendelian randomization (MR) study. Datasets of 41 circulation cytokines and growth factors and the data on cholelithiasis were obtained. Six steps of strict instrumental variable filtration were set, and inverse-variance weighted analysis, MR-Egger regression, and weighted median test were used to identify the causal relationships. Benjamini-Hochberg method was used to adjust the P-values. RESULTS: After adjustments of P-values, four cytokines and growth factors were still causally associated with cholelithiasis significantly: interleukin 2 receptor alpha (adjusted P: 4.59E-02), interleukin 8 (adjusted P: 1.09E-02), monocyte-specific chemokine 3 (adjusted P: 2.73E-04), and stem cell factor (adjusted P: 2.73E-04). In the reverse MR analysis, no significant causal relationship was detected after adjustment. CONCLUSIONS: Four cytokines and growth factors, including interleukin 2 receptor alpha, interleukin 8, monocyte-specific chemokine 3, and stem cell factor, were proven to relate to cholelithiasis causally and unidirectionally.
Assuntos
Citocinas , Interleucina-8 , Humanos , Fator de Células-Tronco , Subunidade alfa de Receptor de Interleucina-2 , Análise da Randomização Mendeliana , Peptídeos e Proteínas de Sinalização Intercelular/genética , Estudo de Associação Genômica AmplaAssuntos
Carcinoma Adenoide Cístico , Neoplasias da Traqueia , Humanos , Glândula Tireoide/patologia , Traqueia/cirurgia , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoide Cístico/patologia , Neoplasias da Traqueia/diagnóstico por imagem , Neoplasias da Traqueia/cirurgia , Pescoço/patologiaRESUMO
Background: Hearing loss is found in more than 5 % of cases worldwide. Hearing loss is divided into three types: Sensorineural hearing loss, Combined hearing loss and Conductive hearing loss. Among them, no less than 50 % of pediatric cases of sensorineural hearing loss are genetic. In Henan, China, there are no statistics on the allele frequency of deafness gene variants. Methods: We divided 2178 subjects enrolled at the Third Affiliated Hospital of Zhengzhou College from January 2019 to March 2021 into a hearing loss group and a normal control group. We performed array and pathogenicity classification for screening the 15 deafness gene variants, calculated and compared the allele frequency of the deafness gene variants, and then compared the hearing loss diagnosis rate between the hearing loss group and the normal control group. Results: We found that in the hearing loss group, the overall allele frequency of all detected variants was 16.6 %. Comparative analysis showed that the allele frequencies of GJB2 c.235delC variant, GJB3 c.538C > T variant and SLC26A4 c.919-2A > G variant were significantly higher than those of the East Asian population average in the gnomAD database. At the same time, our study confirmed that GJB3 c.538C > T variant may not be the disease-causing variant of hearing loss. Conclusions: These results support genetic counseling and rational prediction of risk for deafness.
RESUMO
U-Mo alloys were considered to be the most promising candidates for high-density nuclear fuel. The uniaxial tensile behavior of nanocrystalline U-10Mo alloys with average grain sizes of 8-23 nm was systematically studied by molecular dynamics (MD) simulation, mainly focusing on the influence of average grain size on the mechanical properties and deformation mechanisms. The results show that Young's modulus, yield strength and ultimate tensile strength follow as average grain size increases. During the deformation process, localized phase transitions were observed in samples. Grain boundary sliding and grain rotation, as well as twinning, dominated the deformation in the smaller and larger grain sizes samples, respectively. Increased grain size led to greater localized shear deformation, resulting in greater stress drop. Additionally, we elucidated the effects of temperature and strain rate on tensile behavior and found that lower temperatures and higher strain rates not only facilitated the twinning tendency but also favored the occurrence of phase transitions in samples. Results from this research could provide guidance for the design and optimization of U-10Mo alloys materials.
RESUMO
Vascular smooth muscle cells (VSMCs) are critical elements of the vascular wall and play a crucial role in the genesis and development of atherosclerosis (AS). Increasingly, studies have indicated that long noncoding RNAs (lncRNAs) regulate VSMC proliferation, apoptosis, and other biological processes. Nevertheless, the role of lncRNA NFIA-AS1 (hereinafter referred to as NFIA-AS1) in VSMCs and AS remains unclear. Quantitative real-time PCR (qRT-PCR) was performed to analyze the messenger RNA (mRNA) levels of NFIA-AS1 and miR-125a-3p. CCK-8 and EdU staining were performed to detect VSMC proliferation. VSMC apoptosis was evaluated by flow cytometry. The expression of various proteins was detected using western blotting. The levels of inflammatory cytokines secreted by VSMCs were measured by enzyme linked immunosorbent assay (ELISA). The binding sites of NFIA-AS1 and miR-125a-3p, as well as miR-125a-3p and AKT1, were analyzed using bioinformatics methods and validated using a luciferase reporter assay. The function of NFIA-AS1/miR-125a-3p/AKT1 in VSMCs was clarified through loss- and gain-of-functional experiments. We confirmed that NFIA-AS1 was highly expressed in AS tissues and VSMCs induced by oxidized low-density lipoprotein (Ox-LDL). Knockdown of NFIA-AS1 restrained the exceptional growth of Ox-LDL-induced VSMCs, promoted their apoptosis, and decreased the secretion of inflammatory factors and expression of adhesion factors. In addition, NFIA-AS1 regulated the proliferation, apoptosis, and inflammatory response of VSMCs through the miR-125a-3p/AKT1 axis, suggesting that NFIA-AS1 may be a potential therapeutic target for AS.
RESUMO
BACKGROUND: To evaluate the aqueous humor (AH) levels of cytokines in primary open-angle glaucoma (POAG) patients and cataract patients. METHODS: Thirty-eight POAG patients and 26 cataract patients were recruited. Peripheral blood (PB) was collected from each subject. The POAG group was divided into 2 subgroups according to the severity of visual field defects. The cutoff point of the mean deviation (MD) of the visual field was -12 dB. AH was obtained at the time of anterior chamber puncture during cataract or glaucoma surgery by using a 27-gauge needle attached to a microsyringe. AH and PB levels of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta2 (TGF-ß2) and IL-4 were assayed by enzyme-linked immunosorbent assay. Postoperative intraocular pressures (IOPs) of POAG patients were recorded during the follow-up period. RESULTS: TNF-α and TGF-ß2 showed significantly higher AH levels in the POAG group than in the cataract group (P < 0.001 and P = 0.001, respectively). For the POAG group, preoperative IOPs were significantly positively correlated with AH levels of TNF-α (r2 = 0.129, P = 0.027) and TGF-ß2 (r2 = 0.273, P = 0.001). AH levels of TGF-ß2 were significantly different among cataract patients, POAG patients with MD> -12 dB and POAG patients with MD≤ -12 dB (P = 0.001). AH levels of TNF-α were significantly positively associated with IOP reduction after trabeculectomy (P = 0.025). AH and PB levels of cytokines were not related to the long-term success of trabeculectomy. CONCLUSION: The levels of TNF-α and TGF-ß2 showed different profiles in POAG patients and cataract patients. AH levels of TGF-ß2 were correlated with the severity of glaucomatous neuropathy in POAG patients. The findings suggest possible roles for cytokines in the pathogenesis and development of POAG.
Assuntos
Humor Aquoso , Catarata , Citocinas , Glaucoma de Ângulo Aberto , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Campos Visuais , Humor Aquoso/metabolismo , Citocinas/sangue , Pressão Intraocular , Interleucina-2/sangue , Interleucina-4/sangue , Fator de Crescimento Transformador beta2/sangue , Fator de Necrose Tumoral alfa/sangue , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Intestinal ischemia reperfusion (I/R) is a common clinical pathological process. We previously reported that pharmacological inhibition of protein kinase C (PKC) ßII with a specific inhibitor attenuated gut I/R injury. However, the endogenous regulatory mechanism of PKCßII inactivation is still unclear. Here, we explored the critical role of caveolin-1 (Cav1) in protecting against intestinal I/R injury by regulating PKCßII inactivation. PKCßII translocated to caveolae and bound with Cav1 after intestinal I/R. Cav1 was highly expressed in the intestine of mice with I/R and IEC-6 cells stimulated with hypoxia/reoxygenation (H/R). Cav1-knockout (KO) mice suffered from worse intestinal injury after I/R than wild-type (WT) mice and showed extremely low survival due to exacerbated systemic inflammatory response syndrome (SIRS) and remote organ (lung and liver) injury. Cav1 deficiency resulted in excessive PKCßII activation and increased oxidative stress and apoptosis after intestinal I/R. Full-length Cav1 scaffolding domain peptide (CSP) suppressed excessive PKCßII activation and protected the gut against oxidative stress and apoptosis due to I/R injury. In summary, Cav1 could regulate PKCßII endogenous inactivation to alleviate intestinal I/R injury. This finding may represent a novel therapeutic strategy for the prevention and treatment of intestinal I/R injury.
Assuntos
Caveolina 1 , Traumatismo por Reperfusão , Animais , Camundongos , Apoptose , Caveolina 1/genética , Caveolina 1/metabolismo , Isquemia , Proteína Quinase C beta/genética , Proteína Quinase C beta/metabolismo , Reperfusão , Traumatismo por Reperfusão/metabolismoRESUMO
Objective: To investigate the effect of comprehensive nursing combined with high-quality nursing intervention on the compliance, anxiety, and mental state of patients with chronic hepatitis B undergoing antiviral therapy. Methods: A total of 100 patients with chronic hepatitis B admitted to China-Japan Union Hospital from December 2017 to August 2020 were recruited and assigned to receive either routine nursing (control group, n = 50) or comprehensive nursing plus high-quality nursing (observation group, n = 50) via the random number table method. The outcome measures included compliance, psychological state, and treatment effects. Results: Before the nursing, there was no significant difference in the compliance scores between the two groups of patients (P > 0.05). After the nursing, the observation group had higher compliance scores than the control group (P < 0.001). Before the intervention, the two groups had similar Self-Rating Anxiety Scale (SAS) scores (P > 0.05). After the intervention, patients in the observation group showed lower SAS scores and a lower incidence of negative emotions as compared to the control group (P < 0.001). The observation group showed a better outcome in terms of quality of life, Medical Coping Modes Questionnaire (MCMQ) scores, and the General Self-Efficacy Scale (GSES) scores when compared to those of the control group (P < 0.001). A higher treatment effective rate was witnessed in the observation group in contrast to the control group (P < 0.001). Conclusion: The comprehensive nursing model combined with high-quality nursing intervention improves the psychological state and compliance of patients with chronic hepatitis B, with favorable treatment efficiency, which shows good potential for clinical promotion.
RESUMO
Drug repositioning and drug reuse are the heated topics in the field of oncology in recent years. These two concepts refer to seeking effective drugs for cancer that are not originally intended to treat cancer. The survival benefits are then analyzed by combining the re-positioned drugs with conventional cancer treatment methods. Simvastatin is a clinically commonly used hyperlipidemia drug and exerts the effect of preventing cardiovascular diseases. Recent studies have found that simvastatin has great potential in the treatment of colorectal cancer, and a large number of clinical studies have used simvastatin as an adjuvant drug to help treat metastatic colorectal cancer.
RESUMO
Background: The relationship between sarcopenia and surgery has attracted an increasing number of researchers in recent years. Our study aimed to identify the current research hotspot and status in this field by using bibliometric and visualization analysis. Methods: Publications about the relationship between sarcopenia and surgery that met the inclusion criteria were collected from the Science Citation Index Expanded. The bibliometric and visualized studies were performed using VOSviewer, and R. Results: A total of 2,261 documents on the relationship between sarcopenia and surgery were included in our study. These articles were written by 13,757 authors from 2,703 institutions in 70 countries and were published in 772 journals. The USA is the most productive and influential country in this field (524 publications and 15,220 citations). The Udice French Research Universities was the most productive institution in this field (57 publications), and the University of Alberta had the largest number of citations. Annuals of Surgical Oncology published the most studies in this field. Shen Xian was the most productive author in this field (number of publications = 19), and Baracos Vickie was the most influential author, whose studies in this field had been cited 2,209 times. The cluster analysis was performed and visualized, and the keywords were classified into 6 clusters: Cluster 1 (body composition and nutrition), Cluster 2 (sarcopenia), Cluster 3 (malnutrition and cachexia), Cluster 4 (cancer surgery), Cluster 5 (elderly and frailty), Cluster 6 (neuromuscular scoliosis). Conclusion: The relationship between sarcopenia and surgery was still a controversial and well-discussed topic in recent years. Our study showed that the study in this field mainly focused on sarcopenia, oncology surgery, orthopedics, and nutrition.
RESUMO
Objective: This study aimed to investigate the feasibility of using indocyanine green (ICG) near-infrared (NIR) imaging during lymphadenectomy for oesophageal cancer. Methods: Eighty-seven patients with primary oesophageal cancer were enrolled in this study. All the enrolled patients received an endoscopic injection of ICG between 40â min and 23â h before surgery. Nodal dissection during surgery was performed under fluorescence imaging visualisation, with the NIR signal shown in purple. ICG+ or ICG- nodes were recorded station by station and were microscopically evaluated. Results: Endoscopic peritumoral ICG injection was successfully performed in all patients. Major post-surgery complications included wound infection, pleural effusion, dysphonia, pneumonia and anastomotic fistula. No patients experienced ICG-related adverse events. A total of 2,584 lymph nodes were removed, and the mean number of lymph nodes for each patient was 29.70 ± 9.24. Most of the removed nodes (97.83%) were ICG+, and 3.32% of the ICG+ nodes were metastatic. No metastatic nodes were ICG- or belonged to an ICG- lymph node station. The time from ICG injection to surgery did not affect the number of harvested lymph nodes. Conclusions: The use of ICG-NIR imaging during oesophageal cancer surgery can enhance the visualisation of lymph nodes during surgery. It is a feasible, safe and helpful technique for lymphadenectomy.
RESUMO
Fatty acid ß-oxidation is an essential pathogenic mechanism in nonalcoholic fatty liver disease (NAFLD), and TATA-box binding protein associated factor 9 (TAF9) has been reported to be involved in the regulation of fatty acid ß-oxidation. However, the function of TAF9 in NAFLD, as well as the mechanism by which TAF9 is regulated, remains unclear. In this study, we aimed to investigate the signaling mechanism underlying the involvement of TAF9 in NAFLD and the protective effect of the natural phenolic compound Danshensu (DSS) against NAFLD via the HDAC1/TAF9 pathway. An in vivo model of high-fat diet (HFD)-induced NAFLD and a palmitic acid (PA)-treated AML-12 cell model were developed. Pharmacological treatment with DSS significantly increased fatty acid ß-oxidation and reduced lipid droplet (LD) accumulation in NAFLD. TAF9 overexpression had the same effects on these processes both in vivo and in vitro. Interestingly, the protective effect of DSS was markedly blocked by TAF9 knockdown. Mechanistically, TAF9 was shown to be deacetylated by HDAC1, which regulates the capacity of TAF9 to mediate fatty acid ß-oxidation and LD accumulation during NAFLD. In conclusion, TAF9 is a key regulator in the treatment of NAFLD that acts by increasing fatty acid ß-oxidation and reducing LD accumulation, and DSS confers protection against NAFLD through the HDAC1/TAF9 pathway.
RESUMO
PURPOSE: To analyze the epidemiological characteristics of inpatients who underwent surgery for glaucoma at Tianjin Eye Hospital from 2013 to 2017. METHODS: All glaucoma inpatients who underwent surgery at Tianjin Eye Hospital from 2013 to 2017 were evaluated. The relationships of age and sex with different types of glaucoma were analyzed. The differences in the prevalence and family history of glaucoma among patients with different systemic diseases were compared. Additionally, the effects of different surgical methods for primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) were compared. RESULTS: A total of 4539 patients with glaucoma were retrospectively analyzed. The most prevalent type was PACG (60.15%), followed by secondary glaucoma (SG, 25.53%), POAG (7.6%), uncontrollable intraocular pressure (IOP) after antiglaucoma surgery (4.71%), mixed glaucoma (MG, 10%), and congenital glaucoma (CG, 0.9%). The main surgical methods were phacoemulsification (phaco), phacotrabeculectomy (phaco-trab), and trabeculectomy (trab). The rate of phaco-trab increased, while that of trab decreased. The proportion of women in the PACG group was higher than those in the POAG and SG groups, and there was a pronounced tendency for family clustering (P < 0.001), while in the POAG and SG groups, the proportions of men and those with diabetes were higher (P < 0.05). CONCLUSIONS: In Tianjin Eye Hospital from 2013 to 2017, the main type of glaucoma was PACG. Female sex and a family history of glaucoma were risk factors for PACG, while male sex and hyperglycemia were risk factors for POAG and SG. Among the antiglaucoma surgery methods, the proportion of phaco-trab increased, while the proportion of trab decreased.