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1.
J Affect Disord ; 367: 210-218, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39233239

RESUMO

OBJECTIVE: The prevalence of Lower Urinary Tract Symptoms suggestive of Benign Prostatic Hyperplasia (LUTS/BPH) is notably high and potentially elevates the likelihood of depressive symptoms. This study was designed to employ both cross-sectional and longitudinal methodologies to explore the correlation between LUTS/BPH and depressive symptoms among middle-aged and elderly men in China. METHODS: This investigation utilized data from the China Health and Retirement Longitudinal Study (CHARLS), with the initial dataset from 2015 serving as the baseline and subsequent data from 2018 and 2020 facilitating longitudinal analysis. The study encompassed a baseline cohort of 5156 men aged 45 years and above, and an expansive longitudinal analytical sample of 23,530 participants spanning from 2015 to 2020. The assessment of depressive symptoms was conducted using the 10-item Center for Epidemiological Studies Depressive Symptoms Scale (CESD-10). To investigate the factors associated with LUTS/BPH, the relationship between LUTS/BPH and depressive symptoms, and to evaluate the incidence rate of depressive symptoms onset based on LUTS/BPH status, multivariate logistic analyses and logistic regression models were employed. RESULTS: Our results reveal a markedly higher incidence of depressive symptoms among individuals with LUTS/BPH, at 30.16 %, compared to 22.94 % in those without LUTS/BPH. This pattern was consistent in both mild and moderate depressive symptoms categories. However, the prevalence of severe depressive symptoms did not exhibit a significant disparity between the two groups. Longitudinal analysis spanning from 2015 through 2018 and 2020 further corroborated these observations. Individuals with LUTS/BPH showed a substantially higher incidence of depressive symptoms across all severity levels compared to those without LUTS/BPH. Specifically, the presence of LUTS/BPH was linked to a 53 % heightened risk of mild depressive symptoms, a 45 % increase in moderate depressive symptoms, and an alarming 229 % surge in severe depressive symptoms risk between 2015 and 2018. Additionally, from 2015 to 2020, there was a 30 % increased risk for mild depressive symptoms, a 41 % rise for moderate depressive symptoms, and a 106 % escalation in the risk of severe depressive symptoms among those with LUTS/BPH. CONCLUSION: In middle-aged and older Chinese adults, LUTS/BPH were correlated with an elevated risk of depressive symptoms.

2.
Autophagy ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316516

RESUMO

Metabolic reprogramming is pivotal in cancer stem cell (CSC) self-renewal. However, the intricate regulatory mechanisms governing the crosstalk between metabolic reprogramming and liver CSCs remain elusive. Here, using a metabolic CRISPR-Cas9 knockout screen, we identify ATP6V1D, a subunit of the vacuolar-type H+-translocating ATPase (V-ATPase), as a key metabolic regulator of hepatocellular carcinoma (HCC) stemness. Elevated ATP6V1D expression correlates with poor clinical outcomes in HCC patients. ATP6V1D knockdown inhibits HCC stemness and malignant progression both in vitro and in vivo. Mechanistically, ATP6V1D enhances HCC stemness and progression by maintaining macroautophagic/autophagic flux. Specifically, ATP6V1D not only promotes lysosomal acidification, but also enhances the interaction between CHMP4B and IST1 to foster ESCRT-III complex assembly, thereby facilitating autophagosome-lysosome fusion to maintain autophagic flux. Moreover, silencing CHMP4B or IST1 attenuates HCC stemness and progression. Notably, low-dose bafilomycin A1 targeting the V-ATPase complex shows promise as a potential therapeutic strategy for HCC. In conclusion, our study highlights the critical role of ATP6V1D in driving HCC stemness and progression via the autophagy-lysosomal pathway, providing novel therapeutic targets and approaches for HCC treatment.

3.
Acta Trop ; 260: 107391, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39278520

RESUMO

Buffaloes cannot mount a robust adaptive immune response to secondary infection by Fasciola gigantica. Even if excretory and secretory products (ESPs) exhibit potent immunoregulatory effects during primary infection, research on ESPs in secondary infection is lacking, even though the ESP components that are excreted/secreted during secondary infection are unknown. Therefore, qualitative analysis of ESP during secondary infection was performed and compared with that of primary infection to deepen the recognition of secondary infection and facilitate immunoregulatory molecules screening. Buffaloes were divided into three groups: A (n = 3, noninfected), B (n = 3, primary infection) and C (n = 3, secondary infection). Buffaloes in the primary (0 weeks post infection; wpi) and secondary (-4 and 0 wpi) infection groups were infected with 250 metacercariae by oral administration. Then, sera were collected from groups at different wpi, and interacting proteins were precipitated by coimmunoprecipitation (Co-IP), qualitatively analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to infer their potential functions. In group C, 324 proteins were identified, of which 76 proteins were consistently identified across 7 time points (1, 3, 6, 8, 10, 13, and 16 wpi). Compared with 87 proteins consistently identified in group B, 22 proteins were identified in group C. Meanwhile, 34 proteins were only identified in group C compared to 200 proteins identified in group B. Protein pathway analysis indicated that these proteins were mainly involved in the cellular processes and metabolism of F. gigantica. Among them, 14-3-3θ was consistently identified in group C and may be involved in various cellular processes and innate immune signalling pathways. Members of the HSP family were identified in both groups B and C and may function in both primary and secondary infection processes. The proteins discovered in the present study will help to deepen the understanding of the molecular interactions between F. gigantica and buffalo during secondary infection and facilitate the identification of new potential immunoregulatory molecules.

4.
Cancer Manag Res ; 16: 1189-1204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39282606

RESUMO

Background: The resistance to endocrine therapy can lead to recurrence and metastasis of breast cancer (BC), affecting the survival period. Tiaogan Bushen Xiaoji (TGBSXJ) Formula, a traditional Chinese medicine (TCM) decoction, has been widely used in the treatment of estrogen receptor-positive (ER+) BC. However, the underlying mechanism of TGBSXJ Formula in ER+BC treatment has not been totally elucidated. Methods: Network pharmacology (NP) and RNA sequencing were used to predict the candidate ingredients and explore the potential targets of TGBSXJ Formula. Then, the results of NP and RNA sequencing were investigated by in vitro experiments. Results: Active ingredients of TGBSXJ Formula mainly included Mangiferin, Rutin, Anemarrhena asphodeloides saponin BII, Ganoderic acid A and Acacetin, etc. A protein-protein interaction (PPI) network was created based on the active ingredients of TGBSXJ Formula and target genes of ER+ BC, in which TGF-ß, MMP2 and SMAD3 were defined as the hub genes. In vitro experiments showed that TGBSXJ Formula significantly inhibited the viability, colony ability and migration of ER+ BC cells, and significantly increased the sensitivity to TAM. Western blot analysis showed that TGBSXJ Formula significantly downregulated TGF-ß, E-cadherin, MMP2, MMP9, N-cadherin, p-Smad2 and p-Smad3 in ER+ BC cells. Conclusion: TGBSXJ Formula increases the sensitivity of ER+ BC cells to TAM by inhibiting the TGF-ß/Smad signaling pathway.

5.
Huan Jing Ke Xue ; 45(9): 5548-5556, 2024 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-39323171

RESUMO

This study investigated the impact of single and combined applications of three foliar inhibitors on the accumulation of cadmium (Cd) and arsenic (As) in rice grains. Two rice varieties, Songyazao 1 (for early rice) and Wuxiang Youyue (for late rice), were selected for this experiment. We established nine treatments using a pot experiment method, including a control (CK) treated with no foliar inhibitor and three individual foliar inhibitors: cysteine (L-Cys), potassium sulfide (K2S), and dipotassium hydrogen phosphate (K2HPO4). We then combined the applications of two foliar inhibitors: L-Cys with low/high concentrations of K2S, L-Cys with low/high concentrations of K2HPO4, and K2S with a low concentration of K2HPO4. The results showed that the single and combined applications of foliar inhibitors reduced Cd and As concentrations in rice grains. The Cd content in brown rice treated with L-Cys and K2S/K2HPO4 was reduced below the standard limit for food safety of 0.20 mg·kg-1. Compared to the CK, the content of inorganic arsenic (IAs) in early and late rice decreased by 4.68%-56.75% and 2.84%-16.91%, respectively. Foliar inhibitors applied individually or in combinations facilitated the transport of Cd and As from the stem to the leaf while inhibiting their transport from the leaf to the rice grain. This resulted in the sequestration of Cd and As within the leaf cell wall, ultimately reducing the content of these elements in rice grains. Among the combination treatments, the application of L-Cys and high-concentration K2S achieved the best results. The Cd content in early and late rice decreased by 37.64% and 26.37%, respectively, falling below 0.20 mg·kg-1. The IAs content in early and late rice was reduced to 0.10 mg·kg-1 (below 0.20 mg·kg-1) and 0.24 mg·kg-1, respectively. This study provides a valuable theoretical foundation and empirical data to support the achievement of safe rice production practices.


Assuntos
Arsênio , Cádmio , Cisteína , Oryza , Compostos de Potássio , Sulfetos , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Cádmio/metabolismo , Arsênio/metabolismo , Cisteína/metabolismo , Fosfatos/metabolismo , Folhas de Planta/metabolismo , Poluentes do Solo/metabolismo , Contaminação de Alimentos/análise , Fertilizantes , Sementes/metabolismo , Sementes/química
6.
Artigo em Inglês | MEDLINE | ID: mdl-39293059

RESUMO

Phosphoric acid (PA) leakage and volume expansion are critical factors limiting long-term stable operation of PA-doped polybenzimidazole (PBI) for high-temperature proton exchange membrane fuel cells. Enhancing the interaction between the polymer matrix and PA provides an effective way to minimize PA loss and inhibit excessive membrane swelling. The covalent organic frameworks (COFs) are helpful in improving the performance of PA-PBI membranes due to the robust frameworks, adjustable structures, and good compatibility with polymers. Here, in this work, we synthesized porous COFs named TTA-DFP containing triazine rings and pyridine groups at room temperature for as short as 2 h without oxygen isolation. TTA-DFP was then blended with commercial poly[2,2'-(p-oxidiphenylene)-5,5'-benzimidazole] (OPBI) to prepare composite membranes. The abundant alkaline N sites in TTA-DFP exhibit strong interactions with PA and OPBI, which not only provide more proton transport pathways to promote proton conduction but also immobilize PA in acidophilic micropores to reduce PA leakage. The composite membranes exhibit a much lower volume swelling ratio than that of the OPBI membrane. The PA retention of the composite membrane after 120 h of treatment at 80 °C and 40% relative humidity can reach as high as 84.6%. Particularly, the proton conductivity of the composite membrane doped with 15 wt% TTA-DFP achieves 0.112 S cm-1 at 180 °C without humidification with a swelling ratio of 24.1%. In addition, it has an optimal peak power density of 824.4 mW cm-2 at 180 °C, which is 1.7 times that of the OPBI membrane. The stability of the composite membrane is much better than that of OPBI at a current density of 0.3 A cm-2 at 140 °C for 120 h.

7.
J Perinat Med ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39253747

RESUMO

OBJECTIVES: To estimate the number of pregnancies complicated by vasa previa annually in nine developed countries, and the potential preventable stillbirths associated with undiagnosed cases. We also assessed the potential impact of universal screening for vasa previa on reducing stillbirth rates. METHODS: We utilized nationally-reported birth and stillbirth data from public databases in the United States, United Kingdom, Canada, Germany, Ireland, Greece, Sweden, Portugal, and Australia. Using the annual number of births and the number and rate of stillbirths in each country, and the published incidence of vasa previa and stillbirth rates associated with the condition, we estimated the expected annual number of cases of vasa previa, those that would result in a livebirth, and the potential preventable stillbirths with and without prenatal diagnosis. RESULTS: There were 6,099,118 total annual births with 32,550 stillbirths, corresponding to a summary stillbirth rate of 5.34 per 1,000 pregnancies. The total expected vasa previa cases was estimated to be 5,007 (95 % CI: 3,208-7,201). The estimated number of livebirths would be 4,937 (95 % CI: 3,163-7,100) and 3,610 (95 % CI: 2,313-5,192) in pregnancies with and without a prenatal diagnosis of VP. This implies that prenatal diagnosis would potentially prevent 1,327 (95 % CI: 850-1,908) stillbirths in these countries, corresponding to a potential reduction in stillbirth rate by 4.72 % (95 % CI: 3.80-5.74) if routine screening for vasa previa was performed. CONCLUSIONS: Our study highlights the importance of universal screening for vasa previa and suggests that prenatal diagnosis of prevention could potentially reduce 4-5 % of stillbirths.

8.
Oncogene ; 43(34): 2564-2577, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39020072

RESUMO

Perineural invasion (PNI) is an adverse prognostic feature of pancreatic ductal adenocarcinoma (PDAC). However, the understanding of the interactions between tumors and neural signaling within the tumor microenvironment is limited. In the present study, we found that MUC21 servers as an independent risk factor for poor prognosis in PDAC. Furthermore, we demonstrated that MUC21 promoted the metastasis and PNI of PDAC cells by activating JNK and inducing epithelial-mesenchymal transition (EMT). Mechanistically, glial cell-derived neurotrophic factor, secreted by Schwann cells, phosphorylates the intracellular domain S543 of MUC21 via CDK1 in PDAC cells, facilitating the interaction between MUC21 and RAC2. This interaction leads to membrane anchoring and activation of RAC2, which in turn activates the JNK/ZEB1/EMT axis, ultimately enhancing the metastasis and PNI of PDAC cells. Our results present a novel mechanism of PNI, suggesting that MUC21 is a potential prognostic marker and therapeutic target for PDAC.


Assuntos
Carcinoma Ductal Pancreático , Transição Epitelial-Mesenquimal , Invasividade Neoplásica , Neoplasias Pancreáticas , Proteína RAC2 de Ligação ao GTP , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Fosforilação , Animais , Linhagem Celular Tumoral , Camundongos , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas rac de Ligação ao GTP/genética , Prognóstico , Metástase Neoplásica , Masculino , Feminino , Camundongos Nus
9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(4): 656-660, 2024 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-39041561

RESUMO

OBJECTIVE: To explore the clinical safety and effectiveness of self-draining ureteral stent with thread in kidney transplant recipients in renal transplantation. METHODS: This study is a prospective cohort clinical study in the Department of Urology of Peking University People's Hospital from November 2022 to January 2024. The ureteral stent with thread group, in which a 2-0 Mersilene suture of 20-30 cm was used at the bladder end of the ureteral stent during the operation. On the 9th day after the operation, the suture attached to the end of the ureteral stent was expelled out of the urethral orifice with the urine when the catheter was removed. The ureteral stent could be removed along with the suture. As to the cystoscope group, a ureteral stent was routinely placed during kidney transplantation, and the ureteral stent was removed under local infiltration anesthesia through cystoscopy after the operation. The pain scores [numerical rating scale (NRS)-11] during catheter removal and the incidence of urinary tract infections were observed and compared between the two groups. t test was used to compare the pain scores of indwelling ureteral stents and ureteral stents removal between the two groups, and Chi-square test was used to compare the occurrence of urinary system complications within 3 months after operation between the two groups. P < 0.05 was considered statistically significant. RESULTS: As of March 2024, all the recipients were followed up for an average of 6 months (3 to 12 months) postoperatively. A total of 46 kidney transplantation patients were included, with 21 in the ureteral stent with thread group and 25 in the cystoscope group. There were no statistically significant differences between the two groups in age distribution, male-to-female ratio, and deceased versus live donor grafts. Three months after renal transplantation, there were 15 cases of urinary tract infection in the cystoscope group and 4 cases in the ureteral stent with thread group (P=0.007). No significant urinary fistula, wound infection, or ureteral stenosis occurred in either group. No stent-related complications, stent migration, or stone formation were observed. The postoperative bladder spasm symptom scores for indwelling ureteral stents in the cystoscope group and the ureteral stent with thread group were 4.4±2.5 and 4.6±2.4, respectively, with no statistically significant difference (t=0.29, P=0.773). However, the pain scores during ureteral stent removal were 4.9±1.6 and 3.0±1.0 in the two groups, respectively, with a statistically significant diffe-rence (t=5.017, P < 0.001). The total costs of indwelling and removing ureteral stents in the cystoscopy group and the ureteral stent with thread group were 6 452.0 (5 539.5, 6 452.0) yuan and 3 225.0 (3 225.0, 3 225.0) yuan, respectively, and the difference was statistically significant (P < 0.001). CONCLUSION: Compared with the conventional transplanted kidney ureteral stent, the self-discharge ureteral stent technique with sutures is simpler, has a shorter ureteral stent inlay time, reduces the symptoms of bladder spasms, significantly reduces the cost of catheterization, and has fewer postoperative urinary system complications. It is a worthy improved surgical method to be promoted.


Assuntos
Transplante de Rim , Stents , Ureter , Humanos , Transplante de Rim/efeitos adversos , Stents/efeitos adversos , Ureter/cirurgia , Estudos Prospectivos , Feminino , Masculino , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Suturas , Pessoa de Meia-Idade
10.
Proc Natl Acad Sci U S A ; 121(24): e2311180121, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38830101

RESUMO

As a sustainable and promising approach of removing of nitrogen oxides (NOx), catalytic reduction of NOx with H2 is highly desirable with a precise understanding to the structure-activity relationship of supported catalysts. In particular, the dynamic evolution of support at microscopic scale may play a critical role in heterogeneous catalysis, however, identifying the in situ structural change of support under working condition with atomic precision and revealing its role in catalysis is still a grand challenge. Herein, we visually capture the surface lattice expansion of WO3-x support in Pt-WO3-x catalyst induced by NO in the exemplified reduction of NO with H2 using in situ transmission electron microscopy and first reveal its important role in enhancing catalysis. We find that NO can adsorb on the oxygen vacancy sites of WO3-x and favorably induce the reversible stretching of W-O-W bonds during the reaction, which can reduce the adsorption energy of NO on Pt4 centers and the energy barrier of the rate-determining step. The comprehensive studies reveal that lattice expansion of WO3-x support can tune the catalytic performance of Pt-WO3-x catalyst, leading to 20% catalytic activity enhancement for the exemplified reduction of NO with H2. This work reveals that the lattice expansion of defective support can tune and optimize the catalytic performance at the atomic scale.

11.
BMC Vet Res ; 20(1): 252, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851737

RESUMO

BACKGROUND: The insulin/insulin-like signalling (IIS) pathway is common in mammals and invertebrates, and the IIS pathway is unknown in Fasciola gigantica. In the present study, the IIS pathway was reconstructed in F. gigantica. We defined the components involved in the IIS pathway and investigated the transcription profiles of these genes for all developmental stages of F. gigantica. In addition, the presence of these components in excretory and secretory products (ESPs) was predicted via signal peptide annotation. RESULTS: The core components of the IIS pathway were detected in F. gigantica. Among these proteins, one ligand (FgILP) and one insulin-like molecule binding protein (FgIGFBP) were analysed. Interestingly, three receptors (FgIR-1/FgIR-2/FgIR-3) were detected, and a novel receptor, FgIR-3, was screened, suggesting novel functions. Fg14-3-3ζ, Fgirs, and Fgpp2a exhibited increased transcription in 42-day-old juveniles and 70-day-old juveniles, while Fgilp, Fgigfb, Fgsgk-1, Fgakt-1, Fgir-3, Fgpten, and Fgaap-1 exhibited increased transcription in metacercariae. FgILP, FgIGFBP, FgIR-2, FgIR-3, and two transcription factors (FgHSF-1 and FgSKN-1) were predicted to be present in FgESPs, indicating their exogenous roles. CONCLUSIONS: This study helps to elucidate the signal transduction pathway of IIS in F. gigantica, which will aid in understanding the interaction between flukes and hosts, as well as in understanding fluke developmental regulation, and will also lay a foundation for further characterisation of the IIS pathways of trematodes.


Assuntos
Fasciola , Proteínas de Helminto , Insulina , Transdução de Sinais , Animais , Fasciola/genética , Fasciola/metabolismo , Insulina/metabolismo , Proteínas de Helminto/metabolismo , Proteínas de Helminto/genética
12.
Adv Sci (Weinh) ; 11(32): e2401712, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38900084

RESUMO

Thyroid cancer is the most common type of endocrine cancer, and most patients have a good prognosis. However, the thyroid cancer differentiation status strongly affects patient response to conventional treatment and prognosis. Therefore, exploring the molecular mechanisms that influence the differentiation of thyroid cancer is very important for understanding the progression of this disease and improving therapeutic options. In this study, SETMAR as a key gene that affects thyroid cancer differentiation is identified. SETMAR significantly regulates the proliferation, epithelial-mesenchymal transformation (EMT), thyroid differentiation-related gene expression, radioactive iodine uptake, and sensitivity to MAPK inhibitor-based redifferentiation therapies of thyroid cancer cells. Mechanistically, SETMAR methylates dimethylated H3K36 in the SMARCA2 promoter region to promote SMARCA2 transcription. SMARCA2 can bind to enhancers of the thyroid differentiation transcription factors (TTFs) PAX8, and FOXE1 to promote their expression by enhancing chromatin accessibility. Moreover, METTL3-mediated m6A methylation of SETAMR mRNA is observed and showed that this medication can affect SETMAR expression in an IGF2BP3-dependent manner. Finally, the METTL3-14-WTAP activator effectively facilitates the redifferentiation of thyroid cancer cells via the SETMAR-SMARCA2-TTF axis utilized. The research provides novel insights into the molecular mechanisms underlying thyroid cancer dedifferentiation and provides a new approach for therapeutically promoting redifferentiation.


Assuntos
Diferenciação Celular , Montagem e Desmontagem da Cromatina , Neoplasias da Glândula Tireoide , Fatores de Transcrição , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Humanos , Diferenciação Celular/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Montagem e Desmontagem da Cromatina/genética , Camundongos , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Transição Epitelial-Mesenquimal/genética , Proliferação de Células/genética , Modelos Animais de Doenças
13.
Autophagy ; 20(10): 2146-2163, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38797513

RESUMO

The dysregulation of membrane protein expression has been implicated in tumorigenesis and progression, including hepatocellular carcinoma (HCC). In this study, we aimed to identify membrane proteins that modulate HCC viability. To achieve this, we performed a CRISPR activation screen targeting human genes encoding membrane-associated proteins, revealing TMX2 as a potential driver of HCC cell viability. Gain- and loss-of-function experiments demonstrated that TMX2 promoted growth and tumorigenesis of HCC. Clinically, TMX2 was an independent prognostic factor for HCC patients. It was significantly upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, TMX2 was demonstrated to promote macroautophagy/autophagy by facilitating KPNB1 nuclear export and TFEB nuclear import. In addition, TMX2 interacted with VDAC2 and VADC3, assisting in the recruitment of PRKN to defective mitochondria to promote cytoprotective mitophagy during oxidative stress. Most interestingly, HCC cells responded to oxidative stress by upregulating TMX2 expression and cell autophagy. Knockdown of TMX2 enhanced the anti-tumor effect of lenvatinib. In conclusion, our findings emphasize the pivotal role of TMX2 in driving the HCC cell viability by promoting both autophagy and mitophagy. These results suggest that TMX2 May serve as a prognostic marker and promising therapeutic target for HCC treatment.Abbreviation: CCCP: Carbonyl cyanide 3-chlorophenylhydrazone; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeat; ER: endoplasmic reticulum; HCC: hepatocellular carcinoma; KPNB1: karyopherin subunit beta 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; TFEB: transcription factor EB; TMX2: thioredoxin related transmembrane protein 2; VDAC2: voltage dependent anion channel 2; VDAC3: voltage dependent anion channel 3; WB: western blot.


Assuntos
Autofagia , Carcinoma Hepatocelular , Sobrevivência Celular , Neoplasias Hepáticas , Proteínas de Membrana , Mitofagia , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Mitofagia/efeitos dos fármacos , Mitofagia/genética , Mitofagia/fisiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Autofagia/fisiologia , Autofagia/genética , Sobrevivência Celular/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Canal de Ânion 2 Dependente de Voltagem/metabolismo , Canal de Ânion 2 Dependente de Voltagem/genética , Linhagem Celular Tumoral , Animais , Camundongos , Estresse Oxidativo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Mitocôndrias/metabolismo , Masculino , Regulação Neoplásica da Expressão Gênica , Camundongos Nus
14.
J Environ Manage ; 360: 121140, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754190

RESUMO

Biochar preparation and application is an anticipated pathway for the resource utilization of biogas residue. In this study, biochars were prepared by the pyrolysis of biogas residue from food waste anaerobic digestion (named as BRBCs) under various pyrolysis temperatures (300, 500, 700, and 900 °C), and the effect of pyrolysis temperatures on the physicochemical characteristics of BRBCs was examined. The adsorption performance toward ciprofloxacin (CIP), a typical antibiotic in waterbodies, was also investigated. The results showed that pyrolysis temperature significantly changed the physicochemical properties of BRBCs. In addition, the minerals in the biogas residue, especially SiO2, were rearranged to form a mesoporous structure in biochar through a self-template strategy (without activator). BRBC prepared at 900 °C exhibited a high specific surface area and pore volume, well-developed mesopore structure, and more carbon structure defects, and exhibited the largest CIP adsorption capacity with 70.29 mg g-1, which was ascribed to the combined interaction of pore diffusion, π-π interactions, hydrogen bonding, complexation, and electrostatic forces. Furthermore, the adsorption of CIP by BRBC900 was well described by two-compartment kinetic and Langmuir isotherm models. BRBC900 showed good adsorption performance toward CIP at pH 7-9. The adsorption of CIP by BRBC is a spontaneous, exothermic, entropy-increasing process. Moreover, BRBC also presented a good recycling potential. Therefore, the preparation of mesoporous biochar based on a self-template strategy not only provides an option for the resource utilization of biogas residue but also offers a new option for the treatment of antibiotic wastewater.


Assuntos
Biocombustíveis , Carvão Vegetal , Ciprofloxacina , Pirólise , Ciprofloxacina/química , Carvão Vegetal/química , Biocombustíveis/análise , Adsorção , Poluentes Químicos da Água/química , Temperatura , Porosidade , Cinética
15.
Eur J Pharmacol ; 975: 176659, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38762158

RESUMO

Obstructive sleep apnea syndrome (OSAS), characterized by repeated narrow or collapse of the upper airway during sleep, resulting in periodic reductions or cessations in ventilation, consequent hypoxia, hypercapnia, increased sympathetic activity and sleep fragmentation, places a serious burden on society and health care. Intermittent hypoxia (IH), which cause central nervous system (CNS) inflammation, and ultimately lead to neuropathy, is thought to be a crucial contributor to cognitive impairment in OSAS. Wnt signaling pathway exerts an important role in the regulation of CNS disorders. Particularly, it may be involved in the regulation of neuroinflammation and cognitive dysfunction. However, its underlying mechanism remains poorly understood. Accumulating evidence demonstrated that Wnt signaling pathway may inhibited in a variety of neurological disorders. Recently studies revealed that SUMOylation was participated in the regulation of neuroinflammation. Members of Wnt/ß-catenin pathway may be targets of SUMOylation. In vitro and in vivo molecular biology experiments explored the regulatory mechanism of SUMOylation on Wnt/ß-catenin in IH-induced neuroinflammation and neuronal injury, which demonstrated that IH induced the SUMOylation of ß-catenin, microglia mediated inflammation and neuronal damage. Moreover, SENP1 regulated the de-SUMOylation of ß-catenin, triggered Wnt/ß-catenin pathway, and alleviated neuroinflammation and neuronal injury, thus improving IH-related mice cognitive dysfunction.


Assuntos
Disfunção Cognitiva , Cisteína Endopeptidases , Hipóxia , Microglia , Sumoilação , Via de Sinalização Wnt , Animais , Microglia/metabolismo , Microglia/patologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Camundongos , Cisteína Endopeptidases/metabolismo , Hipóxia/complicações , Hipóxia/metabolismo , Masculino , beta Catenina/metabolismo , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologia , Humanos , Modelos Animais de Doenças
16.
ACS Sens ; 9(6): 3262-3271, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38809959

RESUMO

As trimethylamine (TMA) is widely used in agriculture and industry, inhalation of TMA can cause very serious negative effects on human health. However, most of the current gas sensors for detecting TMA are commonly performed at high temperatures and cannot meet market needs. Inspired by this, we prepared imine covalent organic frameworks (TB-COF) synthesized from two monomers, 1,3,5-tris(4-aminophenyl)benzene (TAPB) and 1,3,5-benzotricarboxaldehyde (BTCA), using acetic acid as a catalyst at room temperature. Based on this, three sensors were prepared for gas sensitivity testing, namely, TA, BT, and TB-COF sensors. The three sensors were tested for 15 different gases at room temperature. From the whole gas sensitivity data, the TB-COF sensor made by compositing TA and BT has a higher sensitivity (6845.9%) to TMA at 500 ppm, which is 6.1 and 5.4 times higher than the response of TA and BT sensors, respectively. The TB-COF sensor adsorbs and desorbs TMA in a controlled 23 s cycle with a low detection limit of 28.6 ppb. This result indicates that TB-COF prepared at room temperature can be used as a gas-sensitive sensing material for real-time monitoring of TMA. The gas sensing results demonstrate the great potential of COFs for sensor development and application and provide ideas for further development of COFs-based gas sensors.


Assuntos
Iminas , Estruturas Metalorgânicas , Metilaminas , Metilaminas/análise , Metilaminas/química , Iminas/química , Estruturas Metalorgânicas/química , Limite de Detecção , Gases/química , Gases/análise
17.
Chin Med J (Engl) ; 137(11): 1324-1331, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38613214

RESUMO

BACKGROUND: Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China. METHODS: Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher's exact test was used for comparison of categorical variables. RESULTS: A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk. CONCLUSIONS: PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.


Assuntos
Doenças Cardiovasculares , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Estudos Transversais , Idoso , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico
18.
Small Methods ; : e2400336, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38517268

RESUMO

Industrializing water electrolyzers demands better electrocatalysts, especially for the anodic oxygen evolution reaction (OER). The prevailing OER catalysts are Ir or Ru-based nanomaterials, however, they still suffer from insufficient stability. An alternative yet considerably less explored approach is to upgrade Rh, a known stable but moderately active element for OER electrocatalysis, via rational structural engineering. Herein, a precise synthesis of assembled RhRuFe trimetallenes (RhRuFe TMs) with an average thickness of 1 nm for boosting overall water splitting catalysis is reported. Favorable mass transport and optimized electronic structure collectively render RhRuFe TMs with an improved OER activity of an overpotential of 330 mV to deliver 10 mA cm-2, which is significantly lower than the Rh/C control (by 601 mV) and reported Rh-based OER electrocatalysts. In particular, the RhRuFe TMs-based water splitting devices can achieve the current density of 10 mA cm-2 at a low voltage of 1.63 V, which is among the best in the Rh-based bifunctional catalysts for electrolyzers. The addition of Fe in RhRuFe TMs can modulate the strain/electron distribution of the multi-alloy, which regulates the binding energies of H* and OH* in hydrogen and oxygen evolution reactions for achieving the enhanced bifunctional OER and HER catalysis is further demonstrated.

19.
Surg Endosc ; 38(4): 1823-1834, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38302758

RESUMO

OBJECTIVES: Seroma represents the most prevalent postoperative complication following laparoscopic inguinal hernia repair, particularly in the case of large inguinoscrotal hernias. This randomized controlled trial was undertaken with the objective of assessing the effects of internal orifice narrowing achieved by suturing the divided distal hernia sac in laparoscopic repair of indirect inguinoscrotal hernias. METHODS: A total of 58 patients aged 18 years or older, were randomized into two groups: Group I, which underwent internal orifice narrowing, and Group II, which served as the control without narrowing. The study's primary endpoint was the incidence and volume of seroma in the inguinal region on postoperative days 1 and 7, as well as at 1, 3, and 6 months following the procedure. Secondary outcomes encompassed metrics like total operative time, acute and chronic pain levels, duration of hospital stay, recurrence rates, and the occurrence of any additional complications. RESULTS: In comparison to the control group, the experimental group exhibited a significantly lower incidence of seroma formation at 7 days (P = 0.001). Furthermore, the ultrasonic assessment indicated a reduced seroma volume in the operative group on postoperative day 7 (8.84 ± 17.71 vs. 52.39 ± 70.78 mL; P < 0.001). Acute pain levels and hospital stay were similar between the two groups (1.22 ± 0.76 vs. 1.04 ± 0.53, P = 0.073; 1.22 ± 0.07 vs. 1.19 ± 0.08, P = 0.627, respectively). Notably, neither chronic pain nor early recurrence, nor any other postoperative complications were observed in either group throughout the follow-up period, which extended for at least 6 months (range: 6-18 months). CONCLUSION: In the context of laparoscopic inguinoscrotal hernia repair, the incidence and volume of seroma can be significantly reduced through the implementation of internal orifice narrowing achieved by suturing the divided distal hernia sac. And, this reduction in seroma formation was not associated elevation in postoperative pain levels or recurrence rates.


Assuntos
Dor Crônica , Hérnia Inguinal , Laparoscopia , Humanos , Dor Crônica/cirurgia , Hérnia Inguinal/cirurgia , Hérnia Inguinal/complicações , Herniorrafia/métodos , Laparoscopia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Recidiva , Seroma/etiologia , Seroma/prevenção & controle , Telas Cirúrgicas/efeitos adversos , Método Duplo-Cego
20.
BMC Pediatr ; 24(1): 70, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245707

RESUMO

BACKGROUND: Sleep disordered breathing (SDB) is broadly recognized to be associated with neurobehavioral deficits, which have significant impacts on developing-aged children and adolescents. Therefore, our study aimed to quantify the proportion of neurobehavioral impairments attributed to SDB in general children and adolescents by population attributable fraction (PAF). METHODS: The study was registered at PROSPERO (ID: CRD42023388143). We collected two types of literature on the prevalence of SDB and the risk of SDB-related neurobehavioral deficits from ten electronic databases and registers, respectively. The pooled effect sizes (Pe, Pc, RR) by random-effects meta-analysis were separately substituted into Levin's formula and Miettinen's formula to calculate PAFs. RESULTS: Three prevalence literature and 2 risk literature, all with moderate/high quality, were included in the quantitative analysis individually. The prevalence of SDB was 11% (95%CI 2%-20%) in children and adolescents (Pe), while the SDB prevalence was 25% (95%CI 7%-42%) in neurobehavioral patients (Pc). SDB diagnosis at baseline was probably associated with about threefold subsequent incidence of neurobehavioral deficits (pooled RR 3.24, 95%CI 1.25-8.41), after multi-adjustment for key confounders. Up to 19.8% or 17.3% of neurobehavioral consequences may be attributed to SDB from Levin's formula and Miettinen's formula, respectively. CONCLUSIONS: A certain number of neurobehavioral consequences may be attributable to SDB. It is essential for clinicians to identify and treat SDB timely, as well as screen for SDB in patients with neurobehavioral impairments. More longitudinal studies of SDB and neurobehavioral deficits are needed in the future to further certify the association between them.


Assuntos
Síndromes da Apneia do Sono , Adolescente , Criança , Humanos , Incidência , Prevalência , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/complicações
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