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OBJECTIVE: With the development of surgical technology, the level of digital medicine is constantly improving. The birth of new technologies has a certain impact on traditional methods. At present, robot-assisted technology has been applied to patients with calcaneal fractures, which poses a challenge to traditional surgery. We aimed to assess whether robot-assisted internal fixation confers certain surgical advantages through a literature review. DESIGN: The databases PubMed, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), and the Wanfang Data Knowledge Service Platform were systematically searched for both randomized and nonrandomized studies involving patients with calcaneal fractures. MAIN RESULTS: Five studies were identified that compared clinical indexes. For the clinical indexes, robot-assisted surgery is generally feasible because of intraoperative fluoroscopy, complications, the Gissane angle, the calcaneal width, and the American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score 3 and 6 months after the operation (P < 0.05). However, on the operation time, Böhler's angle at 3 and 6 months, Gissane angle and calcaneal width at 6 months after the operation did not show good efficacy compared with those of the traditional group (P > 0.05). CONCLUSIONS: Based on the current evidence, the advantages of robot-assisted fixation over traditional fixation are clear. The long-term clinical effects of the two methods are also good, and the short-term effect of robot assistance is better. However, the quality of some studies is low, and more high-quality randomized controlled trials (RCTs) are needed for further verification.
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Calcâneo , Fixação Interna de Fraturas , Fraturas Ósseas , Procedimentos Cirúrgicos Robóticos , Humanos , Calcâneo/lesões , Calcâneo/cirurgia , Calcâneo/diagnóstico por imagem , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Chronic pain was associated with a higher risk of mental disorders (e.g., depression and anxiety). However, the role of 24-h movement behaviors in the association remains unclear. METHODS: A total of 72,800 participants with accelerometer data and free of mental disorders from the UK Biobank were analyzed. The compositional mediation model and isotemporal substitution model were used to explore the associations between chronic pain, 24-h movement behaviors, and the incidence of overall mental disorders, depression, and anxiety. RESULTS: With a median follow-up of 13.36 years, participants with chronic pain had a higher rate of incident overall mental disorders (hazard ratio (HR): 1.281, 95% confidence interval (CI): 1.219 to 1.344), anxiety (HR: 1.391, 95% CI: 1.280 to 1.536), and depression (HR: 1.703, 95% CI: 1.551 to 1.871). Increased sedentary behavior (SB) and reduced moderate-to-vigorous physical activity (MVPA) caused by chronic pain both increased the risk of mental disorders. Twenty-four-hour movement behaviors explained the relationship between chronic pain and overall mental disorders, depression, and anxiety by 10.77%, 5.70%, and 6.86%, respectively. Interaction effects were found between MVPA and chronic pain when predicting the incidence of depression and between MVPA, sleep (SLP), and chronic pain when predicting the incidence of mental disorders. People with chronic pain would recommend at least 0.5 h per day of MVPA and 7 h per day of SLP and restricting SB below 11.5 h per day. CONCLUSIONS: Twenty-four-hour movement behaviors played a significant mediating role in the association between chronic pain and mental disorders. Individuals with chronic pain should engage in more MVPA, less sedentary behavior, and have 7-h sleep per day.
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Dor Crônica , Transtornos Mentais , Humanos , Dor Crônica/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Transtornos Mentais/epidemiologia , Incidência , Reino Unido/epidemiologia , Adulto , Estudos de Coortes , Idoso , Comportamento Sedentário , Exercício Físico/fisiologia , Ansiedade/epidemiologia , Depressão/epidemiologiaRESUMO
Intramedullary nail fixation of intertrochanteric fractures assisted by orthopedic surgical robot navigation is a new surgical method, but there are few studies comparing its efficacy with traditional intramedullary nail fixation. We aimed to assess whether robot-assisted internal fixation confers certain surgical advantages through a literature review. PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wan fang Data Knowledge service Platform were searched to collect randomized and non-randomized studies on patients with calcaneal fractures. Five studies were identified to compare the clinical indexes. For the clinical indexes, the technology of robot-assisted is generally feasible, in time to operation, intraoperative fluoroscopy times, blood loss, pine insertion, tip apex distance (TAD), and Harris score (P < 0.05). However, on the complication and excellent and good rate after operation did not show good efficacy compared with the traditional group (P > 0.05). Based on the current evidence, For the short-term clinical index, the advantages of robot-assisted are clear. The long-term clinical effects of the two methods are also good, but the robot-assisted shows better. However, the quality of some studies is low, and more high-quality randomized controlled trials (RCTs) are needed for further verification.
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Fixação Intramedular de Fraturas , Fraturas do Quadril , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Fraturas do Quadril/cirurgia , Fixação Intramedular de Fraturas/métodos , Resultado do Tratamento , Duração da Cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Pinos OrtopédicosRESUMO
OBJECTIVE: The aim of this study is to investigate the association between Cathepsin B and Parkinson's Disease (PD), with a particular focus on determining the role of N-acetylaspartate as a potential mediator. METHODS: We used summary-level data from Genome-Wide Association Studies (GWAS) for a two-sample Mendelian randomization (MR) analysis, exploring the association between Cathepsin B (3301 cases) and PD (4681 cases). A sequential two-step MR approach was applied (8148 cases) to study the role of N-acetylaspartate. RESULTS: The MR analysis yielded that genetically predicted elevated Cathepsin B levels correlated with a reduced risk of developing PD (p = 0.0133, OR: 0.9171, 95% CI: 0.8563-0.9821). On the other hand, the analysis provided insufficient evidence to determine that PD affected Cathepsin B levels (p = 0.8567, OR: 1.0035, 95% CI: 0.9666-1.0418). The estimated effect of N-acetylaspartate in this process was 7.52% (95% CI = -3.65% to 18.69%). CONCLUSIONS: This study suggested that elevated Cathepsin B levels decreased the risk of developing PD, with the mediation effect of N-acetylaspartate. Further research is needed to better understand this relationship.
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Preharvest sprouting (PHS) is an undesirable trait that decreases yield and quality in rice production. Understanding the genes and regulatory mechanisms underlying PHS is of great significance for breeding PHS-resistant rice. In this study, we identified a mutant, preharvest sprouting 39 (phs39), that exhibited an obvious PHS phenotype in the field. MutMap+ analysis and transgenic experiments demonstrated that OsAAH, which encodes allantoate amidohydrolase, is the causal gene of phs39 and is essential for PHS resistance. OsAAH was highly expressed in roots and leaves at the heading stage and gradually increased and then weakly declined in the seed developmental stage. OsAAH protein was localized to the endoplasmic reticulum, with a function of hydrolyzing allantoate in vitro. Disruption of OsAAH increased the levels of ureides (allantoate and allantoin) and activated the tricarboxylic acid (TCA) cycle, and thus increased energy levels in developing seeds. Additionally, the disruption of OsAAH significantly increased asparagine, arginine, and lysine levels, decreased tryptophan levels, and decreased levels of indole-3-acetic acid (IAA) and abscisic acid (ABA). Our findings revealed that the OsAAH of ureide catabolism is involved in the regulation of rice PHS via energy and hormone metabolisms, which will help to facilitate the breeding of rice PHS-resistant varieties.
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Malolactic fermentation (MLF) is a crucial process to enhance wine quality, and the utilization of indigenous microorganisms has the potential to enhance wine characteristics distinct to a region. Here, the MLF performance of five indigenous Oenococcus oeni strains and six synthetic microbial communities (SynComs), were comparatively evaluated in Cabernet Sauvignon wine. In terms of malate metabolism rate and wine aroma diversity, the strain of O. oeni Oe114-46 demonstrated comparable MLF performance to the commercial strain of O. oeni Oe450 PreAc. Furthermore, the corresponding SynComs (Oe144-46/LpXJ25) exhibited improved fermentation properties, leading to increased viable cell counts of both species, more rapid and thorough MLF, and increased concentrations of important aroma compounds, such as linalool, 4-terpinenol, α-terpineol, diethyl succinate, and ethyl lactate. These findings highlight the remarkable MLF performance of indigenous O. oeni and O. oeni-L. plantarum microbial communities, emphasizing their immense potential in improving MLF efficiency and wine quality.
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Glucose is required for generating heat during cold-induced nonshivering thermogenesis in adipose tissue, but the regulatory mechanism is largely unknown. CREBZF has emerged as a critical mechanism for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). We investigated the roles of CREBZF in the control of thermogenesis and energy metabolism. Glucose induces CREBZF in human white adipose tissue (WAT) and inguinal WAT (iWAT) in mice. Lys208 acetylation modulated by transacetylase CREB-binding protein/p300 and deacetylase HDAC3 is required for glucose-induced reduction of proteasomal degradation and augmentation of protein stability of CREBZF. Glucose induces rectal temperature and thermogenesis in white adipose of control mice, which is further potentiated in adipose-specific CREBZF knockout (CREBZF FKO) mice. During cold exposure, CREBZF FKO mice display enhanced thermogenic gene expression, browning of iWAT, and adaptive thermogenesis. CREBZF associates with PGC-1α to repress thermogenic gene expression. Expression levels of CREBZF are negatively correlated with UCP1 in human adipose tissues and increased in WAT of obese ob/ob mice, which may underscore the potential role of CREBZF in the development of compromised thermogenic capability under hyperglycemic conditions. Our results reveal an important mechanism of glucose sensing and thermogenic inactivation through reversible acetylation.
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Tecido Adiposo Marrom , Glucose , Camundongos , Humanos , Animais , Glucose/metabolismo , Tecido Adiposo Marrom/metabolismo , Acetilação , Tecido Adiposo Branco/metabolismo , Metabolismo Energético , Obesidade/genética , Obesidade/metabolismo , Termogênese/genética , Camundongos Endogâmicos C57BL , Fatores de Transcrição de Zíper de Leucina Básica/metabolismoRESUMO
Grape pomace seeds contain abundant phenolic compounds, which are also present in both soluble and insoluble forms, similar to many other plant matrices. To further increase the extractable soluble phenolics and their antioxidant activities, grape pomace seeds were fermented with different fungi. Results showed that solid-state fermentation (SSF) with Aspergillus niger, Monascus anka, and Eurotium cristatum at 28 °C and 65% humidity had a significantly positive impact on the release of soluble phenolics in grape pomace seeds. Specifically, SSF with M. anka increased the soluble phenolic contents by 6.42 times (calculated as total phenolic content) and 6.68 times (calculated as total flavonoid content), leading to an overall improvement of antioxidant activities, including DPPH (increased by 2.14 times) and ABTS (increased by 3.64 times) radical scavenging activity. Furthermore, substantial changes were observed in the composition and content of individual phenolic compounds in the soluble fraction, with significantly heightened levels of specific phenolics such as chlorogenic acid, syringic acid, ferulic acid, epicatechin gallate, and resveratrol. Notably, during M. anka SSF, positive correlations were identified between the soluble phenolic content and hydrolase activities. In particular, there is a strong positive correlation between glycosidase and soluble phenols (r = 0.900). The findings present an effective strategy for improving the soluble phenolic profiles and bioactivities of grape pomace seeds through fungal SSF, thereby facilitating the valorization of winemaking by-products.
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Soil salinity has a major impact on rice seed germination, severely limiting rice production. Herein, a rice germination defective mutant under salt stress (gdss) was identified by using chemical mutagenesis. The GDSS gene was detected via MutMap and shown to encode potassium transporter OsHAK9. Phenotypic analysis of complementation and mutant lines demonstrated that OsHAK9 was an essential regulator responsible for seed germination under salt stress. OsHAK9 is highly expressed in germinating seed embryos. Ion contents and non-invasive micro-test technology results showed that OsHAK9 restricted K+ efflux in salt-exposed germinating seeds for the balance of K+/Na+. Disruption of OsHAK9 significantly reduced gibberellin 4 (GA4) levels, and the germination defective phenotype of oshak9a was partly rescued by exogenous GA3 treatment under salt stress. RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction analysis demonstrated that the disruption of OsHAK9 improved the GA-deactivated gene OsGA2ox7 expression in germinating seeds under salt stress, and the expression of OsGA2ox7 was significantly inhibited by salt stress. Null mutants of OsGA2ox7 created using clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 approach displayed a dramatically increased seed germination ability under salt stress. Overall, our results highlight that OsHAK9 regulates seed germination performance under salt stress involving preventing GA degradation by mediating OsGA2ox7, which provides a novel clue about the relationship between GA and OsHAKs in rice.
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Giberelinas , Oryza , Giberelinas/farmacologia , Giberelinas/metabolismo , Germinação/fisiologia , Potássio/metabolismo , Oryza/metabolismo , Sementes/metabolismo , Estresse Salino , Proteínas de Membrana Transportadoras/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition-induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet-induced insulin-resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF-κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes.
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Fatores de Transcrição de Zíper de Leucina Básica , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Animais , Humanos , Camundongos , Tecido Adiposo/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/metabolismo , Resistência à Insulina/genética , Macrófagos/metabolismo , Obesidade/metabolismoRESUMO
BACKGROUND: Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. RESULTS: To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. CONCLUSIONS: This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy.
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Adenocarcinoma , Antineoplásicos , Neoplasias do Colo , Nanopartículas , Fotoquimioterapia , Pró-Fármacos , Humanos , Animais , Camundongos , Lipossomos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Adenocarcinoma/tratamento farmacológico , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/tratamento farmacológico , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Nanopartículas/metabolismo , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente TumoralRESUMO
Increased levels of cytosolic DNA in lung tissues play an important role in acute lung injury. However, the detailed mechanisms involved remain elusive. Here, we found that cyclic GMP-AMP synthase (cGAS, a cytosolic DNA sensor) expression was increased in airway epithelium in response to increased cytosolic DNA. Conditional deletion of airway epithelial cGAS exacerbated acute lung injury in mice, cGAS knockdown augmented LPS-induced production of interleukin (IL)-6 and IL-8. Mechanically, deletion of cGAS augmented expression of phosphorylated CREB (cAMP response element-binding protein), and cGAS directly interacted with CREB via its C-terminal domain. Furthermore, CREB knockdown rescued the LPS-induced excessive inflammatory response caused by cGAS deletion. Our study demonstrates that airway epithelial cGAS plays a protective role in acute lung injury and confirms a non-canonical cGAS-CREB pathway that regulates the inflammatory responses in airway epithelium to mediate LPS-induced acute lung injury.
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Lesão Pulmonar Aguda , Lipopolissacarídeos , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , DNA , Interleucina-6 , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Transdução de SinaisRESUMO
Phospholipids play a crucial role in the growth and neurodevelopment of infants. Currently, soybean phospholipids (SPLs) are the common phospholipid component in most infant formulas (IFs), which, however, shows an obvious difference with the phospholipid (PL) composition of human milk fat. Therefore, in the present study, human milk phospholipid analogs (HMPAs) were prepared by mimicking the composition of PE, PC, PI, PS, and SM in breast milk phospholipids and the composition of the major fatty acids (C16:0, C18:0, C18:1, and C18:2), and their digestion and absorption characteristics were explored using in vitro and mice models. The prepared HMPA contained 26.48% PE, 24.64% PC, 36.19% SM, 6.35% PI, and 6.32% PS, with 40.51% C16:0, 17.02% C18:0, 29.19% C18:1, and 13.26% C18:2, showing different digestive properties relative to SPL. There was little effect on the physical and chemical properties of HMPA under in vitro gastric conditions. The hydrolysis degree, fatty acids release rate, and average particle size decreasing rate of HMPA was significantly higher than that of SPL during digestion in vitro intestine (P < 0.05), showing better digestive process relative to SPL. In terms of the mice model, HMPA had a higher hydrolysis degree in the intestinal tract. Based on the area under curve (AUC) analysis of serum fatty acids, it was found that despite HMPA being absorbed at a slower rate than SPL, it was absorbed more than SPL. In summary, the digestion and absorption of HMPA were preferred to SPL, and these obtained results might provide a theoretical basis for the development and utilization of HMPA in IF.
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Leite Humano , Fosfolipídeos , Feminino , Lactente , Humanos , Camundongos , Animais , Fosfolipídeos/análise , Leite Humano/química , Hempa/análise , Ácidos Graxos/análise , Leite/química , DigestãoRESUMO
Self-healing hydrogel products have attracted a great deal of interest in wound healing due to their ability to repair their own structural damage. Herein, an all-natural self-healing hydrogel based on methacrylated chitosan (CSMA) and dialdehyde bacterial cellulose (DABC) is developed. MA is used to modify CS and obtain water-soluble biomaterial-based CSMA with photo crosslinking effects. BC is modified through a simple oxidation method to gain dialdehyde on the polymer chain. The success of the modification is confirmed via FTIR. Hydrogels are formed within 11 min through the establishment of a Schiff base between the amino of CSMA and the aldehyde of DABC. A dynamically reversible Schiff base bond endows hydrogel with good self-healing properties through macroscopic and microscopic observations. We observe the uniform and porous structure in the hydrogel using SEM images, and DABC nanofibers are found to be well distributed in the hydrogel. The compressive strength of the hydrogel is more than 20 kPa and the swelling rate sees over a 10-fold increase. In addition, the CSMA/DABC hydrogel has good cytocompatibility, with cell viability exceeding 90%. These results indicate that the all-natural self-healable CSMA/DABC hydrogel demonstrates strong application potential in wound healing and tissue repair.
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Minimal Residual Disease (MRD) detection has emerged as an independent factor in clinical and pathological cancer assessment offering a highly effective method for predicting recurrence in colorectal cancer (CRC). The ongoing research initiatives such as the DYNAMIC and CIRCULATE-Japan studies, have revealed the potential of MRD detection based on circulating tumor DNA (ctDNA) to revolutionize management for CRC patients. MRD detection represents an opportunity for risk stratification, treatment guidance, and early relapse monitoring. Here we overviewed the evolving landscape of MRD technology and its promising applications through the most up-to-date research and reviews, underscoring the transformative potential of this approach. Our primary focus is to provide a point-to-point perspective and address key challenges relating to the adoption of ctDNA-based MRD detection in the clinical setting. By identifying critical areas of interest and hurdles surrounding clinical significance, detection criteria, and potential applications of basic research, this article offers insights into the advancements needed to evaluate the role of ctDNA in CRC MRD detection, contributing to favorable clinical options and improved outcomes in the management of CRC.
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Relevância Clínica , Neoplasias Colorretais , Humanos , Neoplasia Residual/diagnóstico , Japão , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Biomarcadores Tumorais/genéticaRESUMO
Introduction: The activation of endogenous retroviral (ERV) genes in kidney renal clear cell carcinoma (KIRC) suggests the necessity for further research on their functions. Methods: In this study, KIRC and healthy cohorts were obtained from TGGA and GEO datasets. Subsequently, differential analysis and functional annotation were conducted using GO, KEGG, and GSEA. Clinical outcomes were then observed and utilized in the development of a nomogram. Results: We observed the general low expression of ERVFRD-1 in KIRC tumors compared to normal tissue (P < 0.001) across multiple cohorts. Differential analysis and functional annotation using GO, KEGG, GSEA analysis revealed significant involvement of ERVFRD-1 in tumor immunoregulation: a close relation to the infiltration levels of mast cells and Treg cell (P < 0.001) and occurrence with a variety of immune markers. Methylation status was then applied to uncover potential mechanisms of ERVFRD-1 in KIRC. Notably, higher expression levels of ERVFRD-1 were associated with extended overall survival, disease-specific survival, and progression-free survival. Finally, based on Cox regression analysis, we constructed a nomogram incorporating ERVFRD-1, pathologic T, and age, which exhibited promising predictive power in assessing the survival outcomes of KIRC patients. Discussion: To sum up, our study suggests that ERVFRD-1 plays a role in regulating immunological activity within the tumor microenvironment and is associated with overall survival in KIRC patients. ERVFRD-1 may therefore be a sensitive biomarker for diagnosis, immunotherapy, and prognosis assessment of KIRC.
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Carcinoma , Retrovirus Endógenos , Humanos , Imunoterapia , Biomarcadores , Rim , Microambiente TumoralRESUMO
Bromide ion (Br-) is known as a prevalent component in water environments, which exhibits significant impacts on halonitromethanes (HNMs) formation. This study was performed to explore and compare the formation, toxicity, and mechanisms of HNMs from poly(diallyl dimethyl ammonium chloride) (PDDACl) in the absence and presence of Br- in the UV/monochloramine (UV/NH2Cl) disinfection process. The results showed that chlorinated HNMs were found in the absence of Br-, while brominated (chlorinated) HNMs and brominated HNMs were found in the presence of Br-. Furthermore, the peaks of total HNMs were promoted by 2.0 and 2.4 times, respectively when 1.0 and 2.0 mg L-1 Br- were added. Also, the peaks of total HNMs were enhanced with the increase of the NH2Cl dosage, which were reduced with the increase of pH. It should be noted that Br- induced higher toxicity of HNMs, and the cytotoxicity and genotoxicity of HNMs with the addition of 2.0 mg L-1 Br- were 78.0 and 3.7 times those without the addition of Br-, respectively. Meanwhile, both the reaction mechanisms of HNMs produced from PDDACl were speculated in the absence and presence of Br-. Finally, different HNMs species and yields were discovered in these two real water samples compared to those in simulated waters. These findings of this work will be conducive to understanding the significance of Br- affecting HNMs formation and toxicity in the disinfection process.
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Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Desinfecção/métodos , Brometos , Cloreto de Amônio , Halogenação , Água , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise , CloroRESUMO
A stable and seamless adhesion between the human skin and the hydrogel-based electronic skin is necessary for accurate sensing and human health monitoring in aquatic environments. Despite achieving significant progress in this field, it remains a great challenge to design skin-interfaced conductive hydrogels with high electrical conductivity, stablility, and seamless underwater adhesion to skin. Herein, a skin-inspired conductive multifunctional hydrogel is proposed, which has a wet-adhesive/hydrophilic and a non-adhesive/hydrophobic bilayer structure. The hydrogel shows high stretchability (â¼2400%) and an ultra-low modulus (4.5 kPa), which facilitate the conformal and seamless attachment of the hydrogel to the skin with reduced motion artifacts. Owing to synergistic physical and chemical interactions, this hydrogel can achieve reliable underwater adhesion and display remarkable underwater adhesion strength (388.1 kPa) to porcine skin. In addition, MXene has been employed to obtain high electrical conductivity, create a route for stable electron transport, and reinforce mechanical properties. The hydrogel also possesses self-healing ability, a low swelling ratio (â¼3.8%), biocompatibility, and specific adhesion to biological tissues in water. Facilitated with these advantages, the hydrogel-based electrodes achieve reliable electrophysiological signal detection in both air and wet conditions and demonstrate a higher signal-to-noise ratio (28.3 dB) than that of commercial Ag/AgCl gel electrodes (18.5 dB). Also, the hydrogel can be utilized as a strain sensor with high sensitivity for underwater communication. This multifunctional hydrogel improves the stability of the skin-hydrogel interface in aquatic environments and is expected to be promising for the next-generation bio-integrated electronics.
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Comunicação , Hidrogéis , Humanos , Suínos , Animais , Edema , Condutividade Elétrica , AdesivosRESUMO
Ligand/receptor-mediated targeted drug delivery has been widely recognized as a promising strategy for improving the clinical efficacy of nanomedicines but is attenuated by the binding of plasma protein on the surface of nanoparticles to form a protein corona. Here, it is shown that ultrasonic cavitation can be used to unravel surface plasma coronas on liposomal nanoparticles through ultrasound (US)-induced liposomal reassembly. To demonstrate the feasibility and effectiveness of the method, transcytosis-targeting-peptide-decorated reconfigurable liposomes (LPGLs) loaded with gemcitabine (GEM) and perfluoropentane (PFP) are developed for cancer-targeted therapy. In the blood circulation, the targeting peptides are deactivated by the plasma corona and lose their targeting capability. Once they reach tumor blood vessels, US irradiation induces transformation of the LPGLs from nanodrops into microbubbles via liquid-gas phase transition and decorticate the surface corona by reassembly of the lipid membrane. The activated liposomes regain the capability to recognize the receptors on tumor neovascularization, initiate ligand/receptor-mediated transcytosis, achieve efficient tumor accumulation and penetration, and lead to potent antitumor activity in multiple tumor models of patient-derived tumor xenografts. This study presents an effective strategy to tackle the fluid biological barriers of the protein corona and develop transcytosis-targeting liposomes for active tumor transport and efficient cancer therapy.
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Neoplasias , Coroa de Proteína , Humanos , Lipossomos , Doxorrubicina/farmacologia , Ultrassom , Ligantes , Neoplasias/metabolismo , Sistemas de Liberação de Medicamentos , Peptídeos , Proteínas Sanguíneas , Linhagem Celular TumoralRESUMO
Introduction: Emerging evidence has proven that human endogenous retroviruses (HERVs) play a critical role in the pathogenesis of Acute Myeloid Leukemia (AML), whereas the specific HERVs influencing the prognosis of AML patients have yet to be fully understood. Methods: In this study, a systematic exploration was achieved to identify potential prognostic HERVs for AML, sourced from TCGA and GTEx database. Differential analysis and functional enrichment studies were conducted using GO, KEGG, GSEA, and GSVA. The ESTIMATE algorithm was applied to explore the immune infiltration of HERVs in AML. A prognostic risk-score model was evaluated with predicted yearly accuracy using ROC analysis. Results: Two HERVs Suppressyn and Syncytin-2, were identified as promising prognostic biomarkers, with high discrimination ability based on ROC analysis between AML and healthy cohorts from TCGA. Their expression was notably higher in AML patients compared to those in healthy individuals but correlates with favorable clinical outcomes in sub-groups such as white race, lower WBC counts, favorable and intermediate risks, and NPM1 or IDH1 mutation. Suppressyn and Syncytin-2 participated in immune-related pathways and exhibited correlations with multiple immune infiltration cells, such as T cells, mast cells, and tumor-associated macrophages. Finally, we developed a prognostic risk-scoring model combining Suppressyn and Syncytin-2, where a high risk-score is associated with better prognosis. Discussion: Collectively, our findings revealed that Suppressyn and Syncytin-2 may act as valuable diagnostic and prognostic biomarkers for individuals with AML, while highlighting links between HERV activation, immunogenicity, and future therapeutic targets.