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1.
Front Nutr ; 11: 1342682, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38988856

RESUMEN

Introduction and objective: Nutritional therapy is a crucial component of treatment for severely burned patients. Although overly aggressive enteral nutrition immediately after burn injury has potential risks, nutritional disruption after a severe burn can also increase infection risk and delay wound healing. For approximately six decades, the Ruijin Hospital Burn Center has used two distinct approaches for patients during the early period after burn injury: complete fasting or adaptive feeding. Notably, adaptive feeding more closely resembles enteral nutrition. In this retrospective study, we analyzed factors influencing the selection of either modality, as well as the benefits of adaptive feeding. We sought to promote adaptive feeding as a precursor to initiating enteral nutrition. Patients and methods: This retrospective study analyzed medical data from adult patients with extensive burns between January 2009 and December 2020. All patients had been admitted to the burn department within 24 h after injury and had a burned area comprising >30% of total body surface area. Patients were divided into two groups: adaptive feeding and fasting. We examined the total burned area, full-thickness burned area, burn type, inhalation injury, start time of adaptive feeding, and start time of enteral nutrition. Outcome measures were 28-day mortality and hospital mortality. Results: Univariate analysis revealed significant differences in burn type, percent of total body surface area (TBSA), full-thickness burned area, and inhalation injury between the adaptive feeding and fasting groups (all p < 0.05). Linear regression analysis showed that full-thickness burned area and inhalation injury were the main factors influencing the start time of adaptive feeding in patients with severe burns (p < 0.05). After propensity score matching analysis, the results showed that the start time of enteral nutrition was significantly earlier in the adaptive feeding group (p < 0.01). However, overall mortality, 28-day mortality, and length of hospital stay did not significantly improve in the adaptive feeding group. The incidence of intolerance after enteral nutrition therapy did not significantly differ between groups. Conclusion: The results of the study showed that larger full-thickness burned areas and concomitant inhalation injury were the primary factors considered by physicians when selecting complete fasting for severely burned patients. Moreover, the results indicate that adaptive feeding improves nutritional therapy for severely burned patients by shortening the time between injury and initiation of enteral nutrition. Complete fasting due to concerns about extensive burned area and inhalation injuries does not reduce the incidence of enteral nutrition intolerance; instead, it delays the initiation of enteral nutrition.

2.
Transl Cancer Res ; 13(6): 2691-2703, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38988918

RESUMEN

Background: Glycosylphosphatidylinositol (GPI)-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) plays a crucial role in fatty acid metabolism, which is involved in the progression of colorectal cancer (CRC). The aim of this study was to determine the expressional variations of GPIHBP1 in CRC at different stages and to verify whether this protein affects the shaping of the immune microenvironment of cancer cells. Methods: Variations of GPIHBP1 messenger RNA (mRNA) levels were first analysed using The Cancer Genome Atlas (TCGA) database. Protein levels of GPIHBP1 in cancer nest cells, stromal cells or surrounding normal tissues from 68 patients with CRC were checked by immunohistochemistry. Infiltration of immune cells such as macrophages, myeloid-derived suppressor cells (MDSCs), CD8+ and CD56+ cells was parallelly stained in the same tissues. Ectopic GPIHBP1 expressed colonic tumour cells were transplanted into the back of mice. Tumour growth and immune cell infiltrations were also observed. Results: Compared with those in healthy tissues, GPIHBP1 mRNA and protein levels decreased in the patients with CRC at Dukes A-B stage but gradually increased in the patients at Dukes C-D stage. GPIHBP1 in foci or stroma was positively correlated with recruited macrophages or MDSCs and negatively correlated with recruited CD8+, CD56+ or granzyme+ cells. The mice injected with GPIHBP1 overexpression cells bore large tumours. Histological analysis confirmed the infiltration of many macrophages and MDSCs but less CD8+ T or CD56+ cells. Conclusions: The increased expression of GPIHBP1 is involved in the progression of CRC. High GPIHBP1 level of advanced CRC indicates efficient immune evasion in tumour microenvironment.

3.
Res Sq ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39011117

RESUMEN

Background Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for locally advanced rectal cancer, but only 20-40% of patients completely respond to this treatment. Methods To define the molecular features that are associated with response to nCRT, we generated and collected genomic and transcriptomic data from 712 cancers prior to treatment from our own data and from publicly available data. Results We found that patients with a complete response have decreased risk of both local recurrence and future metastasis. We identified multiple differences in DNA mutations and transcripts between complete and incomplete responders. Complete responder tumors have a higher tumor mutation burden and more significant co-occurring mutations than the incomplete responder tumors. In addition, mutations in DNA repair genes (across multiple mechanisms of repair) were enriched in complete responders and they also had lower expression of these genes indicating that defective DNA repair is associated with complete response to nCRT. Using logistic regression, we identified three significant predictors of complete response: tumor size, mutations within specific network genes, and the existence of three or more specific co-occurrent mutations. In incompletely responder tumors, abnormal cell-cell interaction and increased cancer associated fibroblasts were associated with recurrence. Additionally, gene expression analysis identified a subset of immune hot tumors with worse outcomes and upregulated of immune checkpoint proteins. Conclusions Overall, our study provides a comprehensive understanding of the molecular features associated with response to nCRT and the molecular differences in non-responder tumors that later reoccur. This knowledge may provide critical insight for the development of precision therapy for rectal cancer.

4.
J Am Chem Soc ; 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39011931

RESUMEN

Scarce and expensive iridium oxide is still the cornerstone catalyst of polymer-electrolyte membrane electrolyzers for green hydrogen production because of its exceptional stability under industrially relevant oxygen evolution reaction (OER) conditions. Earth-abundant transition metal oxides used for this task, however, show poor long-term stability. We demonstrate here the use of nitrogen-doped cobalt oxide as an effective iridium substitute. The catalyst exhibits a low overpotential of 240 mV at 10 mA cm-2 and negligible activity decay after 1000 h of operation in an alkaline electrolyte. Incorporation of nitrogen dopants not only triggers the OER mechanism switched from the traditional adsorbate evolution route to the lattice oxygen oxidation route but also achieves oxygen nonbonding (ONB) states as electron donors, thereby preventing structural destabilization. In a practical anion-exchange membrane water electrolyzer, this catalyst at anode delivers a current density of 1000 mA cm-2 at 1.78 V and an electrical efficiency of 47.8 kW-hours per kilogram hydrogen.

5.
Nutr Neurosci ; : 1-10, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012764

RESUMEN

BACKGROUND: Research exploring the link between dietary riboflavin intake and cognitive decline in this demographic is limited. Our aim was to examine the association between riboflavin intake levels and cognitive decline. METHODS: The National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 were utilized in this cross-sectional analysis. The Consortium to Establish a Registry for Alzheimer's Disease test Word Learning delayed recall trial (DR), Digit Symbol Substitution Test (DSST), Animal Fluency Test(AFT) and Z test were used to evaluate cognitive performance. Multivariate logistic regression, restricted cubic spline and subgroup analysis were performed to evaluate the associations between riboflavin intake and cognitive decline. RESULTS: The study included a total of 2255 patients, with 47.9% being male. The incidence of cognitive decline was 23.8%. After adjusting for all selected covariates, we found that high riboflavin intake was associated with a lower risk of cognitive impairment in adults in the United States. When riboflavin intake was used as a Categorical variable, compared to those with the lowest intake, the odds ratio (OR) of individuals with the highest riboflavin intake for DR test, AFT test, DSST test and Z test were 0.73 (95% CI: 0.53~1), 0.68(95% CI: 0.49-0.96),0.53(95% CI: 0.37-0.77) and 0.56(95% CI: 0.39-0.8). The study also found an L-shaped association between riboflavin intake and cognitive decline, with an inflection point at approximately 2.984 mg/d. CONCLUSIONS: Our cross-sectional study in a nationwide sample of American old adults suggests that dietary riboflavin intake was negative associated with cognitive decline.

6.
Clin Cancer Res ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38848042

RESUMEN

PURPOSE: This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage, leveraging advanced imaging techniques to explore the relationship between tumor characteristics, glymphatic function, and aquaporin 4 (AQP4) expression. EXPERIMENTAL DESIGN: In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index and Multiparametric MRI (MTP) for quantitative brain mapping. Tumor and peri-tumor tissues were analyzed for AQP4 expression via immunofluorescence. Correlations between imaging parameters, glymphatic function (DTI-ALPS index), and AQP4 expression were statistically assessed. RESULTS: Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), brain tumor patients exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; p = 0.001) and increased cerebrospinal fluid (CSF) volume (201.376 cm³ vs. 115.957 cm³; p = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, p < 0.001), while AQP4 expression correlated positively with peritumoral brain edema (PTBE) volume (r: 0.989; p < 0.001) and negatively with PD in PTBE areas (ρ: -0.506; p < 0.001). CONCLUSIONS: Our findings highlight the interplay between tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, showing the utility of DTI-ALPS and MTP in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system.

7.
J Diabetes Metab Disord ; 23(1): 859-870, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38932886

RESUMEN

Background: Congestive heart failure (CHF) demonstrates a heightened prevalence in individuals with diabetes mellitus within Intensive Care Units. The occurrence of abnormal chloride levels is frequently observed in critically ill patients, yet its clinical significance remains subject to debate. This study endeavors to explore the relationship between serum chloride levels and in-hospital mortality among patients affected by both congestive heart failure and diabetes. Methods: A retrospective cohort study was conducted, utilizing data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database, focusing on adult patients in the United States. The impact of serum chloride levels upon ICU admission on in-hospital mortality was analyzed using multivariable logistic regression models, generalized additive models and subgroup analysis. Results: The study encompassed 7,063 patients with coexisting diabetes and congestive heart failure. The fully adjusted model revealed an inverse association between serum chloride levels and in-hospital mortality. As a tertile variable (Q3 vs Q1), the odds ratio (OR) was 0.73 with a 95% confidence interval (CI) of 0.54-0.98 (p = 0.039). As a continuous variable, per 1 mmol/L increment, the OR (95% CI) was 0.97 (0.96-0.99, p = 0.01). The relationship between serum chloride and in-hospital mortality demonstrated linearity (non-linear p = 0.958). Stratified analyses further validated the robustness of this correlation. Conclusions: Serum chloride levels exhibited a negative association with in-hospital mortality in patients with both congestive heart failure and diabetes. Nevertheless, prospective, randomized, controlled studies are warranted to corroborate and validate the findings presented in this investigation.

8.
Adv Healthc Mater ; : e2401616, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38895987

RESUMEN

Noninflammatory apoptosis is transformed into inflammatory pyroptosis by activating caspase-3 to lyse gasdermin E (GSDME), and this process can be used as an effective therapeutic strategy. Thus, a selective and powerful inducer of activated caspase-3 plays a vital role in pyroptosis-based cancer therapy. Herein, a human cell membrane vesicle-based nanoplatform (HCNP) is designed for photodynamic therapy (PDT). HCNP is modified with vesicular stomatitis virus G-protein (VSVG) to anchor nano-photosensitizers on the tumor cell membrane. Photosensitizers are bonded to HCNP by clicking chemical reaction as pyroptosis inducers. The results show that HCNP effectively disrupts the mitochondrial function of cells by generating reactive oxygen species (ROS) upon laser irradiation; concomitantly, GSDME is cleaved by activated caspase-3 and promotes pyroptosis of lung cancer cells. Here an effective intervention strategy is proposed to induce pyroptosis based on light-activated PDT.

9.
Int J Mol Sci ; 25(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38928432

RESUMEN

During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen microbiota-hepato-intestinal axis of Tibetan sheep at different altitudes. Therefore, the purpose of this study was to explore the regulatory effect of rumen microorganism-volatile fatty acids (VFAs)-VFAs transporter gene interactions on the key enzymes and genes related to gluconeogenesis in Tibetan sheep. The rumen fermentation parameters, rumen microbial densities, liver gluconeogenesis activity and related genes were determined and analyzed using gas chromatography, RT-qPCR and other research methods. Correlation analysis revealed a reciprocal relationship among rumen microflora-VFAs-hepatic gluconeogenesis in Tibetan sheep at different altitudes. Among the microbiota, Ruminococcus flavefaciens (R. flavefaciens), Ruminococcus albus (R. albus), Fibrobactersuccinogenes and Ruminobacter amylophilus (R. amylophilus) were significantly correlated with propionic acid (p < 0.05), while propionic acid was significantly correlated with the transport genes monocarboxylate transporter 4 (MCT4) and anion exchanger 2 (AE2) (p < 0.05). Propionic acid was significantly correlated with key enzymes such as pyruvate carboxylase, phosphoenolpyruvic acid carboxylase and glucose (Glu) in the gluconeogenesis pathway (p < 0.05). Additionally, the expressions of these genes were significantly correlated with those of the related genes, namely, forkhead box protein O1 (FOXO1) and mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) (p < 0.05). The results showed that rumen microbiota densities differed at different altitudes, and the metabolically produced VFA contents differed, which led to adaptive changes in the key enzyme activities of gluconeogenesis and the expressions of related genes.


Asunto(s)
Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Gluconeogénesis , Hígado , Rumen , Animales , Gluconeogénesis/genética , Ovinos/microbiología , Rumen/microbiología , Rumen/metabolismo , Hígado/metabolismo , Ácidos Grasos Volátiles/metabolismo , Tibet , Altitud , Adaptación Fisiológica , Fermentación
10.
Bioresour Technol ; 406: 130990, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38885727

RESUMEN

Chemoautotrophs, the crucial contributors to biological carbon fixation, derive energy from reducing specific inorganic substances and utilize CO2 for growth. However, the release of extracellular free organic carbon (EFOC) by chemoautotrophic microorganisms can inhibit their own growth and metabolism. To reduce the feedback inhibition effect, a low-release biochar (BC-LR) was applied to adsorb EFOC. BC-LR not only adsorbed EFOC, but also selectively adsorbed the main inhibitory component, low molecular weight organics, in EFOC. In contrast, ordinary biochar could not effectively adsorb EFOC and its addition inhibited microbial growth and CO2 fixation. In Transwell culture, BC-LR promoted microbial growth by 190% and CO2 fixation by 29%, and exhibited better economic advantage, when compared with granular activated carbon. These findings provide a novel insight into the interaction between biochar and autotrophic microbial metabolism, offering an economically feasible approach to mitigate feedback inhibition of metabolites and promoting biological CO2 fixation.

11.
J Immunol ; 213(3): 257-267, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38856632

RESUMEN

Psoriasis is a common inflammatory skin disorder with no cure. Mesenchymal stem cells (MSCs) have immunomodulatory properties for psoriasis, but the therapeutic efficacies varied, and the molecular mechanisms were unknown. In this study, we improved the efficacy by enhancing the immunomodulatory effects of umbilical cord-derived MSCs (UC-MSCs). UC-MSCs stimulated by TNF-α and IFN-γ exhibited a better therapeutic effect in a mouse model of psoriasis. Single-cell RNA sequencing revealed that the stimulated UC-MSCs overrepresented a subpopulation expressing high tryptophanyl-tRNA synthetase 1 (WARS1). WARS1-overexpressed UC-MSCs treat psoriasis-like skin inflammation more efficiently than control UC-MSCs by restraining the proinflammatory macrophages. Mechanistically, WARS1 maintained a RhoA-Akt axis and governed the immunomodulatory properties of UC-MSCs. Together, we identify WARS1 as a master regulator of UC-MSCs with enhanced immunomodulatory capacities, which paves the way for the directed modification of UC-MSCs for escalated therapeutic efficacy.


Asunto(s)
Inmunomodulación , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/inmunología , Animales , Ratones , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos , Triptófano-ARNt Ligasa/genética , Psoriasis/inmunología , Psoriasis/terapia , Modelos Animales de Enfermedad , Análisis de la Célula Individual , Análisis de Secuencia de ARN , Cordón Umbilical/citología , Cordón Umbilical/inmunología , Ratones Endogámicos C57BL , Células Cultivadas
12.
Proc Natl Acad Sci U S A ; 121(25): e2400546121, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38857407

RESUMEN

Reduction of carbon dioxide (CO2) by renewable electricity to produce multicarbon chemicals, such as ethylene (C2H4), continues to be a challenge because of insufficient Faradaic efficiency, low production rates, and complex mechanistic pathways. Here, we report that the rate-determining steps (RDS) on common copper (Cu) surfaces diverge in CO2 electroreduction, leading to distinct catalytic performances. Through a combination of experimental and computational studies, we reveal that C─C bond-making is the RDS on Cu(100), whereas the protonation of *CO with adsorbed water becomes rate-limiting on Cu(111) with a higher energy barrier. On an oxide-derived Cu(100)-dominant Cu catalyst, we reach a high C2H4 Faradaic efficiency of 72%, partial current density of 359 mA cm-2, and long-term stability exceeding 100 h at 500 mA cm-2, greatly outperforming its Cu(111)-rich counterpart. We further demonstrate constant C2H4 selectivity of >60% over 70 h in a membrane electrode assembly electrolyzer with a full-cell energy efficiency of 23.4%.

13.
Cell Death Discov ; 10(1): 298, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38909032

RESUMEN

LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner. Fraction studies revealed that the 1-166aa fragment of LIMA1 was indispensable for the interaction with RNF40, and at least two domains of RNF40 might mediate the association of RNF40 with LIMA1. Notably, treatment with simvastatin dramatically decreased the levels of CHO and TG in control cells rather than cells with overexpressed LIMA1. Moreover, RNF40 significantly decreased lipid content, which could be reversed by LIMA1 overexpression. These findings suggest that E3 ubiquitin ligase RNF40 could directly target LIMA1 and promote its protein degradation in cytoplasm, leading to the suppression of lipid accumulation mediated by LIMA1. Collectively, this study unveils that RNF40 is a novel E3 ubiquitin ligase of LIMA1, which underpins its high therapeutic value to combat dysregulation of lipid metabolism.

14.
Sci Rep ; 14(1): 13412, 2024 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862553

RESUMEN

Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8-9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7-8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17-2.44, p = 0.005), 1.62 (95% CI 1.11-2.36, p = 0.013), and 1.57 (95% CI 1.1-2.24, p = 0.012) respectively. The dose-response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.


Asunto(s)
Calcio , Diabetes Mellitus , Insuficiencia Cardíaca , Mortalidad Hospitalaria , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/sangre , Femenino , Masculino , Anciano , Calcio/sangre , Persona de Mediana Edad , Estudios Retrospectivos , Diabetes Mellitus/sangre , Diabetes Mellitus/mortalidad , Anciano de 80 o más Años
15.
Front Cardiovasc Med ; 11: 1380906, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38689862

RESUMEN

Background: Hypertension (HTN) presents a significant global public health challenge with diverse causative factors. The accumulation of visceral adipose tissue (VAT) due to a high-fat diet (HFD) is an independent risk factor for HTN. While various studies have explored pathogenic mechanisms, a comprehensive understanding of impact of VAT on blood pressure necessitates bioinformatics analysis. Methods: Datasets GSE214618 and GSE188336 were acquired from the Gene Expression Omnibus and analyzed to identify shared differentially expressed genes between HFD-VAT and HTN-VAT. Gene Ontology enrichment and protein-protein interaction analyses were conducted, leading to the identification of hub genes. We performed molecular validation of hub genes using RT-qPCR, Western-blotting and immunofluorescence staining. Furthermore, immune infiltration analysis using CIBERSORTx was performed. Results: This study indicated that the predominant characteristic of VAT in HTN was related to energy metabolism. The red functional module was enriched in pathways associated with mitochondrial oxidative respiration and ATP metabolism processes. Spp1, Postn, and Gpnmb in VAT were identified as hub genes on the pathogenic mechanism of HTN. Proteins encoded by these hub genes were closely associated with the target organs-specifically, the resistance artery, aorta, and heart tissue. After treatment with empagliflozin, there was a tendency for Spp1, Postn, and Gpnmb to decrease in VAT. Immune infiltration analysis confirmed that inflammation and immune response may not be the main mechanisms by which visceral adiposity contributes to HTN. Conclusions: Our study pinpointed the crucial causative factor of HTN in VAT following HFD. Spp1, Postn, and Gpnmb in VAT acted as hub genes that promote elevated blood pressure and can be targets for HTN treatment. These findings contributed to therapeutic strategies and prognostic markers for HTN.

16.
iScience ; 27(6): 109870, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38799573

RESUMEN

Autophagy enhancement in septic liver injury can play a protective role. Nerveless, the mechanism of autophagy-mediated septic liver injury needs further investigation. Our study demonstrated that in septic condition, GLI Family Zinc Finger 2 (GLI2) was elevated, whereas peroxisome-proliferator-activated receptor α (PPARα) was downregulated. Suppressing GLI2 or synovialapoptosis inhibitor 1 (SYVN1) in LPS-exposed cells increased PPARα levels, enhanced cell viability and autophagy, while inhibiting apoptosis. LPS enhanced the GLI2-SYVN1 promoter binding. SYVN1 fostered ubiquitin-mediated degradation of PPARα. IGF2BP3 stabilized GLI2 mRNA by targeting its m6A site. Silencing IGF2BP3 led to decreased GLI2 and SYVN1 but increased PPARα levels, promoting cell survival and autophagy, while repressing apoptosis. This was counteracted by SYVN1 overexpression. In cecal ligation and puncture mice, IGF2BP3, SYVN1, or GLI2 knockdown ameliorated liver damage and augmented autophagy. In summary, IGF2BP3 enhanced GLI2 stability, overexpressed GLI2 subsequent promoted SYVN1 levels by interacting with its promoter, leading to ubiquitinated degradation of PPARα, thereby inhibiting PPARα-mediated autophagy and then exacerbating liver injury in sepsis.

17.
J Hazard Mater ; 472: 134499, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38759282

RESUMEN

Cl- activated peroxymonosulfate (PMS) oxidation technology can effectively degrade pollutants, but the generation of chlorinated disinfection byproducts (DBPs) limits the application of this technology in water treatment. In this study, a method of nanobubbles (NBs) synergistic Cl-/PMS system was designed to try to improve this technology. The results showed the synergistic effects of NBs/Cl-/PMS were significant and universal while its upgrade rate was from 12.89% to 34.97%. Moreover, the synergistic effects can be further improved by increasing the concentration and Zeta potential of NBs. The main synergistic effects of NBs/Cl-/PMS system were due to the electrostatic attraction of negatively charged NBs to Na+ from NaCl, K+ from PMS, and H+ from phenol, which acted as a "bridge" between Cl- and HSO5- as well as phenol and Cl-/HSO5-, increasing active substance concentration. In addition, the addition of NBs completely changed the oxidation system of Cl-/PMS from one that increases environmental toxicity to one that reduces it. The reason was that the electrostatic attraction of NBs changed the active sites and degradation pathway of phenol, greatly reducing the production of highly toxic DBPs. This study developed a novel environmentally friendly oxidation technology, which provides an effective strategy to reduce the generation of DBPs in the Cl-/PMS system.

18.
JAMA Psychiatry ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748415

RESUMEN

Importance: Overweight and obesity affect 340 million adolescents worldwide and constitute a risk factor for poor mental health. Understanding the association between body mass index (BMI) and mental health in adolescents may help to address rising mental health issues; however, existing studies lack comprehensive evaluations spanning diverse countries and periods. Objective: To estimate the association between BMI and mental health and examine changes over time from 2002 to 2018. Design, Setting, and Participants: This was a repeated multicountry cross-sectional study conducted between 2002 and 2018 and utilizing data from the Health Behaviour in School-aged Children (HBSC) survey in Europe and North America. The study population consisted of more than 1 million adolescents aged 11 to 15 years, with all surveyed children included in the analysis. Data were analyzed from October 2022 to March 2023. Main Outcomes and Measures: Mental health difficulties were measured by an 8-item scale for psychological concerns, scoring from 0 to 32, where a higher score reflects greater psychosomatic issues. BMI was calculated using weight divided by height squared and adjusted for age and sex. Data were fitted by multilevel generalized additive model. Confounders included sex, living with parents, sibling presence, academic pressure, the experience of being bullied, family affluence, screen time, and physical activity. Results: Our analysis of 1 036 869 adolescents surveyed from 2002 to 2018, with a mean (SD) age of 13.55 (1.64) years and comprising 527 585 girls (50.9%), revealed a consistent U-shaped association between BMI and mental health. After accounting for confounders, adolescents with low body mass and overweight or obesity had increased psychosomatic symptoms compared to those with healthy weight (unstandardized ß, 0.14; 95% CI, 0.08 to 0.19; unstandardized ß, 0.27; 95% CI, 0.24 to 0.30; and unstandardized ß, 0.62; 95% CI, 0.56 to 0.67, respectively), while adolescents with underweight had fewer symptoms (unstandardized ß, -0.18; 95% CI, -0.22 to -0.15). This association was observed across different years, sex, and grade, indicating a broad relevance to adolescent mental health. Compared to 2002, psychosomatic concerns increased significantly in 2006 (unstandardized ß, 0.19; 95% CI, 0.11 to 0.26), 2010 (unstandardized ß, 0.14; 95% CI, 0.07 to 0.22), 2014 (unstandardized ß, 0.48; 95% CI, 0.40 to 0.56), and 2018 (unstandardized ß, 0.82; 95% CI, 0.74 to 0.89). Girls reported significantly higher psychosomatic concerns than boys (unstandardized ß, 2.27; 95% CI, 2.25 to 2.30). Compared to primary school, psychosomatic concerns rose significantly in middle school (unstandardized ß, 1.15; 95% CI, 1.12 to 1.18) and in high school (unstandardized ß, 2.12; 95% CI, 2.09 to 2.15). Conclusions and Relevance: Our study revealed a U-shaped association between adolescent BMI and mental health, which was consistent across sex and grades and became stronger over time. These insights emphasize the need for targeted interventions addressing body image and mental health, and call for further research into underlying mechanisms.

19.
Front Bioeng Biotechnol ; 12: 1390337, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707496

RESUMEN

Objective: This study aims to develop and evaluate the biocompatibility and osteogenic potential of a novel injectable strontium-doped hydroxyapatite bone-repair material. Methods: The properties of strontium-doped hydroxyapatite/chitosan (Sr-HA/CS), hydroxyapatite/chitosan (HA/CS) and calcium phosphate/chitosan (CAP/CS) were assessed following their preparation via physical cross-linking and a one-step simplified method. Petri dishes containing Escherichia coli and Staphylococcus epidermidis were inoculated with the material for in vitro investigations. The material was also co-cultured with stem cells derived from human exfoliated deciduous teeth (SHEDs), to assess the morphology and proliferation capability of the SHEDs, Calcein-AM staining and the Cell Counting Kit-8 assay were employed. Osteogenic differentiation of SHEDs was determined using alkaline phosphatase (ALP) staining and Alizarin Red staining. For in vivo studies, Sr-HA/CS was implanted into the muscle pouch of mice and in a rat model of ovariectomy-induced femoral defects. Hematoxylin-eosin (HE) staining was performed to determine the extent of bone formation and defect healing. The formation of new bone was determined using Masson's trichrome staining. The osteogenic mechanism of the material was investigated using Tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical studies. Results: X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) showed that strontium was successfully doped into HA. The Sr-HA/CS material can be uniformly squeezed using a syringe with a 13% swelling rate. Sr-HA/CS had a significant antibacterial effect against both E. coli and S. epidermidis (p < 0.05), with a stronger effect observed against E. coli. The Sr-HA/CS significantly improved cell proliferation and cell viability in vitro studies (p < 0.05). Compared to CAP/CS and CS, Sr-HA/CS generated a substantially greater new bone area during osteoinduction experiments (p < 0.05, p < 0.001). The Sr-HA/CS material demonstrated a significantly higher rate of bone repair in the bone defeat studies compared to the CAP/CS and CS materials (p < 0.01). The OCN-positive area and TRAP-positive cells in Sr-HA/CS were greater than those in control groups (p < 0.05). Conclusion: A novel injectable strontium-doped HA bone-repair material with good antibacterial properties, biocompatibility, and osteoinductivity was successfully prepared.

20.
Prog Mater Sci ; 1422024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38745676

RESUMEN

Possessing a unique combination of properties that are traditionally contradictory in other natural or synthetical materials, Ga-based liquid metals (LMs) exhibit low mechanical stiffness and flowability like a liquid, with good electrical and thermal conductivity like metal, as well as good biocompatibility and room-temperature phase transformation. These remarkable properties have paved the way for the development of novel reconfigurable or stretchable electronics and devices. Despite these outstanding properties, the easy oxidation, high surface tension, and low rheological viscosity of LMs have presented formidable challenges in high-resolution patterning. To address this challenge, various surface modifications or additives have been employed to tailor the oxidation state, viscosity, and patterning capability of LMs. One effective approach for LM patterning is breaking down LMs into microparticles known as liquid metal particles (LMPs). This facilitates LM patterning using conventional techniques such as stencil, screening, or inkjet printing. Judiciously formulated photo-curable LMP inks or the introduction of an adhesive seed layer combined with a modified lift-off process further provide the micrometer-level LM patterns. Incorporating porous and adhesive substrates in LM-based electronics allows direct interfacing with the skin for robust and long-term monitoring of physiological signals. Combined with self-healing polymers in the form of substrates or composites, LM-based electronics can provide mechanical-robust devices to heal after damage for working in harsh environments. This review provides the latest advances in LM-based composites, fabrication methods, and their novel and unique applications in stretchable or reconfigurable sensors and resulting integrated systems. It is believed that the advancements in LM-based material preparation and high-resolution techniques have opened up opportunities for customized designs of LM-based stretchable sensors, as well as multifunctional, reconfigurable, highly integrated, and even standalone systems.

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