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1.
Heliyon ; 10(17): e37357, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39296112

RESUMO

Background: Neutrophil extracellular trap (NET) is associated with host response, tumorigenesis, and immune dysfunction. However, the link between NET and the tumor microenvironment (TME) of gastric cancer (GC) remains unclear. Our study aims to characterize the expression patterns of NET-related genes and their relationships with clinicopathological characteristics, prognosis, TME features, and immunotherapy efficacy in GC cohorts. Methods: Transcriptomic and single-cell RNA sequencing profiles of GC with annotated clinicopathological data were obtained from TCGA-STAD (n = 415), GSE62254 (n = 300), GSE15459 (n = 192), and GSE183904 (n = 26). The consensus cluster algorithm was used to classify tumor samples into different NET-related clusters. A NET-related signature was constructed using LASSO regression and verified in four immunotherapy cohorts. ROC and Kaplan-Meier analyses were conducted to evaluate the predictive and prognostic value of the model for immunotherapy efficacy. Results: This study identified two NET-related clusters with distinct clinicopathological features, prognosis, and TME landscapes. The high NET-related cluster, characterized by increased NET-related gene expression, exhibited more aggressive behavior and a worse prognosis (HR = 1.63, P = 0.004) than the low NET-related cluster. DEGs were primarily involved in the chemokine/cytokine-associated pathways. Moreover, the high NET-related cluster had significantly higher levels of TME scores, immune infiltration, and immune effectors (all P < 0.001). The NET-related signature displayed a high predictive accuracy for immunotherapy response (AUC = 0.939, P < 0.001). Furthermore, patients with high NET-related scores consistently harbored a more favorable prognosis in different immunotherapy cohorts (all P < 0.05). Conclusions: This study identified the NET-related signature as a robust model for predicting immunotherapy response in GC, which can help clinicians make appropriate immunotherapy decisions.

2.
Environ Res ; 262(Pt 2): 119807, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39222731

RESUMO

Dechlorane plus (DP) has been detected in a variety of environmental media and in human. Measurement of DPs in hair, urine, and house dust across different habitats allows for the assessment of short-term spatial changes in human exposure to DPs, as well as their excretion in urine. This offers a significant reference point for further research on the behavior of persistent pollutants within organisms. We measured and analyzed the concentrations of DP in the hair and urine of 32 students from a university in Beijing during school and home phases, and in indoor dust from dormitories and some home environments. The results indicated that the concentrations of DP in three types of samples were higher during the home phase compared to the school phase. We compared the fanti values and identified selective enrichment of syn-DP in hair, along with selective excretion of syn-DP in urine. Utilizing molecular docking technique, we simulated the binding effect between DP and the Megalin protein. The results demonstrated that the binding energy of anti-DP to Megalin was higher than that of syn-DP, suggesting that anti-DP has a greater propensity to bind to Megalin and be reabsorbed. This results in higher levels of syn-DP excretion in urine. Finally, we categorized students based on their participation in the organic exposure experiment and their BMI. The results indicated that the concentrations of DP in hair and urine were higher in the exposed group compared to the non-exposed group during the school year. After excluding the effect of exposure, habitat changes were more likely to affect the accumulation and excretion of DP in normal-weight students (BMI ≤24 kg/m2, n = 28), while overweight students (BMI >24 kg/m2, n = 4) were less affected by the effect of habitat because of their higher body fat percentage and their greater ability to accumulate DP.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39244797

RESUMO

Zinc is a significant source of heavy metal pollution that poses risks to both human health and biodiversity. Excessive concentrations of zinc can hinder the growth and development of insects and trigger cell death through oxidative damage. The midgut is the main organ affected by exposure to heavy metals. The silkworm, a prominent insect species belonging to the Lepidoptera class and widely used in China, serves as a model for studying the genetic response to heavy metal stress. In this study, high-throughput sequencing technology was employed to investigate detoxification-related genes in the midgut that are induced by zinc exposure. A total of 11,320 unigenes and 14,723 transcripts were identified, with 553 differentially expressed genes (DEGs) detected, among which 394 were up-regulated and 159 were down-regulated. The Gene Ontology (GO) analysis revealed that 452 DEGs were involved in 18 biological process subclasses, 14 cellular component subclasses and 8 molecular functional subclasses. Furthermore, the KEGG analysis demonstrated enrichment in pathways such as Protein digestion, absorption and Lysosome. Validation of the expression levels of 9 detoxification-related DEGs through qRT-PCR confirmed the accuracy of the RNA-seq results. This study not only contributes new insights into the detoxification mechanisms mechanism of silkworms against zinc contamination, but also serves as a foundation basis for understanding the molecular detoxification processes in lepidopteran insects.

4.
Psychol Res Behav Manag ; 17: 3067-3081, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220632

RESUMO

Background: With the advent of new media technology, WeChat, as China's largest social networking platform, has significantly impacted people's lives. Growing concerns exist about social media usage, particularly regarding mental health issues stemming from problematic smartphone use. However, limited research has explored the relationship between social media usage and mental health among older adults in China, particularly the mechanisms influencing this relationship. This study addresses this gap by investigating the relationship between excessive WeChat use and loneliness among older adults, examining the mediating roles of sensation seeking and fear of missing out (FoMO). Methods: To clarify the intermediary role of sensation seeking and FoMO in the relationship between elderly loneliness and problematic phone use, this study employed the loneliness scale, brief sensation seeking scale, the scale of FoMO and WeChat overuse scale in a questionnaire survey on the Chinese elderly aged 55 to 89 (N=913). A chained mediation model was constructed, with descriptive statistics, Pearson correlation analysis, and mediation effect tests performed. Results: The results indicate that the relationship between loneliness and excessive WeChat use among Chinese elderly is mediated by sensation seeking and FoMO. Conclusion: The findings reveal that loneliness, sensation seeking and FoMO and problematic mobile phone use (WeChat) are interconnected; (ii) sensation seeking and FoMO are the two important intermediary mechanisms between loneliness and problematic mobile phone use; and (iii) sensation seeking and FoMO can act as mediators in the relationship between loneliness and problematic mobile phone use among the elderly. In the difference test of demographic variables, it was found that women had more WeChat overuse behavior than men, and urban residents demonstrated significantly higher levels of overuse than their township residents. The study has revealed the psychological mechanism between loneliness and problematic mobile phone use among the elderly, which provides guiding suggestions for the prevention and intervention of such behaviors in the elderly.

5.
Aging Dis ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39133904

RESUMO

Despite substantial evidence highlighting molecular communication within the components of neurovascular units (NVU), the interactions at the organelle level have been insufficiently explored in recent decades. Mitochondria, for instance, beyond their traditional role as energy supply for intracellular metabolism and survival, provide a novel perspective on intercellular connections through mitochondrial transfer. These transferred mitochondria not only carry bioactive molecules but also signal to mitigate risks in both healthy and pathological conditions. In this review, we summarized mitochondrial transfer events, relevant routes, and underlying molecular mechanisms originating from diverse cell populations within NVU. We particularly focus on the therapeutic potential of this mechanism in treating central nervous system disorders, notably neurodegenerative diseases marked by mitochondrial dysfunction and then highlight the promising prospects of exogenous mitochondrial supplementation as a treatment target.

6.
Front Public Health ; 12: 1398948, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39145158

RESUMO

Background: Rehabilitation therapists often perform physically demanding treatments that may result in work-related injuries, yet related studies are scarce. This study aimed to investigate the work-related injuries of rehabilitation therapists and provide feasible preventive measures. Methods: A cross-sectional study was carried out in 34 regions across China using an online questionnaire. The survey gathered responses primarily from 1,198 rehabilitative therapists working in 120 health institutes. Following data collection, descriptive analysis, chi-square tests, logistic regression, and receiver operating characteristic (ROC) curves were employed to analyze the data. Results: In this study, the incidence of work-related injuries was reported to be 87% (n = 1,041). The top three musculoskeletal issues reported were low back pain (12%), neck pain (10%), and shoulder pain (9%). Logistic regression and ROC curve analysis identified that working as a physiotherapist and years of work experience (OR [95% CI]: 1.03 [0.99-1.07]) were significant contributors to the incidence of work-related injuries. Specifically, neuro-physiotherapists (OR [95% CI]: 3.04 [1.56-5.92]), musculoskeletal physiotherapists (OR [95% CI]: 2.46 [1.16-5.18]), and intensive care physiotherapists (OR [95% CI]: 4.70 [1.24-17.88]) were at higher risk. Furthermore, five factors were proven to be associated with injury prevention as reported by therapists: patient engagement (OR [95% CI]: 0.38 [0.23-0.62]), improving techniques (OR [95% CI]: 0.59 [0.39-0.90]), maintaining exercise habits (OR [95% CI]: 0.59 [0.40-0.86]), utilizing instruments (OR [95% CI]: 0.80 [0.53-1.19]), and strengthening education (OR [95% CI]: 0.43 [0.21-0.90]). Conclusion: The present study investigated the factors contributing to work-related injuries among rehabilitation therapists, with a focus on identifying both risk and preventive measures. These findings offer new perspectives on decreasing injury risk.


Assuntos
Traumatismos Ocupacionais , Fisioterapeutas , Humanos , Estudos Transversais , Masculino , Feminino , Adulto , Inquéritos e Questionários , Traumatismos Ocupacionais/epidemiologia , China/epidemiologia , Fisioterapeutas/estatística & dados numéricos , Pessoa de Meia-Idade , Incidência
7.
Materials (Basel) ; 17(15)2024 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-39124388

RESUMO

Ethylene-vinyl acetate copolymer (EVA), a crucial elastomeric resin, finds extensive application in the footwear industry. Conventional chemical foaming agents, including azodicarbonamide and 4,4'-oxybis(benzenesulfonyl hydrazide), have been identified as environmentally problematic. Hence, this study explores the potential of physical foaming of EVA using supercritical nitrogen as a sustainable alternative, garnering considerable interest in both academia and industry. The EVA formulations and processing parameters were optimized and EVA foams with densities between 0.15 and 0.25 g/cm3 were produced. Key findings demonstrate that physical foaming not only reduces environmental impact but also enhances product quality by a uniform cell structure with small cell size (50-100 µm), a wide foaming temperature window (120-180 °C), and lower energy consumption. The research further elucidates the mechanisms of cell nucleation and growth within the crosslinked EVA network, highlighting the critical role of blowing agent dispersion and localized crosslinking around nucleated cells in defining the foam's cellular morphology. These findings offer valuable insights for producing EVA foams with a more controllable cellular structure, utilizing physical foaming techniques.

8.
Artigo em Inglês | MEDLINE | ID: mdl-39191144

RESUMO

Procambarus clarkii is an economically important species in China; however, its high mortality rate due to pathogenic bacteria, particularly Vibrio parahaemolyticus, results in significant economic loss. This study aimed to understand the immune response of crayfish to bacterial infection by comparing and analyzing transcriptome data of hepatopancreatic tissue from P. clarkii challenged with V. parahaemolyticus or treated with PBS. Physiological indices (TP, Alb, ACP, and AKP) were analyzed, and tissue sections were prepared. After assembling and annotating the data, 18,756 unigenes were identified. A comparison of the expression levels of these unigenes between the control and V. parahaemolyticus groups revealed 4037 DEGs, with 2278 unigenes upregulated and 1759 downregulated in the V. parahaemolyticus group. GO (Gene Ontology) enrichment analysis shows that the DGEs are mainly enriched in cellular anatomical activity, bindinga and cellular process, enrichment analysis of KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways showed that DGEs were mainly enriched in Base excision repair, Phagosome and Longevity regulating pathway. At the same time, lysosome was also enriched. The phagosome and lysosome pathways play a crucial role in the immune defense of crayfish against V. parahaemolyticus injection that will be highlighted. In addition, the expression levels of six selected immune-related DEGs were measured using qRT-PCR, which validated the results of RNA-seq analysis. This study provides a new perspective on the immune system and defense mechanisms of P. clarkii and a valuable foundation for further investigation of the molecular immune mechanisms of this species.

9.
Adv Mater ; 36(36): e2404734, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39081101

RESUMO

The van der Waals (vdW) interface provides two important degrees of freedom-twist and slip-to tune interlayer structures and inspire unique physics. However, constructing diversified high-quality slip stackings (i.e., lattice orientations between layers are parallel with only interlayer sliding) is more challenging than twisted stackings due to angstrom-scale structural discrepancies between different slip stackings, sparsity of thermodynamically stable candidates and insufficient mechanism understanding. Here, using transition metal dichalcogenide (TMD) homobilayers as a model system, this work theoretically elucidates that vdW materials with low lattice symmetry and weak interlayer coupling allow the creation of multifarious thermodynamically advantageous slip stackings, and experimentally achieves 13 and 9 slip stackings in 1T″-ReS2 and 1T″-ReSe2 bilayers via direct growth, which are systematically revealed by atomic-resolution scanning transmission electron microscopy (STEM), angle-resolved polarization Raman spectroscopy, and second harmonic generation (SHG) measurements. This work also develops modulation strategies to switch the stacking via grain boundaries (GBs) and to expand the slip stacking library from thermodynamic to kinetically favored structures via in situ thermal treatment. Finally, density functional theory (DFT) calculations suggest a prominent dependence of the pressure-induced electronic band structure transition on stacking configurations. These studies unveil a unique vdW epitaxy and offer a viable means for manipulating interlayer atomic registries.

10.
Int J Biol Macromol ; 277(Pt 2): 134231, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39074699

RESUMO

To investigate the impact of chlorantraniliprole on Procambarus clarkii, acute toxicity tests were performed. Results indicated that 96 h post-exposure to chlorantraniliprole (60 mg/L) led to the separation of the hepatopancreas basement membrane, causing cell swelling, rupture, and vacuolation. Moreover, acid phosphatase (ACP) and alkaline phosphatase (AKP) activities exhibited divergent trends across four concentrations of chlorantraniliprole (0, 30, 60, and 90 mg/L). Hydrogen peroxide (H2O2) and catalase (CAT) levels significantly increased, while total superoxide dismutase (T-SOD) and malonaldehyde (MDA) activities decreased, indicating oxidative stress in the hepatopancreas. A total of 276 differentially expressed genes (DEGs) were identified, with 204 up-regulated and 72 down-regulated. Out of these, 114 DEGs were successfully annotated and classified into 99 pathways, with a primary focus on the cytochrome P450-mediated xenobiotic metabolism pathway. The DEGs enriched in this pathway, along with transcriptome data, were validated using quantitative-polymerase chain reaction. This study enhances the transcriptome database of P. clarkii and provides fundamental insights into its immune defense and antioxidant mechanisms. Additionally, it lays a theoretical foundation for future research on disease prevention in P. clarkii within rice-shrimp culture systems.


Assuntos
Sistema Enzimático do Citocromo P-450 , Xenobióticos , ortoaminobenzoatos , Animais , ortoaminobenzoatos/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Xenobióticos/metabolismo , Inativação Metabólica/genética , Astacoidea/genética , Astacoidea/efeitos dos fármacos , Astacoidea/metabolismo , Transcriptoma/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Perfilação da Expressão Gênica , Hepatopâncreas/metabolismo , Hepatopâncreas/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos
11.
Eur J Pharmacol ; 979: 176806, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38986830

RESUMO

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-ß1) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD.


Assuntos
Rim , Cadeias Pesadas de Miosina , Insuficiência Renal Crônica , Animais , Humanos , Masculino , Camundongos , Linhagem Celular , Modelos Animais de Doenças , Fibrose , Rim/patologia , Rim/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Motores Moleculares/metabolismo , Proteínas Motores Moleculares/genética , Cadeias Pesadas de Miosina/metabolismo , Cadeias Pesadas de Miosina/genética , Ligação Proteica , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/genética , Fator de Crescimento Transformador beta1/metabolismo , Obstrução Ureteral/patologia , Obstrução Ureteral/metabolismo , Obstrução Ureteral/complicações
12.
J Phys Chem Lett ; 15(28): 7327-7334, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38985131

RESUMO

Methanesulfenic acid, CH3SOH, is a fleeting intermediate in the ·OH-initiated oxidation reactions of dimethyl sulfide (DMS) and dimethyl disulfide (DMDS) in the atmosphere. Herein, we report the characterization and photochemistry of CH3SOH in Ar- and N2-matrices at 10 K. The characterization of CH3SOH with matrix-isolation IR and UV-vis spectroscopy is supported by D and 13C isotope labeling experiments and quantum chemical calculations. In line with the observed absorption at 260 nm for CH3SOH, its photolysis at 254 nm leads to dissociation by yielding the novel water complex H2CS···H2O, which exhibits a five-membered ring structure with intermolecular S···HO and CH···O hydrogen bonding interactions. Upon further irradiation at 193 nm, the H2CS···H2O complex undergoes dehydrogenation to form CS···H2O, which can further convert to HC(O)SH under irradiation at 254 nm. When the photolysis of CH3SOH was performed in an O2-doped Ar-matrix, methanesulfonic acid (MSA, CH3SO3H) was obtained as the oxidation product.

13.
J Am Chem Soc ; 146(29): 20494-20499, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39001838

RESUMO

The photochemistry of nitrous acid (HONO), encompassing dissociation into OH and NO as well as the reverse association reaction, plays a pivotal role in atmospheric chemistry. Here, we report the direct observation of nitrosyl-O-hydroxide (HOON) in the photochemistry of HONO, employing matrix-isolation IR and UV-vis spectroscopy. Despite a barrier of approximately 30 kJ/mol, HOON undergoes spontaneous rearrangement to the more stable HONO isomer through quantum mechanical tunneling, with a half-life of 28 min at 4 K. Kinetic isotope effects and instanton theory calculations reveal that the tunneling process involves the concerted motion of the NO moiety (65.2%) and the hydrogen atom (32.3%). Our findings underscore the significance of HOON as a key intermediate in the photolytic dissociation-association cycle of HONO at low temperatures.

14.
Clin Res Hepatol Gastroenterol ; 48(8): 102430, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39069260

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) is a highly aggressive and invasive malignant tumor of the bile duct, with a poor prognosis and a high mortality rate. Currently, there is a lack of effective targeted treatment methods and reliable biomarkers for prognosis. METHODS: We downloaded RNA-seq and clinical data of CCA from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases as training and test sets. The apoptosis-related genes were obtained from the Molecular Signatures Database (MsigDB) database. We used univariate/multivariate Cox regression and Lasso regression analyses to construct a riskscore prognostic model. Based on the median riskscore, we clustered the patients into high-risk (HR) and low-risk (LR) groups. We carried out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of differentially expressed genes (DEGs) in HR and LR groups. The single sample gene set enrichment analysis (ssGSEA) was employed to analyze the immune infiltration of the HR and LR groups. The CellMiner database was utilized to predict drugs and perform molecular docking on drugs and target proteins. RESULTS: We identified 8 genes with prognostic significance to construct a prognostic model. Results of GO and KEGG demonstrated that DEGs were mainly enriched in biological functions such as fatty acid metabolic processes and pathways such as the cAMP signaling pathway. Results of ssGSEA uncovered that immune cells such as DCs and Macrophages in the HR group, as well as immune functions such as Check-point and Parainflammation, were considerably higher than those in the LR group. Drug sensitivity prediction and results of molecular docking revealed that Rigosertib targeted the prognostic genes MAP3K1. HYPOTHEMYCIN and AMG900 effectively targeted JUN. CONCLUSION: Our project suggested that the prognostic model with apoptotic features can effectively predict prognosis in CCA patients, proffering prognostic biomarkers and potential therapeutic targets for CCA patients.

15.
J Am Chem Soc ; 146(27): 18699-18705, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38943601

RESUMO

Carbonyl nitrenes are versatile intermediates that have been extensively characterized; however, their phosphorus analogues remain largely unknown. Herein, we report the observation of a rare example of carbonyl phosphinidene NH2C(O)P, which was generated through the photolytic (193 nm) dehydrogenation of phosphinecarboxamide (NH2C(O)PH2) in a solid N2-matrix at 12 K. The characterization of NH2C(O)P in the triplet ground state with matrix-isolation IR and ultraviolet-visible (UV-vis) spectroscopy is supported by comprehensive isotope labeling experiments (D and 15N) and quantum chemical calculations. Upon visible-light irradiation at 680 nm, NH2C(O)P inserts into dihydrogen by the reformation of NH2C(O)PH2 with concomitant isomerization to the more stable aminophosphaketene (NH2PCO). Additionally, the photoisomerization of NH2C(O)PH2 to NH2C(OH) = PH along with decomposition by yielding hydrogen-bonded complexes HNCO···PH3 and HPCO···NH3 has been observed in the matrix.

16.
J Colloid Interface Sci ; 672: 446-454, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38850869

RESUMO

The design of pre-catalysts and the rational manipulation of corresponding electrochemical reconstruction are vitally important to construct the highly durable and active catalysts for seawater oxidation, but rather challenging. Herein, a novel core-shell catalyst of Co2(PS3)@Co2P (labeled as CoPS) by epitaxial growth of amorphous cobalt phosphide (Co2P) on crystalline cobalt phosphorous trichalcogenide (Co2(PS3)) is firstly designed as a pre-catalyst for alkaline seawater oxidation. Various characterization techniques are employed to demonstrate that the unique amorphous-crystalline nanowire structure (CoPS) achieves the rapid surface reconstruction into active CoOOH and diversiform oxyanions species (labeled as CoPS-R). Theoretical simulations uncover that the in situ derived oxyanions (PO42-, SO32- and SO42-) on the surface of CoOOH can tune the electron distribution of Co site, thereby optimizing the chemisorption of oxygen evolution reaction (OER) intermediates on CoOOH and reducing the energy barrier of determining step. Consequently, in an alkaline natural seawater solution, the reconstructed CoPS-R catalyst exhibits small overpotentials of 357 and 402 mV for OER at 200 and 500 mA cm-2, respectively, together with an impressive durability over 500 h at a large current density of 500 mA cm-2 benefiting from the strong repulsive effect of the derived PO42-, SO32- and SO42- oxyanions. This work offers a new insight for comprehending the relationship of structure-composition-activity and develops a new approach toward the construction of efficient and robust OER catalysts for seawater electrolysis.

17.
bioRxiv ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38826355

RESUMO

An "induced PARP inhibitor (PARPi) sensitivity by epigenetic modulation" strategy is being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARPi treatments. To expand its clinical applications and identify more efficient combinations, we performed a drug screen by combining PARPi with 74 well-characterized epigenetic modulators that target five major classes of epigenetic enzymes. Both type I PRMT inhibitor and PRMT5 inhibitor exhibit high combination and clinical priority scores in our screen. PRMT inhibition significantly enhances PARPi treatment-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMTs maintain the expression of genes associated with DNA damage repair and BRCAness and regulate intrinsic innate immune pathways in cancer cells. Analyzing large-scale genomic and functional profiles from TCGA and DepMap further confirms that PRMT1, PRMT4, and PRMT5 are potential therapeutic targets in oncology. Finally, PRMT1 and PRMT5 inhibition act synergistically to enhance PARPi sensitivity. Our studies provide a strong rationale for the clinical application of a combination of PRMT and PARP inhibitors in patients with HR-proficient ovarian or breast cancer.

18.
Sleep Breath ; 28(4): 1679-1690, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38739211

RESUMO

OBJECTIVE: This investigation seeks to examine the association between serum vitamin D concentrations and the prevalence of sleep disorders, additionally elucidating the causal relationship via Mendelian Randomization (MR) analysis. MATERIALS AND METHODS: This research employed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016, focusing on adults aged 20-50 years reporting sleep disorders. The research encompassed 4913 American adults. Weighted multivariable logistic regression models and cubic spline analyses were utilized to evaluate the association between serum vitamin D concentrations and the incidence of sleep disorders. Additionally, a two-sample Mendelian Randomization analysis was performed to evaluate the potential causal link between serum vitamin D concentrations and the risk of sleep disorders. RESULTS: Within the 2011-2016 NHANES cohort of the U.S. population, a notable inverse association was detected between serum vitamin D concentrations and sleep disorders (ß = - 3.81, 95% CI: - 6.10 to - 1.52, p = 0.003). After multivariate adjustments, a higher incidence of sleep disorders was associated with lower vitamin D Concentrations (OR 1.52, 95% CI 1.10-2.10, trend p = 0.014). Restricted cubic spline regression analysis indicated a linear association between serum vitamin D concentrations and sleep disorders(non-linearity p > 0.05). Lastly, the two-sample MR analysis yielded evidence supporting a potential causal connection between serum vitamin D concentrations and sleep disorders, with each unit increase in genetically predicted serum vitamin D reducing the odds ratio to 0.78 (95% CI 0.61-0.99, p = 0.044). CONCLUSIONS: These results imply that lower vitamin D concentrations in the population might correlate with a heightened risk of sleep disorders, suggesting the importance of considering vitamin D supplementation when treating sleep disorders.


Assuntos
Análise da Randomização Mendeliana , Inquéritos Nutricionais , Transtornos do Sono-Vigília , Vitamina D , Humanos , Adulto , Pessoa de Meia-Idade , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/sangue , Transtornos do Sono-Vigília/genética , Vitamina D/sangue , Masculino , Feminino , Estados Unidos/epidemiologia , Adulto Jovem , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/genética
19.
Biomed Pharmacother ; 175: 116704, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749181

RESUMO

Long non-coding RNAs (lncRNAs) are pivotal controllers of gene expression through epigenetic mechanisms, Methylation, a prominent area of study in epigenetics, significantly impacts cellular processes. Various RNA base methylations, including m6A, m5C, m1A, and 2'-O-methylation, profoundly influence lncRNA folding, interactions, and stability, thereby shaping their functionality. LncRNAs and methylation significantly contribute to tumor development, especially in lung cancer. Their roles encompass cell differentiation, proliferation, the generation of cancer stem cells, and modulation of immune responses. Recent studies have suggested that dysregulation of lncRNA methylation can contribute to lung cancer development. Furthermore, methylation modifications of lncRNAs hold potential for clinical application in lung cancer. Dysregulated lncRNA methylation can promote lung cancer progression and may offer insights into potential biomarker or therapeutic target. This review summarizes the current knowledge of lncRNA methylation in lung cancer and its implications for RNA epigenetics and pulmonary diseases.


Assuntos
Epigênese Genética , Neoplasias Pulmonares , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Animais , Regulação Neoplásica da Expressão Gênica , Metilação , Pneumopatias/genética , Metilação de DNA/genética
20.
J Invest Dermatol ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38580106

RESUMO

Systemic sclerosis (SSc) is a challenging autoimmune disease characterized by progressive fibrosis affecting the skin and internal organs. Despite the known infiltration of macrophages and neutrophils, their precise contributions to SSc pathogenesis remain elusive. In this study, we elucidated that CD206hiMHCIIlo M2-like macrophages constitute the predominant pathogenic immune cell population in the fibrotic skin of a bleomycin-induced SSc mouse model. These cells emerged as pivotal contributors to the profibrotic response by orchestrating the production of TGF-ß1 through a MerTK signaling-dependent manner. Notably, we observed that neutrophil infiltration was a prerequisite for accumulation of M2-like macrophages. Strategies such as neutrophil depletion or inhibition of CXCR1/2 were proven effective in reducing M2-like macrophages, subsequently mitigating SSc progression. Detailed investigations revealed that in fibrotic skin, neutrophil-released neutrophil extracellular traps were responsible for the differentiation of M2-like macrophages. Our findings illuminate the significant involvement of the neutrophil-macrophage-fibrosis axis in SSc pathogenesis, offering critical information for the development of potential therapeutic strategies.

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