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1.
Photodiagnosis Photodyn Ther ; : 104298, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39089477

RESUMO

OBJECTIVE: To evaluate the efficacy of CO2 fractional laser and microneedling pretreatment combined with ALA-PDT for moderate-to-severe acne, aiming to optimize clinical treatment. METHODS: Patients were randomly divided into three groups: Group A (CO2 fractional laser + ALA-PDT), Group B (microneedling + ALA-PDT), and Group C (ALA-PDT). Each group underwent photodynamic therapy once a week for 3 weeks. Efficacy was assessed at the end of the 4th week, and recurrence was assessed at the end of the 12th week. RESULTS: A total of 150 patients with moderate to severe acne were included in this study, with 50 patients in each group. Four weeks after the end of treatment, the effective rates were 88% for Group A, 62% for Group B, and 36% for Group C. Statistically significant differences were found between the groups (P < 0.05), with Group A showing superior efficacy compared to Group B (P < 0.05). No serious systemic or local adverse reactions were observed in any group. No recurrence was seen in any group 12 weeks after the end of treatment, and some patients continued to show improvement in skin lesions over time. CONCLUSION: Both the CO2 fractional laser group and the microneedling group improved the efficacy of photodynamic therapy for moderate to severe acne compared to the control group, with the CO2 fractional laser group demonstrating better efficacy and fewer adverse effects.

2.
Acta Pharmacol Sin ; 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090392

RESUMO

Aristolochic acids (AAs) have been identified as a significant risk factor for hepatocellular carcinoma (HCC). Ferroptosis is a type of regulated cell death involved in the tumor development. In this study, we investigated the molecular mechanisms by which AAs enhanced the growth of HCC. By conducting bioinformatics and RNA-Seq analyses, we found that AAs were closely correlated with ferroptosis. The physical interaction between p53 and AAs in HepG2 cells was validated by bioinformatics analysis and SPR assays with the binding pocket sites containing Pro92, Arg174, Asp207, Phe212, and His214 of p53. Based on the binding pocket that interacts with AAs, we designed a mutant and performed RNA-Seq profiling. Interestingly, we found that the binding pocket was responsible for ferroptosis, GADD45A, NRF2, and SLC7A11. Functionally, the interaction disturbed the binding of p53 to the promoter of GADD45A or NRF2, attenuating the role of p53 in enhancing GADD45A and suppressing NRF2; the mutant did not exhibit the same effects. Consequently, this event down-regulated GADD45A and up-regulated NRF2, ultimately inhibiting ferroptosis, suggesting that AAs hijacked p53 to down-regulate GADD45A and up-regulate NRF2 in HepG2 cells. Thus, AAs treatment resulted in the inhibition of ferroptosis via the p53/GADD45A/NRF2/SLC7A11 axis, which led to the enhancement of tumor growth. In conclusion, AAs-hijacked p53 restrains ferroptosis through the GADD45A/NRF2/SLC7A11 axis to enhance tumor growth. Our findings provide an underlying mechanism by which AAs enhance HCC and new insights into p53 in liver cancer. Therapeutically, the oncogene NRF2 is a promising target for liver cancer.

3.
Front Public Health ; 12: 1378301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39091521

RESUMO

Objective: This study aims to investigate the Knowledge, Attitude, and Practice (KAP) pertaining to constipation during pregnancy among pregnant women in Shanghai. Methods: Demographic data and KAP scores were collected using a questionnaire. Differences across groups were analyzed using either Wilcoxon-Mann-Whitney tests or Kruskal-Wallis analysis of variance. Spearman's correlation analysis was utilized to evaluate the relationships between KAP scores. Multivariable logistic regression analyses were conducted to identify factors that influence KAP scores. Results: Encompassing 241 individuals (46.6%) aged between 30 and 34 years, with 349 participants (67.5%) being nulliparous. The median scores for knowledge (possible range: 0-26), attitude (possible range: 7-35), and practice (possible range: 14-70) were 22 (18, 24), 26 (23, 29), and 51 (46, 56), respectively. Multivariate analysis indicated that being a medical professional (OR = 2.222, p = 0.043) and receiving education on constipation during pregnancy (OR = 0.432, p < 0.001) were significantly associated with higher knowledge scores. Factors significantly associated with practice included being aged 30-34 years (OR = 2.745, p < 0.001), aged 35 years and above (OR = 2.514, p < 0.001), working in education (OR = 2.310, p = 0.012), and not experiencing constipation before pregnancy (OR = 1.894, p = 0.001). Conclusion: Pregnant women demonstrated satisfactory knowledge, positive attitudes, and proactive practices concerning constipation during pregnancy. To further augment clinical practice, healthcare providers should tailor educational interventions and guidance specifically for pregnant women who are not medical professionals and those who have not received education and guidance related to constipation during pregnancy.


Assuntos
Constipação Intestinal , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Feminino , Gravidez , Adulto , Estudos Transversais , China , Inquéritos e Questionários , Complicações na Gravidez , Gestantes/psicologia
4.
Front Pharmacol ; 15: 1445061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39092232

RESUMO

Background: Globally, the incidence rates of obesity and its related diseases, such as cardiovascular diseases and type 2 diabetes, are continuously rising, posing a significant public health challenge. Studies have indicated a potential correlation between vitamin D deficiency and obesity. However, a quantitative analysis of the studies related vitamin D and obesity is lacking. This investigation aims to fill this gap by providing a comprehensive bibliometric analysis to uncover the collaborative networks, research hotspots, and evolutionary trends within the field of vitamin D and obesity research. Methods: This study retrieved literature related to vitamin D and obesity from the Web of Science database spanning from 2000 to 2023. Bibliometric analysis was conducted using tools such as HistCite, VOSviewer, and CiteSpace to excavate multi-dimensional information including countries, institutions, authors, journals, citations, and keywords. Results: A total of 6,144 records were retrieved, involving 123 countries, 6,726 institutions, and 28,156 authors, published in 1,551 journals. The number of published papers and citations showed a generally increasing trend. The United States led in terms of publication volume and influence, with journals such as Nutrients and Obesity Surgery having the highest publication counts. Nasser M. Al-Daghri was the most prolific and influential author. Keyword clustering revealed that research topics covered metabolic health, nutrition, immunity, and bariatric surgery. Citation burst analysis indicated a shift in research focus from the relationship between dietary calcium and obesity to the preventive effects of vitamin D supplementation on metabolic diseases. Conclusion: The application of bibliometric methods to analyze the research literature in the fields of obesity and vitamin D has provided a comprehensive understanding of the collaborative networks, key research focus, and evolutionary trends in this field, offering insights for guiding future research directions.

5.
Cancer Epidemiol ; 92: 102625, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39094300

RESUMO

BACKGROUND: Patients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. METHODS: Surveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. RESULTS: Totally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. CONCLUSION: As oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

6.
Chem Biodivers ; : e202401646, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39102223

RESUMO

A focused chemical investigation into the polar fractions of a well-known traditional Chinese medicine called Sang-Bai-Pi (the root bark of Morus alba) yielded a panel of prenylated flavanones. The new compounds were identified as four pairs of enantiomers (1a/1b-4a/4b) featuring the same constitution structure, on the basis of HRMS, NMR and ECD analyses. Several previously reported known racemic co-metabolites were also analyzed and separated by HPLC on chiral columns, and the absolute configurations of pure enantiomers were established via ECD technique for the first time. The inhibition of these isolates against the antidiabetic target a-glycosidase was further tested, with most of them showing decent inhibitory activity compared with the positive control acarbose. The interaction mechanism of two selected compounds (3a & 4b) was explored by kinetics experiment, which revealed a mixed type of inhibition pattern toward the enzyme.

7.
Nat Commun ; 15(1): 6610, 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39098904

RESUMO

There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs' long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.


Assuntos
Terapia Trombolítica , Trombose , Ativador de Plasminogênio Tecidual , Animais , Ativador de Plasminogênio Tecidual/uso terapêutico , Humanos , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Masculino , Ratos , Terapia Trombolítica/métodos , Armadilhas Extracelulares/metabolismo , Suínos , Fibrinolíticos/uso terapêutico , Fibrinolíticos/farmacologia , Ratos Sprague-Dawley , Modelos Animais de Doenças , Fibrina/metabolismo , Nanomedicina Teranóstica/métodos , Resistência a Medicamentos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/tratamento farmacológico
8.
Physiol Mol Biol Plants ; 30(7): 1071-1084, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39100882

RESUMO

Lonicera japonica Flos is a valuable herb in the Lonicerae family. While transcriptomic studies on L. japonica have focused on different tissues (stems, leaves, flowers) or flowering stages, few have investigated the molecular mechanisms underlying chemical composition synthesis influenced by exogenous factors, such as foliar fertilization. Moreover, most transcriptomic studies on L. Japonica have been conducted on chlorogenic acid and luteoloside, and the molecular synthesis mechanism of the overall chemical composition has not been analyzed. Methods: We conducted a single-factor, four-level foliar fertilization experiment using yeast polysaccharides. Different yeast polysaccharides concentrations were sprayed on L. japonica for six consecutive days with dynamic sampling. High-performance liquid chromatography determined the active ingredients in each group. The two groups exhibiting the most significant differences were selected for transcriptomic analysis to identify key synthetic genes responsible for L. japonica's active ingredients. Key results: Principal component analysis conducted on samples collected on September 8 revealed significant differences in the active ingredient amounts between the 0.1 g/L yeast polysaccharides treatment group and the control group. Transcriptome sequencing analysis identified 218 significantly differentially expressed genes, including 60 upregulated and 158 downregulated genes. Twelve differential genes involved in the chemical components synthesis pathway of L. japonica under yeast polysaccharides treatment were identified: PAL1, PAL2, PAL3, 4CL1, 4CL, CHS1, CHS2, CHS, CHI1, CHI2, F3H, and SOH. Conclusions: This study contributes to the theoretical understanding of essential synthetic genes associated with L. japonica's active ingredients. It offers data support for further gene exploration and sheds light on the molecular mechanisms underlying L. japonica quality formation. These findings hold significant implications for enhancing the content of secondary metabolites of L. japonica. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01482-1.

9.
Shanghai Kou Qiang Yi Xue ; 33(3): 245-249, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-39104337

RESUMO

PURPOSE: To investigate the effects of erbium laser pretreatment on the bond strength of dentin and enamel,as well as microleakage at the edge of tooth defects repaired with computer-aided design (CAD) and computer-assisted manufacturing (CAM) glass-ceramic restorations for repairing dental defects. METHODS: A total of 62 fresh, nondecayed, nondiscoloration and noncracked wisdom teeth were collected from the Oral Surgery Clinic between January 2020 and January 2023. According to different pretreatment methods, they were randomly divided into two groups, erbium laser group and phosphoric acid group, with 31 teeth in each group. Each group was further divided into two subsets for bond strength testing (16 teeth) and microleakage testing (15 teeth).The shear bond strength between enamel and dentin of both groups was compared, as well as the degree and distribution of microleakage.Statistical analysis was performed with SPSS 17.0 software package. RESULTS: The shear bond strength between enamel and dentin of the erbium laser group was significantly higher than that of the phosphoric acid group (P<0.05); the degree and distribution of microleakage at the lateral walls and gumline of the erbium laser group were significantly lower than those of the phosphoric acid group (P<0.05). The scores of microleakage at the lateral walls of the erbium laser group mainly concentrated in grade 1 and 2, whereas those of the phosphoric acid group mainly concentrated in grade 2. There was significant difference in the distribution of lateral wall microleakage scores between the two groups (P<0.05). The scores of microleakage at the gumline of the erbium laser group mainly concentrated in grade 1 and 2, whereas those of the phosphoric acid group mainly concentrated in grade 2 and 3. There was significant difference in the distribution of gumline microleakage scores between the two groups (P<0.05). CONCLUSIONS: Erbium laser pretreatment can improve bonding strength between glass ionomer cement and dentin and enamel, reduce microleakage at the edge of CAD/CAM glass ionomer cement restorations, and enhance marginal fit.


Assuntos
Desenho Assistido por Computador , Colagem Dentária , Esmalte Dentário , Dentina , Cimentos de Ionômeros de Vidro , Esmalte Dentário/efeitos da radiação , Humanos , Dentina/química , Cimentos de Ionômeros de Vidro/química , Colagem Dentária/métodos , Ácidos Fosfóricos/química , Lasers de Estado Sólido/uso terapêutico , Resistência ao Cisalhamento , Infiltração Dentária/etiologia , Restauração Dentária Permanente/métodos , Érbio/química
10.
J Ethnopharmacol ; 335: 118650, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39094755

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Linggui-Zhugan (LGZG) comprises four herbs and is a classic formula in traditional Chinese medicine. There is strong clinical evidence of its pleiotropic effects in the prevention of diabetes and its related complications. Although several classes of drugs are currently available for clinical management of diabetic kidney disease (DKD), tight glycemic and/or hypertension control may not prevent disease progression. This study evaluated the therapeutic effect of the ethnopharmacological agent LGZG on DKD. AIM OF THE STUDY: This study aimed to investigate the effects of LGZG formula with standard quality control on experimental DKD and its related metabolic disorders in animal model. Meanwhile, the present study aimed to investigate regulatory effects of LGZG on renal proteinase 3 (PR3) to reveal mechanisms underlying renoprotective benefits of LGZG. MATERIALS AND METHODS: LGZG decoction was fingerprinted by high-performance liquid chromatography for quality control. An experimental model of DKD was induced in C57 BL/6J mice by a combination of high-fat diet feeding, uninephrectomy, and intraperitoneal injection of streptozocin. The LGZG decoction was administrated by daily oral gavage. RESULTS: Treatment with LGZG formula significantly attenuated DKD-like traits (including severe albuminuria, mesangial matrix expansion, and podocyte loss) and metabolic dysfunction (disordered body composition and dyslipidemia) in mice. RNA sequencing data revealed a close association of LGZG treatment with marked modulation of signaling pathways related to podocyte injury and cell apoptosis. Mechanistically, LGZG suppressed the DKD-triggered increase in renal PR3 and podocyte apoptosis. In-vitro incubation of mouse immortalized podocytes with LGZG-medicated serum attenuated PR3-mediated apoptosis. CONCLUSION: Our data demonstrated that the LGZG formula protected against DKD in mice and was closely associated with its inhibitory effects on PR3-mediated podocyte apoptosis.

11.
Water Res ; 263: 122173, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39111213

RESUMO

Wastewater treatment plants face significant challenges in transitioning from energy-intensive systems to carbon-neutral, energy-saving systems, and a large amount of chemical energy in wastewater remains untapped. Iron is widely used in modern wastewater treatment. Research shows that leveraging the coupled redox relationship of iron and carbon can redirect this energy (in the form of carbon) towards resource utilization. Therefore, re-examining the application of iron in existing wastewater carbon processes is particularly important. In this review, we investigate the latest research progress on iron for wastewater carbon flow restructuring. During the iron-based chemically enhanced primary treatment (CEPT) process, organic carbon is captured into sludge and its bioavailability is enhanced through iron-based advanced oxidation processes (AOP) pretreatment, further being recovered or upgraded to value-added products in anaerobic biological processes. We discuss the roles and mechanisms of iron in CEPT, AOP, anaerobic biological processes, and biorefining in driving organic carbon conversion. The dosage of iron, as a critical parameter, significantly affects the recovery and utilization of sludge carbon resources, particularly by promoting effective electron transfer. We propose a pathway for beneficial conversion of wastewater organic carbon driven by iron and analyze the benefits of the main products in detail. Through this review, we hope to provide new insights into the application of iron chemicals and current wastewater treatment models.


Assuntos
Carbono , Ferro , Eliminação de Resíduos Líquidos , Águas Residuárias , Ferro/química , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos , Oxirredução , Esgotos/química
12.
Front Immunol ; 15: 1407461, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39136030

RESUMO

Background: Minimal change disease (MCD) is a common cause of adult nephrotic syndrome. Most adults with MCD achieve complete remission (CR) after initial steroid therapy. However, approximately 30% of adults who respond to steroids experience frequent relapses, becoming steroid-dependent and potentially developing refractory MCD. Treating refractory MCD in adults poses a significant challenge. Main body: A 37-year-old woman presented to the nephrology department with a 6-year history of MCD. The diagnosis of MCD was confirmed via renal biopsy. She initially achieved CR with steroid treatment but experienced relapse during steroid tapering. Subsequent CR was achieved with a regimen of steroids and tacrolimus although multiple relapses occurred. Rituximab led to another CR, but its maintenance lasted only 6 months. The response to subsequent rituximab treatments was unsatisfactory. Ultimately, obinutuzumab was selected, resulting in the induction and maintenance of CR for 12 months. Conclusions: This case demonstrates the successful treatment of frequently relapsed, steroid-dependent, and rituximab-resistant MCD with obinutuzumab. Obinutuzumab is a promising therapeutic option for rituximab-resistant MCD.


Assuntos
Anticorpos Monoclonais Humanizados , Nefrose Lipoide , Rituximab , Humanos , Adulto , Feminino , Nefrose Lipoide/tratamento farmacológico , Rituximab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Resistência a Medicamentos , Resultado do Tratamento , Indução de Remissão , Recidiva
13.
Ecotoxicol Environ Saf ; 283: 116853, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39137468

RESUMO

The effect and underlying mechanism of tetrabromobisphenol A (TBBPA), a plastic additive, on biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA USA300) remain unknown. This study first investigated the impact of different concentrations of TBBPA on the growth and biofilm formation of USA300. The results indicated that a low concentration (0.5 mg/L) of TBBPA promoted the growth and biofilm formation of USA300, whereas high concentrations (5 mg/L and 10 mg/L) of TBBPA had inhibitory effects. Further exploration revealed that the low concentration of TBBPA enhance biofilm formation by promoting the synthesis of extracellular proteins, release of extracellular DNA (eDNA), and production of staphyloxanthin. RTqPCR analysis demonstrated that the low concentration of TBBPA upregulated genes associated with extracellular protein synthesis (sarA, fnbA, fnbB, aur) and eDNA formation (atlA) and increased the expression of genes involved in staphyloxanthin biosynthesis (crtM), suggesting a potential mechanism for enhanced resistance of USA300 to adverse conditions. These findings shed light on how low concentrations of TBBPA facilitate biofilm formation in USA300 and highlight the indirect impact of plastic additives on pathogenic bacteria in terms of human health. In the future, in-depth studies about effects of plastic additives on pathogenicity of pathogenic bacteria should be conducted. CAPSULE: The protein and eDNA contents in biofilms of methicillin-resistant Staphylococcus aureus are increased by low concentrations of TBBPA.

14.
Sci Adv ; 10(32): eadp6182, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39121218

RESUMO

Endothelial cells (ECs) are highly plastic, capable of differentiating into various cell types. Endothelial-to-mesenchymal transition (EndMT) is crucial during embryonic development and contributes substantially to vascular dysfunction in many cardiovascular diseases (CVDs). While targeting EndMT holds therapeutic promise, understanding its mechanisms and modulating its pathways remain challenging. Using single-cell RNA sequencing on three in vitro EndMT models, we identified conserved gene signatures. We validated original regulators in vitro and in vivo during embryonic heart development and peripheral artery disease. EndMT induction led to global expression changes in all EC subtypes rather than in mesenchymal clusters. We identified mitochondrial calcium uptake as a key driver of EndMT; inhibiting mitochondrial calcium uniporter (MCU) prevented EndMT in vitro, and conditional Mcu deletion in ECs blocked mesenchymal activation in a hind limb ischemia model. Tissues from patients with critical limb ischemia with EndMT features exhibited significantly elevated endothelial MCU. These findings highlight MCU as a regulator of EndMT and a potential therapeutic target.


Assuntos
Sinalização do Cálcio , Células Endoteliais , Transição Epitelial-Mesenquimal , Mitocôndrias , RNA-Seq , Análise de Célula Única , Animais , Humanos , Mitocôndrias/metabolismo , RNA-Seq/métodos , Camundongos , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Canais de Cálcio/metabolismo , Canais de Cálcio/genética , Isquemia/metabolismo , Isquemia/patologia , Cálcio/metabolismo , Análise da Expressão Gênica de Célula Única
15.
Int J Biol Sci ; 20(10): 3863-3880, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39113716

RESUMO

The mechanisms behind the selection and initial recruitment of primordial follicles (PmFs) from the non-growing PmF pool during each estrous cycle in females remain largely unknown. This study demonstrates that PmFs closest to the ovulatory follicle are preferentially activated in mouse ovaries under physiological conditions. PmFs located within 40 µm of the ovulatory follicles were more likely to be activated compared to those situated further away during the peri-ovulation period. Repeated superovulation treatments accelerated the depletion of the PmF reserve, whereas continuous suppression of ovulation delayed PmF reserve consumption. Spatial transcriptome sequencing of peri-ovulatory follicles revealed that ovulation primarily induces the degradation and remodeling of the extracellular matrix (ECM). This ECM degradation reduces mechanical stress around PmFs, thereby triggering their activation. Specifically, Cathepsin L (CTSL), a cysteine proteinase and lysosomal enzyme involved in ECM degradation, initiates the activation of PmFs adjacent to ovulatory follicles in a distance-dependent manner. These findings highlight the link between ovulation and selective PmF activation, and underscore the role of CTSL in this process under physiological conditions.


Assuntos
Catepsina L , Matriz Extracelular , Folículo Ovariano , Ovulação , Animais , Feminino , Camundongos , Folículo Ovariano/metabolismo , Catepsina L/metabolismo , Ovulação/fisiologia , Matriz Extracelular/metabolismo , Ovário/metabolismo , Ciclo Estral/fisiologia
16.
Angew Chem Int Ed Engl ; : e202413653, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39133139

RESUMO

In proton exchange membrane water electrolysis (PEMWE), the anode oxygen evolution reaction (OER) catalysts rely heavily on the expensive and scarce iridium-based materials. Ruthenium dioxide (RuO2) with lower price and higher OER activity, has been explored for the similar task, but has been restricted by the poor stability. Herein, we developed an anion modification strategy to improve the OER performance of RuO2 in acidic media. The designed multicomponent catalyst based on sulfate anchored on RuO2/MoO3 displays a low overpotential of 190 mV at 10 mA cm-2 and stably operates for 500 hours with a very low degradation rate of 20 µV h-1. When assembled in a PEMWE cell, this catalyst as an anode shows an excellent stability at 500 mA cm-2 for 150 h. Experimental and theoretical results revealed that MoO3 could stabilize sulfate anion on RuO2 surface to suppress its leaching during OER. Such MoO3-anchored sulfate not only reduces the formation energy of *OOH intermediate on RuO2, but also impedes both the surface Ru and lattice oxygen loss, thereby achieving the high OER activity and exceptional durability.

17.
Eur J Cancer ; 210: 114278, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39151323

RESUMO

BACKGROUND: Despite improvements in colorectal cancer (CRC) treatment, the prognosis for advanced CRC patients remains poor. Disruption of protein stability is one of the important factors in cancer development and progression. In this study, we aim to identify and analyze novel dysregulated proteins in CRC, assessing their significance and the mechanisms. METHODS: Using quantitative proteomics, expression pattern analysis, and gain-of-function/loss-of-function experiments, we identify novel functional protein dysregulated by ubiquitin-proteasome axis in CRC. Prognostic significance was evaluated in a training cohort of 546 patients and externally validated in 794 patients. Mechanistic insights are gained through molecular biology experiments, deubiquitinating enzymes (DUBs) expression library screening, and RNA sequencing. RESULTS: MAFF protein emerged as the top novel candidate substrate regulated by ubiquitin-proteasome in CRC. MAFF protein was preferentially downregulated in CRC compared to adjacent normal tissues. More importantly, multicenter cohort study identified reduced MAFF protein expression as an independent predictor of overall and disease-free survival in CRC patients. The in vitro and vivo assays showed that MAFF overexpression inhibited CRC growth, while its knockdown had the opposite effect. Intriguingly, we found the abnormal expression of MAFF protein was predominantly regulated via ubiquitination of MAFF, with K48-ubiquitin being dominant. BAP1 as a nuclear deubiquitinating enzyme (DUB), bound to and deubiquitinated MAFF, thereby stabilizing it. Such stabilization upregulated DUSP5 expression, resulting in the inhibition of ERK phosphorylation. CONCLUSIONS: This study describes a novel BAP1-MAFF signaling axis which is crucial for CRC growth, potentially serving as a therapeutic target and a promising prognostic biomarker for CRC.

18.
ISA Trans ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39152079

RESUMO

Aiming to address the multiscale characteristics and noise corruption problems in the vibration signals of aviation hydraulic pumps, this article develops a novel Multiscale Dynamically Parallel Shrinkage Network (MDPSN) to learn complementary and rich fault-related multiscale features, with the ultimate goal of yielding higher diagnostic accuracy. One significant property is the development of a novel dynamically parallel shrinking module (DPSM) that adaptively generates independent soft thresholds for different scales, effectively shrinking noise-related features to zeros. On one hand, DPSM aggregates and interacts with features at all scales to construct a global feature representation containing richer fault-related information, which is served as the foundation for soft thresholding generation, significantly improving the accuracy and rationality of the generated thresholds. On the other hand, DPSM can adaptively generate individual soft threshold for each scale, allowing each scale to use an independent threshold tailored to its own characteristic to eliminate noise-related information. This avoids the issues of over-denoising or under-denoising caused by the uniform application of thresholds across all scales. Finally, the effectiveness of MDPSN is validated by a series of experiment comparisons on an aviation hydraulic pump dataset and two bearing datasets with various types of noise. The experimental results demonstrate that MDPSN achieves superior diagnostic accuracy compared to five other comparison methods.

19.
Oral Dis ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39155514

RESUMO

OBJECTIVES: This study aimed to investigate the expression and biological significance of Semenogelin 1 (SEMG1), a member of the cancer-testis antigen family, in oral squamous cell carcinoma (OSCC). Further, we explored its potential association with metabolism-related molecules. METHODS: SEMG1 expression levels in OSCC were determined through immunohistochemistry, flow cytometry, and Western blot analyses. To decipher the biological implications of SEMG1 in OSCC, the CAL27 OSCC cell line was either stably overexpressed with SEMG1 or subjected to SEMG1-shRNA knockdown. The relationship between clinicopathological parameters and SEMG1 expression in OSCC patients was also assessed. RESULTS: SEMG1 was found to be overexpressed in OSCC, though its expression was not influenced by the pathological grade. The fluorescent dihydroethidium assay indicated that SEMG1 augmented reactive oxygen species production. The mitochondrial membrane potential assay suggested a significant upregulation of mitochondrial membrane potential by SEMG1. Cell cycle assessments highlighted that SEMG1 overexpression led to a notable rise in cells entering the S-phase. Additionally, a strong correlation between SEMG1 expression and both ENO1 and PKM2 expression in OSCC was observed. CONCLUSIONS: The findings underscore the elevated expression of SEMG1 in OSCC and its contributory role in the tumorigenesis of OSCC patients.

20.
J Am Chem Soc ; 146(33): 22930-22936, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39115250

RESUMO

The incorporation of new coordinate bonds and the development of universal methods for new structures have always been of major interest in metal-organic framework (MOF) research. The poor reversibility makes metal-carbon (M-C) bonds a great challenge to adopt as linkages to construct crystalline MOFs. Herein, three isoreticular microcrystalline MOFs connected by silver-carbon (Ag-C) bonds are presented for the first time and named AgC-MOFs. Their structures contain a double coordination mode (σ and π) between Ag(I) and alkynyl. The three AgC-MOFs all exhibit three-dimensional (3D) frameworks with uniform one-dimensional (1D) hexagonal channels, and the pore width could be tuned from 1.1 to 1.8 nm. The construction of crystalline MOFs using poorly reversible Ag-C coordinate bonds extends the nexuses for the MOF structure and lights up more possibilities for the systematic design of MOFs.

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